Variations in Physicochemical Properties of a Traditional Mercury-Based Nanopowder Formulation: Need for Standard Manufacturing Practices

Rasasindura is a mercury-based nanopowder synthesized using natural products through mechanothermal processing. It has been used in the Ayurvedic system of medicine since time immemorial for various therapeutic purposes such as rejuvenation, treatment of syphilis and in genital disorders. Rasasindura is said to be composed of mercury, sulphur and organic moieties derived from the decoction of plant extracts used during its synthesis. There is little scientific understanding of the preparation process so far. Though metallic mercury is incorporated deliberately for therapeutic purposes, it certainly raises toxicity concerns. The lack of gold standards in manufacturing of such drugs leads to a variation in the chemical composition of the final product. The objective of the present study was to assess the physicochemical properties of Rasasindura samples of different batches purchased from different manufacturers and assess the extent of deviation and gauge its impact on human health. Modern characterization techniques were employed to analyze particle size and morphology, surface area, zeta potential, elemental composition, crystallinity, thermal stability and degradation. Average particle size of the samples observed through scanning electron microscope ranged from 5-100 nm. Mercury content was found to be between 84 and 89% from elemental analysis. Despite batch-to-batch and manufacturer-to-manufacturer variations in the physicochemical properties, all the samples contained mercury in the form of HgS. These differences in the physicochemical properties may ultimately impact its biological outcome.     

Novel therapies for heart failure: vasopressin and selective aldosterone antagonists

Despite favorable improvements in mortality, heart failure (HF) remains a problematic illness due to the ever-present burden of hospitalization. Clearly, novel treatment strategies are needed. This review focuses on two newer pharmacologic targets: arginine vasopressin and aldosterone. Arginine vasopressin receptor antagonists will most likely serve as an adjunct to or replacement of standard diuretic therapy in selected patients. The safety and efficacy of chronic therapy with oral arginine vasopressin receptor antagonists in large groups of congestive HF patients is currently under investigation. Aldosterone antagonism is emerging as a treatment of severe congestive HF. Recent large-scale clinical trials using aldosterone antagonists have proven that those with HF or left ventricular dysfunction postmyocardial infarction derive a survival benefit from aldosterone antagonism. Whether aldosterone antagonism should be prescribed in all patients with HF is unclear; however, in carefully selected and managed patients, aldosterone antagonism is helpful.     

Stent implantation in right-sided patent ductus arteriosus to relieve severe cyanosis in adult patient with pulmonary atresia and ventricular septal defect.

Patients with unrepaired pulmonary atresia and ventricular septal defect may develop stenosis of collaterals or shunts to the pulmonary arteries leading to hypoperfusion of lungs and systemic hypoxemia. A 25-year-old female with pulmonary atresia and ventricular septal defect presented with progressively increasing cyanosis and exercise intolerance. A restrictive right-sided patent ductus arteriosus was identified as the main source of pulmonary blood flow. We report transcatheter implantation of a balloon-expandable stent across the stenosed duct to augment the pulmonary blood flow as a palliative management option. Patient had immediate improvement in arterial oxygen saturation from 66% to 85% with excellent clinical improvement and stable oxygen saturation on 8 months of follow-up.     

Cartilage-specific constitutive expression of TSG-6 protein (product of tumor necrosis factor alpha-stimulated gene 6) provides a chondroprotective,but not antiinflammatory,effect in antigen-induced arthritis

OBJECTIVE: To study the chondroprotective effect of constitutively expressed TSG-6 protein (tumor necrosis factor alpha-induced protein 6; Tnfip6) in cartilage, using antigen-induced arthritis (AIA) in mice. METHODS: Transgenic mice constitutively expressing TSG-6 protein in cartilage were generated. Cartilage-specific constitutive expression of TSG-6 protein was confirmed by in situ hybridization, Western blot analysis, and immunohistochemistry. Control and transgenic mice were immunized with methylated bovine serum albumin (mBSA), and arthritis was induced by the intraarticular injection of mBSA. Mice were monitored up to day 35 after the challenge, and knee joint sections were examined for loss of cartilage proteoglycan (aggrecan) using Safranin O staining and antibodies to neoepitopes generated by various metalloproteinases (MPs). The loss of aggrecan in Safranin O-stained sections was quantified by morphometric methods. RESULTS: Tsg6/tnfip6 transgenic mice constitutively expressed tsg6/tnfip6 messenger RNA and corresponding TSG-6 protein in cartilage from embryonic life through adulthood, without any phenotypic abnormalities. These mice were used for AIA studies. Intraarticular injection of mBSA uniformly induced severe inflammation both in control (wild-type and an irrelevant transgenic line) mice and in tsg6/tnfip6 transgenic mice. In contrast to the mBSA-injected knee joints of control animals that were heavily damaged from day 5, the cartilage of transgenic mice that constitutively expressed TSG-6 protein remained intact for at least 1 week, and this was followed by a relatively reduced loss of aggrecan. Concomitant with the loss of aggrecan, MP-generated neoepitopes accumulated in unprotected joints. By day 35, the proteoglycan content returned to nearly normal levels in tsg6/tnfip6 transgenic mice, whereas it remained low in MP-damaged knee cartilage of control mice. CONCLUSION: TSG-6 protein is known to form a complex with inter-alpha-inhibitor (IalphaI), a potent serine protease inhibitor, which may be immobilized via the hyaluronan (HA)-binding domain of TSG-6 protein in the HA-rich extracellular matrix of cartilage. Thus, the local accumulation of TSG-6 protein and TSG-6 protein-bound IalphaI in tsg6/tnfip6 transgenic mice may inhibit serine proteases and subsequent activation of MPs. It is suggested that this mechanism might protect cartilage from extensive degradation even in the presence of acute inflammation.     

Articular manifestations of human immunodeficiency virus infection

Prospective studies of HIV-positive and HIV-negative individuals, longitudinal prospective studies of HIV-positive patients and the African experience with spondyloarthropathies have provided support for a direct role of HIV infection in producing a variety of articular manifestations. The most common manifestations are arthralgia and the spectrum of spondyloarthropathies, but distinct entities such as HIV-associated arthritis and the painful articular syndrome have also been reported. Although initial reports described patients with mainly asymmetric oligoarthritis, a polyarticular presentation is now seen frequently. In Caucasians, HIV-associated reactive arthritis resembles reactive arthritis in non-HIV-infected persons. Reactive arthritis, psoriatic arthritis and undifferentiated spondyloarthropathy were uncommon in Africa and are now detected more often with the HIV epidemic. Although early reports in Western communities reported asymmetrical oligoarthritis as the usual pattern, polyarticular involvement is now seen frequently. Intravenous drug abuse is the most likely risk factor for septic arthritis, even in HIV-infected persons in Western communities, while HIV infection itself may be more important in developing countries where most patients do not receive highly active antiretroviral therapy (HAART). Recent reports have drawn attention to the development of avascular necrosis of the bone in HIV-positive patients and the risk factors include HAART itself, complications of HAART, HIV infection per se or concomitant conventional risk factors. Many patients respond to conventional symptomatic therapy, and disease-modifying drug therapy is necessary for patients who have persistent and progressive arthritis. The use of HAART can modify the prevalence or expression of the articular syndromes.