HIV-1 coreceptors CCR5 and CXCR4 both mediate neuronal cell death but CCR5 paradoxically can also contribute to protection.

The chemokine receptors CCR5 and CXCR4 serve, in addition to CD4, as coreceptors for human immunodeficiency virus-1 (HIV-1), and infection with HIV-1 can cause dementia. In brain-derived cells, HIV-1 envelope glycoprotein gp120 initiates a signaling cascade that involves p38 mitogen-activated protein kinase and leads to neuronal cell death. Using mixed neuronal/glial cultures from rats and mice genetically deficient in one or both HIV coreceptors, we show here that CCR5, CXCR4 or both can mediate HIV/gp120 neurotoxicity depending on the viral strain. Paradoxically, we also found evidence for a CCR5-mediated neuroprotective pathway. We identify protein kinase Akt/PKB as an essential component of this pathway, which can be triggered by the CCR5 agonists macrophage inflammatory protein-1beta and regulated-and-normal-T-cell-expressed-and-secreted. Moreover, these CCR5 ligands prevent neuronal cell death induced by stromal cell-derived factor-1, a CXCR4 agonist. Both neurons and glia coexpress CXCR4 and CCR5. Ca2+ imaging experiments demonstrate that engagement of CCR5 prevents CXCR4-triggered increases in intracellular free Ca2+. This finding suggests that CCR5 ligands can protect neurons at least, in part, by modulating CXCR4-mediated toxicity through heterologous desensitization.

Self-medication for Acne among Undergraduate Medical Students.

AIMS: This study aims to evaluate the knowledge and pattern of self-medication for acne among undergraduate medical students at a tertiary care teaching hospital. MATERIALS AND METHODS: This cross-sectional study was conducted in II MBBS (Group A), III MBBS Part I (Group B), and III MBBS Part II (Group C) students. Prevalidated questionnaire about knowledge, attitude, and practice of self-medication were administered to participants. Data were analyzed using one-way analysis of variance and Chi-square test. RESULTS: Out of 582 students who responded to questionnaire, 518 suffered from acne. Self-medication practice was observed in 59.2% students. Significantly higher number of female students practiced self-medication (P < 0.0001). Most common source of information was seniors/friends/family members (34.2%). The mildness of illness (42.3%) was the most common reason of self-medication. A total mean score of knowledge was significantly higher in Group C as compared to Group A (P < 0.001) and Group B (P < 0.05). Allopathic medication was preferred by 69.8% students. Seventy-five percentage students read leaflet/package insert/label instruction and expiry date of the medicines. CONCLUSIONS: The participating students lack the knowledge about self-medication for acne. Adequate knowledge and awareness about the appropriate use of medication will reduce the practice of self-medication and improve rational prescribing.

An evaluation of impact of educational interventions on the technique of use of metered-dose inhaler by patients.

OBJECTIVES: The objective of this study is to evaluate the impact of two educational interventions that are demonstration versus pictorial Leaflet in patients using metered-dose inhaler (MDI). MATERIALS AND METHODS: This interventional study was done in patients who were prescribed drugs through MDI at Tuberculosis and Chest Department. The patients were enrolled in Group A or Group B as per random number table method. The method of use of MDI was assessed using a checklist based on the technique described in the WHO Guide to good prescribing. Patients in Group A were taught the use of MDI by demonstration of the technique by the investigator. Patients in Group B were educated about the technique by a pictorial leaflet based on the technique. Patients were followed up after 15 days and assessed for correct technique for use of the MDI. RESULTS: A total 100 patients were included in the study and were allotted to Group A (47) and Group B (53). Ninety-five percent of the patients had been taught by the treating physician about the method of use of MDI. All the patients at the baseline placed the lips tightly around the mouthpiece and held the aerosol as indicated in the manufacturer's instructions while the step least followed was coughing up the sputum before inhalation. The average steps correctly followed by the patients in Group A and B at baseline were 5.17 ± 2.07 and 5.11 ± 2.04, respectively. These improved significantly to 9.19 ± 0.67 and 6.67 ± 0.63 in Group A and B, respectively, postintervention. The five essential steps of using MDI were followed by 25.53% and 26.41% patients preintervention. An improvement in the technique of use of MDI was observed in 85.11% and 49.06% patients (P = 0.003) postintervention. All the ten steps of the technique were followed by 34.04% patients from Group A and none from Group B at postintervention evaluation (P = 0.0001). CONCLUSION: The inhalation technique for the use of MDI used by the patients is inappropriate. Educational interventions such as demonstration or pictorial leaflet help ensure a better use of the MDI.

