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

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

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

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

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

OBJECTIVETo study the effect of total saponins from Entada phaseoloides (TSEP) on islet morphology and skeletal muscle PI3K pathway-related protein expression of type 2 diabetic rats.

METHODType 2 diabetic rats were induced by high-fat diet and low-dose streptozotocin and then randomly divided into 5 groups, i.e. the normal control, the model group, the positive control drug (200 mg x kg(-1) metformin), the low-dose TSEP (25 mg x kg(-1)) group and the high-dose TSEP (50 mg x kg(-1)). Three weeks later, the islet morphology of rat pancreas were observed by HE staining, and protein expressions of insulin receptor substrate-1 (IRS-1), phosphatidylinositol 3-kinase (PI3K), protein tyrosine phosphatase-1B (PTP-1 B) and glucose transporter 4 (GLUT4) in rat skeletal muscle were detected by Western blot.

RESULTCompared with the modal group, TSEP administration groups showed relatively normal structures, clear pancreatic cells and intact capsula structures in pancreatic tissue pathological sections, with the number of pancreatic islets close to the normal control group. Meanwhile, above TSEP administration groups showed increased IRS-1, PI3K and GLUT4 protein expressions in their skeletal muscle tissues and decreased PTP-1B protein expression compared with the model group.

CONCLUSIONTSEP has an effect on protecting pancreatic tissues of type 2 diabetic rats and intervening in abnormal expression of proteins in skeletal muscle tissues.

Animals ; Diabetes Mellitus, Type 2 ; drug therapy ; Fabaceae ; chemistry ; Glucose Transporter Type 4 ; analysis ; Islets of Langerhans ; drug effects ; pathology ; Male ; Muscle, Skeletal ; drug effects ; pathology ; Phosphatidylinositol 3-Kinases ; analysis ; Rats ; Rats, Sprague-Dawley ; Saponins ; therapeutic use

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

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) administration alone or exercise combined with DHEA before steroid treatment on rat hindlimb muscles. METHODS: Male Sprague-Dawley rats were assigned to one of three groups: a steroid group (S, n=10) that had no treatment for 7 days before steroid treatment; a DHEA-steroid group (DS, n=8) that had 0.34 mmol/kg/day DHEA injection once a day for 7 days before steroid treatment and an exercise?steroid group (EDS, n=9) that ran on the treadmill combined with 0.34 mmol/kg/day DHEA injection for 7 days before steroid treatment. At 15 days all rats were anesthetized and soleus, plantaris and gastrocnemius muscles were dissected. Body weight, food intake, muscle weight, myofibillar protein content and cross-sectional area of the dissected muscles were determined. RESULTS: The DS group showed significant increases (p<.05) as compared to the steroid group in body weight, and muscle weight of gastrocnemius muscles. The EDS group showed significant increases (p<.05) as compared to the S group in body weight, muscle weight, myofibrillar protein content, and Type II fiber cross-sectional area of soleus, plantaris and gastrocnemius muscles. CONCLUSION: Exercise combined with DHEA administration before steroid treatment prevents steroid induced muscle atrophy, with exercise combined with DHEA administration being more effective than DHEA administration alone in preventing muscle atrophy.
Animals ; Body Weight ; Dehydroepiandrosterone/*administration & dosage ; Hindlimb ; Male ; Muscle Contraction/drug effects ; Muscle, Skeletal/*drug effects/pathology ; Muscular Atrophy/chemically induced/*prevention & control ; *Physical Conditioning, Animal ; Rats ; Rats, Sprague-Dawley ; Steroids/*toxicity

PURPOSE: The purpose of this study was to examine the effect of DHEA (Dehydroepiandrosterone) on muscle weight and Type I and II fiber cross-sectional area of affected and unaffected hindlimb muscles in rats with neuropathic pain induced by unilateral peripheral nerve injury. METHODS: Neuropathic pain was induced by ligation and cutting of the left L5 spinal nerve. Adult male Sprague-Dawley rats were randomly assigned to one of two groups: The DHEA group (n=10) had DHEA injections daily for 14 days, and the Vehicle group (n=10) had vehicle injections daily for 14 days. Withdrawal threshold, body weight, food intake and activity were measured every day. At 15 days all rats were anesthetized and soleus, plantaris and gastrocnemius muscles were dissected from the both hindlimbs. Body weight, food intake, activity, muscle weight and Type I, II fiber cross-sectional area of the dissected muscles were measured. RESULTS: The DHEA group showed significant increases (p<.05), as compared to the vehicle group for muscle weight of the unaffected plantaris, and in Type II fiber cross-sectional area of the gastrocnemius muscle. The DHEA group demonstrated a higher pain threshold than the vehicle group whereas total diet intake and activity score were not significantly different between the two groups. CONCLUSION: DHEA administration for 14 days attenuates unaffected plantaris and gastrocnemius muscle atrophy.
Animals ; Body Weight ; Dehydroepiandrosterone/*administration & dosage ; Disease Models, Animal ; Eating/drug effects ; *Hindlimb ; Male ; Muscle Fibers, Skeletal/*drug effects/pathology ; Muscle, Skeletal/drug effects ; Muscular Atrophy/*drug therapy ; Pain/etiology ; Pain Measurement ; Peripheral Nerves/*injuries ; Rats ; Rats, Sprague-Dawley