CHANGES IN THE SYSTEM HISTIDINE DECARBOXYLASE-HISTAMINE HISTAMINASE IN NEWBORN THYMECTOMIZED RATS

No abstract

Neuroactive steroids in depression and anxiety disorders: Clinical studies

Certain neuroactive steroids modulate ligand-gated ion channels via non-genomic mechanisms. Especially 3 alpha-reduced pregnane steroids are potent positive allosteric modulators of the gamma-aminobutyric acid type A (GABA(A)) receptor. During major depression, there is a disequilibrium of 3 alpha-reduced neuroactive steroids, which is corrected by clinically effective pharmacological treatment. To investigate whether these alterations are a general principle of successful antidepressant treatment, we studied the impact of nonpharmacological treatment options on neuroactive steroid concentrations during major depression. Neither partial sleep deprivation, transcranial magnetic stimulation, nor electroconvulsive therapy affected neuroactive steroid levels irrespectively of the response to these treatments. These studies suggest that the changes in neuroactive steroid concentrations observed after antidepressant pharmacotherapy more likely reflect distinct pharmacological properties of antidepressants rather than the clinical response. In patients with panic disorder, changes in neuroactive steroid composition have been observed opposite to those seen in depression. However, during experimentally induced panic induction either with cholecystokinine-tetrapeptide or sodium lactate, there was a pronounced decline in the concentrations of 3 alpha-reduced neuroactive steroids in patients with panic disorder, which might result in a decreased GABAergic tone. In contrast, no changes in neuroactive steroid concentrations could be observed in healthy controls with the exception of 3 alpha,5 alpha-tetrahydrodeoxycorticosterone. The modulation of GABA(A) receptors by neuroactive steroids might contribute to the pathophysiology of depression and anxiety disorders and might offer new targets for the development of novel anxiolytic compounds. Copyright (c) 2006 S. Karger AG, Basel

Cytokine profile in community-acquired pneumonia in children

Community-acquired pneumonia (CAP) is one of the most common acute infectious diseases. To date, the incidence of CAP among children was decreased significantly worldwide, mainly due to increasing use of effective preventive measures. Nevertheless, CAP remains a common cause of childhood morbidity and mortality. Pneumonia may develop at any age, but most often it occurs in young children, who are more likely to have a more severe course of pneumonia. Currently, early diagnosis and prognosis of the disease severity in children is an urgent issue. It was found that, in most cases, a panel of conventional biomarkers, including the number of leukocytes, procalcitonin, CRP is not sufficient for the diagnosis of pediatric CAP. There is a demand for new biological markers which, along with clinical evaluation, may significantly improve diagnostics and management of CAP in children, thus reducing the risk of adverse outcomes associated with this disease. Such markers could be found among the cytokines, which are active participants in the CAP pathogenesis. The aim of this study was to determine the level of several cytokines in blood serum of children with CAP and to assess changes in the cytokine profile depending on the patient’s age and severity of the disease. The study included 117 children aged 1 to 18 years with a diagnosis of CAP confirmed by X-ray examination. The comparison group included 28 healthy children who did not have CAP or other signs of acute respiratory viral infection at the time of examination, being free of any chronic pathology requiring outpatient observation. A number of cytokines were determined quantitatively in blood serum, i.e., IL-1β, IFNγ, IL-2, IL-4, IL-6, IL-10, TNFα, IFNλ2 (IL-28A), IFNλ3 (IL-28B), IL-8, MCP-1, IL-17AF, GM-CSF using test systems based on the “sandwich” method of solid-phase ELISA using peroxidase labeling. As a result, it was found that the content of IL-6, IL-17AF, IL-1β, IFNγ, MCP-1, IFNλ2 (IL-28A), IFNλ3 (IL-28B), GM-CSF was significantly higher in the group of children with severe community-acquired pneumonia. The levels of certain cytokines, e.g., IL-6, IFNλ2 (IL-28A), IFNλ3 (IL-28B), GM-CSF varied depending on the age of patients, thus, probably, reflecting the degree of immune system activation in the children of different age groups

