Simultaneous quantification of isoniazid,rifampicin, ethambutol and pyrazinamide by liquid chromatography/tandem mass spectrometry

A remediable cause of poor treatment response in drug‐susceptible tuberculosis (TB) patients may be low plasma levels of one or more of the first‐line anti‐TB drugs. The aim of this work was to develop an accurate and precise LC‐MS/MS method for simultaneous quantification of all four first‐line anti‐TB drugs in plasma suitable for therapeutic drug monitoring (TDM). To adjust for degradation and losses during sample preparation, isotopically labeled compounds were used as internal standards. Plasma samples spiked with internal standards were extracted using protein precipitation with methanol and acetonitrile. Simultaneous separation of all four drugs was accomplished with a Chromolith Reversed‐Phase column and mobile phases consisting of water, methanol, ammonium acetate and formic acid with subsequent mass spectrometric quantification. The linear range of the calibration curve for isoniazid was 0.5–10 mg/L, for rifampicin 0.75–30 mg/L, for ethambutol 0.25–10 mg/L and for pyrazinamide 4–80 mg/L. The lower limit of quantification was 0.5 mg/L, 0.75 mg/L, 0.25 mg/L and 4.0 mg/L, respectively. Precision estimated by the coefficient of variation was <15% for all four drugs. The LC‐MS/MS method can readily be used for simultaneous quantification of first‐line anti‐TB drugs in plasma and is well suited for TDM.     

Effect of hyperthermia and anoxia on glucocorticoid and mineralocorticoid receptor expression in neonatal rat hippocampus

Brief periods of neonatal asphyxia are frequently observed. Within the CNS, the hippocampus is known to be particularly vulnerable to the damaging effects of hypoxia/ischaemia. The hippocampus contains the highest concentration of both mineralocorticoid (MR) and glucocorticoid (GR) receptors and the balance between MR/GR activation influences cell birth and death. MR occupation appears to promote prosurvival actions, while GR overactivation favours neurodegeneration. It has been widely recognized that core body temperature is a critical determinant of the severity of hypoxic–ischemic brain injury; indeed, hyperthermia exacerbates the degree of damage. Therefore, the aim of the present investigation was to study the effect of elevated body temperature in newborn rats under control conditions or during neonatal exposure to a critical anoxia, on changes of MR and GR mRNA expression in the rat hippocampus. 2-day-old rats were exposed to anoxia in 100% nitrogen atmosphere. Rectal temperature was kept at 33 °C (typical for the rat neonates), or elevated to a level typical for febrile (39 °C) adults. Control rats were exposed to atmospheric air under the respective thermal conditions. The changes in MR and GR mRNA expression in hippocampus were examined 24 h after exposure. Our data show that hyperthermia with or without added anoxia, causes induction of MR mRNA expression in neonatal rat hippocampus without any effect on GR mRNA expression. We suggest this elevation of MR plays an important role in modulating the survival of neurons in the injured hippocampus.     

Acute myocardial infarction during pregnancy complicated with pulmonary oedema

Acute myocardial infarction, a rare peripartum event, is accompanied by significant maternal and fetal mortality. We report a 41-year-old woman who developed an acute myocardial infarction during the third trimester of pregnancy. The case of infarction was complicated with pulmonary oedema on the 3 day after delivery. Coronary angiography was performed 7 weeks post partum and no coronary lesions were detected. Therapeutic options in such condition are discussed and review of relevant literature is presented.     

Binding of cadmium on metallothionein in man: an analysis of a fatal poisoning by cadmium iodide

This study presents data on the organ distribution of cadmium, and Cd-protein complexes in the body of a man fatally poisoned with CdJ₂, after an oral dose of about 5 g.The levels of cadmium in different tissues were (in g per g fr. wt.): liver and kidney cortex about 80, kidney medulla, heart and testes 8.9–10.0, bile 1.9, brain 0.5 and blood 1.1.Almost all cadmium detected in the organism was bound to a low molecular weight protein, tentatively identified as metallothionein.Total amount of 18 mg cadmium was excreted in urine within 6 days of hospitalization, most likely due to Ca-EDTA treatment.The data are suggestive that cadmium induced biosynthesis of metallothionein in the subject.This paper was presented at the 2nd Symposium of Toxicology and Seminar of Pharmacology, Dvoák, September 18–19, 1970.     

Psychopharmacotherapy of anxiety, obsessive-compulsive and sleep disorders during pregnancy and lactation

The aim of the third part of our work, associated with psychopharmacotherapy during pregnancy and lactation is to present guidelines of expert--groups concerning the current rules of treating anxiety, obsessive--compulsive and sleep disorders and actual data about spreading of these disorders, pre- and perinatal effects of drugs used and the classification of them according to FDA and the safety of these medications for the breast fed newborn.     

Psychopharmacotherapy of psychotic disorder during pregnancy and lactation

The aim of our work based on the global literature-review is to present the guidelines of the psychopharmacotherapy during pregnancy and lactation recommended by various experts-groups as followed: 1. American Academy of Pediatrics, American Psychiatric Association, American College of Obstetricians and Gynecologists, The Maudsley Guidelines, Department of Psychiatry, Medical University of Mainz, Institute of Psychiatry and Neurology in Warsaw. In the first part the guidelines concerning to psychopharmacotherapy of psychotic disorders have been presented and actual data about spreading of these illnesses, pre- and perinatal effects of drugs used, the classification of neuroleptic drugs according to FDA and the safety of these medicines for the breast fed newborn.     

Leukemia inhibitory factor: an important regulator of endometrial function

PROBLEM: Leukemia inhibitory factor (LIF) is multifunctional cytokine that displays biological activities in different cells, including endometrial cells. The aim of this study is to describe implications of LIF on a physiological function of endometrium. METHOD OF STUDY: The role of LIF in the endometrial function is reviewed and summarized from the available literature. RESULTS: LIF plays an important role in a physiological function of endometrium. In human endometrial LIF expression depends on cellular localizations, steroid hormones, menstrual stages and a local cytokine network. Stronger LIF expression exists in an endometrial epithelium during a luteal phase of the menstrual cycle, which coincides with the time of an implantation. The impairments of the endometrial LIF expression may play a significant role in the pathological processes involving implantation and the infertility. CONCLUSIONS: There is a substantial evidence that LIF is a potential regulator of the endometrial function and might be one of the factors that play a key role in human reproduction.