Effect of melatonin treatment on oxygen consumption by rat liver mitochondria.

The objective of this study was to examine the in vivo effect of melatonin on rat mitochondrial liver respiration. Two experiments were performed: For experiment 1, adult male rats received melatonin in the drinking water (16 or 50 microg/ml) or vehicle during 45 days. For experiment 2, rats received melatonin in the drinking water (50 microg/ml) for 45 days, or the same amount for 30 days followed by a 15 day-withdrawal period. At sacrifice, a liver mitochondrial fraction was prepared and oxygen consumption was measured polarographically in the presence of excess concentration of DL-3-beta-hydroxybutyrate or L-succinate. Melatonin treatment decreased Krebs' cycle substrate-induced respiration significantly at both examined doses. The stimulation of mitochondrial respiration caused by excess concentration of substrate recovered after melatonin withdrawal. Basal state 4 respiration was not modified by melatonin. Melatonin, by curtailing overstimulation of cellular respiration caused by excess Krebs' cycle substrates, can protect the mitochondria from oxidative damage.

Comparative effects of melatonin and vitamin E in restoring aortic relaxation in pancreatectomized rats.

In a previous study we reported the efficacy of melatonin to restore the decreased relaxation response to acetylcholine (ACh) or to sodium nitroprusside (SNP) in aortic rings of rats turned hyperglycemic by subtotal pancreatectomy. The effect was amplified by pre-incubation in a high (44 mmol/l) glucose solution, a situation that resulted in oxidative stress. We hereby compare the effect of another antioxidant, vitamin E, with that of melatonin on ACh response in intact aortic rings or on SNP response in endothelium-denuded aortic rings obtained from pancreatectomized or sham-operated rats. Dose-response curves to ACh or SNP were performed in the presence or absence of melatonin or vitamin E (10-5 mol/1) in 10 or 44 mmol/1 glucose medium. Melatonin was more effective than vitamin E in restoring ACh- or SNP-induced relaxation of aortic rings in a high glucose medium. The differences between the two antioxidants may rely on the ability of melatonin to diffuse readily into intracellular compartments.

Blood sugar concentrations during ketamine or pentobarbitone anesthesia in rats with or without alpha and beta adrenergic blockade.

Plasma glucose concentrations were measured in: 1) conscious and anesthetized rats during an iv glucose tolerance test (IVGTT) and 2) conscious and anaesthetized phentolamine/propranolol blocked rats during an IVGTT. Anesthesia was induced with ketamine (120 mg.kg-1) or pentobarbitone (60 mg.kg-1) ip at -30 min of the beginning of the IVGTT, which was followed by 2 injections of the anesthetic agents at intervals of 30 min. Propranolol (2 mg.kg-1) was given ip at -25 and -5 min. An iv infusion of phentolamine (0.015 mg.min-1) was started at -20 min and continued up to the end of the experiment. During the IVGTT, the anesthetized rats showed a moderate hyperglycemic response to glucose load compared to conscious animals (ketamine: p < 0.01 at 5 min; and p < 0.05 at 10-20 min; pentobarbitone: p < 0.05 at 5-20 min). The hyperglycemic response to glucose administration in the conscious rats was not affected by adrenergic blockade (p > 0.05). While in ketamine anesthetized rats the increased glucose response was abolished by adrenergic blockade (p < 0.05 at 5-10 min), this effect was not seen in pentobarbitone anesthetized animals. These results suggest the existence of an inhibitory tone on insulin secretion and a glycogenolytic response in ketamine anesthetized rats, probably mediated by adrenergic inervation of the pancreas and liver and by circulating catecholamines secreted from the adrenal medulla.

Blood sugar concentrations during ketamine or pentobarbitone anesthesia in rats with or without alpha and beta adrenergic blockade.

Plasma glucose concentrations were measured in: 1) conscious and anesthetized rats during an iv glucose tolerance test (IVGTT) and 2) conscious and anaesthetized phentolamine/propranolol blocked rats during an IVGTT. Anesthesia was induced with ketamine (120 mg.kg-1) or pentobarbitone (60 mg.kg-1) ip at -30 min of the beginning of the IVGTT, which was followed by 2 injections of the anesthetic agents at intervals of 30 min. Propranolol (2 mg.kg-1) was given ip at -25 and -5 min. An iv infusion of phentolamine (0.015 mg.min-1) was started at -20 min and continued up to the end of the experiment. During the IVGTT, the anesthetized rats showed a moderate hyperglycemic response to glucose load compared to conscious animals (ketamine: p < 0.01 at 5 min; and p < 0.05 at 10-20 min; pentobarbitone: p < 0.05 at 5-20 min). The hyperglycemic response to glucose administration in the conscious rats was not affected by adrenergic blockade (p > 0.05). While in ketamine anesthetized rats the increased glucose response was abolished by adrenergic blockade (p < 0.05 at 5-10 min), this effect was not seen in pentobarbitone anesthetized animals. These results suggest the existence of an inhibitory tone on insulin secretion and a glycogenolytic response in ketamine anesthetized rats, probably mediated by adrenergic inervation of the pancreas and liver and by circulating catecholamines secreted from the adrenal medulla.

