Heat pack treatment does not attenuate repeated muscle damage in collegiate females / O tratamento térmico não atenua lesão muscular em mulheres universitárias

OBJECTIVE: Unaccustomed exercise causes transient Delayed Onset Muscle Soreness (DOMS); creatine-kinase and DOMS are indirect markers of muscle damage. Heat pack treatment increases blood flow and relieves pain. We determined the effects of heat pack treatment on DOMS, Creatine-Kinase, pain and jumping following maximum calf-raise exercises. METHODS: Exercise (3 days): calf-raise, 1 movement every 3 seconds until subjects could not maintain movement speed, Recovery: monitored for 7 days. Subjects: 14 female collegiate students (age: 20-22) with previous regular moderate exercise history, divided into heat pack treatment (n = 7; 40ºC, 20-min on both calf muscles immediately after exercise) vs. no treatment (n = 7). Measured parameters: number of daily movements, Creatine-Kinase, one-leg long jumping (JUMP) and perceived pain (PAIN). Maximum dorsiflexion, calf maximum circumference and isometric muscle strength were also measured, but showed no significant variation. RESULTS: There were no differences between groups regarding the number of the calf-raise repetitions; Creatine-Kinase increased significantly from day 3 of the Exercise-period to day 5 of the recovery period and peaked on Recovery day 2 in both groups; it was higher in the treated-group vs. controls; PAIN significantly decreased immediately after the heat pack treatment; DOMS peaked in both groups on day 3 of the Exercise-period, and recovered by day 4 of the recovery period. JUMP values decreased significantly after the initial exercise and recovered to initial values by Day 4 of the recovery period. CONCLUSION: Heat pack treatment for 20 minutes did not minimize DOMS following the maximum calf-raise exercise, but reduced immediate muscle soreness.

OBJETIVO: Exercícios desacostumados causam Dor Muscular Transitória Tardia (DMT); a creatina quinase e a DMT são marcadores indiretos de lesão muscular. Tratamento térmico aumenta o fluxo sanguíneo e alivia a dor. Determinamos os efeitos do tratamento de calor sobr a DMT, a creatina quinase, e a dor causada exercícios máximos de elevação da panturillha. MÉTODOS: Exercício (3 dias): elevação da panturrilha, um movimento cada 3 segundos até que os participantes não puderam manter a velocidade de movimento; esta fase foi seguida por sete dias de recuperação monitorada. Participantes: 14 estudantes universitários do sexo feminino (idade: 20-22) com história anterior exercícios moderados e regulares, divididos em participantes tratados com calor (n = 7; 40 º C, 20 min em ambos os músculos da panturrilha imediatamente após o exercício) vs. nenhum tratamento (n = 7). Os parâmetros medidos foram: número de movimentos diários, creatina quinase, slato em distância com uma única perna (JUMP) e dor percebida (DOR). Foram também medidos a dorsiflexão máxima, circunferência máxima da panturrilha e a força muscular isométrica, que não exibiram variações significativas. RESULTADOS: Não houve diferenças entre os grupos quanto ao número de repetições de elevação de panturrilha; a creatina quinase aumentou significativamente desde o dia 3 do período de exercício até o dia 5 do período de recuperação e chegou ao máximo no dia 2 de recuperação em ambos os grupos; seu valor foi mais elevado no grupo tratado versus controles; a DOR diminuiu significativamente imediatamente após o tratamento de calor; DMT atingiu o pico em ambos os grupos aos 3 dias do período de exercício e desapareceu no dia 4 do período de recuperação. Os valores de JUMP diminuíram significativamente após o exercício inicial e recuperam aos valores iniciais no Dia 4 do período de recuperação. CONCLUSÃO: O tratamento térmico por 20 minutos não minimizou a DMT após o exercício máximo de elevação de panturrilha, mas reduziu a dor muscular imediata.

The clinical and electrodiagnostic characteristics of Pompe disease with post-enzyme replacement therapy findings.

