Náš článek prezentuje kazuistiku pacientky s přetrvávající poruchou vědomí po vyvedení z celkové anestezie. 65letá pacientka s Crohnovou nemocí byla indikována k plánované laparoskopicky asistované ileocékální resekci. Operace proběhla bez komplikací v celkové anestezii. V bezprostředním poanestetickém období dominovala kvantitativní porucha vědomí charakteru výrazné somnolence až soporu. Stav vědomí se s postupujícím časem nelepšil, a proto byly pacientce s podezřením na protrahovaný účinek opioidů aplikovány naloxon a aminofylin. Jejich podání však nevedlo k úpravě stavu vědomí. Po vyloučení všech ostatních příčin poruchy vědomí jsme pomýšleli na centrální anticholinergní syndrom (CAS) a přistoupili k podání fyzostigminu. U pacientky došlo během minut k obnovení plné vigility, zrychlení psychomotorického tempa a zlepšení svalové síly. Další průběh hospitalizace probíhal bez pozoruhodností.

Our article presents a case report of patient with persistent impaired consciousness on awakening from general anesthesia. A 65-year-old patient with Crohn's disease was indicated for scheduled laparoscopic assisted ileocecal resection. The operation was performed without complications under general anesthesia. In the immediate post-anesthetic period, a quantitative disorder of consciousness of the nature of significant somnolence to sopor dominated. The state of consciousness did not improve over time and therefore naloxone and aminophyllin were administered to patients with a suspected prolonged opiate effects. However, their administration did not lead to an adjustment of the consciousness. After excluding all other causes of disturbances of consciousness, we considered central anticholinergic syndrome (CAS) and proceeded to the administration of physostigmine. Patients regained full alertness, accelerated psychomotor pace, and improved muscle strength within a minute. Further course of hospitalization without any sights.

• MeSH
• aminofylin aplikace a dávkování   terapeutické užití   MeSH
• anticholinergní syndrom * diagnóza   farmakoterapie   patologie   MeSH
• celková anestezie škodlivé účinky   MeSH
• cholinesterasové inhibitory aplikace a dávkování   terapeutické užití   MeSH
• Crohnova nemoc chirurgie   MeSH
• diferenciální diagnóza MeSH
• fysostigmin aplikace a dávkování   škodlivé účinky   terapeutické užití   MeSH
• lidé MeSH
• naloxon aplikace a dávkování   terapeutické užití   MeSH
• poruchy vědomí chemicky indukované   farmakoterapie   MeSH
• probouzení z anestezie MeSH
• senioři MeSH
• výsledek terapie MeSH
• Check Tag
• lidé MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• kazuistiky MeSH

AIMS: Organophosphates (OPCs), useful agents as pesticides, also represent a serious health hazard. Standard therapy with atropine and established oxime-type enzyme reactivators is unsatisfactory. Experimental data indicate that superior therapeutic results can be obtained when reversible cholinesterase inhibitors are administered before OPC exposure. Comparing the protective efficacy of five such cholinesterase inhibitors (physostigmine, pyridostigmine, ranitidine, tacrine, or K-27), we observed best protection for the experimental oxime K-27. The present study was undertaken in order to determine if additional administration of K-27 immediately after OPC (paraoxon) exposure can improve the outcome. METHODS: Therapeutic efficacy was assessed in rats by determining the relative risk of death (RR) by Cox survival analysis over a period of 48 h. Animals that received only pretreatment and paraoxon were compared with those that had received pretreatment and paraoxon followed by K-27 immediately after paraoxon exposure. RESULTS: Best protection from paraoxon-induced mortality was observed after pretreatment with physostigmine (RR = 0.30) and K-27 (RR = 0.34). Both substances were significantly more efficacious than tacrine (RR = 0.67), ranitidine (RR = 0.72), and pyridostigmine (RR = 0.76), which were less efficacious but still significantly reduced the RR compared to the no-treatment group (paraoxon only). Additional administration of K-27 immediately after paraoxon exposure (posttreatment) did not further reduce mortality. Statistical analysis between pretreatment before paraoxon exposure alone and pretreatment plus K-27 posttreatment did not show any significant difference for any of the pretreatment regimens. CONCLUSIONS: Best outcome is achieved if physostigmine or K-27 are administered prophylactically before exposure to sublethal paraoxon dosages. Therapeutic outcome is not further improved by additional oxime therapy immediately thereafter.