Adrenocorticotrophic hormone, cortisol and catecholamine concentrations during insulin hypoglycaemia in dogs anaesthetized with thiopentone.

Glucose homeostasis is maintained by complex neuroendocrine control mechanisms. Increases in plasma concentrations of various glucose-raising hormones such as glucagon, catecholamines, adrenocorticotrophic hormone (ACTH), and cortisol are observed under certain conditions associated with stress (haemorrhage and hypoglycaemia). The purpose of this study was to determine the effect of thiopentone anaesthesia on the catecholamine, ACTH and cortisol response to insulin hypoglycaemia in dogs. Blood sugar (BS), plasma catecholamine, and ACTH, and serum cortisol concentrations were measured during the course of (1) an intravenous insulin test (ITT) and (2) an ACTH test in conscious and in anaesthetized fasted dogs. During the ITT, the anaesthetized dogs showed a moderate resistance, compared with conscious dogs, to the hypoglycaemic action induced by insulin (blood sugar concentration 30 min after insulin injection: 2.91 +/- 0.25 vs 1.93 +/- 0.12 mM.L-1; P < 0.01). In addition, decreased epinephrine (220 +/- 27 vs 332 +/- 32 pg.ml-1), ACTH (65 +/- 6 vs 90 +/- 5 pg.ml-1) and cortisol (4.48 +/- 0.3 vs 6.25 +/- 0.5 micrograms.ml-1) concentrations were detected 60 min after insulin injection (P < 0.01). The norepinephrine response to hypoglycaemia was not altered by anaesthesia (273 +/- 33 vs 325 +/- 25 pg.ml-1). Anaesthetized dogs showed a decreased cortisol response to ACTH at 45 min (5.68 +/- 0.54 vs 8.87 +/- 0.47 micrograms.ml-1) when compared with control dogs (P < 0.001). Haemodynamic variables during anaesthesia showed little changes (P < NS); while respiratory rate was altered (P < 0.01 between 60 and 105 min).(ABSTRACT TRUNCATED AT 250 WORDS)

Blood sugar, serum insulin and serum non-esterified fatty acid levels during thiopentone anaesthesia in dogs.

The purpose of this study was to determine the effect of thiopentone anaesthesia on glucose metabolism. Blood sugar (BS), serum immunoreactive insulin (IRI) and serum non-esterified fatty acid (NEFA) concentrations were measured during the course of (1) an intravenous glucose tolerance test (IVGTT), and (2) an intravenous insulin test (ITT), in conscious and anaesthetized fasted dogs. The IVGTTs were repeated in dogs under alpha- or beta-adrenergic blockade, induced by phentolamine or propranolol. During the IVGTT, the anaesthetized dogs showed glucose intolerance (blood sugar levels were higher than in the control group) and little serum IRI response to hyperglycaemia was detected. An attenuated initial decrease and a slower rebound of NEFA concentration was observed in anaesthetized animals than in controls. Phentolamine administration (5 mg.kg-1 iv) partly restored the IRI response without affecting the BS levels; propanolol (1 mg.kg-1 iv) had no effect. Anaesthetized dogs showed a moderate resistance to insulin induced hypoglycaemic action and a lack of serum NEFA response during counter-regulation of hypoglycaemia, while in conscious controls an intense rebound was observed. Hyperinsulinaemia after iv insulin administration was longer in anaesthetized dogs than in controls. The insulin distribution space was 78% of body weight and insulin t1/2 in blood group compared with 54% and 16 min, in controls. We conclude that thiopentone provokes disturbances in glucose and serum NEFA metabolisms and abolishes the serum IRI response to hyperglycaemia. These effects are influenced by extrapancreatic factors regulating serum IRI levels and by an alpha-adrenergic mechanism, via the inhibition of insulin secretion.

[Cardiovascular effects of ketamine anesthesia in rats treated with enalapril and propranolol]. / Efectos cardiocirculatorios de la anestesia con ketamina en ratas tratadas con enalapril y propranolol.

