Plasma Creatine Phosphokinase Research Articles

Tempol a superoxide dismutase mimic reduces cardiac muscle cell death through the control of oxidative stress in streptozotocin-induced diabetes

ABSTRACT Diabetes mellitus (DM) a metabolic disorder resulting in myocardial injury and diabetic cardiomyopathy (DCM) in association with oxidative stress induction. This study was therefore, investigated the potential protective effect of Tempol (TPL) on oxidative cardiac damage in experimental diabetic rats. Rats were assigned to three equal groups: group (NC); normal control rats received citrate buffer injections. Group (DC): diabetic control rats received a single i.p. STZ injection (60 mg/kg body weight), and Group (D/TPL) diabetic rats treated with TPL (10 mg/kg b.w; by i.p. injection) for four weeks. Our results showed a significant increment in plasma creatine phosphokinase (CPK), lactate dehydrogenase (LDH) activities, cholesterol, triglycerides, Nitric oxide (NO), and lipid peroxidation (LPO), In addition, GSH content and antioxidant enzyme activity were significantly deceased in DC group compared to normal control. While TPL treatment significantly ameliorated the observed biochemical abnormalities. Further, TPL reduced number of dead myocardial cells in diabetic-treated rats and, remarkably improved the histopathological alterations of the aorta. The results proved the protective effect of tempol on STZ-induced diabetic cardiomyopathy by reducing myocardial cell death through reducing oxidative stress and inhibition of lipid peroxidation.

Carbon Monoxide Alleviates Post-ischemia-reperfusion Skeletal Muscle Injury and Systemic Inflammation.

Restoration of blood flow in skeletal muscle after a prolonged period of ischemia induces muscular ischemia-reperfusion injury, leading to local injury/dysfunction in muscles followed by systemic inflammatory responses. However, preventive/curative agents for skeletal muscle ischemia injury are unavailable in clinics to date. Increasing evidence has validated that carbon monoxide (CO) prevents the progression of ischemia-reperfusion injury in various organs owing to its versatile bioactivity. Previously, we developed a bioinspired CO donor, CO-bound red blood cells (CO-RBC), which mimics the dynamics of RBC-associated CO in the body. In the present study, we have tested the therapeutic potential of CO-RBC in muscular injury/dysfunction and secondary systemic inflammation induced by skeletal muscle ischemia-reperfusion. The results indicate that CO-RBC rather than RBC alone suppressed elevation of plasma creatine phosphokinase, a marker of muscular injury, in rats subjected to both hind limbs ischemia-reperfusion. In addition, the results of the treadmill walking test revealed a significantly decreased muscular motor function in RBC-treated rats subjected to both hind limbs ischemia-reperfusion than that in healthy rats, however, CO-RBC treatment facilitated sustained muscular motor functions after hind limbs ischemia-reperfusion. Furthermore, CO-RBC rather than RBC suppressed the production of tumour necrosis factor (TNF)-α and interleukin (IL)-6, which were upregulated by muscular ischemia-reperfusion. Interestingly, CO-RBC treatment induced higher levels of IL-10 compared to saline or RBC treatments. Based on these findings, we suggest that CO-RBC exhibits a suppressive effect against skeletal muscle injury/dysfunction and systemic inflammatory responses after skeletal muscle ischemia-reperfusion.

Biochemical indicators of sperm plasma and morphofunctional features of spermatozoa in HIV-infected men

BACKGROUND: The problem of male infertility particularly affects men with HIV infections, as semen volume and sperm motility are reduced by highly active antiretroviral therapy.
 AIM: To analyze the metabolic parameters of spermatozoa, spermograms and spermatozoa morphology in HIV-infected men.
 MATERIALS AND METODS: The study included 47 patients (aged 2546 years) who were under observation at the clinic of Professor M.A. Florova (Samara). 2 groups were formed: main (n=22) HIV-infected patients who want to have children (with an undetectable viral load (4050 copies/ml) and taking antiretroviral therapy); control (n=25) clinically healthy men with one child. The material was taken and the ejaculate was examined according to standardized methods proposed by WHO experts.
 RESULTS: In HIV-infected men, spermatozoa motility was low (the number of progressively motile spermatozoa was 28.503.72%), the spermatozoa concentration was two times lower compared to the control group of men, the morphological characteristics of spermatozoa were significantly worse than in the control group: most often pathology of the head (21.751.10%) and neck of the spermatozoon (22.301.18%) was detected, which negatively affects the fertilizing ability.
 In HIV-infected men, changes in metabolic metabolism were noted: the activity of creatine phosphokinase in both sperm plasma (661.951.08 U/l) and blood plasma (76.901.09 U/l) was lower, than in the control group (844.250.13 and 79.501.37 U/l, respectively), the glucose concentration (8.071.14 mmol/l) was 2 times higher than in the control group (3.061.09 mmol/l), the concentration of calcium 6.530.01 and sodium (119.201.23 mol/l) slightly exceeded those in the group of healthy patients (5.550.08 and 116.850.01 mol/l, respectively). Electron microscopic analysis revealed fragmentation of sperm DNA: the highest percentage of sperm with fragmented DNA was found in men with HIV infection (more than 23%).
 CONCLUSION: It was revealed that in vivo fertilization in HIV-infected men is impossible in most cases. The study forms the basis for a future comprehensive assessment of the state of reproductive function in HIV-infected men to assess their fertility and the need for assisted reproductive technologies.