OBJECTIVE: Pompe disease is a neuromuscular disorder that was progressive and fatal prior to enzyme replacement therapy (ERT). The advent of treatment has made early recognition imperative. Electrodiagnostic (EDx) studies represent a valuable diagnostic tool in Pompe disease, but there has been little contemporary data. METHODS: The records of 29 patients with Pompe disease who had undergone EDx evaluation at Duke University Medical Center from 1999 to 2010 were reviewed. RESULTS: Seventeen children and twelve adults comprised the group. The clinical characteristics of both groups did not differ from expected. Needle electromyography demonstrated spontaneous activity (SA) in 80% of children and 83% of adults. Myotonic discharges were found in 53% of children and 72% of adults, often isolated to the paraspinal muscles in adults. Eight patients had EDx studies performed after ERT with 3 showing improvement after therapy, despite clinical improvement in 6 of 8. CONCLUSIONS: EDx studies remain a helpful tool in diagnosing Pompe disease, but do not appear to be sensitive for monitoring response to ERT based upon this limited sample. SIGNIFICANCE: Paraspinal examination is necessary in adults with symptoms suggestive of Pompe disease, as abnormalities may be isolated to this region. Standard EDx studies are not sufficient to monitor early response to ERT and further research on potential biomarkers is needed.

Creatine kinase injection restores contractile function in creatine-kinase-deficient mouse skeletal muscle fibres.

Viable genetically engineered animals generally exhibit adaptations to the altered genotype, which may mask the role of the protein of interest. We now describe a novel method by which the direct effects of the altered genotype can be distinguished from secondary adaptive changes in isolated adult skeletal muscle cells. We studied contractile function and intracellular Ca2+ handling in single skeletal muscle fibres that are completely deficient of creatine kinase (CK; CK-/-) before and after microinjection of purified CK (injected together with the fluorescent Ca2+ indicator indo-1). The mean total CK activity after CK injection was estimated to be approximately 4 mM s-1, which is approximately 5 % of the activity in wild-type muscle fibres. After CK injection, CK-/- fibres approached the wild-type phenotype in several aspects: (a) the free myoplasmic [Ca2+] ([Ca2+]i) increased and force showed little change during a period of high-intensity stimulation (duty cycle, i.e. tetanic duration divided by tetanic interval = 0.67); (b) [Ca2+]i did not decline during a brief (350 ms) tetanus; (c) during low-intensity fatiguing stimulation (duty cycle = 0.14), tetanic [Ca2+]i increased over the first 10 tetani, and thereafter it decreased; (d) tetanic [Ca2+]i and force did not display a transient reduction in the second tetanus of low-intensity fatiguing stimulation. Conversely, tetanic force in the unfatigued state was lower in CK-/- than in wild-type fibres, and this difference persisted after CK injection. Injection of inactivated CK had no obvious effect on any of the measured parameters. In conclusion, microinjection of CK into CK-/- fibres markedly restores many, but not all, aspects of the wild-type phenotype.

Use of plasma creatine kinase pharmacokinetics to estimate the amount of excercise-induced muscle damage in Beagles.

OBJECTIVE: To assess the effects of moderate exercise on plasma creatine kinase (CK) pharmacokinetics and to estimate exercise-induced muscle damage in dogs. ANIMALS: 6 untrained adult Beagles. PROCEDURE: The study was divided into 3 phases. In phase 1, dogs ran for 1 hour at a speed of 9 km/h, and samples were used to determine the area under the plasma CK activity versus time curve (AUC) induced by exercise. In phases 2 and 3, pharmacokinetics of CK were calculated in dogs during exercise and at rest, respectively. Values for AUC and plasma clearance (CI) were used to estimate muscle damage. RESULTS: At rest, values for Cl, steady-state volume of distribution (Vdss), and mean retention time (MRT) were 0.32+/-0.02 ml/kg of body weight/min, 57+/-173 ml/kg, and 3.0+/-0.57 h, respectively. During exercise, Cl decreased significantly (0.26+/-0.03 ml/kg/min), MRT increased significantly, (4.4+/-0.97 h), and Vdss remained unchanged. Peak of plasma CK activity (151+/-58.8 U/L) was observed 3 hours after completion of exercise. Estimated equivalent amount of muscle corresponding to the quantity of CK released was 41+/-29.3 mg/kg. CONCLUSION AND CLINICAL RELEVANCE: These results revealed that exercise had a minor effect on CK disposition and that the equivalent amount of muscle damaged by moderate exercise was negligible. This study illustrates the relevance for use of the minimally invasive and quantitative pharmacokinetic approach when estimating muscle damage.