It is well-known that ketamine (Kt) anaesthesia produces a rise in blood pressure and heart rate in man. These cardiostimulatory effects were adscribed to several factors such as: a) increased sympathetic nervous system activity by direct stimulation of central nervous structures, b) increased catecholamine release from the peripheral sympathetic system, c) high plasmatic renin levels. However, the quantitative participation of these mechanisms in the cardiovascular effects of this anaesthetic agent is unknown. While some authors have shown a major rise in serum renin activity in experimental anaesthesia, others have been unable to confirm these results. The present study was undertaken to assess if the cardiostimulatory effects of Kt anaesthesia were due to an activation of renin-angiotensin system or to increased sympathetic activity. In consequence we used rats treated with enalapril (an angiotensin-converting enzyme inhibitor) or propranolol prior to anaesthetic procedures. Thirty male Wistar and six spontaneously hypertensive rats (SHR) weighing 240-300 g were used in all the experiments. The rats were randomly grouped into six groups. I- Non-anaesthetized rats, II- Anaesthetized rats (trained in the experimental procedures), III- Anaesthetized rats (without training), IV- Anaesthetized rats previously treated with enalapril, V- Anaesthetized rats pretreated with propranolol, VI- SHR treated with enalapril. The rats of groups IV and VI received enalapril p.o. for three weeks (25 mg/Kg body wt). The animals of group V were submitted to acute beta-adrenergic blockade. Propranolol dose: 10 mg/Kg body wt, was given i.p. 15 min before Kt anaesthesia. Blood pressure and heart rate were measured with a sphygmomanometer and photoelectric sensors and recorded.(ABSTRACT TRUNCATED AT 250 WORDS)

Efectos cardiocirculatorios de la anestesia con ketamina en ratas tratadas con enalapril y propranolol. / [Cardiovascular effects of ketamine anesthesia in rats treated with enalapril and propranolol]

It is well-known that ketamine (Kt) anaesthesia produces a rise in blood pressure and heart rate in man. These cardiostimulatory effects were adscribed to several factors such as: a) increased sympathetic nervous system activity by direct stimulation of central nervous structures, b) increased catecholamine release from the peripheral sympathetic system, c) high plasmatic renin levels. However, the quantitative participation of these mechanisms in the cardiovascular effects of this anaesthetic agent is unknown. While some authors have shown a major rise in serum renin activity in experimental anaesthesia, others have been unable to confirm these results. The present study was undertaken to assess if the cardiostimulatory effects of Kt anaesthesia were due to an activation of renin-angiotensin system or to increased sympathetic activity. In consequence we used rats treated with enalapril (an angiotensin-converting enzyme inhibitor) or propranolol prior to anaesthetic procedures. Thirty male Wistar and six spontaneously hypertensive rats (SHR) weighing 240-300 g were used in all the experiments. The rats were randomly grouped into six groups. I- Non-anaesthetized rats, II- Anaesthetized rats (trained in the experimental procedures), III- Anaesthetized rats (without training), IV- Anaesthetized rats previously treated with enalapril, V- Anaesthetized rats pretreated with propranolol, VI- SHR treated with enalapril. The rats of groups IV and VI received enalapril p.o. for three weeks (25 mg/Kg body wt). The animals of group V were submitted to acute beta-adrenergic blockade. Propranolol dose: 10 mg/Kg body wt, was given i.p. 15 min before Kt anaesthesia. Blood pressure and heart rate were measured with a sphygmomanometer and photoelectric sensors and recorded.(ABSTRACT TRUNCATED AT 250 WORDS)

Efectos cardiocirculatorios de la anestesia con ketamina en ratas tratadas con enalapril y propranolol. / [Cardiovascular effects of ketamine anesthesia in rats treated with enalapril and propranolol]