Shifting gears: Study of immune system parameters of male habitual marathon runners.

Marathon is a running event in which athletes must cover a distance of 42.195 km. In addition to participating in marathons, marathoners have incorporated extensive running into their lifestyle. In the present study, we investigated the effect of long-term strenuous exercise in the form of marathon running on the immune system. We collected peripheral blood samples from 37 male marathoners before/after a race and 37 age/sex/body mass index (BMI)-matched healthy sedentary controls. Hematological and biochemical tests revealed race-induced leukocytosis attributable to neutrophilia and significant increases in plasma lactate dehydrogenase (LDH), creatine phosphokinase (CPK), and cortisol concentrations. Phenotypic analysis of lymphocytes revealed race-induced significant decrease in the number of lymphocytes, memory helper T (Th) cells, naive, memory and activated cytotoxic T (Tc) cells, natural killer (NK), NKT, and B1 cells, and a significant increase in the number of activated Th and regulatory Th cells (Tregs). Compared with controls, marathoners maintained significantly lower levels of memory and activated Th cells and higher levels of activated Tc and B1 cells. Measurement of plasma cytokine levels revealed a pro-inflammatory cytokine polarization that increased after the race. Examination of gene expression of cytokines and Th-cell signature transcription factors in peripheral blood mononuclear cells revealed a significant decrease in tumor necrosis factor α (TNF-α) and interleukin (IL)-17, and a significant increase in IL-6, IL-10 and forkhead box P3 (FoxP3) after the race. Compared with controls, marathoners maintained significantly higher levels of TNF-α. Assessment of the suppressive capacity of Tregs in co-cultures of isolated effector Th cells and Tregs showed significantly increased suppressive capacity of marathoners' Tregs after the race. Compared with controls, marathoners live with permanent changes in certain immune parameters. Marathoners exhibit a stable pro-inflammatory cytokine polarization that increases after the race and is counterbalanced by increased numbers of Tregs overexpressing FoxP3 and having increased suppressive capacity.

Comparison of surgical invasiveness between micro-endoscopic discectomy/microscopic discectomy and conventional hemilaminectomy in dogs.

Micro-endoscopic discectomy (MED) or microscopic discectomy (MD) have been performed for disc herniation in humans. The purpose of this study was to compare the invasiveness of the hemilaminectomy in dogs between the approach using a cylindrical retractor for the MED/MD and a conventional open surgical approaches in dogs. First, as preliminary studies, we analyzed the suitability of the cylindrical retractor for the vertebral body of small to medium-sized dogs on the X-ray computed tomographic images using the three-dimensional analysis software, and confirmed that it was possible to open a bone window of an approximate length of 1.72 clto the spinal canal with the cylindrical retractor with a diameter 17 mm using two medium-sized canine cadavers. Next, to determine difference in the invasiveness of hemilaminectomy, the magnitude of tissue damage, surgical stress and postoperative pain were compared between the conventional open approach (hemilaminectomy group: HL group, n=6) and the surgical approach using the cylindrical retractor (MD group, n=6) in 12 beagle dogs. The plasma creatine phosphokinase, C-reactive protein and cortisol concentrations, incision length and University of Melbourne Pain Scale scores after the hemilaminectomy were significantly lower in the MD group than in the HL group. There were no significant differences between the durations of surgery and the other evaluated indices. The approach using the MD can provide a less invasive hemilaminectomy than the conventional approach in dogs.

