A benzodiazepine, diazepam, has been the leading antidote for seizures caused by nerve agents, the most toxic chemical weapons of mass destruction, since the 1960s. However, its limitations have often brought questions about its usefulness. Extensive effort has been devoted into exploring alternatives, such as other benzodiazepines, anticholinergics, or glutamate antagonists. However, only few showed clear clinical benefit. The only two options to ultimately reach clinical milestones are Avizafone, a water-soluble prodrug of diazepam adopted by the French and UK armed forces, and intramuscular midazolam, adopted by the US Army. The recently FDA-approved new intramuscular application of midazolam brought several advantages, such as rapid onset of action, short duration with predictable pharmacokinetics, increased water solubility for aqueous injectable solutions, and prolonged storage stability. Herein, we discuss the pitfalls and prospects of using midazolam as a substitute in anticonvulsant therapy with a particular focus on military purposes in combat casualty care. We have also considered and discussed several other alternatives that are currently at the experimental level. Recent studies have shown the superiority of midazolam over other benzodiazepines in the medical management of poisoned casualties. While its use in emergency care is straightforward, the proper dose for soldiers under battlefield conditions is questionable due to its sedative effects.

• MeSH
• antikonvulziva * aplikace a dávkování   terapeutické užití   MeSH
• diazepam * aplikace a dávkování   MeSH
• lidé MeSH
• midazolam * aplikace a dávkování   MeSH
• nervová bojová látka * MeSH
• záchvaty * farmakoterapie   chemicky indukované   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

V letech 2010-2015 bylo na Ústavu soudního lékařství v Brně hlášeno celkem 480 novotvarů, které dle dostupné zdravotnické dokumentace a sdělení rodinných příslušníků nebyly před pitvou známy. Z tohoto počtu bylo 71,4 % u mužů a 28,6 % u žen. Ve sledovaném období bylo zaznamenáno celkem 212 případů, kdy byl dříve nediagnostikovaný zhoubný nádor natolik pokročilý, že se bezprostředně podílel na úmrtí. Ilustrativní pitevní nálezy jsou prezentovány na fotografiích na konci článku.

Malignant neoplasms represent the second most common cause of death in men and women in the Czech Republic after cardiovascular diseases. The incidence, prevalence and mortality is recorded in the Czech National Cancer Registry. The most recent data available is from 2013, in this year there were 81 541 patients newly diagnosed with cancer and 26 944 people died of cancer. From a long-term perspective, the incidence of neoplasms is increasing and the mortality is decreasing. In the Institute of Forensic Medicine in Brno there were 480 cases of newly reported malignant tumors during the period 2010-2015, which were not known before the autopsy. 71.4 % of these cases were men and 28.6 % were women. In 212 cases the tumor was advanced and was the immediate cause of death. The total number of deadly cases in men was 149, the age average was 66.2 years. The most common malignant tumor leading to death was of bronchi and lungs (39.6 %), large intestine (9.4 %), pancreas (6.7 %), liver (4.7 %), stomach (4 %) and prostatic gland (4 %). In women the total number of deaths resulting from malignant tumor was 63, the age average was 72.6 years. The most common malignant tumor leading to death was of bronchi and lungs (33.3%), ovary (11.1 %), large intestine (9.5 %), gall bladder (6.3 %) and kidney (6.3 %). Some of the autopsy findings are shown on the photographs at the end of the article.

• MeSH
• bronchopneumonie MeSH
• kachexie MeSH
• lidé středního věku MeSH
• lidé MeSH
• metastázy nádorů MeSH
• nádory břicha MeSH
• nádory děložního čípku MeSH
• nádory jícnu MeSH
• nádory vaječníků MeSH
• nádory ženských pohlavních orgánů MeSH
• nádory * epidemiologie   mortalita   MeSH
• náhlá smrt * etiologie   MeSH
• pitva MeSH
• plicní embolie MeSH
• pneumonie MeSH
• pyelonefritida MeSH
• senioři MeSH
• sepse MeSH
• spinocelulární karcinom MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• kazuistiky MeSH

