Biomedical subjects

M C Carrillo

Publications and source records attributed to M C Carrillo.

At least 19 recordsLinked to original sources

PubMed1997

Impaired trace eyeblink conditioning in bilateral, medial-temporal lobe amnesia.

Trace eyeblink classical conditioning was assessed in patients with bilateral medial-temporal amnesia and matched control participants who had previously shown equivalent delay eyeblink conditioning (J. D. E. Gabrieli et al., 1995). The silent trace interval varied for durations of 500, 750, or 1,000 ms in successive sessions separated by at least 2 weeks; extinction trials followed each session. Patients with amnesia produced significantly fewer conditioned responses (CRs) than did control participants at all trace intervals. Both groups produced fewer CRs as the trace interval lengthened. Thus, the temporal lobe memory system in humans makes an essential contribution to normal acquisition in trace, but not delay, classical eyeblink conditioning.

Adult↗

PubMed1996

Hepatic protein synthesis and serum aminoacid levels during liver regeneration in young and old malnourished rats.

The aim of the present study was to measure protein synthesis in regenerating liver and to evaluate the impact of malnutrition in young and old rats. Two groups of male Wistar rats were used: young rats (4 months old) and old rats (18 months old). The rats were allocated to malnutrition or ordinary food intake for 1 week. Half of each group was sham-operated and the other was partially hepatectomized 2 days before the end of diet manipulation. Hepatic protein synthesis was significantly increased in all hepatectomized groups compared with their respective sham group: young well-nourished hepatectomized rats, 44%; young malnourished hepatectomized rats, 55%; old well-nourished hepatectomized rats, 47%; and old malnourished hepatectomized rats only 21%. Hepatic DNA content was unchanged in all groups and liver RNA content was higher in young malnourished hepatectomized rats (21%, P < 0.05). Serum total amino acid concentration did not change in young well-nourished hepatectomized and young malnourished hepatectomized rats. This value did not show significant changes between old well-nourished hepatectomized and old well-nourished sham, but it increased 14% (P < 0.05) in old malnourished hepatectomized. It was concluded that (a) regeneration is not impaired by malnutrition in young rats and may even be better than in rats eating a normal diet, and (b) the deleterious effect of aging is revealed once old animals are exposed to malnutrition. It is manifested in the decreased rate in hepatic protein synthesis observed in old malnourished hepatectomized rats and in the augmentation of total serum amino acid concentration, where the hypercatabolism induced by hepatectomy is significantly greater.

Age Factors↗

PubMed1996

Upregulation of antioxidant enzyme activities by deprenyl. Implications for life span extension.

In order to elucidate the exact role of antioxidant enzyme activities such as superoxide dismutase (SOD) in the aging process of animals, we compared various enzyme activities in different brain regions and in the liver of young (6-8 mo) and old (28-30 mo) Fischer-344 (F-344) rats. While Mn-SOD activities were elevated 3-5-fold in specific brain regions such as hippocampus, striatum and substantia nigra in brains of old male rats compared with the young, in females both forms of SOD (Cu, Zn- and Mn-) enzyme activities remained essentially unchanged with aging. Continued subcutaneous infusion of deprenyl for 3 weeks caused a 2-3-fold increase in activities of both Cu Zn- and Mn-SOD and a 50-60% increase in CAT activities in striatum and substantia nigra but not in hippocampus, cerebellum or the liver. Further, long-term treatment of old male rats with deprenyl caused a significant increase in the remaining life expectancy from 24 months of age by 34%. In conclusion, activities of antioxidant enzymes in these regions examined do not show any uniform age-associated change, suggesting that changes in these enzyme activities do not have any specific role in the life span of rodents in general terms. In contrast, the results of our deprenyl study suggests the possibility that the protection of catecholaminergic neurons by an upregulation of SOD and CAT activities plays a significant role in the life span of animals.

Animals↗

PubMed1996

Functional mapping of human learning: a positron emission tomography activation study of eyeblink conditioning.