ENZYME ACTIVITY OF CARBOHYDRATE AND AMINOACID METABOLISM, LIPID PEROXIDATION IN CARP TISSUES UNDER THE EFFECT OF 19-NORTESTOSTERONE

The aim of the study was to investigate the activity of a number of enzymes of carbohydrate metabolism, individual amino acids, creatine phosphate, inorganic phosphorus and lipid peroxidation (LPO) in the hepatopancreas and blood plasma of carp (Cyprinus carpio L.) under the influence of the synthetic steroid 19-norethisterone. The experiments were conducted on two-year-old carps, which were kept for 24 hours in aquariums with different concentrations of 19-nortestosterone in water at optimal temperature, oxygen content and pH. The activity of lactate dehydrogenase (LDH), alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatine phosphokinase (CPK) in the supernatant fraction of hepatopancreatic homogenate was monitored by UV-kinetic and colourimetric methods. The activity of isocitrate dehydrogenase (ICDH) was determined spectrophotometrically by the accumulation of NADPH, and lactate dehydrogenase (LDH), glucose-6-phosphate dehydrogenase (Gl-6-PDH) and glucose-6-phosphatase (Gl-6-Phase) - by the accumulation of NADH in the reactions of conversion of the corresponding substrates. Conventional biochemical methods were used to determine the concentration of diene conjugates, malondialdehyde (MDA), lipid hydroperoxides, catalase (CAT) and superoxide dismutase (SOD) activity in blood plasma and supernatant fraction of hepatopancreatic homogenate. Conventional biochemical methods were used to determine the concentration of diene conjugates, malondialdehyde (MDA), lipid hydroperoxides, catalase (CAT) and superoxide dismutase (SOD) activity in blood plasma and the supernatant fraction of hepatopancreatic homogenate. It was found that fish exposed to water with a concentration of synthetic steroid 19-nortestosterone of 50 µg/dm3 for 24 hours had higher levels of MDA and diene conjugates, increased activity of CAT and SOD in blood plasma, increased activity of ALP, ALT, AST, CK, CAT and SOD in the hepatopancreatic supernatant fraction, and LDH remained unchanged, as well as the level of lipid hydroperoxides in blood plasma. Under the influence of 19-nortestosterone, the activity of Gl-6-FDG and IDDG in the mitochondrial fraction of carp hepatopancreas increases, and that of Gl-6-phase in the supernatant. At a concentration of 19-nortestosterone in water of 200 μg/dm3, the content of lipid hydroperoxides in the blood plasma of carp increases, and in the hepatopancreatic supernatant fraction - diene conjugates and SOD activity, while ALP and CPK decrease relative to their values in fish with a low level of xenobiotic in water. The content of MDA, diene conjugates, as well as the activity of CAT, SOD, ALP, CPK and LDH in blood plasma, IDH and Gl-6-PDH in the mitochondrial fraction and Gl-6-Phase and LDH in the hepatopancreatic supernatant did not change, but remained higher than in the control. It was concluded that 19-nortestosterone stimulates carbohydrate metabolism, amino acids alanine and aspartate transamination, creatine phosphate conversion, antioxidant enzyme activity and lipid peroxidation in the hepatopancreas of two-year-old carp. The obtained results deepen the understanding of the mechanism of action of synthetic steroids in bony fish, and the differences in enzyme activity and lipid peroxidation can be important criteria for ecotoxicological assessment of water bodies contaminated with hormonal compounds.

Muscular Adverse Events Associated with Statins

Statins are an important group of lipid lowering medications that have helped to control cardiovascular mortality globally. Muscular side effects, mostly myalgia, is a known adverse event of statins. Intense physical activity, kidney or liver failure, hypothyroidism, inherited or metabolic myopathies, and some medications, are risk factors for statin-induced myalgia. Muscular adverse events are more often observed with higher doses or with the use of lipophilic statins. Much is not known about the precise mechanisms responsible for the statin related muscular adverse effects, a few hypothesis have been suggested. It is important to measure plasma creatine phosphokinase in subjects who encounter myalgia while being treated with statins. In this review we present some general safety information on muscular adverse events caused due to statins.

