5-Hydroxytryptamine Receptor Subtypes and their Modulators with Therapeutic Potentials

5-hydroxytryptamine (5-HT) has become one of the most investigated and complex biogenic amines. The main receptors and their subtypes, e.g., 5-HTI (5-HT1A, 5-HT1B, 5-HTID, 5-HTIE and 5-HT1F), 5-HT2 (5-HT2A, 5-HT2B and 5-HT2C), 5-HT3, 5-HT4, 5-HT5 (5-HT5A, 5-HT5B), 5-HT6 and 5-HT7 have been identified. Specific drugs which are capable of either selectively stimulating or inhibiting these receptor subtypes are being designed. This has generated therapeutic potentials of 5-HT receptor modulators in a variety of disease conditions. Conditions where 5-HT receptor modulators have established their use with distinct efficacy and advantages include migraine, anxiety, psychosis, obesity and cancer therapy-induced vomiting by cytotoxic drugs and radiation. Discovery of 5-HT, its biosynthesis, metabolism, physiological role and the potential of 5-HT receptor modulators in various nervous, cardiovascular and gastrointestinal tract disorders, bone growth and micturition have been discussed in this article

ENDOCRINOLOGICAL ROLE OF LEPTIN IN OBESITY AND ASTHMA

Objective: Role of leptin resistance in correlation between obesity and asthma. Methods: High-caloric diet was given for 8 weeks to induce obesity. Ovalbumin followed by aluminum hydroxide was given to induce asthma. The animal was treated with leptin analog (0.4 mg/kg, i.p. for 7 days) and leptin antagonist (3 mg/kg, p.o., for 7 days). Biochemical parameters such as serum leptin, ghrelin, and tumor necrosis factor alpha (TNF-α) and physical parameters such as tidal volume and airflow rate were estimated to confirm the state of asthma and obesity, respectively. Results: It was found that leptin and ghrelin were elevated in obese and obese asthmatic condition, responsible for leptin resistance. Treatment with leptin analog and leptin antagonist significantly increases and decreases serum leptin levels, respectively. There was no significant change in TNF-α and ghrelin level after leptin analog treatment. The result of respiratory parameters improved with leptin analog. From our study, we found beneficial role of leptin analog in obese asthmatic condition. Conclusion: Leptin is an alternative treatment approach to treat obese asthmatic condition

BIOANALYTICAL METHOD DEVELOPMENT AND VALIDATION OF HCG (HUMAN CHORIONIC GONADOTROPIN)

Objective: To develop and validate simple, rapid, specific, accurate and precise bioanalytical method for determination of the HCG (Human Chorionic Gonadotropin) by RP-HPLC method by using human urine.Methods: The chromatographic separation was performed using Phenom enex C18 (250 x 4.6 mm, 5μ, 300 °A) column. Mobile phase composed of sodium phosphate buffer (pH 7.0, 0.05M) and acetonitrile (87.5:12.5 % v/v) at a flow rate of 1 ml/min. Detection was carried out using UV detector at 215 nm. Bovine serum albumin (BSA) was used as an internal standard (ISTD) and extraction was carried out using protein precipitation method. The method was validated as per USFDA guidelines.Results: The method was linear over the concentration range of 0.37 to 48.4 µg/ml. and correlation coefficient (R2) was found to be 0.9983 and the Lower limit of quantitation (LLOQ) was 0.37 µg/ml. Recovery was found more than 94.0% for HCG. The % CV for interday and intraday precision was found to be less than Ë‚1%.Conclusion: A simple, rapid, specific, accurate and precise analytical method was developed and validated by using human urine.Â

Neuroprotective effects of potassium channel openers on cerebral ischemia–reperfusion injury in diabetic rats

Objectives: This study was done to estimate the potential neuroprotective role of potassium channel openers in cerebral ischemia–reperfusion (IR) injury in streptozotocin (STZ) induced type-I diabetic rats (T1DR). Methods: Potassium channel openers – cromakalim, cinnarizine and nicorandil; potassium channel blocker –glibenclamide, insulin (as an antidiabetic standard), telmisartan (as an anti-hypertensive standard agent) and vitamin E (as an antioxidant and antiapoptotic standard agent) were given for 3 days in streptozotocin (45 mg/kg i.v.) induced type I diabetic rats along with middle cerebral artery occlusion. After 24 h of surgery, plasma glucose, neurobehavioral score, cerebral infarct volume, blood pressure and caspase-3 levels were measured to evaluate the mechanism of potassium channel openers (KCOs) for neuroprotection. Results: Following STZ administration and ischemia–reperfusion, blood sugar, neurobehavioral score, cerebral infarct volume and caspase-3 levels were significantly high in diabetic-IR groups. Treatment with cromakalim, cinnarizine, nicorandil, insulin and vitamin E significantly reduce neurobehavioral score while nicorandil and vitamin E significantly reduced cerebral infarct volume. Caspase-3 levels were significantly reduced by cromakalim and nicorandil treated animals. Except insulin and glibenclamide, none of the agents significantly reduce plasma glucose levels. Conclusion: Treatment of ischemic stroke with potassium channel openers in T1DR is neuroprotective. Inhibition of apoptosis may contribute to their neuroprotective effects after stroke in T1DR

Amyloid beta Protein and Alzheimer's Disease: When Computer Simulations Complement Experimental Studies

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