The effect of sodium valproate on acetic acid-induced colitis in rats

Ulcerative colitis is a chronic recurrent disease with incomplete treatment options. The current article evaluated the effect of sodium valproate on acetic acid-induced ulcerative colitis in rats. Rats were randomly distributed into six groups including Sham group, colitis control group, sodium valproate treatment groups (50, 100 and 300 mg/kg, i.p.) and dexamethasone-treatment group. Dexamethasone was used as a reference drug. Colitis was induced by intracolonic instillation of 2 mL of 3% acetic acid solution. The efficacy of sodium valproate was evaluated by macroscopical and histopathological scoring systems, hematocrit measurement as well as biochemical analysis including myeloperoxidase (MPO) and pro-inflammatory cytokines assessment. Sodium valproate, particularly with doses of 100 and 300 mg/kg significantly improved weight loss, and macroscopic damage, reduced ulcer area, colon weight, microscopic colitis index and elevated hematocrit level. Biochemical experiments showed elevated levels of colonic MPO activity, interleukin 1β (IL-1β), interleukin 6 (IL-6) and tumor necrosis factor-α (TNF-α) in colitis control group. Treatment with sodium valproate at the doses of 100 and 300 mg/Kg) decreased the MPO activity and colonic concentrations of IL-1β, IL-6 and TNF-α. The results provide evidence that sodium valproate has a protective effect in acetic acid-induced ulcerative colitis which might be due to its anti-inflammatory activities, and it may be useful in patients with ulcerative colitis.     

Waist-hip ratio and low HDL predict the risk of coronary artery disease in Pakistanis

OBJECTIVE: To establish risk factor causal associations for coronary artery disease (CAD) in the native Pakistani population. METHODS: We conducted a hospital-based, case-control study of 200 cases with angiographically documented CAD and 200 age- and sex-matched controls without angiographic evidence of CAD. Patients on lipid lowering therapy were excluded. Lifestyle, anthropometric and biochemical risk factors were assessed in both groups. RESULTS: The presence of CAD was associated with current, past or passive smoking, a history of diabetes and high blood pressure, a positive family risk factors in this study; levels were below history of CAD, body fat percentage, waist-hip ratio (WHR), low apolipoprotein A1 or low HDL, lipoprotein (a), glucose, insulin, insulin resistance, C-reactive protein (CRP), total cholesterol to HDL ratio (TC/HDL) and creatinine on univariate conditional logistic regression analysis. In multiple regression analysis, significant independent associations were found with low HDL (OR 0.11; 95% CI 0.04-0.34; p < 0.001) positive family history (OR 1.79; 95% CI 1.09-2.93; p = 0.02), CRP (OR 1.45; 95% CI 1.19-1.75; p < 0.001) and WHR (OR 1.04; 95% CI 1.01-1.08; p = 0.01). Angiograms were also quantified for the extent and severity of CAD by the Gensini scoring system. Quantitative angiographic data showed associations with age (p = 0.01), the duration of diabetes (p = 0.04), WHR (p = 0.06), low HDL (p < 0.001), lipoprotein (a) (p = 0.001), creatinine (p < 0.001) and CRP (p = 0.007). Results indicate that total and LDL cholesterol were not significant currently accepted thresholds for treatment. CONCLUSIONS: The cardiovascular risk profile in this population is consistent with metabolic syndrome where low HDL and WHR can be used to predict the risk of CAD. Results suggest the need to redefine the currently practised approach to CAD management in this population to fit local needs.     

Effect of low-dose aspirin on the development of ovarian hyperstimulation syndrome and outcomes of assisted reproductive techniques in the women with PCOS,a randomized double-blinded clinical trial

Objective

Ovarian hyperstimulation syndrome (OHSS) is a major complication of assisted reproductive technologies (ART). Polycystic ovary syndrome (PCOS) is a risk factor for OHSS. The aim of this randomized clinical trial (RCT) was to study the effect of low-dose aspirin (LDA) on the development of OHSS and ART outcomes in PCOS during ART.

