Antidote.
\r\n\t
",isbn:"978-1-83881-111-2",printIsbn:"978-1-83880-992-8",pdfIsbn:"978-1-83881-112-9",doi:null,price:0,priceEur:0,priceUsd:0,slug:null,numberOfPages:0,isOpenForSubmission:!0,isSalesforceBook:!1,isNomenclature:!1,hash:"acb2875b3bfc189c9881a9b44b6a5184",bookSignature:"Dr. Abdo Abou Jaoudé",publishedDate:null,coverURL:"https://cdn.intechopen.com/books/images_new/11865.jpg",keywords:"Linear Operators, Normal Operators, Spectral Theorem, Applications, Differential Operators, Integral Operators, Functional Calculus, Complex Variables, Complex Analysis, Theory, Recent Advances, Latest Trends",numberOfDownloads:null,numberOfWosCitations:0,numberOfCrossrefCitations:null,numberOfDimensionsCitations:null,numberOfTotalCitations:null,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"April 13th 2022",dateEndSecondStepPublish:"June 21st 2022",dateEndThirdStepPublish:"August 20th 2022",dateEndFourthStepPublish:"November 8th 2022",dateEndFifthStepPublish:"January 7th 2023",dateConfirmationOfParticipation:null,remainingDaysToSecondStep:"6 days",secondStepPassed:!0,areRegistrationsClosed:!1,currentStepOfPublishingProcess:3,editedByType:null,kuFlag:!1,biosketch:"Abdo Abou Jaoudé is a pioneering Associate Professor of Mathematics and Statistics at Notre Dame University-Louaizé. He holds two PhDs in Mathematics and Prognostics from the Lebanese University and Aix-Marseille University. His research interests are in the field of mathematics.",coeditorOneBiosketch:null,coeditorTwoBiosketch:null,coeditorThreeBiosketch:null,coeditorFourBiosketch:null,coeditorFiveBiosketch:null,editors:[{id:"248271",title:"Dr.",name:"Abdo",middleName:null,surname:"Abou Jaoudé",slug:"abdo-abou-jaoude",fullName:"Abdo Abou Jaoudé",profilePictureURL:"https://mts.intechopen.com/storage/users/248271/images/system/248271.jpg",biography:"Abdo Abou Jaoudé has been teaching for many years and has a passion for researching and teaching mathematics. He is currently an Associate Professor of Mathematics and Statistics at Notre Dame University-Louaizé (NDU), Lebanon. He holds a BSc and an MSc in Computer Science from NDU, and three PhDs in Applied Mathematics, Computer Science, and Applied Statistics and Probability, all from Bircham International University through a distance learning program. He also holds two PhDs in Mathematics and Prognostics from the Lebanese University, Lebanon, and Aix-Marseille University, France. Dr. Abou Jaoudé's broad research interests are in the field of applied mathematics. He has published twenty-three international journal articles and six contributions to conference proceedings, in addition to seven books on prognostics, pure and applied mathematics, and computer science.",institutionString:"Notre Dame University - Louaize",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"4",totalChapterViews:"0",totalEditedBooks:"2",institution:{name:"Notre Dame University – Louaize",institutionURL:null,country:{name:"Lebanon"}}}],coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"15",title:"Mathematics",slug:"mathematics"}],chapters:null,productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},personalPublishingAssistant:{id:"252211",firstName:"Sara",lastName:"Debeuc",middleName:null,title:"Ms.",imageUrl:"https://mts.intechopen.com/storage/users/252211/images/7239_n.png",email:"sara.d@intechopen.com",biography:"As an Author Service Manager my responsibilities include monitoring and facilitating all publishing activities for authors and editors. From chapter submission and review, to approval and revision, copyediting and design, until final publication, I work closely with authors and editors to ensure a simple and easy publishing process. I maintain constant and effective communication with authors, editors and reviewers, which allows for a level of personal support that enables contributors to fully commit and concentrate on the chapters they are writing, editing, or reviewing. I assist authors in the preparation of their full chapter submissions and track important deadlines and ensure they are met. I help to coordinate internal processes such as linguistic review, and monitor the technical aspects of the process. As an ASM I am also involved in the acquisition of editors. 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Based on World Health Organization (WHO) data in 2012, almost 190,000 people died worldwide and number of deaths due to poisoning in 2008 exceeded the number of deaths due to motor vehicular crashes; also, poisoning death rate nearly tripled worldwide. Number of patients presenting to the emergency departments with overdose, had been increased both intentionally and accidentally. All the previous facts make Toxicology an important field in emergency medicine [1, 2].
\nManagement of intoxicated patients has a unique approach because of the challenge in diagnosis and treatment of overdose cases. This chapter is focusing on general approaches for intoxicated patients and initial management and on how the history and physical examinations could help physicians to have what drug have been abused as well as review the mechanism of action, physical finding and treatment of the most common drugs-causing toxicity in addition to the drugs with high mortality morbidity rates.
\nApproach for the poisoned patients in emergency includes: resuscitation, history, physical examination and management.
\nThe initial priorities for a poisoned patient presented emergency department are: securing the air-way and breathing and stabilizing the circulation. Inadequate ventilation may need intubation and mechanical ventilation. First-line treatment of hypotension is IV fluid bolus (10–20 mL/kg), if hypotension is not responding to fluid, it may be necessary to add specific antidote. If the patient presented with signs of opioid over dose (low Glasgow coma scale-GCS respiratory depression, meiosis), give him naloxone (0.1–2.0 mg I.V), check blood sugar and treat hypoglycaemia with 50% 50 mL dextrose [3].
\nHistory is very important and can be obtained from the patient, and in case the patient is comatose or cannot give his history, we may take collateral information from family, friends or medical records looking for past psychiatry illness, previous history of suicide or drugs abuse, chronic medication… History must include time, route of entry, quantity, intentional or accidental exposure, availability of drugs at home and if any member of the family has chronic diseases (hypertension, diabetic etc…), missing tablets or any empty pill bottles or other material was found around him [4].
\nPhysical examination of poisoned patients may give clues regarding the substance which has been abused and toxidromes. Physical examination includes: general appearance, mental status (agitated or confused), Skin (cyanosis, flashing, physical signs of intravenous drugs abuse (track marks), eyes: (pupil size reactivity lacrimation and nystagmus), odour (garlic, bitter almonds, glue, alcohol etc.…), Oropharynx hyper salivation or dryness, chest: breath sound, bronchorrhea, wheezing, heart rate, rhythm regularity), abdomen(bowel sound, tenderness, and rigidity), limbs(tremors and fasciculation), patient’s clothing (looking for any medications, illegal drugs) [3].
\nThe term toxidrome was coined in 1970 by Mofenson and Greensher. Toxidromes are group of abnormal physical examination and abnormal vital signs known to present with specific group of medications or substances. Most common toxidromes are Cholinergic, Anticholinergic, Sympathomimetic, opioids, and serotonin syndrome [4, 5].
\nPatients with cholinergic toxidrome present with wet manifestation. SLUDGE+3 killer B’s”or DUMBELLS are simple mnemonics for the common clinical symptoms.
\n“SLUDGE”: Salivation, Lacrimation, Urination, Defecation, GI cramping, Emesis + “Killer B’s”: Bronchorrhea, Bradycardia, and Bronchospasm.
\n“DUMBELLS”: Diarrhoea, Urination, Miosis (small pupils), Bradycardia, Emesis, Lacrimation, Lethargy, and Salivation.
\nMost common Causes: Organophosphate pesticides, Carbamates, Same type Mushrooms and Sarin (warfare agent) [4].
\nPatients with Anticholinergic toxidrome with dry manifestation, delirium, tachycardia, dry flushed skin, dilated pupils, clonus, elevated temperature, decreased bowl sounds, urinary retention. Simple mnemonics: “Hot as a Hare, Mad as a Hatter, Red as a Beet, Dry as a Bone, Blind as a Bat”.
\nMost common Causes: Antihistamines, antiparkinsonians, atropine, scopolamine, amantadine, antipsychotics, antidepressants, muscle relaxants and plants (Jimson weed) [4].
\nPatient present with CNS stimulation and psychomotor agitation, elevated blood pressure, tachycardia, dilated pupils, hyperthermia, diaphoresis and seizure in severe cases.
\nMost common causes: cocaine, amphetamine.
\nMost common clinical presentation of opioids toxidrome are: coma, respiratory depression and meiosis, hypotension, hypothermia, bradycardia and seizure may occur in propoxyphene overdose, but small pupils not always present may present with normal size pupils such in meperidine and, propoxyphene toxicities [4].
\nPatient present with altered mental status, hypertensive, and tachycardia, Myoclonus hyperreflexia, hyperthermia and increase muscles rigidity. Most common causes: SSRI interaction or overdose [4].
\nDecontamination of poisoned patient means remove the patient from the toxin and remove the toxin from patient, either outside patient’s body by gross washing or inside the body by gastrointestinal decontamination or enhance elimination.
\nPatient must be fully undressed and washed thoroughly with copious amount of water; all the clothing must be removed, and decontamination must be in isolated specific area. Gross decontamination used in chemical, biological and radiation exposure.
\nThere are multiple methods used for gastrointestinal decontamination including:
\nEmesis and gastric Lavage.
\nInduced vomiting by ipecac syrup and gastric lavage: those methods were used in the past and now rarely indicated because there is no evidence supporting them. They can decrease absorption and they may also increase the risk of complications. Syrup ipecac and gastric Lavage may be considered in conscious, alert patients with ingestion of potentially number of toxic drugs and present in a very short time after ingestion (<1 h). Contradictions includes: unprotected airway, Corrosive/hydrocarbon ingestion and unstable patient status (hypotensive-seizure) [6].
\nActivated charcoal is super-heating carbonaceous material. Activated charcoal works by reducing the absorption of substance in the gastrointestinal lumen but it is not effective in metal, alcohols, corrosive, and lithium. Most effective action can be achieved when activated charcoal is given within the first hour of ingestion. Contraindications: absent gut motility or perforation, caustic ingestion and unprotected airway (can be given through nasogastric tube if patient intubated).Complications: aspiration of activated charcoal led to pneumonitis, ARDS and other complications such as small bowel obstruction [7].
\nWhole-bowel irrigation is a mechanical cleansing of the whole gastrointestinal track reducing toxin absorption. The whole-bowel irrigation can be done by Polyethylene glycol solution. Indication includes: substance with a prolonged absorption phase like sustained released medication, potential toxin not absorbed by activated charcoal such—(metals, lithium) and Body packers or suffers. Adverse effects of whole bowel irrigation could be: vomiting, bloating and rectal irritation. Contradiction: absent bowel sound or perforation [8].
\nEnhanced elimination is a method used to increase the rate of toxic removal from the body so reducing the severity and duration of clinical intoxication.
\nEnhanced elimination methods are not routinely used in poisoned patients. The indications for Enhanced elimination include [4]:
Severe toxicity
Poor outcome despite supportive care/antidote
Slow endogenous rate of elimination
There are different techniques to enhance elimination:
\nMultiple dose activated charcoal (MDAC): it can be used in cases of carbamazepine, Phenobarbital, Dispone sever toxicities,
\nUrinary alkalinisation:
\nCan be used in cases of Salicylates Phenobarbitone.
\nExtracorporeal elimination (e.g. haemodialysis, hemofiltration, and haemoperfusion, plasmapheresis and exchange transfusion:
\nCan be used in cases of lithium, carbamazepine, salicylates, theophylline, and toxic.
\nAlcohols: ethylene glycol and methanol metformin.
\nAntidote is a substance that can prevent further poisoning from specific substances. The table below showing most common antidote used in emergency department (see Table 1) [4].
\nToxin | \nAntidote | \n
---|---|
Acetaminophen | \nN-acetylcysteine 150 mg/kg dextrose IV over 15–60 min then50 mg/kg NAC IV over 4 h. Then 100 mg/kg NAC IV over 16 h. | \n
Cholinergic (organophosphates, carbamates) | \nAtropine 1–2 mg every 2–3 mins, until there is drying of secretions Pralidoxime (2-PAM) 70 mg/kg IV then infusion at 500 mg/h | \n
Anticholinesterases | \nPhysostigmine 0.5–1 mg IV as a slow push over 5 min and repeat every 10 min | \n
Benzodiazepines | \nFlumazenil 0.2 Mg repeated max dose 2 mg | \n
β-Blockers | \nGlucagon 3–10 mg | \n
Calcium channel blockers | \nCalcium gluconate 10% 10–30 mL IV | \n
Cyanide | \nAmyl nitrite Sodium thiosulfate Sodium nitrite (3% solution) Vitamin B12 | \n
Digoxin | \nDigoxin Fab 5–10 vials | \n
Isoniazid | \nPyridoxine (vitamin B6) 70 mg/kg IV (maximum 5 gm) | \n
Methanol, ethylene glycol | \nEthanol Loading 8 mL/kg of 10% ethanol then 1–2 mL/kg/h of 10% ethanol Fomepizole Loading: 15 mg/kg in 100 mL IV over 30 min Maintenance: 10 mg/kg IV over 30 min every 12 h for 48 h | \n
Narcotics | \nNaloxone 0.1–0.4 mg, may repeated | \n
Tricyclic antidepressants | \nSodium bicarbonate 1–2 mEq/kg IV bolus followed by 2 mEq/kg per h IV infusion | \n
iron | \nDesferrioxamine IV infusion dose of 15 mg/kg/h | \n
methaemoglobinaemia | \nMethylene Blue 1–2 mg/kg (0.1–0.2 mL/kg of 1% solution) IV slowly over 5 min | \n
local anaesthetics | \nIntravenous lipid emulsion 1–1.5 mL/kg 20% IV bolus over 1 min Repeat bolus at 3–5 min Then Infuse 0.25 mL/kg/min | \n
Antidote.
