Evaluation of tolerability and efficacy of glucosamine with chondroitin in the treatment of knee osteoarthritis – a double blind multicentre randomized prospective comparative study.

There are few comparative studies conducted with glucosamine [GlcN1 (glucosamine sulfate with potassium chloride), GlcN2 (glucosamine sulfate plus chondroitin sulfate) along with ChoN3 (chondroitin sulfate alone)] in the treatment of knee osteoarthritis. In this study the treated groups were studied for alleviation of pain and joint stiffness with correlation of measurement of urinary pyridinium cross links such as pyridinoline (Pyr) and deoxypyridinoline (Dpyr). Hence, this study was eventually planned to evaluate the efficacy, safety and tolerability of glucosamine with chondroitin sulfate treated groups. Urinary pyridinium crosslinks such as Pyr and Dpyr measurement are used to monitor the clinical status as well as bone turnover of OA patients. These two collagen crosslinks measured in urine, which provides information both on the pathogenesis of OA as well as the rate of bone turnover. The results of this study suggest that GlcN2 and ChoN3 can relieve pain, improving functional ability and joint mobility so as to enhance the quality of life for osteoarthritis patients.

Anticonvulsant effect of cytoskeletal depolymerizers in combination with potassium channel opener and adenylate cyclase activator; a causative link with nerve growth factor?

Anticonvulsant effect of cytoskeletal depolymerizing drugs in combination with potassium channel (KATP) opener and adenylate cyclase activator was evaluated in animal models of epilepsy. Seizures were induced in the animals by subjecting them to maximal electroshock (MES) or by injecting a chemical convulsant, pentylenetetrazole (PTZ). Moreover a correlation with the nerve growth factor (NGF) was also investigated. The anticonvulsant effect of minoxidil (1200 micrograms/kg i.p.) and Deacetylforskolin (600 micrograms/kg i.p.) was significantly enhanced in the mice pre-treated with cytoskeletal depolymerizing drugs. On the other hand nerve growth factor potentiated the convulsive phenomenon and decreased the seizure threshold in both the electroshock and chemically induced convulsions. Another interesting feature was the interaction of cytochalasin B, a microfilament disrupter in preventing the action of mNGF and PTZ. This study demonstrates the importance of interaction between cytoskeletal structures and signalling molecules in determining the convulsive threshold. This study clearly points to the importance of the nerve growth factor in convulsive phenomenon.

Enigmatic relationship of Pleckstrin homology domain with phospholipid breakdown mediated signal transduction.

Research into phospholipid signaling continues to flourish, as more and more bioactive lipids and proteins are being identified and their actions characterised. The Pleckstrin homology (PH) domain is one such newly recognized protein module thought to play an important role in intracellular signal transduction. The tertiary structures of several PH domains have been determined, some of them complexed with ligands and on the basis of structural similarities between PH domains and lipid binding proteins it has been suggested that PH domains may be binding to lipophilic molecules. In fact many of the proteins that contain this domain can interfere with the membrane association. This review examines the specificity of this binding and illustrates the importance of charge-charge interactions in PIP2-PH domain complex formation. The precise physiological functions of PH domain in vivo remains to be explored therefore this review examines the biochemical aspects of the interaction of PH domains with phospholipid breakdown mediated products and proto-oncogenic serine-threonine kinase (Akt), protein tyrosine kinases, which have been found to be a target of phospholipid second messengers. Thus, number of cellular processes mediated by this way, ranging from insulin signaling and protein synthesis to differentiation and cell survival are regulated by this intracellular signaling protein module.

Reversal of angiotensin converting enzyme (ACE) inhibitor induced vasodilatation by vasopressin in hindquarters of rat.

The effect of exogenously administered vasopressin was observed on captopril induced vasodilatation in hindquarters of anaesthetised rats. Drops of perfusate were counted for 6 min and mean of the outflow was expressed as drops per min (dpm). In the control group (n = 6) the rate of flow was 9.5 +/- 1.04 dpm which increased to 12.33 +/- 1.36 dpm following captopril (200 micrograms/ml) infusion. In test group (n = 6) pretreated with vasopressin (4 I.U./kg 1 hr before) the rate of flow was 9.16 +/- 0.98 dpm which was reduced to 5.5 +/- 1.04 dpm following infusion with captopril. It is concluded that vasopressin reverses the vasodilatory effect of captopril.