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Biomedical subjects

L C Fernandes

Publications and source records attributed to L C Fernandes.

At least 19 recordsLinked to original sources

The effects of peroxovanadate and peroxovanadyl on glucose metabolism in vivo and identification of signal transduction proteins involved in the mechanism of action in isolated soleus muscle.

The insulin-like effects of peroxovanate (POV) and peroxovanadyl (PSV) on rates of lactate formation and glycogen synthesis were measured in isolated incubated soleus muscle preparations. In another experiment rats were made insulin deficient by streptozotocin injection and treated with POV and PSV (0.25 mM) administered in the drinking water and in the course of 7 days glycemia were determined. Also, signal transduction proteins ERK 1 and ERK 2 involved in the insulin signaling were measured in soleus muscle of diabetic rats treated with POV and PSV. Peroxides of vanadate and vanadyl significantly stimulated glucose utilization in soleus muscle preparations in vitro. The stimulation of glycogen synthesis and lactate formation by POV and PSV was similar to insulin stimuli. Rats treated with POV or PSV presented reduction of glycemia, food and fluid intake with amelioration of the diabetic state during the short period of treatment (7 days). POV and PSV modulated ERK1/2 phosphorilation and the insulin administration in these rats caused an addictive effect on phosphorilation state of these proteins.

Animals↗

Effect of chronic fish oil supplementation on renal function of normal and cachectic rats.

In the present study we determined the effect of chronic diet supplementation with n-3 PUFA on renal function of healthy and cachectic subjects by providing fish oil (1 g/kg body weight) to female rats throughout pregnancy and lactation and then to their offspring post-weaning and examined its effect on renal function parameters during their adulthood. The animals were divided into four groups of 5-10 rats in each group: control, control supplemented with fish oil (P), cachectic Walker 256 tumor-bearing (W), and W supplemented with fish oil (WP). Food intake was significantly lower in the W group compared to control (12.66 +/- 4.24 vs 25.30 +/- 1.07 g/day). Treatment with fish oil significantly reversed this reduction (22.70 +/- 2.94 g/day). Tumor growth rate was markedly reduced in the P group (16.41 +/- 2.09 for WP vs 24.06 +/- 2.64 g for W). WP group showed a significant increase in mean glomerular filtration rate compared to P and control (1.520 +/- 0.214 ml min-1 kg body weight-1; P < 0.05). Tumor-bearing groups had low urine osmolality compared to control rats. The fractional sodium excretion decreased in the W group compared to control (0.43 +/- 0.16 vs 2.99 +/- 0.87%; P < 0.05), and partially recovered in the WP group (0.90 +/- 0.20%). In summary, the chronic supplementation with fish oil used in this study increased the amount of fat in the diet by only 0.1%, but caused remarkable changes in tumor growth rate and cachexia, also showing a renoprotective function.

Animals↗

Effects of fish oil on the central nervous system: a new potential antidepressant?

In the last 100 years major depression has increased worldwide. In this study we provided coconut fat (CF, rich in saturated fatty acids) or fish oil (FO, rich in n-3 polyunsaturated fatty acids) to female rats throughout pregnancy and lactation and then to their offspring post-weaning and examined lipid brain profile and the possible effect of FO as antidepressant agent in the offspring in adulthood (F1). Rats were submitted to forced swimming test, elevated plus maze, Morris water maze and open field. Peroxidation rate in the cerebral cortex and hippocampus were measured. Docosahexaenoic acid (DHA) concentration in dam's milk, eicosapentaenoic acid (EPA) and DHA concentration in hippocampus and cerebral cortex from F1 rats FO supplemented increased significantly when compared to control (C) and CF rats. Arachidonic acid/EPA ratio in the cerebral cortex and hippocampus decreased in rats submitted to forced swimming test. Peroxidation rate were not different between the groups. Immobility time in the forced swimming test in FO group was reduced (p < 0.01) when compared to C and CF rats. We conclude that lifelong intake of FO was able to induce an antidepressant effect with EPA and DHA concentration increased in the cerebral cortex and hippocampus.

Animals↗

Naproxen, clenbuterol and insulin administration ameliorates cancer cachexia and reduce tumor growth in Walker 256 tumor-bearing rats.

