Biomedical subjects

O Pastoris

Publications and source records attributed to O Pastoris.

At least 19 recordsLinked to original sources

PubMed2001

Neuromuscular junction disassembly and muscle fatigue in mice lacking neurotrophin-4.

Neurotrophin-4 (NT-4) is produced by slow muscle fibers in an activity-dependent manner and promotes growth and remodeling of adult motorneuron innervation. However, both muscle fibers and motor neurons express NT-4 receptors, suggesting bidirectional NT-4 signaling at the neuromuscular junction. Mice lacking NT-4 displayed enlarged and fragmented neuromuscular junctions with disassembled postsynaptic acetylcholine receptor (AChR) clusters, reduced AChR binding, and acetylcholinesterase activity. Electromyographic responses, posttetanic potentiation, and action potential amplitude were also significantly reduced in muscle fibers from NT-4 knock-out mice. Slow-twitch soleus muscles from these mice fatigued twice as rapidly as those from wild-type mice during repeated tetanic stimulation. Thus, muscle-derived NT-4 is required for maintenance of postsynaptic AChR regions, normal muscular electrophysiological responses, and resistance to muscle fatigue. This neurotrophin may therefore be a key component of an activity-dependent feedback mechanism regulating maintenance of neuromuscular connections and muscular performance.

Acetylcholinesterase↗

PubMed2001

Energy expenditure and nutritional adequacy of rehabilitation paraplegics with asymptomatic bacteriuria and pressure sores.

OBJECTIVE: To measure resting energy expenditure (REE) in a group of people with postacute paraplegia, quantify the impact of asymptomatic bacteriuria and pressure sore(s) on patients' metabolic rate, and estimate the adequacy of patients' nutritional intakes to preserve patients' protein levels. MATERIAL AND METHODS: Ten males with post-acute paraplegia aged 42.1+/-18.7 years. We evaluated: height, body mass index (BMI), resting energy expenditure (REE), total daily calorie requirement (E), 24-h urine creatinine excretion (Cru), creatinine index (CI), and nitrogen balance (NB). RESULTS: Subjects with paraplegia showed high erythrocyte sedimentation rates. As a group, they had normal resting calorie consumption when REE was normalized for unit of urine creatinine (REE/Cru), it was higher in patients than in controls. Six of the 10 patients had a low calorie intake: of these only three had a negative nitrogen balance. CONCLUSION: In conclusion, the resting energy expenditure of the subjects with significant bacteriuria and pressure sore(s) of 23.7 kcal/kg/day suggests that a large portion of patients may have an inadequate calorie protein intake to preserve their nutritional status. The clinical significance of this study is that 28.5 kcal/kg/day may be the lower calorie threshold to meet the metabolic demands of people with apyretic paraplegia with bacteriuria and pressure sore(s).

Adolescent↗

PubMed2001

Effects of the beta(2)-agonist clenbuterol on respiratory and limb muscles of weaning rats.

The aim of this study was to analyze the effects of chronic administration of the beta(2)-agonist clenbuterol (1.5 mg x kg(-1) x day(-1) for 4 wk in the drinking water) on respiratory (diaphragm and parasternal intercostal) and hindlimb (tibialis and soleus) muscles in young rats during postnatal development (21 to 49 postnatal days). The treatment resulted in very little stimulation of muscle growth. Significant slow-to-fast transitions in the expression of myosin heavy chain isoforms and significant increases in the myofibrillar ATPase activity were found in the diaphragm and soleus, whereas tibialis anterior and intercostal muscles did not show any significant fiber-type alteration. Decrease of oxidative enzyme activities and increase of glycolytic enzyme activities were also observed. It is concluded that whereas the growth stimulation is age dependent and only detectable in adult rats, the fiber-type transformation is also present in weaning rats and particularly evident in the soleus and diaphragm. The fiber-type transformation caused by clenbuterol might lead to an enhancement of contractile performance and also to a reduced resistance to fatigue.

Adenosine Triphosphatases↗

PubMed2000

Peripheral plasma amino acid abnormalities in rehabilitation patients with severe brain injury.

