Serum Creatine Phosphokinase Activity Research Articles

Acetamiprid induces cardiotoxicity in rats by dysregulating α7 nAChR and its downstream targets: The ameliorative role of resveratrol

Acetamiprid (ACP) is a novel neonicotinoid insecticide used for controlling insect pests. Resveratrol (RSV) is a natural polyphenol that possesses anti-oxidant, anti-inflammatory and anti-apoptotic actions. The current research explores the mechanism of ACP-induced cardiotoxicity and the alleviative effects of RSV. Male rats were allocated to four groups of ten each. Rats were treated daily for 90 days via oral route. Control rats received distilled water, ACP rats received 25 mg acetamiprid/kg, RSV rats received 20 mg resveratrol/kg and ACP + RSV rats received both ACP and RSV. ACP exposure increased serum creatine phosphokinase activity and cardiac troponin level. It also induced oxidative stress, as evidenced by the glutathione reduction, and malondialdehyde elevation, as well as the detrimental histopathological and immunohistochemical changes in the myocardium. Gene expression analysis revealed down-regulation in the mRNA expression of the survival-related genes α7 nAChR, Erk and Bcl-2, and up-regulation in the apoptosis-related genes Jnk, Bax and Caspase-3. Conversely, the concomitant administration of ACP with RSV alleviated most of the aforementioned toxic impacts. It can be concluded that ACP induces cardiotoxicity by dysregulating the mRNA expression of α7 nAChR and its downstream targets. Additionally, RSV is proved to be a promising ameliorative agent against ACP-induced cardiotoxicity.

THE EFFECT OF DRY WHITE MISTLETOE EXTRACT ON THE CHANGE IN THE RATIO OF MITOCHONDRIAL SUBPOPULATIONS IN THE MYOCARDIUM IN ANIMALS WITH ALCOHOLIC CARDIOMYOPATHY

The aim of the research was to study the cardioprotective effect of dry white mistletoe extract in the context of assessing its effect on changes in the activity of interfibrillary and subsarcolemmal mitochondrial subpopulations of the myocardium in experimental alcoholic cardiomyopathy. Materials and methods. Alcoholic cardiomyopathy was modeled in female Wistar rats by course administration of ethanol at the rate of 3 g of absolute ethanol per 1 kg of animal body weight. The studied extract of white mistletoe leaves and the comparison drug – Trimetazidine – were administered orally at doses of 100 mg /kg and 35 mg/kg, respectively. Changes in troponin I concentration and serum creatine phosphokinase activity, citrate synthase activity in mitochondrial subpopulations, and the content of apoptosis markers – apoptosis-inducing factor and caspase 3 in myocardial tissue homogenate were determined during the work. Results and their discussion. The analysis of the results revealed that in rats with alcoholic cardiomyopathy, but without treatment, there is an increase in the concentration of troponin I and creatine phosphokinase activity, accompanied by an increase in the intensity of apoptosis reactions and citrate synthase activity of interfibrillary mitochondria. The use of Trimetazidine and the extract under analysis contributed to a decrease in troponin I content by 19.1% (p < 0.05) and 24.4%, respectively, and creatine phosphokinase activity by 19.8% (p < 0.05) and 28.4% (p < 0.05). It was also established that the activity of subsarcolemmal mitochondria in animals treated with Trimetazidine and white mistletoe extract increased by 121.9% (p < 0.05) and 306.3% (p < 0.05) with a decrease in the activity of citrate synthase of interfibrillary mitochondria by 27.6% (p < 0.05) and 41.4% (p < 0.05). It should be noted that administration of the comparative drug and the studied extract to rats resulted in a decrease in cardiomyocytes' apoptosis, expressed in a decrease in the concentration of apoptosis-inducing factor and caspase 3. Conclusions. In conditions of alcoholic cardiomyopathy, the negative interfibrillary phenotype of mitochondria prevails, which can contribute to the development of energy deficiency in the heart muscle, increasing the degree of myocardial damage. Based on the data obtained, it can be assumed that the extract of white mistletoe contains an active substance of cardioprotective activity associated with restoring the energy metabolism and suppression of apoptosis in the myocardium.