An inventory of the Aspergillus niger secretome by combining in silico predictions with shotgun proteomics data

<p>Abstract</p> <p>Background</p> <p>The ecological niche occupied by a fungal species, its pathogenicity and its usefulness as a microbial cell factory to a large degree depends on its secretome. Protein secretion usually requires the presence of a N-terminal signal peptide (SP) and by scanning for this feature using available highly accurate SP-prediction tools, the fraction of potentially secreted proteins can be directly predicted. However, prediction of a SP does not guarantee that the protein is actually secreted and current <it>in silico </it>prediction methods suffer from gene-model errors introduced during genome annotation.</p> <p>Results</p> <p>A majority rule based classifier that also evaluates signal peptide predictions from the best homologs of three neighbouring <it>Aspergillus </it>species was developed to create an improved list of potential signal peptide containing proteins encoded by the <it>Aspergillus niger </it>genome. As a complement to these <it>in silico </it>predictions, the secretome associated with growth and upon carbon source depletion was determined using a shotgun proteomics approach. Overall, some 200 proteins with a predicted signal peptide were identified to be secreted proteins. Concordant changes in the secretome state were observed as a response to changes in growth/culture conditions. Additionally, two proteins secreted via a non-classical route operating in <it>A. niger </it>were identified.</p> <p>Conclusions</p> <p>We were able to improve the <it>in silico </it>inventory of <it>A. niger </it>secretory proteins by combining different gene-model predictions from neighbouring Aspergilli and thereby avoiding prediction conflicts associated with inaccurate gene-models. The expected accuracy of signal peptide prediction for proteins that lack homologous sequences in the proteomes of related species is 85%. An experimental validation of the predicted proteome confirmed <it>in silico </it>predictions.</p

VIRMA-dependent N6-methyladenosine modifications regulate the expression of long non-coding RNAs CCAT1 and CCAT2 in prostate cancer

RNA methylation at position N6 in adenosine (m6A) and its associated methyltransferase complex (MTC) are involved in tumorigenesis. We aimed to explore m6A biological function for long non-coding RNAs (lncRNAs) in prostate cancer (PCa) and its clinical significance. m6A and MTC levels in PCa cells were characterized by ELISA and western blot. Putative m6A-regulated lncRNAs were identified and validated by lncRNA profiler qPCR array and bioinformatics analysis, followed by m6A/RNA co-immunoprecipitation. Impact of m6A depletion on RNA stability was assessed by Actinomycin D assay. The association of m6A-levels with PCa prognosis was examined in clinical samples. Higher m6A-levels and VIRMA overexpression were detected in metastatic castration-resistant PCa (mCRPC) cells (p < 0.05). VIRMA knockdown in PC-3 cells significantly decreased m6A-levels (p = 0.0317), attenuated malignant phenotype and suppressed the expression of oncogenic lncRNAs CCAT1 and CCAT2 (p < 0.00001). VIRMA depletion and m6A reduction decreased the stability and abundance of CCAT1/2 transcripts. Higher expression of VIRMA, CCAT1, and CCAT2 as a group variable was an independent predictor of poor prognosis (HR = 9.083, CI95% 1.911–43.183, p = 0.006). VIRMA is a critical factor sustaining m6A-levels in PCa cells. VIRMA downregulation attenuates the aggressive phenotype of PCa by overall reduction of m6A-levels decreasing stability and abundance of oncogenic lncRNAs

Robust Multimodal Image Registration Using Deep Recurrent Reinforcement Learning

The crucial components of a conventional image registration method are the choice of the right feature representations and similarity measures. These two components, although elaborately designed, are somewhat handcrafted using human knowledge. To this end, these two components are tackled in an end-to-end manner via reinforcement learning in this work. Specifically, an artificial agent, which is composed of a combined policy and value network, is trained to adjust the moving image toward the right direction. We train this network using an asynchronous reinforcement learning algorithm, where a customized reward function is also leveraged to encourage robust image registration. This trained network is further incorporated with a lookahead inference to improve the registration capability. The advantage of this algorithm is fully demonstrated by our superior performance on clinical MR and CT image pairs to other state-of-the-art medical image registration methods

