Assessment of serum CK-MM level as a bioindicator for work-related musculoskeletal injuries among Emergency hospital workers.

Musculoskeletal disorders (MSDs) are considered a growing problem among healthcare personnel, especially service workers. The emergency room (ER) service workers are highly exposed to work-related risk factors which predispose them to MSDs. A cross-sectional study was performed on 78 ER workers. Full medical and occupational histories were taken. The Standardized Nordic Questionnaire (SNQ) was used for the assessment of musculoskeletal symptoms. Clinical examination was done with special emphasis on the locomotors system, and serum levels of muscle enzymes, including creatine kinase (CK) and creatine kinase isoenzyme (CK-MM), were measured. The study aims to detect the prevalence of occupational musculoskeletal disorders (MSDs) among ER workers at University hospitals, and assessment of CK-MM as a biomarker used in the early detection of MSDs. We found that 71.8% of the participants were complaining of musculoskeletal disorder in the last 7 days before the study, while only 34.6% were complaining of musculoskeletal disorder in the last 12 months before the study. The knee joint was the most commonly affected site in the past 7 days, by 39.7%. On the other hand, the highest prevalent disorder in the last 12 months was for the ankle joint (17.9%) with significantly high levels of serum CK-MM. In conclusion, musculoskeletal injuries are a common complaint among healthcare occupations, especially among ER service workers that need regular health education and ergonomic training programs. Monitoring of serum CK-MM level with cut-off value 90 ng\ml could be used as a novel approach for the early detection of work-related musculoskeletal disorders.

Sex Differences in Neuromuscular Fatigue and Changes in Cost of Running after Mountain Trail Races of Various Distances.

INTRODUCTION: Women have been shown to experience less neuromuscular fatigue than men in knee extensors (KE) and less peripheral fatigue in plantar flexors (PF) after ultratrail running, but it is unknown if these differences exist for shorter trail running races and whether this may impact running economy. The purpose of this study was to characterize sex differences in fatigability over a range of running distances and to examine possible differences in the postrace alteration of the cost of running (Cr). METHODS: Eighteen pairs of men and women were matched by performance after completing different races ranging from 40 to 171 km, divided into SHORT versus LONG races (<60 and >100 km, respectively). Neuromuscular function and Cr were tested before and after each race. Neuromuscular function was evaluated on both KE and PF with voluntary and evoked contractions using electrical nerve (KE and PF) and transcranial magnetic (KE) stimulation. Oxygen uptake, respiratory exchange ratio, and ventilation were measured on a treadmill and used to calculate Cr. RESULTS: Compared with men, women displayed a smaller decrease in maximal strength in KE (-36% vs -27%, respectively, P < 0.01), independent of race distance. In SHORT only, women displayed less peripheral fatigue in PF compared with men (Δ peak twitch: -10% vs -24%, respectively, P < 0.05). Cr increased similarly in men and women. CONCLUSIONS: Women experience less neuromuscular fatigue than men after both "classic" and "extreme" prolonged running exercises but this does not impact the degradation of the energy Cr.

Electroconvulsive therapy use in the adult U.S. correctional setting: A case report and literature review.

Mr. C is a 45-year-old male inmate who was found in his cell unresponsive and mute. He had poor food and fluid intake for the last four days and was later found standing in place, frozen, and resistant to movement when encouraged by a corrections officer to rest in his bed. His symptoms were consistent with catatonia, a severe motor syndrome that can be life-threatening. The patient had a psychiatric history of bipolar I disorder with multiple past episodes of catatonia. Lorazepam was ineffective at reversing his catatonic symptoms, and his serum creatinine kinase level eventually began to rise, suggestive of muscle breakdown and worsening severity. The treating psychiatrist wanted access to electroconvulsive therapy (ECT) to treat Mr. C's catatonia but encountered numerous legal and logistical barriers which made this treatment option unavailable. The article reviews the scant literature on ECT use in the adult U.S. correctional system, identifies barriers, and discusses a recommended ECT referral process for inmates.

Decreased running economy is not associated with decreased force production capacity following downhill running in untrained, young men.

