A therapeutic approach to treat cardiovascular dysfunction of diabetes

Diabetes greatly increases risk of cardiovascular dysfunction and interruptions of matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) have been shown to reduce the risk by alteration in extracellular matrix. We hypothesized that minocycline induced MMP-2 and MMP-9 inhibition can be enhanced by aspirin (through its COX and tPA inhibitory action) and this combination can reduce cardiovascular dysfunction of diabetes. Four weeks after diabetes induction (streptozotocin, 55 mg/kg, i.p.), rats were treated with minocycline (50 mg/kg, p.o.), aspirin (50 mg/kg, p.o.), or minocycline (50 mg/kg, p.o.) plus aspirin (50 mg/kg, p.o.) for a period of next four weeks. At the end of eighth week arterial pressure, heart rate and left ventricular pressure were recorded. Contractile response to phenylephrine (10^?5 M) and relaxation responses to acetylcholine (10^?9–10^?4 M) were obtained from aortic rings of diabetic rats. Gel zymography was performed to evaluate MMP-2 and MMP-9 levels. Heart rate, mean arterial pressure, dp/dt_max and dp/dt_min were found significantly decreased in STZ diabetic rats when compared with normoglycemic group. Treatment with combination of minocycline and aspirin significantly ameliorate these compared to vehicle treated diabetic group. Endothelium-dependent relaxation responses induced by acetylcholine were decreased in diabetic rats and significantly higher in combination treated group. Collagen, MMP-2 and MMP-9 levels were significantly decreased in combined treated group when compared with diabetic control. Present study revealed that aspirin potentate minocycline induced MMP-2 and MMP-9 inhibition to ameliorate cardiovascular dysfunction of diabetes and this combination can be an approach for the treatment.     

Enhancement of nootropic effect of duloxetine and bupropion by caffeine in mice

Objective:The existing evidence suggests an association between depression and memory impairment. The objective of present study was to assess the effect of low dose caffeine with duloxetine and bupropion on memory.Results:Caffeine with duloxetine treated group was better than other combination treated groups in terms of a significant decrease in TL and increase in the time spent in target quadrant recorded.Conclusion:Combining lower dose of caffeine with duloxetine may enhance cognitive benefits than respective monotherapies.KEY WORDS: And bupropion, caffeine, duloxetine, memory     

Migraine: current concepts and emerging therapies

Migraine is a recurrent incapacitating neurovascular disorder characterized by attacks of debilitating pain associated with photophobia, phonophobia, nausea and vomiting. Migraine affects a substantial fraction of world population and is a major cause of disability in the work place. Though the pathophysiology of migraine is still unclear three major theories proposed with regard to the mechanisms of migraine are vascular (due to cerebral vasodilatation), neurological (abnormal neurological firing which causes the spreading depression and migraine) and neurogenic dural inflammation (release of inflammatory neuropeptides). The modern understanding of the pathogenesis of migraine is based on the concept that it is a neurovascular disorder. The drugs used in the treatment of migraine either abolish the acute migraine headache or aim its prevention. The last decade has witnessed the advent of Sumatriptan and the 'triptan' class of 5-HT1B/1D receptor agonists which have well established efficacy in treating migraine. Currently prophylactic treatments for migraine include calcium channel blockers, 5-HT2 receptor antagonists, beta adrenoceptor blockers and gamma-amino butyric acid (GABA) agonists. Unfortunately, many of these treatments are non specific and not always effective. Despite such progress, in view of the complexity of the etiology of migraine, it still remains undiagnosed and available therapies are underused. In this article, the diverse pieces of evidence that have linked the different theories of migraine with its pathophysiology are reviewed. Furthermore, the present therapeutic targets and futuristic approaches for the acute and prophylactic treatment of migraine, with a special emphasis to calcitonin gene-related peptide, are critically evaluated.     

