Antiplatelet effects of glycoproteins IIb-IIIa antagonist monafram

First Russian glycoprotein (GP) IIb-IIIa antagonist, preparation Monafram, is the F(ab')2 fragment of anti-GP IIb-IIIa monoclonal antibody FRaMon. In in vitro experiments it was shown that Monafram blocked platelet aggregation induced by ADP and thrombin; reduced secretion from platelet granules; and due to simultaneous interaction with two GP IIb-IIIa molecules almost irreversibly bound to platelet surface. Monafram clinical trials were performed in healthy volunteers (n = 10) and in patients with ischemic heart disease undergoing high risk coronary angioplasty (n = 153). Monafram intravenous bolus administration at 0.25 mg/kg decreased ADP-induced platelet aggregation by more than 90, 80, 60 and 30% at 1, 12, 24 and 72 h after injection, respectively. No significant differences were detected between antiaggregatory effects of Monafram and ReoPro introduced at 0.25 mg/kg bolus + 12 h infusion at 0.125 microg/kg per min. Durable inhibition of aggregation after Monafram administration was mediated by platelet-bound preparation--free Monafram was cleared from plasma within 12 h, while platelet-bound preparation occupied more than 90, 70-80 and 40-50% of GP IIb-IIIa at 1, 12-24 and 72 h after injection, respectively. Major bleedings and allergic reactions were detected in none of patients, deep thrombocytopenia--in one patient and antibodies against Monafram--in 5% of patients. Within one month after coronary angioplasty Monafram decreased the number of end points (fatal and nonfatal myocardial infarction and angina recurrence) from 11.4 to 3.3%.     

Flow laser cytometry for evaluation of the human immune system

Some flow laser cytometry (FLC) techniques intended for studies of the immune system cells are reviewed. A widespread analytical method is the phenotyping of lymphocytes by the markers they express. The use of FLC permits the evaluation of practically all functional parameters of immunocompetent cells. Thus, to analyze their ingestive and microbicidal activity fluorochrome-labeled microorganisms are used. The apploication of indicator dyes makes it possible to evaluate calcium mobilization and formation of active forms of oxygen. FLC is used for the identification of cytokines inside the cell and in the medium. The authors propose tests for the analysis of the proliferative activity of lymphocytes, the cytotoxicity of natural killers, the evaluation of apoptosis and protein processing with monocytes/macrophages.     

The influence of partial androgen deficiency of aging men (PADAM) on the impulse regime of incretion of several hormones and mitotic activity

This research work is devoted to an important subject--study of the impulse regime of the incretion of a series of hormones among men with partial androgen deficience of aging men (PADAM). The results of this study suggest that PADAM leads to a breakdown of the impulse regime of incretion of a series of hormones, including luteinizing hormone (LH), follicle stimulating hormone (FSH), and somatotropic hormones (STH), as well as cortisol and insulin among men of older age groups. These changes accompany the development of metabolic syndrome (X-syndrome); their development can be inversed through androgen-replacement therapy.     

Valid and reliable instruments for arm-hand assessment at ICF activity level in persons with hemiplegia: a systematic review

Background

Loss of arm-hand performance due to a hemiparesis as a result of stroke or cerebral palsy (CP), leads to large problems in daily life of these patients. Assessment of arm-hand performance is important in both clinical practice and research. To gain more insight in e.g. effectiveness of common therapies for different patient populations with similar clinical characteristics, consensus regarding the choice and use of outcome measures is paramount. To guide this choice, an overview of available instruments is necessary. The aim of this systematic review is to identify, evaluate and categorize instruments, reported to be valid and reliable, assessing arm-hand performance at the ICF activity level in patients with stroke or cerebral palsy.

Methods

A systematic literature search was performed to identify articles containing instruments assessing arm-hand skilled performance in patients with stroke or cerebral palsy. Instruments were identified and divided into the categories capacity, perceived performance and actual performance. A second search was performed to obtain information on their content and psychometrics.

Results

Regarding capacity, perceived performance and actual performance, 18, 9 and 3 instruments were included respectively. Only 3 of all included instruments were used and tested in both patient populations. The content of the instruments differed widely regarding the ICF levels measured, assessment of the amount of use versus the quality of use, the inclusion of unimanual and/or bimanual tasks and the inclusion of basic and/or extended tasks.

Conclusions

Although many instruments assess capacity and perceived performance, a dearth exists of instruments assessing actual performance. In addition, instruments appropriate for more than one patient population are sparse. For actual performance, new instruments have to be developed, with specific focus on the usability in different patient populations and the assessment of quality of use as well as amount of use. Also, consensus about the choice and use of instruments within and across populations is needed.     

