Creatine Phosphokinase Isoenzyme Research Articles

Arthrospira platensis Nanoparticles Mitigate Aging-Related Oxidative Injured Brain Induced by D-galactose inRats Through Antioxidants, Anti-Inflammatory, and MAPK Pathways.

Loss of normal function is an inevitable effect of aging. Several factors contribute to the aging process, including cellular senescence and oxidative stress. We investigate how Arthrospira platensis Nanoparticles (NSP) protect against aging injury induced by d-galactose (D-gal) in the rat. So, we subcutaneously (S/C) injected D-gal at 200 mg/kg BW to see if Arthrospira platensis Nanoparticles (NSP) might protect against the oxidative changes generated by D-gal. NSP (0.5 mg/kg body weight once daily by gastric gavage) was given to all groups apart from the control and D-gal groups. The d-gal + NSP group was supplemented with 200 mg of D-gal per kg BW once a day and NSP 0.5 mg/kg BW given orally for 45 days. Biochemical, mRNA expression, and histological investigations of brain tissues were used to evaluate the oxidative alterations caused by d-gal and the protective role of NSP. Our data demonstrated that d-gal was causing significant reductions in relativebrain and body weight with increased malondialdehyde (MDA) and redox oxygen species (ROS) levels and increases in serum creatine phosphokinase (CPK) and creatine phosphokinase isoenzyme BB (CPK-BB) with marked decreases in the level of antioxidant enzyme activity in the brain and acetylcholinesterase activity augmented with a phosphorylated H2A histone family member X (γ-H2AX) level increased. The D-gal group had considerably higher phosphorylated p38 mitogen-activated protein kinases (P38MAPK) and C-Jun N-terminal (JNK) kinases. The d-gal administration stimulates the apoptotic gene expression by downregulating the brain superoxide dismutase (SOD), catalase (CAT), and nuclear factor erythroid 2-related factor 2 (Nrf2). The NSP administration saved these parameters in the direction of the control. The brain histopathologic and immunohistochemistry analysis findings support our findings on NSP's protective role. The NSP may be a promising natural protective compound that can prevent aging and preserve health.

ECG and Biomarker Profile in Patients with Acute Heart Failure: A Pilot Study.

Biomarkers, electrocardiogram (ECG) and Holter ECG are basic, accessible and feasible cardiac investigations. The combination of their results may lead to a more complex predictive model that may improve the clinical approach in acute heart failure (AHF). The main objective was to investigate which ECG parameters are correlated with the usual cardiac biomarkers (prohormone N-terminal proBNP, high-sensitive cardiac troponin I) in patients with acute heart failure, in a population from Romania. The relationship between certain ECG parameters and cardiac biomarkers may support future research on their combined prognostic value. In this prospective case-control study were included 49 patients with acute heart failure and 31 participants in the control group. For all patients we measured levels of prohormone N-terminal proBNP (NT-proBNP), high-sensitive cardiac troponin I (hs-cTnI) and MB isoenzyme of creatine phosphokinase (CK-MB) and evaluated the 12-lead ECG and 24 h Holter monitoring. Complete clinical and paraclinical evaluation was performed. NT-proBNP level was significantly higher in patients with AHF (p < 0.001). In patients with AHF, NT-proBNP correlated with cQTi (p = 0.027), pathological Q wave (p = 0.029), complex premature ventricular contractions (PVCs) (p = 0.034) and ventricular tachycardia (p = 0.048). Hs-cTnI and CK-MB were correlated with ST-segment modification (p = 0.038; p = 0.018) and hs-cTnI alone with complex PVCs (p = 0.031). The statistical relationships found between cardiac biomarkers and ECG patterns support the added value of ECG in the diagnosis of AHF. We emphasize the importance of proper ECG analysis of more subtle parameters that can easily be missed. As a non-invasive technique, ECG can be used in the outpatient setting as a warning signal, announcing the acute decompensation of HF. In addition, the information provided by the ECG complements the biomarker results, supporting the diagnosis of AHF in cases of dyspnea of uncertain etiology. Further studies are needed to confirm long-term prognosis in a multi-marker approach.

Prevalence of Cardiovascular Dysfunction and its Association with Outcomes in Patients with Acute Pancreatitis