Effects of soy isoflavone on cardiac dysfunction in geripause-like rats: comparisons with hormone-replacement therapy

Background Cardiovascular diseases are a primary cause of morbidity and mortality worldwide. The prevalence of cardiovascular disease as well as inflammation in postmenopausal women is higher than premenopausal women. Objective The present study investigated cardiac dysfunction elicited by estrogen deprivation and aging and assessed a possible beneficial impact of isoflavones compared with estradiol-replacement therapy. Materials and methods Forty aged female rats were equally divided into four groups. Except for sham-operated animals in group 1 (negative control), all other rats were ovariectomized. One month after surgery, animals were assigned to groups 3 and 4. Rats in the former group were treated with 17β-estradiol, 100 μg/kg, intramuscular, every other day. Animals in group 4 were administered soy isoflavones (SIF), 40 mg/kg/day orally. Treatments continued for 1 month. Results and conclusion Compared with control rats, ovariectomized animals showed cardiac dysfunction and inflammation evidenced by dyslipidemia and elevated serum creatine phosphokinase and lactate dehydrogenase activity, angiotensin II, cardiac malondialdehyde and nitric oxide levels, and serum tumor necrosis factor-α and interleukin-6 levels. These impacts were concurrent with significant decreases in cardiac catalase activity and total antioxidant capacity. Treatment with SIF was more effective in mitigating inflammation and cardiac dysfunction compared with estradiol-replacement therapy. Histopathological examination of heart tissues supports these biochemical findings. SIF are a safe and well-tolerated alternative to estradiol for improving cardiac dysfunction elicited by menopause and age.

Ameliorating effect of Withania somnifera root extract in Escherichia coli–infected broilers

The present study was undertaken to investigate the effect of aqueous Withania somnifera root (WSR) extract in broiler chicks experimentally infected with Escherichia coli O78 @ 107 CFU/0.5 ml intraperitoneally. Clinical signs and mortality due to colibacillosis observed in infected chicks were mild and lasted for short duration in WSR extract supplemented group as compared with the nonsupplemented group. A significant increase in serum alanine transaminase, aspartate transaminase, lactate dehydrogenase, and creatine phosphokinase activities and a decrease in total protein and albumin concentrations were observed in the infected groups, though these changes were of lower magnitude in WSR extract supplemented group. A significantly higher activity of oxidative blood parameters such as superoxide dismutase, catalase, glutathione reductase, and glutathione-S-transferase enzymes were noticed in WSR extract supplemented group. The WSR extract supplemented group revealed significantly higher E. coli–specific antibody titer and enhanced lymphocyte proliferation response as compared with the nonsupplemented group. The gross and histopathological lesions of colibacillosis were mild in the WSR extract–supplemented infected group as compared with the nonsupplemented infected group. Withania somnifera root extract supplementation produced 31.48 and 34.38% protection in the gross and histopathological lesions in E. coli infected chicks, respectively. It is concluded that supplementation of 20% WSR extract @ 20 ml/L of water caused a reduction in the severity, mortality, and recovery period of E. coli infection and enhanced the humoral and cellular immune responses suggesting its protective effect on limiting the pathology of E. coli infection in broiler chickens.

Protective effects of apocynin against cadmium toxicity and serum parameters; evidence of a cardio-protective influence