The present study investigated the relationships between changes in running economy (RE) and indirect muscle damage markers following downhill running (DHR) to test the hypothesis that decreased RE after DHR would be associated with decreases in muscle function. Forty-five young men ran downhill (-15%) for 30 min at the velocity corresponding to 70% of their peak oxygen uptake (VO2peak). Oxygen uptake (VO2) and other parameters possibly associated with RE (blood lactate concentration, perceived exertion, stride length and frequency) were measured during 5-minute level running at the velocity corresponding to 80%VO2peak before, immediately after and 1-3 days after DHR. Knee extensor maximal voluntary contraction torque (MVC), rate of torque development, vertical jump performance, muscle soreness and serum creatine kinase activity were assessed at the same time points. The values of the dependent variables were compared among time points by one-way ANOVAs followed by Bonferroni post-hoc tests when appropriate. Pearson's correlation tests were used to examine relationships between changes in VO2 (RE parameter) and changes in muscle damage parameters. VO2 during the level run increased (p < 0.05) immediately after DHR (18.3 ± 4.6%) and sustained until 2 days post-DHR (11.7 ± 4.2%). MVC decreased (p < 0.05) immediately (-21.8 ± 6.1%) to 3 days (-13.6 ± 5.9%) post-DHR, and muscle soreness developed 1-3 days post-DHR. The magnitude of changes in VO2 did not significantly (p < 0.05) correlate with the changes in muscle damage makers (r = -0.02-0.13) nor stride length (r = -0.05) and frequency (r = -0.05). The absence of correlation between the changes in VO2 and MVC suggests that strength loss was not a key factor affecting RE.

Assessment of muscle fiber adaptation in footballers using a new ELISA assay of myosin isoforms.

BACKGROUND: To measure the impact of training models on injury incidence, data of health and performance were integrated to study fiber adaptation during a competitive season. We studied football players over a season, analyzing hours of exposure to sport by serum changes in fast and slow myosin, creatine kinase and lactate dehydrogenase. METHODS: A new assay was developed to measure the myosin isoforms in 49 non-sporting volunteers and in 27 professional football players. RESULTS: Myosin isoforms in volunteers with mean ages of 30±8 were 1553 µg/L fast and 1284 µg/L slow; in the group with of 56±7 were 1426 µg/L fast and 1046 µg/L slow. Slow myosin was significantly lower in older subjects (-18%). Samples from the players in preseason had lower mean scores for fast myosin (1123 µg/L) and higher for slow myosin (2072 µg/L) than reference volunteers. During the season, myosins reached the maximum with the maximum load (1537 µg/L fast, 2195 µg/L slow but decreased and adapted to the high level of demand (425 µg/L fast, 1342 µg/L slow). CK and LDH were maximal at the pre-season (227 U/L, 333 U/L) while myosin levels were maximal at the beginning of season (1537 µg/L, 2195 µg/L). CONCLUSIONS: Measuring serum myosin isoforms we identify the type and amount of damage caused by training and matches, making it a new control tool capable of advising training towards a minimum of blood slow myosin but controlling the fast fiber participating and be able to improve the performance of the players.

Routine creatine kinase testing does not provide clinical utility in the emergency department for diagnosis of acute coronary syndromes.

BACKGROUND: Despite the high sensitivity and negative predictive value of contemporary high-sensitivity troponin T assays (hsTnT), creatine kinase (CK) continues to be routinely tested for the diagnosis of acute coronary syndrome (ACS). We conducted a study to identify the clinical utility of routine CK measurement, its relevance in clinical decision making in the era of hsTnT, and the potential cost-savings achievable by limiting its use. METHODS: We conducted a retrospective review of all adult patients presenting to a tertiary care center in the year 2017. We identified patients presenting with cardiac complaints who had non-diagnostic hsTnT and positive CK. These patients underwent chart review to determine whether a diagnosis of AMI was made. RESULTS: A total of 36,251 presentations were reviewed. 9951 had cardiac complaints and 8150 had CK measured. 82% of these patients had hsTnT and CK measured; 2012 of these patients had non-diagnostic hsTnT with positive CK. Of these 2012 patients, only 1 was subsequently diagnosed with AMI (0.012%). CK provided no diagnostic benefit over hsTnT alone in > 99.9% of cases. With a cost for CK of $4/test, we estimated that routine CK testing costs at least $32,000 per year in our center, and over $100,000 per year across the region. CONCLUSION: Routine CK testing does not provide a significant benefit to patient care and therefore represents an unnecessary system cost. Routine CK testing for the diagnosis of AMI should be eliminated from emergency departments in the era of hsTnT assays.

