Combination of selective androgen and estrogen receptor modulators in orchiectomized rats.

PURPOSE: Selective androgen and estrogen receptor modulators, ostarine (OST) and raloxifen (RAL), reportedly improve muscle tissue and offer therapeutic approaches to muscle maintenance in the elderly. The present study evaluated the effects of OST and RAL and their combination on musculoskeletal tissue in orchiectomized rats. METHODS: Eight-month-old Sprague Dawley rats were analyzed. Experiment I: (1) Untreated non-orchiectomized rats (Non-ORX), (2) untreated orchiectomized rats (ORX), (3) ORX rats treated with OST during weeks 0-18 (OST-P), (4) ORX rats treated with OST during weeks 12-18 (OST-T). Experiment II: 1) Non-ORX, (2) ORX, 3) OST-P, (4) ORX rats treated with RAL, during weeks 0-18 (RAL-P), 5) ORX rats treated with OST + RAL, weeks 0-18 (OST + RAL-P). The average daily doses of OST and RAL were 0.4 and 7 mg/kg body weight (BW). Weight, fiber size, and capillarization of muscles, gene expression, serum markers and the lumbar vertebral body were analyzed. RESULTS: OST-P exerted favorable effects on muscle weight, expression of myostatin and insulin growth factor-1, but increased prostate weight. OST-T partially improved muscle parameters, showing less effect on the prostate. RAL-P did not show anabolic effects on muscles but improved body constitution by reducing abdominal area, food intake, and BW. OST + RAL-P had an anabolic impact on muscle, reduced androgenic effect on the prostate, and normalized food intake. OST and RAL improved osteoporotic bone. CONCLUSIONS: The OST + RAL treatment appeared to be a promising option in the treatment of androgen-deficient conditions and showed fewer side effects than the respective single treatments.

Topical application of cerium nitrate prevents burn edema after burn plasma transfer.

Thermal injuries of more than 20% body surface area (BSA) result in systemic capillary leakage with subsequent edema. This can similarly be induced by burn plasma transfer (BPT) from burned individuals to healthy rats. We evaluated if cerium nitrate (CN) bathing can prevent edema after BPT. Therefore, donor rats (DR) underwent thermal injury (100 degrees C water, 30%BSA, 12 s) for positive controls and were additionally bathed in CN (0.05M, at 10 and 120 min) for study groups. For negative controls DR underwent shamburn (37 degrees C water, 30%BSA, 12 s). DR-plasma (harvested 4 h post trauma) was transferred to healthy individuals. Intravital microscopy was performed in mesenteric venules (0/60/120 min). Edema was assessed by FITC-albumin extravasation. Additionally, leukocyte sticking (cells/mm(2)) and micro hemodynamic parameters were assessed. Significant systemic capillary leakage was observed after BPT at 120 min. Edema formation was significantly lower in negative controls. Topical CN application after 10 and 120 min reduced FITC-efflux to baseline levels. Adherent leukocytes increased slightly in all groups. Leukocyte-sticking tended to be reduced after CN bathing. In conclusion, BPT induces burn edema in healthy individuals. CN bathing after 10 and 120 min reduces mediator levels in burned individuals. Therefore, BPT after CN application does not induce burn shock anymore. Burn edema is partially independent from leukocyte activation because CN significantly influences macromolecular leakage whereas leukocyte activation is not significantly altered.

Effect of different immunosuppressive agents on acute pancreatitis: a comparative study in an improved animal model.

BACKGROUND: Immunosuppressive drugs have been associated with the development and progression of acute pancreatitis after organ transplantation. Consequently, a reduction or a change in immunosuppressive therapy has been recommended once posttransplantation pancreatitis has been suspected. However, it is not known which of the available immunosuppressive agents is most harmful to the pancreas and which may be used safely in this situation. The objective of this study was to investigate the effect of different immunosuppressive drugs in various dosages on intrapancreatic protease activation, acinar cell necrosis, and mortality in an improved model of acute necrotizing pancreatitis in the rat. The rat model of acute necrotizing pancreatitis, like posttransplantation pancreatitis, is characterized by ischemia and microcirculatory disorders. METHOD: Acute pancreatitis was induced in rats by using a combination of low-dose controlled intraductal glycodeoxycholic acid superimposed on intravenous cerulein hyperstimulation. Six hours thereafter, animals were randomized to intravenous therapy with 2, 10, or 50 mg/kg/day prednisolone (PRED); 3, 15, or 60 mg/kg/day cyclosporine A (CsA); 10 mg/kg/day azathioprine (AZA); 0.6 mg/kg/day orthoclone OKT3 (OKT3); or saline. After 36 hr, surviving animals were killed to determine acinar cell necrosis and trypsinogen activation peptides levels (TAP) in blood and ascites. RESULTS: Compared with saline-treated control rats, animals treated with 60 mg/kg/day CsA developed significantly more acinar cell necrosis and had increased amounts of TAP in ascites. Likewise, there was more extensive acinar cell necrosis in animals subjected to AZA therapy. However, this was not associated with incremental TAP. Animals treated with 3 or 15 mg/kg/day CsA, OKT3, or PRED showed no significant changes in these target parameters. Animals given 10 or 50 mg/kg/day PRED even had decreased hematocrit values and produced significantly less ascites than animals in the other groups. CONCLUSION: The present results suggest that AZA and high doses of CsA aggravate acute pancreatitis and should, therefore, be avoided once posttransplantation pancreatitis has been suspected, whereas lower doses of CsA, OKT3, and PRED may be used safely. PRED can even be used at higher doses as may be required when graft rejection is suspected.

Propofol-induced alterations in the microcirculation of hamster striated muscle.

To investigate the effects of propofol on small vessels, we have measured changes in diameter and blood flow in microcirculatory venules and arterioles. Studies were carried out in the dorsal skinfold chamber of hamsters by intravital fluorescence microscopy. A bolus injection of propofol 25 mg kg-1 dilated small and collecting venules by a mean value of 18% and arterioles by 13%. Blood flow in venules increased by up to 69%. Intralipid dilated arterioles and post-capillary venules by 26% and 30%, respectively. After 4 h of continuous infusion (0.2-0.8 mg kg-1), only blood flow in post-capillary venules increased (66% propofol and 92% Intralipid). Post-capillary and collecting venules dilated in both groups. Therefore, propofol and Intralipid induced venodilatation and enhanced blood flow after bolus administration. After 4 h, despite dilatation in both groups, only post-capillary venules showed enhanced blood flow. These observations suggest redistribution of blood flow after prolonged administration of propofol.

31P-NMR spectroscopy of phosphate compartmentation during ischaemia in hearts protected by cardioplegic treatment.

Four tissue compartments, differing in proton and inorganic phosphate concentration, were resolved by 31P-NMR spectroscopy in samples from dog hearts after cardioplegic treatment with HTK solution. Inversion of the physiological cytoplasmic-mitochondrial pH gradient was observed. The considerable ensuing acidosis of the matrix is discussed with regard to a possible delocalization of ferrous ions.