D. Tedeschi

Coenzyme Q10, exercise lactate and CTG trinucleotide expansion in myotonic dystrophy

Steinerts myotonic dystrophy (DM) is a genetic autosomal dominant disease and the most frequent muscular dystrophy in adulthood. Although causative mutation is recognized as a CTG trinucleotide expansion on 19q13.3, pathogenic mechanisms of multisystem involvement of DM are still under debate. It has been suggested that mitochondrial abnormalities can occur in this disease and deficiency of coenzyme Q 10 (CoQ10) has been considered one possible cause for this. The aim of this investigation was to evaluate, in 35 DM patients, CoQ10 blood levels and relate them to the degree of CTG expansion as well as to the amount of lactate production in exercising muscle as indicator of mitochondrial dysfunction. CoQ10 concentrations appeared significantly reduced with respect to normal controls: 0.85 +/- 0.25 vs. 1.58 +/- 0.28 microg/ml (p < 0.05). Mean values of blood lactate were significantly higher in DM patients than controls (p < 0.05) both in resting conditions (2.9 +/- 0.55 vs. 1.44 +/- 1.11 mmol/L) and at the exercise peak (6.77 +/- 1.79 vs. 4.90 +/- 0.59 mmol/L), while exercise lactate threshold was anticipated (30-50% vs. 60-70% of the predicted normal maximal power output, p < 0.05). Statistical analysis showed that serum CoQ10 levels were significantly (p < 0.05) inversely correlated with both CTG expansion degree and lactate values at exercise lactate threshold level. Our data indicates the occurrence of reduced CoQ10 levels in DM, possibly related to disease pathogenic mechanisms associated with abnormal CTG trinucleotide amplification.

Behaviour of mean erythrocyte volume during submaximal treadmill exercise in the horse

Abstract: The aim of this work was to study the role of spleen contraction in the modification of circulating erythrocyte mean volume during treadmill exercise in the horse. Red blood cells count (RBC), haematocrit (Hct), haemoglobin (Hgb), mean cellular volume (MCV), mean cellular haemoglobin (MCH), mean cellular haemoglobin concentration (MCHC) and red cell distribution width (RDW) were evaluated in five Haflinger mares performing a submaximal incremental test on the treadmill. Blood was collected every minute during the trial without stopping the treadmill. Significant changes of all measured parameters, except for MCH, have been observed. Hct values increased significantly from the 2nd minute from the start of the test. MCV and MCHC values were significantly different from their basal values from the 6th minute of exercise, with MCV being increased and MCHC decreased, suggesting cellular swelling. Hct modifications during brief submaximal exercise have been shown to be mainly and directly related to mobilization of the pool of red blood cells stored in the spleen. However, the evidence in this study of different times of onset of changes between Hct and erythrocyte indices (MCV and MCHC) suggests that exercise-induced alterations in red cell indices are not related to spleen emptying.

Application of a constant blood withdrawal method in equine exercise physiology studies

The aim of the present study was to test a constant blood withdrawal method (CBWM) to collect blood samples from horses during treadmill exercise. CBWM was performed in 4 Standardbreds and 5 Haflinger horses. A peristaltic pump was used to control blood aspiration from an i.v. catheter via an extension line. Blood was collected using an automatic fractions collector, with a constant delay time between the drawing of blood and sample collection. Blood withdrawal using CBWM was made during a treadmill standardised exercise test (SET). A blood flow of 12 m/min was used and samples collected every 60 s during the entire period of exercise. The volume of blood collected in each sample tube was 12.1+/-0.2 ml, with a delay time of mean +/- s.d. 25.3+/-0.8 s. Plasma lactate kinetics based on measurement of lactate in each fraction showed an exponential increase during the first 13 min of exercise (10.5 min of SET and 2.5 min recovery). The peak plasma lactate concentration was observed between 2.5 and 5.5 min after the end of SET. CBWM permits the kinetics of lactate and other blood-borne variables to be studied over time. This method could be a valuable aid for use in studying equine exercise physiology.

Potential involvement of ubiquinone in myotonic dystrophy pathophysiology: new diagnostic approaches for new rationale therapeutics

Abstract An impairment of mitochondrial function may contribute to the pathophysiology of myotonic dystrophy (MyD). Coenzyme Q10 (CoQ10) deficiency has been previously observed, even if in an restricted sample of patients. The aim of this investigation was to obtain more information about coenzyme Q10 and its relationships to the aerobic metabolism in a group of MyD patients. Serum CoQ10 appeared significantly reduced with respect to normal controls: 0.93±0.22 vs. 1.58±0.28 μg/ml (p<0.05). Moreover, the results demonstrated an inverse tendency between CoQ10 levels and the CTG expansion degree. Basal blood lactate levels were significantly higher than controls (p<0.05). A borderline inverse correlation between CoQ10 and lactate, corresponding to lactate threshold, was found. These data suggest a possible role of CoQ10 in the pathogenesis of MyD, which may be mediated by mechanisms of cellular damage common to the oxidative pathway. Therapeutic strategies may be devised by virtue of this rationale.