Homone

Developmented and introduction into clinical practice of the sciatic nerve blockade as method of guided anesthesia/analgesia for pain syndromes and surgical interventions on the lower legs. Anaesthesia was analyzed in 35 patients. In 15 patients used the blockade of the sciatic nerve bifurcation proposed method with the popliteal fossa in acute and chronic pain syndromes and comparison with spinal anesthesia in 20. Blockade of the sciatic nerve at the site of its bifurcation provides a highly efficient and long-lasting nerve block zones of innervation is sufficient to perform the surgery...

Anesthesiological support of 47 patients, while performing reconstructive operations on the lower extremities arteries in presence of the third level of operative risk (according to ASA), was analyzed; of them in 24 - a spinal anesthesia was applied, in 23 - a reduced spino-epidural anesthesia. Application of a spino-epidural anesthesia/analgesia with reduction of the dose of a spinal component and usage of analgesia instead of anesthesia secures lesser intraoperative oscillations of hemodynamic indices in comparison with such while performing spinal anesthesia, as well as better antinociceptive protection, is also characterized by small toxic impact on the patient, demands application of a sedative and the infusion therapy of lesser volume...

This paper explores arguments for and against same-sex marriage as 'movement advocacy' in the USA as a backdrop to the proposition that, despite the influence of US discourses on South African debates about same-sex marriage, US discussions are less important to understanding South African responses than controversies about marriage itself in the country. The paper works in two sections. First it sketches legal and critical tensions within the USA around the implications of same-sex marriage activism, drawing on work from Franke, Brandzel, Grossman, Puar and others...

Experience of surgical treatment was summarized and its results were analyzed in patients, suffering biliary calculous disease, coexistent with other surgical diseases of abdominal organs. Main aspects of diagnosis and prognosis for efficacy of simultant operations were presented, and there were also adduced the method of prognosis of the operative treatment results in such patients, the proposed principle of determination of indications and contraindications for performance of simultant laparoscopic operations, a scale of the risk estimation for performance of such operative interventions...

Auditory steady-state responses (ASSRs) are widely applied to test brain's ability to follow external stimulation in neuropsychiatric disorders. It is known that ASSRs are related to GABAergic transmission. Female sex steroid homones - both estrogens and progesterone - affect functioning of GABAergic system. However, it is not known how these hormones affect brain's ability to entrain. This study was designed to test the ability to synchronize to 40 Hz stimulation during different phases of the menstrual cycle...

Bone is a dynamic tissue that undergoes renewal and repair throughout life through the process of bone remodelling. Skeletal homeostasis is achieved through coupled and balanced bone resorption and bone formation. Several local and systemic factors regulate these processes, including sex hormones. Estrogenes and androgens influence growth, maturation and maintenance of bone mass. Sex homones act on bone through multiple mechansims. Sex hormones influence synthesis and secretion of many growth factors and cytokines, and play therefore a central role in the regulation of bone metabolism...

Ames dwarf mice, which are small and deficient in growth homone (GH), prolactin (PRL), and thyroid stimulating hormone (TSH) live much longer (1-1.25 years) than their normal siblings. It was of interest to examine the response of these animals to caloric restriction (CR) because of the possibility that dwarf mice are voluntarily caloric restricted. We are testing the hypothesis that this possible natural caloric restriction will negate any benefits of an imposed CR on lifespan. Male and female Ames dwarf mice and their normal counterparts have been fed ad libitum (AL) or a 30% CR diet for 25-29 months...

In most large scale trials the prognosis of ischemic heart failure is worse than in patients with non-ischemic etiology. The therapeutic effect of essential drugs such as ACE-inhibitors, betablockers and diuretics is similar, but response to some other drugs (amiodarone, amlodipine, digoxin, growth homone) is better in non-ischemic heart failure. Of great practical importance is the recognition of hibernating myocardium in coronary artery disease, since revascularisation may significantly improve left ventricular function...

Family and personal history as well as clinical examination are the basic data to be known before laboratory examinations should be started. To obtain results that can be correctly interpreted, the blood sampling has to be done in the early morning hours between day 1 and 5 of the cycle, and for some homones on an empty stomach. Depending on the clinical data, the hormonal screening can be selective and well directed, or it has to be broader. The presence or absence of galactorrhea, of hot flushes and of androgenization or virilization play an important role for the decision about the hormones to be determined...

OBJECTIVE: To explore the effects of soy protein on the expression of SREBP-1,2 in rats feeding normal and high-fat diet. METHODS: Forty eight Sprague-Dawley SPF class rats were randomly divided into 4 groups matched by body weight, soy protein group, casein group, soy protein-high fat group, casein-high fat group. The experiment diets were fed for 28 d. Then the rats were sacrificed off cervical, determined serum levels of homone and the level of gene expression...

Chronic renal failure, characterised by two factors acting in opposite directions with respect to the serum thyroid homone levels was chosen for the study. Healthy controls, donors undergoing nephrectomy and renal transplant recipients were studied. In transplant recipients, presurgical levels of total thyroxine(TT4), free triiodothyronine(FT3) and free thyroxine(FT4) were lower than controls, and immediately after the release of arterial clamps, there was an upsurge of total triiodothyronine (TT3), TT4, FT3 and FT4 due to administered and/or endogeneously secreted catecholamines...