First time acetaminophen had been clinically used was in 1950 and since that time acetaminophen become most common over-the-counter antipyretic and analgesic used in public. Acetaminophen is the most common cause of acute liver failure in the United States [9, 10].
\nAcetaminophen metabolized in the liver and converted to nontoxic metabolites via glucuronidation (40–67%) and sulfation (20–46%). In therapeutic doses of acetaminophen, the small amount of NAPQI formed which detoxified by conjugation with reduced glutathione (GSH). Glutathione is an important tripeptide which is reduced in a NADPH dependent reaction, and used to reduce oxidants (such as NAPQI).
\nIn large overdoses of APAP, the usual pharmacokinetic pathways are overwhelmed and saturation of the nontoxic pathways occurs. Endogenous glutathione is depleted and NAPQI cannot be detoxified. Leaving excess NAPQI to bind to intracellular proteins, cause cell death [11].
\nSymptoms are frequently nonspecific or absent in early Acetaminophen toxicity.
\nClinical presentation of Acetaminophen toxicity divided into four stages:
Stage I (first 24 h): Patients may present nausea, vomiting, malaise, anorexia, or may be asymptomatic. Also hypokalaemia and metabolic acidosis can be found in blood test.
-Stage II (Days 2–3): patients develop nausea, vomiting, right upper quadrant abdominal pain and laboratory evidence of hepatotoxicity. Aminotransferases (AST and ALT) elevate into thousands.
-Stage III (3–4 days) defined by maximum hepatotoxicity, Patients exhibit coma, encephalopathy, coagulopathy, renal failure, Jaundice, acute respiratory distress syndrome (ARDS), sepsis and cerebral oedema.
-Stage IV (7–8 d): recovery or deterioration to multi-organ failure and death [12, 13].
After initial support of airway, breathing and circulation, the clinician should consider gastrointestinal (GI) decontamination by activated charcoal. The cornerstone of acetaminophen overdose is N-acetylcysteine (NAC). NAC serves as a precursor to glutathione and may also directly reduce NAPQI. Clinical data suggest that if therapy is initiated within 8 h of ingestion, NAC is completely effective in preventing hepatotoxicity. Although NAC decreases in efficacy after 8 h, the drug has a benefit at all points in time, even for patients with fulminant hepatic failure.
\nN-acetylcysteine should only be given to patients with hepatotoxicity or risk of developing hepatotoxicity. The Rumack-Matthew nomogram is a tool for determining potential hepatotoxicity based on Acetaminophen level and time after ingestion. The nomogram is used to determine the risk for APAP hepatotoxicity for patients who present within 24 h of an acute ingestion. Risk determination of hepatotoxicity becomes more difficult when the nomogram is not applicable. Examples of such cases would be when the time of ingestion is unknown, when patients present more than 24 h after the ingestion and following ingestions that occur over many hours. In all of these cases NAC should be administered immediately. If aminotransferases (ALT, AST) are normal and APAP concentration is undetectable, the NAC may be discontinued. Otherwise, treatment with NAC should be continued.
\nN-acetylcysteine dose Oral 140 mg/kg loading dose 70 mg/kg q4 h × 17 doses or Intravenous 150 mg/kg loading dose 50 mg/kg over 4 h 100 mg/kg over 16 h [14, 15, 16] (Figures 1 and 2).
\nRumack-Matthew nomogram.
ECG changes in TCA toxicity.
Cyclic antidepressants were used to depression, but now their use has reduced greatly because of the presences of more safe agents. Cyclic antidepressants were most common antidepressants associated with overdose-related deaths in 2013 [17].
\nCA has multiple pharmacologic effects.
\nCyclic antidepressants are inhibiting postsynaptic histamine receptors, causing sedation, decrease level of conscious and coma.
\nAntimuscarinic effects are divided to central and peripheral. Inhibition central acetylcholine receptors cause agitation, delirium, confusion, hallucinations, slurred speech, ataxia and coma. Inhibition Peripheral acetylcholine receptors inhibition cause dilated pupils, tachycardia, hyperthermia, hypertension, dry skin, ileus, urinary retention, increased muscle tone and tremor [18].
\nThis effects cause sedation, orthostatic hypotension, tachycardia and pupillary constriction, but because of the antimuscarinic effects, this action usually offsets pupillary dilatation [18].
\nThis effect produces mydriasis, diaphoresis, tachycardia, early hypertension, myoclonus and hyperreflexia.
\nThis effect produces decreased conduction velocity, increases the duration of repolarization and depressed myocardial contractility which lead to heart blocks, bradycardia and widening of the QRS complex [19].
\nThis effect produces QT interval prolongation and rarely torsades de pointes can be seen [19].
\nSymptoms occur typically within 2 h of ingestion, which varies from mild antimuscarinic symptoms to severe cardio-toxicity. Patient may present with drowsiness, confusion, slurred speech, ataxia, sinus tachycardia, urinary retention, myoclonus and hyperreflexia. Serious toxicity is almost seen within 6 h of ingestion and patient present with: coma, cardiac conduction delays, supraventricular tachycardia, hypotension, respiratory depression, ventricular tachycardia and seizures [20, 21].
\n\n
Sinus tachycardia, most common
Right axis deviation of the terminal 40 milliseconds positive terminal R wave in lead aVR and a negative S wave in lead I)
Prolongation of QRS,(risk of seizures increases if the QRS complex is >100 milliseconds)
Prolongation QT, PR
Brugada pattern is seen 10–15%
Treatment starts with supportive management securing airway, bolus i.v fluid in case of hypotension, GI decontamination with activated charcoal within 1 h of ingestion.
\nAdd vasopressors if hypotensive refractory to IV normal saline. Cardiac conduction abnormalities, ventricular dysrhythmias, or hypotension refractory to IV fluid are indicated to start blood alkalization by Sodium bicarbonate Keep blood pH 7.50–7.55. Seizures, treat with Benzodiazepines if seizure refractory use Phenobarbital 10–15 mg/kg, The medication contraindication in CA toxicity are: Class I antiarrhythmic (lidocaine, phenytoin, and flecainide), Class III antiarrhythmic (amiodarone, sotalol), Β-blockers, Ca channel blockers, Physostigmine and Flumazenil [22, 23].
\nAspirin is the most common analgesic antiplatelet therapy used in cardiovascular and cerebrovascular disease. Aspirin is over-the-counter drugs and widespread used lead to accidental and intentional toxicity [24].
\nSalicylate Inhibit cyclooxygenase leads to decreased synthesis of prostaglandins; prostacyclin and thromboxane. It also leads to platelet dysfunction and gastric mucosal injury. Salicylate Stimulate the chemoreceptor trigger zone in the medulla which causes nausea and vomiting. Also activate respiratory centre of the medulla leading to hyperventilation and respiratory alkalosis. Uncoupling of oxidative and Inhibit the Krebs which lead to metabolic acidosis [25].
\nSalicylate toxicity divided to
Acute salicylate toxicity manifests initially through GI, CNS effects and metabolic effects. Gastric irritation, vomiting and nausea may predominate early in the course and are more predominant in the acute poisoning. Rising CNS salicylate concentrations produce tinnitus, diminished auditory acuity, vertigo and hyperventilation. As the poisoning continues, the CNS effects may progress to agitation, hallucinations, delirium, seizure and lethargy. The metabolic effects of salicylate toxicity cause uncoupling of oxidative phosphorylation leading to temperature elevation (an indicator of severe toxicity) and a large anion gap metabolic acidosis. Subsequent squeal of salicylate toxicity include renal failure, acute lung injury and platelet dysfunction.
\nIn contrast, chronic poisoning occurs over a longer period of time, when patients ingest more drug than they can eliminate over a prolonged period. These patients tend to be older and the overdose is unintentional. The initial presenting signs and symptoms include those of acute toxicity although with slower onset and lesser severity. Chronic toxicity may easily be confused in the elderly for sepsis, ketoacidosis, delirium, dementia, CHF or respiratory failure. Diagnostic delay in the chronically poisoned patient has been shown to cause increased morbidity and mortality.
\nStabilization of the airway, breathing and circulation are the first steps in management. Intubation may increases the severity of the aspirin toxicity, so it is better to be avoided, but if intubation is necessary patients need appropriately high minute ventilation sitting. In case of volume depleted and acidosis, start treatment with I. V fluid. Gastrointestinal decontamination with Activated charcoal may help in early ingestion. Whole bowel irrigation (WBI) is useful in case of massive ingestions or sustained preparation or enteric-coated. Sever Salicylate toxicity treated with serum Alkalinisation by sodium bicarbonate with a aim of a serum pH of ~7.5.Patients may need haemodialysis and the indications for haemodialysis are clinical deterioration, severe acid-base disturbance, altered mental status, and acute lung injury, failure of serum and urine alkalinisation and renal failure [26, 27, 28].
\nOpioid abuse is a significant medical and social problem in the world. In the past 10 years, the number of abuses and deaths from opioid overdoses had been increased. Opioids are all substances related to opium. They have analgesic and sedative effects. Opiate is extracted from the poppy plants [29].
\nThere are three main opioid receptors: μ (mu), κ (kappa), and δ (delta), and Opioids have agonists effect on this receptors. Stimulation of opioids receptors will cause miosis, respiratory depression, cough suppression, euphoria and decreased GI motility.
\nClassic signs of opioid intoxication toxidrome, depressed mental status, decreased respiratory rate miosis, (constricted) pupils. Other finding includes: decreased bowel sounds orthostatic hypotension, urinary retention and localized urticaria. Normal pupil examination can be seen, meperidine diphenoxylate, propoxyphene toxicity and co-ingestion of other toxin such as sympathomimetic or anticholinergic.
\nSame opioids have specific clinical feature (Table 2) [30, 32]:
\nOpioids agent | \nSpecific clinical feature | \n
---|---|
Dextromethorphan | \nSerotonin toxicity; at high doses | \n
Loperamide | \nQRS and QT prolongation; Wide-complex tachycardia | \n
Meperidine | \nSeizure, normal pupils size Serotonin syndrome (in combination with other agents) | \n
Methadone | \nlong-acting; QT prolongation, Torsade de Pointes | \n
Oxycodone | \nQT interval prolongation | \n
Tramadol | \nSeizure | \n
Heroin | \nAcute lung injury | \n
Opioids with specific clinical feature.
Body packing: swallowing packets or containers of drug for the purposes of smuggling.
Body stuffing: swallowing of a smaller quantity of drug because of fear of arrest.
Secure Airway and maintain adequate oxygenation and ventilation by using bag-valve mask are the first important steps in treatment; serum glucose should be checked. After that administer naloxone 0.4 mg IV, in non-opioid-dependent with minimal respiratory depression abut if patient is opioid-dependent present with minimal respiratory depression, administer small dose of naloxone, 0.1 mg IV, because larger doses can induce opioid withdrawal symptoms. Patients presenting with apnea or near-apnea and cyanosis, start naloxone, 2 mg IV regardless of drug use history, can be repeated IV every 3 min [30, 31, 32].
\nCocaine is one of the most potent Sympathomimetic, extracted from the leaves of the coca by indigenous to South America; therapeutically, first time Cocaine was used in 1884 as a local anaesthetic for ophthalmologic procedures. In the United States Cocaine is one of the most common causes of acute drug-related emergency department visits.
\nCocaine stimulates alpha and adrenergic receptors by increasing levels of norepinephrine, causing vasoconstriction in cardiovascular system, also inhibits neuronal serotonin reuptake which lead to euphoria. Cocaine blocks Sodium (Na+) channel causing QRS interval prolongation [33, 34].
\nCocaine toxicity may cause sympathomimetic and vasoconstrictive effects on variety systems (cardiovascular, CNS …etc.).