Assessment of plasma creatine kinase as biomarker for levodopa-induced dyskinesia in Parkinson's disease.

We tested in a translational approach the usefulness of plasma creatine kinase (CK) as an objective biomarker for levodopa-induced dyskinesia (LID). Plasma CK levels were measured in five dyskinetic parkinsonian non-human primates (NHP) and in ten PD patients with LID who participated in a treatment trial with simvastatin. Plasma CK levels were increased in dyskinetic NHP and correlated with LID severity while they were not affected by LID severity in PD patients.

Thermoregulation and markers of muscle breakdown in malignant hyperthermia susceptible volunteers during an acute heat tolerance test.

OBJECTIVES: The study was undertaken to compare the thermal and biochemical responses to a heat tolerance test (HTT) of malignant hyperthermia (MH) susceptible individuals, volunteers who have suffered heat illness (HI) and control volunteers. METHODS: Three groups of male volunteers (n=6 in each group) were recruited to the study: MHS - civilian volunteers previously diagnosed as MH susceptible; EHI - military volunteers with a history of exertional HI; CON - military volunteers with no history of HI or MH. For the HTT, volunteers walked on a treadmill at 60% maximal oxygen uptake in a hot environment. Measurements were made of core and skin temperatures, heat flow, whole body sweat rate and serum lactate, creatine kinase and myoglobin concentrations. RESULTS: There were no differences in deep body temperature, oxygen uptake or serum lactate and creatine kinase concentrations between the three groups. One MHS volunteer and two EHI volunteers failed to achieve thermal balance with rectal temperature continuing to rise throughout the test and reaching 39.5°C, the rectal temperatures of the other volunteers plateaued at a mean (SD) of 38.7 (0.4)°C demonstrating thermal tolerance on this test. Serum myoglobin concentration and the increase in serum myoglobin was higher in MHS than EHI and CON Post HHT (P<0.05). CONCLUSION: MH susceptibility does not always predispose an individual to heat intolerance during an acute HTT, but does appear to increase muscle breakdown. The inclusion of serum myoglobin measurements to a HTT may help to distinguish patients that are potentially MHS, and who otherwise demonstrate thermal tolerance.

Isometric pre-conditioning blunts exercise-induced muscle damage but does not attenuate changes in running economy following downhill running.

Running economy (RE) is impaired following unaccustomed eccentric-biased exercises that induce muscle damage. It is also known that muscle damage is reduced when maximal voluntary isometric contractions (MVIC) are performed at a long muscle length 2-4 days prior to maximal eccentric exercise with the same muscle, a phenomenon that can be described as isometric pre-conditioning (IPC). We tested the hypothesis that IPC could attenuate muscle damage and changes in RE following downhill running. Thirty untrained men were randomly assigned into experimental or control groups and ran downhill on a treadmill (-15%) for 30 min. Participants in the experimental group completed 10 MVIC in a leg press machine two days prior to downhill running, while participants in the control group did not perform IPC. The magnitude of changes in muscle soreness determined 48 h after downhill running was greater for the control group (122 ±â€¯28 mm) than for the experimental group (92 ±â€¯38 mm). Isometric peak torque recovered faster in the experimental group compared with the control group (3 days vs. no full recovery, respectively). No significant effect of IPC was found for countermovement jump height, serum creatine kinase activity or any parameters associated with RE. These results supported the hypothesis that IPC attenuates changes in markers of muscle damage. The hypothesis that IPC attenuates changes in RE was not supported by our data. It appears that the mechanisms involved in changes in markers of muscle damage and parameters associated with RE following downhill running are not completely shared.

Malignant Hyperthermia Susceptibility and Fitness for Duty.

