New polyomavirus species identified in nutria, Myocastor coypus polyomavirus 1.

A novel polyomavirus (PyVs) comprising 5,422 bp was identified by high-throughput sequencing (HTS) in pooled organs of nutria (Myocastor coypus). The new genome displays the archetypal organization of PyVs, which includes open reading frames for the regulatory proteins small T antigen (sTAg) and large T antigen (LTAg), as well as for the capsid proteins VP1, VP2 and VP3. Based on the International Committee on Taxonomy of Viruses (ICTV) Polyomaviridae Study Group criteria, this genome comprises a new PyVs species for the Alphapolyomavirus genus and is putatively named "Myocastor coypus Polyomavirus 1" . The complete genome sequence of this Myocastor coypus Polyomavirus 1 (McPyV1) isolate is publically available under the GenBank accession no. MH182627.

Simultaneous determination of drugs in human autopsy material using phase-optimized liquid chromatography.

In legal medicine in many cases drugs are detected in autopsy material without connection to the cause of death, and until now no further investigations have taken place. In our study more than 50 drugs were measured directly in several compartments. The deceased had received continual therapeutic treatment, treatment during an operation or an unsuccessful emergency therapy. Liquid-liquid extraction and an LC-MS/MS method were developed for the determination of these drug concentrations. When measuring many transitions in a biological matrix, two problems should be excluded: ion suppression and too few measurement points per peak. A relatively short operation time and sufficient separation were achieved by column, eluent and gradient optimization with POPLC (phase-optimized liquid chromatography). Various autopsy materials from about 170 cases were investigated. In particular, in nine cases with four or more simultaneously determined drugs, their distribution in the compartments is very interesting for pharmacokinetic examinations. The distribution patterns of the drugs in the compartments of one individual deceased were compared. This meant that the great differences between subjects that are normally encountered these studies could be excluded. Measurements of drug concentrations in human autopsy material deepens knowledge of the respective drugs' pharmacokinetics.

Distribution of metoprolol in human autopsy material.

In forensic medicine autopsy material is primarily investigated to find out the cause of death. But the results of corresponding toxicology measurements often involve more information. With screening methods drugs were detected not being related to the cause of death. Liquid/liquid extraction and LC/MS/MS methods were used for the determination of drug concentrations. In seven cases metoprolol could be determined in different autopsy materials. In all cases the dosage of the drug was unknown. In cases with oral application probably the patients took a normal customary continuous dosage. Intoxication with metoprolol could be excluded in all cases. The concentrations of metoprolol in blood were all in the therapeutic range. The time between oral intake and death was unknown. Therefore and because of the low number of cases statistic calculations were not meaningful and an individual case study was necessary. In three cases the highest concentration of metoprolol was found in the liver. Probably, metoprolol was taken shortly before the person died. In the other cases the highest concentration of metoprolol was found in urine. This means the elimination process of the drug predominated at the time of death. In all cases the concentrations of metoprolol were similar in the compartments heart blood, venous blood and brain. In this study it was possible to measure the distribution of metoprolol in human directly in several compartments. Measurement of drug concentrations in human autopsy material deepen the knowledge of its pharmacokinetics.

[Statins and ASS for primary prevention of cardiovascular and cerebrovascular disease]. / Medikamentöse Primärprävention kardiovaskulärer und zerebrovaskulärer Erkrankungen.

Whereas statins and acetylsalicylic acid (ASA) are considered gold standard for secondary prevention following myocardial infarction or atherotrombotic stroke, there are inconsistent data on the use of these drugs for primary prevention in patients with increased cardiovascular risk. Some meta-analyses indicated that the use of statins and ASA for primary prevention of cardiovascular disease can reduce the risk of cardiovascular events such as ischemic stroke or myocardial infarction. However, the effects of primary prevention with statins and ASA on mortality varied in the data included in these meta-analyses. Therefore the guidelines of the German College of General Practitioners and Family Physicians recommend primary prevention with statins and ASA only in those patients who have a 10-year risk of cardiovascular events which exceeds 20 %. Divergently, primary prevention with ASA is not recommended by the European Society of Cardiology. Observational studies suggested that treatment success of primary prevention with statins and ASA depends on various factors such as adherence to medication and prescription behavior of physicians. This review summarizes the current literature on primary prevention of cardiovascular events with ASA and statins.

Elucidation of Neu-P11 metabolism in urine of volunteers by liquid chromatography-tandem mass spectrometry.

