Creatine Kinase Values Research Articles

Quantification of intramyocardial hemorrhage volume using magnetic resonance imaging with three-dimensional T1-weighted sequence in patients with ischemia-reperfusion injury: a semi-automated image processing technique.

Although intramyocardial hemorrhage (IMH) is a poor prognostic factor caused by ischemia reperfusion injury, little evidence is available regarding the association between IMH volume and biomarkers. In the present study, we measured IMH volume using three-dimensional (3D) T1-weighted magnetic resonance imaging (T1-MRI) and investigated its association with biomarkers. Moreover, the accuracy of semi-automatic measurement of IMH volume was validated. We retrospectively enrolled 33 consecutive patients (mean age 67 ± 11years) who underwent cardiac MRI after reperfusion therapy for acute myocardial infarction. IMH was observed in 4 patients (12.1%). Receiver operating characteristics (ROC) analysis of creatine kinase (CK) and CK-muscle/brain (CK-MB) tests for detecting IMH were performed. IMH volume measured using semi-automatic methods by a 2 standard deviation (SD) threshold was compared to manual measurements using the Spearman's correlation coefficient (ρ) and Bland-Altman analyses. ROC analysis revealed optimal cutoff values of CK: 2460IU/l and CK-MB: 231IU/l (area under the curve: 0.95 and 0.91; sensitivity: 86% and 79%; specificity: 100% for both). IMH volume with the 2SD threshold correlated with that of the manual measurement [5.84g (3.30 to 9.00)g vs. 8.07g (5.37 to 9.33); ρ: 0.85, p < 0.01; bias (limit of agreement): -0.01g (-0.51 to 0.49); intraclass correlation coefficients 0.84 (0.75 to 0.90)]. Our findings could help identify the risk of IMH after reperfusion therapy with biomarkers. 3D T1-MRI can semi-automatically provide accurate IMH volume without being time-consuming.

3. Dermatomyositis and underlying bilateral benign endometrioma

IntroductionThe link between ovarian malignancy and paraneoplastic dermatomyositis is well established. Association with underlying benign ovarian pathology is much less certain, with only scarce case report evidence available. This represents the first case of dermatomyositis with associated bilateral ovarian chocolate cysts.Case descriptionA 45-year-old female presented with classical features of dermatomyositis, with a background of hypertension and non-alcoholic fatty liver disease. She had proximal limb weakness, neck flexor weakness, dysphagia and dysphonia, accompanied by a scaly, erythematous rash over her face, chest, abdomen and lateral thighs. Serum creatine kinase (CK) at presentation was 4923 IU/L. An MRI scan of her thighs showed widespread muscle oedema affecting both legs and the pelvis, including the quadriceps, iliacus and psoas muscles. A punch biopsy of the skin on her thigh showed only post inflammatory pigmentation. Lung volumes were reduced (FEV1 69% predicted). Video fluoroscopy confirmed moderate-severe pharyngeal stage dysphagia. CT scan of the chest, abdomen and pelvis revealed enlarged, unilocular cysts in each ovary, the right cyst measuring 7 cm and the left, 5 cm in maximal diameter. Subsequent transvaginal ultrasound confirmed bilateral unilocular, thick walled cysts with a ground-glass appearance, which would be consistent with benign endometriomas. A further interval ultrasound after 1 month showed no change in their appearance or size. Serum CA125 was 104 kU/L.The patient was treated with 3 pulses of 1g intravenous (IV) methylprednisolone, followed by 2 courses of IV immunoglobulin 2g/kg over 5 days. This was followed by a gradually reducing course of oral prednisolone, starting at 50mg OD PO alongside 15mg weekly of oral methotrexate. She has responded well to treatment, with near normalisation of her objective manual muscle testing scores and normalisation of the serum CK value. Surgery is now planned for a total abdominal hysterectomy and bilateral oophorectomy.DiscussionExtensive investigation has not demonstrated any other underlying malignancy to account for the development of dermatomyositis. Initial limited and unsustained clinical response to IV methylprednisolone prompted further treatment with IV immunoglobulin. Surgical histology results are now awaited to confirm the suspected diagnosis. It will be very interesting to see if surgical removal of the cysts has any impact on the clinical manifestation of disease.Key learning pointsBenign ovarian pathology should not be dismissed as a potential underlying mechanism for development of dermatomyositis.Conflicts of interestThe authors have declared no conflicts of interest.

