phosphocreatine and Weight-Gain

Seizures and neurologic involvement have been reported in patients infected with Shiga toxin (Stx) producing

Topics: Amygdala; Animals; Brain; Calcium-Binding Proteins; Cell Culture Techniques; Cerebral Cortex; Disease Models, Animal; DNA-Binding Proteins; Endothelial Cells; Erythrocytes; Escherichia coli; Hemolytic-Uremic Syndrome; Hippocampus; Humans; Kidney; Magnetic Resonance Imaging; Male; Mice; Microfilament Proteins; Microglia; Nervous System; Phosphocreatine; Rabbits; Repressor Proteins; Shiga Toxin; Shiga Toxin 2; Spectrum Analysis; Thalamus; Toxicity Tests; Tumor Necrosis Factor-alpha; Weight Gain; Weight Loss

Nitrosative stress, that is, enhanced peroxynitrite formation, has been documented in both experimental and clinical diabetic neuropathy (DN), but its pathogenetic role remains unexplored. This study evaluated the role for nitrosative stress in two animal models of type 1 diabetes: streptozotocin-diabetic mice and diabetic NOD mice. Control (C) and streptozotocin-diabetic (D) mice were treated with and without the potent peroxynitrite decomposition catalyst FP15 (5 mg kg(-1) d(-1)) for 1 wk after 8 wk without treatment. Sciatic nerve nitrotyrosine (a marker of peroxynitrite-induced injury) and poly(ADP-ribose) immunoreactivities were present in D and absent in C and D+FP15. FP15 treatment corrected sciatic motor and hind-limb digital sensory nerve conduction deficits and sciatic nerve energy state in D, without affecting those variables in C. Nerve glucose and sorbitol pathway intermediate concentrations were similarly elevated in D and D+FP15 vs C. In diabetic NOD mice, a 7-day treatment with either 1 or 3 mg kg(-1) d(-1) FP15 reversed increased tail-flick latency (a sign of reduced pain sensitivity); the effect of the higher dose was significant as early as 3 days after beginning of the treatment. In conclusion, nitrosative stress plays a major role in DN in, at least, type 1 diabetes. This provides the rationale for development of agents counteracting peroxynitrite formation and promoting peroxynitrite decomposition, and their evaluation in DN.

Topics: Animals; Blood Glucose; Creatine; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 1; Diabetic Neuropathies; Metalloporphyrins; Mice; Mice, Inbred NOD; Neural Conduction; Neurons, Afferent; Oxidative Stress; Peroxynitrous Acid; Phosphocreatine; Poly (ADP-Ribose) Polymerase-1; Poly(ADP-ribose) Polymerases; Reactive Nitrogen Species; Sciatic Nerve; Tyrosine; Weight Gain

Biopsy samples were obtained from the vastus lateralis muscle of eight subjects after 0, 20, 60, and 120 s of recovery from intense electrically evoked isometric contraction. Later (10 days), the same procedures were performed using the other leg, but subjects ingested 20 g creatine (Cr)/day for the preceding 5 days. Muscle ATP, phosphocreatine (PCr), free Cr, and lactate concentrations were measured, and total Cr was calculated as the sum of PCr and free Cr concentrations. In five of the eight subjects, Cr ingestion substantially increased muscle total Cr concentration (mean 29 +/- 3 mmol/kg dry matter, 25 +/- 3%; range 19-35 mmol/kg dry matter, 15-32%) and PCr resynthesis during recovery (mean 19 +/- 4 mmol/kg dry matter, 35 +/- 6%; range 11-28 mmol/kg dry matter, 23-53%). In the remaining three subjects, Cr ingestion had little effect on muscle total Cr concentration, producing increases of 8-9 mmol/kg dry matter (5-7%), and did not increase PCr resynthesis. The data suggest that a dietary-induced increase in muscle total Cr concentration can increase PCr resynthesis during the 2nd min of recovery from intense contraction.

Topics: Administration, Oral; Adult; Biopsy; Body Weight; Creatine; Humans; Lactates; Male; Muscles; Phosphocreatine; Reference Values; Weight Gain