O. Pastoris | University of Pavia (original) (raw)
Papers by O. Pastoris
International Journal of Immunopathology and Pharmacology, 2012
Neurobiology of Aging, 1991
Il Farmaco; edizione scientifica, 1980
Dose/action and time/action relationships relative to the effect of the in vivo treatment with so... more Dose/action and time/action relationships relative to the effect of the in vivo treatment with some biological molecules (cytidine, uridine and glutamine) on several enzymatic activities connected with cerebral metabolism (lactate dehydrogenase, malate dehydrogenase, total NADH cytochrome c reductase, cytochrome oxidase and citrate synthase) were studied in the normal rat brain. While time/action curves were found to be in agreement with classical pharmacodynamic descriptions, dose/action curves exhibited a varying behavior according to the biological substrate tested (brain homogenate in toto or crude mitochondrial fraction from brain in toto). Often enzymatic activity changes as a function of dose failed to show linear correlations, a parabolic pattern being observed. At any rate, the changes affecting several cerebral enzymatic activities may account for some pharmacodynamic properties of the biological molecules tested.
Il Farmaco; edizione scientifica, 1984
The content of "energy-rich" phosphates was markedly decreased in rat cerebral cortex a... more The content of "energy-rich" phosphates was markedly decreased in rat cerebral cortex after 20 min of severe hypoglycemia, followed by partial restitution during the recovery period. The adenine nucleotide pool remained reduced even if the energy charge returned to normal. During hypoglycemia the non-glucose endogenous substrates were provided by glycolytic intermediates, by Krebs' cycle intermediates and by related amino acids. Other substrates for brain oxidation were provided by the breakdown of phospholipids and fatty acids. After a 20 min period of post-hypoglycemic recovery, partial restoration of carbohydrates and amino acids occurred, the amino acid pool size being still reduced. The alterations in phospholipids and fatty acids persisted, while there was a tendency towards normalization of the free fatty acid cerebral content. During the post-hypoglycemic recovery, treatment with some specific metabolic modulators (i.e., uridine, L-acetylcarnitine, hopantenate,...
Il Farmaco; edizione scientifica, 1984
On rat cerebral and cerebellar cortex, severe hypoglycemia with isoelectric EEG induced extensive... more On rat cerebral and cerebellar cortex, severe hypoglycemia with isoelectric EEG induced extensive deterioration of the energy state and gross alteration of amino acid contents. During recovery, tissue glucose concentration returned to normal, while the rate of glycogen synthesis was slow, both lactate and pyruvate concentrations increasing to above normal. In the recovery period, the ATP concentration increased but the adenine nucleotide pool remained reduced, even if the ADP and AMP contents were close to normal. Phosphocreatine was restored to normal concentrations with reciprocal changes in creatine content. During recovery there was a rise in glutamate and glutamine concentrations, gamma-aminobutyrate content returning to normal value. Ammonia and aspartate decreased below normal, while alanine increased above normal. The effect of some drugs on the post-hypoglycemic recovery was tested: (a) Ergot alkaloids (dihydroergocristine, dihydroergocriptine, dihydroergocornine); (b) Vinc...
Il Farmaco; edizione scientifica
The effect of hypoxia and post-hypoxic recovery were studied in gastrocnemius muscle of young-adu... more The effect of hypoxia and post-hypoxic recovery were studied in gastrocnemius muscle of young-adult and mature beagle dogs. Furthermore, the possible interference of pharmacological treatment with nicergoline was evaluated in these conditions. Muscular glycolytic fuels, intermediates and end-products (glycogen, glucose, glucose 6-phosphate, pyruvate, lactate), Kreb's cycle intermediates (citrate, alpha-ketoglutarate, succinate, malate) and related free amino acids (glutamate, alanine), ammonium ion, energy store and mediators (ATP, ADP, AMP and creatine phosphate), and the energy charge potential were evaluated. Furthermore, in the crude extract and/or mitochondrial fraction of another portion of the same gastrocnemius muscle the maximum rate (Vmax) of some muscular enzymes related to the anaerobic glycolytic pathway (hexokinase, lactate dehydrogenase), the Kreb's cycle (citrate synthase, malate dehydrogenase), the aminoacid pool related to the Krebs' cycle (glutamate de...