A study of the use of drugs in patients suffering from psoriasis and their impact on quality of life.

OBJECTIVE: To study the use of drugs in patients suffering from psoriasis and their effect on quality of life (QOL). MATERIALS AND METHODS: This was a prospective, observational study carried out in newly diagnosed patient of psoriasis at Department of Pharmacology and Outpatient Department of Skin and Venereal diseases at tertiary care teaching hospital, and patients were divided into three groups: Group A: topical therapy alone, Group B: methotrexate with topical therapy, and Group C: cyclosporine with topical therapy. The efficacy of drug was measured using Psoriasis Area Severity Index (PASI). QOL was measured using Psoriasis Disability Index. Patients were followed up at 1 month and 6 months of treatment. Statistical analysis was done using analysis of variance (ANOVA) test. RESULTS: A total 126 patients were enrolled, out of which 114 patients completed the study. PASI score was reduced significantly (P < 0.001) in each treatment group and QOL score was significantly (P < 0.001) decrease in Group B and C as compared to baseline at the end of 6 months. A significant (P < 0.001) reduction in PASI score and QOL was observed in patients of Group B and C as compared to Group A. Correlation between efficacy and QOL was not significant in all three treatment groups. CONCLUSION: Combination therapy (topical + systemic) is more efficacious and associated with significant improvement of QOL as compared to topical therapy alone. Methotrexate and cyclosporine are equally efficacious in treating and improving the QOL in patients suffering from psoriasis.

Structural and functional analysis of a salt stress inducible gene encoding voltage dependent anion channel (VDAC) from pearl millet (Pennisetum glaucum).

We have cloned and characterized a gene encoding voltage-dependent anion channel from Pennisetum glaucum (PgVDAC). PgVDAC was identified while isolating genes that were differentially up-regulated following salt stress. The genomic organization of PgVDAC clone was well conserved compared to other plant VDAC genes in terms of number of introns, their position and phasing, however, the primary amino acid sequence of voltage dependent anion channel (VDAC) proteins did not show much conservation with other plant VDACs but their secondary and tertiary structures are well conserved as predicted by in silico structural and CD spectra analyses and results show it to be a typical membrane-spanning beta-barrel leading to the formation of pore in the membrane. The heterologous expression of PgVDAC protein in yeast strain lacking the endogenous mitochondrial VDAC gene could not functionally complement it as was also previously observed for the potato VDAC. Using real-time quantitative PCR analysis it was found that transcript expression profile of PgVDAC was quantitatively and kinetically up-regulated in response to salinity, desiccation, cold and exogenous application of salicylic acid (SA); however, there was no effect of exogenous application of abscisic acid (ABA) on its expression. Constitutive over-expression of PgVDAC appears to be deleterious in transgenic rice plant; however, low level of up-regulation imparted salinity stress adaptive response. A search for a more suitable inducible transgene system is currently under way to understand PgVDAC expression levels in plant development and its role in stress adaptation.

Effect of nifedipine, a calcium channel inhibitor, on sedation produced by reserpine, clonidine and propranolol in mice.

Spontaneous motor activity, rotarod test and observational rating of sedation were employed to study effect of nifedipine on sedation produced by reserpine, clonidine and propranolol. Reserpine (2 mg kg-1), clonidine (4 mg kg-1), and propranolol (40 mg kg-1) significantly reduced spontaneous motor activity and staying capacity of animals on accelerating rotarod (P < 0.01). Observational sedation was also caused significantly as indicated by a higher score in test. Nifedipine (2 mg kg-1) produced no sedation or excitation on its own. Reduction in spontaneous motor activity produced by reserpine and clonidine was partially reversed in animals treated with nifedipine (P < 0.01). A similar effect of nifedipine was also evident on the observational sedation induced by reserpine and clonidine. Effect of these drugs on rotarod times was nearly totally antagonised by nifedipine. Nifedipine did not oppose the sedation produced by propranolol which actually became significantly greater in the animals pretreated with nifedipine in all three tests. It is concluded that nifedipine antagonizes the sedation produced by reserpine and clonidine, probably by blocking central alpha 2-adrenoceptors. The sedative effect of propranolol can be potentiated by nifedipine possibly because of a pharmacokinetic interaction.