Targeting the leptin receptor: To evaluate therapeutic efficacy and anti-tumor effects of Doxil, in vitro and in vivo in mice bearing C26 colon carcinoma tumor.

Leptin is an appetite regulatory hormone that is secreted into the blood circulation by the adipose tissue and it functions via its over expressed receptors (Ob-R) in a wide variety of cancers. In the present study, the function of a leptin-derived peptide (LP16, 91-110 of Leptin) was investigated as a targeting ligand to decorate PEGylated liposomal doxorubicin (PLD, Doxil®) surface and the anti-tumor activity and therapeutic efficacy of Doxil in C26 (Colon Carcinoma) tumor model were also evaluated. As a result of this, Doxil with different LP16 peptide density (25, 50, 100 and 200 peptide on the surface of each liposome) was successfully prepared and characterized. In vitro results showed significant enhanced cytotoxicity and cellular binding and uptake of LP16-targeted Doxil formulations (LP16-Doxil) in C26 cells as compared to Doxil. In BALB/c mice bearing C26 murine carcinoma, at a dose of 15 mg/kg, LP16-Doxil groups (100 ligand) significantly suppressed the growth of the tumor and showed higher inclination to tumor as compared to non-targeted Doxil. This study revealed that the potential of LP16 peptide targeting increased the therapeutic efficacy of Doxil and highlighted the importance of optimizing the ligand density to maximize the targeting ability of the nanocarriers and merits further investigations.

Beneficial Effect of Leptin on Spatial Learning and Memory in Streptozotocin-Induced Diabetic Rats.

BACKGROUND: Diabetes mellitus is a chronic disease which may be accompanied by cognitive impairments. The expression of the obesity gene (ob) is decreased in insulin-deficient diabetic animals and increased after the administration of insulin or leptin. Plasma leptin levels are reduced in the streptozotocin (STZ)-induced diabetic rats. Therefore, the deleterious effects of diabetes on memory may be due to the reduction of leptin. AIMS: Investigate the effect of subcutaneous injection of leptin on spatial learning and memory in STZ-induced diabetic rats. STUDY DESIGN: Animal experimentation. METHODS: The rats were divided into three groups: 1-control, 2- diabetic, and 3- diabetic-leptin. Diabetes was induced in groups 2 and 3 by STZ injection (55 mg/kg) intraperitoneally (i.p). The animals received leptin (0.1 mg/kg) or saline subcutaneously (s.c) for 10 days before behavioral studies. Then, they were examined in the Morris water maze over 3 blocks after 3 days of the last injection of leptin. RESULTS: The travelled path length and time spent to reach the platform significantly increased in the diabetic group (p<0.001) and decreased with leptin treatment (p<0.01 & p<0.001 respectively); also, a significant increase in path length and time was observed between the diabetic-leptin group and the diabetic group (p<0.01, p<0.001, respectively) in the probe test. CONCLUSION: Leptin can exert positive effects on memory impairments in diabetic rats.

Effect of exogenous leptin on serum levels of lipids, glucose, renal and hepatic variables in both genders of obese and streptozotocin-induced diabetic rats.

OBJECTIVES: Leptin exerts various effects on appetite and body weight. Disruption of the obesity gene is precedent to fatness. Insulin or glucose elevates leptin, but streptozotocin reduces it. However, controversial data exist for the effects of leptin on diabetes and leptin level in each gender. Leptin can damage the kidney function but little evidence exists for its hepatic effects. The aim of this study was to investigate the probable sex-dependent differences in blood sugar levels, lipid profile, and renal and hepatic biochemical factors in the obesity and streptozotocin-induced diabetic rats after leptin administration. MATERIALS AND METHODS: Wistar rats of both sexes were randomly divided into two groups, namely obese and diabetic rats. Each group was further divided into male and female subgroups. Extra fat and carbohydrate was added to the diet to induce obesity. Furthermore, streptozotocin (55 mg/kg, IP) was injected to induce diabetes. The treatment groups received leptin (0.1 mg/kg SC) for 10 days, and then, blood samples were taken from the orbital sinus for laboratory evaluations. RESULTS: Leptin resulted in a significant weight loss in both sexes (P<0.001), food intake reduction in male rats (P<0.05), LDL reduction in female rats (obese (P<0.05) and diabetic (P<0.001)), and glucose level decline in the female diabetic rats (P<0.001). However, total protein concentration, LFT (liver function tests), urea and creatinin concentrations among different groups did not show any significant changes. CONCLUSION: Leptin caused some discrepant results, especially regarding the LDL and glucose levels in diabetic female rats.

Effect of tetracycline administration on serum amylase activity in calves.

Tetracycline and related compounds are used extensively as broad spectrum antibiotics in the treatment of bacterial infections in ruminants. Tetracycline may cause acute pancreatitis which may result in increased serum amylase activity. However, it has been shown that administration of oxytetracycline in human results in decrease serum amylase activity. In this study changes in serum amylase activity were measured in 20 clinically healthy calves following intravenous injection of oxytetracycline hydrochloride at 10 mg/kg of body weight. Blood samples were collected at 30, 60, and 120 minutes after oxytetracycline injection. Serum amylase activity was measured using the amyloclastic assay. The activity of serum amylase was increased significantly (P < 0.05) at 30 (40.5%), 60 (35.1%), and 120 (39.3%) minutes after oxytetracycline hydrochloride administration. To the authors' knowledge this is the first study on the acute effect of tetracycline administration on serum amylase activity in calves.