Síndrome neuroléptico maligno en sujetos sin patología psiquiátrica previa y en enfermos psiquiátricos. Estudio comparativo de una cohorte de 21 enfermos / Malignant neuroleptic syndrome in subjects without previous psychiatric disorders and in psychiatric patients. Comparative study of a cohort of 21 patients

Fundamento: Observar las semejanzas y diferencias que presenta el síndrome neuroléptico maligno en pacientes psiquiátricos y en sujetos previamente sanos. Pacientes y métodos: Serie de casos clínicos valorados por el autor. Se confrontaron (comparación de medias): leucocitosis, temperatura, valor de la creatinfosfocinasa, latencia en horas desde la administración del fármaco y el desarrollo de los síntomas, fármaco y dosis involucrados, días de estancia hospitalaria y líquido cefalorraquídeo. Además, se contrastó (prueba de la *2 [test exacto de Fisher y corrección de Yates]): nivel de alerta, rigidez, inestabilidad autonómica y la presencia de trastornos del movimiento. Un valor de p < 0,05 fue significativo en ambos casos. Resultados: Fueron 13 varones y 8 mujeres; edad media de 41,5 años. Ocho pertenecieron al grupo sano y 13 al grupo psiquiátrico (12 pacientes con diagnóstico de esquizofrenia). Siete enfermos del primer grupo consultaron por síndrome confusional agudo agitado (cinco por consumo de alcohol). En el grupo psiquiátrico fue por un brote psicótico con agresividad (12 pacientes). El haloperidol estuvo involucrado en 17 enfermos (80,95 por ciento). La cifra de leucocitos, neutrófilos y linfocitos fueron mayores en el grupo previamente sano (p < 0,03; 0,0009; 0,004, respectivamente). La latencia en horas y la dosis del fármaco fueron menores en ese mismo grupo (p < 0,0003; 0,00001). El resto de variables no evidenció diferencia. Todos presentaron hipertermia, rigidez, trastorno del nivel de alerta y elevaciones de la creatinfosfocinasa. Conclusiones: Los pacientes previamente asintomáticos, con alcoholismo y cuadro confusional agudo pueden desarrollar síndrome neuroléptico maligno después de recibir una dosis media de 19,28 mg de haloperidol y tras una latencia de 31,25 h. Creemos que la deshidratación y el efecto tóxico del alcohol contribuyen para esta mayor susceptibilidad (AU)

[Bioavailability of muscle creatine kinase in sheep. Application to the assessment of local tolerance to injectable veterinary formulations]. / Biodisponibilité de la créatine kinase musculaire chez le mouton. Application à l'évaluation de la tolérance locale de formulations vétérinaires injectables.

Pharmacokinetic variables of skeletal muscle creatine kinase were determined in sheep after intravenous and intramuscular administration of the semipurified enzyme. Catheters implanted in the jugular vein were used for both intravenous injections and blood withdrawals. Blood sample collection by vacutainer and hemolysis may in fact have considerable effects on the measurement of creatine kinase activity in plasma. The change in the enzyme activity versus time in the plasma, after intravenous administration (123 +/- 38 U/kg) of creatine kinase, was fitted by a biexponential model. The mean volume of the central compartment (45 +/- 5 mL/kg) was approximately equal to the plasma volume. Plasma half-life and plasma clearance of creatine kinase were 3.7 +/- 1.7 h and 23 +/- 8 mL.kg-1.h-1, respectively. Mean plasma bioavailability of creatine kinase after intramuscular administration (357 +/- 36 U/kg) in both the loins and the gluteal mass was 42%. Maximal plasma activity was observed 4 and 5 h after injection and the half-life of the terminal phase was 7.3 or 8.6 h according to the muscle. The extent of muscle damage after intramuscular administrations of 21 veterinary drug formulations (one product per animal) was estimated from the total creatine kinase activity released in plasma during the 72 h following the injection. Equivalent weights of damaged muscle ranged from 1.4 to 83.3 g according to the irritant potency of the test formulation. Results differed only moderately between the injection sites (right and left gluteal mass) in the same animal. It can be concluded from this study that, in sheep: i) the bioavailability of creatine kinase from different injection sites (gluteal mass and loins) is comparable; and ii) the intra-individual variability in the estimation of muscle damage is moderate. Once validated, this non-invasive approach for local tolerance studies could be of value in assessing and comparing the irritant potency of veterinary drugs and in reducing the number of animals required.