Cancer cachexia is characterized by anorexia and intense peripheral catabolism. We examine the potential benefits of combination of different anabolic agents such as insulin and clenbuterol associated to prostaglandin synthesis inhibitor (naproxen) on tumor growth, cachexia and renal function in Walker 256 tumor-bearing rats (WK). Groups were separated into WK, and WK with naproxen (WK N) or naproxen plus clenbuterol (WK NCb) or naproxen plus clenbuterol plus insulin (WK NCbI). Treatment begins at the 4th day after tumor inoculation, at the 14th day they were killed, glycemia, lacticidemia, glycogen content from liver, soleus and gastrocnemius muscles, tumor mass, body weight and kidney function were determined. Glycemia and glycogen content were reduced and lacticidemia increased in WK (p<0.05) as compared to control rats. The glycogen content recovered in all treated groups. Tumor weight was significantly reduced by the different treatments. At the 14th weight change (carcass-initial body weight) in the control increased by 38% and in the WK -2%. Naproxen treatment (WK N) induced an increased by 14%. The inclusion of clenbuterol (WK NCb) and insulin (WK NCbI) by 38 and 41%, respectively. Mean glomerular filtration rate (GFR) increased in the WK (p<0.05) as compared to control, but in the WK NCb the GFR was similar to control. Our results suggest that naproxen is able to reduce tumor growth and its association with insulin and clenbuterol induce mass weight gain and recovery energy fuel.

Adrenergic beta-Agonists↗

Indirect costs of migraine in a public Brazilian hospital.

OBJECTIVES: To evaluate the indirect costs of migraine affecting employees of a public Brazilian hospital. BACKGROUND: Migraine is a common primary headache which has a negative influence on the well-being and quality of life, as well as the professional life, of affected individuals. METHODS: Our series consisted of 846 employees with migraine. The Lost Hours Equivalence Index, which considers both the hours lost due to the absence from work and reduction in productivity, was used to estimate the number of working hours lost due to migraine. RESULTS: Of the employees with migraine studied, 91% presented a mean 56.9% loss of productivity. The mean number of total lost working hours per month due to migraine was 6.5. The estimated total indirect cost of migraine was R $986 903.77 (US $815 622.54), implicating costs of R $241.30 (US $199.42) per employee per year. CONCLUSIONS: Based on its impact on life and the resulting costs, migraine should be considered a public health problem and thus measures should be adopted to reduce its impact on the individual and on society.

Absenteeism↗

[Migraine prevalence and impact in employees of the clinical hospital of the medical school of Ribeirão Preto-USP].

Headache is a common symptom in the population, with a life prevalence around 90%. It results in an important impact in the life quality of sufferers. The aim of this study is to evaluate the prevalence of migraine among employees of an university hospital (HC), as well as to measure the headache intensity, interference and impact in the daily activities. A total of 1890 employees had answered to a questionnaire which made possible to carry out diagnosis of migraine. Life prevalence of this headache type was 30. 4%. Pain was considered intense, most of the time, by 86% of the migraneurs. It was verified an important impact in the daily life aspects as much during as between the headache attacks. It can be concluded that migraine represents a public health problem among the HC employees. Because migraine brings about an important impact in the life quality of those workers, it is possible that a reduction of working capacity with considerable economic burden exists. This problem deserves, thus, special attention, through a better diagnostic and treatment.

Brazil↗

[Hospital costs of acute headaches in a Brazilian public emergency room unit].

Headache is one of the most frequent complain in the medical practice and a very common cause of medical assistance searching in emergency rooms, leading to considerable high costs. The headache cases assisted during the year of 1996 of an emergency room unit (UE - USP) at Ribeirão Preto, SP, Brazil, had been retrospectively studied. During that year a number of 1254 patients searched the UE - USP with major complain of acute headache, among which 64 needed hospitalization. The estimated costs due to consultation, investigation and clinical treatment of the acute headaches was in the order of R$ 138 573.31 (US$ 76 985.17). The expenses related only to laboratorial exams were R$ 23 801.54 (US$ 13 223.07). The surgical expenses were R$ 5 817.90 (US$ 3 232.17). The total cost was R$ 144 391.21 (US$ 80 217.34) which corresponds to R$ 115.14 (US$ 63.97) per patient. This calculus instigates an additional discussion about the costs and effectiveness of the current public health policy, where the financial resources are less abundant than the State dependant population's needs.