Background and Aim: Acute pancreatitis is a rapid progressive abdominal inflammatory disease with acute onset in clinics which turns into severe acute pancreatitis. In approximately 20% of patients characterized by different parameters such as gland flaky necrosis, multiple organ dysfunction syndrome (MODS), inflammatory cell infiltration in large number, and hemorrhage. Electrocardiography and electromyography variations are the common cardiac failure in patients with acute pancreatitis. Elevated cardiac enzymes could be other factors for cardiac failure with acute pancreatitis. The present study aimed to assess the prevalence of cardiovascular dysfunction and its association in patients with acute pancreatitis. Methodology: This cross-sectional study was carried out on 120 acute appendicitis patients in the department of Gastroenterology at Northwest General Hospital & Research Centre, Hayatabad Peshawar for the duration of six months from June 2021 to November 2021. All the patients who met the inclusion criteria were enrolled. Echocardiography and CK-MB (creatine phosphokinase isoenzyme) was measured for evaluating myocardial function after admission. All the patients underwent physical, clinical, and laboratory examination. The findings of Electrocardiography (ECG) were recorded. Acute appendicitis severity, duration of hospital stay, infection, computed tomography severity index (CTSI), and mortality were different outcomes. Results: Of the total 120 patients, about 83 (69.2%) were males and 37 (30.8%) were females. The overall mean age was 37.84±12.46 years. Out of 120 acute pancreatitis patients, the prevalence of gallstone disease, organic failure, respiratory failure, acute kidney failure, and cardiovascular dysfunction was 51 (43.3%), 47 (39.2%), 37 (30.8%), 19 (15.8%), and 9 (7.5%) respectively. Elevated CK-MB and ECG changes were seen in 32 (26.7%) and 42 (35%) respectively. The ECG variations and elevated CK-MB were related with severity of acute pancreatitis (p<0.05), duration of hospital (OR: 18.9 ± 10.6 vs. 11.7 ± 6.8, p = 0.005), CTSI (6.9 ± 3.1 vs. 4.7 ± 2.9, p = 0.001), increased necrosis (2.34, 95%CI= 0.3-11.8, p=0.011), and mortality (OR= 5.46, 95% CI= 1.2-34.9, p=0.05). The incidence of Left ventricular systolic dysfunction (LVEF) and left ventricular diastolic dysfunction (LVDD) was 15 (12.5%) and 31 (25.8%) respectively. Conclusion: The present study found that elevated CK-MB were significantly associated with higher CTSI, Prolonged hospital stay, severity of acute pancreatitis, LVDD, increased necrosis, and mortality. CK-MB increased levels have been reported as an indicator for cardiac failure and acute pancreatitis. There was a significant association between increased CK-MB levels and cardiovascular organ failure, pancreatic necrosis, and left ventricular diastolic dysfunction. Keywords: Cardiovascular dysfunction, Acute pancreatitis, Outcomes

7MO Oritinib (SH-1028) a third-generation EGFR tyrosine kinase inhibitor in locally advanced or metastatic NSCLC patients with positive EGFR T790M: Results of a single-arm phase II trial

Oritinib (SH-1028) is a third-generation EGFR-TKI selectively targeting both sensitive EGFR and EGFR T790M mutations. Herein, we report the efficacy and safety of oritinib in EGFR T790M-positive advanced NSCLC patients from the phase II study (NCT03823807). Eligible patients were locally advanced or metastatic NSCLC patients aged ≥ 18 years, with centrally confirmed EGFR T790M mutation. Patients with asymptomatic, stable CNS metastases were eligible into the study. Oritinib 200 mg was given orally once daily until disease progression or unacceptable toxicity. Primary efficacy endpoint was objective response rate (ORR). Secondary efficacy endpoints included disease control rate (DCR), progression-free survival (PFS), duration of response (DOR) and overall survival (OS). Between December 2019 and March 2021, 228 patients were enrolled and 227 patients received at least one dose of oritinib. The median age of 227 patients was 62 years old, 57.3% of patients were female and 24.7% received systemic chemotherapies. At data cutoff (September 17, 2021), 137 of 227 patients achieved confirmed partial responses with ORR of 60.4% (95% CI: 42.4%, 68.8%) by IRaC. The DCR was 92.5% (88.3%, 95.6%), the mPFS was 12.6 months (95% CI: 9.7, 15.3), the mDOR was 12.5 months (95% CI: 11.2, NA) and the mOS was immature. The most common (≥10%) treatment-emergent adverse events (TEAEs) included diarrhea (45.4%), increased blood creatine phosphokinase (26.0%), anaemia (20.3%), decreased white blood cell count (15.4%), decreased appetite (15.0%), increased blood creatine phosphokinase isoenzyme (13.2%), nausea (13.2%), vomiting (13.2%), increased serum creatine (12.8%), upper respiratory tract infection (12.3%), increased aspartate aminotransferase (11.9%), cough(11.9%), decreased platelet count (11.0%), constipation (10.6%). Grade≥3 TEAEs included increased blood creatine phosphokinase (4.0%), hypertension (3.1%), death (2.6%), diarrhea (2.2%). No interstitial lung disease were reported. Oritinib demonstrated potential clinical benefit and tolerable in advanced NSCLC patients with EGFR T790M mutation.

The disquietude of clozapine continuation during the COVID-19 pandemic.

The disquietude of clozapine continuation during the COVID-19 pandemic.