Alcohol-induced damage to skeletal muscles in women with chronic alcohol intoxication

In Russia, there is a high level of alcohol consumption among women in doses that represent a high risk of developing alcoholic diseases, manifested, in particular, by damage to skeletal muscles.The purpose of the study. Analysis of clinical, biochemical, neurophysiological, as well as morphometric and immunohistochemical features of alcoholic skeletal muscle damage in women with chronic alcohol intoxication.Material and methods. A clinical and laboratory examination of 30 women aged 20 to 60 years with chronic alcohol intoxication was performed, which included the determination of creatine phosphokinase (CPK) and insulin-like growth factor I (IGF-I) in blood plasma, stimulation and needle electromyography (EMG), as well as morphological and immunohistochemical examination of biopsies of the quadriceps femoris.Results. Myopathic syndrome in the form of proximal para-or tetraparesis was observed in 73.3% of the examined women in combination with a decrease in IGF-1 at normal values of CPK in blood plasma. The EMG results indicated the absence of changes in the parameters of the potentials of motor units, characteristic of primary muscular lesions, and of conduction disturbances along the femoral nerve. Morphometric and immunohistochemical studies of skeletal muscle biopsies showed a decrease in the cross-sectional area of muscle fibers of types I and II without signs of muscle tissue necrosis.Conclusion. Chronic alcoholic myopathy is a common manifestation of alcoholic disease in women with long-term alcohol intoxication. The severity of the atrophic process in the skeletal muscle is comparable to the degree of proximal paresis. Violations of systemic protein synthesis and acceleration of apoptosis are considered as pathogenetic mechanisms of the atrophic process in the muscles in chronic alcoholic myopathy in women.

Sex-dependent vulnerability of fetal nonhuman primate cardiac mitochondria to moderate maternal nutrient reduction.

Poor maternal nutrition in pregnancy affects fetal development, predisposing offspring to cardiometabolic diseases. The role of mitochondria during fetal development on later-life cardiac dysfunction caused by maternal nutrient reduction (MNR) remains unexplored. We hypothesized that MNR during gestation causes fetal cardiac bioenergetic deficits, compromising cardiac mitochondrial metabolism and reserve capacity. To enable human translation, we developed a primate baboon model (Papio spp.) of moderate MNR in which mothers receive 70% of control nutrition during pregnancy, resulting in intrauterine growth restriction (IUGR) offspring and later exhibiting myocardial remodeling and heart failure at human equivalent ∼25 years. Term control and MNR baboon offspring were necropsied following cesarean-section, and left ventricle (LV) samples were collected. MNR adversely impacted fetal cardiac LV mitochondria in a sex-dependent fashion. Increased maternal plasma aspartate aminotransferase, creatine phosphokinase (CPK), and elevated cortisol levels in MNR concomitant with decreased blood insulin in male fetal MNR were measured. MNR resulted in a two-fold increase in fetal LV mitochondrial DNA (mtDNA). MNR resulted in increased transcripts for several respiratory chain (NDUFB8, UQCRC1, and cytochrome c) and adenosine triphosphate (ATP) synthase proteins. However, MNR fetal LV mitochondrial complex I and complex II/III activities were significantly decreased, possibly contributing to the 73% decreased ATP content and increased lipid peroxidation. MNR fetal LV showed mitochondria with sparse and disarranged cristae dysmorphology. Conclusion: MNR disruption of fetal cardiac mitochondrial fitness likely contributes to the documented developmental programming of adult cardiac dysfunction, indicating a programmed mitochondrial inability to deliver sufficient energy to cardiac tissues as a chronic mechanism for later-life heart failure.

Utilizing Dynamic Phosphorous-31 Magnetic Resonance Spectroscopy for the Early Detection of Acute Compartment Syndrome: A Pilot Study on Rats.

Introduction: Disasters, including terrorism and earthquakes, are significant threats to people and may lead to many people requiring rescue. The longer the rescue takes, the higher the chances of an individual contracting acute compartment syndrome (ACS). ACS is fatal if diagnosed too late, and early diagnosis and treatment are essential. Objective: To assess the ability of dynamic phosphorus magnetic resonance spectroscopy (31P-MRS) in the early detection of muscular damage in ACS. Materials and Methods: Six ACS model rats were used for serial 31P-MRS scanning (9.4 Tesla). Skeletal muscle metabolism, represented by the levels of phosphocreatine (PCr), inorganic phosphate (Pi), and adenosine triphosphate (ATP), was assessed. The PCr/(Pi + PCr) ratio, which decreases with ischemia, was compared with simultaneously sampled plasma creatine phosphokinase (CPK), a muscle damage marker. Results: The PCr/(Pi + PCr) ratio significantly decreased after inducing ischemia (from 0.86 ± 0.10 to 0.18 ± 0.06; p < 0.05), while CPK did not change significantly (from 89 ± 29.46 to 241.50 ± 113.28; p > 0.05). The intracellular and arterial pH index decreased over time, revealing significant differences at 120 min post-ischemia (from 7.09 ± 0.01 to 6.43 ± 0.13, and from 7.47 ± 0.03 to 7.39 ± 0.04, respectively). In the reperfusion state, the spectra and pH did not return to the original values. Conclusions: The dynamic 31P-MRS technique can rapidly detect changes in muscle bioenergetics. This technique is a promising non-invasive method for determining early muscular damage in ACS.

