A pharmacoinformatic approach on Cannabinoid receptor 2 (CB2) and different small molecules: Homology modelling, molecular docking, MD simulations, drug designing and ADME analysis.

CB2 receptor belongs to the family of G-protein coupled receptors (GPCRs), which extensively controls a range of pointer transduction. CB2 plays an essential role in the immune system. It also associates in the pathology of different ailment conditions. In this scenario, the synthetic drugs are inducing side effects to the human beings after the drug use. Therefore, this study is seeking novel alternate drug molecules with least side effects than conventional drugs. The alternative drug molecules were chosen from the natural sources. These molecules were selected from cyanobacteria with the help of earlier research findings. The target and ligand molecules were obtained from recognized databases. The bioactive molecules are selected from various cyanobacterial species, which are selected by their biological and pharmacological properties, after, which we incorporated to the crucial findings such as homology modelling, molecular docking, MD simulations along with absorption, distribution, metabolism, and excretion (ADME) analysis. Initially, the homology modelling was performed to frame the target from unknown sequences of CB2, which revealed 44% of similarities and 66% of identities with the A2A receptor. Subsequently, the CB2 protein molecule has docked with already known and prepared bioactive molecules, agonists and antagonist complex. In the present study, the agonists (5) and antagonist (1) were also taken for comparing the results with natural molecules. At the end of the docking analysis, the cyanobacterial molecules and an antagonist TNC-201 are revealed better docking scores with well binding contacts than the agonists. Especially, the usneoidone shows better results than other cyanobacterial molecules, and it is very close docking scores with that of TCN-201. Therefore, the usneoidone has incorporated to MD simulation with Cannabinoid receptors 2 (CB2). In MD simulations, the complex (CB2 and usneoidone) reveals better stability in 30 ns. Based on the computational outcome, we concluded that usneoidone is an effectual and appropriate drug candidate for activating CB2 receptors and it will be serving as a better component for the complications of CB2. Moreover, these computational approaches can be motivated to discover novel drug candidates in the pharmacological and healthcare sectors.

Analysis of humoral immune response of animals exposed to bacterial antigens.

From the Aeromonas hydrophila strain, five different types of antigens such as heat killed antigen, whole cell antigen, heat killed antigen with antiserum, whole cell antigen with antiserum and nucleotide antigens were prepared and injected into the experimental fish (Catla catla) groups for the study of immunomodulation. Analysis of immunogenicity of antigens against the fish Catla catla was estimated. The A. hydrophila produced ß hemolytic pattern on the blood agar plate. B lymphocyte counts using rosette forming assay revealed a significant decrement in pathogens exposed fishes as compared to controls. Fishes exposed to pathogenic strains (1/10(th) sublethal concentration) for 3 weeks showed a reduction in PFC. The effect or pathogenic antigens in direct spleenic plaque forming cells (1 g M producing cells) showed a reduction in the secondary plaque forming cell in the first 3 weeks and a time- and dose-dependent decrease in primary and secondary PFC response. A remarkable observation enhancement in B cell production due to immune complex of antigens was noted in the present study. The enhancement of this type of immune responses confirms the potential of immune complexes to be used as vaccines.

Pamidronate infusion in patients with systemic sclerosis results in changes in blood mononuclear cell cytokine profiles.

A single infusion of pamidronate was given to patients with systemic sclerosis (scleroderma, SSc) to assess effects on cytokine production by peripheral blood mononuclear cells (PBMC) and lymphocyte subsets. Eighteen patients with SSc received a single intravenous dose of 60 mg of pamidronate and were followed for 6 months. Assessment of cytokine production [interferon (IFN)-gamma, interleukin (IL)-10, transforming growth factor (TGF)-beta1, tumour necrosis factor (TNF)-alpha and IL-4] by PBMC and lymphocyte subsets by flow cytometry was carried out before and after the pamidronate infusion. Unstimulated PBMC produced increased amounts of IFN-gamma and TNF-alpha and reduced levels of TGF-beta1 for up to 24 weeks after the infusion. gammadelta T cells from patients with SSc were activated in vitro and produced increased IFN-gamma. The effects of pamidronate on modulation of cytokine profiles in patients with SSc may merit future study.

Effect of zafirlukast on methacholine and ultrasonically nebulized distilled water challenge in patients with mild asthma.

BACKGROUND: Bronchial asthma is a chronic inflammatory disease characterized by airway inflammation and hyperresponsiveness due to the release of multiple mediators, such as cysteinyl-leukotrienes (cys-LTs). OBJECTIVE: Our study was designed to investigate whether oral pretreatment with zafirlukast (a cys-LTs receptor antagonist) reduces bronchoconstriction against methacholine (MC) and ultrasonically nebulized distilled water (UNDW) challenge in patients with mild asthma. METHODS: Fourteen non-atopic patients (8 males, 20-42 years, forced expiratory volume in 1 s (FEV(1)) 97% SD +/- 0.4) with mild, intermittent bronchial asthma performed a sequential weekly pulmonary function test following challenge with MC or UNDW 2 h after zafirlukast or placebo administration, according to a single-blind method. RESULTS: We found that pretreatment with zafirlukast significantly decreased bronchoconstriction MC (maximum FEV(1) drop -10.75% SD +/- 1.89, p < 0.001) and UNDW induced (maximum FEV(1) drop -12% SD +/- 0.15, p < 0.001), while pretreatment with placebo did not protect patients against FEV(1) drop following MC (maximum FEV(1) drop -33.22% SD +/- 1.42, p < 0.001) and UNDW challenge (maximum FEV(1) drop -30.02% SD +/- 0.4, p < 0.001). CONCLUSIONS: Pretreatment with zafirlukast significantly reduced bronchoconstriction against MC and UNDW challenge in individuals with mild intermittent asthma, indicating that cys-LTs receptor antagonists might be useful as preventive therapy in these patients population.

Are there gender differences in the use of peak flow meters?

To determine if there are gender differences in correct use of peak flow meters (PEM), third-year doctor of pharmacy students (n = 83; 52 females, 31 males) were instructed in a classroom on correct use of a PFM, including demonstrations. Students were then immediately divided into five groups, given a PFM, and assessed for three attempts in private individual sessions. Males had superior performance on the first attempt for total score (p < 0.05) and for "inhale fully" (p < 0.05). On the second attempt, the total score was not different, but males scored higher on "exhale as fast and as hard as you can" (p < 0.05). Controlled gender studies examining use of PFM in adult and pediatric patients with asthma are warranted.

Gender differences in metered-dose inhaler-spacer device technique.

STUDY OBJECTIVE: To determine whether gender affects the correct use of a metered-dose inhaler (MDI)-spacer device. DESIGN: Prospective, observational study. SETTING: University classrooms. PATIENTS: Eighty-three students in their third year of a Doctor of Pharmacy program. INTERVENTION: Students were given the device and received 20 minutes of education on its use. They then were asked to perform the technique. Assessment and retraining were done, as necessary, by clinicians who were experienced with the device. Students returned 1 week later to perform the technique again. MEASUREMENTS AND MAIN RESULTS: The performance of men versus women was analyzed with chi 2 tests and the Student's t test. Power analysis indicated that 30 students were needed in each group. CONCLUSION: There were no significant differences between men and women in proper MDI-spacer technique.