INTRODUCTION: Malignant hyperthermia (MH) is an inherited hypermetabolic condition characterized by uncontrolled calcium release from the sarcoplasmic reticulum of skeletal muscle, usually from exposure to inhaled general anesthetics and/or the depolarizing neuromuscular blocking agent succinylcholine. Multiple case reports now reveal that crises may be precipitated by environmental factors such as exercise or high ambient temperatures. Common signs of an MH crisis include life-threatening hyperthermia, metabolic acidosis, muscle rigidity, and tachycardia. Treatment consists of stopping triggering agents, administering dantrolene, and actively cooling the patient. MH is a medically disqualifying condition for service in the U.S. Armed Forces. However, patients with MH-causative mutations may never have experienced an MH episode. If they previously have had an event concerning for MH, details are often sparse and a formal evaluation is absent. MATERIALS AND METHODS: We present 2 case reports with military service implications, one as a formal applicant to the service academies and the other as the father of an active duty Navy chief. Both patients experienced prior MH-like reactions to anesthesia but had not undergone testing with a caffeine-halothane contracture test (CHCT) or genetic analysis. Both patients underwent skeletal muscle biopsies of the left vastus lateralis with nontriggering anesthetics at Children's National Medical Center in Washington, DC, and MH diagnostic CHCT at the Uniformed Services University of the Health Sciences (USUHS) in Bethesda, Maryland. The CHCT was performed according to the North American MH Registry Protocol. With USUHS Institutional Review Board approval, ryanodine receptor type 1 gene (RYR1) and L-type calcium channel α-1 subunit gene (CACNA1S) sequencing was performed on the remaining muscle at USUHS. RESULTS: Each subject was CHCT positive, confirming a diagnosis of MH. One was found to have a known MH-causative gene mutation. The applicant to the service academy was therefore determined unfit for military service. The active duty son of the MH-positive patient underwent muscle biopsy and CHCT in order to continue his military career. CONCLUSION: A personal or familial history concerning for MH raises important questions on fitness for duty in the U.S. Armed Forces. Department of Defense regulation uniformly defines MH as a disqualifying condition; however, screening for a history of anesthetic complications during accession into the military is inconsistent. Medical standards across the services are also variable in the context of a familial history of MH. These case reports highlight the need for clinicians to seek expert consultation about how to proceed with MH-related issues. They also stress the importance of applying current understanding of heritable conditions to our fitness for duty determinations. Further investigation is also recommended to establish an MH-susceptible individual's propensity for exercise or heat-related injury outside the operating room. Department of Defense policy may thereafter be updated to reflect a quantitative assessment of MH's relative risk during inherently strenuous military operations.

Measuring recovery: An adapted Brief Assessment of Mood (BAM+) compared to biochemical and power output alterations.

OBJECTIVES: Biochemical (e.g. creatine kinase (CK)) and neuromuscular (e.g. peak power output (PPO)) markers of recovery are expensive and require specialist equipment. Perceptual measures are an effective alternative, yet most validated scales are too long for daily use. DESIGN: This study utilises a longitudinal multi-level design to test an adapted Brief Assessment of Mood (BAM+), with four extra items and a 100mm visual analogue scale to measure recovery. METHODS: Elite under-21 academy soccer players (N=11) were monitored across five games with data (BAM+, CK and PPO) collected for each game at 24h pre, 24h and 48h post-match. Match activity data for each participant was also collected using GPS monitors on players. RESULTS: BAM+, CK and PPO had significant (p<.05) linear and quadratic growth curves across time and games that matched the known time reports of fatigue and recovery. Multi-level linear modelling (MLM) with random intercepts for 'participant' and 'game' indicated only CK significantly contributed to the variance of BAM+ scores (p<.05). Significant correlations (p<.01) were found between changes in BAM+ scores from baseline at 24 and 48h post-match for total distance covered per minute, high intensity distance covered per minute, and total number of sprints per minute. CONCLUSIONS: Visual and inferential results indicate that the BAM+ appears effective for monitoring longitudinal recovery cycles in elite level athletes. Future research is needed to confirm both the scales reliability and validity.

Assessment of Fatigue and Recovery in Male and Female Athletes After 6 Days of Intensified Strength Training.

