The morphological and histochemical neurosecretory magnocellular system in the rat after administration of chlorpromazine

The effect of chlorpromazine (CPZ) on the neurosecretory action of the hypothalamo- hypophyseal system was investigated in 72 male rats. The experimental animals received CPZ in a dose of 0.4 mg, 4.0 mg and 20.0 mg/kg b.w. for 30 days. The rats were sacrificed by decapitation at 24 h and 7 days after the last dose of the drug. The neurosecretory material was stained with paraldehyde fuchsin in the supraoptic nucleus, paraventricular nucleus, eminentia mediana and neurohypophysis, the tigroid was stained with toluidine blue and the acid phosphatase activity was evaluated histoenzymatically. It was found that CPZ reduced the content of the neurosecretory material after 24 h, while an increase was observed 7 days after the last drug administration

Dactinomycin-induced veno-occlusive disease in rats. The hepatoprotective action of amifostine. Evaluation in a light and electron microscope

The purpose of the study was to draw upan experimental model of hepatic veno-occlusive disease (VOD) induced by dactinomycin (ACT) and to investigate the possible hepatoprotective effects of Ethyol (amifostine). Pathological changes corresponding to a VOD picture of varying intensification were found in the liver samples obtained from all the rats receiving ACT. Amifostine appears to act protectively to liver changes caused by dactinomycin

A preliminary evaluation of thyroid and respiratory tract neuroendocrine cells in the rat after experimental hypercalcaemia

The goal of this study was to investigate the influence of experimentally induced hypercalcaemia (after 100000 UI Vigantol and CaCl2) on neuroendocrine cells (NECs) in the thyroid and airways in the rat. After 24 h, 7 days and 14 days the thyroid and lungs were collected. Paraffin sections were immunocytochemically stained with specific antibodies against CGRP, calcitonin (CT) and synaptophysin (SY) in the airway NECs and thyroid C cells. The largest hypercalcaemia were observed in experimental rats after 7 days. More significant changes in the number and size of neuroendocrine cells were observed in the thyroid gland as well as in the airways. In the airways only a slight increase in the number of neuroepithelial bodies (NEBs) was observed, some of which gave evidence of hypertrophy symptoms

Effects of CP 55,940 — agonist of CB1 cannabinoid receptors on ghrelin and somatostatin producing cells in the rat pancreas

Cannabinoids participate in the modulation of numerous functions in the human organism, increasing the sense of hunger, affecting carbohydrate and lipid metabolism, and controlling systemic energy balance mechanisms. Moreover, they influence the endocrine system functions, acting via two types of receptors, CB1 and CB2. The aim of the present study was to examine the number, distribution and activity of ghrelin and somatostatin producing endocrine cells in the pancreas of rats after a single administration of selective CP 55,940 agonist of CB1 receptor. The study was performed on 20 rats. Neuroendocrine cells were identified by immunohistochemical reactions, involving specific antibodies against ghrelin and somatostatin. The distribution and number of ghrelin- and somatostatin-immunoreactive cells were separately studied in five pancreas islets of each section. A performed analysis showed a decreased number of somatostatin-immunoreactive cells and a weak immunoreactivity of ghrelin and somatostatin containing neuroendocrine cells in the pancreatic islets of experimental rats, compared to control animals. The obtained results suggest that a single administration of a selective CP 55,940 agonist of CB1 receptor influences the immunoreactivity of endocrine cells with ghrelin and somatostatin expression in the pancreas islets

Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial

Background: Glucagon-like peptide 1 receptor agonists differ in chemical structure, duration of action, and in their effects on clinical outcomes. The cardiovascular effects of once-weekly albiglutide in type 2 diabetes are unknown. We aimed to determine the safety and efficacy of albiglutide in preventing cardiovascular death, myocardial infarction, or stroke. Methods: We did a double-blind, randomised, placebo-controlled trial in 610 sites across 28 countries. We randomly assigned patients aged 40 years and older with type 2 diabetes and cardiovascular disease (at a 1:1 ratio) to groups that either received a subcutaneous injection of albiglutide (30–50 mg, based on glycaemic response and tolerability) or of a matched volume of placebo once a week, in addition to their standard care. Investigators used an interactive voice or web response system to obtain treatment assignment, and patients and all study investigators were masked to their treatment allocation. We hypothesised that albiglutide would be non-inferior to placebo for the primary outcome of the first occurrence of cardiovascular death, myocardial infarction, or stroke, which was assessed in the intention-to-treat population. If non-inferiority was confirmed by an upper limit of the 95% CI for a hazard ratio of less than 1·30, closed testing for superiority was prespecified. This study is registered with ClinicalTrials.gov, number NCT02465515. Findings: Patients were screened between July 1, 2015, and Nov 24, 2016. 10 793 patients were screened and 9463 participants were enrolled and randomly assigned to groups: 4731 patients were assigned to receive albiglutide and 4732 patients to receive placebo. On Nov 8, 2017, it was determined that 611 primary endpoints and a median follow-up of at least 1·5 years had accrued, and participants returned for a final visit and discontinuation from study treatment; the last patient visit was on March 12, 2018. These 9463 patients, the intention-to-treat population, were evaluated for a median duration of 1·6 years and were assessed for the primary outcome. The primary composite outcome occurred in 338 (7%) of 4731 patients at an incidence rate of 4·6 events per 100 person-years in the albiglutide group and in 428 (9%) of 4732 patients at an incidence rate of 5·9 events per 100 person-years in the placebo group (hazard ratio 0·78, 95% CI 0·68–0·90), which indicated that albiglutide was superior to placebo (p<0·0001 for non-inferiority; p=0·0006 for superiority). The incidence of acute pancreatitis (ten patients in the albiglutide group and seven patients in the placebo group), pancreatic cancer (six patients in the albiglutide group and five patients in the placebo group), medullary thyroid carcinoma (zero patients in both groups), and other serious adverse events did not differ between the two groups. There were three (<1%) deaths in the placebo group that were assessed by investigators, who were masked to study drug assignment, to be treatment-related and two (<1%) deaths in the albiglutide group. Interpretation: In patients with type 2 diabetes and cardiovascular disease, albiglutide was superior to placebo with respect to major adverse cardiovascular events. Evidence-based glucagon-like peptide 1 receptor agonists should therefore be considered as part of a comprehensive strategy to reduce the risk of cardiovascular events in patients with type 2 diabetes. Funding: GlaxoSmithKline

