PURPOSE: The purpose of this study was to examine the effect of anorexia and neuropathic pain induced by cisplatin on hindlimb muscles of rats. METHODS: Adult male Sprague-Dawley rats were divided into two groups, a cisplatin-treated group (n=10) and a control group (n=10). In the cisplatin-treated group, cisplatin at a dose of 2 mg/kg was injected intraperitoneally two times a week up to a cumulative dose of 20 mg/kg over 5 weeks, and in the control group saline (0.9% NaCl) was injected intraperitoneally at the same dose and duration as the cisplatin-treated group. At 34 days all rats were anesthetized, after which the soleus and plantaris muscles were dissected. Withdrawal threshold, body weight, food intake, activity, muscle weight, Type I and II fiber cross-sectional areas and myofibrillar protein content of the dissected muscles were determined. RESULTS: Compared with the control group, the cisplatin-treated group showed significant decreases (p<.05) in withdrawal threshold, activity, food intake, body weight, Type I and II fiber cross-sectional areas, myofibrillar protein content and weight of the soleus and plantaris muscles. CONCLUSION: Muscular atrophy in hindlimb occurs due to anorexia and neuropathic pain induced by the cisplatin treatment.
Animals ; *Anorexia ; Body Weight ; Cisplatin/*toxicity ; Eating ; Hindlimb ; Injections, Intraperitoneal ; Male ; Motor Activity ; Muscle Fibers, Skeletal/metabolism/pathology ; Muscle Proteins/metabolism ; Muscle, Skeletal/*drug effects/physiology ; Neuralgia/*chemically induced/pathology ; Rats ; Rats, Sprague-Dawley

Animals ; Antioxidants ; pharmacology ; Ascorbic Acid ; pharmacology ; Cumulative Trauma Disorders ; metabolism ; Lipid Peroxidation ; drug effects ; Male ; Muscle, Skeletal ; injuries ; pathology ; Oxidation-Reduction ; Oxidative Stress ; drug effects ; Rats

OBJECTIVETo study the relation between the nitric-oxide synthase (NOS) expression and nitric oxide (NO) content in the skeletal muscles and the injury condition of soft tissue in the 3rd lumbar vertebrae syndrome model rats, and to observe the effect of acupotomology therapy.

METHODSOne hundred and twenty-eight adult SD rats were allocated to 4 groups randomly: normal group, model group, aminoguanidin group and acupotomology treatment group, 32 rats in each group. NOS expression, NO content and injury of the soft tissue in the 3rd lumbar vertebra were observed on the 1st, 3rd, 7th and 14th day after the acupotomology treatment and aminoguanidine intervention.

RESULTS1) Inducible NOS (iNos) activity and NO content in model group was significantly higher (F = 522.860, P < 0.01), in acupotomology group and aminoguanidine group was significantly lower than the model group (FiNOS = 28.894, P < 0.01), and iNOS activity and NO content in all groups was in competence with the condition of soft tissue injuries. 2) Endothelium NOS (eNOS) expression raised in model group and acupotomology group, and achieve peak on the 7th day. There was significant difference between the eNOS expression in acupotomology group and the model group (FeNOS = 3.454, P < 0.05). 3) The expression of neuron NOS (nNOS) in the model group, aminoguanidine group and acupotomology group had no significant (FnNOS = 0.962, P > 0.05).

CONCLUSIONAcupotomology treatment can restrain the development of high content NO, release the inflammatory reaction and injury condition, improve microcirculation, prevent the development of scar tissue of the injured soft tissue, and has significant recovering effectiveness in the soft tissue injured model rats.

Animals ; Disease Models, Animal ; Gene Expression Regulation, Enzymologic ; Guanidines ; therapeutic use ; Lumbar Vertebrae ; drug effects ; metabolism ; pathology ; surgery ; Male ; Muscle, Skeletal ; drug effects ; metabolism ; pathology ; Nitric Oxide ; metabolism ; Nitric Oxide Synthase ; metabolism ; Rats ; Rats, Sprague-Dawley ; Syndrome ; Time Factors

OBJECTIVETo study the effects of Jiaotai Pill (JTP) and its single components on ectopic fat accumulation in rats with type 2 diabetes mellitus (T2DM).

METHODSThe T2DM model of rat was established by injection of streptozotocin from tail vein and high fat-caloric diet feeding. Model rats were randomly divided into the model group and four treated groups were treated respectively with JTP and its single components, Rhizoma Coptidis, Cinnamon and metformin, via gastric perfusion. Meanwhile, a normal control group was also set up. Body weight (BW), liver index (LI), levels of fasting plasma glucose (FPG), fasting serum insulin (FINS) and insulin resistance index (HOMA-IR), plasma activities of liver associated enzymes (LAE), triglyceride (TG) contents and pathological changes of liver, heart and muscle were determined before and after a 8-week treatment.