ObjectiveApocynin (4-hydroxy-3-methoxyacetophenone) an NADPH oxidase inhibitor isolated from the medicinal plant Picrorhiza kurroa (Scrophulariaceae) has been reported to possess antihypertensive properties. Cadmium exposures are reported to induce tissue damage leading to hypertension. The study was designed to evaluate the effect of apocynin on anti-atherogenic index (AAI), coronary risk index (CRI), cardio-protective index as well as biochemical and electrolyte parameters in the blood following cadmium exposure. MethodThirty-six (36) adult male Sprague-Dawley rats were randomly divided into 6 groups. Group 1 as control, 2 and 3 receiving 50 and 100 mg/kg body weight apocynin respectively, group 4 received 100 mg/L cadmium chloride (CdCl2) in their drinking water, while group 5 and 6 received 100 mg/L CdCl2 in their drinking and 50 and 100 mg/kg body weight apocynin respectively for eight weeks. Cadmium concentrations were determined using atomic absorption spectroscopy (AAS). Biochemical and electrolyte parameters in serum were determined using an automated biochemical multi-analyzer at the end of eight weeks. ResultsApocynin did not significantly (p < 0.05) alter cadmium accumulation in the aorta but caused a significant (p < 0.05) increase in the kidney. Exposures to cadmium resulted in a statistically significant (p < 0.05) increase in concentrations of serum potassium, bicarbonate, total bilirubin, and creatine phosphokinase (CPK) activity; which were ameliorated with apocynin. No significant change was observed in the concentrations of albumin, glucose, urea, creatinine nor GGTP, AST, AAI, CRI, cardioprotective index and other lipid parameters. ConclusionApocynin showed some protective effects on cadmium-induced tissue damage, and these effects could be tissue specific.

Effect of a leucine-enriched essential amino acids mixture on muscle recovery.

[Purpose] The aim of this study was to determine whether the consumption of a leucine-enriched essential amino acid mixture (LEAA), which is known to increase protein synthesis in muscles, alleviates muscle damage and accelerates recovery by ameliorating muscle damage. [Participants and Methods] A double-blind, randomized crossover trial was conducted over a 5-week period. Ten untrained males (age, 23.0 ± 1.6 years) were asked to repeatedly flex and extend their elbows for 10 counts/set × 5 sets at full power while using a dynamometer. The participants took 3.6-g supplements (LEAA mixture or placebo) 3 times daily on day 0 and for the next 7 days. Changes in serum creatine phosphokinase (CPK) activity and myoglobin concentration as markers of muscle tissue damage were evaluated prior to and after exercise and on days 1, 2, 3, 5, and 7. [Results] The relative ratio of the changes in peak serum CPK activity measured on day 5 was significantly lower after taking LEAA than after taking the placebo. [Conclusion] LEAA consumption suppressed exercise-induced elevation of muscle damage markers in blood, which suggests that LEAA could attenuate muscle damage and aid muscle recovery.

The role of endothelial dysfunction in children with pyelonephritis against fibrylogenesis disorders

Annotation: The prevalence of microbial inflammatory diseases of the urinary system, according to epidemiological studies, is 29.0 per 1000 children. Over the past decades, an unfavourable tendency towards an increase in the pediatric population of chronic pathology has been observed, treatment complicated by a significant pathomorphosis of the disease. Aim of the research: analysis of the frequency of birth defects in the development of organs of the urinary system, as a visceral marker of violation of the fibrillogenase, in children with different variants of pyelonephritis. Materials and methods: 148 children with pyelonephritis from 3 to 18 years were examined. According to the results of catamnestic observation, they were divided into 2 groups: I - 92 people, children with pyelonephritis, in which catamnesis was diagnosed 3 or more episodes of recurrence of pyelonephritis in 2 years, II - 56 children with pyelonephritis, in which for 2 years no relapse of the disease was noted. The control group consisted of 65 somatically healthy children of the same age. All children had a routine comprehensive clinical and laboratory examination and clinical and laboratory markers of fibrillogenic disorder (phenotypic signs of undifferentiated connective tissue dysplasia (UCTD), excretion of oxyproline with urine) were established. Results: In children with recurrent pyelonephritis, phenotypic signs of undifferentiated connective tissue dysplasia. For this purpose, the activity of endothelin-1 fraction, alkaline phosphatase and serum creatine phosphokinase, excretion of creatinine and glycosaminoglycans with daily urine in children with pyelonephritis was studied. On average, the level of endothelin-1 in blood plasma in practically all children in group I was significantly higher (1.815±0.03 fmol/l, q=0.92, p≤0.01) more than in the 10th time, than in children with APN (0.179±0.02 fmol/l, q=0.78 p≤0.01) and healthy children (0.077±0.01 fmol/l, q=0.03). Conclusions: In children with recurrent pyelonephritis, compared with the data of children with acute non-recurrent pyelonephritis, phenotypic signs of undifferentiated dysplasia of connective tissue were significantly more marked. Thus, the negative role of UCTD in the course of pyelonephritis in children has been confirmed. It has been shown that UCTD in children with pyelonephritis is manifested not only by phenotypic features, but also by visceral, such as BD US, which leads to the chronization of the process with frequent relapses.

Evaluating the Effect of Vitamin C on Myocardial Angiogenesis Under Oxidative Stress Induced by Exhaustive Exercise in Rat

Background: The main purpose of the present study was to assess the effects of exhaustive swimming with the consumption of a vitamin C supplement on indices of myocardial oxidative stress and gene expression related to angiogenesis. Methods: Wistar rats were randomly divided into six groups of normal (C), 100 and 200 mg/kg of vitamin C, (VC100 and VC200), exercise with 100 and 200 mg/kg of vitamin C (Ex+VC100 and Ex+VC200) and exercise without treatment (Ex). Finally, the serum activity of serum creatine phosphokinase (CK) and lactate dehydrogenase (LDH) and heart tissue oxidant/antioxidant parameters, besides gene expression of Vascular endothelial growth factor-B (VEGF-B), angiopoietin 1 (ANGPT-1) and matrix metalloproteinases 2 (MMP-2) was measured. Results: Significant increase in LDH level was seen in group Ex which was remarkably attenuated in group Ex+VC200 (p&lt;0.001). The tissue oxidative stress was observed in group Ex where daily intake of vitamin C could remarkably regulate this property (p&lt;0.01). Vitamin C could ameliorate significant upper gene expression of VEGF-B and MMP-2 remarkably (p&lt;0.05). Conclusion: Oxidative condition in myocardial besides over expression of MMP-2, could be concluded as a detrimental condition resulting from exhaustive swimming that continued by the proteolytic release of CK and LDH from the muscle. Upper gene expression of VEGF-B and MMP-2 besides no changes of ANGPT-1 can be concluded as an early stage of angiogenesis. All these events were somehow attenuated by vitamin C which confirmed its beneficial effects as an antioxidant and the role of oxidation properties in the regulation of angiogenesis.

Dendrobine targeting JNK stress signaling to sensitize chemotoxicity of cisplatin against non-small cell lung cancer cells in vitro and in vivo

BackgroundLung cancer is a leading cause of cancer-related death worldwide. Cisplatin-based chemotherapy is the standard treatment for lung cancer, but chemoresistance and adverse effects especially cardiotoxicity limit its efficacy. PurposeThe efficacy of combination treatment of dendrobine, a plant alkaloid isolated from Dendrobium nobile, with cisplatin was examined as a possible anti-non-small cell lung cancer strategy. MethodsThe cytotoxicity of dendrobine and cisplatin against A549 lung cancer cells was analyzed by MTT and colony formation assays. Apoptosis was measured by annexin V/PI double staining. Apoptosis-related proteins were assessed by western blotting and qPCR analysis. In vivo efficacy was determined using A549 xenograft in nude mice. JNK and Bim inhibition were achieved by siRNA knockdown and/or chemical inhibition. Cardiotoxicity was assessed by serum creatine phosphokinase activity assay. ResultsDendrobine induced apoptotic cell death through mitochondrial-mediated pathway. Combination treatment of dendrobine with cisplatin showed enhanced cytotoxicity through stimulation of JNK/p38 stress signaling pathways and, consequently, the induction of apoptosis involving pro-apoptotic proteins Bax and Bim. In addition, dendrobine attenuated the body weight reduction and cardiotoxicity induced by cisplatin in nude mice. ConclusionThe combination treatment showed enhanced anticancer activity toward non-small cell lung cancer cells without aggravating the cardiotoxic effects of cisplatin suggesting that the combination strategy deserves further investigation for human lung cancer treatment.

The Effect of Maternal Supplementation of Zinc, Selenium, and Cobalt as Slow-Release Ruminal Bolus in Late Pregnancy on Some Blood Metabolites and Performance of Ewes and Their Lambs.

The aim of this study was to determine the effect of the supplementation of a slow-release bolus of zinc (Zn), selenium (Se), and cobalt (Co) at late gestation (6week prepartum) on performance and some blood metabolites of Mehraban ewes and their lambs until weaning. Seventy pregnant ewes, 6weeks prior to expected lambing, were randomly divided into two groups (35 heads each) including (1) control group and (2) slow-release bolus group. Blood samples of ewes were obtained on day 10 prepartum and 45 and 90days postpartum, and milk samples were collected on day 45. Blood samples of lambs were collected on days 10, 45, and 90. Body weight at birth and weaning and average daily gain were higher and percentage of mortality and white muscle disease rate were lower in lambs whose mothers were given a bolus (P < 0.05). Slow-release bolus administration increased serum alkaline phosphatase and whole blood glutathione peroxidase activity, plasma concentrations of Zn, Se, and vitamin B12 in ewes and their lambs (P < 0.05). In addition, serum creatine phosphokinase activity of lambs whose mothers were given bolus was lower (P < 0.05). Serum concentration of T3 in bolus given ewes and their lambs was higher (P < 0.05) and serum T4 concentration was lower (P < 0.05). Zinc, Se, and vitamin B12 concentrations in milk were significantly higher in treated ewes (P < 0.05). Obtained results showed that maternal supplementation of zinc, selenium, and cobalt as slow-release ruminal bolus in late pregnancy improved some mineral status of ewes and their lambs until weaning and led to higher body weights of lambs at weaning.

The quality of colostrum and vitality of calves, born from cows with different reaction to stress experiences

The article presents the results of studying cortisol concentration and creatine phosphokinase activity in the blood serum of 40 half-sib Ukrainian black and white dairy cows an hour after planned blood extraction, which was a stress experience. We divided the cows into three groups according to the distribution of cortisol concentration in the animals: I – high, II – average and III – low stress resistance. During the research, the cows from these groups were in their fourth month of lactation after their first calving. They were kept untethered in their summer quarters, natural pastures. The aim of the research was to identify the differences in the quality of colostrum, the vitality of the calves up to the age of 6 months, the vitality of the mother-cows, and also the influence of their different adaptation potentials in cases of abortion and stillborn calves among the cows from different groups. At the dairy complex where the research was conducted, the quality of the cows’ colostrum is not monitored. This is typical for most dairy plants of Ukraine. We found that the classes of A and M immunoglobulins did not depend upon which particular groups the animals belonged to, whereas the content of immunoglobulins of class G is 6.7 g/l higher, and the content of total protein is 8.9 g/l higher in the yield of colostrum of the cows from group 1. The influence of cows’ different levels of resistance to stress experiences on their incidence of abortions and stillborn calves was not determined. Gastroenteritis occurred among calves of cows from group 3 three times more often than with those of group 1. Vitality of calves from cows of groups 1 and 2 was significantly higher. Therefore, technological stress experiences of mother-cows have a negative effect upon the quality of colostrum and upon the vitality of calves. This factor ought to be taken into consideration in the exploitation of animals, especially during pregnancy in order to minimise stress and help individuals with less strong nervous systems. Solving the complex problems of increasing the vitality of calves involves in part guaranteeing their provision with colostrum immunity by compulsory control of the colostrum’ quality using a special aerometer (Colostrometer).

Clinical/genetic characteristics of patients with congenital muscular dystrophy caused by mutations in the LMNA gene

To study clinical/genetic characteristics of congenital muscular dystrophy caused by mutations in the LMNA gene in 5 patients from the Russian population. DNA samples of 42 probands, aged from 2 months to 9 years, with characteristic signs of congenital muscular dystrophy from nonrelated families were studied. The diagnosis was based on the results of genealogical analysis, neurological examination, serum creatine phosphokinase activity, results of electroneuromyography. In the Russian population, the frequency of congenital muscular dystrophy caused by mutations in the LMNA gene is not less than 12% of all cases of this group of diseases. The results indicate the presence of major mutation c.94_96delAAC in the LMNA gene. Specific phenotypic features of this form of congenital muscular dystrophy with symptoms of progressive flaccid paralysis with predominant lesions of axial muscles and plantar flexor muscles of the foot are described.

New Estimation Method of Total Creatine Phosphokinase Release in Early Stage in Acute Myocardial Infarction

In this paper, we introduce a new estimation method for total creatine phosphokinase release based on a physiological model of the serum creatine phosphokinase (CPK) activity change that can be used to estimate the total CPK release accurately, as early as possible, without frequent blood sampling. The physiological model and a new calculation method were applied to the serum CPK activity change of patients who suffered acute myocardial infarction (AMI). According to the results, the physiological model showed good agreement with the serum CPK activity change and the estimated value of the total CPK release also agreed well with that calculated using the conventional technique with clinically acceptable accuracy.

Effect of feeding citrus peel extracts on growth performance, serum components, and intestinal morphology of broilers exposed to high ambient temperature during the finisher phase

The main aim of the current experiment was to assess the potential of dietary orange peel extract (OPE) and lemon peel extract (LPE) as promoters of broiler resistance to high ambient temperature. The experiment was conducted as a 2×3 factorial arrangement of treatments with 2 levels of OPE (0 and 200mg/kg feed) and 3 levels of LPE (0, 200, and 400mg/kg feed). At d 25, a total of 288 Ross 308 broilers were randomly assigned to 6 dietary treatments with 4 replicates of 12 broiler chickens each. The temperature was increased to 34°C with 50% relative humidity for 5h daily starting from d 28 until d 38. At the end of the trial (d 38), 4 male broiler chickens per pen were sampled for determination of serum components and variables of intestinal morphology. Dietary OPE and LPE did not affect weight gain, feed intake, and feed conversion ratio of broiler chickens. The inclusion of 200mg/kg OPE increased serum total protein, but reduced serum lactate dehydrogenase and creatine phosphokinase activity in broiler chickens (P<0.05). Lemon peel extract supplementation decreased the activity of lactate dehydrogenase quadratically (P=0.039) and creatine phosphokinase linearly (P=0.037). No differences in the other blood characteristics and intestinal traits were observed with the exception of muscularis thickness of duodenum, which was reduced when LPE was added to the diet (linear, P=0.011). These results indicate that OPE, LPE, and their combination might modify some blood components and the proximal intestinal morphology, but without beneficial effect on growth performance of broiler chickens under hot conditions.

Arthrodèses transforaminales : intérêts de l’abord minimal invasif

Background and purposeTransforaminal lumbar interbody fusion (TLIF) is an effective technique, which can achieve a fusion rate of up to 90%. The minimally invasive approach has become increasingly popular because it is able to minimize iatrogenic soft tissue and muscle injury. Although the minimally invasive TLIF technique has gained popularity, its effectiveness compared with open TLIF has yet to be established. The authors prospectively compared the outcomes of patients who underwent mini-open TLIF with patients who underwent open TLIF. MethodsBetween 2007 and 2008, 50 patients underwent TLIF for grade 1 spondylolisthesis; 25 mini-open TLIF and 25 open TLIF. The mean age in each group was 48years, and there was no statistically significant difference between the groups. Data were collected perioperatively. Pain and functional disability were measured using a visual analogue scale (VAS) and the Oswestry disability index (ODI) at 3months, 6months, 1year and 2years. In addition, foraminal and disc height were measured at the same intervals and the fusion was evaluated at 1year on CT-scan. Soft tissue damage was evaluated by measuring the serum myoglobin and creatine phosphokinase activity. ResultsThe mean VAS improved from 7 to 2.8 and the ODI decreased from 30/50 to 15/50 and fusion rate at 1 year was 98%. There was no statistical difference for the clinical and radiological outcomes between the groups. The mean operative time was 186min for the open group, 170min for the mini-open group (P<0.05) and the mean blood loss was 486mL for the open group and 148mL for the mini-open group (P<0.01). ConclusionThe mini-open TLIF procedure for symptomatic low grade spondylolisthesis is an effective option which achieves similar clinical and radiological outcomes and reduces perioperative morbidity as well as soft tissue damage.

Biochemical effects of Solidago virgaurea extract on experimental cardiotoxicity

Cardiovascular diseases (CVDs) are the major health problem of advanced as well as developing countries of the world. The aim of the present study was to investigate the protective effect of the Solidago virgaurea extract on isoproterenol-induced cardiotoxicity in rats. The subcutaneous injection of isoproterenol (30 mg/kg) into rats twice at an interval of 24 h, for two consecutive days, led to a significant increase in serum lactate dehydrogenase, creatine phosphokinase, alanine transaminase, aspartate transaminase, and angiotensin-converting enzyme activities, total cholesterol, triglycerides, free serum fatty acid, cardiac tissue malondialdehyde (MDA), and nitric oxide levels and a significant decrease in levels of glutathione and superoxide dismutase in cardiac tissue as compared to the normal control group (P < 0.05). Pretreatment with S. virgaurea extract for 5 weeks at a dose of 250 mg/kg followed by isoproterenol injection significantly prevented the observed alterations. Captopril (50 mg/kg/day, given orally), an inhibitor of angiotensin-converting enzyme used as a standard cardioprotective drug, was used as a positive control in this study. The data of the present study suggest that S. virgaurea extract exerts its protective effect by decreasing MDA level and increasing the antioxidant status in isoproterenol-treated rats. The study emphasizes the beneficial action of S. virgaurea extract as a cardioprotective agent.

Effect of Ramadan fasting on anthropometric parameters, blood Pressure, creatine phosphokinase activity, serum calcium and phosphorus in healthy students of Shri Ram Murti smarak institute of medical sciences, Bareilly-UP

Background: Ramadan is the holiest month in the Islamic calendar. Ramadan is 28-30 days fast in which food, liquids and smoking during the day light hours is prohibited. This custom provides a unique opportunity to study the biochemical changes over this time. Objective: To explore any favourable and unfavourable consequences of Ramadan fasting. Materials and Methods: The study was performed on twenty healthy male students of Shri Ram Murti Smarak Institute of Medical Sciences, Bareilly, in the month of Ramadan (July-Aug, 2012). Body weight, waist circumference, blood pressure was monitored three times: one week before the beginning of Ramadan, mid of Ramadan (15th day) and at the end (29th day). Blood samples were also taken at the same times and evaluated for serum creatine phosphokinase (CPK) activity, calcium and phosphorus. Results: Body weight and waist circumference was found to be significantly (p

Inhibition of extracellular signal-regulated kinase 1/2 signaling has beneficial effects on skeletal muscle in a mouse model of Emery-Dreifuss muscular dystrophy caused by lamin A/C gene mutation

BackgroundAutosomal Emery-Dreifuss muscular dystrophy is caused by mutations in the lamin A/C gene (LMNA) encoding A-type nuclear lamins, intermediate filament proteins of the nuclear envelope. Classically, the disease manifests as scapulo-humeroperoneal muscle wasting and weakness, early joint contractures and dilated cardiomyopathy with conduction block; however, move variable skeletal muscle involvement can be present. Previously, we demonstrated increased activity of extracellular signal-regulated kinase (ERK) 1/2 in hearts of LmnaH222P/H222P mice, a model of autosomal Emery-Dreifuss muscular dystrophy, and that blocking its activation improved cardiac function. We therefore examined the role of ERK1/2 activity in skeletal muscle pathology.MethodsSections of skeletal muscle from LmnaH222P/H222P mice were stained with hematoxylin and eosin and histological analysis performed using light microscopy. ERK1/2 activity was assessed in mouse tissue and cultured cells by immunoblotting and real-time polymerase chain reaction to measure expression of downstream target genes. LmnaH222P/H222P mice were treated with selumetinib, which blocks mitogen-activated protein kinase/extracellular signal-regulated kinase kinase 1/2 that activates ERK1/2, from 16 to 20 weeks of age to assess the effects of treatment on muscle histology, ERK1/2 activity and limb grip strength.ResultsWe detected enhanced activation of ERK1/2 in skeletal muscle of LmnaH222P/H222P mice. Treatment with selumetinib ameliorated skeletal muscle histopathology and reduced serum creatine phosphokinase and aspartate aminotransferase activities. Selumetinib treatment also improved muscle function as assessed by in vivo grip strength testing.ConclusionsOur results show that ERK1/2 plays a role in the development of skeletal muscle pathology in LmnaH222/H222P mice. They further provide the first evidence that a small molecule drug may be beneficial for skeletal muscle in autosomal Emery-Dreifuss muscular dystrophy.

Therapeutic effect of fucoidan‐stimulated endothelial colony‐forming cells in peripheral ischemia

Fucoidan, an antithrombotic polysaccharide, can induce endothelial colony-forming cells (ECFC) to adopt an angiogenic phenotype in vitro. We evaluated the effect of fucoidan on vasculogenesis induced by ECFC in vivo. We used a murine hindlimb ischemia model to probe the synergic role of fucoidan-treatment and ECFC infusion during tissue repair. We found that exposure of ECFC to fucoidan prior to their intravenous injection improved residual muscle blood flow and increased collateral vessel formation. Necrosis of ischemic tissue was significantly reduced on day 14, to 12.1% of the gastronecmius cross-sectional surface area compared with 40.1% in animals injected with untreated-ECFC. ECFC stimulation with fucoidan caused a rapid increase in cell adhesion to activated endothelium in flow conditions, and enhanced transendothelial extravasation. Fucoidan-stimulated ECFC were resistant to shear stresses of up to 21 dyn cm(-2). Direct binding assays showed strong interaction of fucoidan with displaceable binding sites on the ECFC membrane. Bolus intramuscular administration of fucoidan 1 day after surgery reduces rhabdomyolysis. Mice injected with fucoidan (15 mg kg(-1)) had significantly lower mean serum creatine phosphokinase (CPK) activity than control animals. This CPK reduction was correlated with muscle preservation against necrosis (P < 0.001). Fucoidan greatly increases ECFC-mediated angiogenesis in vivo. Its angiogenic effect would be due in part to its transportation to the ischemic site and its release after displacement by proteoglycans present in the extracellular matrix. The use of ECFC and fucoidan together, will be an efficient angiogenesis strategy to provide therapeutic neovascularization.

Characterization of a canine model of glycogen storage disease type IIIa

SUMMARYGlycogen storage disease type IIIa (GSD IIIa) is an autosomal recessive disease caused by deficiency of glycogen debranching enzyme (GDE) in liver and muscle. The disorder is clinically heterogeneous and progressive, and there is no effective treatment. Previously, a naturally occurring dog model for this condition was identified in curly-coated retrievers (CCR). The affected dogs carry a frame-shift mutation in the GDE gene and have no detectable GDE activity in liver and muscle. We characterized in detail the disease expression and progression in eight dogs from age 2 to 16 months. Monthly blood biochemistry revealed elevated and gradually increasing serum alanine transaminase (ALT), aspartate transaminase (AST) and alkaline phosphatase (ALP) activities; serum creatine phosphokinase (CPK) activity exceeded normal range after 12 months. Analysis of tissue biopsy specimens at 4, 12 and 16 months revealed abnormally high glycogen contents in liver and muscle of all dogs. Fasting liver glycogen content increased from 4 months to 12 months, but dropped at 16 months possibly caused by extended fibrosis; muscle glycogen content continually increased with age. Light microscopy revealed significant glycogen accumulation in hepatocytes at all ages. Liver histology showed progressive, age-related fibrosis. In muscle, scattered cytoplasmic glycogen deposits were present in most cells at 4 months, but large, lake-like accumulation developed by 12 and 16 months. Disruption of the contractile apparatus and fraying of myofibrils was observed in muscle at 12 and 16 months by electron microscopy. In conclusion, the CCR dogs are an accurate model of GSD IIIa that will improve our understanding of the disease progression and allow opportunities to investigate treatment interventions.