Basic and applied histochemistry, 1989
Muscle biopsies from quadriceps femoris muscle of normal subjects and subjects with symptoms of c... more Muscle biopsies from quadriceps femoris muscle of normal subjects and subjects with symptoms of congenital myopathy, aged 1-3 years, were examined for morphological and biochemical differences. Four patients showed clinical signs of Congenital Fibre Type Disproportion (CFTD) as described originally by Brooke (1973), while the other cases showed only signs of hypotonia and diffuse weakness as described by Clancy et al. (1980). No morphological differences between patients with different clinical signs were found in any biopsy sample from the quadriceps femoris muscle, as regards fibre size; type I fibres were always smaller than type II fibres. The difference in fibre size was more than 15% in all cases, and the variability coefficient of the larger type II fibres was less than 250. Nevertheless, as regards fibre occurrence, two patients showed more type I fibres than type II fibres, four patients showed more type II fibres than type I fibres and one patient had a marked type II fibr...
Nutrition in Clinical Practice, 1997
To investigate the effects of a low‐protein diet (LPD) in chronic renal failure (CRF), muscle bio... more To investigate the effects of a low‐protein diet (LPD) in chronic renal failure (CRF), muscle biopsies were performed on eight nondialyzed patients before and after 1 year of reduced protein intake (0.5 g/kg/d) with calorie intake equal to 1.4 x resting energy expenditure (1.4 x REE). Serum parathormone, glucagon, insulin levels, blood HCO3‐, and pH were measured before and after LPD. The bicycle exercise test also was performed to evaluate exercise tolerance. The control group consisted of 12 healthy sedentary subjects matched for sex, age, and weight. Twelve months of LPD caused an increase in muscle adenosine triphosphate (ATP) concentration (p .001) and a reduction both in citrate (p < .05) and α‐ketoglutarate (p < .05) concentrations. Citrate synthase (p < .05) and alanine aminotransferase (p < .05) activities decreased. No significant changes were noted in hormonal and blood acid‐base status. Patients with CRF reported reduced muscle weakness during physical activi...
Pharmacological Research, 1994
The characteristics of the energy metabolism were evaluated in the gastrocnemius muscle from 3- a... more The characteristics of the energy metabolism were evaluated in the gastrocnemius muscle from 3- and 24-month-old rats in normoxia or subjected to either mild or severe chronic (4 weeks) intermittent normobaric hypoxia. Furthermore, 4-week treatment with saline or the TRH-analogue posatireline was performed. The muscular concentration of the following metabolites related to the energy metabolism 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; energy charge potential. Furthermore the maximum rate 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 age-related decrease in muscular glucose 6-phosphate, pyruvate and alanine concentrations and increase in citrate concentration were consistent with the age-related decreased hexokinase and increased citrate synthase activities. Ageing was characterized by a decrease in muscular creatine phosphate concentration, while the energy mediators and the energy charge potential were unchanged. The chronic (4 weeks) intermittent normobaric mild and severe hypoxia-induced alterations of the components in the anaerobic glycolytic pathway, tricarboxylic acid cycle and energy storage, that were magnified in the skeletal muscle from the oldest animals. The effect of the chronic treatment with the TRH-analogue posatireline suggests that the action of central nervous system-acting drugs could also be related to their direct influence on the muscular biochemical mechanisms related to the energy transduction.
