The effects of trimetazidine on lipopolysaccharide-induced oxidative stress in mice

The effects of trimetazidine, a novel anti-ischemic agent, on the development of oxidative stress induced in mice with lipopolysaccharide endotoxin were investigated. The drug was administered orally once daily at doses of 1.8, 3.6 or 7.2 mg/kg for two days prior to intraperitoneal (i.p.) injection of lipopolysaccharide E (200 μg/kg) and at time of endotoxin administration. Mice were euthanized 4 h after administration of the lipopolysaccharide. Lipid peroxidation (malondialdehyde; MDA), reduced glutathione (GSH) and nitric oxide (nitrite/nitrate) concentrations were measured in brain and liver. The administration of lipopolysaccharide increased oxidative stress in both the brain and liver tissue. MDA increased by 33.9 and 107.1 %, GSH decreased by 23.9 and 84.3 % and nitric oxide increased 70.3 and 48.4 % in the brain and liver, respectively. Compared with the lipopolysaccharide control group, brain MDA decreased by 26.2 and 36.7 %, while GSH increased by 18.2 and 25.8 % after the administration of trimetazidine at 3.6 and 7.2 mg/kg, respectively. Brain nitric oxide decreased by 45.3, 50.8 and 57.0 % by trimetazidine at 1.8, 3.6 and 7.2 mg/kg, respectively. In the liver, MDA decreased by 18.7, 30.7 and 49.4 % and GSH increased by 150.3, 204.8 and 335.4 % following trimetazidine administration at 1.8, 3.6 and 7.2 mg/kg. Meanwhile, nitric oxide decreased by 17.3 % by 7.2 mg/kg of trimetazidine. These results indicate that administration of trimetazidine in the presence of mild systemic inflammatory response alleviates oxidative stress in the brain and liver

SNARE phosphorylation: a control mechanism for insulin-stimulated glucose transport and other regulated exocytic events

Trafficking within eukaryotic cells is a complex and highly regulated process; events such as recycling of plasma membrane receptors, formation of multivesicular bodies, regulated release of hormones and delivery of proteins to membranes all require directionality and specificity. The underpinning processes, including cargo selection, membrane fusion, trafficking flow and timing, are controlled by a variety of molecular mechanisms and engage multiple families of lipids and proteins. Here, we will focus on control of trafficking processes via the action of the SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) family of proteins, in particular their regulation by phosphorylation. We will describe how these proteins are controlled in a range of regulated trafficking events, with particular emphasis on the insulin-stimulated delivery of glucose transporters to the surface of adipose and muscle cells. Here, we focus on a few examples of SNARE phosphorylation which exemplify distinct ways in which SNARE machinery phosphorylation may regulate membrane fusion

Methanol extract of smokeless tobacco alters inflammation and nociception process in animal models

Purpose: To investigate the inflammatory and nociceptive alterations due to the use of Nicotiana tabacum or smokeless tobacco (MEST) owing to the fact that it is used by some people to relieve dental pain.Methods: Hepatic biochemical indicators and thiobarbituric acid reactive substances assay were used to assess MEST toxicity and pharmacological doses selection. The effects on inflammation of different pharmacological doses (100, 200 and 500 mg/kg i.p.) of MEST were evaluated using xylene-induced ear edema and cotton pellet granuloma tests. Indomethacin (10 mg/kg, i.p.) was used as positive standard drug, whereas the vehicle 0.5 % CMC treated group was considered as negative control. Acetic acid-induced abdominal contraction test and formalin-induced hind paw licking model were utilized to assess the role of MEST in nociception. Indomethacin (10 mg/kg i.p.) and diclofenac sodium (10 mg/kg i.p.) were used as positives standard drugs. The vehicle used was 0.5% CMC which served as the negative control.Results: MEST (50 %, 200 mg/kg) and indomethacin (47.5 %) both elicited a significant (p < 0.001) anti-edematogenic effect on xylene-induced ear edema. MEST also showed a significant (p < 0.001) inhibitory effect on granuloma formation at all administered doses as compared to the untreated groups which was comparable to standard drug indomethacin. The number of acetic acid induced writhings was observed to be significantly increased (p < 0.001) by MEST at all doses, unlike diclofenac that led to significant reduction (p < 0.001) in the number of writhings, when compared to the untreated group. MEST also showed a significant (p < 0.05) dose-dependent reduction of the hind paw licking caused by formalin when compared to the vehicle control.Conclusion: These results signify that administration of MEST induces inflammatory and nociceptive alterations. However, the extract is not recommended for dental pain due to its other toxic effects that have previously been reported.Keywords: Nicotiana tabacum, Smokeless tobacco, Inflammation, Nociceptio

