A novel sarsasapogenin glycoside from Asparagus racemosus elicits protective immune responses against HBsAg

The aim of the present investigation was to evaluate the adjuvant potential of a novel sarsasapogenin glycoside (immunoside) isolated from Asparagus racemosus in combination with hepatitis B surface antigen (HBsAg). Various in vitro and animal derived protocols were used to determine the response of immunoside adjuvanted with HBsAg and the results were compared with alum adjuvanted with HBsAg. Several biomarkers such as antibody titre (IgG, IgG1/IgG2a) were measured in mice sera. Cell proliferation, cytokines (IL-2, IFN-γ and IL-4), and lymphocyte sub-populations (CD4/CD8, CD3 and CD19) were determined in splenocytes from mice administered subcutaneously with test substances. In these cells CD4/CD8 derived IFN-γ release was also determined. Macrophage preparations were used for the determination of IL-12, IFN-γ and nitrite content. Seroconversion potential was compared with a standard vaccine. Acute safety evaluation of immunoside was done in mice. Effect of immunoside on red blood cell haemolysis was determined. The results have suggested that immunoside potentially enhanced anti-HBsAg immune response via augmenting Th1/Th2 response in a dose dependent manner.     

Equivalent occupancy of dopamine D1 and D2 receptors with clozapine: differentiation from other atypical antipsychotics

OBJECTIVE: Clozapine, the prototype of atypical antipsychotics, remains unique in its efficacy in the treatment of refractory schizophrenia. Its affinity for dopamine D(4) receptors, serotonin 5-HT(2A) receptor antagonism, effects on the noradrenergic system, and its relatively moderate occupancy of D(2) receptors are unlikely to be the critical mechanism underlying its efficacy. In an attempt to elucidate the molecular/synaptic mechanism underlying clozapine's distinctiveness in refractory schizophrenia, the authors studied the in vivo D(1) and D(2) receptor profile of clozapine compared with other atypical antipsychotics. METHOD: Positron emission tomography with the radioligands [(11)C]SCH23390 and [(11)C]raclopride was used to investigate D(1) and D(2) receptor occupancy in vivo in 25 schizophrenia patients receiving atypical antipsychotic treatment with clozapine, olanzapine, quetiapine, or risperidone. RESULTS: Mean striatal D(1) occupancies ranged from 55% with clozapine to 12% with quetiapine (rank order: clozapine > olanzapine > risperidone > quetiapine). The striatal D(2) occupancy ranged from 81% with risperidone to 30% with quetiapine (rank order: risperidone > olanzapine > clozapine > quetiapine). The ratio of striatal D(1)/D(2) occupancy was significantly higher for clozapine (0.88) relative to olanzapine (0.54), quetiapine (0.41), or risperidone (0.31). CONCLUSIONS: Among the atypical antipsychotics, clozapine appears to have a simultaneous and equivalent occupancy of dopamine D(1) and D(2) receptors. Whether its effect on D(1) receptors represents agonism or antagonism is not yet clear, as this issue is still unresolved in the preclinical arena. This distinctive effect on D(1)/D(2) receptors may be responsible for clozapine's unique effectiveness in patients with schizophrenia refractory to other typical and atypical antipsychotics.     

Differences in the mechanism of metabolic regulation of ATP-sensitive K+ channels containing Kir6.1 and Kir6.2 subunits

AIMS: ATP sensitive K(+) channels (K(ATP)) sense adenine nucleotide concentrations and thus couple the metabolic state of the cell to membrane potential. The hetero-octameric complex of a sulphonylurea receptor (SUR2B) and an inwardly rectifying K(+) channel (Kir6.1) and the corresponding native channel in smooth muscle are relatively insensitive to variations in intracellular ATP. Activation of these channels in blood vessels during hypoxia/ischaemia is thought to be mediated via hormonal regulation such as cellular adenosine release or the release of mediators from the endothelium. In contrast, intracellular ATP prominently inhibits Kir6.2 containing complexes, such as those present in cardiac myocytes. Thus, we investigated differences in the mechanism of metabolic regulation of Kir6.1 and Kir6.2 containing K(ATP) channels. METHODS AND RESULTS: We have heterologously expressed K(ATP) channel subunits in HEK293 and CHO cells and studied their function using (86)Rb efflux and patch clamping. We show that rodent Kir6.1/SUR2B has direct intrinsic metabolic sensitivity independent of any regulation by protein kinase A. In contrast to Kir6.2 containing complexes, this was not endowed by the ATP sensitivity of the pore forming subunit but was instead a property of the SUR2B subunit. Mutagenesis of key residues within the nucleotide-binding domains (NBD) implicated both domains in governing the metabolic sensitivity. CONCLUSION: Kir6.1\SUR2B has intrinsic sensitivity to metabolism endowed by the likely processing of adenine nucleotides at the NBD of SUR2B.     