\nCardiovascular: patients with cocaine toxicity present with high blood pressure and dysrhythmias include tachycardia, such as sinus tachycardia, SVT, and AF. ECG changes include rightward shift of the terminal portion of the QRS complex and prolongation the QT interval. Patients may present with acute coronary syndromes (cocaine-associated acute coronary syndrome), aortic and coronary artery dissection, myocarditis and cardiomyopathy. CNS: patients with Cocaine present with a variety CNS clinical features including: agitation, seizures, and coma. Pulmonary: mainly seen in patients who smoke crack cocaine includes pulmonary haemorrhage, barotrauma, pneumonitis and asthma.
\nGastrointestinal: Cocaine may cause intestinal ischemia, bowel necrosis and ischemic colitis, also increase risk for bleeding and ulcer perforation. Renal: acute kidney failure may occur because of rhabdomyolysis [35, 36, 37].
\nSecuring the airway and adequate breathing are initial steps in treatment. CNS manifestation (agitation, seizure) treated with sedation by Benzodiazepines, patient with Hyperthermia should be cooled rapidly, severe hypertension not responding to sedation can be treated with a sodium nitroprusside infusion or phentolamine; (avoid Β-ac blockers). Cocaine toxicity with acute coronary syndrome are treated with aspirin and nitroglycerin also may add calcium channel blockers, wide-complex tachycardia with cocaine toxicity treated with serum alkalinisation by sodium bicarbonate, make sure serum Ph do not exceed 7.55. Intravenous lipid emulsion can be used in severe cocaine toxicity, with refractory cardiovascular instability or refractory wide-complex tachycardia [37].
\nCardiac glycosides were used in treatment of heart failure since long time. Since 1785 glycosides found in plants like lily of the valley foxglove and oleander. Digoxin is most common digitalis drug used today for treatment of atrial fibrillation and congestive heart failure [38].
\nDigoxin inhibits Na + -K + -ATPase during repolarization which leading to increase in intracellular sodium and a decrease in intracellular potassium leading to increase in the intracellular concentration of calcium causing Positive inotropic, also increase automaticity and shorten the repolarization intervals of the atria and ventricles [39].
\nDigoxin toxicity divided to acute and chronic toxicities.
\nThe cause of acute toxicity is usually intentional or accidental ingestion, symptoms usually abrupt in onset, patients present with nausea, vomiting, non-specific abdominal pain, headache and dizziness. Sever toxicity may cause confusion and coma, Bradydysrhythmia and atrioventricular block or supraventricular tachydysrhythmia and hyperkalaemia. Xanthopsia is a classic eye future in digoxin toxicity (viewing yellow-green halos around objects), but the most common finding is nonspecific changes in their colour vision. Serum digoxin level usually marked elevated [40, 41].
\nChronic toxicity is commonly and mainly seen in elderly patients and common causes are interaction with other medications (calcium channel antagonists, amiodarone, β-receptor antagonists, and diuretics) or renal insufficiency which causes decree the clearance of digoxin.
\nIn contract of acute toxicity, where Gastrointestinal symptoms are prominent in chronic toxicity CNS symptoms (weakness, fatigue, confusion, or delirium) are more prominent. Ventricular dysrhythmias are commonly seen in chronic toxicity. Serum potassium level can be normal or decreased, also serum digoxin level usually minimally elevated [40, 41].
\nGeneral supportive care is an Initial step in treatment of digoxin toxicity; it includes securing airway and adequate ventilation and boluses of fluid IV in case of hypotension. Activated charcoal helps in early acute ingestion [42], Atropine can be given in case of Symptomatic bradycardia). Digoxin-specific antibody fragments (digoxin-Fab) are antidotes for digoxin. The indication to use (digoxin- Fab) includes Life-threatening dysrhythmias unresponsive to standard therapy and hyperkalaemia excess 6 mEq/L. [43] Digoxin-Fab doses are based on the total-body load of digoxin, which can be calculated from either the estimated dose ingested or the serum digoxin level, each vial of Digoxin-Fab reverses approximately 0.5 mg of ingested digoxin. If the amount of ingested digitalis is unknown, digoxin Fab 10 vials for adults empirically can be given. Hyperkalaemia is treated with insulin, dextrose, sodium bicarbonate. The use of calcium salts in digoxin induced hyperkalaemia is controversial because old literature shows increase incidence of ventricular dysrhythmias and increase mortality [44].
\nBeta adrenergic antagonists (beta blockers) are groups of medications which have been used in treatment of different cardiovascular, neurological and ophthalmological diseases more than 30 years, Bête blockers toxicity has significant morbidity and mortality [17].
\nBeta receptors are divided by location and action to beta 1, beta 2, and beta 3 (see the Table 3).
\n\n | Location | \nAction | \nAntagonism | \n
---|---|---|---|
B1 | \nMyocardium Kidney Eye | \nIncreases inotropy Increases chronotropy Stimulates renin release | \nDecreases inotropy Decreases chronotropy Inhibits renin release | \n
B2 | \nBronchial smooth muscle Skeletal muscle Liver Vascular | \nbronchodilation Relaxes uterus Increases force of contraction Stimulates glycogenolysis and gluconeogenesis Vasodilation | \nCauses bronchospasm Inhibits glycogenolysis and gluconeogenesis Minimal vasoconstriction | \n
B3 | \nAdipose tissue Skeletal muscle | \nStimulates lipolysis Stimulates thermogenesis | \nInhibits lipolysis Inhibits thermogenesis | \n
Beta receptor: Locations and actions.
There are two groups of beta-blockers: selective and non-selective.
\nCompetitive antagonism of the beta receptor decreases cellular levels of cyclic adenosine monophosphate (cAMP). Beta-1 selective blocker causing in depressed myocardial contractility, decreased automaticity in pacemaker cells, and decreased conduction through the AV node. Non- selective beta blockade results in systemic effects including bronchoconstriction, impaired gluconeogenesis and decreased insulin release. Same Beta blockers (e.g., propranolol) have high lipid solubility leading to rapid cross of the blood brain barrier into the central nervous system, causing a neurological manifestation such as seizures and delirium [45, 47].
\nThe major system affected by β-blocker toxicity is the cardiovascular system; patients present with bradycardia and hypotensive. The cause of bradycardia is sinus node suppression or conduction abnormalities but ingestion of β-blockers with partial agonist activity may cause hypertension and tachycardia as early presentation. The β-blockers with sodium channel block affect may cause a wide-complex bradycardia.
\nSotalol causes potassium channels block leading to prolonging the QT interval.
\nΒ-Blockers also have effect on CNS and pulmonary system. Neurologic features include delirium, coma and seizures with more lipophilic. Β-blockers (propranolol) have more neurological manifestations. Bronchospasm and hypoglycaemia can be in β-blockers toxicity [47, 48].
\nGI decontamination can be done by giving Activated charcoal within 1 h of ingestion and air way is the main aim treatment in beta-blocker toxicity focusing on restore perfusion to critical organ systems by increasing cardiac output by: fluid resuscitation and glucagon (3–10 mg), vasopressor (e.g., epinephrine) and high dose Insulin- glucose (insulin 1 unit/kg IV bolus). Intravenous lipid emulsion therapy may be used in case of sever toxicity and refractory to treatment. In case of refractory to pharmacologic therapy, haemodialysis, haemoperfusion, cardiac pacing, placement of intra-aortic balloon pumps can be used. Wide QRS-interval dysrhythmias due to sodium channel blockade treated with sodium bicarbonate 2–3 mEq/kg over 1–2 min [49, 50].
\nCalcium channel blockers (CCBs) are mainly used in the treatment of cardiovascular diseases such as hypertension, coronary artery disseise- CAD and cardiac arrhythmias Calcium channel blockers one most prescribed cardiovascular drugs and can be immediate-release or extended-release [17].
\nThe calcium channel blockers (CCBs) can be divided into two major groups based upon their major physiologic effects: the dihydropyridines, group which mainly block the L-type calcium channels in the vasculature and the non-dihydropyridines, which selectively block L-type calcium channels in the myocardium such as verapamil. Dihydropyridine group toxicity causes arterial vasodilation and reflex tachycardia, whereas non-dihydropyridines toxicity cause peripheral vasodilation decreased cardiac inotropy, and bradycardia [46].
\nCardiovascular system is the most affected system in CCBs toxicity. Patient present with hypotension and bradycardia or reflex tachycardia. Verapamil or diltiazem toxicity usually patients present with sinus bradycardia, on the hand dihydropyridine overdoses cause peripheral vasodilatation causing reflex tachycardia [55]. CCBs have not primary effect on pulmonary and CNS System; CNS symptoms (seizures, delirium, and coma) occur secondary to decrease organ perfusion. Cardiogenic pulmonary oedema and acute lung injury (non-cardiogenic pulmonary oedema) have also been reported in severe toxicity [48].
\nFirst step in management is secure airway, stabilize ventilation and circulation.
\nDecontamination can be done by oral activated charcoal if patient present within 1 h of ingestion also the whole-bowel irrigation is useful in case of extended-release CCBs. Hypotension treated with IV fluid, Calcium chloride or calcium gluconate, glucagon (3–10 mg), if not responding start Vasopressors (e.g., norepinephrine). If symptoms refractory to vasopressor therapy start, high dose Insulin -glucose. If patient still not responding, lipid emulsion can be started. Finally, circulatory support measures, such as the placement of intra-aortic balloon pumps may be used in case of sever toxicity not responding to standard therapy [49, 50, 51].
\nCarbon monoxide (CO) is an odourless, tasteless, colourless and non-irritating gas.
\nPotential sources of Carbon monoxide (CO) are automotive exhaust, fuelled heaters, Wood- or coal-burning stoves, Structure fires and gasoline-powered generators other than fires.
\nThe incidence of co -poisoning increases during winter time because the use of space heaters, wood-burning stoves and charcoal burning for heat.
\nCarbon monoxide (CO) diffuses fast in the pulmonary capillary membrane and because of his rapid binding affinity (more than oxygen by 200 times), carbon monoxide bind to haemoglobin, that cause impaired releasing oxygen to tissue leading to shift the oxyhaemoglobin dissociation curve to the left [51].
\nCarbon monoxide poisoning have variable clinical picture depend on severity of exposure ranging from non-specific symptoms like headache, nausea and dizziness in mild to moderate cases to confusion, seizure and coma in severe cases patients may present with mild fever, tachycardia, tachypnoea and hypertension. Acute myocardial injury and life-threatening dysrhythmias are the most cardiovascular complications in case of severe Carbon monoxide poisoning. Delayed neuropsychiatric syndrome is long term neurological complication in severe cases characterized with different symptoms including cognitive deficiency, movement disorders and focal neurologic deficit. The standard pulse oximetry cannot differentiate carboxyhaemoglobin from oxyhaemoglobin, so it is unreliable in the diagnosis or screen carbon monoxide poisoning, so measuring carboxyhaemoglobin level in an arterial blood gas helps in diagnosis [52, 53, 54, 55].
\nAfter securing the airway, the most important step in treatment is oxygen 100% via non-rebreathing mask or intubation and mechanically ventilation with 100% oxygen if the patient is comatose and cannot secure his air way, half-life of carboxyhaemoglobin in room air 250–320 min while via non-rebreathing with 100% oxygen decreased to 90 min. Hyperbaric oxygen therapy could be considered in certain cases, the indication for Hyperbaric oxygen includes Pregnancy with carboxyhaemoglobin level > 15%, Carboxyhaemoglobin >25%, evidence of acute myocardial ischemia, and severe metabolic acidosis [56].
\nIron tablets are usually available in homes with small children and young women especially pregnant women. Because of its colour, sugar taste and appearance like a candy make iron tablet more attractive for accidental ingestion for children [57].
\nIron exerts a direct corrosive effect on the gastrointestinal tract at high plasma concentrations; it also possesses cytotoxic actions, particularly on the liver, leading to hepatocellular necrosis. Additionally, iron has a direct cardio- toxic effect acting as a negative inotrope and inhibits thrombin leading to a coagulopathy independent of hepatotoxicity. The direct corrosive effects and cellular toxicity contribute to metabolic acidosis [58].
\nSerious iron poisoning usually causes symptoms within 6 h of the overdose and if the ingested elemental iron more than 20 mg/kg body, the symptoms of iron poisoning typically occur in 5 stages:
First step stabilize the air way, breathing and circulation. An abdominal x-ray may be helpful to confirm the presence of iron tablets. Consider GI decontamination by whole bowel irrigation if the patient is stable and has no contraindications, especially for large ingestions of modified release products, providing the airway can be protected. Activated charcoal does not bind iron. Asymptomatic patients need observation for 6 h and serum iron levels less than 300–350 mcg/dL may be discharged.
\nChelation therapy with deferoxamine is indicated for patients with serum iron levels >350 mcg/dL and have evidence of toxicity, or levels of >500 mcg/dL regardless of signs or symptoms. In patients with significant clinical manifestations of toxicity persistent emesis, metabolic acidosis, chelation therapy should not be delayed while one awaits serum iron levels. Haemodialysis does not remove iron effectively but should be considered on a supportive basis for acute renal failure as this will facilitate removal of the iron-deferoxamine complex [61, 62].