Regional cerebral blood flow (rCBF) was measured using positron emission tomography during eyeblink conditioning in young adults. Subjects were scanned in three experimental conditions: delay conditioning, in which binaural tones preceded air puffs to the right eye by 400 msec; pseudoconditioning, in which presentations of tone and air puff stimuli were not correlated in time; and fixation rest, which served as a baseline control. Compared with fixation, pseudoconditioning produced rCBF increases in frontal and temporal cortex, basal ganglia, left hippocampal formation, and pons. Learning-specific activations were observed in conditioning as compared with pseudoconditioning in bilateral frontal cortex, left thalamus, right medial hippocampal formation, left lingual gyrus, pons, and bilateral cerebellum; decreases in rCBF were observed for bilateral temporal cortex, and in the right hemisphere in putamen, cerebellum, and the lateral aspect of hippocampal formation. Blood flow increased as the level of learning increased in the left hemisphere in caudate, hippocampal formation, fusiform gyrus, and cerebellum, and in right temporal cortex and pons. In contrast, activation in left frontal cortex decreased as learning increased. These functional imaging results implicate many of the same structures identified by previous lesion and recording studies of eyeblink conditioning in animals and humans and suggest that the same brain regions in animals and humans mediate multiple forms of associative learning that give meaning to a previously neutral stimulus.

Adult↗

PubMed1996

Long term treatment with (-)deprenyl reduces the optimal dose as well as the effective dose range for increasing antioxidant enzyme activities in old mouse brain.

C57BL mice of the male sex received different doses of (-)deprenyl (0.25, 0.5, 1.0 mg/kg per injection 3 times a week, s.c.) for 3 months beginning at the age of 26 months. At the age of 29 months, animals were sacrificed and superoxide dismutase (SOD) and catalase (CAT) activities were examined in several brain regions. The dose of 0.5 mg/kg (3 times a week) was most effective in increasing SOD and CAT activities in S. nigra, striatum and cerebral cortex but not in hippocampus or cerebellum. The dose of 0.25 mg/kg was also effective in increasing enzyme activities, but the effect was much lower than the dose of 0.5 mg/kg. The magnitudes of increase in enzyme activities with the dose of 0.5 mg/kg, however, were generally much lower than respective values we previously found in animals treated with (-)deprenyl for only 3 weeks. The highest dose of 1.0 mg/kg had negligible effect. Enzyme activities in all groups of animals that were examined 2 weeks after the last (-)deprenyl dose were practically the same as respective control values. Together with the results from our previous study with short term (-)deprenyl treatment in old mice, these results replicate our previous findings in old female rats. We showed that longer term treatment with (-)deprenyl reduces the optimal dose for increasing antioxidant enzyme activities by a factor of 5 to 10. The present study further indicates that longer term treatment with (-)deprenyl also reduces the effective dose range of (-)deprenyl as well as the magnitude of increase of enzyme activities. If the effect of (-)deprenyl for increasing these antioxidant enzyme activities in selective brain regions is causally related to its effect of increasing average life expectancies of animals, the selection of a proper dose of the drug may be a critical factor for life span studies in which the drug, is administered for more than one year.

Aging↗

PubMed1996

Sex-related differences in the effect of aluminum on calcium transport in the small intestine of the rat.

Everted sacs of distinct segments of small intestine from male and female rats were incubated with 2 microM of aluminum (Al). In duodenum, Al significantly diminished calcium flux (JCams) in cycling females (31%, P < 0.01) and in males (17%, P < 0.05). Incubation under anaerobic conditions nullified the inhibition of Al on JCams both in male and in female duodenal sacs. Jejunal and ileal JCams measured under aerobic conditions were not modified by the presence of Al in mucosal fluid compared to Al-free controls, neither in males nor in cycling females. In ovariectomized female rats treated with estrogen the studies of dose-response curves showed that the sensitivity to the effect of Al on JCams was raised (the dose that produced half maximum response diminished) with increasing 17 beta-estradiol serum levels, without changes in the maximum response. In castrated male rats injected with testosterone, the effect of Al on duodenal JCams was found to be independent of testosterone levels. In summary, our results demonstrated that the Al inhibition on duodenal JCams was influenced by sexual hormone levels in females but was independent of them in males.