Pharmacological Research, 1995
Nutritional Neuroscience, 2008
Neurobiology of Aging, 1992
Mechanisms of Ageing and Development, 1990
Metabolite concentrations in gastrocnemius and soleus muscles were compared in young-adult (4 mon... more Metabolite concentrations in gastrocnemius and soleus muscles were compared in young-adult (4 months), mature (12 months) and senescent (24 months) rats after continuous (72 consecutive hours) exposure to normobaric hypoxia or normoxia with the intraperitoneal administration of the vasodilator naftidrofuryl or saline solution for 30 days consecutively before hypoxia. The following metabolites were assessed in gastrocnemius muscle in relation to: (a) energy mediators: ATP, ADP, AMP; (b) energy store: creatine phosphate; (c) anaerobic glycolysis: glycogen, glucose, glucose 6-phosphate, pyruvate, lactate; (d) Krebs' cycle: citrate, alpha-ketoglutarate, malate; (e) free amino acids related to Krebs' cycle: aspartate, glutamate, alanine; and (f) ammonia. In the soleus muscle only ATP, creatine phosphate, glycogen, glucose, glucose 6-phosphate, pyruvate, lactate, citrate, alpha-ketoglutarate malate, aspartate and glutamate were assessed. Aging does not seem to affect soleus and gastrocnemius muscles in the same way. Some gastrocnemius muscle metabolites show linear changes in their concentrations with aging, while for the soleus muscle the only linear change relates to glucose 6-phosphate. As regards the influence of hypoxia on muscular metabolism, all the most important changes observed in metabolite concentrations in comparison with control values take place at the age of 4 and 24 months. Furthermore, as regards naftidrofuryl action, the most important variations observed concern only 4-month-old animals. Finally our data show that only in certain cases has pharmacological treatment been able to modify the influence of hypoxic conditions on the concentration of muscle metabolites, regardless of the age of the animals.
Mechanisms of Ageing and Development, 1990
The synaptic energy state may be defined by the redox state of the intramitochondrial NAD-couple ... more The synaptic energy state may be defined by the redox state of the intramitochondrial NAD-couple (delta Gox-red) and the phosphorylation state of adenine nucleotide system (delta GATP). The biological energy 'lost' by the system during the coupled reactions is calculated as delta delta G = delta Gox-red-delta GATP. These evaluations are performed in synaptosomes isolated from the forebrain of rats of different ages (20, 60 and 100 weeks of age) and incubated in Krebs-Henseleit-Hepes (pH 7.4) buffer, for 10 min at 24 degrees C. The animals are submitted for 10 min to different degrees of in vivo hypoxia. To better elucidate the mechanism of action, the effects of the pretreatment with agents inducing vasodilation (papaverine), or acting on cerebral carbohydrate metabolism (hopanthenate), or on neurotransmission and cerebral metabolism (theniloxazine) are tested. In synaptosomes isolated from the forebrain of animals submitted to moderate degree of hypoxia (PaO2 = 32-29 mmHg) the efficiency of the system is quite similar to that observed in normoxia, with the exception of the older rats. In synaptosomes isolated from the forebrain of rats submitted to severe degree of hypoxia (PaO2 = 20-18 mmHg) the efficiency is altered as a function of both aging and severity of hypoxemia. Drug pretreatment may partially interfere with the delta delta G by hypoxemia, the action being related to the rat age and hypoxic degrees. The age-related decrease in the efficiency of the coupled states seems to be related to alteration in the phosphorylation state of adenine nucleotides.
Journal of Neuroscience Research, 1982
Some metabolites (glycogen, glucose, glucose‐6‐phosphate, pyruvate, lactate, citrate, α‐ketogluta... more Some metabolites (glycogen, glucose, glucose‐6‐phosphate, pyruvate, lactate, citrate, α‐ketoglutarate, succinate, fumarate, malate, glutamate, aspartate, γ‐aminobutyrate, glutamine, alanine, NH+4) were measured in rat cerebral cortex after 5 minutes of complete compression ischemia, as well as after 5, 15, or 30 minutes of recirculation following 5 minutes of ischemia.Complete ischemia induced a drop of glycolytic substrates and intermediates, consistent with the increase of lactate, succinate, alanine, and γ‐aminobutyrate, and with the decrease of malate, fumarate, and α‐ketoglutarate. These events may be regarded as an expression of the activation of the γ‐aminobutyrate cycle and of the succinate cycle, where succinate itself, in the absence of O2, acts as a terminal electron acceptor.During post‐ischemic recovery, cerebral parameters tended to normalize, except for the further increase of alanine and the still higher than normal content of both succinate and γ‐aminobutyrate, as a...