\nThe term toxic alcohol has generally referred to isopropanol, methanol, and ethylene glycol (EG). Poisoning involving toxic alcohols are relatively uncommon, but remain important causes of suicide or epidemic poisonings; Mortality and morbidity of toxic alcohols are high if prompt diagnosis and treatment are not initiated rapidly [63, 64].
\nMethanol also called methyl alcohol is found in paint removers or photocopying fluid, de-icing products and windshield wiper fluid. Methanol metabolism in the liver by alcohol dehydrogenase to formaldehyde. Aldehyde dehydrogenase then rapidly converts formaldehyde to formic acid with no appreciable accumulation of formaldehyde in the blood.
\nThe formic acid inhibits cytochrome c in the mitochondria, shifting the cell to anaerobic glycolysis, leading to lactic acid accumulation. The clinical features of methanol poisoning are the triad of severe anion gap metabolic acidosis, visual changes, and mental status depression. Other methanol intoxication symptoms include headache, light-headedness, nausea, vomiting, abdominal pain and dyspnoea. Methanol may produce pancreatitis by direct toxic effect on the pancreas.
\nEthylene glycol is found in radiator antifreeze, metal cleaners, and degreasing agents. It has no smell or colour and tastes sweet. Ethylene glycol is metabolized in the liver to glycolaldehyde by alcohol dehydrogenase. Glycolaldehyde is then converted to glycolic acid which is then converted to oxalic acid. Oxalic acid combines with serum calcium to form the classic calcium oxalate crystals found in the urine of patients who have consumed ethylene glycol.
\nEthylene glycol causes an elevated anion gap metabolic acidosis. The neurologic effects of ethylene glycol are coma, seizures, meningism, muscle spasms, and paralysis of the extraocular muscles. It can also affect the heart and lungs, causing tachycardia, hyperventilation, ARDS, and heart failure. Hypocalcaemia and resulting QT prolongation are due to serum calcium combining with oxalic acid. Lastly, kidney failure is due to these calcium crystals depositing into renal tubules.
\nIsopropyl alcohol is found in solvents and disinfectants. It is also found in mouthwashes, lotions, as well as rubbing alcohol and hand sanitizers. It is also hepatically metabolized by alcohol dehydrogenase to acetone. Isopropanol produces an increased osmole gap; however, it normally does not produce a metabolic acidosis unless concomitant hypotension causes lactic acidosis. It can cause haemorrhagic gastritis and profound inebriation with cerebellar signs and coma [64, 65, 66, 67, 68, 69, 70].
\nAn osmolar gap more than 10 mOsm/kg is suggestive of ethylene glycol, methanol, isopropanol, ethylene oxide, or acetone toxicity. A high anion gap metabolic acidosis may be revealed at later stages of methanol and ethylene glycol poisoning. Hypoglycaemia may be detected with isopropanol, while hyperglycaemia and hypocalcaemia may be detected in methanol and ethylene glycol poisonings, respectively. Hyperkalaemia due to acidosis is observed in methanol and ethylene glycol poisoning, whereas hypokalaemia due to vomiting may occur in ethanol intoxication.
\nUrine calcium oxalate crystals can be seen in ethylene glycol intoxication. These findings should be evaluated together with the other manifestations and observations [71, 72].
\nAny patient with serious poisoning may present in a critical condition. As with all poisoned patients, initial stabilization must be instituted before other possible treatments can be employed Initial evaluation should be focused on the improvement of vital signs: airway, respiration and circulation.
\nConsider toxic alcohol poisoning in a patient with an unexplained elevated anion gap metabolic acidosis and elevated osmolar gap.
\nFomepizole competitively inhibits alcohol dehydrogenase, which is involved in the metabolism of all alcohols, including ethanol. It is given to prevent the build-up of toxic metabolites from ethylene glycol (glycolic acid, glyoxylic acid, and oxalic acid) and methanol (formic acid) whose deposition in tissues can cause irreparable damage.
\nFomepizole is indicated for methanol or ethylene glycol ingestion resulting in a metabolic acidosis with an elevated osmolar gap and a serum Methanol or ethylene glycol level of at least 20 mg/dL.
\nHaemodialysis is indicated for toxic alcohol poisoning with an elevated osmolar gap and/or severe metabolic acidosis refractory to standard therapy, refractory hypotension, or end organ damage (i.e. acute renal failure. Vitamin Supplementation: Give folic or folinic acid to patients with methanol toxicity to divert metabolism away from formic acid to carbon dioxide and water. Give folic acid, pyridoxine, and thiamine to patients with EG toxicity to divert metabolism to nontoxic metabolites [73, 74, 75, 76].
\nOrganophosphates (OP) are used in insecticides for domestic and agricultural use. They are also the main toxins in nerve gases like Sarin. OP pesticide self-poisoning is a major clinical and public-health problem across much of rural Asia [77].
\nThe most serious poisoning of OP occurs by ingestion; cutaneous absorption and inhalation of sprays rarely cause serious toxicity. OP is extremely toxic pesticides, which produce acetylcholine excess with muscarinic, nicotinic and CNS effects.
\nPatients present with degrees of cholinergic crisis, usually within 4 h of ingestion or exposure. Specific manifestations include: Muscarinic manifestations like bronchospasm, vomiting, pinpoint pupils, bradycardia and hypotension, excessive sweating, lacrimation, salivation, profuse diarrhoea and urination (Table 4).
\nDiarrhoea | \n
Urination | \n
Miosis | \n
Bronchospasm | \n
Emesis | \n
Lacrimation | \n
Salivation | \n
DUMBELS mnemonic for signs of cholinergic excess.
Over-stimulation of nicotinic receptors causes tachycardia, hypertension and sweating. Accumulation of acetylcholine at the neuromuscular junction causes initial stimulation followed by depolarization and paralysis. This appears first as fasciculations, cramps and muscle weakness. Central nervous system (CNS) effects include delirium, coma and seizures. Most deaths are due to respiratory failure. Toxicity from gradual, cumulative exposure may be much more subtle. These patients commonly exhibit vague confusion or other central nervous system complaints; mild visual disturbances; or chronic abdominal cramping, nausea, and diarrhoea. A unique effect of organophosphorus insecticides results from “aging,” the irreversible conformational change that occurs when the organophosphorus agent is bound to the cholinesterase enzyme for a prolonged time, causing clinical effects to persist for a prolonged time. On average, some aging for commercial organophosphorus agents will occur by 48 h but may take longer. The intermediate syndrome is distinct from OP in the following ways: start within 24–96 h after recovery from acute cholinergic crisis, cranial nerves INNERVATED muscle and proximal muscles weakness, and rapid clinical recovery over 4–18 days. Any patient with a clinically apparent cholinergic syndrome should be treated empirically without waiting for laboratory confirmation of decreased cholinesterase activity [78].
\nMedical management of OP pesticide poisoning demands close observation, timely institution of antidote in adequate doses and duration and good supportive. The Treating staff should wear protective clothing. The patient’s clothes should be removed and destroyed and the patient should be showered in a designated decontamination area.
\nTreatment includes: resuscitation of patients giving oxygen, a muscarinic antagonist (usually atropine), fluids and an acetylcholinesterase reactivator (an oxime that reactivates acetylcholinesterase by removal of the phosphate group).
\nRespiratory support is given as necessary. Patients must be carefully observed after stabilization for changes in atropine needs, worsening respiratory function because of intermediate syndrome, and recurrent cholinergic features occurring with fat-soluble OP [79].
\nPoisoned patient in emergency department have unique Approach because of difficulties in obtain history, poisoned patients need careful physical examination looking for toxidromes or sign of illegal drugs abuse. Intoxicated patient’s management started with resuscitation and stabilization of air way, breathing and circulation. Consider decontamination in early time post ingestion. Most of the patient need laboratory test includes full cell count and electrolytes and kidney functions, specific drug level. Paracetamol level must be send for every present with history intestinal over dose. Symptomatic treatment is cornerstone treatment for post intoxicated patient also antidotes need for specific substances in specific conditions. Finally physicians in emergency department need to call the local poisoning centre to help them in management.
\nThough the “discovery” of biofilms is ascribed to Anton van Leeuwenhoek in 1676 using a novel magnifying device, and possibly to Robert Hooke two decades earlier, and biofilms were recognised in a marine setting about a century ago, they were of no medical interest until two studies described them in a medical device and in sputum in 1972 and 1974 respectively. The latter was a description of aggregates of
Examples of implantable devices.
Anatomical sites of common implantable devices.
Many definitions of “biofilm” are found in the literature, and they can be based on either structure or function. Many of the definitions and their accompanying images are derived from in vitro models, and the appearance of mushroom-like structures and water-channels are not seen in biofilms occurring in vivo [6]. A definition based on functional aspects of biofilms is more useful in a medical context. This could be reduced to a population of bacteria or other micro-organisms, often associated with a surface, and enveloped in an extracellular matrix, showing insusceptibility to antimicrobials and to the host immune system, and ability to persist for long periods.
The basis of this functional definition is the paucity of nutrients, including iron, and oxygen in the depths of the biofilm leading to a bacterial stress response caused by a crisis in energy generation and transport [7]. The bacterial stress response is mediated by the intracellular signal sigma-B. The bacterial response to this is to downregulate all synthetic functions not needed in biofilm mode, such as cell wall material, toxin and other non-essential protein synthesis, and DNA replication. These are the targets for common antibiotics, and beta-lactams, glycopeptides, aminoglycosides, macrolides and fluoroquinolones all become significantly less effective against biofilm bacteria. Other factors contribute to the lack of effect of antibiotics, including a slowing of their penetration into the biofilm, though this is rarely a major factor. The bacterial stress response results in significantly reduced cell metabolic activity and loss of some synthetic activities leading to auxotrophy for heme and menadione, and sometimes other substances such as thymidine. This biofilm phenotype is crucial to the clinical impact of biofilm infections; the colonies of biofilm bacteria when grown from clinical samples in the laboratory are typically less than ten times the size of their planktonic counterparts, and are known as small colony variants or SCV. The molecular control and regulation of biofilm phenotype has been described in detail by Proctor et al. [8]. SCV are important in biofilm infections not only because their metabolism leads to antibiotic insusceptibility, but because, though they can be internalised by professional and non-professional phagocytes, they are not killed and survive inside the phagocytic cells. Auxotrophic SCV of
The biofilm phenotype, and SCV in particular, are important in treatment of biofilm infections. Surviving intracellular bacteria are protected from further immune assault and from most therapeutic antibiotics, which do not accumulate inside host cells sufficiently to kill SCV [24]. These factors mean that the amount of antibiotic required to kill bacteria in biofilm mode is typically 500–1000 times the minimum inhibitory concentration as measured in the clinical laboratory. Such concentrations are not achievable by intravenous or oral therapy, and eradication of biofilm infection usually requires extensive surgery to debride the site and to remove all surgical hardware.
Development of biofilms in surgery depends on a sequence of events. Initially, the causative bacteria must be able to gain access to the site of biofilm formation, usually an implantable device. In modern surgery most device pathogens originate on the patient’s skin or mucous membranes, consisting mainly of coagulase-negative staphylococci (CoNS), typically
The sequence of events involved in development of a biofilm infection involving a surgically implanted device are (Figure 3):
Access to the device from the source. Though heavy contamination of the air in the operating environment has historically been associated with surgical infection, modern operating room design and ventilation has meant that this source has declined in importance, and most surgical infections are caused by bacteria originating on the patient’s skin or mucous membranes. Bacteria reach the incision from the cut edges of the skin, or from contamination from surrounding skin surfaces, during surgery. The causative bacteria are therefore often present when the device is implanted.
Attachment to the device. Many bacteria possess adhesins on their surfaces that allow them to attach to biomaterials (vitronectin—binding protein etc) but more often they employ specific adhesins for the glycoproteins, platelets and other host-derived materials that rapidly coat all implanted materials [26, 27].
Once bacteria have attached to the surface or conditioning film, they begin to proliferate and to develop intercellular adhesins such as polysaccharide intercellular adhesin (PIA) in staphylococci. This substance is integral to further development of biofilm, and is encoded by the
Sequence of events in development of biofilm infection. Here implant has an antimicrobial coating, but within minutes this is covered by a glycoprotein conditioning film produced by the patient. This usually prevents the activity of the coating and bacteria now adhere to the conditioning film. Within a few hours the attached bacteria begin to produce an extracellular matrix and to multiply. Powerful antibacterial activity is essential now, as after this point, it is almost inevitable that a biofilm will develop, within a few weeks.
Clear understanding of the sequence of events and periods of risk is essential for effective planning of preventative measures.