Efectos de dos protocolos de entrenamiento sobre el lactato sanguíneo en caballos de paso fino

Objetivo: Comparar los efectos de un protocolo de entrenamiento de resistencia (ER) con un protocolo tradicional (ET) sobre la concentración sanguínea de lactato y CK. Materiales y Métodos: Se aplicaron dos protocolos de entrenamiento durante 6 meses divididos en tres etapas. Se realizaron pruebas de esfuerzo antes de comenzar los protocolos de entrenamiento y al finalizar cada una de las etapas. En cada prueba se tomaron muestras de sangre venosa en reposo, durante el ejercicio y en recuperación para medir el lactato (L), y al inicio y al final para medir la creatin kinasa (CK) e inferir las adaptaciones metabólicas y musculares. Se calculó la diferencia de medianas del lactato basal por medio de la U Mann Whitney y se comparó la diferencia de medias del porcentaje de aclaramiento entre los grupos a través de la T de Students. Resultados: Se encontró una diferencia significativa en el porcentaje de depuración de lactato entre ER y ET. También hubo un aumento significativo de los valores de CK intra-grupos, antes y después de las pruebas, pero manteniéndose dentro de los rangos de referencia. Discusión: El ER aumentó la capacidad de metabolizar el lactato pos-ejercicio en potros con entrenamiento de resistencia, aunque no hubo diferencias entre la máxima producción de L entre el grupo ER y ET. El comportamiento de la CK dentro de los rangos de referencia indica que no hubo daño muscular en los potros de ambos grupos.

Association of SLCO1B1 and ABCB1 Genetic Variants with Atorvastatin-induced Myopathy in Patients with Acute Ischemic Stroke.

Certain patients experience muscle-related adverse effects after taking atorvastatin. Genetic factors play an important role in the occurrence of statin-induced myopathy. We aimed to identify genetic variants associated with statin-induced myotoxicity. We prospectively enrolled 1,102 acute ischemic stroke patients who underwent atorvastatin treatment for the first time after admission. Patients were separated into case and control groups after a follow-up of 3 months. We used a biochemical definition of myopathy consisting of serum creatine kinase values more than ten times the upper limit of normal for the reference laboratory (150 U/L). Fifty single nucleotide polymorphisms (SNPs) from seven genes of ABCB1, CoQ2, HTR3B, RYR2, CYP3A5, HTR7 and SLCO1B1 were selected and genotyped. The effects of genetic polymorphisms on myopathy were observed. 61 cases and 110 controls were recruited in the study. Compared with the controls, the cases had a significant higher mutant frequency of the allele A (ABCB1, rs2373588) (OR = 2.01, 95%CI = 1.10-3.67, P = 0.001) and a significant lower mutant frequency of the allele A (SLCO1B1, rs976754) (OR = 1.85, 95%CI = 1.12-3.03, P = 0.042). Genotypes or alleles of the other SNPs had no significant difference between the two groups (P > 0.05). Our findings reveal that SLCO1B1 and ABCB1 genetic variants are associated with statin-induced myopathy. These are valuable biomarkers for the evaluation of atorvastatin safety.

Biochemical Response Comparisons of a Competitive Microcycle Vs. Congested Fixture Periods in Elite Level European Champions League Soccer Players

The aim of this investigation was to analyses differences between post-game biochemical responses in congested (CP, when two consecutive games were played within 4 days or less) vs. non-congested (NCP, when two consecutive games were played within 5 days or more) periods. Assessment of creatine kinase (CK) and salivary cortisol (sCort) and immunoglobulin-A (sIgA) were performed across 12 separate training macrocycles of 14 competitive professional matches. The NCP analysis revealed significantly higher CK values from one day after match day (MD+1) than values found in MD and MD+2 (Effect size (ES): 0.82-1.13, p&lt;0.0033). The CP analysis revealed no significant changes in CK values between MD, MD+1 and MD+2. Higher values on MD+2 in CP vs. NCP were also revealed (ES:0.27, p&lt;0.05). No significant changes in sCort and sIgA were observed. Congested competitive periods induce significant biochemical changes revealed amongst elite soccer players that should influence their preparation and management

Defining Features of Patients who Develop Takotsubo Cardiomyopathy during Myasthenic Crisis: A Systematic Review of Case Studies.