Journal of Neuroscience Research, 1991
Journal of Cerebral Blood Flow & Metabolism, 1982
The synaptosomal fractions obtained from the motor area of the cerebral cortex of normocapnic, no... more The synaptosomal fractions obtained from the motor area of the cerebral cortex of normocapnic, normoxic, or hypoxic, untreated beagle dogs and of pentobarbital (Nembutal®)- or cytidine diphosphate (CDP)-choline-treated dogs were incubated and analyzed for ATP, ADP, AMP, creatine phosphate, pyruvate, and lactate. The data were compared with data obtained by the surface freezing technique from the whole contralateral cortical area. The in vivo intracarotid perfusion of the drug differentially affected the content of the metabolites and their ratio. This occurred whether the evaluations were performed in the incubated synaptosomal preparations or in whole cerebral tissue, both during normoxia and after hypoxia (15 min; Pao2= 17–19 mm Hg). Thus intracarotid perfusion of nembutal increased the synaptosomal phosphorylation state both in normoxic and in hypoxic animals, whereas the effect on the metabolism of the contralateral cortical motor area as a whole was in all cases less than that ...
Journal of Cardiothoracic and Vascular Anesthesia, 1991
The purpose of this work was to evaluate the biochemical changes in the myocardial cell using car... more The purpose of this work was to evaluate the biochemical changes in the myocardial cell using cardioplegia supplemented with creatine phosphate (CP). Many previous studies have demonstrated the beneficial effect of CP on the ischemic myocardium and its mechanism of action has been assumed to be mainly extracellular. Based on the assumption that CP could also exert some influence on myocardial cellular metabolism, this investigation was carried out. Forty patients undergoing mitral valve replacement were divided into two groups: group 1 was treated with standard cardioplegic solution, and group 2 was treated with cardioplegic solution enriched with CP at a concentration of 10 mmol/L. Samples of papillary muscle, obtained from the removed valve, were studied by means of biochemical methods in order to assess the enzyme activities and the metabolites of the different biochemical pathways related to energy metabolism in the myocardial cell. One papillary muscle sample was used to determine enzyme activities spectrophotometrically; another was used to evaluate metabolite concentrations by spectrophotometric or spectrophotofluorimetric methods. The rate of spontaneous functional recovery after rewarming and weaning from cardiopulmonary bypass (CPB) also was evaluated. In group 2, the Vmax of enzymatic activities was significantly greater (hexokinase, malate dehydrogenase, glutamate dehydrogenase, total NADH cytochrome c reductase) and a better functional state of the heart was observed after CPB. On the basis of the clinical and biochemical data, it is concluded that the myocardium was better preserved when CP was added to the cardioplegic solution. Therefore, the results suggest a possible interaction of exogenous CP with cellular metabolism.
Experimental Physiology, 2003
Beta-agonists and glucocorticoids are frequently coprescribed for chronic asthma treatment. In th... more Beta-agonists and glucocorticoids are frequently coprescribed for chronic asthma treatment. In this study the effects of 4 week treatment with beta-agonist clenbuterol (CL) and glucocorticoid dexamethasone (DEX) on respiratory (diaphragm and parasternal) and limb (soleus and tibialis) muscles of the mouse were studied. Myosin heavy chain (MHC) distribution, fibres cross sectional area (CSA), glycolytic (phosphofructokinase, PFK; lactate dehydrogenase, LDH) and oxidative enzyme (citrate synthase, CS; cytochrome oxidase, COX) activities were determined. Muscle samples were obtained from four groups of adult C57/B16 mice: (1) Control (2) Mice receiving CL (CL, 1.5 mg kg(-1) day(-1) in drinking water) (3) Mice receiving DEX (DEX, 5.7 mg kg(-1) day(-1) s.c.) (4) Mice receiving both treatments (DEX + CL). As a general rule, CL and DEX showed opposite effects on CSA, MHC distribution, glycolytic and mitochondrial enzyme activities: CL alone stimulated a slow-to-fast transition of MHCs, an increase of PFK and LDH and an increase of muscle weight and fibre CSA; DEX produced an opposite (fast-to-slow transition) change of MHC distribution, a decrease of muscle weight and fibre CSA and in some case an increase of CS. The response varied from muscle to muscle with mixed muscles, as soleus and diaphragm, being more responsive than fast muscles, as tibialis and parasternal. In combined treatments (DEX + CL), the changes induced by DEX or CL alone were generally minimized: in soleus, however, the effects of CL predominated over those of DEX, whereas in diaphragm DEX prevailed over CL. Taken together the results suggest that CL might counteract the unwanted effects on skeletal muscles of chronic treatment with glucocorticoids.