Obituary for Charles Rider Roe, MD

Early in his career at Duke University, Charlie pioneered the development and application of creatine phosphokinase isoenzymes and creatine kinase myocardial band analysis for cardiac injury. His interest in isoenzymes in Reye syndrome led him to sabbatical studies of organic acidurias at the Medical Research Council with Alec Lawson and Ron Chalmers. Upon returning to Duke, he created the Mass Spectrometry Facility with David Millington. This led to the discovery of propionylcarnitine in methylmalonic acidemia and propionic acidemia and many other disease-specific acylcarnitines. He also helped to pioneer the application of tandem mass spectrometry to newborn screening. He recruited other geneticists (Y-T Chen, SG Kahler) and genetic counselors, who together created a medical genetics training program. He collaborated with scientists and trainees from around the world. Work with Henri Brunengraber and others began the development of triheptanoin as a truly new therapy for long-chain fatty acid disorders. When he left Duke in 1995 to direct the Summers Metabolic Institute he concentrated on his work with triheptanoin, and expanded newborn screening. He was a member of numerous scientific societies and support organizations for fatty acid disorders and organic acidemias. He is survived by his wife Diane, five children from two marriages, and eight grandchildren.

Cardioprotective effects of alpha-mangostin on doxorubicin-induced cardiotoxicity in rats.

The main adverse effect of doxorubicin is cardiotoxicity. Oxidative stress and apoptosis induction have been suggested as mechanisms involved in its cardiotoxicity. In this study, cardioprotective effects of alpha-mangostin against doxorubicin-induced cardiotoxicity have been investigated in rats. Forty-two rats were divided as follows: Control, doxorubicin (2mg/kg every 48 hr), alpha-mangostin (200 mg/kg), alpha-mangostin (50, 100, 200 mg/kg) + doxorubicin (2mg/kg every 48 hr), and vitamin E (200 IU/kg) + doxorubicin (2mg/kg every 48 hr). Alpha-mangostin was administered by gavage for 19 days, while doxorubicin (12 days) and vitamin E (19 days) were injected intraperitoneally. Doxorubicin decreased heart rate, increased electrocardiogram signal components duration and reduced systolic and diastolic arterial blood pressure, and caused histological damage in the heart of rats. Doxorubicin decreased heart weight and heart/body weight ratio, as well as elevated creatine phosphokinase isoenzyme and lactate dehydrogenase. Doxorubicin increased malondialdehyde, inflammatory biomarkers, and caspases 3 and 9 and decreased reduced glutathione content in heart tissue but co-administration of alpha-mangostin (100 mg/kg) restored all doxorubicin toxic effects. Results show that alpha-mangostin has protective effects against doxorubicin-induced cardiotoxicity by antioxidant, antiinflammatory, and antiapoptotic effects that may ameliorate doxorubicin cardiotoxicity in human chemotherapy without reduction in its anticancer effect.

NRF2 Inhibits Cardiomyocyte Pyroptosis Via Regulating CTRP1 in Sepsis-Induced Myocardial Injury.

C1q/tumor necrosis factor-related protein 1 (CTRP1) has been demonstrated as a crucial regulator in myocardial injury (MI). The present study aims to evaluate the mechanism of CTRP1 in sepsis-induced MI. The septic mouse model was established via cecal ligation and puncture and the in vitro cell model was established via lipopolysaccharide treatment. The mouse survival rate within 96 h was recorded. Morphologic changes of cardiomyocytes were observed and cell viability and cardiac functions were detected. CTRP1 and nuclear factor erythroid 2-related factor (Nrf2) expressions, creatine troponin-T, and creatine phosphokinase isoenzyme levels, and expressions of pyroptotic markers were determined. The binding relationship between Nrf2 and the CTRP1 promotor was predicted and verified. Rescue experiments were designed to confirm the role of CTRP1. CTRP1 was poorly expressed in septic mice. CTRP1 overexpression inhibited cardiomyocyte pyroptosis and improved cardiac functions, MI, and survival rate in septic mice. Nrf2was decreased in cecal ligation and puncture -treated mice. Nrf2 overexpression promoted CTRP1 expression via binding to the CTRP1 promotor and suppressed cardiomyocyte pyroptosis. CTRP1 downregulation abolished the inhibitory effect of Nrf2 overexpression on cardiomyocyte pyroptosis. Overall, Nrf2 promoted CTRP1 expression via binding to the CTRP1 promotor to inhibit cardiomyocyte pyroptosis, thereby alleviating MI in septic mice.