RESULTSAs compared with the normal rats, BW, LI, LAE activities, HOMA-IR, TG contents of the liver, heart and muscle were all increased in the model rats (P<0.05 or P<0.01), with pathologic appearance of fatty degeneration in different degrees. Compared with the model group, LI, LAE, HOMA-IR, and TG contents in the liver, heart and muscle tissues were decreased in different extents in the four treated groups (P<0.05 or P<0.01), and the histology of tissues in them was restored to near normal. Compared with the metformin treated group, the hepatic and muscular TG contents decreased in the JTP treated group (P<0.01), and the muscular TG content in the Rhizoma Coptidis treated group were lower (P<0.05). And the gamma-GT level in the JTP treated group was the lowest in the three Chinese drugs treated groups (P<0.01).

CONCLUSIONSThe disturbances of glucose and lipid metabolism and abnormality of liver function in T2DM rats could be improved by JTP and its single components. The mechanism might be related to their effects in improving insulin resistance and reducing ectopic fat accumulation.

Adiposity ; drug effects ; Animals ; Diabetes Mellitus, Experimental ; drug therapy ; Diabetes Mellitus, Type 2 ; drug therapy ; Drugs, Chinese Herbal ; therapeutic use ; Insulin Resistance ; Intra-Abdominal Fat ; pathology ; Lipid Metabolism ; drug effects ; Liver ; pathology ; Male ; Muscle, Skeletal ; metabolism ; Phytotherapy ; Rats ; Rats, Wistar

PURPOSE: The purpose of this study was to determine the effect of dehydroepiandrosterone (DHEA) on recovery of muscle atrophy induced by Parkinson's disease. METHODS: The rat model was established by direct injection of 6-hydroxydopamine (6-OHDA, 20 microg) into the left striatum using stereotaxic surgery. Rats were divided into two groups; the Parkinson's disease group with vehicle treatment (Vehicle; n=12) or DHEA treatment group (DHEA; n=22). DHEA or vehicle was administrated intraperitoneally daily at a dose of 0.34 mmol/kg for 21 days. At 22-days after DHEA treatment, soleus, plantaris, and striatum were dissected. RESULTS: The DHEA group showed significant increase (p<.01) in the number of tyrosine hydroxylase (TH) positive neurons in the lesioned side substantia nigra compared to the vehicle group. Weights and Type I fiber cross-sectional areas of the contralateral soleus of the DHEA group were significantly greater than those of the vehicle group (p=.02, p=.00). Moreover, extracellular signal-regulated kinase (ERK) phosphorylation significantly decreased in the lesioned striatum, but was recovered with DHEA and also in the contralateral soleus muscle, Akt and ERK phosphorylation recovered significantly and the expression level of myosin heavy chain also recovered by DHEA treatment. CONCLUSION: Our results suggest that DHEA treatment recovers Parkinson's disease induced contralateral soleus muscle atrophy through Akt and ERK phosphorylation.
Animals ; Corpus Striatum/drug effects/metabolism ; Dehydroepiandrosterone/*pharmacology/therapeutic use ; Extracellular Signal-Regulated MAP Kinases/metabolism ; Male ; Muscle Fibers, Slow-Twitch/drug effects ; Muscle, Skeletal/drug effects/metabolism ; Muscular Atrophy/drug therapy/*etiology/*pathology ; Myosins/metabolism ; Neurons/drug effects/enzymology ; Oxidopamine/toxicity ; Parkinson Disease, Secondary/*chemically induced/*complications ; Phosphorylation ; Proto-Oncogene Proteins c-akt/metabolism ; Rats ; Rats, Sprague-Dawley ; Tyrosine 3-Monooxygenase/metabolism

Telbivudine is an L-nucleoside analogue with potent antiviral activity against hepatitis B virus (HBV). Clinical trials have shown that telbivudine has a more potent and sustained antiviral activity with a lower frequency of viral resistance than lamivudine. Although there are several reports concerning the safety profile of telbivudine, most adverse events are described as mild and transient in nature. Here we report two cases of telbivudine-induced myopathy in patients with chronic hepatitis B who were siblings.
Adult ; Antiviral Agents/adverse effects/*therapeutic use ; Creatine Kinase/blood ; Electromyography ; Hepatitis B, Chronic/*drug therapy/metabolism/pathology ; Humans ; Male ; Muscle, Skeletal/pathology ; Muscular Diseases/etiology ; Siblings ; Thymidine/adverse effects/*analogs & derivatives/therapeutic use

