[Chemical-toxicological diagnosis of hellebore (veratrum) poisoning]. / Khimiko-toksikologicheskaya diagnostika otravlenii chemeritsei.

The problem of laboratory diagnosis of acute and fatal poisoning by hellebore, which is possible when used in traditional medicine, the erroneous use of hellebore preparations orally or use of various types of this plant for food, remains relevant. Currently, in the practice of chemical-toxicological laboratories and the bureau of forensic medical examination there is no single approach to the laboratory diagnosis of such poisoning. The diagnosis is most often based on anamnesis. In this regard, the development and validation of a legally significant methodology for the determination of hellebore alkaloids in various biological objects seems relevant. The physicochemical and toxic properties of alkaloids of various types of hellebore are characterized. It was shown that for the identification of hellebore alkaloids, it is advisable to use HPLC-MS/MS as the most sensitive and specific instrumental method corresponding to the characteristics of hellebore alkaloids (high molecular weight, high thermal lability, high polarity).

The Mechanism of Action of Ethoxidol on Oxidative Stress Indices in Heart Failure and Hypotension.

The aim of the investigation was to study the effect of 2-ethyl-6-methyl-3-hydroxypyridine malate (Ethoxidol) on the concentration of oxidative stress metabolites in patients with chronic heart failure (CHF) and hypertension. MATERIALS AND METHODS: 126 patients with FC I-III CHF have been examined. In addition to their individual therapy these patients received intravenous infusions of Ethoxidol. Blood content of 2,3-diphosphoglycerate (2,3-DPG), oxygen tension (рО2), pH, concentration of total peroxides, lactate, and aldosterone were identified. 2,3-DPG levels (g/L erythrocytes) in whole blood samples were determined by an enzyme assay using the reagent kit (Rosh, Germany), values of рО2, рСО2, рН, lactate in the venous blood were measured using gas analyzer Stat Profil pHOx Ultra (Nova Biomedical, USA). Indices of oxidative stress, i.e. the concentration of plasma total peroxides, were investigated by ELISA using OxyStat kit (Biomedica, Austria). Peripheral venous blood samples were collected from all patients before and 6 days after the daily intravenous Ethoxidol infusion. RESULTS: In patients with FC I, II, III CHF, on day 7 after intravenous Ethoxidol infusion at a dose of 100 mg/day, statistically significant growth (p=0.0002) of PaO2 level by 15.7, 17.4, and 22.8%, respectively, was noted. In patients with FC I, II, III CHF in the group receiving standard therapy, statistically significant (p=0.002) reduction of 2,3-DPG level by 2.7, 2.4, and 4.0%, respectively, was registered. On day 7 after the infusion of Ethoxidol at a dose of 100 mg/day, its decrease by 5.7, 10.5, and 26.2%, respectively (p<0.0001), was also observed. CONCLUSION: The increased concentrations of active oxygen forms have been established to negatively affect various bodily functions and adversely influence the pathophysiology of numerous diseases. Application of antioxidants, including Ethoxidol presented by us in this article, may become a clue to the development of preventive measures for many serious diseases.

[In vitro equivalence evaluation of betahistine generic medicinal products as a tool potentially determining the efficacy of pharmacotherapy]. / Otsenka ékvivalentnosti in vitro vosproizvedennykh preparatov betagistina kak instrumenta, potentsial'no opredeliaiushchego éffektivnost' farmakoterapii.

AIM: To compare release parameters of various betahistine drugs in vitro using a comparative dissolution kinetics test. MATERIAL AND METHODS: Objects of research are solid dosage forms (tablets) containing betahistine in a dose of 24 mg permitted for medical use in the Russian Federation. A method of comparative dissolution kinetics test was carried out as follows. The study was performed on a paddle stirrer at a speed of 50 rpm in three different pH dissolution media (pH 1.2, 4.5, 6.8), simulating the main sections of the digestive tract in which the active ingredient was decomposed, released and absorbed. This was performed in a quality controlled environment using a citrate buffer solution with pH 6.8. The time points for sampling the medium were 10 min, 15 min, 20 min and 30 min. RESULTS: The results of betahistine release were significant (RSD<10%) for all time points, except the first time point (RSD<20%). Regardless of pH, there was a complete release (≥85% over 15 minutes, <10%) of betahistine from betaserc, 24 mg, tablets (manufactured by Mylan Laboratories SAS). The dissolution profiles of betahistine in other investigational drugs did not show complete drug release (parameter <85% in 15 minutes, <10%) in different pH media. Therefore, dissolution profiles of the studied drugs were not comparable to the reference profile. CONCLUSION: Starting from 10 minutes, the reference drug of betahistine (betaserc, 24 mg) has a consistently higher release at different pH levels (representing the various stages of gastric digestion), vs. other studied generic analogues showing significantly lower levels of betahistine release. None of the studied drugs were found to be equivalent in vitro.

[Hepatoprotective activity of aqueous extract from Caragana jubata (Pall.) Poir. shoots in the model of acute hepatitis induced by acetaminophen in rats]. / Gepatoprotektornaia aktivnost' vodnogo izvlecheniia iz pobegov Caragana jubata (Pall.) Poir. na modeli ostrogo gepatita, indutsirovannogo atsetaminofenom u krys.

The aim of the study was to investigate the hepatoprotective activity of an aqueous extract of Caragana jubata (Pall.) Poir. Acute experimental hepatitis was induced by acetaminophen administration of 1000 mg/kg. Studies were conducted in white Wistar rats. The aqueous extract of C. jubata demonstrated the hepatoprotective effect, comparable to that of the reference preparation "Carcil". This was manifested by the normalization of biochemical blood parameters (ALT, AST, alkaline phosphatase, cholesterol, total bilirubin) and antioxidant activity of liver homogenates, determined by the method based on oxidation of luminol induced by 2,2¢-azo-bis-2-amidinopropane. Normalization of morphofunctional indices was also shown in a histological study of liver of rats that received aqueous extract from C. jubata.