Acute Disease↗

The effect of melatonin chronic treatment upon macrophage and lymphocyte metabolism and function in Walker-256 tumour-bearing rats.

Melatonin is the main hormone involved in the neuroendocrine-immune axis. It also presents antitumour activity. To evaluate the role of melatonin on the progression of Walker-256 tumour in rats we determined the effect of the hormone on some biochemical and functional aspects of macrophage and lymphocytes from cachectic rats. An important finding observed in immune cells from tumour-bearing (TB) rats is the impairment on glutamine and glucose metabolism in such cells. These changes are very similar to those observed in pinealectomized rats (PNX). The increased production of lactate and the flux of glucose through the Krebs cycle and the reduction in glutamine consumption seems to be involved in the immunosuppression presented in the TB and PNX animals. Melatonin treatment restored the changes observed in the metabolism of glucose and glutamine and stimulated the proliferation of lymphocytes from tumour-bearing rats. The results indicate that the effect of melatonin upon tumour growth involves the stimulation of the immune system by the hormone.

Animals↗

Glucose metabolism in the erythrocytes of the buffalo (Bubalus bubalis).

14CO2 production from [1-14C] glucose, the rate of glycolysis measured by the value of lactate production and the activities of various enzymes were determined in buffalo erythrocytes. Buffalo red cell glycolytic metabolites were estimated and used for the calculation of the mass action ratios of reactions catalyzed by the glycolytic enzymes of Bubalus bubalis. A comparison of the values of the mass action ratios with the equilibrium constants of the various glycolytic reactions indicate that hexokinase, phosphofructokinase, phosphoglycerate kinase and pyruvate kinase reactions are displaced from equilibrium, suggesting a regulatory role for each of these enzymes in buffalo erythrocyte glycolysis.

Animals↗

Insulin treatment can abolish changes in glucose and glutamine metabolism of lymphocytes and macrophages caused by the implantation of the Walker 256 tumour.

Activation of lymphocytes and macrophages by the implantation of tumour cells (10(7) cells per rat) into the left flank of rats increased the conversion of glucose to lactate and of glutamine to glutamate and aspartate and the decarboxylation of [U-14C]-glucose and [U-14C]-glutamine in incubated cells. In addition, the amount of GLUT1 was increased in macrophages. The effect of insulin treatment on glucose and glutamine metabolism of lymphocytes and macrophages activated by Walker 256 tumour implantation was also examined. For this purpose, insulin was injected subcutaneously (4 U/100 g b.w. daily) after the fourth day of tumour implantation and the rats were killed 10 days afterwards. Insulin treatment fully reverted the changes due to tumour implantation in the metabolism of glucose and glutamine in lymphocytes and of glucose in macrophages.

Animals↗

Insulin and prostaglandins as signals between tumor and the host immune system.

The development of malignant tissue in vivo is partially favored by the immunosuppression that occurs in cancer patients. However, the signals between tumor and immune tissues remain to be identified. We present evidence that prostaglandins may act as one of these signals by a direct action on cells of the immune system, or by inhibition of insulin secretion which in turn suppresses immune function, or both.

Animals↗

Metabolism of a chylomicron-like emulsion in rats with Walker 256 tumor: influence of a polyunsaturated (n-6) compared with a saturated fatty acid-rich diet.