Since the days of Semmelweis, Lister and others in the mid–to late 1800s, personal hygiene of the surgeon, aseptic technique and antisepsis have become accepted norms. Since the 1950s, when bacteria-laden operating room air was identified as a major factor in surgical infection [36], greatly improved practices and ventilation systems have made this a minor source. Two main forms of ventilation are in use in modern operating rooms: plenum, and laminar flow with high efficiency particulate air (HEPA) filtration. While it is clear that the numbers of airborne bacteria are significantly reduced when laminar flow is used [37] there has never been a clear causative link between either this reduction or the actual bacteria and surgical infection, leading the USA CDC to downgrade their initial recommendation [38]. More recently, reports have appeared of small but significantly increased infection rates when laminar flow is used [39, 40] and this appears to be due to flaws in its design and manner of use [41]. For most types of implant surgery, plenum (conventional) ventilation appears to be satisfactory so long as other precautions are taken (Figure 4).
Sequence of surgical preventative events.
Care bundles have been proposed for infection reduction in various healthcare settings. A bundle is a collection of interventions that are expected to contribute to reduced risk of infection, but which singly might have weak or no evidence base. A measure such as ensuring that only three people are present in the operating room during a procedure is not supported by any clear evidence but it is intuitively likely to be beneficial if only in reinforcing operating room discipline. A bundle must be directed towards behaviour change on the part of relevant staff members, and it works best if they contribute to its content, and formally agree to abide by it. Some bundles insist on contents being evidence-based, but the quality of evidence is usually very weak for individual components. However, when bundles are properly applied, they are often very effective in reducing surgical infection [42, 43] and in any case they and their contents should form part of a well-managed surgical discipline. Usually no single component can be identified to explain their success, but clinical trial evidence has shown that violations of the bundle are associated with re-emergence of infection [43].
As the major source of pathogens is the patient’s skin, attention has been directed towards the effectiveness of preoperative skin preparation. Two main antiseptics are in use: chlorhexidine and povidone iodine. Each can be formulated in water or 70% alcohol. A report by the World Health Organisation (WHO) favouring chlorhexidine [44] has been called into question on the basis of quality of evidence [45]. However, sampling is usually by swabbing of the skin surface, and almost none of the many studies on surgical skin preparation explore the effectiveness of any agent on bacteria resident in the dermis, though an early study showed that full thickness skin biopsy was necessary [46]. This has since been confirmed [47, 48]. When skin biopsy is used, neither antiseptic in alcohol is able to eradicate resident skin bacteria, and though reduced, the remaining numbers are often sufficient to cause a biomaterial-associated infection [25]. Two studies on the penetration of both aqueous and alcoholic chlorhexidine into human skin using full thickness biopsy have found it to be minimal [49, 50]. Further measures are therefore necessary. Some researchers have investigated the effect of antiseptic-soaked material to protect the incision from the skin edges during surgery, and while this is commonly used, there have been no quantitative studies to show benefit. Intravenous antibiotics are almost universally used in surgery, ideally as a single dose 30–60 min before incision, but extra doses are commonly used postoperatively though they offer no benefit over that of the single pre-operative dose. Antibiotic prophylaxis is undoubtedly highly effective in reducing infection risk in many types of surgery, including colorectal surgery [51] and orthopaedic surgery [52] but probably less so in neurosurgery due to limited penetration of systemic antibiotics intracranially. However, it is probably inevitable that a small number of bacteria will reach the implant during operation, and further measures have been directed to attempts to eradicate these. As knowledge of attached bacteria and biofilms has shown that very high concentrations of antibiotics are necessary, some surgeons have used either antiseptic or antibiotic irrigation [53, 54], or have simply added antibiotic powder to the incision before closure [55, 56, 57] with successful reduction in infection rates and complications. This intervention gives extremely high local antibiotic levels not reachable by systemic administration, yet avoids most of the complications associated with the latter method.
Other methods of prevention accept that despite efforts, bacteria will reach the implant, and aim to prevent their attachment or to kill them when attached. Various “anti-fouling” surfaces have been investigated with the aim of allowing host cell and tissue proliferation but preventing bacterial attachment [58, 59] but none of these has yet reached clinical application, largely because of the complex relationship between implant surface, host tissue environment, and bacterial surface adhesins. Biomaterials designed to kill bacteria that do attach to them have generally included coatings of silver, antiseptic or antibiotic and combinations of these, often with a vehicle to bind the antimicrobial to the biomaterial surface. Such coatings have several disadvantages. The normal host reaction to the implant of deposition of plasma proteins [26, 27] also obliterates the antimicrobial coating in many cases, making it ineffective. Silver is susceptible to this due its avidity for proteins [60], and it can also be inactivated by chloride [61] which is abundant in the human body. Silver ions have also been shown to be cytotoxic in certain conditions [62]. Clinical studies on silver-processed devices give very variable results, and there is doubt about their cost-effectiveness in wound dressings [63]. A recent randomised controlled trial of silver-containing catheters intended to reduce ventriculitis in people with hydrocephalus shunts found no difference from plain catheters [64]. Another randomised controlled trial of silver-processed urinary catheters again found no significant difference from plain catheters [65]. In both of these clinical settings, biofilms play a key role, and the goal is to prevent bacterial proliferation and biofilm development on the catheters. Both have fluid containing proteins and chloride flowing through them.
Another approach has been impregnation of catheter material with antimicrobials. Though the impregnation processes differ, two catheter types can be considered: those containing rifampicin and minocycline, and those containing rifampicin and clindamycin. The first type has been used in central venous catheters [66] and external ventricular drains [67]. The second type has been used in hydrocephalus shunts and external ventricular drains. In all cases they have shown effectiveness in reducing device -related infection. The advantage of impregnation over coatings is that they give a long duration of activity: coatings are usually washed away by fluid after a few days, whereas the surface of an impregnated material is continually replenished by migrating antimicrobials until the depot in the material is depleted, usually several weeks later (Figure 5). This is important when the implantable device is at risk of contamination for an extended period.
Principle of impregnated biomaterial. Antimicrobial molecules are motile within the device matrix and can migrate to the surface to replace those removed by fluid flow.
In order to formulate an effective preventive strategy, knowledge of the source and nature of device pathogens and the period during which the device is at risk is essential (Table 1). As many biofilm infections are caused by micro-organisms originating in or on the patient, a knowledge of the distribution of these is useful. The normal bacterial flora of the skin differs according to age and sex, but particularly depending on the anatomical site. The most common bacteria found on the skin are staphylococci, particularly members of the CoNS. These are typified by
Implant/device | Duration of use | Main source of pathogens | Period of risk | |
---|---|---|---|---|
At insertion | During use | |||
Hydrocephalus shunt | indefinite | Patient’s skin | ++ | — |
External ventricular drain | Few days-weeks | Patient’s skin/environment | ± | ++ |
Joint replacement | Indefinite | Patient’s skin | ++ | ± |
Urinary catheter 1 | <28 days | Patient/environment | ± | ++ |
Urinary catheter 2 | ~90 days | Patient/environment | ± | ++ |
Peritoneal dialysis catheter | Indefinite | Patient/environment | ± | ++ |
Vascular graft | Indefinite | Patient | ++ | + |
Prosthetic heart valve | Indefinite | Patient | + | ++ |
Spinal instrumentation | Indefinite | Patient | ++ | ± |
Venous access device | Days—months | Patient/environment | ± | ++ |
Sutures | Days | Patient/healthcare worker | + | ± |
Periods of risk of infection of common implantable devices.
Topographical distribution of common biofilm pathogens (after Grice et al. [
The time at which the implant is at risk of microbial contamination also varies. While there is always a risk at the time of implantation, in some implants this is the main time, and the risk of subsequent contamination is proportionally small. Examples of this are hydrocephalus shunts and joint replacements. In other implants the risk at insertion is significantly outweighed by that during use. Examples are external ventricular drains (EVD) for raised intracranial pressure, urinary catheters, venous access catheters and peritoneal dialysis catheters, all of which can be contaminated from environmental sources or from the hands of staff or users during use. Other examples are vascular grafts and prosthetic heart valves, which are at risk from hematogenous seeding from bacteria entering the bloodstream at a distant site.
When planning strategies for prevention of biofilm infections involving antimicrobials, it is therefore important to match the antimicrobial to the most likely pathogen(s). If systemic antimicrobial prophylaxis is contemplated, then the adverse effects of this must be taken into consideration if there is a need for prolonged administration due to extended period of risk. If antimicrobial materials or devices are to be used, these must address not only the likely pathogen(s) but also the duration of protective activity required.
International guidelines indicate that for most surgical procedures, any systemic antimicrobial prophylaxis should be administered as one dose 30–60 min before start of surgery [75, 76]. Extension of this prophylaxis beyond 24 hours does not reduce surgical infection further, but it does increase the incidence of acute kidney injury and
The difficulty in treating biofilm infections in surgery emphasises the importance of effective prevention. However, this is not always possible. The nature of the biofilm phenotype and its implications for antibiotic treatment mean that further surgery is almost inevitable, and this usually involves removal of the device. This might be relatively simple, as in the case of a venous access catheter or a urinary catheter, but it can be both surgically complicated and hazardous, as in the case of spinal instrumentation or prosthetic heart valves.
Attempts to eradicate established biofilm with antibiotics usually fail. A comparison of treatment regimens for hydrocephalus shunt infections showed that results with shunt removal and antibiotics were significantly superior to those with antibiotics alone [79]. Successful treatment of joint replacement infections relies on device removal and extensive debridement of infected tissue, with prolonged antibiotic therapy. However, understanding of biofilm biology has led to advances in this area. The biofilm phenotype takes a few weeks to “mature” to the point where full insusceptibility to antibiotics is expressed, and this has been exploited in development of a regimen for treatment of prosthetic joint infection when the diagnosis can be made within 3–4 weeks of insertion [80]. In this regimen, known as Debridement, Antibiotics and Implant Retention (DAIR), surgical treatment of the infected joint prosthesis is carried out on a planned basis after careful investigation to establish the causative micro-organism and its antimicrobial susceptibilities, to allow consultation with specialists including Microbiology/Infectious Diseases, and to determine that the implant is stable (Figure 7). Infections due to multi-drug-resistant bacteria, fungi or multiple bacteria are not suitable for this approach. During the operation, the prosthetic components are exposed and the acetabular module is removed, leaving the main metal prosthesis in place. All infected tissue is removed and samples are sent for microbiological examination. Copious irrigation with antiseptic is applied, and biodegradable antibiotic—eluting beads can be inserted to provide high local concentrations. The choice of antibiotic in the beads should be made in consultation with a microbiologist. The joint is then closed and a long postoperative course of suitable antibiotics is then started [81]. The success rate of DAIR compared to conventional full implant removal and replacement is slightly lower. Moreover, despite the very thorough surgical debridement and long courses of antibiotics, often for over a year, relapse can occur [82], illustrating the difficulty in eradication of biofilms. DAIR spares the patient the much more extensive surgical removal of the main implant components, and the second surgery to inert fresh implants a few weeks later.
Possibility of retention of infected implant based on knowledge of biofilm phenotype maturation (based on Zimmerli and Trampuz, 2004) [
Most biofilm infections in surgery are chronic and persistent, sometimes for many years [83]. It is important to distinguish between “late infection,” implying an infection contracted long after surgery, such as hematogenously, and “delayed infection,” meaning that the infection appears long after surgery even though it was contracted at the operation. Delayed infection in spine instrumentation is usually due to infection with CoNS or
Acute postoperative biofilm infections usually appear within days or weeks of surgery, with failure of wound healing, drainage of pus or other fluid from the wound, local pain and swelling, fever and general illness. Delayed or chronic infections of joint prostheses present with persistent pain and restricted mobility, local swelling and sometimes a sinus. In the absence of a sinus, diagnosis might be delayed as it is often difficult to distinguish infective from mechanical complications. Aspiration of synovial fluid often gives a diagnosis but sensitivity is low [87, 88]. Delayed infection in spine instrumentation similarly presents with persistent pain, tenderness and possibly a draining sinus. Delayed infections in hydrocephalus shunts are very uncommon now that the preferred route of drainage is to the abdomen (ventriculoperitoneal, VP), but the ventriculo-atrial (VA) route is still used in some cases. In VP shunts infection usually presents within a few months as it leads to obstruction, but this does not happen in VA shunts and symptoms might not appear, or at least become recognisable, for several years. During this time, bacteria are being discharged from the biofilm in the shunt into the bloodstream, and this might give rise to periods of ill-health or sporadic fevers. It also provokes production of antibodies to the bacteria, and eventually the concentrations of circulating antigen and antibody, and therefore immune complexes, become so high that they precipitate on basement membranes of joints, renal glomeruli, alveoli and microvascular system. The presenting clinical picture can therefore be a confusing array of disorders from hematuria, hemorrhagic skin rashes, arthropathy, and chronic cough [89, 90]. Clinical diagnosis can therefore be very difficult, and a high level of suspicion is needed. Aspiration of cerebrospinal fluid from the shunt often gives the diagnosis, but blood cultures can be negative in the later stages.