SERUM CREATINE PHOSPHOKINASE ACTIVITY IN RABBIT DURING REGENERATION OF EXPERIMENTALLY DAMAGED MUSCLE TISSUE AND AFTER ITS STIMULATION BY TRANSPLANTED MSC

According to statistics, in modern veterinary practice, the percentage of muscle injuries among sport and working animals ranges from 40–70% of sports injuries. Quite often there are cases with muscle injuries of skeletal muscles, namely extremities. This scientific work describes the research methodology, stages of research step-by-step, and studies the relationship of dynamics of the activity of a single biochemical blood indicator. The essence of the method was to model the injury of muscle tissue performed by the skin and fascia dissection and cutting off in the area of midplane of the pelvic head of the biceps femoris muscle, measuring 1.5 x 1.5 cm to a depth of 1.5 cm of muscle tissue on 105 laboratory animals, divided into 4 groups with the use of various treatment methods. We analyze the results of one of the most effective biochemical methods for diagnosing muscle fiber of skeletal system damage and compare the activity of the enzyme creatine phosphokinase iso-enzyme depending on the stage of the study. Other research methods such as clinical, biochemical, ultrasonographic, histological research methods were recorded on 4, 7, 10, 14, 21, and 28 days. We analyzed the latest literature sources and concluded that on the 4th and 7th days, the level of creatine phosphokinase in the groups with intravenous administration, intramuscular administration of allogeneic mesenchymal stem cells is higher than the reference values but significantly lower compared to the control groups and the traditional method of treatment. But we observe a significant decrease in serum creatine phosphokinase levels in crawls on 10th day in the intravenous administration group compared to the control group of animals in 2 times, compared to traditional treatment in 1.6 times. The group of animals with intramuscular administration has reference values on the 14th day, compared with the control in 1.3 times lower, traditional treatment in 1.2 times. And on 21th day, we get reference values for a group of animals with traditional treatment. The level of creatine phosphokinase activity decreases in the control group of animals on 28th day of the research, which indicates a complete muscle rupture. The results of studies showed that the highest activity of the creatine phosphokinase enzyme during the study was shown by groups of animals with control and traditional treatment, which indicated significant structural, functional and destructive disorders of the muscle fibers of skeletal tissues with severe trauma. Thus, it is noted that the activity of the enzyme in conditions of damage of skeletal muscle tends to increase in accordance with the severity of the injury.

Ameliorative impact of taurine on oxidative damage induced by Ipomoea carnea toxicity in wistar male rats through modulation of oxidative stress markers, apoptotic and Nrf2 pathway

ObjectivesThe adverse deleterious influences of Ipomoea carnea on brain tissue and Taurine's relative ability to prevent this neurotoxicity have been examined. MethodsWe utilized sixty Wistar male rats weighing 1752 g. The rats were allotted into 4 groups of fifteen each: The control group got saline i.p. daily for eight weeks; the Ipomoea carnea extract (ICE) group received ICE (15 mg/kg b.w./day) orally for eight weeks. Taurine-treated rats, in which rats were administered Taurine (200 mg·kg−1, i.p./Day) for 2 months. Taurine + ICE group in which rats were supplemented with (200 mg·kg−1, i.p. Taurine + ICE 15 mg/kg b.w./day orally) for 2 months. ResultThe findings indicated that Ipomoea persuaded an increase in lipid peroxidation markers as well as a disruption in antioxidant homeostasis, along with brain and serum cholinesterase (AChE) elevated levels, tumor necrosis factor (TNF), total creatine phosphokinase (CPK), creatine phosphokinase isoenzymes BB (CPK-BB), and lactate dehydrogenase (LDH). A considerable drop (P < 0.05) in the brain superoxide dismutase (SOD), catalase (CAT), and GSH in Ipomoea carnea. SOD, CAT, and GSH levels were enhanced in the Taurine co-treated group but did not achieve control levels. Ipomoea Furthermore, Induced apoptosis in brain tissue by Ipomoea carnea reflected in pro-apoptotic Bax, P53, and caspase 3 overexpression., while taurine upregulated the anti-apoptotic Bcl2 in addition to Histopathologic, electron microscope, and immunohistological brain examination finding support our finding concerning the protective role of taurine. ConclusionOur study proved the protective role of taurine as a supplement could recover Ipomoea carnea -induced oxidative changes and brain damage.

Sulfonylureas Use Is Not Associated With Increased Infarct Size in Patients With Type 2 Diabetes and ST-Segment Elevation Myocardial Infarction.