Regional oxygen saturation change rate for detection of leg ischemia in minimally invasive cardiac surgery.

The criteria for placement of distal perfusion cannulas vary among reports. This cohort study aimed to establish a reproducible method to monitor critical leg ischemia during minimally invasive cardiac surgery. We included 121 patients who underwent minimally invasive cardiac surgery via right thoracotomy with right femoral arterial cannulation from 2015 to 2018. The change rate of regional oxygen saturation (ΔrSO2) was calculated as follows: rSO2 (baseline) - rSO2 (actual number)/rSO2 (baseline). Patients were divided into Group N (ΔrSO2 < 40%): 100/121 (83%) and Group H (ΔrSO2 > 40%, <10 minutes if >40%): 21/121 (17%). A distal perfusion cannula was placed when ΔrSO2 was >40% over 10 minutes. No patients experienced significant leg ischemia. Significantly longer cardiopulmonary bypass and aortic cross-clamp times were observed in Group H than in Group N (cardiopulmonary bypass time, 129 ± 36 minutes (Group N) vs. 151 ± 34 minutes (Group H), p = 0.01). ΔrSO2 correlated positively with plasma creatine phosphokinase elevation (R = 0.40, p < 0.001) on postoperative day 1. Serum lactate on intensive care unit admission showed a significant positive correlation (R = 0.40, p < 0.001) with ΔrSO2. ΔrSO2 measurement by near-infrared spectroscopy can facilitate distal leg perfusion monitoring and assist surgeons in preventing critical leg ischemia during minimally invasive cardiac surgery.

Effect of minimally invasive percutaneous endoscopic technique in treatment of lum bar disc herniatien and its effect on plasma factor C-reactive protein, creatine phosphokinase and interleukin-6

Effect of minimally invasive percutaneous endoscopic technique in treatment of lum bar disc herniatien and its effect on plasma factor C-reactive protein, creatine phosphokinase and interleukin-6

Curcumin and Nanocurcumin Oral Supplementation Improve Muscle Healing in a Rat Model of Surgical Muscle Laceration.

To compare the effects of curcumin and nanocurcumin oral supplementation on the muscle healing rate of an animal model of surgical muscle laceration. Thirty-two male adult rats were randomly divided into sham, control, curcumin, and nanocurcumin groups. Partial transection of the gastrocnemius muscle was made in the right limb of the control and treatment groups. The sham and control groups received normal saline, curcumin group received 500 mg/kg of curcumin and nanocurcumin group received 100 mg curcumin-loaded nanomicelles orally every day. They euthanized two weeks later and the specimens were stained by hematoxylin-eosin (H&E) and Masson's trichrome methods. Aspartate transaminase (AST) and creatine phosphokinase(CPK) were measured in blood samples. The percentage of collagen fibers in the nanocurcumin group was significantly lesser than the control and curcumin groups (p<0.001). Muscle fiber regeneration in the treatment groups was significantly higher than the control group (p<0.001). The blood vessels of the nanocurcumin group were significantly more than other groups (p<0.001). Plasma AST had a significant difference in the control group compared to the sham and nanocurcumin groups (p=0.026). The plasma CPK level of the control group was also significantly higher than other groups (p<0.001). In conclusion, although oral curcumin supplementation has little effects because of its poor bioavailability, embedding it in nanoparticles could enhance its systemic effects in promoting the muscle healing process.

Establishment and characterization of a mouse model of rhabdomyolysis by coadministration of statin and fibrate

