Microwave-assisted synthesis and anticonvulsant activity of 5,6-bisaryl-1,2,4-triazine-3-thiol derivatives

A series of 5,6-bisaryl-1,2,4-triazine-3-thiol derivatives were synthesized through microwave-promoted chemistry by condensation of the aromatic 1,2-diketones and thiosemicarbazide in a mixed green solvent. Subsequently, S-alkylation of 1,2,4-triazine-3-thiols afforded S-substituted derivatives. The anticonvulsant activity of the synthesized compounds was evaluated in vivo by electroshock and pentylenetetrazole (PTZ)-induced seizures tests. Among them, compound 4a bearing 4-pyridylmethylthio moiety on the triazine ring showed the highest protection in both electroshock and PTZ-induced seizures tests. Compound 4a showed no sign of neurotoxicity at the dose of 100 mg/kg in both rotarod and chimney tests.     

On the benefit of galls of Quercus brantii Lindl. in murine colitis: the role of free gallic acid

Introduction

In this study we investigated the effect of gall of Quercus brantii Lindl., a traditional Iranian medicine, in a murine model of experimental colitis induced in male rats by rectal administration of 2,4,6-trinitrobenzene sulfonic acid (TNBS).

Material and methods

Quantification of the main active components was done for estimation of total phenolic content and free gallic acid. Gall of Quercus brantii Lindl. in two forms (gall powder and gall hydro alcoholic extract) was gavaged for 10 days (500 mg/kg). Ten days after induction of colitis, colonic status was examined by macroscopic, microscopic and biochemical analyses. Colonic tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) were analyzed as biomarkers of inflammatory condition. To determine the role of oxidative stress (OS) in colitis, the levels of cellular lipid peroxidation (LPO), total antioxidant power (TAP) and myeloperoxidase (MPO) were measured in colon tissues.

Results

TNBS-induced colitis exhibited a significant increase in colon MPO activity and concentrations of cellular LPO, TNF-α and IL-1β, while TAP was significantly reduced. Microscopic evaluations of the colonic damage in the colitis group revealed multifocal degenerative changes in the epithelial lining and areas of necrosis, extensive mucosal and sub-mucosal damage with congested blood vessels, edema and hemorrhages along with extensive infiltration of inflammatory cells. Parameters including macroscopic and microscopic scores, TNF-α, IL-1β, LPO, TAP and MPO improved by both gall extract and gall powder of Quercus brantii Lindl. and reached close to normal levels. The level of total phenols (GAE/100 g of sample) and free gallic acid were estimated to be 88.43 ±7.23 (mean ± SD) and 3.74% of dry weight, respectively.

Conclusions

The present study indicates that the gall of Quercus brantii Lindl. is able to exert antioxidative and anti-inflammatory effects on the biochemical and pathological parameters of colitis.     

Evaluation of cardiac masses by CMR—strengths and pitfalls: a tertiary center experience

Cardiovascular magnetic resonance (CMR) imaging is often considered the reference method to assess cardiac tumors. However, little data exists concerning the effectiveness of CMR for the accurate diagnosis of cardiac masses. We sought to understand the diagnostic value of CMR for evaluation of suspected cardiac mass. A total of 249 consecutive CMR cases performed at a single center from January 2005 to June 2013 for evaluation of masses found on echocardiography or computed tomography (CT) were included. All the clinical data and imaging features of these patients were retrospectively reviewed and medical records were verified for follow up care. More than half of the patients referred for evaluation of masses found at echocardiography or CT were found to have no evidence of mass by CMR. CMR correctly differentiated between thrombus and myxoma in 88.4 % cases. Malignant masses were accurately diagnosed on CMR. However, CMR missed or misdiagnosed a few cases of benign masses. Diagnosing cardiac masses remains an important use for imaging, despite technical difficulties with current imaging modalities. CMR can play a key role in confirming presence or absence of a mass. Additionally, in the presence of a mass, CMR can provide accurate differentiation of pseudomasses, benign and malignant masses. However, the limitations of CMR must be recognized.     

Tissue cultures of Withania somnifera: Morphogenesis and withanolide synthesis

Tissue cultures were established from axillary meristems of the plant Withania somnifera. Growth hormones influenced the morphogenetic responses of the cultures. The explants gave multiple shoots in Murashige and Skoog's (MS) medium supplemented with benzyladenine (BA), rooting in MS+coconut milk (CM) (10%) and callus formation in MS+2,4-dichlorophenoxyacetic acid (2,4-D) (2.0 ppm). Callus cultures failed to synthesize withanolides. Multiple shoot cultures synthesized significant levels of withanolides and their concentrations varied with different growth hormones.     