Background.Myasthenic crisis can induce Takotsubo cardiomyopathy leading to transient systolic and diastolic left ventricular dysfunction and wall-motion abnormalities, including the characteristic apical ballooning. We aimed to define the clinical features of this disease entity.Methods.A systematic review was conducted to examine the characteristics of Takotsubo cardiomyopathy presenting in myasthenia gravis patients. Case reports were accessed by searching MEDLINE/PubMed, Google Scholar, CINAHL, and Web of Science databases. 523 articles were identified and 14 were selected for review.Results.Takotsubo cardiomyopathy presenting in myasthenia gravis’ patients tends to affect women between the ages of 40 to 77. History of atrial fibrillation or hypertension was found in a minority of cases. Generalized weakness, fatigue, dysphagia and respiratory distress were common at presentation. Vital signs demonstrated normal blood pressure without tachycardia or bradycardia. Elevated values of troponins, creatine kinase (CK), and CK-MB isoenzymes were recorded. ST-segment elevation followed by T-wave inversion were predominantly found on electrocardiograms. Apical abnormalities in the form of ballooning, hypokinesia, or sparing and reduced left ventricular ejection fraction (≤45%) were observed using transthoracic echocardiogram or left ventriculography. Coronary angiography demonstrated no obstructive lesions. Ventilatory support, cholinesterase inhibitors and glucocorticoids resulted in the recovery or improvement of the left ventricular ejection fraction and hemodynamic stability. Only a minority of patients died of refractory heart failure. Treatment with inotropes and/or vasopressors led to poorer outcomes, including death or intractable heart failure.Conclusion.The management of Takotsubo cardiomyopathy developing in myasthenia gravis patients should focus on addressing the myasthenic crisis, while proving supportive care in and intensive care setting.

Clinical long-time course, novel mutations and genotype-phenotype correlation in a cohort of 27 families with POMT1-related disorders

BackgroundThe protein O-mannosyltransferase 1, encoded by the POMT1 gene, is a key enzyme in the glycosylation of α-dystroglycan. POMT1–related disorders belong to the group of dystroglycanopathies characterized by a proximally pronounced muscular dystrophy with structural or functional involvement of the brain and/or the eyes. The phenotypic spectrum ranges from the severe Walker-Warburg syndrome (WWS) to milder forms of limb girdle muscular dystrophy (LGMD). The phenotypic severity of POMT1-related dystroglycanopathies depends on the residual enzyme activity. A genotype-phenotype correlation can be assumed.ResultsThe clinical, neuroradiological, and genetic findings of 35 patients with biallelic POMT1 mutations (15 WWS, 1 MEB (muscle-eye-brain disease), 19 LGMD) from 27 independent families are reported. The representative clinical course of an infant with WWS and the long-term course of a 32 years old patient with LGMD are described in more detail. Specific features of 15 patients with the homozygous founder mutation p.Ala200Pro are defined as a distinct and mildly affected LGMD subgroup. Ten previously reported and 8 novel POMT1 mutations were identified. Type and location of each of the POMT1 mutations are evaluated in detail and a list of all POMT1 mutations reported by now is provided. Patients with two mutations leading to premature protein termination had a WWS phenotype, while the presence of at least one missense mutation was associated with milder phenotypes. In the patient with MEB-like phenotype two missense mutations were observed within the catalytic active domain of the enzyme.ConclusionsOur large cohort confirms the importance of type and location of each POMT1 mutation for the individual clinical manifestation and thereby expands the knowledge on the genotype-phenotype correlation in POMT1-related dystroglycanopathies. This genotype-phenotype correlation is further supported by the observation of an intrafamiliar analogous clinical manifestation observed in all affected 13 siblings from 5 independent families. Our data confirm the progressive nature of the disease also in milder LGMD phenotypes, ultimately resulting in loss of ambulation at a variable age. Our data define two major clinical POMT1 phenotypes, which should prompt genetic testing including the POMT1 gene: patients with a severe WWS manifestation predominantly present with profound neonatal muscular hypotonia and a severe and progressive hydrocephalus with involvement of brainstem and/or cerebellum. The presence of an occipital encephalocele in a WWS patient might point to POMT1 as causative gene within the different genes associated with WWS. The milder LGMD phenotypes constantly show markedly elevated creatine kinase values in combination with microcephaly and cognitive impairment.