OBJECTIVE: Acute severe brain injury causes an increased mobilization of amino acids from tissue. The plasma amino acid profile of patients undergoing rehabilitation after brain injury is unknown. This study was aimed at delineating the plasma amino acid profile of rehabilitation patients with brain injury. DESIGN: Peripheral plasma aminogram, lactate, pyruvate, glycerol, ketone body, and carnitine concentrations were determined in 11 patients with brain injury (34.6+/-15 years old, 60+/-16.8 days after injury) and in 8 controls. Resting energy expenditure and nitrogen balance were also determined. RESULTS: (1) All essential amino acids and about 50% of nonessential amino acids were significantly lower in brain injury patients than in controls (p < .05). (2) Plasma amino acids were lower irrespective of either energy and protein intake or nitrogen balance. (3) Total carnitine concentration and esterified/free carnitine ratio were higher in brain injury patients than in controls (p < .05). CONCLUSIONS: Rehabilitation patients with brain injury may have an important reduction of their plasma aminogram. Muscle tissue depletion and the persistence of a hypercatabolic state caused by subclinical infections, pressure sores, and immobility may contribute to this reduction.

Adolescent↗

PubMed2000

The effects of aging on enzyme activities and metabolite concentrations in skeletal muscle from sedentary male and female subjects.

Aging affects the metabolic capacity of skeletal muscle, in particular the glycolytic and respiratory capacities. The purpose of this study was to quantify biochemical alterations due to aging in muscular metabolic capacity in human skeletal muscles in sedentary subjects. The activities of various marker enzymes and metabolites related to glycolysis, Krebs' cycle and the electron transfer chain and high energy phosphate compounds were measured in muscle biopsies from the rectus abdominis, vastus lateralis, and gluteus maximus muscles of 76 sedentary subjects (32 males and 44 females) between 15 and 91 yr. No significant differences between males and females were found, but changes related to age were: a decrease in hexokinase and lactate dehydrogenase activities in the rectus abdominis; a decrease in citrate synthase activity and citrate in the vastus lateralis; an increase in pyruvate kinase activity and a decrease in ATP and creatine phosphate concentrations in the gluteus maximus. These data suggest that distinct muscles may respond differently to aging regardless of sex in sedentary subjects.

Adolescent↗

PubMed1999

Despite good compliance, very low fat diet alone does not achieve recommended cholesterol goals in outpatients with coronary heart disease.

AIM: A low-saturated, low-cholesterol diet is important in the treatment of hypercholesterolaemia in patients with coronary heart disease. The aim of this study was to investigate the efficacy of a very low fat diet to achieve a targeted serum low density lipoprotein (LDL) cholesterol level (</=2.59mmol x l-1) in outpatients with coronary heart disease. METHODS: One hundred and twenty-six male patients (all ex-smokers) with coronary heart disease and a serum LDL cholesterol >3.37mmol x l-1 were investigated 12-14 weeks after an acute coronary event. After overnight fasting each patient had (a) his resting energy expenditure measured (indirect calorimetry using standard protocol) and (b) venous blood sampled from a forearm vein to determine lipid profile. All the patients were randomly allocated to four groups of treatment: Group A on a very low fat diet (resting energy expenditure-fat diet, where fat intake was </=20% resting energy expenditure): Group B on a low fat diet from the National Cholesterol Education program (National Cholesterol Education Program step 2 diet): Group C on resting energy expenditure-fat diet+simvastatin 10mg daily; Group D on National Cholesterol Education Program step 2 diet+simvastatin 10mg daily. For all patients the prescribed energy intakes were equal to their respective resting energy expenditures. RESULTS: At 6 months, the average decrease in serum LDL cholesterol was not different between Group A and Group B, but the increase in high density lipoprotein cholesterol (HDL) (+29%) observed in Group A led to a reduced LDL cholesterol/HDL cholesterol ratio (P<0.001). As expected, a more important serum lipid improvement was found in the groups supplemented with diet+drug association, but the decrease in LDL cholesterol was higher in Group C than in Group D (-37+/-9.7% vs -24. 5+/-15%;P<0.00001) as well as LDL cholesterol/HDL cholesterol ratio (P<0.001). No patient on diet alone achieved the recommended LDL cholesterol level </=2.59mmol x l-1. CONCLUSION: Diet alone does not allow patients with coronary heart disease to achieve the recommended blood cholesterol levels, even if its fat content is highly reduced.

