Polypharmacology Approach Against Migraine with Aura and Brain Edema for the Development of an Efficient Inhibitor and its Analogues.

BACKGROUND: Polypharmacology is a design or use of pharmaceutical agents in which single drug is used to treat multiple diseases. Aquaporin proteins are identified to treat migraine with aura and brain edema. This study focuses on Aquaporin-1 and Aquaporin-4. AQP-1 is expressed in small afferent sensory nerve fibers. Over-expression of peripheral nervous system causes migraine. METHODS: AQP-4 is an abundant channel water protein in brain that regulates water transport to prevent homeostasis. Over-expression of AQP-4 contributes to water imbalance in ischemic pathology resulting in cerebral edema. Purpose of this study is to identify a potent inhibitor for the treatment of migraine with aura and brain edema. RESULTS: As in the recent studies, no conventional methodologies have been focused through the approach of polypharmacology. Structures of AQP-1 and AQP- 4 proteins were retrieved from PDB (Protein Data Bank). PyRx software was used to perform molecular docking. CONCLUSION: Analogues of ligands were analyzed which contained significant similarities of associated proteins to get efficient inhibitor. Toxicity of lead compound was measured through admetSAR. A lead compound was predicted to treat these diseases.

Surgical outcome of spelenectomy in Thalassemia major in children.

OBJECTIVE: To determine the surgical outcome of splenectomy in children with thalassemia major. METHODS: It is an observational and descriptive study conducted in Department of Paediatric Surgery in collaboration with hematology, radiology, anesthesia and paediatric intensive care department at The Children's Hospital and the Institute of Child Health, Multan during the period of September 2007 to September 2013. A total of 50 patients suffering from thalassemia major already diagnosed and under management reffered from haematology department for splenectomy were included in this study. After admission, patients were assessed on the basis of history, clinical examination, and necessary investigations before surgery and later on follow-up. Investigations carried were CBC, PT, APTT, Viral markers, ECG, X-ray Chest, abdominal ultrasonography and ECHO if necessary. Splenectomy was performed after prophylactic vaccination against post splenectomy infections. Follow up was performed for at least two years. Blood transfusion requirements and number of hospital visits per annum before and after splenectomy were calculated and results analyzed statistically using SPSS-20. RESULTS: Fifty patients were included in this study. Out of these fifty, 43 (86%) male and 7(14%) were female with a mean age of 9 years. Average blood transfusion requirement was 250 ml/kg/year, interval of blood transfusion was two weeks and twenty five visits per year before splenectomy. After splenectomy, requirement of blood transfusion reduced to 125ml/kg/year, interval between transfusion increased to one month and hospital visits reduced up to twelve per year. CONCLUSION: Blood transfusion requirement and number of hospital visits per year are decreased and interval between transfusions is increased after splenectomy. Splenectomy should not be delayed when indicated. Preoperative vaccination decreases the chance of post splenectomy infection.