• MeSH
• analýza přežití MeSH
• cholinesterasové inhibitory aplikace a dávkování   toxicita   MeSH
• fysostigmin aplikace a dávkování   chemie   MeSH
• krysa rodu rattus MeSH
• organofosfáty toxicita   MeSH
• oximy aplikace a dávkování   chemie   MeSH
• paraoxon chemie   toxicita   MeSH
• postexpoziční profylaxe MeSH
• potkani Wistar MeSH
• preexpoziční profylaxe MeSH
• proporcionální rizikové modely MeSH
• pyridostigmin-bromid aplikace a dávkování   chemie   MeSH
• ranitidin chemie   farmakologie   MeSH
• reaktivátory cholinesterázy farmakologie   MeSH
• takrin aplikace a dávkování   chemie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

The aim of the presented research was the preparation of an innovative carrier with significantly improved properties for the fast and sensitive detection of cholinesterase inhibitors such as nerve agents. This innovative carrier was in the form of spherical pellets containing different amounts of Neusilin. Neusilin is a synthetic and amorphous form of magnesium aluminometasilicate with a high specific surface area, and the immobilized enzyme butyrylcholinesterase with an activity of 50nkat·g-1. Pellets were prepared by the extrusion-spheronization method and dried in a hot air oven under two conditions - at 30°C for 72h and at 60°C for 24h. Dried pellets were consequently impregnated with a solution containing butyrylcholinesterase. Impregnated pellets were evaluated for their quality parameters, enzymatic activity and inhibition. Activity and inhibition were tested according to the standard Ellman's method. It was observed that the addition of Neusilin significantly increased the hardness, intraparticular porosity, sphericity and activity of the carriers as well as intensity of the color transition. Therefore it is shown that these carriers have unquestionable advantages over common carriers of their kind. Drying temperatures have been shown to have no effect on properties of pellets except for a change in their size. Results were confirmed by statistical evaluation using ANOVA and PCA.

• MeSH
• butyrylcholinesterasa chemie   MeSH
• celulosa chemie   MeSH
• cholinesterasové inhibitory chemie   MeSH
• enzymy imobilizované chemie   MeSH
• fysostigmin chemie   MeSH
• lékové formy MeSH
• nosiče léků chemie   MeSH
• pomocné látky chemie   MeSH
• poréznost MeSH
• povidon chemie   MeSH
• sarin MeSH
• silikáty chemie   MeSH
• sloučeniny hliníku chemie   MeSH
• sloučeniny hořčíku chemie   MeSH
• tvrdost MeSH
• Publikační typ
• časopisecké články MeSH

Pre-treatment with reversible acetylcholinesterase (AChE) inhibitors before organophosphorous compound (OPC) exposure can reduce OPC-induced mortality. However, pyridostigmine, the only substance employed for such prophylaxis, is merely efficacious against a limited number of OPCs. In search of more efficacious and broad-range alternatives, we have compared in vivo the ability of five reversible AChE inhibitors (pyridostigmine, physostigmine, ranitidine, tacrine and K-27) to reduce mortality induced by the OPC azinphos-methyl. Protection was quantified using Cox analysis by determining the relative risk (RR) of death in rats that were administered these AChE inhibitors in equitoxic dosage (25% of LD01) 30 min before azinphos-methyl exposure. Azinphos-methyl-induced mortality was significantly reduced by all five tested compounds as compared with the reference group that was only exposed to azinphos-methyl without prior pre-treatment (RR = 1). The most efficacious prophylactic agents were K-27 (RR = 0.15) and physostigmine (RR = 0.21), being significantly more efficacious than ranitidine (RR = 0.62) and pyridostigmine (RR = 0.37). Pre-treatment with tacrine (RR = 0.29) was significantly more efficacious than pre-treatment with ranitidine, but the difference between tacrine and pyridostigmine was not significant. Our results indicate that prophylactic administration of the oxime K-27 may be a promising alternative in cases of imminent OPC exposure. Copyright © 2014 John Wiley & Sons, Ltd.

• MeSH
• azinfos-methyl * toxicita   MeSH
• cholinesterasové inhibitory * farmakologie   MeSH
• fysostigmin farmakologie   MeSH
• krysa rodu rattus MeSH
• oximy farmakokinetika   MeSH
• potkani Wistar MeSH
• proporcionální rizikové modely MeSH
• pyridinové sloučeniny farmakologie   MeSH
• pyridostigmin-bromid farmakologie   MeSH
• ranitidin farmakologie   MeSH
• takrin farmakologie   MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH

• MeSH
• Atropa belladonna toxicita   MeSH
• belladonnové alkaloidy * farmakokinetika   toxicita   MeSH
• Datura stramonium toxicita   MeSH
• diazepam aplikace a dávkování   terapeutické užití   MeSH
• fysostigmin aplikace a dávkování   terapeutické užití   MeSH
• Hyoscyamus toxicita   MeSH
• lidé MeSH
• nauzea MeSH
• otrava rostlinami * diagnóza   terapie   MeSH
• skopolaminové deriváty * farmakokinetika   toxicita   MeSH
• Check Tag
• lidé MeSH

Obidoxime, a weak acetylcholine-esterase (AChE) inhibitor, exerts muscarinic receptor antagonism with a significant muscarinic M2 receptor selective profile. The current examinations aimed to determine the functional significance of muscarinic M2 receptors in the state of AChE inhibition, elucidating muscarinic M2 and M3 receptor interaction. In the in vitro examinations, methacholine evoked concentration-dependent bladder contractile and atrial frequency inhibitory responses. Although atropine abolished both, methoctramine (1 μmol/L) only affected the cholinergic response in the atrial preparations. However, in the presence of methoctramine, physostigmine, an AChE inhibitor, increased the basal tension of the bladder strip preparations (+68%), as well as the contractile responses to low concentrations of methacholine (< 5 μmol/L; +90-290%). In contrast to physostigmine, obidoxime alone raised the basal tension (+58%) and the responses to low concentrations of methacholine (< 5 μmol/L; +80-450%). Physostigmine concentration-dependently increased methacholine-evoked responses, similarly to obidoxime at low concentrations. However, at large concentrations (> 5 μmol/L), obidoxime, because of its unselective muscarinic receptor antagonism, inhibited the methacholine bladder responses. In conclusion, the current results show that muscarinic M2 receptors inhibit muscarinic M3 receptor-evoked contractile responses to low concentrations of acetylcholine in the synaptic cleft. The muscarinic M2 and M3 receptor crosstalk could be a counteracting mechanism in the treatment of AChE inhibition when using reactivators, such as obidoxime.

• MeSH
• antagonisté muskarinových receptorů farmakologie   MeSH
• atropin farmakologie   MeSH
• cholinesterasové inhibitory farmakologie   MeSH
• diaminy farmakologie   MeSH
• fysostigmin farmakologie   MeSH
• interakce mezi receptory a ligandy MeSH
• krysa rodu rattus MeSH
• methacholinchlorid farmakologie   MeSH
• močový měchýř účinky léků   enzymologie   metabolismus   MeSH
• obidoxim chlorid farmakologie   MeSH
• receptor muskarinový M2 antagonisté a inhibitory   MeSH
• receptor muskarinový M3 antagonisté a inhibitory   MeSH
• srdeční síně účinky léků   enzymologie   metabolismus   MeSH
• svalová kontrakce účinky léků   MeSH
• techniky in vitro MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Intestinal microcirculatory disturbances play an important role in the pathophysiology of sepsis. A neural anti-inflammatory pathway has been suggested as a potential target for therapy that may dampen systemic inflammation. The aim of this study is to investigate the effects of physostigmine, a cholinesterase inhibitor, on the intestinal microcirculation and vascular contractility in experimental endotoxemia. Endotoxemia was induced in Lewis rats by intravenous lipopolysaccharide (LPS) administration. Animals were treated with either physostigmine or saline (control) following LPS challenge. The intestinal microcirculation, including leukocyte-endothelial interaction, functional capillary density (FCD) and non-perfused capillary density (NCD), was examined by intravital microscopy (IVM) 2 hours after LPS administration. The impact of physostigmine on vascular contractility of rat aortic rings was examined by in vitro myography. Physostigmine significantly reduced the number of adhering leukocytes in intestinal submucosal venules (V1 venules: -61%, V3 venules: -36%) of LPS animals. FCD was significantly increased by physostigmine treatment (circular muscle layer: +180%, longitudinal muscle layer: +162%, mucosa: +149%). Low concentrations of physostigmine produced significant contraction of aortic ring preparations, whereas high concentrations produced relaxation. In conclusion, physostigmine treatment significantly improved the intestinal microcirculation in experimental endotoxemia by reducing leukocyte adhesion and increasing FCD.