Alkaline Phosphatase↗

PubMed1995

Is intestinal cytosolic glutathione S-transferase an alternative detoxification pathway in two-thirds hepatectomized rats?

The present study was designed to investigate the effect of partial (two-thirds) hepatectomy (PH) on hepatic and intestinal glutathione S-transferases (GSTs) activities. A significant decrease of cytosolic hepatic GSTs activity was observed after the PH. The lowest value of hepatic GSTs was obtained 48 h after the surgery. On the other hand, intestinal GSTs activities increased after PH, reaching the highest values 48 h after the hepatic lobes resection. The hepatic GSTs activities diminution was attributed, in part, to the high accumulation of bile acids in the liver tissue of hepatectomized rats, also demonstrated by a higher retention of [14C] taurocholate. The kinetic analysis performed with 1-chloro-2,4-dinitrobenzene (CDNB) as substrate showed two sets of parameters, indicating the presence of isozymes of high and low affinities. Vmax1 and Vmax2 were lower in PH rats suggesting a non competitive inhibition mechanism. The inhibitory effect of bile acids decreased during liver regeneration process of hepatectomized rats disappearing at 7 days after PH. Conversely, in non regenerating rats (GABA treated) the inhibitory mechanism was still observed at 7 days after the surgery. The increase of intestinal GSTs activities (isozymes of high and low affinities) was attributed to the presence of polyamines, mainly putrescine, produced during the hepatic regeneration process. In this regard, it was showed that GABA treatment, which inhibits polyamine synthesis, completely abolished the increase on intestinal GSTs activities. Finally, the treatment with exogenous putrescine showed that in hepatectomized and sham-operated rats, the polyamine induced GSTs activities in both tissues. In PH rats, the putrescine dependent increase of hepatic GSTs was masked by the inhibitory effect of bile acids. In addition, a summation effect of endogenous and exogenous putrescine was probably the reason of the induction of intestinal GSTs after PH. The GSH/GSSG ratio did not change during the treatments, as well as the microsomal GST activity of both tissues. The work points out the hypothetical detoxification power of the intestine during the hepatocellular insufficiency which follows a two-thirds hepatectomy.

Animals↗

PubMed1995

Acute regulation of hepatic glutathione S-transferase by insulin and glucagon.

The intravenous administration of insulin plus glucose in anesthetized rats caused, within 30 min, an increase of about 56% in hepatic cytosolic glutathione S-transferase (GST) activity, but it did not affect the microsomal enzyme. The injection of glucagon resulted, at the same time, in a 43% drop in the hepatic cytosolic GST, without affecting the microsomal GST. The insulin-dependent increase in cytosolic GST activity was abolished by the pretreatment of the animals with an inhibitor of protein synthesis (cycloheximide). A kinetic analysis revealed a non-competitive inhibition caused by glucagon upon the cytosolic enzyme. In addition, the presence of insulin did not interfere with the effectiveness of glucagon, and vice versa. We propose that: (1) the effect of insulin on hepatic cytosolic GST activity requires protein synthesis; (2) glucagon produces an inhibition of hepatic cytosolic GST, which could be mediated by cytosolic effectors such as adenosine 3'-5'-cyclic monophosphate (cAMP); (3) the effects of glucagon and insulin were not mutually exclusive; (4) hepatic microsomal GST is regulated by different mechanism(s).

Animals↗

PubMed1995

Intact delay-eyeblink classical conditioning in amnesia.

The status of classical conditioning in human amnesia was examined by comparing conditioning of the eyeblink response (the unconditional response) to a tone conditioned stimulus (CS) paired with an airpuff unconditioned stimulus (US) in the delay paradigm between 7 amnesic and 7 age- and education-matched normal control participants. Amnesic patients exhibited normal baseline performance in pseudoconditioning and normal acquisition and extinction of conditioned responses in terms of the number, latency, and magnitude of eyeblinks. These results indicate that in humans, as in rabbits, brain structures critical for declarative memory are not essential for the acquisition of elementary CS-US associations.