Depending on the site of the infection and presence of an implant, sometimes blood cultures are positive, indicating systemic spread of the infection, and risk of sepsis. Blood inflammatory markers such as erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels are usually raised. Swab cultures from the wound might yield the infecting pathogen, but they might be misleading due to contamination [91]. Surgical exploration of the incision and deeper layers allows tissue samples to be taken and these are more likely to yield the pathogen(s). Such samples should always be taken during debridement surgery [92], using fresh instruments for each of up to six separate samples [81, 93]. In view of the anaerobic preference of
The impact of biofilm infections in surgery on healthcare systems, economies and personal lives of patients is immense. The financial cost can only be estimated and published figures do not usually take into account “unseen” costs such as loss of earnings due to disability, increased dependency, and financial burden on carers.
The physical and mental trauma of surgery such as joint replacement, reconstructive breast implant or hydrocephalus treatment can be made unimaginably worse by postoperative biofilm infection.
The significant difficulty in successfully treating biofilm infections with antibiotics, due largely to the biofilm phenotype, is now well recognised, and the importance of commensal bacteria previously thought to be harmless, such as
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She is also Invisalign certified. She’s working as a Senior Lecturer in the Department of Orthodontics, SRM Dental College since November 2019. She is actively involved in teaching orthodontics to the undergraduates and the postgraduates. Her clinical research topics include new orthodontic brackets, fixed appliances and TADs. She’s published 4 articles in well renowned indexed journals and has a published patency of her own. Her private practice is currently limited to orthodontics and works as a consultant in various clinics.",institutionString:null,institution:{name:"SRM Dental College",country:{name:"India"}}},{id:"323731",title:"Prof.",name:"Deepak M.",middleName:"Macchindra",surname:"Vikhe",slug:"deepak-m.-vikhe",fullName:"Deepak M. Vikhe",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/323731/images/13613_n.jpg",biography:"Dr Deepak M.Vikhe .\n\n\t\n\tDr Deepak M.Vikhe , completed his Masters & PhD in Prosthodontics from Rural Dental College, Loni securing third rank in the Pravara Institute of Medical Sciences Deemed University. He was awarded Dr.G.C.DAS Memorial Award for Research on Implants at 39th IPS conference Dubai (U A E).He has two patents under his name. He has received Dr.Saraswati medal award for best research for implant study in 2017.He has received Fully funded scholarship to Spain ,university of Santiago de Compostela. He has completed fellowship in Implantlogy from Noble Biocare. \nHe has attended various conferences and CDE programmes and has national publications to his credit. His field of interest is in Implant supported prosthesis. Presently he is working as a associate professor in the Dept of Prosthodontics, Rural Dental College, Loni and maintains a successful private practice specialising in Implantology at Rahata.\n\nEmail: drdeepak_mvikhe@yahoo.com..................",institutionString:null,institution:{name:"Pravara Institute of Medical Sciences",country:{name:"India"}}},{id:"204110",title:"Dr.",name:"Ahmed A.",middleName:null,surname:"Madfa",slug:"ahmed-a.-madfa",fullName:"Ahmed A. Madfa",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/204110/images/system/204110.jpg",biography:"Dr. Madfa is currently Associate Professor of Endodontics at Thamar University and a visiting lecturer at Sana'a University and University of Sciences and Technology. He has more than 6 years of experience in teaching. His research interests include root canal morphology, functionally graded concept, dental biomaterials, epidemiology and dental education, biomimetic restoration, finite element analysis and endodontic regeneration. Dr. Madfa has numerous international publications, full articles, two patents, a book and a book chapter. Furthermore, he won 14 international scientific awards. Furthermore, he is involved in many academic activities ranging from editorial board member, reviewer for many international journals and postgraduate students' supervisor. Besides, I deliver many courses and training workshops at various scientific events. Dr. Madfa also regularly attends international conferences and holds administrative positions (Deputy Dean of the Faculty for Students’ & Academic Affairs and Deputy Head of Research Unit).",institutionString:"Thamar University",institution:null},{id:"210472",title:"Dr.",name:"Nermin",middleName:"Mohammed Ahmed",surname:"Yussif",slug:"nermin-yussif",fullName:"Nermin Yussif",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/210472/images/system/210472.jpg",biography:"Dr. Nermin Mohammed Ahmed Yussif is working at the Faculty of dentistry, University for October university for modern sciences and arts (MSA). Her areas of expertise include: periodontology, dental laserology, oral implantology, periodontal plastic surgeries, oral mesotherapy, nutrition, dental pharmacology. She is an editor and reviewer in numerous international journals.",institutionString:"MSA University",institution:null},{id:"204606",title:"Dr.",name:"Serdar",middleName:null,surname:"Gözler",slug:"serdar-gozler",fullName:"Serdar Gözler",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/204606/images/system/204606.jpeg",biography:"Dr. Serdar Gözler has completed his undergraduate studies at the Marmara University Faculty of Dentistry in 1978, followed by an assistantship in the Prosthesis Department of Dicle University Faculty of Dentistry. Starting his PhD work on non-resilient overdentures with Assoc. Prof. Hüsnü Yavuzyılmaz, he continued his studies with Prof. Dr. Gürbüz Öztürk of Istanbul University Faculty of Dentistry Department of Prosthodontics, this time on Gnatology. He attended training programs on occlusion, neurology, neurophysiology, EMG, radiology and biostatistics. In 1982, he presented his PhD thesis \\Gerber and Lauritzen Occlusion Analysis Techniques: Diagnosis Values,\\ at Istanbul University School of Dentistry, Department of Prosthodontics. As he was also working with Prof. Senih Çalıkkocaoğlu on The Physiology of Chewing at the same time, Gözler has written a chapter in Çalıkkocaoğlu\\'s book \\Complete Prostheses\\ entitled \\The Place of Neuromuscular Mechanism in Prosthetic Dentistry.\\ The book was published five times since by the Istanbul University Publications. Having presented in various conferences about occlusion analysis until 1998, Dr. Gözler has also decided to use the T-Scan II occlusion analysis method. Having been personally trained by Dr. Robert Kerstein on this method, Dr. Gözler has been lecturing on the T-Scan Occlusion Analysis Method in conferences both in Turkey and abroad. Dr. Gözler has various articles and presentations on Digital Occlusion Analysis methods. He is now Head of the TMD Clinic at Prosthodontic Department of Faculty of Dentistry , Istanbul Aydın University , Turkey.",institutionString:"Istanbul Aydin University",institution:{name:"Istanbul Aydın University",country:{name:"Turkey"}}},{id:"240870",title:"Ph.D.",name:"Alaa Eddin Omar",middleName:null,surname:"Al Ostwani",slug:"alaa-eddin-omar-al-ostwani",fullName:"Alaa Eddin Omar Al Ostwani",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/240870/images/system/240870.jpeg",biography:"Dr. Al Ostwani Alaa Eddin Omar received his Master in dentistry from Damascus University in 2010, and his Ph.D. in Pediatric Dentistry from Damascus University in 2014. Dr. Al Ostwani is an assistant professor and faculty member at IUST University since 2014. \nDuring his academic experience, he has received several awards including the scientific research award from the Union of Arab Universities, the Syrian gold medal and the international gold medal for invention and creativity. Dr. Al Ostwani is a Member of the International Association of Dental Traumatology and the Syrian Society for Research and Preventive Dentistry since 2017. He is also a Member of the Reviewer Board of International Journal of Dental Medicine (IJDM), and the Indian Journal of Conservative and Endodontics since 2016.",institutionString:"International University for Science and Technology.",institution:{name:"Islamic University of Science and Technology",country:{name:"India"}}},{id:"42847",title:"Dr.",name:"Belma",middleName:null,surname:"Işik Aslan",slug:"belma-isik-aslan",fullName:"Belma Işik Aslan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/42847/images/system/42847.jpg",biography:"Dr. Belma IşIk Aslan was born in 1976 in Ankara-TURKEY. After graduating from TED Ankara College in 1994, she attended to Gazi University, Faculty of Dentistry in Ankara. She completed her PhD in orthodontic education at Gazi University between 1999-2005. Dr. Işık Aslan stayed at the Providence Hospital Craniofacial Institude and Reconstructive Surgery in Michigan, USA for three months as an observer. She worked as a specialist doctor at Gazi University, Dentistry Faculty, Department of Orthodontics between 2005-2014. She was appointed as associate professor in January, 2014 and as professor in 2021. Dr. Işık Aslan still works as an instructor at the same faculty. She has published a total of 35 articles, 10 book chapters, 39 conference proceedings both internationally and nationally. Also she was the academic editor of the international book 'Current Advances in Orthodontics'. She is a member of the Turkish Orthodontic Society and Turkish Cleft Lip and Palate Society. She is married and has 2 children. Her knowledge of English is at an advanced level.",institutionString:"Gazi University Dentistry Faculty Department of Orthodontics",institution:null},{id:"178412",title:"Associate Prof.",name:"Guhan",middleName:null,surname:"Dergin",slug:"guhan-dergin",fullName:"Guhan Dergin",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/178412/images/6954_n.jpg",biography:"Assoc. Prof. Dr. Gühan Dergin was born in 1973 in Izmit. He graduated from Marmara University Faculty of Dentistry in 1999. He completed his specialty of OMFS surgery in Marmara University Faculty of Dentistry and obtained his PhD degree in 2006. In 2005, he was invited as a visiting doctor in the Oral and Maxillofacial Surgery Department of the University of North Carolina, USA, where he went on a scholarship. Dr. Dergin still continues his academic career as an associate professor in Marmara University Faculty of Dentistry. He has many articles in international and national scientific journals and chapters in books.",institutionString:null,institution:{name:"Marmara University",country:{name:"Turkey"}}},{id:"178414",title:"Prof.",name:"Yusuf",middleName:null,surname:"Emes",slug:"yusuf-emes",fullName:"Yusuf Emes",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/178414/images/6953_n.jpg",biography:"Born in Istanbul in 1974, Dr. Emes graduated from Istanbul University Faculty of Dentistry in 1997 and completed his PhD degree in Istanbul University faculty of Dentistry Department of Oral and Maxillofacial Surgery in 2005. He has papers published in international and national scientific journals, including research articles on implantology, oroantral fistulas, odontogenic cysts, and temporomandibular disorders. Dr. Emes is currently working as a full-time academic staff in Istanbul University faculty of Dentistry Department of Oral and Maxillofacial Surgery.",institutionString:null,institution:{name:"Istanbul University",country:{name:"Turkey"}}},{id:"192229",title:"Ph.D.",name:"Ana Luiza",middleName:null,surname:"De Carvalho Felippini",slug:"ana-luiza-de-carvalho-felippini",fullName:"Ana Luiza De Carvalho Felippini",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/192229/images/system/192229.jpg",biography:null,institutionString:"University of São Paulo",institution:{name:"University of Sao Paulo",country:{name:"Brazil"}}},{id:"256851",title:"Prof.",name:"Ayşe",middleName:null,surname:"Gülşen",slug:"ayse-gulsen",fullName:"Ayşe Gülşen",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/256851/images/9696_n.jpg",biography:"Dr. Ayşe Gülşen graduated in 1990 from Faculty of Dentistry, University of Ankara and did a postgraduate program at University of Gazi. \nShe worked as an observer and research assistant in Craniofacial Surgery Departments in New York, Providence Hospital in Michigan and Chang Gung Memorial Hospital in Taiwan. \nShe works as Craniofacial Orthodontist in Department of Aesthetic, Plastic and Reconstructive Surgery, Faculty of Medicine, University of Gazi, Ankara Turkey since 2004.",institutionString:"Univeristy of Gazi",institution:null},{id:"255366",title:"Prof.",name:"Tosun",middleName:null,surname:"Tosun",slug:"tosun-tosun",fullName:"Tosun Tosun",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/255366/images/7347_n.jpg",biography:"Graduated at the Faculty of Dentistry, University of Istanbul, Turkey in 1989;\nVisitor Assistant at the University of Padua, Italy and Branemark Osseointegration Center of Treviso, Italy between 1993-94;\nPhD thesis on oral implantology in University of Istanbul and was awarded the academic title “Dr.med.dent.”, 1997;\nHe was awarded the academic title “Doç.Dr.” (Associated Professor) in 2003;\nProficiency in Botulinum Toxin Applications, Reading-UK in 2009;\nMastership, RWTH Certificate in Laser Therapy in Dentistry, AALZ-Aachen University, Germany 2009-11;\nMaster of Science (MSc) in Laser Dentistry, University of Genoa, Italy 2013-14.