Biperiden is a drug used in Parkinson disease treatment and it serves also as an antiseizures compound in organophosphates poisoning. It acts as antagonist of muscarinic receptor activated by acetylcholine while the enzyme acetylcholinesterase (AChE) cleaves acetylcholine in synaptic junction into choline and acetic acid. This enzyme is inhibited by various compounds; however there has not been proposed evidence about interaction with biperiden molecule. We investigated this interaction using standard Ellman's assay and experimental findings were critically completed with an in silico prediction by SwissDock docking software. Uncompetitive mechanism of action was revealed from Dixon plot and inhibition constant (Ki ) was calculated to be 1.11 mmol/l. The lowest predicted binding energy was -7.84 kcal/mol corresponding to H-bond between biperiden molecule and Tyr 341 residuum in protein structure of AChE. This interaction seems to be further stabilized by π-π interaction with Tyr 72, Trp 286, and Tyr 341. In conclusion, biperiden appears as a very weak inhibitor but it can serve as a lead structure in a pharmacological research.

• MeSH
• acetylcholinesterasa metabolismus   MeSH
• biperiden chemie   farmakologie   terapeutické užití   MeSH
• cholinesterasové inhibitory chemie   farmakologie   terapeutické užití   MeSH
• enzymatické testy MeSH
• lidé MeSH
• molekulární modely MeSH
• Parkinsonova nemoc farmakoterapie   enzymologie   MeSH
• substrátová specifita účinky léků   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

Aerosols formed during shooting events were studied with various techniques including the wide range size resolving sampling system Nano-ID(®) Select, followed by inductively coupled plasma mass spectrometry chemical analysis, scanning electron microscopy, and fast mobility particle sizing. The total lead mass aerosol concentration ranged from 2.2 to 72 µg m(-3). It was shown that the mass concentration of the most toxic compound lead is much lower than the total mass concentration. The deposition fraction in various compartments of the respiratory system was calculated using the ICRP lung deposition model. It was found that the deposition fraction in the alveolar range varies by a factor >3 for the various aerosols collected, depending on the aerosol size distribution and total aerosol concentration, demonstrating the importance of size resolved sampling in health risk evaluation. The proportion of the total mass of airborne particles deposited in the respiratory tract varies from 34 to 70%, with a median of 55.9%, suggesting the health risk based upon total mass significantly overestimates the accumulated dose and therefore the health risk. A comparison between conventional and so called 'green' ammunition confirmed significant lowering of concentrations of lead and other toxic metals like antimony in the atmosphere of indoor shooting ranges using 'green' ammunition, although higher concentrations of manganese and boron were measured. These metals are likely to be the constituents of new types of primers. They occur predominantly in the size fraction <250 nm of aerosols.

• MeSH
• aerosoly analýza   MeSH
• inhalační expozice analýza   MeSH
• látky znečišťující vzduch v pracovním prostředí analýza   MeSH
• lidé MeSH
• mikroskopie elektronová rastrovací MeSH
• monitorování životního prostředí metody   MeSH
• otrava těžkými kovy MeSH
• otrava prevence a kontrola   MeSH
• pracovní expozice analýza   MeSH
• sporty * MeSH
• střelné zbraně * MeSH
• teoretické modely MeSH
• těžké kovy analýza   MeSH
• velikost částic MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• hodnotící studie MeSH
• práce podpořená grantem MeSH

• MeSH
• lékařská onkologie metody   trendy   MeSH
• management bolesti MeSH
• management nemoci MeSH
• nádory diagnóza   epidemiologie   etiologie   terapie   MeSH

• Konspekt
• Patologie. Klinická medicína
• NLK Obory
• onkologie
• NLK Publikační typ
• kolektivní monografie