Experimental Gerontology, 2000
International Journal of Immunopathology and Pharmacology, 2012
Neurobiology of Aging, 1991
Il Farmaco; edizione scientifica, 1980
Dose/action and time/action relationships relative to the effect of the in vivo treatment with so... more Dose/action and time/action relationships relative to the effect of the in vivo treatment with some biological molecules (cytidine, uridine and glutamine) on several enzymatic activities connected with cerebral metabolism (lactate dehydrogenase, malate dehydrogenase, total NADH cytochrome c reductase, cytochrome oxidase and citrate synthase) were studied in the normal rat brain. While time/action curves were found to be in agreement with classical pharmacodynamic descriptions, dose/action curves exhibited a varying behavior according to the biological substrate tested (brain homogenate in toto or crude mitochondrial fraction from brain in toto). Often enzymatic activity changes as a function of dose failed to show linear correlations, a parabolic pattern being observed. At any rate, the changes affecting several cerebral enzymatic activities may account for some pharmacodynamic properties of the biological molecules tested.
Il Farmaco; edizione scientifica, 1984
The content of "energy-rich" phosphates was markedly decreased in rat cerebral cortex a... more The content of "energy-rich" phosphates was markedly decreased in rat cerebral cortex after 20 min of severe hypoglycemia, followed by partial restitution during the recovery period. The adenine nucleotide pool remained reduced even if the energy charge returned to normal. During hypoglycemia the non-glucose endogenous substrates were provided by glycolytic intermediates, by Krebs' cycle intermediates and by related amino acids. Other substrates for brain oxidation were provided by the breakdown of phospholipids and fatty acids. After a 20 min period of post-hypoglycemic recovery, partial restoration of carbohydrates and amino acids occurred, the amino acid pool size being still reduced. The alterations in phospholipids and fatty acids persisted, while there was a tendency towards normalization of the free fatty acid cerebral content. During the post-hypoglycemic recovery, treatment with some specific metabolic modulators (i.e., uridine, L-acetylcarnitine, hopantenate,...
Il Farmaco; edizione scientifica, 1984
On rat cerebral and cerebellar cortex, severe hypoglycemia with isoelectric EEG induced extensive... more On rat cerebral and cerebellar cortex, severe hypoglycemia with isoelectric EEG induced extensive deterioration of the energy state and gross alteration of amino acid contents. During recovery, tissue glucose concentration returned to normal, while the rate of glycogen synthesis was slow, both lactate and pyruvate concentrations increasing to above normal. In the recovery period, the ATP concentration increased but the adenine nucleotide pool remained reduced, even if the ADP and AMP contents were close to normal. Phosphocreatine was restored to normal concentrations with reciprocal changes in creatine content. During recovery there was a rise in glutamate and glutamine concentrations, gamma-aminobutyrate content returning to normal value. Ammonia and aspartate decreased below normal, while alanine increased above normal. The effect of some drugs on the post-hypoglycemic recovery was tested: (a) Ergot alkaloids (dihydroergocristine, dihydroergocriptine, dihydroergocornine); (b) Vinc...
Il Farmaco; edizione scientifica
The effect of hypoxia and post-hypoxic recovery were studied in gastrocnemius muscle of young-adu... more The effect of hypoxia and post-hypoxic recovery were studied in gastrocnemius muscle of young-adult and mature beagle dogs. Furthermore, the possible interference of pharmacological treatment with nicergoline was evaluated in these conditions. Muscular glycolytic fuels, intermediates and end-products (glycogen, glucose, glucose 6-phosphate, pyruvate, lactate), Kreb's cycle intermediates (citrate, alpha-ketoglutarate, succinate, malate) and related free amino acids (glutamate, alanine), ammonium ion, energy store and mediators (ATP, ADP, AMP and creatine phosphate), and the energy charge potential were evaluated. Furthermore, in the crude extract and/or mitochondrial fraction of another portion of the same gastrocnemius muscle the maximum rate (Vmax) of some muscular enzymes related to the anaerobic glycolytic pathway (hexokinase, lactate dehydrogenase), the Kreb's cycle (citrate synthase, malate dehydrogenase), the aminoacid pool related to the Krebs' cycle (glutamate de...