\n\nDr.Tosun worked as Research Assistant in the Department of Oral Implantology, Faculty of Dentistry, University of Istanbul between 1990-2002. \nHe worked part-time as Consultant surgeon in Harvard Medical International Hospitals and John Hopkins Medicine, Istanbul between years 2007-09.\u2028He was contract Professor in the Department of Surgical and Diagnostic Sciences (DI.S.C.), Medical School, University of Genova, Italy between years 2011-16. \nSince 2015 he is visiting Professor at Medical School, University of Plovdiv, Bulgaria. \nCurrently he is Associated Prof.Dr. at the Dental School, Oral Surgery Dept., Istanbul Aydin University and since 2003 he works in his own private clinic in Istanbul, Turkey.\u2028\nDr.Tosun is reviewer in journal ‘Laser in Medical Sciences’, reviewer in journal ‘Folia Medica\\', a Fellow of the International Team for Implantology, Clinical Lecturer of DGZI German Association of Oral Implantology, Expert Lecturer of Laser&Health Academy, Country Representative of World Federation for Laser Dentistry, member of European Federation of Periodontology, member of Academy of Laser Dentistry. Dr.Tosun presents papers in international and national congresses and has scientific publications in international and national journals. He speaks english, spanish, italian and french.",institutionString:null,institution:{name:"Istanbul Aydın University",country:{name:"Turkey"}}},{id:"171887",title:"Prof.",name:"Zühre",middleName:null,surname:"Akarslan",slug:"zuhre-akarslan",fullName:"Zühre Akarslan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/171887/images/system/171887.jpg",biography:"Zühre Akarslan was born in 1977 in Cyprus. She graduated from Gazi University Faculty of Dentistry, Ankara, Turkey in 2000. \r\nLater she received her Ph.D. degree from the Oral Diagnosis and Radiology Department; which was recently renamed as Oral and Dentomaxillofacial Radiology, from the same university. \r\nShe is working as a full-time Associate Professor and is a lecturer and an academic researcher. \r\nHer expertise areas are dental caries, cancer, dental fear and anxiety, gag reflex in dentistry, oral medicine, and dentomaxillofacial radiology.",institutionString:"Gazi University",institution:{name:"Gazi University",country:{name:"Turkey"}}},{id:"256417",title:"Associate Prof.",name:"Sanaz",middleName:null,surname:"Sadry",slug:"sanaz-sadry",fullName:"Sanaz Sadry",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/256417/images/8106_n.jpg",biography:null,institutionString:null,institution:null},{id:"272237",title:"Dr.",name:"Pinar",middleName:"Kiymet",surname:"Karataban",slug:"pinar-karataban",fullName:"Pinar Karataban",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/272237/images/8911_n.png",biography:"Assist.Prof.Dr.Pınar Kıymet Karataban, DDS PhD \n\nDr.Pınar Kıymet Karataban was born in Istanbul in 1975. After her graduation from Marmara University Faculty of Dentistry in 1998 she started her PhD in Paediatric Dentistry focused on children with special needs; mainly children with Cerebral Palsy. She finished her pHD thesis entitled \\'Investigation of occlusion via cast analysis and evaluation of dental caries prevalance, periodontal status and muscle dysfunctions in children with cerebral palsy” in 2008. She got her Assist. Proffessor degree in Istanbul Aydın University Paediatric Dentistry Department in 2015-2018. ın 2019 she started her new career in Bahcesehir University, Istanbul as Head of Department of Pediatric Dentistry. In 2020 she was accepted to BAU International University, Batumi as Professor of Pediatric Dentistry. She’s a lecturer in the same university meanwhile working part-time in private practice in Ege Dental Studio (https://www.egedisklinigi.com/) a multidisciplinary dental clinic in Istanbul. Her main interests are paleodontology, ancient and contemporary dentistry, oral microbiology, cerebral palsy and special care dentistry. She has national and international publications, scientific reports and is a member of IAPO (International Association for Paleodontology), IADH (International Association of Disability and Oral Health) and EAPD (European Association of Pediatric Dentistry).",institutionString:null,institution:null},{id:"202198",title:"Dr.",name:"Buket",middleName:null,surname:"Aybar",slug:"buket-aybar",fullName:"Buket Aybar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/202198/images/6955_n.jpg",biography:"Buket Aybar, DDS, PhD, was born in 1971. She graduated from Istanbul University, Faculty of Dentistry, in 1992 and completed her PhD degree on Oral and Maxillofacial Surgery in Istanbul University in 1997.\nDr. Aybar is currently a full-time professor in Istanbul University, Faculty of Dentistry Department of Oral and Maxillofacial Surgery. She has teaching responsibilities in graduate and postgraduate programs. Her clinical practice includes mainly dentoalveolar surgery.\nHer topics of interest are biomaterials science and cell culture studies. She has many articles in international and national scientific journals and chapters in books; she also has participated in several scientific projects supported by Istanbul University Research fund.",institutionString:null,institution:null},{id:"260116",title:"Dr.",name:"Mehmet",middleName:null,surname:"Yaltirik",slug:"mehmet-yaltirik",fullName:"Mehmet Yaltirik",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/260116/images/7413_n.jpg",biography:"Birth Date 25.09.1965\r\nBirth Place Adana- Turkey\r\nSex Male\r\nMarrial Status Bachelor\r\nDriving License Acquired\r\nMother Tongue Turkish\r\n\r\nAddress:\r\nWork:University of Istanbul,Faculty of Dentistry, Department of Oral Surgery and Oral Medicine 34093 Capa,Istanbul- TURKIYE",institutionString:null,institution:null},{id:"172009",title:"Dr.",name:"Fatma Deniz",middleName:null,surname:"Uzuner",slug:"fatma-deniz-uzuner",fullName:"Fatma Deniz Uzuner",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/172009/images/7122_n.jpg",biography:"Dr. Deniz Uzuner was born in 1969 in Kocaeli-TURKEY. After graduating from TED Ankara College in 1986, she attended the Hacettepe University, Faculty of Dentistry in Ankara. \nIn 1993 she attended the Gazi University, Faculty of Dentistry, Department of Orthodontics for her PhD education. After finishing the PhD education, she worked as orthodontist in Ankara Dental Hospital under the Turkish Government, Ministry of Health and in a special Orthodontic Clinic till 2011. Between 2011 and 2016, Dr. Deniz Uzuner worked as a specialist in the Department of Orthodontics, Faculty of Dentistry, Gazi University in Ankara/Turkey. In 2016, she was appointed associate professor. Dr. Deniz Uzuner has authored 23 Journal Papers, 3 Book Chapters and has had 39 oral/poster presentations. She is a member of the Turkish Orthodontic Society. Her knowledge of English is at an advanced level.",institutionString:null,institution:null},{id:"332914",title:"Dr.",name:"Muhammad Saad",middleName:null,surname:"Shaikh",slug:"muhammad-saad-shaikh",fullName:"Muhammad Saad Shaikh",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Jinnah Sindh Medical University",country:{name:"Pakistan"}}},{id:"315775",title:"Dr.",name:"Feng",middleName:null,surname:"Luo",slug:"feng-luo",fullName:"Feng Luo",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Sichuan University",country:{name:"China"}}},{id:"423519",title:"Dr.",name:"Sizakele",middleName:null,surname:"Ngwenya",slug:"sizakele-ngwenya",fullName:"Sizakele Ngwenya",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of the Witwatersrand",country:{name:"South Africa"}}},{id:"419270",title:"Dr.",name:"Ann",middleName:null,surname:"Chianchitlert",slug:"ann-chianchitlert",fullName:"Ann Chianchitlert",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Walailak University",country:{name:"Thailand"}}},{id:"419271",title:"Dr.",name:"Diane",middleName:null,surname:"Selvido",slug:"diane-selvido",fullName:"Diane Selvido",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Walailak University",country:{name:"Thailand"}}},{id:"419272",title:"Dr.",name:"Irin",middleName:null,surname:"Sirisoontorn",slug:"irin-sirisoontorn",fullName:"Irin Sirisoontorn",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Walailak University",country:{name:"Thailand"}}},{id:"355660",title:"Dr.",name:"Anitha",middleName:null,surname:"Mani",slug:"anitha-mani",fullName:"Anitha Mani",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"SRM Dental College",country:{name:"India"}}},{id:"355612",title:"Dr.",name:"Janani",middleName:null,surname:"Karthikeyan",slug:"janani-karthikeyan",fullName:"Janani Karthikeyan",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"SRM Dental College",country:{name:"India"}}},{id:"334400",title:"Dr.",name:"Suvetha",middleName:null,surname:"Siva",slug:"suvetha-siva",fullName:"Suvetha Siva",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"SRM Dental College",country:{name:"India"}}},{id:"334239",title:"Prof.",name:"Leung",middleName:null,surname:"Wai Keung",slug:"leung-wai-keung",fullName:"Leung Wai Keung",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Hong Kong",country:{name:"China"}}}]}},subseries:{item:{id:"4",type:"subseries",title:"Fungal Infectious Diseases",keywords:"Emerging Fungal Pathogens, Invasive Infections, Epidemiology, Cell Membrane, Fungal Virulence, Diagnosis, Treatment",scope:"Fungi are ubiquitous and there are almost no non-pathogenic fungi. Fungal infectious illness prevalence and prognosis are determined by the exposure between fungi and host, host immunological state, fungal virulence, and early and accurate diagnosis and treatment. \r\nPatients with both congenital and acquired immunodeficiency are more likely to be infected with opportunistic mycosis. Fungal infectious disease outbreaks are common during the post- disaster rebuilding era, which is characterised by high population density, migration, and poor health and medical conditions.\r\nSystemic or local fungal infection is mainly associated with the fungi directly inhaled or inoculated in the environment during the disaster. The most common fungal infection pathways are human to human (anthropophilic), animal to human (zoophilic), and environment to human (soilophile). Diseases are common as a result of widespread exposure to pathogenic fungus dispersed into the environment. \r\nFungi that are both common and emerging are intertwined. In Southeast Asia, for example, Talaromyces marneffei is an important pathogenic thermally dimorphic fungus that causes systemic mycosis. Widespread fungal infections with complicated and variable clinical manifestations, such as Candida auris infection resistant to several antifungal medicines, Covid-19 associated with Trichoderma, and terbinafine resistant dermatophytosis in India, are among the most serious disorders. \r\nInappropriate local or systemic use of glucocorticoids, as well as their immunosuppressive effects, may lead to changes in fungal infection spectrum and clinical characteristics. Hematogenous candidiasis is a worrisome issue that affects people all over the world, particularly ICU patients. CARD9 deficiency and fungal infection have been major issues in recent years. Invasive aspergillosis is associated with a significant death rate. Special attention should be given to endemic fungal infections, identification of important clinical fungal infections advanced in yeasts, filamentous fungal infections, skin mycobiome and fungal genomes, and immunity to fungal infections.\r\nIn addition, endemic fungal diseases or uncommon fungal infections caused by Mucor irregularis, dermatophytosis, Malassezia, cryptococcosis, chromoblastomycosis, coccidiosis, blastomycosis, histoplasmosis, sporotrichosis, and other fungi, should be monitored. \r\nThis topic includes the research progress on the etiology and pathogenesis of fungal infections, new methods of isolation and identification, rapid detection, drug sensitivity testing, new antifungal drugs, schemes and case series reports. It will provide significant opportunities and support for scientists, clinical doctors, mycologists, antifungal drug researchers, public health practitioners, and epidemiologists from all over the world to share new research, ideas and solutions to promote the development and progress of medical mycology.",coverUrl:"https://cdn.intechopen.com/series_topics/covers/4.jpg",hasOnlineFirst:!0,hasPublishedBooks:!1,annualVolume:11400,editor:{id:"174134",title:"Dr.",name:"Yuping",middleName:null,surname:"Ran",slug:"yuping-ran",fullName:"Yuping Ran",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bS9d6QAC/Profile_Picture_1630330675373",biography:"Dr. Yuping Ran, Professor, Department of Dermatology, West China Hospital, Sichuan University, Chengdu, China. Completed the Course Medical Mycology, the Centraalbureau voor Schimmelcultures (CBS), Fungal Biodiversity Centre, Netherlands (2006). International Union of Microbiological Societies (IUMS) Fellow, and International Emerging Infectious Diseases (IEID) Fellow, Centers for Diseases Control and Prevention (CDC), Atlanta, USA. Diploma of Dermatological Scientist, Japanese Society for Investigative Dermatology. Ph.D. of Juntendo University, Japan. Bachelor’s and Master’s degree, Medicine, West China University of Medical Sciences. Chair of Sichuan Medical Association Dermatology Committee. General Secretary of The 19th Annual Meeting of Chinese Society of Dermatology and the Asia Pacific Society for Medical Mycology (2013). In charge of the Annual Medical Mycology Course over 20-years authorized by National Continue Medical Education Committee of China. Member of the board of directors of the Asia-Pacific Society for Medical Mycology (APSMM). Associate editor of Mycopathologia. Vice-chief of the editorial board of Chinses Journal of Mycology, China. 