Gabexate mesilate (GM) is a trypsin inhibitor, and mainly used for treatment of various acute pancreatitis, including traumatic pancreatitis (TP), edematous pancreatitis, and acute necrotizing pancreatitis. However, due to the characteristics of pharmacokinetics, the clinical application of GM still needs frequently intravenous administration to keep the blood drug concentration, which is difficult to manage. Specially, when the blood supply of pancreas is directly damaged, intravenous administration is difficult to exert the optimum therapy effect. To address it, a novel thermosensitive in-situ gel of gabexate mesilate (GMTI) was developed, and the optimum formulation of GMTI containing 20.6% (w/w) P-407 and 5.79% (w/w) P188 with different concentrations of GM was used as a gelling solvent. The effective drug concentration on trypsin inhibition was examined after treatment with different concentrations of GMTI in vitro, and GM served as a positive control. The security of GMTI was evaluated by hematoxylin-eosin (HE) staining, and its curative effect on grade II pancreas injury was also evaluated by testing amylase (AMS), C-reactive protein (CRP) and trypsinogen activation peptide (TAP), and pathological analysis of the pancreas. The trypsin activity was slightly inhibited at 1.0 and 5.0 mg/mL in GM group and GMTI group, respectively (P<0.05 vs. P-407), and completely inhibited at 10.0 and 20.0 mg/mL (P<0.01 vs. P-407). After local injection of 10 mg/mL GMTI to rat leg muscular tissue, muscle fiber texture was normal, and there were no obvious red blood cells and infiltration of inflammatory cells. Furthermore, the expression of AMS, CRP and TAP was significantly increased in TP group as compared with control group (P<0.01), and significantly decreased in GM group as compared with TP group (P<0.01), and also slightly inhibited after 1.0 and 5.0 mg/mL GMTI treatment as compared with TP group (P<0.05), and significantly inhibited after 10.0 and 20.0 mg/mL GMTI treatment as compared with TP group (P<0.01). HE staining results demonstrated that pancreas cells were uniformly distributed in control group, and they were loosely arranged, partially dissolved, with deeply stained nuclei in TP group. Expectedly, after gradient GMTI treatment, pancreas cells were gradually restored to tight distribution, with slightly stained nuclei. This preliminary study indicated that GMTI could effectively inhibit pancreatic enzymes, and alleviate the severity of trauma-induced pancreatitis, and had a potential drug developing and clinic application value.
Amylases ; metabolism ; Animals ; C-Reactive Protein ; metabolism ; Delayed-Action Preparations ; chemical synthesis ; pharmacokinetics ; pharmacology ; Gabexate ; chemistry ; pharmacokinetics ; pharmacology ; Gels ; Male ; Muscle, Skeletal ; drug effects ; enzymology ; Oligopeptides ; metabolism ; Pancreas ; drug effects ; enzymology ; pathology ; Pancreatitis ; drug therapy ; enzymology ; etiology ; pathology ; Poloxamer ; chemistry ; Rats ; Rats, Sprague-Dawley ; Serine Proteinase Inhibitors ; chemistry ; pharmacokinetics ; pharmacology ; Temperature ; Wounds, Penetrating ; complications ; drug therapy ; enzymology ; pathology

OBJECTIVETo investigate the effect of Jiaotai Pill (, JTP) at different constitutional proportions on insulin signaling through phosphatidylinositol 3-kinase (PI3K) pathway in the skeletal muscle of diabetic rats.

METHODSThe rat model of type 2 diabetes mellitus (T2DM) was established by intravenous injection of a small dose of streptozotoein plus high fat diet feeding. JTP at the same dosage of cinnamon and the increasing dosage of Coptis chinensis was administered to diabetic rats for nine weeks respectively. Plasma glucose and insulin levels were assayed. The expressions of proteins were determined by Western blot method.

RESULTSAll the three formulations of JTP decreased plasma glucose and fasting insulin levels as well as increased the protein expressions of insulin receptor β (InsRβ) subunit, insulin receptor substrate-1 (IRS-1), PI3K p85 subunit and glucose transporter 4 (GLUT4) in skeletal muscle. Meanwhile, JTP increased the tyrosine phosphorylation of InsRβ subunit and IRS-1, and reduced the serine phosphorylation of IRS-1 in skeletal muscle. Interestingly, the effect of JTP on improving insulin sensitivity was not dose-dependent. In contrast, JTP containing the least amount of Coptis chinensis exhibited the best effect.

CONCLUSIONJTP at different constitutional proportions attenuates the development of diabetes in a rat model of T2DM. The mechanism might be associated with enhancing insulin signaling through PI3K pathway in the skeletal muscle.