Aims: This retrospective study assessed the association between sulfonylureas use and infarct size in patients with type 2 diabetes (T2DM) and ST-segment elevation myocardial infarction (STEMI) by myocardial enzymology indexes and cardiac magnetic resonance (CMR) imaging.Methods: Patients presenting STEMI between July 2013 and August 2019 were included in a retrospective database at our institution. Antidiabetic agents used before STEMI were recorded. Patients with maximum recorded troponin I (max cTNI) and creatine phosphokinase isoenzyme (CK-MB) within the first 72 h of chest pain onset were selected. Infarct size was quantified by CMR imaging, and cardiovascular outcomes were also obtained at 30 days and 6 months follow-up. Multivariable regression models explored potential risk factors associated with infarct size and clinical outcomes.Results: A total of 254 T2DM and STEMI patients were included, with 101 sulfonylurea users and 153 non-users. Sulfonylureas users were not associated with higher max cTnI and max CK-MB compared to non-users. Among 65 CMR patients, no significant differences in infarct size were detected between sulfonylureas users and non-users. Whereas, the incidence of microvascular obstruction (MVO) was higher in patients receiving sulfonylureas than those taking non-sulfonylureas (88.0 vs. 62.5%, p = 0.023). No higher cardiovascular events of sulfonylureas users vs. non-users were observed, except for heart failure events (24.0 vs. 2.5% at 30 days, p = 0.011; 28.0 vs. 2.5% at 6 months, p = 0.004). Multivariable regression analyses verified that sulfonylureas users increased the risks of MVO.Conclusions: Sulfonylureas use did not associate with larger infarct size in patients with T2DM and STEMI. A potentially higher incidence of MVO in sulfonylurea users was found. Notably, since most patients presented after a relatively long period of ischemia and glibenclamide was not used by the included patients in this observational study, the results of this study should not be extrapolated to clinical settings with short periods of ischemia or to patients using glibenclamide.

Mogroside IIe Ameliorates Cardiomyopathy by Suppressing Cardiomyocyte Apoptosis in a Type 2 Diabetic Model.

Mogroside IIe is primarily present in the unripe fruit of Siraitia grosvenorii (Swingle) C. Jeffrey, and it is the predominant saponin component. The purpose of this study was to investigate the effects of mogroside IIe (MGE IIe) on myocardial cell apoptosis in diabetic cardiomyopathy (DCM) rats by establishing a high-sugar and high-fat diet–induced model of type 2 diabetes (T2D) in SD rats and a homocysteine (Hcy)-induced apoptotic model in rat H9c2 cardiomyocytes. The results showed that MGE IIe decreased the levels of fasting blood glucose (FBG), total cholesterol (TC), triglyceride (TG), and low-density lipoprotein (LDL) levels, but increased the levels of high-density lipoprotein (HDL) in the SD rat model. Furthermore, MGE IIe decreased the levels of lactate dehydrogenase 2 (LDH2), creatine phosphokinase isoenzyme (CKMB), and creatine kinase (CK), and improved heart function. Additionally, MGE IIe inhibited the secretion of interleukin-1 (IL-1), IL-6, and tumor necrosis factor-α (TNF-α), improved myocardial morphology, and reduced myocardial apoptosis in the SD rat model. Furthermore, MGE IIe inhibited the mRNA and protein expression of active-caspase-3, -8, -9, -12, and Bax and Cyt-C, and promoted the mRNA and protein expression of Bcl-2 in the SD rat model. Furthermore, MGE IIe suppressed homocysteine-induced apoptosis of H9c2 cells by inhibiting the activity of caspases-3, -8, -9, and -12. In conclusion, MGE IIe inhibits the apoptotic pathway, thereby relieving DCM in vivo and in vitro.

Malignant hyperthermia when dantrolene is not readily available

BackgroundMalignant hyperthermia is a rare but life-threatening pharmacogenetic muscle disorder characterized by abnormal hypermetabolic reactions and commonly triggered in susceptible individuals by volatile anesthetics or succinylcholine, or both. Unfortunately, the specific medicine dantrolene is not readily available in many countries including China. The aim of this study was to find the characteristics of malignant hyperthermia under the situation that dantrolene is not readily available.MethodsThe cases of malignant hyperthermia reported on the most commonly used databases in China from 1985 to 2020 were analyzed. The inclusion criteria were the MH episodes only related to anesthesia. The exclusion criteria were dubious MH episodes only caused by Ketamine administration or MH episodes irrelevant to anesthesia. Independent samples t-test and Pearson’s chi-squared test were applied to assess the difference between the survived and death cases.ResultsNinety-two cases of malignant hyperthermia reported on the most commonly used databases in China from 1985 to 2020 were analyzed. Median (IQR [range]) age was 18.5 (11.8–37.0 [0–70.0]) years. Compared with the survived cases, the death cases had higher maximum end-tidal partial pressure of CO2 (P = 0.033), the maximum arterial partial pressure of CO2 (P = 0.006), temperature first measured when the patient was first discovered abnormal (P = 0.012), and maximum temperature (P < 0.001). Besides, the death cases had less minimum pH (P < 0.001) and higher potassium (P < 0.001) and were more likely to have coagulation disorders (p = 0.018). Concerning treatment, cases used furosemide (P = 0.024), mannitol (P = 0.029), blood purification treatment (P = 0.017) had the advantage on the outcome. Creatine phosphokinase, myoglobin, and MB isoenzyme of creatine phosphokinase differed greatly among cases during the first week. 43 (46.7%) cases had congenital diseases. 12 (13.0%) cases were reported with abnormal laboratory test results or abnormal signs that are possibly relevant before anesthesia.ConclusionsIn countries that dantrolene is not readily available, early warning, diagnosis, and prompt effective therapies are crucial for MH patients to survive.