Aged↗

PubMed1998

Effect of L-carnitine on myocardial metabolism: results of a balanced, placebo-controlled, double-blind study in patients undergoing open heart surgery.

The effects of L-carnitine on cardiac performance after open heart surgery were evaluated in a balanced, placebo-controlled, double-blind study in 38 patients. Preoperative haemodynamic status was good in all of them. Seventeen subjects underwent mitral valve replacement and 19 patients coronary artery bypass grafting. Five grams L-carnitine were given intravenously over 2 h, twice daily for 5 consecutive days; moreover, 10 g L-carnitine in 1500 ml cardioplegia were administered through the aortic root after aortic cross-clamping. Surgery was always planned on treatment day 3. The post-ischaemic functional recovery of the heart was assessed by clinical parameters, as well as by biochemical and ultrastructure evaluations on biopsy specimens. No differences were found between the control and the treatment group with respect to all clinical parameters of cardiac performance after cardiopulmonary bypass. At anaesthesia induction, serum carnitine was significantly increased in treated patients, but carnitine concentrations in the right atrial biopsy obtained just before aortic declamping were similar in the two groups. In patients with mitral valve replacement, L-carnitine therapy was associated with significantly higher concentrations of pyruvate, ATP and creatine phosphate in papillary muscle. Glycogen levels were also higher in the treated group, but the difference was not statistically significant. Myocardial ultrastructure on septal biopsies, obtained within 5 min from weaning from extracorporeal circulation, showed better preservation scores for all considered parameters (nucleus, sarcoplasmic reticulum, mitochondria and cellular oedema) in the treated subjects, although the difference reached statistical significance only for nuclei. When biochemical and ultrastructural data are considered, these findings suggest that L-carnitine improves myocardial metabolism. However, it cannot be concluded that L-carnitine provides an advantageous support therapy for well-compensated patients requiring cardiac surgery. In contrast, the positive effects of L-carnitine on cardiac recovery after bypass might become clinically relevant in the surgical setting for haemodynamically compromised patients, in which further investigations are required.

Aged↗

PubMed1998

Metabolite concentrations in skeletal muscle of different aged rats submitted to hypoxia and pharmacological treatment with nicergoline.

The energy metabolism of the gastrocnemius and soleus muscles in young-adult, mature, and senescent rats was evaluated after 72 h of continuous exposure to normobaric hypoxia or normoxia. The effects of treatment with the alpha-adrenergic antagonist nicergoline were also investigated. In the gastrocnemius muscle we evaluated the concentrations of some significative metabolites involved in anaerobic glycolysis and the Krebs' cycle, free amino acids related to the Krebs' cycle, ammonia, some energy mediators, and the energy store creatine phosphate. In the soleus muscle a selection of these was evaluated. In both muscles aging was similarly characterized by a decrease in muscular creatine phosphate concentration, while the energy mediators and the energy charge potential remained unchanged. Singly, some gastrocnemius muscle metabolites showed linear changes in their concentrations with aging, while for the soleus muscle the only linear change regarded glucose-6-phosphate. Continuous normobaric hypoxia induced greater changes at the age of 4 and 24 months than at 12 months. Chronic treatment with nicergoline modified the influence of hypoxic conditions on muscle metabolites concentrations only in some cases, regardless of the age of the animals. Further investigations are necessary before any firm conclusions can be drawn about the pharmacological activity of nicergoline on hypoxia in aged rats.

Adrenergic alpha-Antagonists↗

PubMed1997

Altered muscle energy metabolism in post-absorptive patients with chronic renal failure.