The novel melatonin agonist Neu-P11 is used in treatment of physiological insomnia. In animal studies Neu-P11 showed sleep-promoting effects. In a phase 1 study Neu-P11 was administered to cohorts of healthy young male volunteers in an ascending single dose study. Up to now the metabolism of this new drug in humans has not been investigated. The first aim of this study was to identify possible metabolites in pooled urine samples of the first collecting period (0-8 h) of volunteers with the highest Neu-P11 oral dosage (200 mg). The objective of the second part of the study was to estimate the concentrations of the main metabolites of Neu-P11 - in this urine sample. The analyte Neu-P11 and metabolites were separated from human urine using dilution and precipitation with acetonitrile. Samples were analyzed for formation of both phase I and phase II metabolites using LC-MS/MS in precursor ion mode, product ion mode, neutral loss mode and the multi-reaction monitoring mode (MRM). Urine samples were analyzed before and after addition of beta-glucuronidase and sulfatase. In the pooled urine sample eight metabolites could be proved. The parent drug, the sulfated demethylated Neu-P11, the sulfated 6OH-Neu-P11 and the di-oxygenated product gave the highest signals in these urine samples and probably had the highest concentration. But quantification without reference substances is not possible. So in the second part of the study the urine samples were additionally analyzed with UV-detection for a better estimation of the metabolite concentrations. The concentration of the sulfated metabolites was more than ten times higher than the concentration of the unchanged drug in urine. Other metabolites were not measurable with UV-detection. The di-oxygenated Neu-P11 and an additional mono-oxygenated Neu-P11 showed relatively high signals in MS/MS. Probably the other metabolites, namely glucuronides, unconjugated demethylated Neu-P11 and unconjugated 6OH-Neu-P11, were formed at a lesser extent.

[Dietary supplements--evaluation of patient inquiries at a drug information service]. / Nahrungsergänzungsmittel--Evaluation der Patientenanfragen an einen Arzneimittelberatungsdienst.

BACKGROUND: Dietary supplements are a product group of foods, which are meant to supplement the general nutrition with micronutrients and other substances. They are widely used in Germany. We evaluated the frequency of their use and of information requirements concerning dietary supplements in patients who contacted the independent drug information service at TU Dresden. PATIENTS AND METHODS: All inquiries from 2008 to 2010 were evaluated regarding information requirement about dietary supplements, the kind of products used and characteristics of patients using supplements. Sociodemographic characteristics, kind and number of drugs and dietary supplements as well as underlying diseases were recorded from the inquiring patients. RESULTS: 23.3 % of persons looking for advice used dietary supplements. The most frequently used product groups included vitamins and minerals (52.5 %) as well as plant extracts (14.0 %). Information requirements were especially high for plant extracts and for products containing glucosamine/chondroitin and lutein/zeaxanthin. Users of dietary supplements were exposed to a higher number of different products than non-users. CONCLUSIONS: Information requirements were primarily detected for products without clearly proven benefits or for supplements which are advertised to relieve certain diseases or symptoms although the product characteristics do not support such utilization. The frequency of use of dietary supplements among patients which already receive multiple medications substantiates the necessity to include dietary supplements in assessments of drug interactions and to scrutinize indications for supplement use.

Distribution of metoprolol, tramadol, and midazolam in human autopsy material.

In this study it was possible to measure the distribution of metoprolol, tramadol, and midazolam in human directly in several compartments. In the legal medicine autopsy material is normally investigated to find out the cause of death. But the results of corresponding toxicology measurements often involve more information. With screening methods drugs were detected without connection to the cause of death. The deceased had either a continual therapeutic treatment, a treatment during an operation, or an unsuccessful urgent therapy. A liquid/liquid extraction and a LC/MS/MS method were developed for the determination of the drug concentrations. Different autopsy materials of about 120 cases were investigated. Most frequently the drugs metoprolol, tramadol, and midazolam could be proved and determined simultaneously. Metoprolol was found in seven cases, tramadol in seven cases and midazolam in thirteen cases. The dosage of the drugs was unknown. Therefore and because of the low number of cases statistic calculations were not meaningful and an individual case study was necessary. In all cases with oral metoprolol application the patients probably took a normal customary continuous dosage. The concentrations of tramadol in blood were in the toxic range in three cases. The distribution of tramadol in the compartments was independent of the dosage. The time between oral intake of metoprolol or tramadol and death was unknown. With the distribution pattern of metoprolol in the compartments it was possible to estimate the duration between drug intake and death. In most cases midazolam was given intravenously during an operation or an unsuccessful urgent therapy. Sometimes the time between dosage and death was documented. The duration between application of the drug and death played the crucial role for the distribution of midazolam in the compartments. Measurements of drug concentrations in human autopsy material deepen the knowledge of the respective drugs' pharmacokinetics.