Subacute toxicity of vatsanabha (aconitum ferox, ranunculaceae) collected from different regions of India and Nepal

Introduction: Aconitum ferox wall is considered as one of the most poisonous plants in the world and well known for its toxicity. The Vatsanabha (Sanskrit terminology) is mentioned as Mahavisha (most toxic) in Ayurveda literature. The aim of our study was to evaluate and compare the toxic effects of a root of Vatsanabha (A. ferox) aqueous extract on hematological, cardiac, and serum biochemical parameters and histopathological changes in the heart. Methods: A. ferox crude powder was prepared from tuber root collected from three geographical location: Naradevi root, Sikkim root and Dolpa root and dosed in three groups Naradevi root dosing Group (NRG), Sikkim root dosing group, and Dolpa root dosing group (DRG), respectively. They were orally administered on Wistar albino rat for 28 consecutive days at doses of 1/5th of the respective median lethal dose of dried crude powder per kg body weight in 20 ml of stock solution. Results: The results showed significant changes in serum glutamic-pyruvic transaminase, alkaline phosphatase, high-density lipoprotein in NRG, and serum glutamic-oxaloacetic transaminase, cardiac parameters-creatinine kinase MB, lactate dehydrogenase in DRG. Marked pathological changes were perceived in the brain, heart, lungs, and jejunum tissue. Conclusion: The marketed sample shows multiple visceral toxicity and higher altitude sample has greater toxicity on brain and cardiac tissue. This study recommends creatine phosphokinase (CPK) isoenzyme testing: CPK-BB, CPK-MB, etc., on the heart and brain to assess the exact source of the damaged tissue.

Effects and mechanisms of glucose-insulin-potassium on post-procedural myocardial injury after percutaneous coronary intervention.

ObjectiveTo evaluate the effects and mechanisms of glucose-insulin-potassium (GIK) on post-procedural myocardial injury (PMI) after percutaneous coronary intervention (PCI).MethodsA total of 200 non-diabetic patients with documented coronary heart disease (CHD) were divided into the Group GIK and Group G, with 100 patients in each group. Patients in Group G were given intravenous infusion of glucose solution 2 hours before PCI. As compared, patients in Group GIK were given GIK.ResultsBoth post-procedural creatine phosphokinase isoenzyme MB (CK-MB; 62.1 ± 47.8 vs. 48.8 ± 52.6 U/L, P = 0.007) and cTnI (0.68 ± 0.83 vs. 0.19 ± 0.24 ng/mL, P < 0.001) in Group GIK were significantly higher than those in Group G. In Group G, 9.0% and 4.0% of patients had post-procedural increases in CK-MB 1-3 times and > 3 times, which were significantly lower than those in Group GIK (14.0% and 7.0%, respectively; all P values < 0.01); 13.0% and 7.0% of patients had post-procedural increases in cTnI 1-3 times and > 3 times, which were also significantly lower than those in Group GIK (21.0% and 13.0%, respectively; all P < 0.001). Pre-procedural (10.2 ± 4.5 vs. 5.1 ± 6.3, P < 0.001) and post-procedural rapid blood glucose (RBG) levels (8.9 ± 3.9 vs. 5.3 ± 5.6, P < 0.001) in Group G were higher than those in Group GIK. In adjusted logistic models, usage of GIK (compared with glucose solution) remained significantly and independently associated with higher risk of post-procedural increases in both CK-MB and cTnI levels > 3 times. Furthermore, pre-procedural RBG levels < 5.0mmol/L were significantly associated with higher risk of post-procedural increases in both CK-MB and cTnI levels.ConclusionsIn non-diabetic patients with CHD, the administration of GIK may increase the risk of PMI due to hypoglycemia induced by GIK.

25‑OH‑PPD inhibits hypertrophy on diabetic cardiomyopathy via the PI3k/Akt/GSK‑3β signaling pathway