[The application of the screening techniques for the purpose of chemical toxicological and forensic chemical analysis]. / Skriningovye metody v khimiko-toksikologicheskom i sudebno-khimicheskom analize.

The application of the screening techniques for the purpose of chemical toxicological and forensic chemical analysis has the objective to detect and identify the life-threatening substances within the shortest possible time period for distinguishing them from a large number of other chemical compounds amenable to the toxicological evaluation. Such methods acquire special importance for forensic chemical expertise in the cases of a negative result of the primary examination. The present article provides information about the history of development of the screening techniques.

[Mitomycin C after endoscopic endonasal dacryocystorhinostomy]. / Primenenie mitomitsina-S pri éndoskopicheskoi éndonazal'noi dakriotsistorinostomii.

Mitomycin-C (MMC) is the most frequently used agent for prevention of excessive scarring at the osteotomy site after endoscopic endonasal dacryocystorhinostomy (EEDCR), which, however, being applied during the final stage of the surgery, shows questionable effectiveness. AIM: to evaluate the effectiveness of a new administration route of mitomycin C in EEDCR. MATERIAL AND METHODS: The study included 86 patients (95 cases) in the age range of 62.3±9 years with primary acquired nasolacrimal duct obstruction. All patients underwent P.J. Wormald modification of EEDCR and were further divided into 2 groups. In group 1, MMC was injected into the nasal cavity and lacrimal sac mucosa, while in group 2 it was applied locally according to the standard procedure. To measure tissue concentrations of MMC, mucosal biopsies were taken in patients of Group 1. Systemic absorption of MMC was studied through blood samples in both groups. Clinical efficacy was assessed in 14±5 months after surgery. RESULTS: immediately after injection, the average tissue concentration of mitomicyn C in patients of Group 1, was 390±10 µg/g and 30 minutes later - 120±20 µg/g. No mitomycin C was found in Day 1 tissue samples and in any of the blood samples. Positive clinical results were reported in 97.9% of cases from Group 1 and in 87.2% of cases from Group 2. CONCLUSION: The method of injecting MMC during the final stage of EEDCR has proved clinically effective and safe and can be recommended for use in clinical practice.

[The comparative analysis of the methods for the determination of phosphatidylethanol in blood as a biological marker of alcohol abuse]. / Sravnitel'nyi analiz metodik opredeleniia fosfatidilétanola v krovi kak biomarkera zloupotrebleniia alkogolem.

The confirmation of the fact of alcohol abuse is currently an important problem of both medical and social significance. Of all biological markers of alcohol consumption presently in use, blood phosphatidylethanol (PEth) is considered to be most sensitive and specific one. Therefore it has promising prospects for the further application. There is no universally accepted method for the calculation of the phosphatidylethanol concentration in human blood. For this reason, the present article places emphasis on the comparative characteristic of various methods for the determination of this substance.

[PERSONALIZED MEDICINE IN INTERNAL MEDICINE].

Personalized medicine - a new direction in medicine, which is based on the study of various biomarkers and the use of new methods of molecular analysis (primarily evaluating the activity of isoenzymes of cytochrome P450), allowing individualized approach to the selection of both the drugs and the selection of the dosing regimen for the purpose of maximize the effectiveness and safety of pharmacotherapy. This personalized medicine is to change the development and use of preventive and curative interventions. Genetic polymorphism isozymes of cytochrome P450 may determine the individual activity of a particular isozyme, and thus, to predict the clinical effectiveness, and in some cases, the risk of adverse reactions. The article is an example of the use of information on the activity of cytochrome P450 in clinical practice in matters of diagnosis, treatment and prevention of diseases. The scheme of the five best-known activity of isoenzymes of cytochrome P450 is shown.

Interchangeability evaluation of multisource Ibuprofen drug products using biowaiver procedure.

The WHO biowaiver procedure for BCS Class II weak acids was evaluated by running two multisource IR ibuprofen drug products (Ibuprofen, 200 mg tablets, Tatchempharmpreparaty, Russia and Ibuprofen, 200 mg tablets, Biosintez, Russia) with current Marketing Authorizations (i.e. in vivo bioequivalent) through that procedure. Risks associated with excipients interaction and therapeutic index were considered to be not critical. In vitro dissolution kinetic studies were carried out according WHO Guidance (WHO Technical Report Series, No. 937, Annexes 7 and 8) using USP Apparatus II (paddle method) at 75 rpm. Dissolution profiles of test and reference ibuprofen tablets were considered equivalent in pH 4.5 using factors f(1) (13) and f(2) (72) and not equivalent in pH 6.8 (factor f(1) was 26 and f(2) was 24). Drug release of ibuprofen at pH 1.2 was negligible due to its weak acid properties. Therefore, two in vivo bioequivalent tablets were declared bioinequivalent by this procedure, indicating that procedure seems to be over-discriminatory.

Pheno- and genotyping the prescription of drugs metabolized by CYP2D6.

Mutant alleles CYP2D63 and CYP2D64 were detected by PCR in 33 individuals. All examinees were given 50 mg methoprolol (orally). Plasma concentrations of the drug and its major metabolite was determined by high performance liquid chromatography and arterial pressure and heart rate were monitored. The rate of methoprolol metabolism was significantly lowered in subjects with CYP2D64 mutation. This determined blood pressure decrease and bradycardia in these subjects after drug intake.