Nerve agents belong to the most dangerous chemical warfare agents and can be/were misused by terrorists. Effective prophylaxis and treatment is necessary to diminish their effect. General principles of prophylaxis are summarized (protection against acetylcholinesterase inhibition, detoxification, treatment "in advance" and use of different drugs). They are based on the knowledge of mechanism of action of nerve agents. Among different examinations, it is necessary to test prophylactic effectivity in vivo and compare the results with protection in vitro. Chemical and biological approaches to the development of new prophylactics would be applied simultaneously during this research. Though the number of possible prophylactics is relatively high, the only four drugs were introduced into military medical practice. At present, pyridostigmine seems to be common prophylactic antidote; prophylactics panpal (tablets with pyridostigmine, trihexyphenidyl and benactyzine), transant (transdermal patch containing HI-6) are other means introduced into different armies as prophylactics. Scavenger commercionally available is Protexia®. Future development will be focused on scavengers, and on other drugs either reversible cholinesterase inhibitors (e.g., huperzine A, gallantamine, physostigmine, acridine derivatives) or other compounds.
- MeSH
- cholinesterasy metabolismus MeSH
- lidé MeSH
- molekulární modely MeSH
- nervová bojová látka chemie farmakologie MeSH
- reaktivátory cholinesterázy chemie farmakologie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Novel tacrine-benzyl quinolone carboxylic acid (tacrine-BQCA) hybrids were designed based on multi-target directed ligands (MTLDs) paradigm, synthesized and evaluated in vitro as inhibitors of human acetylcholinesterase (hAChE) and human butyrylcholinesterase (hBChE). Tacrine moiety is represented herein as 7-methoxytacrine, 6-chlorotacrine or unsubstituted tacrine forming three different families of seven members, i.e. 21 compounds in overall. Introducing BQCA, a positive modulator of M1 muscarinic acetylcholine receptors (mAChRs), the action of novel compounds on M1 mAChRs was evaluated via Fluo-4 NW assay on the Chinese hamster ovarian (CHO-M1WT2) cell line. All the novel tacrine-BQCA hybrids were able to block the action of hAChE and hBChE in micromolar to nanomolar range. The hAChE kinetic profile of 5p was found to be mixed-type which is consistent with our docking experiments. Moreover, selected ligands were assessed for their potential hepatotoxicity on HepG2 cell line and presumable permeation through the blood-brain barrier by PAMPA assay. Expected agonistic profile towards M1 mAChRs delivered by BQCA moiety was not confirmed. From all the hybrids, 5o can be highlighted as non-selective cholinesterase inhibitor (hAChE IC50 = 74.5 nM; hBChE IC50 = 83.3 nM) with micromolar antagonistic activity towards M1 mAChR (IC50 = 4.23 μM). A non-selective pattern of cholinesterase inhibition is likely to be valuable during the onset as well as later stages of AD.
- MeSH
- acetylcholinesterasa metabolismus MeSH
- Alzheimerova nemoc farmakoterapie metabolismus MeSH
- buněčné linie MeSH
- butyrylcholinesterasa metabolismus MeSH
- chinoliny chemie farmakologie MeSH
- cholinesterasové inhibitory chemická syntéza chemie farmakologie MeSH
- Cricetulus MeSH
- lidé MeSH
- molekulární struktura MeSH
- takrin chemie farmakologie MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- vztahy mezi strukturou a aktivitou MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Maternal diabetes is associated with changes of the placental structure. These changes include great variability of vascularity manifested by strikingly hypovascular as well as hypervascular terminal villi. In this paper, normal placental terminal villi and pathological villi of type 1 diabetic placentas were compared concerning the structure of villous stroma, spatial arrangement of villous capillary bed and quantitative assessment of capillary branching pattern. Formalin fixed and paraffin embedded specimens of 14 normal and 17 Type 1 diabetic term placentas were used for picrosirius staining, vimentin and desmin immunohistochemistry and confocal microscopy. 3D models of villi and villous capillaries were constructed from stacks of confocal optical sections. Hypervascular as well as hypovascular villi of diabetic placenta displayed changed structure of villous stroma, i.e. the collagen envelope around capillaries looked thinner and the network of collagen fibers seemed less dense. The desmin immunocytochemistry has shown that stromal cells of hypervascular as well as hypovascular villi appeared nearly or completely void of desmin filaments. In comparison with normal villi, capillaries of hypovascular villi had a smaller diameter and displayed a markedly wavy course whereas in hypervascular villi numerous capillaries occurred in reduced stroma and often had a large diameter. The quantitative assessment of capillary branching has shown that villous capillaries are more branched in diabetic placentas. It is concluded that type 1 maternal diabetes enhances the surface area of the capillary wall by elongation, enlargement of diameter and higher branching of villous capillaries and disrupts the stromal structure of terminal villi.