Study of the adjuvanticity of lysine lipopeptides; carbamate analogs elicit strong Th1 and Th2 response to ovalbumin in mice

Bacterial lipoproteins and their synthetic analogs are strong immune modulators of the early host responses. In view of the strong adjuvanticity of bacterial lipopeptide mimics bearing lysine residues, a focused library of lipidated dipeptides and tripeptides has been synthesized with a view to understand the pattern of activity vis a vis the site and extent of lipidation. Compounds 4, 5 and 14 stimulate OVA specific IgG titer, neutralization of antibodies (IgG1 and IgG2a), T lymphocyte sub-sets (CD4/CD8) and its production of soluble mediators for Th1 (IFN-γ)/Th2 (IL-4) cytokines and costimulatory molecules (CD80/CD86) which are ideal traits of immune adjuvants. The results support lipidated lysine dipeptides as potent enhancers of humoral and cell mediated immune responses and thus might become promising immune-adjuvants for self adjuvanted vaccines.     

HIV-related liver disease: infections versus drugs

HIV-infected individuals have myriad causes of hepatotoxicity that range from mild hepatitis to significant liver failure with its associated morbidity and mortality, especially in the setting of chronic viral hepatitis (HCV and HBV). Immune restoration by HAART therapy can contribute liver-related toxicity in HIV-coinfected patients. Clinicians need to be aware of this problem and individualize management in this challenging clinical scenario. Avoidance of potentially hepatotoxic agents or close monitoring during treatment of HIV may prevent liver failure in patients who have HIV. Furthermore, vaccination against hepatitis A virus and HBV in nonimmune HIV individuals may prevent acquisition of hepatitis A virus and HBV infections in patients who have HIV. Finally, treatment of HIV, and, if appropriate, treatment of those who are coinfected with HCV and HBV with close monitoring, may improve the outcome of patients who have HIV and are at risk fo r significant hepatotoxicity during treatment from immune restoration or hypersensitivity reactions.     

Comparison of sublingual, vaginal, and oral misoprostol in cervical ripening for first trimester abortion

Objectives:

To compare the effectiveness and tolerability of misoprostol as a cervical ripening agent in first trimester abortion through three different routes of administration before surgical evacuation (SE).

Materials and Methods:

It was a hospital based prospective randomized open labeled parallel study. A total of 150 randomly selected married women were divided in three groups for sublingual (S/L), vaginal and oral 400 μg of misoprostol single dose administration. The drug was administered 3-4 h before SE in the S/L and vaginal groups and 12 h before the procedure in the oral group. Efficacy was assessed on the basis of time taken for ripening, dilatation achieved, duration of the procedure, intra-operative blood loss, and pain score. The tolerability was noted on the basis of side effects.

Results:

The mean time taken for cervical ripening was less in sublingual administration (3.7±1.2 hr) as compared to the vaginal and oral routes. The S/L group had significant cervical dilatation (P<0.001) and the duration of SE was less as compared to the vaginal and oral routes. However, the mean intraoperative blood loss was more in sublingual as compared to the vaginal and oral groups. The intra-operative pain score of the S/L group was significantly lower (1.9±1.1, P<0.05) as compared to the vaginal (2.6±1.7) or oral route (3.3±1.7). Loose motions and nausea/vomiting were more with the S/L and oral routes while blood loss was more in the vaginal route.

Conclusion:

Administration of misoprostol by the sublingual route is better than the oral and vaginal routes for cervical ripening.     

Salivary blood group antigens and microbial flora

To cite this article:
Int J Dent Hygiene 9 , 2011; 117–121
DOI: 10.1111/j.1601‐5037.2010.00451.x
Tabasum ST, Nayak RP. Salivary blood group antigens and microbial flora. Abstract: Objective: Secretor is an individual with ability to produce blood group reactive substances in the exocrine glands and to secrete these substances in the body fluids such as saliva. In saliva the blood reactive antigens are found primarily on mucins which exhibit microheterogenicity and different subtypes of these molecules. This study was done to find out if the salivary blood group antigens have any role in the adherence of certain selected microorganism in the oral cavity. Methods: Unstimulated whole saliva and sub gingival plaque samples were collected from subjects with clinically healthy gingival, chronic gingivitis and chronic periodontitis with probing pocket depth ≥4 mm and attachment loss ≥1 mm. Secretor status was determined by using Haemagglutination Inhibition Assay. Unstimulated whole saliva and sub gingival plaque samples were collected to culture and isolate the selected microorganisms. The clinical scores, secretor status and the presence or absence of selected microorganisms were compared within the groups using Chi‐square test and students unpaired t‐test. Results: The numbers of secretors were more in the healthy group (22.2%) and non secretors were more in the chronic periodontitis group (22.2%). The clinical scores were higher in the in non secretors compared to the secretors in all the three groups. P intermedia and P gingivalis were prevalent among non secretors in chronic gingivitis group. (P = 0.075 and P = 0.032) and chronic periodontitis group (P = 0.068 and P = 0.009).