Endocrine regulation of the reproduction in crustaceans: Identification of potential targets for toxicants and environmental contaminants

Progress in ecotoxicological research documents that crustaceans are highly vulnerable to diverse chemicals and toxicants in the environment. In particular, pollutants affecting endocrine homeostasis in crustaceans (i.e., endocrine disruptors) are intensively studied, and serious reproductive disorders have been documented. In this review, current knowledge about the endocrine regulation of the crustacean reproduction is put together with the published ecotoxicological data with an attempt to summarize the potential of xenobiotics to affect crustacean reproduction. Following gaps and trends were identified: (1) Studies are required in the field of neurohormone (serotonin and dopamine) regulation of the reproduction and possible modulations by environmental toxicants such as antidepressant drugs. (2) Molting-related parameters (regulated by ecdysteroid hormones) are closely coordinated with the development and reproduction cycles in crustaceans (cross-links with methyl farnesoate signalling), and their susceptibility to toxicants should be studied. (3) Other biochemical targets for xenobiotics were recently discovered in crustaceans and these should be explored by further ecotoxicological studies (e.g., new information about ecdysteroid receptor molecular biology). (4) Some sex steroid hormones known from vertebrates (testosterone, progesterone) have been reported in crustaceans but knowledge about their targets (crustacean steroid receptors) and signalling is still limited. (5) Determination of the sex in developing juveniles (affecting the sex ratio in population) is a sensitive parameter to various xenobiotics (including endocrine disruptors) but its modulation by general environmental stress and non-specific toxicity should be further studied.     

Human exposure to mycotoxins in Egypt

This investigation examined the exposure of Egyptian infants to Aflatoxin M₁ (AfM₁) and of lactating mothers to Aflatoxin B₁, using AfM₁ in human milk as a biomarker for exposure to AfB₁. The presence of ochratoxin A (OA) in human milk was also investigated to determine the levels of infants exposure to OA from human milk. The results indicated that AfM₁ was found in 66 (55 %) of 120 human milk samples with a mean of 0.3 ± 0.53 ng/mL (range 0.02 to 2.09 ng/mL). OA was found in 43 (35.8 %) of 120 human milk samples with a mean of 21.1 ± 13.7 ng/mL (range 5.07 to 45.01 ng/mL), which will cause a daily intake of OA from human milk exceeding the suggested tolerable dose of 5 ng/kg_-1 of OA body weight. On the other side AfM₁ was found in 25 % of blood samples (5 out of 20 samples), at a mean of 1.18 ng/mL, but it was detected only in one urine sample (1 out of 20 samples). OA was detected only in 2 out of 13 blood samples (15.4 %) with an average 3.67 ng/mL. Whereas OA was not detected in all analyzed urine samples.     

Mechanisms of inhibition of vascular-platelet hemostasis by salivary gland secretion of the medicinal leech Hirudo medicinalis

The mechanism of inhibition of the vascular-platelet stage of hemostasis by medicinal leech salivary gland secretion was studied. It was shown that the secretion blocks platelet adhesion on the surface of collagens belonging to different genetic classes, inhibits the primary attachment of platelets and completely suppresses their spreading on collagen surface. Whatever its antithrombin activity, the leech secretion inhibits platelet aggregation stimulated by various inductors, e. g., ADP, prostaglandin endoperoxide analog U-46619, Ca2+ ionophore A23187, arachidonic acid. The secretion possessing the antithrombin activity causes a greater inhibition of the thrombin-stimulated aggregation than that devoid of this activity. Leech secretion stimulates adenylate cyclase of platelet membranes in a receptor-mediated fashion and increases the level of cAMP. The active substance is a low molecular weight, thermostable trypsin-resistant fraction of the secretion. Stimulation of adenylate cyclase is not mediated by adenosine receptors. It is supposed that the mechanism of this activating effect involves platelet prostaglandin receptors.     

Asymmetry of modifications of the electrical activity of the rat cortex induced by intraventricular injections of thyrotropin-releasing hormone

We studied modifications in the mass electrical activity of the cortex (ECoG) induced by injections of thyrotropin-releasing hormone (TRH) into the left or right lateral brain ventricle in rats kept under conditions close to free behavior. It was found that these effects are characterized by a significant interhemisphere asymmetry. We postulate that the pharmacological (in particular, antidepressive) effects of TRH are related to its ability to intensify inhibitory processes in the left cerebral hemisphere and activating processes in the right hemisphere.Neirofiziologiya/Neurophysiology, Vol. 36, Nos. 5/6, pp. 386–390, September–December, 2004.This revised version was published online in April 2005 with a corrected cover date and copyright year.