First record of Toxoplasma gondii antibodiesin Royal Bengal tigers (Panthera tigris tigris) and Asiatic lions (Panthera leo persica) in India.

The purpose of this study was to detect the antibodies against Toxoplasma gondii in Royal Bengal tigers (Panthera tigris tigris), Asiatic lions (Panthera leo persica), leopards (Panthera pardus), and elephants (Elephas maximus indicus) residing in the Mahendra Chaudhury Zoological Park, in Chhatbir, Punjab (India) during winter and monsoon seasons. Using indirect ELISA, 20 serum samples were analysed during the winter season. Results indicated that 1 lion (5%) tested seropositive, and 3 tigers and 1 lion (20%) were considered suspect. During the monsoon, 4 individuals (2 tigers and 2 lions, 20%) were seropositive, whereas only 1 tiger (5%) gave suspected results. Significantly higher globulin, creatinine, blood urea nitrogen, phosphorus, and creatine kinase values were recorded in seropositive and suspected groups. Levels of albumin, glucose, calcium, sodium, and iron decreased significantly in the seronegative group. Results from sero-testing 40 rodents trapped in and around the park depicted the presence of antibodies against Toxoplasma gondii in 1 individual. This study reveals the haemato-biochemical alterations in both seropositive and suspected wild felids for toxoplasmosis. Moreover, it provides the first serological evidence of T. gondii exposure in wild felids, notably Royal Bengal tigers and Asiatic lions, in India.

Relationship between Muscle Damage Magnitude and Sense of Knee Position

It has been proposed in the literature that muscle damage may temporarily and negatively affect proprioceptive capacity, which can be tested through the ability to replicate angles, while muscle damage can be verified by quantifying creatine kinase (CK) in the bloodstream. PURPOSE: to verify the relationship between muscle damage and sense of position in the isokinetic dynamometer, in knee extensors, after an eccentric exercise protocol. METHODS: ten male college students (age: 20.6 ± 1.8 years, body mass: 75.0 ± 11.7 kg, height: 177.4 ± 6.9 cm), with no prior experience with resistance exercises, were submitted to an eccentric exercise protocol, in the isokinetic dynamometer, for induction of muscle damage composed of two phases: 1st phase: 10 sets of 10 repetitions with 30 seconds of rest (100 eccentric contractions) - Speed ​​= 30 ° / s. There was a 5 minute break between the phases. 2nd phase: 11 sets of 10 repetitions and 30 seconds of rest (110 eccentric contractions) - Speed ​​= 180 ° / s. To evaluate the muscle damage was used the values of CK peak found in the post-tests shortly after exercise, 24h, 48h, 72h and 96h. To verify the sense of position, the subjects, blindfolded, should find the angle of 60° in the right knee on the isokinetic dynamometer. Was used a subtraction of the target value (60°) by the angle performed by the subjects on the day of CK peak. The normality of the sample data was verified using the Shapiro-wilk test and Pearson's correlation was applied between peak CK and significance level of 5%. RESULTS: There was a significant correlation (p = 0.014) between CK and knee position sense, with r = 0.742 classified as strong (Devore, 2006). CONCLUSIONS: the induction of muscle damage caused by eccentric exercise significantly influences the subjects' proprioception, since the higher the CK values, the greater the angular discrepancies between the expected value and the one performed by the subjects.

Moderate-intensity aerobic exercise improves physical fitness in bethlem myopathy.

Bethlem myopathy is caused by dysfunctional collagen VI assembly, leading to varying degrees of hyperlaxity, contractures and muscle weakness. Previous studies demonstrate that cardiovascular training is safe and beneficial in patients with myopathies. However, exercise exacerbates the dystrophic phenotype in collagen VI-knockout mice. Six men with Bethlem myopathy were included (4 training; 2 controls). After training, 2 patients detrained. Patients performed 10 weeks of home-based, moderate-intensity exercise monitored by a pulse-watch. The primary outcome was change in peak oxygen uptake (VO2peak ). Secondary outcomes were performances in functional tests. VO2peak improved in the training group (16%, P = 0.017). Detraining led to regression of VO2peak toward baseline values (-8%; P = 0.03). No change was seen in the control group (-7%; P = 0.47). Performance in functional tests did not change significantly. Creatine kinase values were stable during the study. Moderate-intensity exercise seems to safely improve oxidative function in patients with Bethlem myopathy. Muscle Nerve 60: 183-188, 2019.