Raeder, C, Wiewelhove, T, Simola, RÁDP, Kellmann, M, Meyer, T, Pfeiffer, M, and Ferrauti, A. Assessment of fatigue and recovery in male and female athletes after 6 days of intensified strength training. J Strength Cond Res 30(12): 3412-3427, 2016-This study aimed to analyze changes of neuromuscular, physiological, and perceptual markers for routine assessment of fatigue and recovery in high-resistance strength training. Fourteen male and 9 female athletes participated in a 6-day intensified strength training microcycle (STM) designed to purposefully overreach. Maximal dynamic strength (estimated 1 repetition maximum [1RMest]; criterion measure of fatigue and recovery); maximal voluntary isometric strength (MVIC); countermovement jump (CMJ) height; multiple rebound jump (MRJ) height; jump efficiency (reactive strength index, RSI); muscle contractile properties using tensiomyography including muscle displacement (Dm), delay time (Td), contraction time (Tc), and contraction velocity (V90); serum concentration of creatine kinase (CK); perceived muscle soreness (delayed-onset muscle soreness, DOMS) and perceived recovery (physical performance capability, PPC); and stress (MS) were measured before and after the STM and after 3 days of recovery. After completing the STM, there were significant (p ≤ 0.05) performance decreases in 1RMest (%[INCREMENT] ± 90% confidence limits, ES = effect size; -7.5 ± 3.5, ES = -0.21), MVIC (-8.2 ± 4.9, ES = -0.24), CMJ (-6.4 ± 2.1, ES = -0.34), MRJ (-10.5 ± 3.3, ES = -0.66), and RSI (-11.2 ± 3.8, ES = -0.73), as well as significantly reduced muscle contractile properties (Dm, -14.5 ± 5.3, ES = -0.60; V90, -15.5 ± 4.9, ES = -0.62). After days of recovery, a significant return to baseline values could be observed in 1RMest (4.3 ± 2.8, ES = 0.12), CMJ (5.2 ± 2.2, ES = 0.28), and MRJ (4.9 ± 3.8, ES = 0.32), whereas RSI (-7.9 ± 4.5, ES = -0.50), Dm (-14.7 ± 4.8, ES = -0.61), and V90 (-15.3 ± 4.7, ES = -0.66) remained significantly reduced. The STM also induced significant changes of large practical relevance in CK, DOMS, PPC, and MS before to after training and after the recovery period. The markers Td and Tc remained unaffected throughout the STM. Moreover, the accuracy of selected markers for assessment of fatigue and recovery in relation to 1RMest derived from a contingency table was inadequate. Correlational analyses also revealed no significant relationships between changes in 1RMest and all analyzed markers. In conclusion, mean changes of performance markers and CK, DOMS, PPC, and MS may be attributed to STM-induced fatigue and subsequent recovery. However, given the insufficient accuracy of markers for differentiation between fatigue and recovery, their potential applicability needs to be confirmed at the individual level.

Evaluation of Daptomycin Exposure and Efficacy and Safety Endpoints To Support Risk-versus-Benefit Considerations.

The choice of an antimicrobial agent must balance optimization of efficacy endpoints with the minimization of safety events. The risk versus benefit of daptomycin for patients with Staphylococcus aureus bacteremia with or without infective endocarditis receiving daptomycin at 6, 8, and 10 mg/kg of body weight/day was assessed. The relationships between the area under the concentration-time curve over 24 h (AUC)/MIC ratio and both clinical response and time to decreased susceptibility were evaluated using data from patients with such infections who received daptomycin at 6 mg/kg/day. Using these relationships, plus the previously identified relationship between the minimum concentration and an elevation in the creatine phosphokinase (CPK) concentration (CPK elevation) (S. M. Bhavnani, C. M. Rubino, P. G. Ambrose, and G. L. Drusano, Clin Infect Dis 50:1568-1574, 2010) and Monte Carlo simulation, the probability of each outcome by MIC for daptomycin at 6, 8, and 10 mg/kg/day was calculated. The function for exposure-response relationships for clinical response (P = 0.06) and time to decreased susceptibility (P = 0.01) resembled U and inverted U shapes, respectively. Multivariable analyses demonstrated AUC/MIC ratio, creatinine clearance, albumin concentration, and disease category to be predictors of clinical response. The results of simulations failed to demonstrate large improvements in the probabilities of clinical success among cohorts of simulated patients defined by the above-described predictive factors or the probability of decreased susceptibility at 30 days when the daptomycin dose was increased from 6 to 10 mg/kg/day. The probability of CPK elevation increased from 0.073 to 0.156 over this dose range. These data can be used to inform risk-versus-benefit decisions for daptomycin dose selection in patients with S. aureus bacteremia with or without infective endocarditis. The risk of CPK elevation, which is reversible, should be weighed in the context of the mortality and severe morbidity associated with these types of serious staphylococcal infections.

Effect of Muscle-Damaging Eccentric Exercise on Running Kinematics and Economy for Running at Different Intensities.