Basic and applied histochemistry, 1989
Muscle biopsies from quadriceps femoris muscle of normal subjects and subjects with symptoms of c... more Muscle biopsies from quadriceps femoris muscle of normal subjects and subjects with symptoms of congenital myopathy, aged 1-3 years, were examined for morphological and biochemical differences. Four patients showed clinical signs of Congenital Fibre Type Disproportion (CFTD) as described originally by Brooke (1973), while the other cases showed only signs of hypotonia and diffuse weakness as described by Clancy et al. (1980). No morphological differences between patients with different clinical signs were found in any biopsy sample from the quadriceps femoris muscle, as regards fibre size; type I fibres were always smaller than type II fibres. The difference in fibre size was more than 15% in all cases, and the variability coefficient of the larger type II fibres was less than 250. Nevertheless, as regards fibre occurrence, two patients showed more type I fibres than type II fibres, four patients showed more type II fibres than type I fibres and one patient had a marked type II fibr...
Nutrition in Clinical Practice, 1997
To investigate the effects of a low‐protein diet (LPD) in chronic renal failure (CRF), muscle bio... more To investigate the effects of a low‐protein diet (LPD) in chronic renal failure (CRF), muscle biopsies were performed on eight nondialyzed patients before and after 1 year of reduced protein intake (0.5 g/kg/d) with calorie intake equal to 1.4 x resting energy expenditure (1.4 x REE). Serum parathormone, glucagon, insulin levels, blood HCO3‐, and pH were measured before and after LPD. The bicycle exercise test also was performed to evaluate exercise tolerance. The control group consisted of 12 healthy sedentary subjects matched for sex, age, and weight. Twelve months of LPD caused an increase in muscle adenosine triphosphate (ATP) concentration (p .001) and a reduction both in citrate (p < .05) and α‐ketoglutarate (p < .05) concentrations. Citrate synthase (p < .05) and alanine aminotransferase (p < .05) activities decreased. No significant changes were noted in hormonal and blood acid‐base status. Patients with CRF reported reduced muscle weakness during physical activi...
Pharmacological Research, 1994
The characteristics of the energy metabolism were evaluated in the gastrocnemius muscle from 3- a... more The characteristics of the energy metabolism were evaluated in the gastrocnemius muscle from 3- and 24-month-old rats in normoxia or subjected to either mild or severe chronic (4 weeks) intermittent normobaric hypoxia. Furthermore, 4-week treatment with saline or the TRH-analogue posatireline was performed. The muscular concentration of the following metabolites related to the energy metabolism 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; energy charge potential. Furthermore the maximum rate 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 age-related decrease in muscular glucose 6-phosphate, pyruvate and alanine concentrations and increase in citrate concentration were consistent with the age-related decreased hexokinase and increased citrate synthase activities. Ageing was characterized by a decrease in muscular creatine phosphate concentration, while the energy mediators and the energy charge potential were unchanged. The chronic (4 weeks) intermittent normobaric mild and severe hypoxia-induced alterations of the components in the anaerobic glycolytic pathway, tricarboxylic acid cycle and energy storage, that were magnified in the skeletal muscle from the oldest animals. The effect of the chronic treatment with the TRH-analogue posatireline suggests that the action of central nervous system-acting drugs could also be related to their direct influence on the muscular biochemical mechanisms related to the energy transduction.