Animals ; Body Weight ; drug effects ; Diabetes Mellitus, Experimental ; drug therapy ; enzymology ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Glucose Tolerance Test ; Glucose Transporter Type 4 ; metabolism ; Homeostasis ; drug effects ; Insulin ; metabolism ; Insulin Receptor Substrate Proteins ; metabolism ; Insulin Resistance ; Male ; Muscle, Skeletal ; drug effects ; enzymology ; metabolism ; pathology ; Phosphatidylinositol 3-Kinases ; metabolism ; Phosphorylation ; Phosphotyrosine ; metabolism ; Protein Subunits ; metabolism ; Rats ; Rats, Wistar ; Receptor, Insulin ; metabolism ; Signal Transduction ; drug effects

PURPOSE: The purpose of this study was to examine the effects of Cu/Zn SOD on reduction of hindlimb muscular atrophy induced by cisplatin in rats. METHODS: Forty-two rats were assigned to three groups; control group, Cisplatin (CDDP) group and cisplatin with Cu/Zn SOD (CDDP-SOD) group. At day 35 hindlimb muscles were dissected. Food intake, activity, withdrawal threshold, muscle weight, and Type I, II fiber cross-sectional area (CSA) of dissected muscles were measured. Relative SOD activity and expression of MHC and phosphorylated Akt, ERK were measured after dissection. RESULTS: Muscle weight and Type I, II fiber CSA of hindlimb muscles in the CDDP group were significantly less than the control group. Muscle weight and Type I, II fiber CSA of hindlimb muscles, food intake, activity, and withdrawal thresholds of the CDDP-SOD group were significantly greater than the CDDP group. There were no significant differences in relative SOD activities of hindlimb muscles between the CDDP-SOD and CDDP groups. MHC expression and phosphorylated Akt, ERK of hindlimb muscles in the CDDP-SOD group were significantly greater than the CDDP group. CONCLUSION: Cu/Zn SOD attenuates hindlimb muscular atrophy induced by cisplatin through increased food intake and activity. Increment of phosphorylated Akt, ERK may relate to attenuation of hindlimb muscular atrophy.
Animals ; Body Weight/drug effects ; Cisplatin/*toxicity ; Disease Models, Animal ; Extracellular Signal-Regulated MAP Kinases/metabolism ; Hindlimb ; Male ; Muscle, Skeletal/*drug effects/enzymology/metabolism ; Muscular Atrophy/*chemically induced/metabolism/pathology ; Phosphorylation ; Proto-Oncogene Proteins c-akt/metabolism ; Rats ; Rats, Sprague-Dawley ; Recombinant Proteins/biosynthesis/genetics/pharmacology ; Superoxide Dismutase/genetics/metabolism/pharmacology ; Superoxides/metabolism

In vivo electroporation has emerged as a leading technology for developing nonviral gene therapies, and the various technical parameters governing electroporation efficiency have been optimized by both theoretical and experimental analysis. However, most electroporation parameters focused on the electric conditions and the preferred vehicle for plasmid DNA injections has been normal saline. We hypothesized that salts in vehicle for plasmid DNA must affect the efficiency of DNA transfer because cations would alter ionic atmosphere, ionic strength, and conductivity of their medium. Here, we show that half saline (71 mM) is an optimal vehicle for in vivo electroporation of naked DNA in skeletal muscle. With various salt concentrations, two reporter genes, luciferase and beta-galactosidase were injected intramuscularly under our optimal electric condition (125 V/cm, 4 pulses x 2 times, 50 ms, 1 Hz). Exact salt concentrations of DNA vehicle were measured by the inductively coupled plasma-atomic emission spectrometer (ICP-AES) and the conductivity change in the tissue induced by the salt in the medium was measured by Low-Frequency (LF) Impedance Analyzer. Luciferase expression in-creased as cation concentration of vehicle dec-reased and this result can be visualized by X-Gal staining. However, at lower salt concentration, transfection efficiency was diminished because the hypoosmotic stress and electrical injury by low conductivity induced myofiber damage. At optimal salt concentration (71 mM), we observed a 3-fold average increase in luciferase expression in comparison with the normal saline condition (p < 0.01). These results provide a valuable experimental parameter for in vivo gene therapy mediated by electroporation.
Animals ; Comparative Study ; DNA/*administration & dosage/metabolism ; Drug Delivery Systems ; Electric Conductivity ; Electroporation/methods ; Escherichia coli/genetics ; Female ; Gene Therapy/*methods ; *Gene Transfer Techniques ; Genes, Reporter ; Injections, Intramuscular ; Luciferase/metabolism ; Mice ; Mice, Inbred BALB C ; Muscle, Skeletal/drug effects/*metabolism/pathology ; Osmolar Concentration ; Plasmids/genetics/*metabolism ; Sodium Chloride/*pharmacology ; Transfection ; Vehicles/*administration & dosage ; beta-Galactosidase/metabolism