Adult↗

PubMed1995

Impaired delay eyeblink conditioning in amnesic Korsakoff's patients and recovered alcoholics.

The performance of amnesic Korsakoff patients in delay eyeblink classical conditioning was compared with that of recovered chronic alcoholic subjects and healthy normal control subjects. Normal control subjects exhibited acquisition of conditioned responses (CRs) to a previously neutral, conditioned tone stimulus (CS) following repeated pairings with an unconditioned air-puff stimulus, and demonstrated extinction of CRs when the CS was subsequently presented alone. Both amnesic Korsakoff patients and recovered chronic alcoholic subjects demonstrated an impairment in their ability to acquire CRs. These results indicate that the preservation of delay eyeblink conditioning in amnesia must depend on the underlying neuropathology of the amnesic syndrome. It is known that patients with amnesia caused by medial temporal lobe pathology have preserved conditioning. We have now demonstrated that patients with amnesia caused by Korsakoff's syndrome, as well as recovered chronic alcoholic subjects, have impaired conditioning. This impairment is most likely caused by cerebellar deterioration resulting from years of alcohol abuse.

Aged↗

PubMed1995

Role of calcium fluxes in the action of glucagon on cytosolic glutathione S-transferase activity in rat liver slices.

In a previous study we demonstrated that the administration of 20 micrograms/kg b.wt. of glucagon to rats caused a significant diminution of hepatic cytosolic glutathione S-transferase (GST) activity. This inhibition was non-competitive and reversible. We suggested that the effect would be mediated by cytosolic effectors. The present work was performed to characterize the mechanism involved in this inhibition. Liver tissue slices (170 to 200 mg) were incubated during different periods of time (0, 5, 10, 15, 20 and 30 min.) with several concentrations of glucagon (10(-5) M, 10(-8) M and 10(-10) M), dibutiryl cyclic AMP (10(-4) M, 10(-6) M and 10(-9) M), divalent cation ionophore A23187 (10(-4) M, 10(-6) M and 10(-9) M) or vasopressin (10(-7) M, 5 x 10(-7) M and 10(-8) M). The incubation was done with or without calcium in the medium. In all cases the cytosolic GST activity were determined in liver slices. The percentage of inhibition of GST activity was directly related to the increase of concentration of the test substances. An inhibition between 40% to 45% after 10 min. of incubation with the highest concentrations was observed (except vasopressin which caused 10% of inhibition). 10(-10) M glucagon did not produce a decrease of GST activity. The inhibition disappeared in calcium-free incubated slices, but direct relationship between plasma-membrane calcium influx and inhibition of GST activity (r = 0.950, P < 0.001, n = 24) could be obtained. By using calmodulin antagonists, we conclude that the inhibition process of the enzyme was mediated by calmodulin. In summary, we propose that plasma-membrane calcium influx induced by high concentrations of glucagon activates calmodulin, which promotes a modification (actually a methylation, according to other authors) on GST, thereby causing a decrease in its activity.

Animals↗

PubMed1994

Short-term feeding of a diet enriched in phospholipids increases bile formation and the bile acid transport maximum in rats.

