Leptin, a pleiotropic adipokine, is a central regulator of appetite and weight and a key immunomodulatory protein. Although inborn leptin deficiency causes weight gain, it is unclear whether induced leptin deficiency in adult wild-type animals would be orexigenic. Previous work with a potent competitive leptin antagonist did not induce a true metabolic state of leptin deficiency in mice because of a short circulating half-life. In this study, we increased the half-life of the leptin antagonist by pegylation, which resulted in significantly increased bioavailability and retaining of antagonistic activity. Mice administered the pegylated antagonist showed a rapid and dramatic increase in food intake with weight gain. Resulting fat was confined to the mesenteric region with no accumulation in the liver. Serum cholesterol, triglyceride, and hepatic aminotransferases remained unaffected. Weight changes were reversible on cessation of leptin antagonist treatment. The mechanism of severe central leptin deficiency was found to be primarily caused by blockade of transport of circulating leptin across the blood-brain barrier with antagonisms at the arcuate nucleus playing a more minor role. Altogether we introduce a novel compound that induces central and peripheral leptin deficiency. This compound should be useful in exploring the involvement of leptin in metabolic and immune processes and could serve as a therapeutic for the treatment of cachexia.

No abstract

Condom-loaded Foley's catheter is as effective as Bakri balloon in the management of primary atonic PPH following vaginal delivery but requires a significant bit longer time to stop the attack.

No abstract

Placenta accreta/percreta is a serious cause of intractable post-partum haemorrhage during caesarean section and a common cause of peripartum hysterectomy. In this case series, we evaluated the use of multiple 8 sutures as a novel procedure to preserve the uterus in these cases. Seven women with placenta accreta/percreta were initially managed with bilateral uterine artery ligation. The procedure was resorted to in cases that did not respond to ligation (five women). Women were followed up for up to 24 months to report complications.