A review of the efficacy of traditional Iranian medicine for inflammatory bowel disease

The etiology of inflammatory bowel disease(IBD) is not yet known,but many factors such as defects in the immune system,oxidative stress,microbial content in the gastrointestinal tract,nuclear factor(NF)-κB,nitric oxide(NO),cyclooxygenase-2(Cox-2),and leukotriene B4(LB4) are thought to play a role in its pathogenesis.In traditional Iranian medicine(TIM),several medicinal plants are thought to be effective for the treatment of IBD.In this study,information on all of these remedies were derived from all available old sources such as documents or notes and books and were added to the information derived from modern medical databases covering all in vitro,in vivo and clinical trials.For some of these plants,only one or two mechanisms of action have been found such as in Cassia fistula,Lepidium sativum,and Bunium persicum.However,for some plants various mechanisms of action are known.For example,Commiphora mukul is effective in IBD due to its immunomodulatory,antioxidant,and antibacterial properties and it decreases NF-κB,NO and Cox-2.Another herb,Plantago ovata,has immunomodulatory,antioxidant,anti-inflammatory and wound healing activities and decreases NO and LB4.Considering the mechanisms of action of these plants,the combination of some of them may be useful because of their many mechanisms of action such as Pistacia lentiscus,Bunium persicum,Solanum nigrum,Plantago ovata,Boswellia,Solanum nigrum,Plantago ovata and Commiphora mukul.For some of the herbal products used in TIM such as oleogum resin from Commiphora myrrha,seeds of Ocimum basilicum,seeds of Linum usitatissimum,gum resin of Dracaena cinnabari,seeds of Plantago major,seeds of Lallementia royleana,and seeds of Allium porrum,there is no or not enough studies to confirm their benefits in IBD.It is suggested that an evaluation of the effects of these plants on different aspects of IBD should be performed.     

Efficacy and tolerability of alosetron for the treatment of irritable bowel syndrome in women and men: a meta-analysis of eight randomized, placebo-controlled, 12-week trials

BACKGROUND: Stimulated 5-hydroxytryptamine-3 (5-HT(3)) receptors promote intestinal motility, secretion, and sensation, effects that are related to the known pathophysiology of irritable bowel syndrome (IBS). A previous meta-analysis of 6 randomized controlled trials of the 5-HT(3)-receptor antagonist alosetron found that this agent was associated with global improvement in symptoms, pain, and discomfort in patients with IBS. OBJECTIVE: This was a meta-analysis of randomized, placebo-controlled trials that evaluated the efficacy and tolerability of alosetron for the management of IBS. It updated and expanded on the previous meta-analysis. METHODS: PubMed, EMBASE, SCOPUS, Web of Science, and the cochrane central Register of controlled Trials were searched from 1966 through September 2007 for placebo-controlled trials that examined the efficacy and tolerability of alosetron in the management of IBS. The search terms were alosetron, 5-HT, irritable bowel, functional bowel diseases, and irritable colon. No language restriction was applied. The data were analyzed in terms of 2 main outcomes: global improvement in IBS symptoms and adequate relief of IBS pain and discomfort. RESULTS: Eight multicenter, randomized, placebo-controlled, 12-week clinical trials met the criteria for inclusion in the meta-analysis. The studies included 4,170 patients with IBS (80% female) who were randomized to receive either alosetron or placebo. All patients met the Rome criteria for IBS, and all subtypes of IBS were represented. Most patients had diarrhea-predominant IBS; only 2.6% of patients had constipation-predominant IBS. In the 3 trials included in the analysis of global improvement in symptoms, alosetron was significantly more effective than placebo (relative risk [RR] = 1.60; 95% CI, 1.44-1.76; P <0.001). In the 6 trials included in the analysis of adequate relief of IBS pain and discomfort, there was also a significant difference in favor of alosetron (RR = 1.31; 95% CI, 1.20-1.43; P < 0.001). Analysis of adequate relief of IBS pain and discomfort by sex also indicated significant differences between alosetron and placebo in both sexes (female: RR = 1.34 [95% cI, 1.21-1.48]; male: RR = 1.23 [95% CI, 1.02-1.47]). The analysis of tolerability, which was based on data from 7 studies, found a significant difference between alosetron and placebo (RR = 1.19; 95% cI, 1.07-1.31; P<0.001). The only adverse events that occurred with a significantly higher incidence in those treated with alosetron compared with placebo were constipation in 8 trials (RR = 4.35; 95% CI, 3.01-6.26; P < 0.001) and abdominal pain and discomfort in 5 trials (RR = 1.96; 95% CI, 1.46-2.64; P < 0.001). In the alosetron group, there were 4 cases of ischemic colitis (0.16%) and 2 cases of serious complications of constipation (0.08%); neither of these was reported in the placebo group. Alosetron was not associated with any deaths. CONCLUSIONS: Alosetron was effective in these men and women with IBS. constipation was the most frequently reported adverse event associated with alosetron therapy. Ischemic colitis and serious complications of constipation were reported in a small number of patients treated with alosetron.