Earlier studies suggested that the secretory rate maximum (SRm) of bile acid and the cholestasis which occurs after the SRm is reached may be determined by the hepatic or extrahepatic biliary phospholipid pool. We therefore investigated whether bile formation and the bile acid SRm could be influenced by feeding a diet enriched in phospholipids. Male rats were fed phospholipid (PLD) or triacylglycerol (TgD)-enriched diet for 3 days, and bile formation as well as biliary lipid output were measured on the 4th day. In other similarly fed groups, cholic acid was infused in stepwise increasing doses to determine the effect of PLD on the SRm of cholic acid. The plasma lipid levels were significantly lower in PLD and TgD diets compared to basal diet. But, while the levels of total cholesterol (CH), HDL-CH, and phospholipid (PH) were not significantly altered by PLD compared to TgD, the triacylglycerol levels were markedly increased by PLD. In the liver of PLD fed rats, triacylglycerol and CH ester contents decreased by 39 and 62%, respectively, while free CH and PH contents were not significantly changed. The PLD significantly augmented spontaneous bile flow, bile acid, PH and CH secretion rates compared to TgD diet (65, 124, 164 and 654%, respectively). The enhanced biliary secretory function was associated with an increase in pericanalicular vacuoles and diverticuli in centrilobular hepatocytes. Compared to TgD fed rats, PLD rats showed a 2-fold decrease in the ratio of cholic acid/chenodeoxycholic acid in bile and a significant decrease in the % contribution of taurine conjugated BA. The PH fatty acids in bile were similar in both groups except that in PLD group the % contribution of C18:2 was higher than in TgD group. No differences were found in plasma membrane CH/PH content or total fatty acid composition. During bile acid infusion, the SRm and the total cholic acid secreted were significantly higher in the PLD than in the TgD rats. Moreover, the cholestatic response observed after high bile acid dose was markedly reduced by PLD. The results show that short-term feeding of PLD induces changes in CH and bile acid metabolism which result in enhanced biliary output of CH and PH. The enhanced pool of biliary lipid may protect plasma membranes from the deleterious effects of high bile acid concentrations.

Animals↗

PubMed1994

(-)Deprenyl increases the life span as well as activities of superoxide dismutase and catalase but not of glutathione peroxidase in selective brain regions in Fischer rats.

(-)Deprenyl, a MAO-B inhibitor that is also known to be effective for symptoms of Parkinson's disease, when injected subcutaneously (sc) in male Fischer-344 rats at a dose of 0.5 mg/kg per day (3 times a week) from 18 months of age, significantly increased the remaining life expectancy. The average life span after 24 months was 34% greater in treated rats than in saline-treated control animals. Furthermore, a short-term (3 wk) continuous sc infusion of deprenyl significantly increased activities of superoxide dismutase and catalase but not of glutathione peroxidase in selective brain regions such as s. nigra, striatum, and cerebral cortex, but not in hippocampus or cerebellum, or the liver. The optimal dose for increasing these activities, however, differed greatly depending on the sex and age of animals, with a 10-fold lower value for young female than male rats. Interestingly, aging caused an increase and a decrease in the optimal dose in female and male rats, respectively. In addition, treatment for a longer term tended to reduce the optimal dosage in the same animal group. The results clearly demonstrate that deprenyl increases antioxidant enzyme activities in selective brain regions. If this effect of deprenyl is causally related to its life-prolonging effect, the dosage to be used for any life span study would be a critical factor, with the dosage differing widely depending on sex, age of animal, and mode and duration of drug administration.

Animals↗

PubMed1994

The effect of a long term (6 months) treatment with (-)deprenyl on antioxidant enzyme activities in selective brain regions in old female Fischer 344 rats.

The effect of long term treatment with (-)deprenyl (s.c. injection three times a week for 6 months) on superoxide dismutase (SOD) and catalase (CAT) in selective brain regions was examined in old (22 months) female Fischer 344 rats. The three doses of deprenyl used (0.1, 0.25 and 0.5 mg/kg/day) increased the activities of both enzymes in substantia nigra, striatum and cerebral cortices essentially in a dose dependent manner. However, for CAT activities in cerebral cortices, the smallest dose of 0.1 mg/kg/day was most effective, while the highest dose (0.5 mg/kg/day) had no effect. In contrast to these brain regions, there were no significant differences in enzyme activities between control and deprenyl-treated groups in the hippocampus and cerebellum. If the effect of deprenyl on the life span of female F-344 rats is causally related to its effect on antioxidant enzyme activities in selective brain regions as shown in this study, then a dose of 0.25 or 0.5 mg/kg/day appears to be most appropriate. Since this dose is much lower than the dose suggested by our previous short term (3 week) experiments, an even longer term experiment is necessary to determine the optimal dose of deprenyl to increase free radical scavenging and thus possibly extend lifespan.

Aging↗

PubMed1994

(-)deprenyl increases activities of superoxide dismutase and catalase in certain brain regions in old male mice.