Gender-related differences regarding susceptibility to chemical exposure to neurotoxicants have not received sufficient attention. Although a significant number of epidemiological studies on the neurodevelopmental effects of metal exposure have been published in the last twenty years, not many of these studies have considered the possible gender-specific effects of such exposure. This review is focused on studies in which the gender differences in pre- and/or postnatal exposures to five metals (mercury, lead, manganese, cadmium, and arsenic) and neurodevelopment were evaluated. A significant number of experimental and epidemiological studies on brain effects of exposure to neurotoxic substances has been published, however not many of them have considered the possible gender-specific effects of such exposure. Subtle and less subtle differences exist in brain function. They exist due to effects of sex hormones as well as to effects that sex hormones exert on the uterus during development, leading to persisting epigenetic markers. Recent human and animal studies suggest that gender dimorphic profiles are emerging in terms of neurotoxicity, moreover that gender differences in neurotoxicity are more widespread than one may expect. If a risk factor is underestimated in one gender, or if gender specific symptoms are not recognized, timely treatment may be delayed. Knowing that one gender is more vulnerable to poisoning helps to carry out a more effective prevention strategy, that is more efficient than the global approaches. In addition, it has significant consequences on public health concerns and outcomes. Our work is complemented by a critical analysis of some previously published studies.

• MeSH
• arsen toxicita   MeSH
• centrální nervový systém MeSH
• dítě MeSH
• dospělí MeSH
• krev účinky léků   MeSH
• lidé MeSH
• metaanalýza jako téma MeSH
• mladiství MeSH
• neurologické manifestace * MeSH
• olovo toxicita   MeSH
• otrava arsenem MeSH
• otrava nervového systému rtutí MeSH
• otrava olovem MeSH
• otrava MeSH
• předškolní dítě MeSH
• prenatální poškození MeSH
• teratogeneze MeSH
• těžké kovy * toxicita   MeSH
• výzkum * MeSH
• znečištění životního prostředí * MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• práce podpořená grantem MeSH
• přehledy MeSH

While sepsis is a leading cause of acute kidney injury in critically ill patients, the relationship between immune response and acute kidney injury in less severely ill patients with infection is not known. Here we studied the epidemiology, 1-year mortality, and immune response associated with acute kidney injury in 1836 hospitalized patients with community-acquired severe and non-severe pneumonia. Acute kidney injury developed in 631 patients of whom 329 had severe and 302 had non-severe sepsis. Depending on the subgroup classification, 16-25% of the patients with non-severe pneumonia also developed acute kidney injury. In general, patients with acute kidney injury were older, had more comorbidity, and had higher biomarker concentrations (interleukin-6, tumor necrosis factor, D-dimer) even among patients without severe sepsis. The risk of death associated with acute kidney injury varied when assessed by Gray's survival model and after adjusting for differences in age, gender, ethnicity, and comorbidity. This risk was significantly higher immediately after hospitalization but gradually fell over time in the overall cohort and in those with non-severe pneumonia. A significantly higher risk of death (hazard ratio 1.29) was also present in those never admitted to an intensive care unit. Hence acute kidney injury is common even among patients with non-severe pneumonia and is associated with higher immune response and an increased risk of death.

• MeSH
• fibrin-fibrinogen - produkty degradace imunologie   MeSH
• financování organizované MeSH
• hospitalizace statistika a číselné údaje   MeSH
• imunitní systém - jevy MeSH
• interleukin-6 imunologie   MeSH
• jednotky intenzivní péče statistika a číselné údaje   MeSH
• kohortové studie MeSH
• komorbidita MeSH
• kritický stav mortalita   MeSH
• ledviny imunologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• pneumonie epidemiologie   MeSH
• prospektivní studie MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• sepse epidemiologie   imunologie   mortalita   MeSH
• studie případů a kontrol MeSH
• TNF-alfa imunologie   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Geografické názvy
• Spojené státy americké MeSH