Protective effect of ST-93 against ouabain induced arrhythmias in guinea pigs

ST-93, a clonidine analog was studied for its antiarrhythmic activity in anaesthetised guinea pigs against ouabain induced arrhythmia. The amount of ouabain required (micrograms/kg) for the production of ventricular premature best. Ventricular fibrillation and cardiac arrest was recorded in control and drug treated group of animals. Both ST-93 and clonidine produced significant antiarrhythmic effect in guinea pigs. This protective effect was significantly blocked by yohimbine, suggesting that the antiarrhythmic effect is mediated through presynaptic alpha 2-adrenoceptors.     

Vanillic acid derivatives from the green algae Cladophora socialis as potent protein tyrosine phosphatase 1B inhibitors

A novel vanillic acid derivative (1) and its sulfate adduct (2) were isolated from a green algae, Cladophora socialis. The structures of 1 and 2 were elucidated from NMR and HRESIMS experiments. Both compounds showed potent inhibitory activity against protein tyrosine phosphatase 1B (PTP1B), an enzyme involved in the regulation of insulin cell signaling. Compounds 1 and 2 had IC50 values of 3.7 and 1.7 microM, respectively.     

Niphatoxin C, a cytotoxic tripyridine alkaloid from Callyspongia sp

As part of our studies to discover P2X 7 receptor antagonists, the sponge Callyspongia sp. was investigated. A new tripyridine alkaloid niphatoxin C ( 1) was isolated and had P2X 7 receptor antagonism; however, cytotoxicity of THP-1 cells was the predominant biological effect at higher concentrations. Its structure was determined by 1- and 2-D NMR spectroscopy.     

Retinal nerve fiber layer evaluation of spectral domain optical coherence tomograph and scanning laser polarimeter to diagnose glaucoma

Purpose

To compare the abilities of retinal nerve fiber layer (RNFL) parameters of spectral domain optical coherence tomograph (SDOCT) and scanning laser polarimeter (GDx enhanced corneal compensation; ECC) in detecting glaucoma.

Methods

In a cross-sectional study, 215 eyes of 165 subjects (106 eyes of 79 glaucoma patients and 109 eyes of 86 controls) referred by general ophthalmologists for glaucoma evaluation underwent RNFL imaging with SDOCT and GDx ECC. Ability of RNFL parameters of SDOCT to discriminate glaucoma eyes from control eyes was compared with that of GDx ECC using area under operating characteristic curves (AUCs), sensitivities at fixed specificities, and likelihood ratios (LRs).

Results

AUC of the average RNFL thickness of SDOCT to differentiate glaucoma from control eyes (0.868) was comparable (P=0.32) to that of GDx ECC (0.855). Sensitivity at 95% specificity was 63.2% for average RNFL thickness of SDOCT and 48.1% for the average RNFL measurement of GDx ECC. LRs of outside normal limits category of SDOCT parameters ranged between 5.6 and 7.7 while the same of GDx ECC parameters ranged between 3.1 and 3.7. LRs of within normal limits category of SDOCT parameters ranged between 0.18 and 0.24 while the same of GDx ECC parameters ranged between 0.20 and 0.32.

Conclusion

Though AUCs and sensitivities at fixed specificities were comparable between the RNFL parameters of SDOCT and GDx ECC in diagnosing glaucoma, LRs indicated that the RNFL parameters of SDOCT were better in ‘ruling in'' glaucoma.     

In vitro anti-inflammatory activities of blacklip abalone (Haliotis rubra) in RAW 264.7 macrophages

Abalone (Haliotis sp) has been used as a traditional functional food for many years by different cultures believing that consumption provides health benefits. We investigated the anti-inflammatory activity from blacklip abalone visceral waste. An extract was prepared from the viscera using digestion with the food grade proteases papain and bromelain followed by anion exchange chromatography (AEC). The anti-inflammatory potential of the extract and AEC fractions were investigated in comparison to a plant-derived positive control (quercetin) through the inhibition of lipopolysaccharide-stimulated nitric oxide production in RAW 264.7 monocytes. Significant anti-inflammatory activity was observed in response to the abalone extract and the unbound AEC material over a concentration (based on collagen) range of 12–96?µg/mL. Overall, results indicated that blacklip abalone extract has anti-inflammatory activity in vitro, warranting further investigation into the bioactive constituents that may be potential anti-inflammatory therapeutics.