Skeletal muscle biopsies were performed on 12 healthy sedentary subjects and on 22 non-dyalized chronic renal failure patients (CRF) on a free diet and after overnight fasting. Parathormone, glucagon and insulin were determined at the same time of biopsies. CRF patients showed significantly low ATP and creatine phosphate levels. Regarding enzyme activities, a high hexokinase Vmax was found, while the pyruvate kinase activity was lower than in the control group. For the tricarboxylic acid cycle, citrate synthase, succinate dehydrogenase and malate dehydrogenase activities were higher; total NADH cytochrome c reductase activity was also high, while cytochrome oxidase activity was slightly lower. Both alanine aminotransferase and aspartate aminotransferase activities were considerably high in comparison with the control group. In conclusion, our study revealed a hypermetabolic TCA cycle, but impaired oxidative phosphorylation, which partly explained the reduced ATP concentration. Excessive protein intake and hormonal derangements may play a role in these metabolic changes.

Adenosine Triphosphate↗

PubMed1996

Biochemical analysis of muscle biopsy in overnight fasting patients with severe chronic heart failure.

To better characterize the role of skeletal muscle in chronic heart failure we studied energetic charge, metabolites and enzyme activity in the energy production pathway. We selected 15 males with severe chronic heart failure (NYHA class III, stable clinical conditions and in normal nutritional status) and seven controls. Controls and patients were submitted to biopsy of the vastus lateralis muscle in resting and fasting conditions. Hormone profiles were also evaluated. Our results showed near normal ATP, ADP and AMP concentrations, but there were substantially more reductions in glycogen (46 +/- 5 vs 77 +/- 6 mumoles glycosidic units.g-1 fresh tissue) and creatine phosphate (5 +/- 1 vs 13 +/- 1 mumoles.g-1 fresh tissue) in patients than in controls. We also found a reduction in glycolytic activity (pyruvate kinase 1009 +/- 79 vs 1625 +/- 26 nmoles. min-1.mg protein-1), despite normal tricarboxylic acid cycle velocity, an increase in alanine amino-transferase (964 +/- 79 vs 425 +/- 34 nmoles. min-1.mg protein-1) and in aspartate aminotransferase (515 +/- 44 vs 291 +/- 56 nmoles.min-1.mg protein-1). An increase was also observed in total NADH cytochrome c reductase (128 +/- 14 vs 68 +/- 5 nmoles.min-1.mg protein-1), while cytochrome oxidase activity was normal. The cortisol/insulin ratio was slightly elevated (77 +/- 4 vs 32 +/- 12). In conclusion, normonutritive patients with severe heart failure show an imbalance in the energy production/utilization ratio. The impairment is probably due both to a decrease in production and an increase in consumption of energy owing to greater cellular workload and/or a hypercatabolic state.

Adenine Nucleotides↗

PubMed1996

Pyruvate dehydrogenase deficiency in a child responsive to thiamine treatment.

We report the clinical features in a 4-year-old child who was investigated for a suspected metabolic disorder but was subsequently diagnosed as having a pyruvate dehydrogenase deficiency. A muscle biopsy was performed and the data obtained suggested thiamine treatment which resulted in a regression of the clinical findings and a return to normal values of blood lactic and pyruvic acids. The interruption of thiamine supplementation after 1 year of treatment led to a prompt recurrence of the previous clinical and biochemical symptoms.

Biopsy↗

PubMed1995

Modifications by chronic intermittent hypoxia and drug treatment on skeletal muscle metabolism.

The energy metabolism was evaluated in gastrocnemius muscle from 3-month-old rats subjected to either mild or severe 4-week intermittent normobaric hypoxia. Furthermore, 4-week treatment with CNS-acting drugs, namely, alpha-adrenergic (delta-yohimbine), vasodilator (papaverine, pinacidil), or oxygen-increasing (almitrine) agents was performed. The muscular concentration of the following metabolites was evaluated: glycogen, glucose, glucose 6-phosphate, pyruvate, lactate, lactate-to-pyruvate ratio; citrate, alpha-ketoglutarate, succinate, malate; aspartate, glutamate, alanine; ammonia; ATP, ADP, AMP, creatine phosphate. Furthermore the Vmax of the following muscular enzymes was evaluated: hexokinase, phosphofructokinase, pyruvate kinase, lactate dehydrogenase; citrate synthase, malate dehydrogenase; total NADH cytochrome c reductase; cytochrome oxidase. The adaptation to chronic intermittent normobaric mild or severe hypoxia induced alterations of the components in the anaerobic glycolytic pathway [as supported by the increased activity of lactate dehydrogenase and/or hexokinase, resulting in the decreased glycolytic substrate concentration consistent with the increased lactate production and lactate-to-pyruvate ratio] and in the mitochondrial mechanism [as supported by the decreased activity of malate dehydrogenase and/or citrate synthase resulting in the decreased concentration of some key components in the tricarboxylic acid cycle]. The effect of the concomitant pharmacological treatment suggests that the action of CNS-acting drugs could be also related to their direct influence on the muscular biochemical mechanisms linked to energy transduction.