It is well-known that ketamine (Kt) anaesthesia produces a rise in blood pressure and heart rate in man. These cardiostimulatory effects were adscribed to several factors such as: a) increased sympathetic nervous system activity by direct stimulation of central nervous structures, b) increased catecholamine release from the peripheral sympathetic system, c) high plasmatic renin levels. However, the quantitative participation of these mechanisms in the cardiovascular effects of this anaesthetic agent is unknown. While some authors have shown a major rise in serum renin activity in experimental anaesthesia, others have been unable to confirm these results. The present study was undertaken to assess if the cardiostimulatory effects of Kt anaesthesia were due to an activation of renin-angiotensin system or to increased sympathetic activity. In consequence we used rats treated with enalapril (an angiotensin-converting enzyme inhibitor) or propranolol prior to anaesthetic procedures. Thirty male Wistar and six spontaneously hypertensive rats (SHR) weighing 240-300 g were used in all the experiments. The rats were randomly grouped into six groups. I- Non-anaesthetized rats, II- Anaesthetized rats (trained in the experimental procedures), III- Anaesthetized rats (without training), IV- Anaesthetized rats previously treated with enalapril, V- Anaesthetized rats pretreated with propranolol, VI- SHR treated with enalapril. The rats of groups IV and VI received enalapril p.o. for three weeks (25 mg/Kg body wt). The animals of group V were submitted to acute beta-adrenergic blockade. Propranolol dose: 10 mg/Kg body wt, was given i.p. 15 min before Kt anaesthesia. Blood pressure and heart rate were measured with a sphygmomanometer and photoelectric sensors and recorded.(ABSTRACT TRUNCATED AT 250 WORDS)

[Effects of beta-adrenergic blocking with propranolol on the mechanisms of glucose regulation in the dog]. / Efectos del bloqueo beta-adrenérgico con propranolol sobre los mecanismos de regulación de la glucemia en el perro.

Propranolol (P) administration is known to cause hypoglycemia in insulin-dependent diabetic patients. The mechanisms whereby this response is produced remain controversial. Some authors postulate an inhibition in the beta-adrenergic action of catecholamines, responsible for hepatic glycogenolysis, while others indicate that these hormones are not so important in the regulation of blood sugar (BS) level. The present studies were undertaken to assess the mechanism whereby hypoglycemia is developed in the dog, with or without beta-adrenergic blockade. Unanesthetized male mongrel dogs were used, weighing 10-20 kg body wt., fed on dog chow pellets and water ad libitum up to 18-22 hours before the test performances. The dogs were randomly grouped into two groups, A and B in which the effect of P on several hormonal and metabolic responses basally and during insulin (I) test, were respectively studied. Group A was constituted by two subgroups of 6 animals each; the animals of one subgroup were beta-blocked, receiving P p.o. for 10 days (80 mg every 8 hours); the dogs of the remaining subgroup received only P excipient in the same way as the treated ones, for the same period. As P treatment was completed, blood samples were taken by venipuncture, in a peripheral vein, at 0 and 60 min. Some biological controls of beta-blockade, assessed at 0, 30 and 60 min, indicated that mean pulse rate (+/- SE) in the control dogs was 123 +/- 2, 128 +/- 2 and 128 +/- 3 beats/min while in the P treated ones was 106 +/- 2, 103 +/- 1 and 103 +/- 3 respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Efectos del bloqueo beta-adrenérgico con propranolol sobre los mecanismos de regulación de la glucemia en el perro. / [Effects of beta-adrenergic blocking with propranolol on the mechanisms of glucose regulation in the dog]

Propranolol (P) administration is known to cause hypoglycemia in insulin-dependent diabetic patients. The mechanisms whereby this response is produced remain controversial. Some authors postulate an inhibition in the beta-adrenergic action of catecholamines, responsible for hepatic glycogenolysis, while others indicate that these hormones are not so important in the regulation of blood sugar (BS) level. The present studies were undertaken to assess the mechanism whereby hypoglycemia is developed in the dog, with or without beta-adrenergic blockade. Unanesthetized male mongrel dogs were used, weighing 10-20 kg body wt., fed on dog chow pellets and water ad libitum up to 18-22 hours before the test performances. The dogs were randomly grouped into two groups, A and B in which the effect of P on several hormonal and metabolic responses basally and during insulin (I) test, were respectively studied. Group A was constituted by two subgroups of 6 animals each; the animals of one subgroup were beta-blocked, receiving P p.o. for 10 days (80 mg every 8 hours); the dogs of the remaining subgroup received only P excipient in the same way as the treated ones, for the same period. As P treatment was completed, blood samples were taken by venipuncture, in a peripheral vein, at 0 and 60 min. Some biological controls of beta-blockade, assessed at 0, 30 and 60 min, indicated that mean pulse rate (+/- SE) in the control dogs was 123 +/- 2, 128 +/- 2 and 128 +/- 3 beats/min while in the P treated ones was 106 +/- 2, 103 +/- 1 and 103 +/- 3 respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Phaeohyphomycosis in El Salvador caused by Exophiala spinifera.

We identified Exophiala spinifera as the causal agent in a case of subcutaneous phaeohyphomycosis in El Salvador. Identification was based on the morphology of the fungus in tissue and the microscopic features of the culture obtained from the biopsy material. This case is the first of this type to be documented from Central America.