Rhabdomyolysis is characterized by elevation of plasma creatine phosphokinase (CPK) level, and multiple organ disorders, especially renal failure, as well as approximately 50% of acquired rhabdomyolysis are caused by pharmaceuticals. Statins are known to cause rhabdomyolysis, and its incidence is ≥10 times higher with coadministration of statin and fibrate. The purpose of this study is to establish a mouse model of drug-induced rhabdomyolysis by coadministration of statin and fibrate to clarify the mechanisms of its myotoxicity. We administered lovastatin (LV) and gemfibrozil (GF) with a glutathione synthesis inhibitor, L-buthionine-(S,R)-sulfoximine (BSO), to C57BL/6 J female mice once daily for 3 days. The plasma levels of CPK and aspartate aminotransferase (AST) were prominently increased, and the increase in plasma miR-206-3p and miR-133-3p levels, not the increase of miR-122-5p and miR-208-3p levels, suggested skeletal muscle–specific toxicity. The caspase 3/7 activity and mRNA levels of oxidative stress–related factors were elevated in skeletal muscle. Pharmacokinetic parameters showed that blood levels of statin were significantly increased by coadministered GF. The possibility of kidney injury was examined as in clinical rhabdomyolysis. In histological examination, vacuoles were observed in renal proximal tubules, and the plasma renal injury marker, lipocalin 2/neutrophil gelatinase-associated lipocalin (Lcn2/Ngal), was markedly increased in the mice coadministered LV and GF, suggesting mild complications of acute kidney injury. A quantitative comparison of the myotoxic potential of various statins was successfully performed using the present method. In this study, a rhabdomyolysis mouse model was established by coadministration of the clinically using statin and fibrate. This mouse model may be useful to identify drugs that have high risk for rhabdomyolysis.

Acute kidney injury model established by systemic glutathione depletion in mice.

Glutathione (GSH) is one of the most extensively studied tripeptides. The roles for GSH in redox signaling, detoxification of xenobiotics and antioxidant defense have been investigated. A drug-induced rhabdomyolysis mouse model was recently established in L-buthionine-(S,R)-sulfoximine (BSO; a GSH synthesis inhibitor)-treated normal mice by co-administration of antibacterial drug and statin. In these models, mild kidney injury was observed in the BSO only-treated mice. Therefore, in this study, we studied kidney injury in the GSH-depleted mouse. BSO was intraperitoneally administered twice a day for 7days to normal mice. The maximum level of plasma creatine phosphokinase (351487±53815U/L) was shown on day 8, and that of aspartate aminotransferase was shown on day 6. Increased levels of blood urea nitrogen, plasma creatinine, urinary kidney injury molecule-1 and urinary creatinine were observed. An increase of mRNA expression level of renal lipocalin 2/neutrophil gelatinase-associated lipocalin was observed. Degeneration and necrosis in the skeletal muscle and high concentrations of myoglobin (Mb) in blood (347-203925ng/mL) and urine (2.5-68583ng/mL) with large interindividual variability were shown from day 5 of BSO administration. Mb-stained regions in the renal tubule and renal cast were histologically observed. In this study, the GSH-depletion treatment established an acute kidney injury mouse model due to Mb release from the damaged skeletal muscle. This mouse model would be useful for predicting potential acute kidney injury risks in non-clinical drug development.

Factors associated with changes in creatine phosphokinase (CPK) in trauma patients submitted to the "Red Wave", with evolution to rhabdomyolysis.

to identify and analyze factors associated with plasma creatine phosphokinase (CPK) levels in trauma victims with progression to rhabdomyolysis. we conducted a prospective, longitudinal study, with 50 patients submitted to the "Red Wave" protocol, with evolution to rhabdomyolysis after hospital admission. We studied the variables age, gender, trauma scores, mechanism and outcome, CPK at admission and final, intervals of days between laboratory evaluations, surgery and complications. We stratified CPK values in <500U/L, ≥500 - <1000 U/L, and ≥1000U/L, with calculation of the difference between the initial and final values. at admission, 83% of patients (n=39) had CPK≥1000U/L, with predominance of blunt trauma and thoracic injury (p<0.05), as well as orthopedic fracture, acute renal failure and gastrointestinal bleeding, CPK being lower in those without acute renal injury, with a trend towards statistical significance. There were no differences in final CPK stratification. Factors that were independently associated with the greater CPK variation were, positively, hospitalization time greater than one week and compartment syndrome, and negatively, acute renal injury. the CPK level of 1000U/L remains the lower limit, with importance for early intervention in worsening conditions such as digestive hemorrhage, acute renal injury and compartment syndrome, which implied greater absolute differences between initial and final CPK, in addition to blunt trauma, thoracic injury and orthopedic fracture.