Non-linear Wave Propagation and Safety Standards for Diagnostic Ultrasound Devices

Safety standards for clinical diagnostic ultrasonic devices were developed for use in relatively low-frequency systems (1–10 MHz), under the assumption that non-linear effects would be negligible. This article reviews ways in which neglecting non-linear wave propagation affects the measurements and calculations required to comply with safety standards and U.S. Food and Drug Administration guidance that recognizes these standards. An attempt is made to evaluate whether ignoring non-linear effects could result in significant error in the exposure quantities defined in these standards at either low or high frequencies, based on published literature. This article maintains that although non-linear effects have been considered in some parts of safety standards related to hydrophone requirements, the coverage is inadequate, especially for modern equipment with high working frequencies. A new approach is required to assess the magnitude of thermal heating for recently developed high-frequency systems to incorporate non-linear effects. In contrast, the current approach for evaluating the risk of cavitation can be used after appropriate modifications.     

Investigating the Antiangiogenic,Anti-drug Resistance and Apoptotic Effects of Soy Isoflavone Extract Alone or in Combination with Docetaxel on Murine 4T1 Breast Tumor Model

Background: One major concern in the treatment of cancer patients during chemotherapy is drug resistance. Here we investigated the effects of soy isoflavone extracts alone or in combination with Docetaxel on the drug resistance, angiogenesis, apoptosis, and tumor volume in mouse 4T1 breast tumor model. Methods: Sixty female BALB/c mice were randomly divided into 4 groups: control, dietary soy isoflavone extract [Iso, 100 mg/kg diet (0.01%)], Docetaxel (10 mg/kg) injection, and the combination of dietary soy isoflavone extract and intravenous Docetaxel injection (Docetaxel + Iso). One week after the third injection, the breast tumors of eight mice from each group were excised to analyze NF-κBp65′ vascular endothelial growth factor receptor-2 (VEGFR2) and Pgp gene and protein expressions and the other seven mice were monitored for survival rate analysis until they died. Results: NF-κBp65 gene and protein expressions were significantly lower in the Docetaxel + Iso group in comparison with that of the Docetaxel group. VEGFR2 protein expression in the Docetaxel + Iso and Iso groups was significantly lower than that of the Docetaxel group. Conclusion: These findings may indicate that the combined use of isoflavone extracts together with chemotherapeutic agents has more efficient anti-carcinogenic effects than their individual use.     

Vertical transmission of dengue: first case report from Bangladesh

We report a case of vertical transmission of dengue infection in a new born from Bangladesh. The mother was primigravida with an uneventful antenatal period except the fever she developed at 37 weeks of gestation. She underwent cesarean section for decreased fetal movement. The fever lasted for 7 days and was associated with intense bodyache, and a positive tourniquet test. She did not experience any hemorrhages including from the surgical wound. Her platelet count fell at its lowest to 100,000/mm3. She had bilateral mild pleural effusions and positive anti-dengue antibodies (both IgG and IgM). She received symptomatic treatment. The baby was deeply meconium stained and was resuscitated by a pediatrician. His postnatal period went well until day-3 of life when he developed fever and respiratory distress. There were no signs of meconiun aspiration syndrome (MAS) and the septic work up was negative. The platelets count fell to its lowest of 40,000/mm3 on day-3 and day-5 of his illness. Anti-dengue antibodies (both IgG and IgM) were positive with a nearly four-fold rise of IgM antibodies in the convalescent sera. The boy was treated with platelet transfusions and was discharged on day-6 after becoming ill. This report emphasizes that in a dengue epidemic or when dengue is endemic (which Bangladesh has experienced recently), a pregnant woman with fever, myalgia and/or bleeding manifestations should raise a high suspicion that the baby may develop the disease, and both the mother and baby should be closely followed-up. Viral isolation could not be done due to the unavailability of the test.     