A subcutaneous continuous infusion of (-)deprenyl for 3 weeks in old C57BL male mice increased superoxide dismutase (SOD) and catalase (CAT) activities in s. nigra, striatum and cerebral cortex but not in hippocampus, cerebellum or liver. The doses of 0.5 and 1.0 mg/kg/day were most effective, while with a higher dose (2.0 mg/kg/day), deprenyl tended to lose its effect slightly and with a lower dose (0.25 mg/kg/day) deprenyl was clearly less effective. The results suggest that deprenyl can increase antioxidant enzyme activities in certain brain regions in mice as was previously demonstrated in rats of both sexes and different ages; this raises the possibility that deprenyl has this particular effect in animal species other than rats.

Aging↗

PubMed1994

(-)Deprenyl increases activities of superoxide dismutase (SOD) in striatum of dog brain.

Seven beagle dogs were administered sucrose (control animals) or different doses of (-)deprenyl orally by means of capsules for 3 weeks. Activities of Cu Zn-SOD and Mn-SOD were determined in striatum and hippocampus in these animals. There was a significant dose-dependent increase in activities of total as well as in both types of SOD enzymes in striatum but not in hippocampus. The results suggest that this monoamine oxidase B inhibitor can increase antioxidant enzyme activities in striatum but not in hippocampus in the dog, thus showing brain region selectivity. These results are in accordance with previously published observations in rats.

Animals↗

PubMed1994

Moderate long-term physical activity improves the age-related decline in bile formation and bile salt secretion in rats.

This study examined the effect of moderate long-term exercise, begun soon after weaning, on the age-related decline in bile formation and the secretory rate maximum (SRm) of taurocholate (TC), the major bile salt (BS) in rats. Eight-month-old sedentary (S) female Sprague-Dawley rats showed a significant decrease in basal and TC-stimulated bile formation when compared with 2.5-month-old S controls. As in younger rats, decreased biliary phospholipid (PL) output was associated with the TC SRm, but this change appeared much more rapidly in S animals, which also exhibited significant increased plasma lipids and higher TC concentrations in plasma and liver at the end of the TC infusion. Exercise significantly improved bile flow (BF), including the bile salt-dependent and -independent fractions under basal and TC-stimulated conditions in 8 month-old rats. Although all the biliary parameters evaluated were improved, maximal BF and PL secretion values were affected the most and were virtually not different from those obtained in younger S animals. Exercise also significantly lowered the age-related elevation of plasma PL. Thus, moderate long-term exercise exerts a beneficial effect on hepatobiliary function and the BS SRm, an effect that may be attributed in part to increased availability of a biliary PL pool previously implicated in regulation of the BS SRm.

Age Factors↗

PubMed1993

Chronic treatment of (-)deprenyl prolongs the life span of male Fischer 344 rats. Further evidence.

Seventy male Fischer 344 (F-344) rats were treated with s.c. injection of (-)deprenyl (0.5 mg/kg, n = 35) or physiological saline (n = 35) 3 times a week from the age of 18 months until the time of their natural death. The fifty percent survival time was 28 months in control animals and 30 months in the deprenyl treated group. The mean survival time after the start of treatment (18 months) and after 24 months were 378.3 +/- 97.4 days (mean +/- SD) and 196.3 +/- 97.4 days, respectively, in deprenyl treated rats and 328.7 +/- 108.8 days and 146.7 +/- 108.7 days in control rats. The increases in average life expectancies caused by deprenyl treatment (15% from 18 months and 34% from 24 months) were both statistically significant (P < 0.05, two-tailed t-test). The average body weights were comparable for both groups but the variation of body weight was greater in control groups, thus excluding the possibility that the life prolonging effect of deprenyl results from reduced dietary intake. The results confirm those of two previous studies (1,2) which reported a significant life prolonging effect of deprenyl in aged rats and lend added support to the results of a study on male F-344 rats where the effect was only marginally significant (16% increase after 24 months, P = 0.048 by one-tailed t test) (2).

Animals↗