Evidence of Clinical Pathology Abnormalities in People with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) from an Analytic Cross-Sectional Study.

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating disease presenting with extreme fatigue, post-exertional malaise, and other symptoms. In the absence of a diagnostic biomarker, ME/CFS is diagnosed clinically, although laboratory tests are routinely used to exclude alternative diagnoses. In this analytical cross-sectional study, we aimed to explore potential haematological and biochemical markers for ME/CFS, and disease severity. We reviewed laboratory test results from 272 people with ME/CFS and 136 healthy controls participating in the UK ME/CFS Biobank (UKMEB). After corrections for multiple comparisons, most results were within the normal range, but people with severe ME/CFS presented with lower median values (p < 0.001) of serum creatine kinase (CK; median = 54 U/L), compared to healthy controls (HCs; median = 101.5 U/L) and non-severe ME/CFS (median = 84 U/L). The differences in CK concentrations persisted after adjusting for sex, age, body mass index, muscle mass, disease duration, and activity levels (odds ratio (OR) for being a severe case = 0.05 (95% confidence interval (CI) = 0.02–0.15) compared to controls, and OR = 0.16 (95% CI = 0.07–0.40), compared to mild cases). This is the first report that serum CK concentrations are markedly reduced in severe ME/CFS, and these results suggest that serum CK merits further investigation as a biomarker for severe ME/CFS.

Localized rest and stress human cardiac creatine kinase reaction kinetics at 3T.

Changes in the kinetics of the creatine kinase (CK) shuttle are sensitive markers of cardiac energetics but are typically measured at rest and in the prone position. This study aims to measure CK kinetics during pharmacological stress at 3 T, with measurement in the supine position. A shorter “stressed saturation transfer” (StreST) extension to the triple repetition time saturation transfer (TRiST) method is proposed. We assess scanning in a supine position and validate the MR measurement against biopsy assay of CK activity. We report normal ranges of stress CK forward rate (kf CK) for healthy volunteers and obese patients.TRiST measures kf CK in 40 min at 3 T. StreST extends the previously developed TRiST to also make a further kf CK measurement during <20 min of dobutamine stress. We test our TRiST implementation in skeletal muscle and myocardium in both prone and supine positions. We evaluate StreST in the myocardium of six healthy volunteers and 34 obese subjects. We validated MR‐measured kf CK against biopsy assays of CK activity.TRiST kf CK values matched literature values in skeletal muscle (kf CK = 0.25 ± 0.03 s−1 vs 0.27 ± 0.03 s−1) and myocardium when measured in the prone position (0.32 ± 0.15 s−1), but a significant difference was found for TRiST kf CK measured supine (0.24 ± 0.12 s−1). This difference was because of different respiratory‐ and cardiac‐motion‐induced B0 changes in the two positions. Using supine TRiST, cardiac kf CK values for normal‐weight subjects were 0.15 ± 0.09 s−1 at rest and 0.17 ± 0.15 s−1 during stress. For obese subjects, kf CK was 0.16 ± 0.07 s−1 at rest and 0.17 ± 0.10 s−1 during stress. Rest myocardial kf CK and CK activity from LV biopsies of the same subjects correlated (R = 0.43, p = 0.03).We present an independent implementation of TRiST on the Siemens platform using a commercially available coil. Our extended StreST protocol enables cardiac kf CK to be measured during dobutamine‐induced stress in the supine position.