Anaesthetic efficacy and biochemical effects of 1,8-cineole in rainbow trout (Oncorhynchus mykiss , Walbaum, 1792)

The aim of the present study was to investigate the anaesthetic efficacy and biochemical effects of 1,8-cineole (cineole) in rainbow trout (Oncorhynchus mykiss). The fish were exposed to 200, 300, 400, 500, 600 and 800 μl/L cineole and time of induction of anaesthesia and recovery from anaesthesia were recorded. Thereafter, the fish haematological and biochemical responses to anaesthesia with different concentrations of cineole were studies. Moreover, the haematological and biochemical response of fish anaesthetized for 300 s with either cineole (283 μl/L) or eugenol (25 μl/L) were compared. Cineole at the concentrations of 200–800 μl/L induced stages 2, 3 and 4 anaesthesia within 109-29.3, 226-59 and 418-117 s respectively. Increase in anaesthesia induction time led to higher stress responses and enzymes’ activity characterized by elevation in red blood cell (RBC), white blood cell (WBC), blood haematocrit and haemoglobin, and plasma cortisol, glucose and lactate levels, and aspartate aminotransferase (AST), alkaline phosphatase (ALP), lactate dehydrogenase and creatine phosphokinase (CPK) activities. However, cineole concentrations had no significant effects on plasma alanine aminotransferase (ALT) activity and ions levels. Comparison of cineole with eugenol showed that cineole showed less change in blood RBC and plasma AST, ALP, CPK, cortisol and glucose levels compared to eugenol. In conclusion, cineole is efficient to anaesthetize trout at concentrations of 200–800 μl/L. Increase in cineole concentration shortens anaesthesia induction time, stress response and probably tissue damage. The concentrations of 600–800 μl/L cineol is recommended for rapid sampling as it causes the least stress and enzymatic responses. The present results suggest that cineole causes slightly lower side effects in trout compared to eugenol.

Characterization of plasma metabolites at late gestation and lactation in early parity sows on production and post-weaning reproductive performance1

Lactation is a very energy demanding period for sows. The current study provides a better understanding of the biochemical response of first- (n = 246) or second-parity (n = 127) sows during late gestation through lactation and assesses relationships with piglet production and dam reproductive performance. Plasma samples were collected from first- or second-parity dams at late gestation (110 d gestation [d110G]), d 1 post-farrowing (d1PF), and weaning (WN) then analyzed for various stress and protein metabolism compounds, including; creatine, creatine phosphokinase (CPK) activity, creatinine, urea nitrogen, albumin, and lactate. Litter performance was measured as number of piglets nursed and piglet ADG. Post-weaning reproductive performance was assessed by measuring weaning-to-estrus interval (WEI) and subsequent ovulation rate collected at time of harvest. Plasma creatine and CPK activity increased (P < 0.05) between d110G and d1PF. Plasma creatinine decreased (P < 0.05) from d110G through WN in first-parity dams, but remained similar between d110G and d1PF before declining (P < 0.05) at WN in second-parity dams. Plasma urea nitrogen increased (P < 0.05) over the course of the study and was negatively (P < 0.05) associated with piglet ADG at d110G and d1PF and with ovulation rate at d110G (P < 0.05). Similarly, plasma albumin increased (P < 0.05) in first-parity dams over the course of the study, whereas it plateaued (P < 0.05) at d1PF and remained similar (P > 0.10) through WN in second-parity dams. First-parity dams had less (P < 0.05) plasma lactate at d110G than at d1PF or WN. However, second-parity dams had increased (P < 0.05) plasma lactate at d110G and d1PF, then decreased (P < 0.05) levels at WN. Plasma lactate at WN was positively (P < 0.05) associated with WEI in first-parity dams, but negatively (P < 0.05) related to WEI at d1PF in second-parity dams. Plasma lactate levels at all time points were positively (P < 0.05) associated with ovulation rate in second-parity dams. The biochemical profile of these dams differed by parity and merits further investigations into these differences to identify methods to improve physiological response to lactation for improved animal welfare, production, and reproductive performance.

Abstract 14124: A Marked Increase in Myocardial Oxidative Stress Associated With Sympathetic Hyperactivity is Related to Transient Myocardial Dysfunction in Patients With Takotsubo Cardiomyopathy