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Initial biochemical studies have been exclusively analytic: dissecting, purifying, and examining individual components of a biological system; in the apt words of Efraim Racker (1913 –1991), “Don’t waste clean thinking on dirty enzymes.” Today, however, biochemistry is becoming more agglomerative and comprehensive, setting out to integrate and describe entirely particular biological systems. The ‘big data’ metabolomics can define the complement of small molecules, e.g., in a soil or biofilm sample; proteomics can distinguish all the comprising proteins, e.g., serum; metagenomics can identify all the genes in a complex environment, e.g., the bovine rumen. This Biochemistry Series will address the current research on biomolecules and the emerging trends with great promise.",coverUrl:"https://cdn.intechopen.com/series/covers/11.jpg",latestPublicationDate:"June 24th, 2022",hasOnlineFirst:!0,numberOfOpenTopics:4,numberOfPublishedChapters:314,numberOfPublishedBooks:31,editor:{id:"31610",title:"Dr.",name:"Miroslav",middleName:null,surname:"Blumenberg",fullName:"Miroslav Blumenberg",profilePictureURL:"https://mts.intechopen.com/storage/users/31610/images/system/31610.jpg",biography:"Miroslav Blumenberg, Ph.D., was born in Subotica and received his BSc in Belgrade, Yugoslavia. He completed his Ph.D. at MIT in Organic Chemistry; he followed up his Ph.D. with two postdoctoral study periods at Stanford University. Since 1983, he has been a faculty member of the RO Perelman Department of Dermatology, NYU School of Medicine, where he is codirector of a training grant in cutaneous biology. Dr. Blumenberg’s research is focused on the epidermis, expression of keratin genes, transcription profiling, keratinocyte differentiation, inflammatory diseases and cancers, and most recently the effects of the microbiome on the skin. He has published more than 100 peer-reviewed research articles and graduated numerous Ph.D. and postdoctoral students.",institutionString:null,institution:{name:"New York University Langone Medical Center",institutionURL:null,country:{name:"United States of America"}}},subseries:[{id:"14",title:"Cell and Molecular Biology",keywords:"Omics (Transcriptomics; Proteomics; Metabolomics), Molecular Biology, Cell Biology, Signal Transduction and Regulation, Cell Growth and Differentiation, Apoptosis, Necroptosis, Ferroptosis, Autophagy, Cell Cycle, Macromolecules and Complexes, Gene Expression",scope:"The Cell and Molecular Biology topic within the IntechOpen Biochemistry Series aims to rapidly publish contributions on all aspects of cell and molecular biology, including aspects related to biochemical and genetic research (not only in humans but all living beings). We encourage the submission of manuscripts that provide novel and mechanistic insights that report significant advances in the fields. Topics include, but are not limited to: Advanced techniques of cellular and molecular biology (Molecular methodologies, imaging techniques, and bioinformatics); Biological activities at the molecular level; Biological processes of cell functions, cell division, senescence, maintenance, and cell death; Biomolecules interactions; Cancer; Cell biology; Chemical biology; Computational biology; Cytochemistry; Developmental biology; Disease mechanisms and therapeutics; DNA, and RNA metabolism; Gene functions, genetics, and genomics; Genetics; Immunology; Medical microbiology; Molecular biology; Molecular genetics; Molecular processes of cell and organelle dynamics; Neuroscience; Protein biosynthesis, degradation, and functions; Regulation of molecular interactions in a cell; Signalling networks and system biology; Structural biology; Virology and microbiology.",annualVolume:11410,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/14.jpg",editor:{id:"165627",title:"Dr.",name:"Rosa María",middleName:null,surname:"Martínez-Espinosa",fullName:"Rosa María Martínez-Espinosa",profilePictureURL:"https://mts.intechopen.com/storage/users/165627/images/system/165627.jpeg",institutionString:null,institution:{name:"University of Alicante",institutionURL:null,country:{name:"Spain"}}},editorTwo:null,editorThree:null,editorialBoard:[{id:"79367",title:"Dr.",name:"Ana Isabel",middleName:null,surname:"Flores",fullName:"Ana Isabel Flores",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRpIOQA0/Profile_Picture_1632418099564",institutionString:null,institution:{name:"Hospital Universitario 12 De Octubre",institutionURL:null,country:{name:"Spain"}}},{id:"328234",title:"Ph.D.",name:"Christian",middleName:null,surname:"Palavecino",fullName:"Christian Palavecino",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000030DhEhQAK/Profile_Picture_1628835318625",institutionString:null,institution:{name:"Central University of Chile",institutionURL:null,country:{name:"Chile"}}},{id:"186585",title:"Dr.",name:"Francisco Javier",middleName:null,surname:"Martin-Romero",fullName:"Francisco Javier Martin-Romero",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bSB3HQAW/Profile_Picture_1631258137641",institutionString:null,institution:{name:"University of Extremadura",institutionURL:null,country:{name:"Spain"}}}]},{id:"15",title:"Chemical Biology",keywords:"Phenolic Compounds, Essential Oils, Modification of Biomolecules, Glycobiology, Combinatorial Chemistry, Therapeutic peptides, Enzyme Inhibitors",scope:"Chemical biology spans the fields of chemistry and biology involving the application of biological and chemical molecules and techniques. In recent years, the application of chemistry to biological molecules has gained significant interest in medicinal and pharmacological studies. This topic will be devoted to understanding the interplay between biomolecules and chemical compounds, their structure and function, and their potential applications in related fields. Being a part of the biochemistry discipline, the ideas and concepts that have emerged from Chemical Biology have affected other related areas. This topic will closely deal with all emerging trends in this discipline.",annualVolume:11411,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/15.jpg",editor:{id:"441442",title:"Dr.",name:"Şükrü",middleName:null,surname:"Beydemir",fullName:"Şükrü Beydemir",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y00003GsUoIQAV/Profile_Picture_1634557147521",institutionString:null,institution:{name:"Anadolu University",institutionURL:null,country:{name:"Turkey"}}},editorTwo:{id:"13652",title:"Prof.",name:"Deniz",middleName:null,surname:"Ekinci",fullName:"Deniz Ekinci",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002aYLT1QAO/Profile_Picture_1634557223079",institutionString:null,institution:{name:"Ondokuz Mayıs University",institutionURL:null,country:{name:"Turkey"}}},editorThree:null,editorialBoard:[{id:"241413",title:"Dr.",name:"Azhar",middleName:null,surname:"Rasul",fullName:"Azhar Rasul",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRT1oQAG/Profile_Picture_1635251978933",institutionString:null,institution:{name:"Government College University, Faisalabad",institutionURL:null,country:{name:"Pakistan"}}},{id:"178316",title:"Ph.D.",name:"Sergey",middleName:null,surname:"Sedykh",fullName:"Sergey Sedykh",profilePictureURL:"https://mts.intechopen.com/storage/users/178316/images/system/178316.jfif",institutionString:null,institution:{name:"Novosibirsk State University",institutionURL:null,country:{name:"Russia"}}}]},{id:"17",title:"Metabolism",keywords:"Biomolecules Metabolism, Energy Metabolism, Metabolic Pathways, Key Metabolic Enzymes, Metabolic Adaptation",scope:"Metabolism is frequently defined in biochemistry textbooks as the overall process that allows living systems to acquire and use the free energy they need for their vital functions or the chemical processes that occur within a living organism to maintain life. Behind these definitions are hidden all the aspects of normal and pathological functioning of all processes that the topic ‘Metabolism’ will cover within the Biochemistry Series. Thus all studies on metabolism will be considered for publication.",annualVolume:11413,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/17.jpg",editor:{id:"138626",title:"Dr.",name:"Yannis",middleName:null,surname:"Karamanos",fullName:"Yannis Karamanos",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002g6Jv2QAE/Profile_Picture_1629356660984",institutionString:null,institution:{name:"Artois University",institutionURL:null,country:{name:"France"}}},editorTwo:null,editorThree:null,editorialBoard:[{id:"243049",title:"Dr.",name:"Anca",middleName:null,surname:"Pantea Stoian",fullName:"Anca Pantea Stoian",profilePictureURL:"https://mts.intechopen.com/storage/users/243049/images/system/243049.jpg",institutionString:null,institution:{name:"Carol Davila University of Medicine and Pharmacy",institutionURL:null,country:{name:"Romania"}}},{id:"203824",title:"Dr.",name:"Attilio",middleName:null,surname:"Rigotti",fullName:"Attilio Rigotti",profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institutionString:null,institution:{name:"Pontifical Catholic University of Chile",institutionURL:null,country:{name:"Chile"}}},{id:"300470",title:"Dr.",name:"Yanfei (Jacob)",middleName:null,surname:"Qi",fullName:"Yanfei (Jacob) Qi",profilePictureURL:"https://mts.intechopen.com/storage/users/300470/images/system/300470.jpg",institutionString:null,institution:{name:"Centenary Institute of Cancer Medicine and Cell Biology",institutionURL:null,country:{name:"Australia"}}}]},{id:"18",title:"Proteomics",keywords:"Mono- and Two-Dimensional Gel Electrophoresis (1-and 2-DE), Liquid Chromatography (LC), Mass Spectrometry/Tandem Mass Spectrometry (MS; MS/MS), Proteins",scope:"With the recognition that the human genome cannot provide answers to the etiology of a disorder, changes in the proteins expressed by a genome became a focus in research. Thus proteomics, an area of research that detects all protein forms expressed in an organism, including splice isoforms and post-translational modifications, is more suitable than genomics for a comprehensive understanding of the biochemical processes that govern life. The most common proteomics applications are currently in the clinical field for the identification, in a variety of biological matrices, of biomarkers for diagnosis and therapeutic intervention of disorders. From the comparison of proteomic profiles of control and disease or different physiological states, which may emerge, changes in protein expression can provide new insights into the roles played by some proteins in human pathologies. Understanding how proteins function and interact with each other is another goal of proteomics that makes this approach even more intriguing. Specialized technology and expertise are required to assess the proteome of any biological sample. Currently, proteomics relies mainly on mass spectrometry (MS) combined with electrophoretic (1 or 2-DE-MS) and/or chromatographic techniques (LC-MS/MS). MS is an excellent tool that has gained popularity in proteomics because of its ability to gather a complex body of information such as cataloging protein expression, identifying protein modification sites, and defining protein interactions. The Proteomics topic aims to attract contributions on all aspects of MS-based proteomics that, by pushing the boundaries of MS capabilities, may address biological problems that have not been resolved yet.",annualVolume:11414,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/18.jpg",editor:{id:"200689",title:"Prof.",name:"Paolo",middleName:null,surname:"Iadarola",fullName:"Paolo Iadarola",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bSCl8QAG/Profile_Picture_1623568118342",institutionString:null,institution:{name:"University of Pavia",institutionURL:null,country:{name:"Italy"}}},editorTwo:{id:"201414",title:"Dr.",name:"Simona",middleName:null,surname:"Viglio",fullName:"Simona Viglio",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRKDHQA4/Profile_Picture_1630402531487",institutionString:null,institution:{name:"University of Pavia",institutionURL:null,country:{name:"Italy"}}},editorThree:null,editorialBoard:[{id:"72288",title:"Dr.",name:"Arli Aditya",middleName:null,surname:"Parikesit",fullName:"Arli Aditya Parikesit",profilePictureURL:"https://mts.intechopen.com/storage/users/72288/images/system/72288.jpg",institutionString:null,institution:{name:"Indonesia International Institute for Life Sciences",institutionURL:null,country:{name:"Indonesia"}}},{id:"40928",title:"Dr.",name:"Cesar",middleName:null,surname:"Lopez-Camarillo",fullName:"Cesar Lopez-Camarillo",profilePictureURL:"https://mts.intechopen.com/storage/users/40928/images/3884_n.png",institutionString:null,institution:{name:"Universidad Autónoma de la Ciudad de México",institutionURL:null,country:{name:"Mexico"}}},{id:"81926",title:"Dr.",name:"Shymaa",middleName:null,surname:"Enany",fullName:"Shymaa Enany",profilePictureURL:"https://mts.intechopen.com/storage/users/81926/images/system/81926.png",institutionString:"Suez Canal University",institution:{name:"Suez Canal University",institutionURL:null,country:{name:"Egypt"}}}]}]}},libraryRecommendation:{success:null,errors:{},institutions:[]},route:{name:"profile.detail",path:"/profiles/129030",hash:"",query:{},params:{id:"129030"},fullPath:"/profiles/129030",meta:{},from:{name:null,path:"/",hash:"",query:{},params:{},fullPath:"/",meta:{}}}},function(){var e;(e=document.currentScript||document.scripts[document.scripts.length-1]).parentNode.removeChild(e)}()