Pharmacological Research, 1995
Nutritional Neuroscience, 2008
Neurobiology of Aging, 1992
Mechanisms of Ageing and Development, 1990
Metabolite concentrations in gastrocnemius and soleus muscles were compared in young-adult (4 mon... more Metabolite concentrations in gastrocnemius and soleus muscles were compared in young-adult (4 months), mature (12 months) and senescent (24 months) rats after continuous (72 consecutive hours) exposure to normobaric hypoxia or normoxia with the intraperitoneal administration of the vasodilator naftidrofuryl or saline solution for 30 days consecutively before hypoxia. The following metabolites were assessed in gastrocnemius muscle in relation to: (a) energy mediators: ATP, ADP, AMP; (b) energy store: creatine phosphate; (c) anaerobic glycolysis: glycogen, glucose, glucose 6-phosphate, pyruvate, lactate; (d) Krebs' cycle: citrate, alpha-ketoglutarate, malate; (e) free amino acids related to Krebs' cycle: aspartate, glutamate, alanine; and (f) ammonia. In the soleus muscle only ATP, creatine phosphate, glycogen, glucose, glucose 6-phosphate, pyruvate, lactate, citrate, alpha-ketoglutarate malate, aspartate and glutamate were assessed. Aging does not seem to affect soleus and gastrocnemius muscles in the same way. Some gastrocnemius muscle metabolites show linear changes in their concentrations with aging, while for the soleus muscle the only linear change relates to glucose 6-phosphate. As regards the influence of hypoxia on muscular metabolism, all the most important changes observed in metabolite concentrations in comparison with control values take place at the age of 4 and 24 months. Furthermore, as regards naftidrofuryl action, the most important variations observed concern only 4-month-old animals. Finally our data show that only in certain cases has pharmacological treatment been able to modify the influence of hypoxic conditions on the concentration of muscle metabolites, regardless of the age of the animals.
Mechanisms of Ageing and Development, 1990
The synaptic energy state may be defined by the redox state of the intramitochondrial NAD-couple ... more The synaptic energy state may be defined by the redox state of the intramitochondrial NAD-couple (delta Gox-red) and the phosphorylation state of adenine nucleotide system (delta GATP). The biological energy 'lost' by the system during the coupled reactions is calculated as delta delta G = delta Gox-red-delta GATP. These evaluations are performed in synaptosomes isolated from the forebrain of rats of different ages (20, 60 and 100 weeks of age) and incubated in Krebs-Henseleit-Hepes (pH 7.4) buffer, for 10 min at 24 degrees C. The animals are submitted for 10 min to different degrees of in vivo hypoxia. To better elucidate the mechanism of action, the effects of the pretreatment with agents inducing vasodilation (papaverine), or acting on cerebral carbohydrate metabolism (hopanthenate), or on neurotransmission and cerebral metabolism (theniloxazine) are tested. In synaptosomes isolated from the forebrain of animals submitted to moderate degree of hypoxia (PaO2 = 32-29 mmHg) the efficiency of the system is quite similar to that observed in normoxia, with the exception of the older rats. In synaptosomes isolated from the forebrain of rats submitted to severe degree of hypoxia (PaO2 = 20-18 mmHg) the efficiency is altered as a function of both aging and severity of hypoxemia. Drug pretreatment may partially interfere with the delta delta G by hypoxemia, the action being related to the rat age and hypoxic degrees. The age-related decrease in the efficiency of the coupled states seems to be related to alteration in the phosphorylation state of adenine nucleotides.
Journal of Neuroscience Research, 1982
Some metabolites (glycogen, glucose, glucose‐6‐phosphate, pyruvate, lactate, citrate, α‐ketogluta... more Some metabolites (glycogen, glucose, glucose‐6‐phosphate, pyruvate, lactate, citrate, α‐ketoglutarate, succinate, fumarate, malate, glutamate, aspartate, γ‐aminobutyrate, glutamine, alanine, NH+4) were measured in rat cerebral cortex after 5 minutes of complete compression ischemia, as well as after 5, 15, or 30 minutes of recirculation following 5 minutes of ischemia.Complete ischemia induced a drop of glycolytic substrates and intermediates, consistent with the increase of lactate, succinate, alanine, and γ‐aminobutyrate, and with the decrease of malate, fumarate, and α‐ketoglutarate. These events may be regarded as an expression of the activation of the γ‐aminobutyrate cycle and of the succinate cycle, where succinate itself, in the absence of O2, acts as a terminal electron acceptor.During post‐ischemic recovery, cerebral parameters tended to normalize, except for the further increase of alanine and the still higher than normal content of both succinate and γ‐aminobutyrate, as a...