Antidepressant effect of methanol extract of smokeless tobacco and identification of its bioactive components

Purpose: To investigate the antidepressant effect of methanol extract of smokeless tobacco and identify its bioactive compounds. Methods: Adult Wistar rats were randomly assigned to five groups of five rats each: normal control group, standard (reference) control group as well as 100, 200 and 500 mg/kg extract group. The extract, standard drug (imipramine) and normal saline were administered via the intraperitoneal (i.p.) route. The rats were subjected to forced swim test (FST) and tail suspension test (TST) to assess the antidepressant effect of methanol extract of smokeless tobacco. Gas chromatography–mass spectrometry (GC-MS) was used to identify the bioactive compounds of the extract. Results: The oral LD50 of the extract was > 2000 mg/kg. Significant decrease in immobility time was observed after single administration of imipramine (p < 0.05). The extract significantly and dosedependently decreased the immobility time, but increased climbing and swimming times, when compared with normal control group (p < 0.05). The immobility time of stressed rats regardless of sex was significantly and dose-dependently lowered, relative to normal control group (p < 0.05). Four major compounds were identified in the extract: nicotine (45.88 %); 1,5-dimethyl-2-pyrrolidinone (23.00 %), nhexadecanoic acid (11.31 %) and vitamin A aldehyde (9.38 %). Conclusion: These results demonstrate that the methanol extract of smokeless tobacco possesses antidepressant and mood-elevating effects in rats. However, its use should be discouraged since it contains a number of hazardous and carcinogenic components such as N-nitroso compounds and benzo(a)pyrene which are categorized as Class-I carcinogens

Multichannel blind deconvolution using a generalized Gaussian source model

In this paper, we present an algorithm for the problem of multi-channel blind deconvolution which can adapt to un-known sources with both sub-Gaussian and super-Gaussian probability density distributions using a generalized gaussian source model. We use a state space representation to model the mixer and demixer respectively, and show how the parameters of the demixer can be adapted using a gradient descent algorithm incorporating the natural gradient extension. We also present a learning method for the unknown parameters of the generalized Gaussian source model. The performance of the proposed generalized Gaussian source model on a typical example is compared with those of other algorithm, viz the switching nonlinearity algorithm proposed by Lee et al. [8]. © Association for Scientific Research

A special perturbation method in orbital dynamics

The special perturbation method considered in this paper combines simplicity of computer implementation, speed and precision, and can propagate the orbit of any material particle. The paper describes the evolution of some orbital elements based in Euler parameters, which are constants in the unperturbed problem, but which evolve in the time scale imposed by the perturbation. The variation of parameters technique is used to develop expressions for the derivatives of seven elements for the general case, which includes any type of perturbation. These basic differential equations are slightly modified by introducing one additional equation for the time, reaching a total order of eight. The method was developed in the Grupo de Dinámica de Tethers (GDT) of the UPM, as a tool for dynamic simulations of tethers. However, it can be used in any other field and with any kind of orbit and perturbation. It is free of singularities related to small inclination and/or eccentricity. The use of Euler parameters makes it robust. The perturbation forces are handled in a very simple way: the method requires their components in the orbital frame or in an inertial frame. A comparison with other schemes is performed in the paper to show the good performance of the method

Novel fuzzy-based optimization approaches for the prediction of ultimate axial load of circular concrete-filled steel tubes