Changes in biochemical parameters in horses during 40 km and 80 km endurance races

Abstract During intensive physical activity horses are exposed to thermolysis, electrolyte loss and rising amounts of catabolic products, which results in alterations of biochemical blood parameters due to the horse’s adaptation to metabolic stress. The aim of the present study was to determine the effect of intensive physical activity on serum biochemical parameters in horses competing in 40 and 80 km endurance races. Blood samples were taken from 28 horses before and after the race over four competitions, with a total of 53 samples analyzed. Biochemical parameters studied included creatine kinase, lactate dehydrogenase, aspartate aminotransferase, urea, creatinine, gamma-glutamyl transferase, glucose, triglycerides, cholesterol, sodium, potassium, calcium and magnesium. The extent of change in pre- and post-race values was compared between categories of age, gender, breed, distance and average speed of horses. Creatine kinase and blood glucose values prior to the race were higher than the reference values. Values of renal parameters and parameters of muscle damage increased after the races, and the degree of change was more pronounced at longer racing lengths, as well as at lower average speed. Electrolyte loss was more prominent during longer races. This study demonstrated that endurance races cause evident changes in serum electrolyte concentrations, renal parameters and markers of muscle damage in horses. These changes are observable in horses at both short and long duration endurance races.

Calcified Plaques in Patients With Acute Coronary Syndromes

ObjectivesThis study conducted detailed analysis of calcified culprit plaques in patients with acute coronary syndromes (ACS). BackgroundCalcified plaques as an underlying pathology in patients with ACS have not been systematically studied. MethodsFrom 1,241 patients presenting with ACS who had undergone pre-intervention optical coherence tomography imaging, 157 (12.7%) patients were found to have a calcified plaque at the culprit lesion. Calcified plaque was defined as a plaque with superficial calcification at the culprit site without evidence of ruptured lipid plaque. ResultsThree distinct types were identified: eruptive calcified nodules, superficial calcific sheet, and calcified protrusion (prevalence of 25.5%, 67.4%, and 7.1%, respectively). Eruptive calcified nodules were frequently located in the right coronary arteries (44.4%), whereas superficial calcific sheet was most frequently found in the left anterior descending coronary arteries (68.4%) (p = 0.012). Calcification index (mean calcification arc × calcification length) was greatest in eruptive calcified nodules, followed by superficial calcific sheet, and smallest in calcified protrusion (median 3,284.9 [interquartile range (IQR): 2,113.3 to 5,385.3] vs. 1,644.3 [IQR: 1,012.4 to 3,058.7] vs. 472.5 [IQR: 176.7 to 865.2]; p < 0.001). The superficial calcific sheet group had the highest peak post-intervention creatine kinase values among the groups (eruptive calcified nodules vs. superficial calcific sheet vs. calcified protrusion: 241 [IQR: 116 to 612] IU/l vs. 834 [IQR: 141 to 3,394] IU/l vs. 745 [IQR: 69 to 1,984] IU/l; p = 0.032). ConclusionsThree distinct types of calcified culprit plaques are identified in patients with ACS. Superficial calcific sheet, which is frequently located in the left anterior descending coronary artery, is the most prevalent type and is also associated with greatest post-intervention myocardial damage. (Identification of Predictors for Coronary Plaque Erosion in Patients With Acute Coronary Syndrome; NCT03479723)

Selection of modeling time for type 2 diabetes mellitus mouse

To analyze the changes of blood biochemical index and the pathological changes of myocardium and kidney in type 2 diabetic mouse at different time points, which can provide the basis for the selection of type 2 diabetic modeling time for later research. After 6 weeks of feeding with high-fat diet, 24 healthy male ICR mice were injected with streptozocin (STZ, 30 mg/kg) intraperitoneally for 5 days to establish diabetic models. After 9 days, a random blood glucose ≥ 11.1 mmol / L was measured as diabetic mice. 4, 6 and 8 weeks after successfully preparing the diabetic mouse, 8 diabetic mice (a group)would be sacrificed each time. Then the biochemical and pathological conditions were analyzed: ① the indexes of heart and kidney were calculated. ②the serum levels of creatine kinase (CK), lactate dehydrogenase (LDH), creatinine (Cr) and blood urine nitrogen (BUN) were determined. ③ Histopathological changes of myocardium and renal tissues were observed by hematoxylin and eosin (HE) staining. Masson staining was used to observe the fibrosis of myocardium. PAS staining was adopted to observe the pathological changes of renal tissue. In addition, 8 ICR male mice were taken as the control group. At the 4th, 6th and 8th week, cardiac organ coefficient, the values of LDH and CK were all increased compared with the control group. Cardiomyocyte hypertrophy and myocardial fibrosis could be observed. Renal organ coefficient, the values of Cr and BUN were increased. Glomerular hypertrophy, basement membrane thickening and atrophy could be perceived. At the 6th week, related biochemical and pathological changes in diabetic mice were comparatively obvious and breeding time was relatively short. Thus, 6 weeks after the preparation of the diabetic mice would be the optimal time for type 2 diabetes mellitus modeling, proper for inventions of drugs and other research purposes including pathology, physiology, biochemistry, etc.