Cíl studie: Sledovat a porovnat některé biochemické změny v krvi a moči v časné fázi experimentálního modelu sepse. Typ studie: Experimentální, prospektivní studie. Název a sídlo pracoviště: JIP I. interní klinika LF UK a FN Plzeň, ARK FN u svaté Anny v Brně. Materiál a metoda: 12 prasat o hmotnosti 24 kg (18; 30) bylo sledováno po dobu 12 hodin po navození experimentální, objemově resuscitované G" sepse kontinuální intravenózní infuzí Pseudomonas aeruginosa. V rámci původního experimentálního protokolu zaměřeného na výzkum úlohy NO a oxidačního stresu na splanchnickou cirkulaci a metabolismus jsme v hodinových intervalech sledovali hemodynamiku a diurézu. V časových intervalech To, T2,T6 a T12 bylo prováděno biochemické vyšetření moče a krve. V krvi byly sledovány hodnoty acidobazické rovnováhy, krevní plyny, laktát, ionty a kreatinin. V moči bylo sledováno pH, natrium, kalium, kreatinin a osmolalita. Výsledky: Rozvoj metabolické acidózy, pozorovaný již v T2, vedl v T12 k signifikantnímu poklesu pH moče z 6,2 (5,0; 8,0) na 5,5 (5,0; 7,2). Sepse vedla k retenci natria a kalia, přičemž jejich vzájemný poměr se vyvíjel náhodně. Osmolalita moči signifikantně poklesla z 664 mmol . kg1 (489; 811) na 338 mmol . kg1 (167; 625). Závěr: Po navození experimentální sepse jsou biochemické změny v krvi během několika hodin následovány změnami moče. Využitelnost těchto časných změn v klinické praxi je nutno podrobit další analýze.

Objective: To compare biochemical changes in the blood and urine in the early phase of an experimental model of sepsis. Design: Experimental, prospective trial. Setting: ICU of the 1st Medical Department, Charles University, Medical School and Teaching Hospital Plzeň, Czech Republic. Department of Anaesthesia and Intensive Care, St. Anns University Hospital Brno, Czech Republic. Materials and methods: Twelve pigs weighing 24 kg (18; 30) were studied for 12 hrs after the induction of experimental G-negative volume-resuscitated sepsis. The sepsis was induced with a continuous live Pseudomonas aeruginosa i.v. infusion. Within the scope of the originál protocol aimed at researching the role of NO and oxidative stress on the splanchnic perfusion and metabolism, the haemodynamic parameters and diuresis were monitored in hourly intervals. At time points To, T2,T6 and T12 a biochemical analysis of the blood and urine was performed. The blood analysis comprised the acid-base status, blood gases, electrolytes, lactate and creatinine. The urine analysis included the pH, sodium, potassium, creatinine and osmolality measurements. Results: Development of metabolic acidosis (present at T2) lead to a significant drop in the urinary pH from 6.2 (5.0;8.0) to 5.5 (5.0;7.2). Sepsis caused sodium and potasssium retention, the sodium/potassium ratio changed randomly. Osmolality of the urine decreased significantly from 664 (489:811) mmol . kg-1 to 338 (167;625) mmol. kg1. Conclusion: Experimental G-negative sepsis lead to a decrease in the blood pH followed by a decrease in the urinary pH within a few hours. The clinical relevance of these early changes warrants further evaluation.

• MeSH
• acidobazická rovnováha MeSH
• acidóza metabolismus   MeSH
• biologické markery krev   moč   MeSH
• financování vládou MeSH
• lidé MeSH
• modely u zvířat MeSH
• prasata mikrobiologie   MeSH
• Pseudomonas aeruginosa MeSH
• sepse krev   moč   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH

• MeSH
• antioxidancia farmakologie   MeSH
• chelátory farmakologie   MeSH
• chrom škodlivé účinky   MeSH
• finanční podpora výzkumu jako téma MeSH
• kyselina lipoová farmakokinetika   farmakologie   MeSH
• modely u zvířat MeSH
• myši MeSH
• otrava kadmiem farmakoterapie   MeSH
• otrava olovem farmakoterapie   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši MeSH
• zvířata MeSH

• MeSH
• biochemie MeSH

• Konspekt
• Biochemie. Molekulární biologie. Biofyzika
• NLK Obory
• biochemie