Disposition of creatine kinase activity in dog plasma following intravenous and intramuscular injection of skeletal muscle homogenates.

The fate of skeletal muscle-derived creatine kinase (CK) was investigated in six dogs. After i.m. and i.v. injections of 3000 g and 105,000 g supernatants of dog muscle homogenates, plasma CK activity was measured up to 48 h. There was no significant difference in pharmacokinetic parameters dependent on the type of supernatant injected. After i.v. injection, the volume of distribution of CK was equal to the plasma volume, CK clearance was relatively low (about 0.5 mL/kg/min) and its terminal half-life of elimination was about 2.5 h. After i.m. injection, the CK terminal half-life was about 6.5 h, demonstrating a flip-flop mechanism, i.e. a limiting absorption process from the site of injection. Bioavailability after i.m. injection was about 65%, and the rate of absorption from muscle injection site was relatively slow: peak activity occurred at the second hour post administration, and most CK activity had been absorbed by 24 h. These pharmacokinetic parameters can be used as a basis for a minimally invasive means of quantitating muscle damage either after intramuscular drug administration or in canine sports medicine.

Compared kinetics of plasma creatine kinase activity in rabbits after intravenous injection of different preparations of skeletal muscle.

The purpose of this study was to compare the disposition parameters of creatine kinase (CK) in rabbits after intravenous bolus administration of 3 CK preparations: 1) purified CK; 2) CK obtained from a muscular extract after a 3,000 g centrifugation (ie with cell remains) (3,000 g CK); or 3) a 105,000 g centrifugation (ie the cytosolic soluble phase) (105,000 g CK). The plasma half-lives were not significantly different (approximately 9 h). In contrast, the clearance of 3,000 g CK (3.25 +/- 0.33 ml.kg-1.h-1) was significantly lower than that of the 2 others (7.00 +/- 0.49 ml.kg-1.h-1 and 4.63 +/- 0.65 ml.kg-1.h-1 for 105,000 g and purified CK, respectively). These findings suggest that purified CK preparation is not the most appropriate form for determination of enzyme pharmacokinetic parameters following muscle damage.

[Combined drug-surgical therapy of acute ischemia syndrome]. / Die kombinierte medikamentös-chirurgische Therapie des akuten Ischämiesyndroms.

Acute ischaemia of the lower leg caused by arterial thrombosis often leads to amputation. Thrombolytic therapy of a distal arterial thrombosis yields unsatisfactory results when lower leg thrombosis is superimposed on chronic superficial femoral artery occlusion. 31 cases of acute ischaemia of the lower leg were initially treated with short bursts of catheter lysis followed by surgical reconstruction. Improved results were obtained through the use of combined medical and surgical treatment.

Clearance of serum creatine kinase activity.

There is confusion regarding the calculation of serum creatine kinase (CK) activity clearance from an elimination rate constant and a distribution volume derived from one- and two-compartment serum enzyme elimination models. We measured serum CK activity clearance from hepatic enzyme extraction and compared this direct measurement with clearance calculated assuming one- and two-compartment elimination models after bolus and constant infusions of a purified preparation of the MM isoenzyme of CK (MM-CK) activity. Although serum CK activity appears to confer on the body the characteristics of first-order disposition from two compartments, clearance is estimated equally well by one-, two-, and noncompartmental models of disposition and is essentially identical to the hepatic clearance of CK activity. As long as the rate constant and distribution volume are compatible and appropriate for a given elimination model, clearance, the product of the two, will be properly estimated regardless of the model chosen.

[Protein-containing liposomes and their organ distribution following intravenous administration]. / Beloksoderzhashchie liposomy i ikh raspredelenie po organam pri vnutrivennom vvedenii.

Comparative characteristics of the distribution of phophokinase-125I was studied in rats after the intravenous injection in free or liposome-entrapped state. Significant increase of protein entrapment by the organs and prolonged tissue retention (up to 6 days) were found after the liposomes administration as compared to injection of free material (no label was found after 24 hrs). Intracellular localisation of the label in the liver was revealed autoradiographically 24 hrs after the liposome injection; it was absent after its injection in free state. Enzyme assay in liver homogenates revealed intact specific activity after liposome administration, and confirmed the quantitative data obtained with radiolabeled protein.