Ameliorating effect of microdoses of a potentized homeopathic drug,Arsenicum Album,on arsenic-induced toxicity in mice

Background  

Arsenic in groundwater and its accumulation in plants and animals have assumed a menacing proportion in a large part of West Bengal, India and adjoining areas of Bangladesh. Because of the tremendous magnitude of the problem, there seems to be no way to tackle the problem overnight. Efforts to provide arsenic free water to the millions of people living in these dreaded zones are being made, but are awfully inadequate. In our quest for finding out an easy, safe and affordable means to combat this problem, a homeopathic drug, Arsenicum Album-30, appears to yield promising results in mice. The relative efficacies of two micro doses of this drug, namely, Arsenicum Album-30 and Arsenicum Album-200, in combating arsenic toxicity have been determined in the present study on the basis of some accepted biochemical protocols.     

Leukocytes utilize both alpha4 and alpha5 integrins for intraislet infiltration in non-obese diabetic mice

The loss of insulin-producing cells during the development of type 1 diabetes is dependent on leukocyte infiltration of beta-islets in the pancreas. Injection of antibodies to integrins and their ligands has been shown to prevent the development of diabetes in non-obese diabetic (NOD) mice. However, little is known about the progression of infiltration by leukocytes after their homing and extravasation into the pancreas. In the present study, the effect of monoclonal antibodies (mAbs) to alpha4 and alpha5 integrins on leukocytes that had infiltrated the islets was characterized in NOD mice at 10 weeks of age when insulitis was in progress, or in mice with recent onset of diabetes. Injection of mAbs to either alpha4 or alpha5 integrins had little effect on the extent of leukocyte infiltration in 10-week-old or diabetic mice. In contrast, leukocyte infiltration was significantly reduced upon injection of mAbs to both alpha4 and alpha5 integrins. The reduction in leukocyte infiltration was due to decreases in the percentage of islets with intraislet infiltration. However, the observed effect of mAbs to alpha4 and alpha5 integrins was reversible, since intraislet infiltration resumed upon termination of antibody treatment. Results suggest that after homing to the pancreas, leukocytes utilize both alpha4 and alpha5 integrins for intraislet infiltration.     

Incidence and outcome of adenovirus disease in transplant recipients after reduced-intensity conditioning with alemtuzumab.

Adenoviruses are emerging as a major cause of infectious complications after allogeneic transplantation. We evaluated the incidence and outcome of symptomatic adenovirus infection or adenovirus disease after alemtuzumab-based reduced-intensity conditioning in 86 consecutive patients. The overall probability of adenovirus disease was 18.4% (11/86 patients). Five patients died of progressive adenovirus disease, and this was the most important infectious cause of mortality in this cohort. The probability of nonrelapse mortality was 49% in patients with adenovirus disease compared with 25.5% in those without (P=.007). The severity of lymphocytopenia and continuation of immunosuppressive therapy were the most important risk factors for progressive adenovirus disease and death. In contrast, patients who were not receiving immunosuppressive therapy or had had it reduced or withdrawn cleared the virus. We also detected a correlation between the lack of preemptive anti-cytomegalovirus (CMV) therapy for CMV reactivation and the risk of progressive adenovirus disease (P=.05). Our findings highlight the emergence of adenovirus as an important posttransplantation pathogen even after reduced-intensity conditioning and demonstrate the effect of the severity of lymphocytopenia, anti-CMV prophylaxis, and immunosuppressive therapy on the outcome of adenovirus disease.     

The prevalence of antiphospholipid antibodies in cases of recurrent pregnancy loss

Antiphospholipid antibodies (aPL) are a diverse family of autoantibodies reactive against negatively charged phospholipid-protein complexes. The clinically significant members include lupus anticoagulant (LA), anticardiolipin antibody (aCL) and reaginic antibodies causing biological false positive (BFP) venereal disease laboratory test (VDRL). Although detected in various clinical scenarios, unexplained fetal loss in women of reproductive age group is the commonest association. Fifty pregnant women of first and second trimester with a history of two or more unexplained pregnancy losses were studied for the presence of LA, aCL and reaginic antibodies. Thirty pregnant women of the same trimester without any history of fetal loss were taken as control. LA was detected in nine (18%) cases and aCL in 12 (24%) cases of the study group. The control group was negative for any autoantibody. The prevalence of aPL in the study group found to be statistically significant. Detection of aPL must be considered in women with previous pregnancies complicated by unexplained fetal wastage.     

Interaction of endothelin-1 with vasoactive factors in mediating glucose-induced increased permeability in endothelial cells

Alteration of endothelins (ET) and/or their receptors may be important in mediating vascular dysfunction in diabetes. We investigated mechanisms regulating ET-1 expression in human umbilical vein endothelial cells (HUVEC) in response to glucose and the functional significance of these mechanisms. Permeability across HUVEC, grown in medium containing either low (5 mmol/l) or high (25 mmol/l) D-glucose were investigated. L-glucose was used as a control. ET-1, ET(A), and ET(B) mRNA were assessed by semiquantitative RT-PCR. ET-1 immunoreactivity and F-actin microfilament assembly were investigated using confocal microscopy. Increased transendothelial permeability was noted in cells cultured in high glucose or when the cells grown in low (physiologic) glucose were incubated with ET-1, vascular endothelial growth factor (VEGF), or N (G) -nitro-L-arginine methyl ester but not when they were incubated with ET-3, N(G)-nitro-D-arginine methyl ester, or L-glucose. Increased permeability was associated with increased ET-1, ET(A), and ET(B) mRNA expression and augmented ET-1 immunoreactivity. High glucose induced increased permeability, increased ET-1, ET(A), and ET(B) mRNA expression. ET-1 immunoreactivity was blocked by the protein kinase C (PKC) inhibitor chelerythrine, the specific PKC isoform inhibitor 379196, VEGF-neutralizing antibody, or the ET(A) blocker TBC11251, but was not blocked by the specific ET(B) blocker BQ788 or by a VEGF-non-neutralizing antibody. Increased permeability was also associated with deranged F-actin assembly in the endothelial cells and by derangement of endothelial cell junctions as assessed by electron microscopy. Data from this study suggest that high glucose-induced increased permeability may be induced through increased ET-1 expression and disorganization of F-actin assembly. ET-1 expression and increased permeability may occur secondary to PKC isoform activation and may be modulated by VEGF and nitric oxide.     

Development and evaluation of a phage typing scheme for Vibrio cholerae O139

The scenario of cholera that existed previously changed in 1992 and 1993 with the emergence of toxigenic Vibrio cholerae O139 in India. The genesis of the new serogroup formed the impetus to search for O139 phages in and around the country. A total of five newly isolated phages lytic to V. cholerae O139 strains were used for the development of this phage typing scheme. These phages differed from each other and also differed from the existing O1 phages in their lytic patterns, morphologies, restriction endonuclease digestion profiles, and immunological criteria. With this scheme, 500 V. cholerae O139 strains were evaluated for their phage types, and almost all strains were found to be typeable. The strains clustered into 10 different phage types, of which type 1 (38.2%) was the dominant type, followed by type 2 (22.4%) and type 3 (18%). Additionally, a comparative study of phage types in 1993 and 1994 versus those from 1996 to 1998 for O139 strains showed a higher percentage of phage type 1 (40.5%), followed by type 3 (18.8%) during the period between 1993 and 1994, whereas phage type 2 (32. 1%) was the next major type during the period from 1996 to 1998. This scheme comprising five newly isolated phages would be another useful tool in the study of the epidemiology of cholera caused by V. cholerae O139.     

Microbiology of systemic fungal infections

The increased incidence of systemic fungal infections in the past two decades has been overwhelming. Earlier, it was pathogenic dimorphic fungi, which were known to cause systemic infections. However, starting from the 1960s, opportunistic fungi started causing more number of infections, especially in the immunocompromised host. More recently, newer and less common fungal agents are being increasingly associated with infection in immunosuppressed hosts. Amongst dimorphic fungi, infections due to Histoplasma capsulatum and Penicillium marneffei are increasingly reported in patients with AIDS in India. H. capsulatum is found country wide, but P marneffei remains restricted to Manipur state. Although both varieties of C. neoformans, C. neoformans var. neoformans (serotypes A & D), and C. neoformans var. gattii (serotypes B & C) are reported in India, most of the cases reported are of serotype A. Increased incidence of cryptococcosis is reported from all centers with the emergence of AIDS. Systemic infection due to species under Candida, Aspergillus and zygomycetes is widely prevalent in nosocomial setting, and outbreaks due to unusual fungi are reported occasionally from tertiary care centers. This global change in systemic fungal infections has emphasized the need to develop good diagnostic mycology laboratories in this country and to recognize this increasingly large group of potential fungal pathogens.     

Studies on the euglycemic and hypolipidemic potentials of the novel indole analogue of thiazolidinedione, DRF 2189

Euglycemic and hypolipidemic activities of a novel indole analogue of thiazolidinedione, DRF 2189 (CAS 172647-53-9), have been evaluated in different animal models. Compared to troglitazone (CAS 97322-87-7), DRF 2189 exhibited interesting plasma glucose and triglyceride lowering activity in genetically diabetic and obese db/db mice. It also produced a significant reduction in plasma glucose, triglyceride, total cholesterol levels and improvement in oral glucose tolerance in another genetic mouse model, the ob/ob mice. In high-fat diet fed Sprague-Dawley rats, DRF 2189 treatment showed improvement in plasma lipid parameters. Like other thiazolidinediones, this compound also possesses peroxisome proliferator activated receptor gamma (PPAR gamma) transactivation potential. In anaesthetized rat experiment, DRF 2189 produced a transient fall in blood pressure without any change in the ECG pattern. It showed non-specific smooth muscle relaxant activity against acetylcholine, histamine and potassium chloride induced contractions in isolated guinea pig ileum. A twenty-eight-day toxicity study in Wistar rats did not show any signs of treatment related adverse effects. The overall antidiabetic and hypolipidemic activities of DRF 2189 are comparable with rosiglitazone (CAS 155141-29-0) and superior to troglitazone. In conclusion, results from these preclinical studies indicate that DRF 2189, a novel thiazolidinedione, has a marked potential for the management of type-2 diabetes.     

Evidence of cross-link formation of vitreous collagen during experimental ocular inflammation

Purpose: To determine the mechanisms of vitreous changes during ocular inflammation. Methods: We investigated vitreous changes, with special emphasis on collagen, in an experimental model of ocular inflammation induced by intravitreal injection of endotoxin (Escherichia coli) in rabbits. Results: Inflammation caused gel contraction and loss of elasticity, accompanied by release of a water-like liquid from the gel, and increases in the amount of insoluble material and highmolecular-weight components of vitreous collagen, presumably due to extensive cross-links of the collagen molecules. Those changes were partially inhibited by intravitreal injection of superoxide dismutase. Conclusions: The crosslinks of vitreous collagen may promote vitreous gel contraction and release of a water-like liquid from the gel. Superoxide anion may play a role in this process.