Intra-Abdominal Fat Adipocyte Hypertrophy through a Progressive Alteration of Lipolysis and Lipogenesis in Metabolic Syndrome Rats.

This study evaluates the progressive participation of enzymes involved in lipolysis and lipogenesis, leading to adipocyte hypertrophy in a metabolic syndrome (MS) rat model caused by chronic consumption of 30% sucrose in drinking water. A total of 70 male Wistar rats were divided into two groups: C and MS. Each of these groups were then subdivided into five groups which were sacrificed as paired groups every month from the beginning of the treatment until 5 months. The intra-abdominal fat was dissected, and the adipocytes were extracted. Lipoprotein lipase (LPL), hormone-sensitive lipase (HSL), protein kinases A (PKA), and perilipin A expressions were determined. The LPL and HSL activities were evaluated by spectrophotometry. Histological staining was performed in adipose tissue. Significant increases were observed in blood pressure, HOMA-IR, leptin, triglycerides, insulin, intra-abdominal fat, and number of fat cells per field (p = 0.001) and in advanced glycosylation products, adipocyte area, LPL, HSL activities and/or expression (p ≤ 0.01) in the MS groups progressively from the third month onward. Lipogenesis and lipolysis were increased by LPL activity and HSL activity and/or expression. This was associated with hyperinsulinemia and release of non-esterified fatty acids causing a positive feedback loop that contributes to the development of adipocyte hypertrophy.

Effect of oophorosalpingo-hysterectomy on serum antioxidant enzymes in female dogs.

There are few studies evaluating the oxidant-antioxidant status after oophorosalpingohysterectomy (OSH) in female dogs. Here we determined the effect of OSH on antioxidant enzymes in serum, and quantified morphological changes in subcutaneous adipocytes. Lateral OSH was performed in 12 female dogs. The concentration of 17ß-estradiol (17ß-E2), the activities of extracellular superoxide dismutase (SOD-ec), glutathione peroxidase (GPx), glutathione-S-transferase (GST) and glutathione reductase (GR) were determined. Glutathione (GSH), glutathione disulfide (GSSG), lipid peroxidation (LPO), total antioxidant capacity (TAC), carbonylation and vitamin C were measured in serum. Subcutaneous adipose tissue was obtained to determine morphological changes and cell number, under basal conditions and six months after OSH. The SOD-ec, GPx and GST activities increased significantly (p ≤ 0.05), LPO, carbonylation and GSSG also increased. GSH and vitamin C decreased (p = 0.03). 17ß-E2 tended to decrease six months after OSH. Hypertrophy of subcutaneous adipocytes was observed after OSH from the first month and was accentuated after six months (p = 0.001). The results suggest that 17ß-E2 decreases after OSH and alters the antioxidant enzyme activities in serum thus, redox balance is altered. These changes are associated with an increase in body weight and hypertrophy of subcutaneous adipose tissue.

Comparative pharmacokinetics of a new oral long-acting formulation of doxycycline hyclate: A canine clinical trial.

Doxycicline is used in dogs as treatment of several bacterial infections, mycoplasma, chlamydia and rickettsial diseases. However, it requires long treatments and several doses to be effective. The aim of this study was to determine the pharmacokinetics of four formulations of doxycycline hyclate, administered orally, with different proportions of excipients, acrylic acid-polymethacrylate-based matrices, to obtain longer therapeutic levels than conventional formulation. Forty-eight dogs were randomly assigned in five groups to receive a single oral dose (20mg/kg) of doxycycline hyclate without excipients (control) or a long-acting formulation containing doxycycline, acrylic acid polymer, and polymethacrylate in one of the following four proportions: DOX1(1:0.25:0.0035), DOX2(1:0.5:0.0075), DOX3 (1:1:0.015), or DOX4(1:2:0.0225). Temporal profiles of serum concentrations were obtained at several intervals after each treatment. Therapeutic concentrations were observed for 60h for DOX1 and DOX4, 48h for DOX2 and DOX3 and only 24h for DOX-C. None of the pharmacokinetic parameter differed significantly between DOX1 and DOX2 or between DOX3 and DOX4; however, the findings for the control treatment were significantly different compared to all four long-acting formulations. Results indicated that DOX1 had the most adequate pharmacokinetic-pharmacodynamic relationships for a time-dependent drug and had longer release times than did doxycycline alone. However, all four formulations can be effective depend on the minimum effective serum doxycycline concentration of the microorganism being treated. These results suggest that the use of any of these formulations can reduce the frequency of administration, the patient's stress, occurrence of adverse effects and the cost of treatment.