An accurate estimation of the axial compression capacity of the concrete-filled steel tubular (CFST) column is crucial for ensuring the safety of structures containing them and preventing related failures. In this article, two novel hybrid fuzzy systems (FS) were used to create a new framework for estimating the axial compression capacity of circular CCFST columns. In the hybrid models, differential evolution (DE) and firefly algorithm (FFA) techniques are employed in order to obtain the optimal membership functions of the base FS model. To train the models with the new hybrid techniques, i.e., FS-DE and FS-FFA, a substantial library of 410 experimental tests was compiled from openly available literature sources. The new model\u2019s robustness and accuracy was assessed using a variety of statistical criteria both for model development and for model validation. The novel FS-FFA and FS-DE models were able to improve the prediction capacity of the base model by 9.68% and 6.58%, respectively. Furthermore, the proposed models exhibited considerably improved performance compared to existing design code methodologies. These models can be utilized for solving similar problems in structural engineering and concrete technology with an enhanced level of accuracy

Bacterial sepsis in patients with visceral leishmaniasis in Northwest Ethiopia

Background and Objectives. Visceral leishmaniasis (VL) is one of the neglected diseases affecting the poorest segment of world populations. Sepsis is one of the predictors for death of patients with VL. This study aimed to assess the prevalence and factors associated with bacterial sepsis, causative agents, and their antimicrobial susceptibility patterns among patients with VL. Methods. A cross-sectional study was conducted among parasitologically confirmed VL patients suspected of sepsis admitted to the University of Gondar Hospital, Northwest Ethiopia, from February 2012 to May 2012. Blood cultures and other clinical samples were collected and cultured following the standard procedures. Results. Among 83 sepsis suspected VL patients 16 (19.3%) had culture confirmed bacterial sepsis. The most frequently isolated organism was Staphylococcus aureus (68.8%; 11/16), including two methicillin-resistant isolates (MRSA). Patients with focal bacterial infection were more likely to have bacterial sepsis (P<0.001). Conclusions. The prevalence of culture confirmed bacterial sepsis was high, predominantly due to S. aureus. Concurrent focal bacterial infection was associated with bacterial sepsis, suggesting that focal infections could serve as sources for bacterial sepsis among VL patients. Careful clinical evaluation for focal infections and prompt initiation of empiric antibiotic treatment appears warranted in VL patients

Integration of reproductive health services for men in health and family welfare centers in Bangladesh

Since the mid-1970s, the Bangladesh national family planning program primarily focused on motivating women to use modern contraceptive methods and encouraging them to seek services from clinics. In addition, female field workers were recruited to deliver contraceptive methods at homes. The program design facilitated women’s access to information and medical care through clinics and home visits. In the process, however, the medical needs of males were marginalized. Men generally seek services from pharmacies, private practitioners, and district hospitals, and often ignore preventive steps and postpone seeking medical care for chronic health conditions. In cases of acute illness, they often resort to self-medication. As noted in this report, the study’s aim was to integrate male reproductive health services within the existing government female-focused health-care delivery system. The study concluded that reproductive health services for men could easily be integrated into the health and family welfare centers without affecting the clinics’ focus on serving women and children

Integration of reproductive health service for men in health and family welfare centers in Bangladesh

Over the last 30 years, Bangladesh’s national family planning (FP) program has mainly concentrated its promotional efforts on women’s adoption of FP. While the government policy has been effective in influencing women to accept contraceptive methods, men’s role in FP has been completely neglected. Similarly, male RH services are hardly available at Health and Family Welfare Centres (HFWCs). This report describes a project aimed at integrating male RH services within the existing government female-focused health-care-delivery system. The study was implemented by NIPORT in collaboration with the Directorate of Family Planning and the Population Council. Interventions resulted in a substantial rise of male clients in the clinics, however nearly all came for the treatment of general health problems. Only a small number of male RTI/STI clients sought services from the clinics. Although unexpected, there was a substantial rise in the number of female clients. The study concluded that RH services for men could be easily integrated into HFWCs without affecting the female and child focus of the clinics and that augmentation of the total number of patients at HFWCs will lead to more effective use of resources and decreased cost of treatment