- MeSH
- diabetes mellitus 1. typu patologie MeSH
- dospělí MeSH
- kapiláry patologie MeSH
- konfokální mikroskopie MeSH
- lidé MeSH
- mladý dospělý MeSH
- novorozenec MeSH
- placenta krevní zásobení patologie MeSH
- studie případů a kontrol MeSH
- těhotenství při diabetu patologie MeSH
- těhotenství MeSH
- zobrazování trojrozměrné MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- novorozenec MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Placentas from pregnancies complicated by Type 1 diabetes mellitus (DM 1) display altered vascular morphology and function. Here we studied the extent of pericyte coverage in microvessels of normal pregnancies and pregnancies complicated by DM 1. We used smooth muscle actin (SMA) as a marker for quantitation of pericyte coverage in placental capillaries. The extent of pericyte coverage around the vessel circumference was 38 ± 11% in normal vs. 33 ± 10% in DM 1 pregnancies. We found that there is no statistically significant difference in the extent of pericyte coverage around the capillary circumference between DM 1 and normal pregnancies.
- MeSH
- diabetes mellitus 1. typu patologie MeSH
- lidé MeSH
- mikrocévy patologie MeSH
- pericyty patologie MeSH
- placenta krevní zásobení patologie MeSH
- studie případů a kontrol MeSH
- těhotenství při diabetu patologie MeSH
- těhotenství MeSH
- Check Tag
- lidé MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Avascular necrosis is the most devastating complication associated with slipped capital femoral epiphysis. In this case report, we present the clinical and radiological outcome of two patients after proximal femoral osteotomy for avascular necrosis associated with slipped capital femoral epiphysis. The Iowa hip score was used to assess the function. Periodic radiographic observations showed no progression of the collapse, and bone remodelling of the necrotic femoral head. Our evaluation of patients who underwent proximal femoral osteotomy for avascular necrosis prior to collapse of the femoral head suggests that its use resulted in acceptable clinical outcome with bone remodelling of the necrotic area (Fig. 4, Ref. 16).
- MeSH
- hlavice femuru radiografie chirurgie MeSH
- lidé MeSH
- mladiství MeSH
- nekróza hlavice femuru etiologie chirurgie MeSH
- osteotomie MeSH
- skluz epifýzy komplikace MeSH
- Check Tag
- lidé MeSH
- mladiství MeSH
- mužské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- kazuistiky MeSH
- MeSH
- asistovaná reprodukce MeSH
- demografie MeSH
- Publikační typ
- kongresy MeSH
- Geografické názvy
- Česká republika MeSH
- Slovenská republika MeSH
Kazuistika popisuje úspěšnou resuscitaci mladého muže, jenž byl nalezen po 15 hodinách od suicidálního pokusu (intoxikace karbamazepinem) v hluboké hypotermii (19ºC) se zástavou oběhu. K ohřevu nemocného byl použit mimotělní oběh. Nemocný byl úspěšně odpojen od mimotělního oběhu, vyveden ze šokového stavu včetně těžké rabdomyolýzy a intoxikace karbamazepinem a propuštěn do domácího léčení bez neurologického deficitu.
The case-history describes successful resuscitation of a young man who was found after 15 hours following attempted suicide (intoxication with carbamazepine) in deep hypothermia (19 °C) with cardiac arrest. For rewarming the patient extracorporeal circulation was used. The patient was successfully disconnected from the extracorporeal circulation, relieved ofthe shock incl. severe rhabdomyolysis and intoxication with carbamazepine and discharged to domiciliary treatment without suffering from a neurological deficiency.
- MeSH
- hypotermie etiologie terapie MeSH
- karbamazepin otrava MeSH
- lidé MeSH
- mimotělní oběh metody využití MeSH
- otrava etiologie terapie MeSH
- resuscitace metody využití MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