Comparative bioavailability of a newly developed Irbesartan 300 mg containing preparation

Introduction: Irbesartan (CAS registry: 138402-11-6) is a potent, orally active, selective antagonist of the angiotensin II receptors (type AT1) indicated for the treatment of arterial hypertension and chronic heart failure. Aim: The objective of the present study was to demonstrate the bioequivalence of an oral test preparation (Irbesartan 300 mg film-coated tablets Tchaikapharma High Quality Medicines Inc., Bulgaria) and a reference (Aprovel 300 mg film-coated tablets, Sanofi Clir SNC, France), by comparing the rate and extent of absorption of both products upon a single oral administration of the tablets under fasting conditions in healthy volunteers. Methodology: The study was carried out as a single-center, open-label, randomised, twoperiod, single dose, crossover oral bioequivalence study in 40 healthy male and female subjects under fasting conditions. During each study period blood samples for analysis of irbesartan were taken prior to dosing and at 0.25, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24, 36, 48 and 72 hours after dosing. The separated plasma was analyzed in the bioanalytical division of Anapharm Europe with a validated method using reversed phase high performance liquid chromatography coupled to a tandem mass spectrometry detector (RP-LC/MS/MS). Results: The point estimates with 90% confidence intervals of the geometric mean ratios of test and reference (T/R) in the study were found to be 102.39% (95.55% - 109.71%) for Cmax and 98.56 % (92.72 % - 104.76 %) for AUC0-72. Thus, the corresponding ratios of Cmax and AUC0-72 met the predetermined criteria for bioequivalence (90% confidence intervals of the geometric mean ratios of test and reference within the 80.00% - 125.00%). Both products were generally very well tolerated. Conclusions: Irbesartan 300 mg film-coated tablets, Tchaikapharma High Quality Medicines Inc., Bulgaria) and Aprovel 300 mg film-coated tablets (Sanofi Clir SNC, France), are bioequivalent with regard to the rate and extent of absorption

Slx8 removes Pli1-dependent protein-SUMO conjugates including SUMOylated Topoisomerase I to promote genome stability

Peer reviewedPublisher PD

Assessing the effectiveness of the Ramsar Convention in preserving wintering waterbirds in the Mediterranean

lthough biological conservation is based on international agreements, its effectiveness depends on how countries implement such recommendations as effective conservation tools. The Ramsar Convention is the oldest international treaty for wetland and waterbird conservation, establishing the world's largest network of protected areas. However, since it does not constitute any binding measure, its effectiveness in protecting wintering waterbird populations at an international scale has been questioned. Here, we use long-term (1991–2012) count data to assess the effectiveness of the Ramsar Convention in the Mediterranean Basin. We compared abundance and temporal trends of 114 waterbird species between 251 Ramsar wetlands and 3486 non-Ramsar wetlands. We found that the Ramsar network is critical for wintering waterbirds, concentrating nearly half of all waterbirds counted in the Mediterranean Basin in only 7% of monitored wetlands. Waterbird trends followed a northwestsoutheast gradient, with a population decrease in the East. A significant and positive Ramsar effect on population trends was only found for the species of higher conservation concern in the Maghreb, particularly when a management plan was implemented. The Ramsar Convention was previously used on very important wetlands for waterbirds in Southern Europe, but is now an underused conservation tool. Our study suggests weaknesses in the use of Ramsar as an effective conservation tool in most of the Mediterranean Basin. However, the Ramsar Convention effectiveness to enhance waterbird populations in the Maghreb should encourage strengthening the Ramsar Convention. It should be done particularly in countries with limited environmental agreements and by systematic implementation of management plans. Conservation measures International conventions Protected areas Protection status Monitoring WetlandsacceptedVersio

A photoinduced pH jump applied to drug release from cucurbit[7]uril

A proof-of-principle for the application of a photoinduced pH jump for delivery of the Hoechst 33258 drug by disassembly of its host-guest complex with cucurbit[7]uril is described