Haematological and biochemical alterations in native sheep experimentally infected with bluetongue virus serotype-2

The study was designed to determine the haematological and biochemical alterations in sero-negative native sheep following the experimental bluetongue virus serotype-2 (BTV-2) infection. The BTV infected group comprised 14 sheep inoculated with 6 ml of clarified virus containing 1×106/ml TCID50 of BTV-2 by intradermal route. The uninfected control group comprised 6 animals inoculated with 6 ml of cell culture medium without virus by intradermal route. The blood and serum samples were analyzed at 0, 1, 2, 3, 7, 11, 14, 21 and 45 days post-infection (dpi). Significant changes were observed in all the haematological and biochemical parameters studied. Marked leucopenia was observed from 2 to 7 dpi in BTV infected group. Significant leucocytosis was documented during 11 to 14 dpi in infected group. Significant thrombocytopenia was observed during 2 to 14 dpi whereas significantly low packed cell volume (PCV) and haemoglobin (Hb) values were observed between 3 and 21 dpi in BTV infected group. Differential leucocyte count revealed significantly low lymphocyte percentage on day 3 and high on day 11 in infected group. The various biochemical enzymes like alanine aminotransferase (ALT) showed significantlyhigh values during 3 to 21 dpi, aspartate aminotransferase (AST) during 3 to 21 dpi, alkaline phosphatise (ALP) during 3 to 11 dpi and creatine kinase (CK) during 7 to 14 dpi in BTV infected group. The result of our study demonstrated significantly decreased levels of total leucocyte count, total platelet count, haemoglobin and PCV values while significantly increased levels of ALT, AST, ALP and CK values in BTV infected group. On histopathological examination, spleen and lymph nodes showed depletion of lymphoid cells, liver and kidney showed degeneration, congestion and haemorrhage at many places. The BTV nucleic acid was detected from blood and tissues by RT-PCR. These findings indicated the damage to various soft tissue organs and muscles as a sequel to vascular endothelial damages caused by BTV.

Routinely Available Biomarkers as Long-Term Predictors of Developing Systolic Dysfunction in Completely Revascularized Patients with Acute ST Elevation Myocardial Infarction

SUMMARYThe aim of this study was to assess the efficacy of high-sensitivity C-reactive protein (hsCRP), cardiac troponin T (cTnT) and creatine kinase (CK) as long-term predictors of reduced systolic function in patients with acute ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI) with complete revascularization. This prospective study evaluated consecutive patients with acute STEMI who had normal left ventricular ejection fraction (LVEF ≥50%) at admission with single-vessel disease and underwent complete revascularization. Blood samples were collected from admission to day 7. The primary endpoint was reduction of LVEF <50% after 12 months. The study included 47 patients, median age 59±10 years, 74.5% of them men. Patients who developed systolic dysfunction (LVEF <50%) had significantly higher mean values of cTnT after 24 hours (5.11 vs. 2.82 µg/L, p=0.010) and peak values of CK (3375.5 vs. 1865 U/L, p=0.008). There was no significant relation between hsCRP and development of reduced LVEF (p=0.541). In conclusion, cTnT and CK could serve as long-term predictors of reduced left ventricular systolic function (<50%) in acute STEMI patients with normal systolic function at admission, single-vessel coronary disease and complete revascularization during primary PCI.

Predictive value of plasma and peritoneal creatine kinase in horses with strangulating intestinal lesions.

To determine the ability of plasma and peritoneal creatine kinase (CK) to predict the presence of a strangulating lesion in horses presented for colic. Prospective clinical study. Ten healthy control horses and 61 clinical colic cases. Creatine kinase activity was measured in peritoneal fluid and plasma of 10 healthy horses and 61 horses presenting for colic (40 horses with nonstrangulating lesions and 21 horses with strangulating lesions). Information on other blood and peritoneal fluid variables, signalment, results from the physical examination, outcome, requirement for surgery, and lesion location and type were retrieved from the medical records of horses presenting for colic. A peritoneal CK cutoff level of 16 IU/L yielded a sensitivity of 95.2% and a specificity of 84.6% (positive predictive value [PPV] = 76.9% and negative predictive value [NPV] = 97%, respectively) for predicting a strangulating lesion. A peritoneal lactate cutoff level of 3.75 mmol/L yielded a sensitivity of 81% and a specificity of 92% (PPV = 85% and NPV = 90%, respectively) for predicting a strangulating lesion. Peritoneal CK concentration was a sensitive indicator of the presence of a strangulating lesion in horses presenting with colic, whereas peritoneal lactate concentration was a more specific indicator. Measuring CK in peritoneal fluid may be a useful adjunct to clinical case presentation to accelerate the diagnosis and definitive treatment of horses presenting with strangulating intestinal lesions, thereby improving their outcome.

Statin-associated immune-mediated necrotizing myopathy: a retrospective analysis of individual case safety reports from VigiBase.

Statins represent an effective treatment for hyperlipidaemia. Immune-mediated necrotising myopathy (IMNM), a form of statin myopathy, has recently been described, and is characterized by elevated creatine kinase, presence of antibodies against HMG-CoA and no improvement after drug discontinuation, even with immunosuppressive treatment. Information on IMNM is mainly from case reports and small case series. Therefore, all reported cases of IMNM in VigiBase, the WHO global database of individual case safety reports (ICSRs) including the underlying reporting patterns, were analysed to characterize more detailed this adverse drug reaction. ICSRs of IMNM up to October 1, 2016 were extracted from VigiBase. Corresponding case narratives were requested from responsible national authorities to maximize the available data. The reports were analysed in terms of reporting criteria, co-reported terms, patient demographics, clinical data, administered medication, latency time, seriousness of the reaction and outcome. One hundred one deduplicated ICSRs of IMNM were reported from 17 countriesuntil October 2016. Approximately two thirds of the cases were from the year 2016. Slightly more males than females were affected (52 [57%] males vs 39 [42%] females). Median reported patient age was 68years (range 16 - 87years). Ninety-one cases (99%) were classified as serious. Median latency time was 26months (range 1 - 288months). Median creatine kinase value was 6860U/L (range 576 - 35,000U/L). In total, eight patients (9%) had recovered from IMNM. Atorvastatin was the most frequently reported statin in 80% of cases. The number of IMNM reports has increased in recent years. IMNM associated with statin treatment seems to occur worldwide. Most IMNM cases were reported with atorvastatin. No dose dependency of statin-associated IMNM pathogenesis was identified.

Efficacy of Multi-exon Skipping Treatment in Duchenne Muscular Dystrophy Dog Model Neonates

Duchenne muscular dystrophy (DMD) is caused by mutations in DMD, which codes for dystrophin. Because the progressive and irreversible degeneration of muscle occurs from childhood, earlier therapy is required to prevent dystrophic progression. Exon skipping by antisense oligonucleotides called phosphorodiamidate morpholino oligomers (PMOs), which restores the DMD reading frame and dystrophin expression, is a promising candidate for use in neonatal patients, yet the potential remains unclear. Here, we investigate the systemic efficacy and safety of early exon skipping in dystrophic dog neonates. Intravenous treatment of canine X-linked muscular dystrophy in Japan dogs with a 4-PMO cocktail resulted in ∼3%-27% in-frame exon 6-9 skipping and dystrophin restoration across skeletal muscles up to 14% of healthy levels. Histopathology was ameliorated with the reduction of fibrosis and/or necrosis area and centrally nucleated fibers, significantly in the diaphragm. Treatment induced cardiac multi-exon skipping, though dystrophin rescue was not detected. Functionally, treatment led to significant improvement in the standing test. Toxicity was not observed from blood tests. This is the first study to demonstrate successful multi-exon skipping treatment and significant functional improvement in dystrophic dogs. Early treatment was most beneficial for respiratory muscles, with implications for addressing pulmonary malfunction in patients.