Adenine Nucleotides↗

PubMed1995

Biochemical evaluations in skeletal muscles of primates with MPTP Parkinson-like syndrome.

The toxic effects of the neurotoxin MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) in primates can be exploited for investigating the physiopathology of Parkinson's disease which may also cause functional alterations of skeletal muscles, whose biochemical modifications have been studied very little. Some enzyme activities related to energy transduction in skeletal muscles were evaluated (gastrocnemius, soleus and biceps) from MPTP-treated monkeys. Systemically administered MPTP altered the enzyme activities related to: (i) the anaerobic glycolytic pathway (decrease in hexokinase and phosphofructokinase activities; increase in lactate dehydrogenase activity); (ii) the tricarboxylic acid cycle (decrease in malate dehydrogenase activity); (iii) the electron transfer chain (decrease in cytochrome oxidase activity related to complex IV). No alteration in mitochondrial Complex I was observed. Treatment with an ergot alkaloid derivative (dihydroergocryptine) modified some alterations in the muscle enzyme activities and reduced the rigidity and some autonomic dysfunction.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

PubMed1995

Effects of hypoxia on enzyme activities in skeletal muscle of rats of different ages. An attempt at pharmacological treatment.

The activities of enzymes related to energy metabolism in the gastrocnemius and soleus muscles in young-adult (4 months), mature (12 months) and senescent (24 months) rats were compared after 72 h of continuous exposure to normobaric hypoxia or normoxia after alpha-adrenergic antagonist nicergoline or saline solution had been given intraperitoneally for 30 consecutive days. The maximum rates (Vmax) of the following enzyme activities in the crude extract and/or the mitochondrial fraction of each muscle specimen were evaluated: (1) for the anaerobic glycolytic pathway: hexokinase, phosphofructokinase, pyruvate kinase and lactate dehydrogenase; (2) for the tricarboxylic acid cycle; citrate synthase and malate dehydrogenase; (3) for the electron transfer chain; cytochrome oxidase; and (4) for the NAD+/NADH redox state: total NADH cytochrome c reductase. The significant differences between the enzyme activities at different ages or under different experimental conditions in the two tissue preparations of the two muscles were determined by ANOVA. MCA and ETA were used to evaluate the net effects of the experimental conditions. Ageing did not seem to affect the soleus and gastrocnemius muscles in the same way. Changes were seen only in the glycolytic pathway enzymes in the crude extract from the gastrocnemius muscle. In the soleus muscle changes in enzyme activities as a function of ageing were also found in the mitochondrial fraction. We also found that hypoxia caused greater changes in 12-month-old rats than in those of other ages (especially in the enzyme activities of the gastrocnemius muscle). Finally out data show that only in certain cases was the pharmacological treatment able to modify the influence of hypoxic conditions on the levels of enzyme activities, regardless of the age of animals.

Adrenergic alpha-Antagonists↗

PubMed1993

Infantile mitochondria encephalomyopathies: report on 4 cases.