The present study investigated the inhibitory effects and the associated mechanism of the compound 25-OH-PPD (PPD) on cardiac hypertrophy, fibrosis and inflammation. The signaling pathways associated with diabetic mellitus cardiomyopathy (DMCM) were investigated using a rat model. DMCM Sprague-Dawley rats were induced by injection of streptozotocin. The animals were divided into 5 groups as follows: Normal group (NG group), diabetic group, PPD treatment group, PPD/LY294002 group (inhibitor of PI3K/Akt) and PPD/LiCl group [inhibitor of glycogen synthase kinase (GSK) 3β]. The studies were carried out during the 12 weeks following induction of diabetes and the levels of plasma brain natriuretic peptide (BNP), creatine phosphokinase isoenzyme (CK-MB) were measured. In addition, the volume of myocardial collagen fraction (CVF) was tested. The expression levels of the inflammatory cytokines, including transforming growth factor beta 1 (TGF-β1), connective tissue growth factor (CTGF), cell adhesion molecules α-smooth muscle actin (α-SMA) and vascular adhesion molecule 1 (VCAM-1) and associated signaling proteins (Akt, GSK-3β) were measured by biochemical analyses. The levels of BNP and CK-MB, the volume of CVF, the expression levels of TGF-β1, CTGF, α-SMA and VCAM-1 in the diabetic group were higher compared with those of the normal control group (P<0.05). Conversely, the levels of these molecules were significantly decreased in the PPD treatment groups (P<0.05). The aforementioned effects were partially eliminated in the PPD/LY294002 and PPD/LiCl groups. In addition, PPD treatment significantly increased the expression levels of p-Akt and decreased the levels of phosphorylated GSK-3β compared with those of the DMCM group (P<0.05). The data demonstrated that the protective effects of 25-OH-PPD against DMCM may be attributed to the PI3k/Akt/GSK-3β signaling pathway, via the suppression of the α-SMA/VCAM axis and the downregulation of TGF-β1 and CTGF expression.

Prevalence of cardiovascular dysfunction and its association with outcome in patients with acute pancreatitis.

Organ failure (OF) is the most important predictor of outcome in severe acute pancreatitis (SAP). Cardiovascular failure (CVSF) occurs in a variable proportion of patients with SAP. We aimed to study myocardial dysfunction in acute pancreatitis (AP) and its impact on the outcome. In this prospective study between January 2011 and July 2012, consecutive eligible patients of AP were enrolled. Myocardial function was assessed by measuring CK-MB (creatine phosphokinase isoenzyme) and echocardiography at admission. Electrocardiography (ECG) findings at admission were noted. Patients were managed in a high dependency unit using a step-up approach and followed up during hospital stay for their outcome. The outcome variables were computed tomography severity index (CTSI), the severity of AP, infection, need for intervention, length of hospital stay, and mortality. Of the 65 patients (mean age 39.55 ± 13.14years; 67.7% males; etiology: alcohol 47.7%, gallstone disease 43.1%, and others 3%), 28 (43%) had organ failure. Respiratory failure was present in 21 (32.3%) patients, acute kidney injury (AKI) in 11 (16.9%) patients, and cardiovascular dysfunction was present in 4 (6.2%) patients. ECG changes were present in 26 (40%) patients with ST segment depression with T wave inversion being the most common (n = 22, 85%). Elevated CK-MB level (more than two times normal) was seen in 18 (27.7%) patients and was associated with increased necrosis (odds ratio = 2.44, 95% confidence interval = 0.5-12.3, p = 0.021), CTSI (7.7 ± 2.7 vs. 5.0 ± 3.0, p = 0.002), severity of AP (p = 0.05), CVSF (p = 0.005), hospital stay (19.3 ± 12.3 vs. 12.3 ± 7.0, p = 0.006), and mortality (odds ratio = 6.42, 95% confidence interval = 1.0-38.9, p = 0.045). Left ventricular systolic dysfunction (left ventricular ejection fraction [LVEF] < 55%) was seen in 9 (13.8%) patients, all of whom had mild systolic dysfunction and left ventricular diastolic dysfunction (LVDD) was seen in 17 (26.2%) patients. There was no association between poor LVEF or LVDD and necrosis, severity of AP, infection, need for intervention, duration of hospital stay, and mortality. Elevated CK-MB levels were associated with increased necrosis, higher CTSI, the severity of AP, cardiovascular failure, prolonged hospital stay, LVDD, and mortality. Echocardiographic findings namely left ventricular systolic and diastolic dysfunctions were not associated with severity or outcome of AP.

Лабораторные критерии мониторинга патологического процесса у больных с хроническим остеомиелитом голени на этапах восстановительного лечения

Purpose Search for laboratory criteria of pathological process monitoring in patients with chronic osteomyelitis of the tibia at the stages of its management using the method of transosseous distraction osteosynthesis. Materials and methods Biochemical parameters of blood serum were studied in 15 patients with chronic posttraumatic osteomyelitis of the tibia. Sequester necrectomy with subsequent osteosynthesis of the tibia with the Ilizarov apparatus was performed in all patients at the first stage. At the second stage, the defect was filled in with distraction regenerate according to Ilizarov. Depending on the bone defect size, the patients were divided into two groups. The defect size was from 3 to 5 cm in patients of the first group (n = 7, mean age 42.4 ± 6.9 years). In the patients of the second group (n = 8, mean age 37.5 ± 7.8 years) the size of the defect was from 7 to 12 cm. Results It was found that the changes in the activity of the bone isoenzyme of acid phosphatase (TRAP), alkaline phosphatase, creatine phosphokinase, lactate and C-reactive protein (CRP) did not differ significantly between the groups during their treatment. At the same time, the concentration of CRP, sialic acids and the activity of TRAP in the first stage perids of treatment was significantly increased in patients of both groups relative to the reference norm. In patients of the second group, the concentration of sialic acids was higher than the values of group 1 and the reference group in the periods of 7-21 days of fixation. Nevertheless, at the beginning of the second stage of treatment (distraction), the level of all the studied parameters was not significantly different from the norm. Conclusion Normalization of TRAP activity, concentration of CRP and sialic acids values can be attributed to additional diagnostic features on the basis of which it is possible to start the second stage of treatment (distraction) in patients with chronic osteomyelitis of the tibia.