• MeSH
• cholinesterasové inhibitory aplikace a dávkování   terapeutické užití   MeSH
• endotoxemie metabolismus   patofyziologie   MeSH
• fysostigmin aplikace a dávkování   terapeutické užití   MeSH
• krysa rodu rattus MeSH
• mikrocirkulace účinky léků   MeSH
• modely nemocí na zvířatech MeSH
• potkani inbrední LEW MeSH
• sepse MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

• MeSH
• aflatoxiny toxicita   MeSH
• Alzheimerova nemoc farmakoterapie   MeSH
• berberin * analogy a deriváty   farmakologie   terapeutické užití   MeSH
• cholinesterasové inhibitory * farmakologie   chemie   izolace a purifikace   klasifikace   terapeutické užití   MeSH
• cholinesterasy chemie   metabolismus   MeSH
• fenylkarbamáty farmakologie   terapeutické užití   MeSH
• fysostigmin farmakologie   terapeutické užití   MeSH
• insekticidy chemie   metabolismus   MeSH
• karbamáty chemie   metabolismus   MeSH
• karbofuran toxicita   MeSH
• kognitivní poruchy farmakoterapie   MeSH
• lidé MeSH
• myasthenia gravis farmakoterapie   MeSH
• neostigmin aplikace a dávkování   terapeutické užití   MeSH
• organofosforové sloučeniny chemie   metabolismus   MeSH
• parkinsonské poruchy farmakoterapie   MeSH
• pesticidy chemie   metabolismus   MeSH
• receptory N-methyl-D-aspartátu * antagonisté a inhibitory   chemie   terapeutické užití   MeSH
• rostliny MeSH
• takrin * analogy a deriváty   farmakologie   škodlivé účinky   terapeutické užití   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH

The resolving power of multicomponent spectral analysis and the computation reliability of the stability constants and molar absorptivities determined for five variously protonated anions of physostigmine salicylate by the SQUAD(84) and SPECFIT/32 programs has been examined with the use of simulated and experimental spectra containing overlapping spectral bands. The reliability of the dissociation constants of drug was proven with goodness-of-fit tests and by examining the influence of pre-selected noise level s(inst)(A) in synthetic spectra regarding the precision s(pK) and also accuracy of the estimated dissociation constants. Precision was examined as the linear regression model s(pK)=β(0)+β(1)s(inst)(A). In all cases the intercept β(0) was statistically insignificant. When an instrumental error s(inst)(A) is small and less than 0.5 mAU, the parameters' estimates are nearly the same as the bias ΔpK=pK(a,calc)-pK(a,true) is quite negligible. In all four dissociation constants the bias seems to be quite small even though for pK(a4) it is a little bit higher, i.e., +0.05 for s(inst)(A) about 1.0 mAU. In the interval of s(inst)(A) from 0.1 to 1.0 mAU all four dissociation constants pK(i) are accurate enough. Of the various regression diagnostics considered, the goodness-of-fit is the most efficient criterion of whether the parameters found adequately represent the data. The magnitude of instrumental error s(inst)(A) only slightly affects the shape of a Cattel's scree graph s(k)(A)=f(k) to determine the true number of light-absorbing species in the equilibrium mixture.

• MeSH
• absorpce MeSH
• chemické modely MeSH
• fysostigmin analýza   chemie   MeSH
• kinetika MeSH
• koncentrace vodíkových iontů MeSH
• počítačová simulace MeSH
• povrchové vlastnosti MeSH
• protony MeSH
• regresní analýza MeSH
• reprodukovatelnost výsledků MeSH
• software MeSH
• spektrofotometrie metody   MeSH
• termodynamika MeSH
• titrace metody   MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

The occurrence of sleep disorder in three half sibling Lipizzaner is described. Sleepiness, swaying, stumbling, carpal joints buckling and falling down onto the carpal joints had been present since early foal age in all of them. Clinical signs had gradually reduced since the age of 2 years in cases 1 and 3. Sleepiness was induced by going out from the stable in adulthood. A physostigmine test was performed in all three affected horses and produced positive results in cases 1 and 3. The result of the test in case 2 was unclear due to the almost continuous sleepiness of the foal. Hypocretin-1 concentration in the cerebrospinal fluid was established using a standardised radioimmunoassay in case 1 (317.85 pg/mL), case 2 (303.43 pg/mL) and five adult control horses (275.2 ± 47.9 [SD] pg/mL) and was considered as normal in all horses. The sire of the affected horses has had 19 other registered offspring who did not show clinical signs of sleep disorder and also dams of all three cases produced healthy foals. Based on the demographic and clinical data together with the responses to the physostigmine challenges, the diagnosis of familial equine narcolepsy was made.

• MeSH
• fysostigmin diagnostické užití   MeSH
• intracelulární signální peptidy a proteiny MeSH
• koně MeSH
• narkolepsie diagnóza   genetika   veterinární   MeSH
• nemoci koní diagnóza   genetika   MeSH
• neuropeptidy MeSH
• zvířata MeSH
• Check Tag
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH