Evaluation of antimicrobial activity and bronchodialator effect of a polyherbal drug-Shrishadi

Objective

To investigate antimicrobial and bronchodialator effect of hydroalcholic extract of polyherbal drug Shirishadi containing Shirisha (Albezzia lebbeck), Nagarmotha (Cyprus rotandus) & Kantakari (Solanum xanthocarpum).

Methods

Antimicrobial activity was evaluated by disc diffusion method and MIC, MBC, MFC were calculated by micro dilution method. Hydroalcholic extract of this preparation was investigated for its phytochemical analysis, phenol and flavonoid were determined by spectrophotometric method and in vivo bronchodilator effect was analysed by convulsion time.

Results

The phytochemical tests revealed presence of alkaloids, anthraquinones, carbohydrates, flavonoids, saponins and tannins. The antimicrobial result showed the MIC of 6.25 mg/mL against Staphylococcus aureus and 12.5 mg/mL for Escherichia coli and 12.5 mg/mL against remaining bacteria tested, with strong antifungal activity. The maximum inhibition zone is found against Pseudomonas aeruginosa with MIC 16 mg/mL. Drug showed significant bronchodilator effect with 27.86% & 36.13% increase in preconvulsion time of guinea pigs pretreated with 100 & 200 mg/kg body weight of extract.

Conclusions

The study reveals that the extracts possess antibacterial activity and antifungal activity in a dose dependent manner. This antimicrobial property may be due to presence of several saponins, further studies are highly needed for the drug development.     

Protective role of intestinal bacterial metabolism against baicalin-induced toxicity in HepG2 cell cultures

Baicalin, a glycoside present in Scutellaria baicalensis Georgi, is metabolized to its aglycone, baicalein, in intestine. In the present study, possible role of metabolism of baicalin by intestinal bacteria to baicalein in baicalin-induced toxicity was investigated in HepG2 cell cultures. As an intestinal bacterial metabolic system for baicalin, human fecal preparation containing intestinal microflora (fecalase) was employed. Initially, when cytotoxic effects of baicalin and baicalein were compared, baicalin was more cytotoxic than baicalein in HepG2 cells. When baicalin was incubated with fecalase, it was metabolized to baicalein. In addition, baicalin-incubated with fecalase reduced cytotoxicity of HepG2 cells in a concentration-dependent manner. Moreover, baicalin-incubated with fecalase significantly caused an increase in Bcl-2 expression together with a decrease in Bax expression and cleaved Caspase-3. Furthermore, anti-apoptotic effect by the incubation of baicalin with fecalase was also confirmed by the terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick-end labeling assay. Taken all together, the findings suggested that metabolism of baicalin by human fecalase to baicalein might have protective effects against baicalin-induced toxicity in HepG2 cells.     

Biotransformation of geniposide by human intestinal microflora on cytotoxicity against HepG2 cells

Intestinal microflora (IM) is able to produce toxic and carcinogenic metabolites and induce more potent cytotoxicity against cells than non-metabolites. This study was performed to investigate the cytotoxic responses of geniposide (GS) and its metabolite and to determine the role of metabolism by IM in GS-induced cytotoxicity. Genipin (GP), a GS metabolite, increased cytotoxic effects in cells, but GS did not. Following GS incubation with IM for metabolic activation, increased cytotoxicity was detected compared to GS. Western blot analysis revealed that the activated GS inhibited Bcl-2 expression with a subsequent increase in Bax expression. Likewise, GS activation by IM stimulated caspase-3 and the production of reactive oxygen species (ROS). In addition, activated GS-induced apoptosis was confirmed by apoptosis and ROS assays; N-acetyl-l-cysteine (NAC) suppressed ROS production and apoptotic cell death. Activated GS induced sustained JNK phosphorylation. Moreover, activated GS-induced cell death was reversed by SP600125. Taken together, these findings suggest that human IM is able to metabolize GS into GP, and the related biological activities induce apoptosis through ROS/JNK signaling.     

Autologous Stem Cell Transplantation for Multiple Myeloma: Identification of Prognostic Factors

IntroductionThe purpose of this study was to evaluate the effect of prognostic factors on the outcome of patients with MM after ASCT.Patients and MethodsWe analyzed results of 170 consecutive patients (121 male and 49 female) of MM who underwent ASCT. Patients' median age was 52 years (range, 26-68 years). High dose melphalan (200 mg/m²) was used for conditioning. One hundred thirty-two patients (77.6%) had evidence of chemosensitive disease before transplant. Response was assessed using European Group for Blood and Bone Marrow Transplantation criteria.ResultsPost ASCT 44.7% of patients achieved CR, 24.7% had very good partial response (VGPR), and 21.2% had partial response (PR). Presence of pretransplant chemosensitive disease (CR, VGPR, and PR) and transplant within 12 months of diagnosis for years before 2006 were associated with higher response rates on multivariate analysis. At a median follow-up of 84 months, median overall (OS) and event-free survival (EFS) is 85.5 and 41 months, respectively. Estimated OS and EFS at 60 months is 62 ± 0.04% and 41 ± 0.04%, respectively. Patients who responded to transplant (CR, VGPR, and PR) had a longer OS (P < .001) and EFS (P < .001). Additionally, patients who achieved CR post transplant had a longer OS (P < .001) and EFS (P < .001). Patients who received novel agents for induction pretransplant had a longer OS (P < .001) and EFS (P < .002).ConclusionOutcome after ASCT is better for myeloma patients with pretransplant chemosensitive disease and those who achieve CR after transplant.     

Sero-Surveillance to Assess Immunity to Rubella and Assessment of Immunogenicity and Safety of a Single dose of Rubella Vaccine in School Girls

Background:

Rubella vaccination is not yet included in National Immunization Schedule in India. Serosurvey is frequently used to assess epidemiologic pattern of Rubella in a community. Serosurveys in different parts of India have found that 6–47% of women are susceptible for Rubella infection. The present serosurveillance was conducted in Jammu, India, in two public schools.

Objective:

To determine serological status of Rubella antibodies of school girls and assessment of immunogenicity and reactogenicity of Rubella immunization in seronegative girls.

Materials and Methods:

The current study was conducted to determine Rubella serostatus in peripubertal schoolgirls aged 11–18 years and also to assess immunogenicity and safety of Rubella vaccine (R-Vac) of Serum Institute of India Ltd., Pune, in seronegative girls. For screening, pre-vaccination serum Rubella IgG antibodies were determined and to assess immunogenicity of the vaccine, post-vaccination IgG antibodies were compared with pre-vaccination levels. Safety assessment was done for a period of 8 weeks, post-vaccination.

Results:

A total of 90 (32.7%) seronegative girls were vaccinated. All girls (100%) became seropositive, post-vaccination. Clinically relevant and statistically significant increase in anti-Rubella IgG titres was observed. The adverse events were mild and self-limiting.

Conclusions:

R-Vac vaccine used in the study demonstrated an excellent safety and immunogenicity profile.     

Multi-gene testing in neurological disorders showed an improved diagnostic yield: data from over 1000 Indian patients

Journal of Neurology - Neurological disorders are clinically heterogeneous group of disorders and are major causes of disability and death. Several of these disorders are caused due to genetic...     

Regional subcortical shape analysis in premanifest Huntington's disease

Huntington's disease (HD) involves preferential and progressive degeneration of striatum and other subcortical regions as well as regional cortical atrophy. It is caused by a CAG repeat expansion in the Huntingtin gene, and the longer the expansion the earlier the age of onset. Atrophy begins prior to manifest clinical signs and symptoms, and brain atrophy in premanifest expansion carriers can be studied. We employed a diffeomorphometric pipeline to contrast subcortical structures’ morphological properties in a control group with three disease groups representing different phases of premanifest HD (far, intermediate, and near to onset) as defined by the length of the CAG expansion and the participant's age (CAG‐Age‐Product). A total of 1,428 magnetic resonance image scans from 694 participants from the PREDICT‐HD cohort were used. We found significant region‐specific atrophies in all subcortical structures studied, with the estimated abnormality onset time varying from structure to structure. Heterogeneous shape abnormalities of caudate nuclei were present in premanifest HD participants estimated furthest from onset and putaminal shape abnormalities were present in participants intermediate to onset. Thalamic, hippocampal, and amygdalar shape abnormalities were present in participants nearest to onset. We assessed whether the estimated progression of subcortical pathology in premanifest HD tracked specific pathways. This is plausible for changes in basal ganglia circuits but probably not for changes in hippocampus and amygdala. The regional shape analyses conducted in this study provide useful insights into the effects of HD pathology in subcortical structures.