Microscope-assisted anterior cervical discectomy and fusion combined with posterior minimally invasive surgery through tubular retractors for multisegmental cervical spondylotic myelopathy: A retrospective study.

This study aimed to investigate the clinical efficacy and outcome of combined microscope-assisted anterior cervical discectomy and fusion (ACDF) with posterior minimally invasive surgery through tubular retractors for patients with multisegmental cervical spondylotic myelopathy (MCSM).This retrospective study included 28 patients (19 males and 9 females) with multisegmental cervical spondylotic myelopathy, who underwent combined microscope-assisted ACDF with posterior minimally invasive surgery through tubular retractors in our single center between January 2012 and December 2016. The evaluated postoperative clinical outcomes were operation time, length of hospitalization, blood loss, levels of creatine phosphokinase isoenzyme MM (CPK-MM), Japanese Orthopedic Association (JOA) scores, visual analogue scale (VAS) scores, Cobb angle of C2–C7, and radiological assessments (included X-rays, computed tomography scans, and magnetic resonanceimaging images).The mean surgery time was 198.42 ± 17.53 minutes, the average hospitalization length of hospital was 7.59 ± 1.38 days, and the mean follow-up time was 13 ± 2.45 months. On average, about 36.42 ± 10.15 mL of blood was lost and CPK-MM increased to 331.75 ± 23.15 IU/mL postoperatively (P < .001). The mean modified JOA scores increased from 8.21 ± 0.69 preoperatively to 13.96 ± 1.57 postoperatively (P < .001), whereas the mean VAS scores decreased from 6.64 ± 1.28 preoperatively to 0.39 ± 0.50 postoperatively (P < .001). Cobb angle of C2–C7 increased from 13.86° ± 5.69° preoperatively to 14.10° ± 5.56° postoperatively (P = .16).In conclusion, combined microscope-assisted ACDF with posterior minimally invasive surgery through tubular retractors appears to be a safe and effective treatment for patients with MCSM.

The protective effect of Luteolin on myocardial ischemia/reperfusion (I/R) injury through TLR4/NF-κB/NLRP3 inflammasome pathway.

The purpose of the present study was to investigate the effect of Luteolin(Lut) on myocardial ischemia reperfusion injury and explore the underlying mechanism. Myocardial ischemia reperfusion injury (I/R) model was induced with 30min of left anterior descending (LAD) occlusion followed by 24h of reperfusion. In vivo, the rats were randomly divided into 5 groups: (1)Sham, (2)I/R, (3)I/R+Lut(40mg/kg), (4)I/R+Lut(80mg/kg) and (5)I/R+Lut(160mg/kg). In vitro, the H9c2 cells were assigned to five groups: (1)control, (2)hypoxia-reoxygenation(H/R), (3)H/R+Lut(5μM), (4)H/R+Lut(10μM) and (5)H/R+Lut(20μM). The H9c2 cells were stimulated with H/R protocol in the presence or absence of TAK-242, a TLR4 inhibitor. As a result, Lut ameliorated myocardial ischemia reperfusion injury and hypoxia-reoxygenation as evidenced by triphenyl tetrazolium chloride (TTC) staining and MTT assay, respectively. Lut was founded to decrease the levels of aspartate transaminase(AST), creatine phosphokinase-isoenzyme (CK-MB) and lactate dehydrogenase (LDH) in serum. Moreover, Lut could reduce the contents of interleukin-1β(IL-1β), interleukin-18 (IL-18) and tumor necrosis factor-α (TNF-α) in serum of rats and supernant of H9c2 cells. In addition, Lut remarkably downregulated the expressions of toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88) and nuclear factor kappa B (NF-κB). Lut also inhibited the upregulations of inflammasome components, such as NOD-like receptor 3(NLRP3), apoptosis-associated speck-like protein containing CARD(ASC) in I/R-induced rats and H/R-induced H9c2 cells. In conclusion, Lut exhibited strong favorable cardioprotective effect on myocardial I/R injury which might be related to the down-regulation of the TLR4-meidated NF-κB/NLRP3 inflammasome in vivo and in vitro.