Efficient induction of CD8 T-associated immune protection by vaccination with mRNA transfected dendritic cells

Dendritic cells are excellent targets for antigen-specific immune intervention. Here we attempted to introduce a CD8 T cell-dependent epitope into dendritic cells for presentation on major histocompatibility complex class I and induction of immunity. Murine bone-marrow-derived dendritic cells were subjected to electroporation with mRNA transcribed in vitro from a plasmid encoding lymphocytic choriomeningitis virus glycoprotein or enhanced green fluorescent protein under the control of a T7 promotor. The transfection efficiency of dendritic cells was 22 to 40%. Maturation was not inhibited by the electroporation. Dendritic cells electroporated with the appropriate antigen induced cell number-dependent in vitro proliferation in CD8 T cells expressing a transgenic receptor recognizing the 33 to 41 sequence of lymphocytic choriomeningitis virus glycoprotein in association with H-2Kb/Db, indicating correct synthesis, processing, and presentation of the epitope. Naive C57BL/6 mice vaccinated with electroporated dendritic cells and challenged with lymphocytic choriomeningitis virus were protected. Vaccination induced epitope-specific T cells as assessed by tetramer staining in blood and spleen. These results indicate that targeting dendritic cells with antigen-encoding mRNA can induce antigen-specific CD8 T cell responses as well as protective anti-viral immunity in vivo. Targeting dendritic cells with antigen-encoding mRNA may find wider application for immune intervention in disorders such as autoimmunity and cancer.     

Central noradrenergic blockade prevents autotomy in rat: implication for pharmacological prevention of postdenervation pain syndrome

Following transection of peripheral nerve, rats exhibit autotomy, which is considered to be the animal model of postdenervation pain syndrome. It has been suggested that phantom limb pain is a result of peripheral denervation leading to reorganization of somatosensory pathways, particularly in the cerebral cortex, which is shown to depend upon central noradrenergic activity. In this study, sciatic and saphenous nerves were sectioned in the left hindpaw of 30 adult rats resulting in complete loss of pain sensation in the hindpaw. A group of rats received normal saline, compared to another group which received N-(2-) Chloroethyl-N-ethyl-2-bromobenzylamine (DSP4) injection 24 h prior to transection. The latter group was also compared to a third group whose central noradrenergic system were also blocked by bilateral injection of 6-OHDA into the ascending noradrenergic bundle 1 week prior to transection. A fourth group received contralateral cortical ablation in addition to peripheral nerve transection and was compared to the first group whose cortex remained intact. The animals were observed daily for 60 days and autotomy was scored in accordance to the system of Wall et al. After 1 week, control animals began to exhibit autotomy. In contrast, autotomy was absent in rats treated with DSP4, similar to rats which received 6-OHDA. Rats which had contralateral cortical ablation showed a considerably delayed onset of autotomy and a reduction in final autotomy scores. We conclude that autotomy, as a model of postdenervation pain syndrome, can be prevented by blockade of noradrenergically mediated cortical reorganization. The clinical implications of this finding are discussed.     

Neuropsychological and quantitative oculometric study of a case of sporadic Creutzfeldt-Jakob disease at predementia stage

A quantitative assessment of eye movements and a detailed neuropsychological profile were conducted at predementia stage in a patient who later had histological confirmation of sporadic Creutzfeldt-Jakob disease (CJD). The patient was a middle aged man who presented with abnormal eye movements and poor balance. Neuropsychological deficits suggested orbito-mesial dysfunction, resembling progressive supranuclear palsy. Oculometry showed accurate but dramatically slowed saccades, with normal pursuit movements. Neuropsychology and quantitative oculometry may be of value in the differential diagnosis and earlier detection of dementia-akinetic-rigid syndromes; in particular, because of the highly stereotyped nature of saccades, routine quantitative oculometry can reveal significant impairment at a very early stage in some cases and could thus facilitate earlier diagnosis.