Four muscle biopsies from the quadriceps femoris muscle of children with symptoms suggesting mitochondrial encephalomyopathy were examined for morphological and biochemical differences. From a biochemical point of view, our patients showed a derangement of mitochondrial metabolism and in particular a marked deficit in the activity of cytochrome c oxidase. In all patients there was an abnormally high rise of lactate and pyruvic acid levels in blood before and after glucose loading. Results of morphological and enzyme histochemical studies showed smaller muscle fibre diameters than in normal children. Typical red ragged fibres and ultrastructural abnormalities in muscle mitochondria were present in 1 case only. Three patients showed focal changes in the distribution of some sarcoplasmic oxidative enzyme activities. The present findings suggest that the main metabolic disorder, pointed out by biochemical studies, is scarcely reflected by morphological and ultrastructural studies in the early stages of mitochondriopathies.

Biopsy↗

PubMed1992

Muscle phosphofructokinase deficiency in a myopathic child with severe mental retardation and aplasia of cerebellar vermis.

Muscle phosphofructokinase (PFK) deficiency in man is responsible for at least two forms of myopathy; one is characterized by painful contractures of muscles and typically occurs in adults, whereas the other is often disabling and typically occurs in childhood, with psychomotor and growth retardation. In this investigation, a young myopathic patient with severe mental retardation and aplasia of the cerebellar vermis presented with muscular hypotrophy of the limbs, generalized hypotonia, convergent strabismus and marked pain during passive movement. Biopsy of quadriceps femoris muscle showed variation in the fiber size with sarcoplasmic areas positive for periodic acid-Schiff stain. Histochemical qualitative reaction for PFK showed no staining of muscle fibers; ultrastructural studies showed abnormal accumulation of glycogen granules in both intermyofibrillar and subsarcolemmal areas. While some enzyme activities in the muscular crude extract were significantly lower than in controls, direct assay of PFK revealed no activity, thus demonstrating that the child's myopathy was due to the lack of PFK activity.

Cerebellum↗

PubMed1991

Age-related acute depletion of cerebral glutathione by peroxidative stress.

Cyclohexene-1-one and cycloheptene-1-one cause a severe age-related depletion of reduced glutathione (GSH) in the forebrain of 5- or 15- or 25-month-old rats. Chronic pretreatment with phosphatidylcholine partially inhibits the GSH depletion in old forebrains by the prooxidants tested, suggesting that in aged animals alterations in mitochondrial inner membrane phospholipid composition and/or cytochrome oxidase activity might play a role in oxygen free-radical production.

Aging↗

PubMed1991

Sequential damage in mitochondrial complexes by peroxidative stress.

The biochemical characteristics of the electron transfer chain are evaluated in purified non-synaptic ("free") mitochondria from the forebrain of 60-week-old rats weekly subjected to peroxidative stress (once, twice, or three times) by the electrophilic prooxidant 2-cyclohexene-1-one. The following parameters are evaluated: (a) content of respiratory components, namely ubiquinone, cytochrome b, cytochrome c1, cytochrome c; (b) specific activity of enzymes, namely citrate synthase, succinate dehydrogenase, rotenone-sensitive NADH: cytochrome c reductase, cytochrome oxidase; (c) concentration of reduced glutathione (GSH). Before the first peroxidative stress induction, the rats are administered for 8 weeks by intraperitoneal injection of vehicle, papaverine, delta-yohimbine, almitrine or hopanthenate. The rats are treated also during the week(s) before the second or third peroxidative stress. The cerebral peroxidative stress induces: (a) initially, a decrease in brain GSH concentration concomitant with a decrease in the mitochondrial activity of cytochrome oxidase of aa3-type (complex IV), without changes in ubiquinone and cytochrome b populations; (b) subsequently, an alteration in the transfer molecule cytochrome c and, finally, in rotenone-sensitive NADH-cytochrome c reductase (complex I) and succinate dehydrogenase (complex II). The selective sensitivity of the chain components to peroxidative stress is supported by the effects of the concomitant subchronic treatment with agents acting at different biochemical steps. In fact, almitrine sets limits to its effects at cytochrome c content and aa3-type cytochrome oxidase activity, while delta-yohimbine sets limits to its effects at the level of tricarboxylic acid cycle (citrate synthase) and/or of intermediary between tricarboxylic acid cycle and complex II (succinate dehydrogenase).(ABSTRACT TRUNCATED AT 250 WORDS)

Almitrine↗