The objective of this study was to explore the changes in running kinematics and economy during running at different intensities 1 and 24 hours after a muscle-damaging bench-stepping exercise. Healthy, physically active adult women were recruited for this study. The subjects' running kinematics, heart rate, gas exchange, minute ventilation, and perceived exertion were continuously recorded during the increasing-intensity running test on a treadmill for different testing conditions: a control condition and 1 and 24 hours after the bench-stepping exercise test. Two muscle damage markers, muscle soreness and blood creatine kinase (CK) activity, were measured before and 24 hours after the stepping exercise. Muscle soreness and blood CK activity were significantly altered (exact p ≤ 0.05, Monte Carlo test) 24 hours after the bench-stepping exercise. The stride length, stride frequency, and support time at different running intensities did not change. Twenty-four hours after the previous step exercise, ankle dorsiflexion in the support phase was significantly higher during severe-intensity running, the range of knee flexion at the stance phase was significantly lower during moderate-intensity running, and knee flexion at the end of the amortization phase was significantly lower during heavy-intensity running compared with the control values (exact p ≤ 0.05, Monte Carlo test). The running economy at moderate and heavy intensities, maximum ventilation, and maximum heart rate did not change. We conclude that, given moderate soreness in the calf muscles 24 hours after eccentric exercise, the running kinematics are slightly but significantly changed without a detectable effect on running economy.

A case report comparing clinical, imaging and neuropsychological assessment findings in twins discordant for the VCP p.R155C mutation.

Inclusion body myopathy, Paget disease of bone and/or frontotemporal dementia is an autosomal dominant disease caused by mutations in the Valosin Containing Protein (VCP) gene. We compared clinical findings including MRI images and neuropsychological assessment data in affected and unaffected twin brothers aged 56 years from a family with the p.R155C VCP gene mutation. The affected twin presented with a 10 year history of progressive proximal muscle weakness, difficulty swallowing, gastroesophageal reflux, fecal incontinence, and peripheral neuropathy. Comprehensive neuropsychological testing revealed rapid cognitive decline in the absence of any behavioral changes in a span of 1 year. This case illustrates that frontotemporal dementia related cognitive impairment may precede behavioral changes in VCP disease as compared with predominance of behavioral impairment reported in previous studies. Our findings suggest that there is a need to establish VCP disease specific tools and normative rates of decline to detect pre-clinical cognitive impairment among affected individuals.

Clinical and financial impact of removing creatine kinase-MB from the routine testing menu in the emergency setting.

CONTEXT: Cardiac troponins T and I have replaced creatine kinase-MB (CK-MB) as the criterion standard for diagnosing myocardial injury. However, many laboratories still routinely perform a high volume of CK-MB testing in conjunction with troponin. PURPOSE: The purpose of this study is to study the clinical and financial impact of removing CK-MB from the routine emergency department (ED) test menu at a large academic medical center. METHODS: Creatine kinase-MB was removed from ED ordering templates and laboratory requisitions (ie, intervention), although the test could still be manually ordered. Data for creatine kinase (CK), CK-MB, and troponin T (TnT) specimens ordered during a 12-month period (6 months preintervention and 6 months postintervention) (n = 14571) was downloaded from our laboratory information system. All specimens with (1) normal TnT (ie, <0.01 ng/mL), (2) elevated CK-MB (ie, >6.6 ng/mL), and (3) elevated CK-MB index (ie, >5) were considered discrepant and independently reviewed by 2 ED clinicians for the presence of an acute coronary syndrome and for documentation of final diagnosis. Creatine kinase, CK-MB, and TnT ED volumes preintervention and postintervention were analyzed to assess laboratory cost savings. RESULTS: Of the 6444 cases included in the analysis, only 17 were discrepant. Of all 17 cases, no patients were diagnosed with acute coronary syndrome. After removing CK-MB from the templates and requisitions, CK-MB and CK volumes decreased by 80% and 76%, respectively, translating to annual reagent cost savings of approximately $47000. CONCLUSIONS: Creatine kinase-MB can be removed from the routine ED test menu without adversely affecting patient care. In addition, substantial cost savings can be achieved by reducing unnecessary CK-MB testing and associated CK orders.

Assessment of the prophylactic role of aspirin and/or clopidogrel on experimentally induced acute myocardial infarction in hypercholesterolemic rats.