Journal of Neuroscience Research, 1991
Journal of Cerebral Blood Flow & Metabolism, 1982
The synaptosomal fractions obtained from the motor area of the cerebral cortex of normocapnic, no... more The synaptosomal fractions obtained from the motor area of the cerebral cortex of normocapnic, normoxic, or hypoxic, untreated beagle dogs and of pentobarbital (Nembutal®)- or cytidine diphosphate (CDP)-choline-treated dogs were incubated and analyzed for ATP, ADP, AMP, creatine phosphate, pyruvate, and lactate. The data were compared with data obtained by the surface freezing technique from the whole contralateral cortical area. The in vivo intracarotid perfusion of the drug differentially affected the content of the metabolites and their ratio. This occurred whether the evaluations were performed in the incubated synaptosomal preparations or in whole cerebral tissue, both during normoxia and after hypoxia (15 min; Pao2= 17–19 mm Hg). Thus intracarotid perfusion of nembutal increased the synaptosomal phosphorylation state both in normoxic and in hypoxic animals, whereas the effect on the metabolism of the contralateral cortical motor area as a whole was in all cases less than that ...
Journal of Cardiothoracic and Vascular Anesthesia, 1991
The purpose of this work was to evaluate the biochemical changes in the myocardial cell using car... more The purpose of this work was to evaluate the biochemical changes in the myocardial cell using cardioplegia supplemented with creatine phosphate (CP). Many previous studies have demonstrated the beneficial effect of CP on the ischemic myocardium and its mechanism of action has been assumed to be mainly extracellular. Based on the assumption that CP could also exert some influence on myocardial cellular metabolism, this investigation was carried out. Forty patients undergoing mitral valve replacement were divided into two groups: group 1 was treated with standard cardioplegic solution, and group 2 was treated with cardioplegic solution enriched with CP at a concentration of 10 mmol/L. Samples of papillary muscle, obtained from the removed valve, were studied by means of biochemical methods in order to assess the enzyme activities and the metabolites of the different biochemical pathways related to energy metabolism in the myocardial cell. One papillary muscle sample was used to determine enzyme activities spectrophotometrically; another was used to evaluate metabolite concentrations by spectrophotometric or spectrophotofluorimetric methods. The rate of spontaneous functional recovery after rewarming and weaning from cardiopulmonary bypass (CPB) also was evaluated. In group 2, the Vmax of enzymatic activities was significantly greater (hexokinase, malate dehydrogenase, glutamate dehydrogenase, total NADH cytochrome c reductase) and a better functional state of the heart was observed after CPB. On the basis of the clinical and biochemical data, it is concluded that the myocardium was better preserved when CP was added to the cardioplegic solution. Therefore, the results suggest a possible interaction of exogenous CP with cellular metabolism.
Experimental Physiology, 2003
Beta-agonists and glucocorticoids are frequently coprescribed for chronic asthma treatment. In th... more Beta-agonists and glucocorticoids are frequently coprescribed for chronic asthma treatment. In this study the effects of 4 week treatment with beta-agonist clenbuterol (CL) and glucocorticoid dexamethasone (DEX) on respiratory (diaphragm and parasternal) and limb (soleus and tibialis) muscles of the mouse were studied. Myosin heavy chain (MHC) distribution, fibres cross sectional area (CSA), glycolytic (phosphofructokinase, PFK; lactate dehydrogenase, LDH) and oxidative enzyme (citrate synthase, CS; cytochrome oxidase, COX) activities were determined. Muscle samples were obtained from four groups of adult C57/B16 mice: (1) Control (2) Mice receiving CL (CL, 1.5 mg kg(-1) day(-1) in drinking water) (3) Mice receiving DEX (DEX, 5.7 mg kg(-1) day(-1) s.c.) (4) Mice receiving both treatments (DEX + CL). As a general rule, CL and DEX showed opposite effects on CSA, MHC distribution, glycolytic and mitochondrial enzyme activities: CL alone stimulated a slow-to-fast transition of MHCs, an increase of PFK and LDH and an increase of muscle weight and fibre CSA; DEX produced an opposite (fast-to-slow transition) change of MHC distribution, a decrease of muscle weight and fibre CSA and in some case an increase of CS. The response varied from muscle to muscle with mixed muscles, as soleus and diaphragm, being more responsive than fast muscles, as tibialis and parasternal. In combined treatments (DEX + CL), the changes induced by DEX or CL alone were generally minimized: in soleus, however, the effects of CL predominated over those of DEX, whereas in diaphragm DEX prevailed over CL. Taken together the results suggest that CL might counteract the unwanted effects on skeletal muscles of chronic treatment with glucocorticoids.
Experimental Gerontology, 2000