Introduction: Sympathetic hyperactivity is considered as one of the most likely pathogenic mechanism in takotsubo cardiomyopathy (TC). However, little is known about the relationship between sympathetic hyperactivity and myocardial oxidative stress (OS). Hypothesis: We hypothesized that cardiac sympathetic hyperactivity was associated with cardiac myocardial OS, and OS related to transient myocardial dysfunction in patients with TC compared with acute anteroseptal myocardial infarction (AMI). Methods: In 8 TC patients and 8 AMI patients (NYHA 3), ECG, echocardiography, cardiac catheterization and serial measurements of plasma catecholamines, urinary (U) 8-hydroxy-2’-deoxyguanosine (8-OHdG) as a marker of OS and plasma CPK were performed for two weeks from onset. Results: Blood sampling from coronary sinus (CS) and aorta (Ao) at 1st day showed that norepinephrine (NE) levels and 8-OHdG level in CS were significantly higher than those in Ao and peripheral blood, indicating that an increase in myocardial OS was associated with cardiac sympathetic hyperactivity. NE levels in peripheral blood were peaked out at 1st day and 2-times higher in TC than in AMI within a week, while the max CPK value in TC was significantly lower than that in AMI. Dual scintigraphy of 201Tl and 123I-meta-iodobenzylguanidine was performed at 7th day showed that cardiac sympathetic nervous injury was much larger than myocardial perfusion damage in all TC patients. U-8OHdG level (ng/mg Cr; normal range:&lt;10.0) in TC was elevated in parallel with the profile of plasma NE level (1st day: 65.6±24.5, 4th day: 19.1±8.3, 7th day: 16.4±9.1), while it was decreased to almost normal range after percutaneous coronary intervention for left anterior descending artery in AMI (1st day: 24.3±13.8, 4th day: 9.8±3.4, 7th day: 12.3±2.7). Interestingly, difference in serum 8-OHdG levels (CS vs Ao) in TC increased proportionally with wall motion score (WMS) as an index of LV dysfunction (R=0.93, p&lt;0.001), while difference in serum NA levels (CA vs Ao) in TC did not. U-8OHdG level in TC was positively correlated with WMS at each day (1st day, 7th day). Conclusions: These findings suggest that myocardial OS induced by cardiac sympathetic hyperactivity may play a critical role in transient LV dysfunction in TC.

Antimalarial activity of artefenomel (OZ439), a novel synthetic antimalarial endoperoxide, in patients with Plasmodium falciparum and Plasmodium vivax malaria: an open-label phase 2 trial

SummaryBackgroundArtefenomel (OZ439) is a novel synthetic trioxolane with improved pharmacokinetic properties compared with other antimalarial drugs with the artemisinin pharmacophore. Artefenomel has been generally well tolerated in volunteers at doses up to 1600 mg and is being developed as a partner drug in an antimalarial combination treatment. We investigated the efficacy, tolerability, and pharmacokinetics of artefenomel at different doses in patients with Plasmodium falciparum or Plasmodium vivax malaria.MethodsThis phase 2a exploratory, open-label trial was done at the Hospital for Tropical Diseases, Bangkok, and the Shoklo Malaria Research Unit in Thailand. Adult patients with acute, uncomplicated P falciparum or P vivax malaria received artefenomel in a single oral dose (200 mg, 400 mg, 800 mg, or 1200 mg). The first cohort received 800 mg. Testing of a new dose of artefenomel in a patient cohort was decided on after safety and efficacy assessment of the preceding cohort. The primary endpoint was the natural log parasite reduction per 24 h. Definitive oral treatment was given at 36 h. This trial is registered with ClinicalTrials.gov, number NCT01213966.FindingsBetween Oct 24, 2010, and May 25, 2012, 82 patients were enrolled (20 in each of the 200 mg, 400 mg, and 800 mg cohorts, and 21 in the 1200 mg cohort). One patient withdrew consent (before the administration of artefenomel) but there were no further dropouts. The parasite reduction rates per 24 h ranged from 0·90 to 1·88 for P falciparum, and 2·09 to 2·53 for P vivax. All doses were equally effective in both P falciparum and P vivax malaria, with median parasite clearance half-lives of 4·1 h (range 1·3–6·7) to 5·6 h (2·0–8·5) for P falciparum and 2·3 h (1·2–3·9) to 3·2 h (0·9–15·0) for P vivax. Maximum plasma concentrations, dose-proportional to 800 mg, occurred at 4 h (median). The estimated elimination half-life was 46–62 h. No serious drug-related adverse effects were reported; other adverse effects were generally mild and reversible, with the highest number in the 1200 mg cohort (17 [81%] patients with at least one adverse event). The most frequently reported adverse effect was an asymptomatic increase in plasma creatine phosphokinase concentration (200 mg, n=5; 400 mg, n=3; 800 mg, n=1; 1200 mg, n=3).InterpretationArtefenomel is a new synthetic antimalarial peroxide with a good safety profile that clears parasitaemia rapidly in both P falciparum and P vivax malaria. Its long half-life suggests a possible use in a single-dose treatment in combination with other drugs.FundingBill & Melinda Gates Foundation, Wellcome Trust, and UK Department for International Development.