INTRODUCTION: Hyperlipidemia is a risk factor for cardiovascular diseases such as acute infarction. Inflammation and platelet activation are critical phenomena in acute myocardial infarction (AMI). AIM: The aim of the study was to assess potential protective effects of aspirin and/or clopidogrel on AMI in hypercholesterolemic rats. METHODS: Forty adult male Wistar rats were divided into five groups (eight rats in each). Group I included normal healthy rats. The other 32 rats were subjected to induction of hypercholesterolemia by high-fat diet for 3 weeks, followed by induction of AMI by subcutaneous injections of isoproterenol (85 mg/kg/day, for 2 days). Rats were divided into the following groups: group II, rats with induced hypercholesterolemia and AMI; group III, hypercholesterolemic rats that received aspirin 30 mg/kg/day orally for 7 days before induction of AMI; group IV, hypercholesterolemic rats that received clopidogrel 10 mg/kg/day orally for 7 days before induction of AMI; and group V, hypercholesterolemic rats treated with both aspirin and clopidogrel in the same doses for 7 days before induction of AMI. Serum levels of pentraxin 3 (PTX3), transforming growth factor-ß1 (TGF-ß1), creatine kinase (CK), lactate dehydrogenase (LDH), total cholesterol and triglycerides were estimated in all rats. RESULTS: Isoproterenol-induced AMI in hypercholesterolemic rats was associated with an increase in serum levels of PTX3, TGF-ß1, CK and LDH. Aspirin and/or clopidogrel pretreatment for 1 week led to a reduction of their levels as compared with non-treated rats. However, the reduction caused by combination of aspirin and clopidogrel was more than that caused by each drug separately. CONCLUSION: Combination of aspirin and clopidogrel could be a therapeutic option for hypercholesterolemic patients to attenuate the complex vascular inflammatory process which is a key step in the setting of AMI.

Application of multivariate modeling for radiation injury assessment: a proof of concept.

Multivariate radiation injury estimation algorithms were formulated for estimating severe hematopoietic acute radiation syndrome (H-ARS) injury (i.e., response category three or RC3) in a rhesus monkey total-body irradiation (TBI) model. Classical CBC and serum chemistry blood parameters were examined prior to irradiation (d 0) and on d 7, 10, 14, 21, and 25 after irradiation involving 24 nonhuman primates (NHP) (Macaca mulatta) given 6.5-Gy (60)Co Υ-rays (0.4 Gy min(-1)) TBI. A correlation matrix was formulated with the RC3 severity level designated as the "dependent variable" and independent variables down selected based on their radioresponsiveness and relatively low multicollinearity using stepwise-linear regression analyses. Final candidate independent variables included CBC counts (absolute number of neutrophils, lymphocytes, and platelets) in formulating the "CBC" RC3 estimation algorithm. Additionally, the formulation of a diagnostic CBC and serum chemistry "CBC-SCHEM" RC3 algorithm expanded upon the CBC algorithm model with the addition of hematocrit and the serum enzyme levels of aspartate aminotransferase, creatine kinase, and lactate dehydrogenase. Both algorithms estimated RC3 with over 90% predictive power. Only the CBC-SCHEM RC3 algorithm, however, met the critical three assumptions of linear least squares demonstrating slightly greater precision for radiation injury estimation, but with significantly decreased prediction error indicating increased statistical robustness.

Mechanisms and assessment of statin-related muscular adverse effects.

Statin-associated muscular adverse effects cover a wide range of symptoms, including asymptomatic increase of creatine kinase serum activity and life-threatening rhabdomyolysis. Different underlying pathomechanisms have been proposed. However, a unifying concept of the pathogenesis of statin-related muscular adverse effects has not emerged so far. In this review, we attempt to categorize these mechanisms along three levels. Firstly, among pharmacokinetic factors, it has been shown for some statins that inhibition of cytochrome P450-mediated hepatic biotransformation and hepatic uptake by transporter proteins contribute to an increase of systemic statin concentrations. Secondly, at the myocyte membrane level, cell membrane uptake transporters affect intracellular statin concentrations. Thirdly, at the intracellular level, inhibition of the 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase results in decreased intracellular concentrations of downstream metabolites (e.g. selenoproteins, ubiquinone, cholesterol) and alteration of gene expression (e.g. ryanodine receptor 3, glycine amidinotransferase). We also review current recommendations for prescribers.