The glucagon gene is expressed not only in the alpha cells of the pancreatic islets but also in the endocrine cells of the intestinal epithelium (so-called L-cells), and in certain neurons of the brain stem. Whereas in the pancreas, glucagon, the hyperglycaemic hormone, is cleaved out of the 160 amino acid precursor, proglucagon, leaving behind proglucagon fragments (PG 1-30 and PG 72-158, the so-called major proglucagon fragment (MPGF)) that are probably inactive, the intestinal processing leads to the formation of glicentin (PG 1-69; action uncertain) and glucagon-like peptides 1 (PG 78-107amide, a potent incretin homone, regulating insulin secretion, glucagon secretion, gastrointestinal motility and appetite) and 2 (PG 126-158, a regulator of gut mucosal growth and integrity)...

Parathyroid hormone-related protein (PTHrP) plays an important role in regulating embryonic skeletal development and is abnormally regulated in the pathogenesis of skeletal complications observed with many cancers and osteoporosis. It exerts its action through binding to a G-protein-coupled seven-transmembrane cell-surface receptor (GPCR). Structurally, GPCRs are very difficult to study by X-ray crystallography. In this study, a monoclonal antibody Fab fragment which recognizes the same region of PTHrP as its receptor, PTH1R, was used to aid in the crystallization of PTHrP...

A series of inhibitors of Pim-2 kinase identified by high-throughput screening is described. Details of the hit validation and lead generation process and structure-activity relationship (SAR) studies are presented. Disclosure of an unconventional binding mode for 1, as revealed by X-ray crystallography using the highly homologous Pim-1 protein, is also presented, and observed binding features are shown to correlate with the Pim-2 SAR. While highly selective within the kinase family, the series shows similar potency for both Pim-1 and Pim-2, which was expected on the basis of homology, but unusual in light of reports in the literature documenting a bias for Pim-1...

Aminopeptidase N (APN) or CD13 is a conserved type II integral membrane zinc-dependent metalloprotease in the M1 family of ectoenzymes. APN is abundant in the kidneys and central nervous system. Identified substrates include Angiotensin III (Ang III); neuropeptides, including enkephalins and endorphins; and homones, including kallidan and somatostatin. It is developmentally expressed, a myelomonocytic marker for leukemias, and a receptor for coronovirus. There is evolving support for APN in the regulation of arterial blood pressure and the pathogenesis of hypertension...

With the transition from manual to robotic HTS in the last several years, assay optimization has become a significant bottleneck. Recent advances in robotic liquid handling have made it feasible to reduce assay optimization timelines with the application of statistically designed experiments. When implemented, they can efficiently optimize assays by rapidly identifying significant factors, complex interactions, and nonlinear responses. This article focuses on the use of statistically designed experiments in assay optimization...

Histone lysine methylation has important roles in the organization of chromatin domains and the regulation of gene expression. To analyze its function and modulate its activity, we screened for specific inhibitors against histone lysine methyltransferases (HMTases) using recombinant G9a as the target enzyme. From a chemical library comprising 125,000 preselected compounds, seven hits were identified. Of those, one inhibitor, BIX-01294 (diazepin-quinazolin-amine derivative), does not compete with the cofactor S-adenosyl-methionine, and selectively impairs the G9a HMTase and the generation of H3K9me2 in vitro...

Numerous assay methods have been developed to identify small-molecule effectors of protein kinases, but no single method can be applied to all isolated kinases. The authors developed a set of 3 high-throughput screening (HTS)-compatible biochemical assays that can measure 3 mechanistically distinct properties of a kinase active site, with the goal that at least 1 of the 3 would be applicable to any kinase selected as a target for drug discovery efforts. Two assays measure catalytically active enzyme: A dissociation-enhanced lanthanide fluoroimmuno assay (DELFIA) uses an antibody to quantitate the generation of phosphorylated substrate; a second assay uses luciferase to measure the consumption of adenosine triphosphate (ATP) during either phosphoryl-transfer to a peptide substrate or to water (intrinsic ATPase activity)...

An uHTS campaign was performed to identify selective inhibitors of PKC-theta. Initial triaging of the hit set based on selectivity and historical analysis led to the identification of 2,4-diamino-5-nitropyrimidines as potent and selective PKC-theta inhibitors. A homology model and initial SAR is presented demonstrating that a 2-arylalkylamino substituent in conjunction with suitable 4-diamino substituent are essential for achieving selectivity over many kinases. Additional hit to lead profiling is presented on selected compounds...

High-throughput screening is routinely employed as a method for the identification of novel hit structures. Large numbers of active compounds are typically procured in this way and must undergo a rigorous validation process. This process is described in detail for a collection of screening hits identified as inhibitors of IkappaB kinase-beta (IKKbeta), a key regulatory enzyme in the nuclear factor-kappaB (NF-kappaB) pathway. From these studies, a promising hit series was selected. Subsequent lead generation activities included the development of a pharmacophore hypothesis and structure-activity relationship (SAR) for the hit series...