Atrasentan and renal events in patients with type 2 diabetes and chronic kidney disease (SONAR): a double-blind, randomised, placebo-controlled trial

Background: Short-term treatment for people with type 2 diabetes using a low dose of the selective endothelin A receptor antagonist atrasentan reduces albuminuria without causing significant sodium retention. We report the long-term effects of treatment with atrasentan on major renal outcomes. Methods: We did this double-blind, randomised, placebo-controlled trial at 689 sites in 41 countries. We enrolled adults aged 18–85 years with type 2 diabetes, estimated glomerular filtration rate (eGFR)25–75 mL/min per 1·73 m 2 of body surface area, and a urine albumin-to-creatinine ratio (UACR)of 300–5000 mg/g who had received maximum labelled or tolerated renin–angiotensin system inhibition for at least 4 weeks. Participants were given atrasentan 0·75 mg orally daily during an enrichment period before random group assignment. Those with a UACR decrease of at least 30% with no substantial fluid retention during the enrichment period (responders)were included in the double-blind treatment period. Responders were randomly assigned to receive either atrasentan 0·75 mg orally daily or placebo. All patients and investigators were masked to treatment assignment. The primary endpoint was a composite of doubling of serum creatinine (sustained for ≥30 days)or end-stage kidney disease (eGFR <15 mL/min per 1·73 m 2 sustained for ≥90 days, chronic dialysis for ≥90 days, kidney transplantation, or death from kidney failure)in the intention-to-treat population of all responders. Safety was assessed in all patients who received at least one dose of their assigned study treatment. The study is registered with ClinicalTrials.gov, number NCT01858532. Findings: Between May 17, 2013, and July 13, 2017, 11 087 patients were screened; 5117 entered the enrichment period, and 4711 completed the enrichment period. Of these, 2648 patients were responders and were randomly assigned to the atrasentan group (n=1325)or placebo group (n=1323). Median follow-up was 2·2 years (IQR 1·4–2·9). 79 (6·0%)of 1325 patients in the atrasentan group and 105 (7·9%)of 1323 in the placebo group had a primary composite renal endpoint event (hazard ratio [HR]0·65 [95% CI 0·49–0·88]; p=0·0047). Fluid retention and anaemia adverse events, which have been previously attributed to endothelin receptor antagonists, were more frequent in the atrasentan group than in the placebo group. Hospital admission for heart failure occurred in 47 (3·5%)of 1325 patients in the atrasentan group and 34 (2·6%)of 1323 patients in the placebo group (HR 1·33 [95% CI 0·85–2·07]; p=0·208). 58 (4·4%)patients in the atrasentan group and 52 (3·9%)in the placebo group died (HR 1·09 [95% CI 0·75–1·59]; p=0·65). Interpretation: Atrasentan reduced the risk of renal events in patients with diabetes and chronic kidney disease who were selected to optimise efficacy and safety. These data support a potential role for selective endothelin receptor antagonists in protecting renal function in patients with type 2 diabetes at high risk of developing end-stage kidney disease. Funding: AbbVie

Early education of child from the perspective of selected experiences and student research

This article is a report of individuating qualititative research on perception of early education by 55 senior students of the full-time and part-time BA programme of studies preparing for teaching kindergarten and early education. Quoted and interpreted are only some of the very diverse examples of events, descriptions of student observations and research conducted in the years 2008-2010 in Warsaw and its surroundings. They indicate that education on this level is a highly formalized process and focused on observable behavior of the child, leading to a measureable result. Additionally, both the teachers and the students participating in the study have shown a significant lack of psychopedagogical knowledge and low reflexivity. Unfortunately, these conclusions are consistent with the critical assessments formulated by the scientific community on the basis of research and analysis undertaken due to reforms of the education system in recent years.Udostępnienie publikacji Wydawnictwa Uniwersytetu Łódzkiego finansowane w ramach projektu „Doskonałość naukowa kluczem do doskonałości kształcenia”. Projekt realizowany jest ze środków Europejskiego Funduszu Społecznego w ramach Programu Operacyjnego Wiedza Edukacja Rozwój; nr umowy: POWER.03.05.00-00-Z092/17-00

Variable contexts of early school education

In this work, the plate bending formulation of the boundary element method - BEM, based on the Reissner's hypothesis, is extended to the analysis of plates reinforced by beams taking into account the membrane effects. The formulation is derived by assuming a zoned body where each sub-region defines a beam or a slab and all of them are represented by a chosen reference surface. Equilibrium and compatibility conditions are automatically imposed by the integral equations, which treat this composed structure as a single body. In order to reduce the number of degrees of freedom, the problem values defined on the interfaces are written in terms of their values on the beam axis. Initially are derived separated equations for the bending and stretching problems, but in the final system of equations the two problems are coupled and can not be treated separately. Finally are presented some numerical examples whose analytical results are known to show the accuracy of the proposed model