OBJECTIVE: Defects in lipid metabolism secondary to development of cancer are frequently observed and, in experimental animals, manipulation of the lipid content of the diet can significantly influence tumor growth. The effects of a high polyunsaturated fat vs a high saturated fat diet upon the chylomicron metabolism of rats bearing Walker 256 tumor were examined. METHODS: Chylomicron-like emulsions labeled with radioactive lipids were injected into rats bearing the tumor and control rats. The two groups were previously given a high polyunsaturated (n-6) (15% fat) or a high saturated fat diet (15% fat) for 6 weeks. Following injection, plasma samples were collected at 8 time intervals in 60 minutes and tissue fragments were excised after the animals were killed, for determination of the plasma fractional clearance rate (FCR, min-1) and organ uptake of radioactive lipids. RESULTS: FCR of the emulsion triacylglycerols (TG) and cholesteryl oleate ether (CE) decreased in the tumor-bearing rats fed the polyunsaturated fat-rich diet (FCR-TG control = 0.26 +/- 0.09, tumor = 0.11 +/- 0.04; FCR-CE controls = 0.18 +/- 0.05, tumor = 0.10 +/- 0.02), as did activity of the lipoprotein and hepatic lipases (p < 0.05). This indicates that in this group, the presence of the tumor elicited defective lipolysis and delayed removal of the emulsion from the plasma. In the group fed the saturated fatty acid-rich diet, however, these alterations were not observed (FCR-TG control = 0.21 +/- 0.11, tumor = 0.20 +/- 0.08; FCR-CE control = 0.13 +/- 0.06, tumor = 0.10 +/- 0.05). The uptake by several tissues of the emulsion CE was similar in all rat groups. CONCLUSION: The saturated fat-rich diet avoids the deficiency in chylomicron lipolysis elicited by the implanted Walker 256 tumor.

Animals↗

Metabolism of glucose, glutamine and pyruvate in lymphocytes from Walker 256 tumor-bearing rats.

This study examined the effect of Walker 256 tumor growth in vivo on the metabolism of glucose, glutamine and pyruvate in lymphocytes. A comparison between the metabolism of Walker 256 tumor cells obtained in vivo with that of lymphocytes was also carried out. Lymphocytes and tumor cells were isolated and incubated for 1 h for the following measurements: lactate production from glucose (5.6 mM) and pyruvate (3 mM), glutamate and aspartate formation from glutamine (3 mM) and decarboxylation of [U-14C]-glucose, [U-14C]-glutamine, [1-14C]-pyruvate and [3-14C]-pyruvate. The presence of the tumor increased lactate production (2.7-fold from glucose and 2-fold from pyruvate), decarboxylation of [U-14C]-glucose (3.7-fold) and [1-14C]-pyruvate (4.4-fold) and the formation of aspartate (6.3-fold) and glutamate (4.6-fold) from glutamine. The conversion of glucose to lactate and CO2 was higher in tumor cells as compared to lymphocytes. Tumor cells also showed a higher production of glutamate and an 8-fold increased decarboxylation rate of [U-14C]-glutamine in tumor cells, which was more active than that of lymphocytes even from tumor-bearing rats. Tumor growth stimulated glucose and glutamine metabolism in lymphocytes; however, the importance of this fact for the function of these cells remains to be elucidated.

Animals↗

The effects of orthovanadate, vanadyl and peroxides of vanadate on glucose metabolism in skeletal muscle preparations in vitro.

The insulin-like effects of various vanadium compounds (orthovanadate, vanadyl and peroxides of vanadate) on rates of glucose oxidation, lactate formation and glycogen synthesis were measured in isolated incubated epitrochlearis (mainly type II fibres) and soleus (mainly type I fibres) muscle preparations. There was a small stimulation of the rate of glucose utilisation in soleus muscle preparations in vitro by orthovanadate (1 mM). Orthovanadate or vanadyl, at 1 mM, had little effect on the rates of lactate formation or glycogen synthesis in isolated incubated epitrochlearis muscle preparations. In contrast, peroxides of vanadate (peroxovanadates, at 1 mM) significantly stimulated glucose utilisation in both soleus and epitrochlearis muscle preparations in vitro. The stimulation of the rate of glycogen synthesis was associated with an increase in the percentage of glycogen synthase in the I (or a) form. Peroxovanadates were administered in the drinking water to rats made insulin deficient by streptozotocin treatment. There was no decrease in the elevated level of blood glucose over an 8 day administration period.

Animals↗

Metabolic changes of several adipose depots as caused by aging.

In this study, metabolic changes of several adipose depots as caused by aging were investigated. Key enzyme activity of glutaminolysis, pentose-phosphate pathway and Krebs cycle were measured. The rates of lipogenesis from 3H2O, lipoprotein lipase (LPL) activity and rate of lipolysis in vitro were also determined. The results obtained indicate a reduced capacity for lipogenesis in several adipose depots by aging. The authors concluded that hypertrophy of adipose tissue reported during aging is possible due to increased LPL activity and reduced rate of lipolysis.

Adipose Tissue↗

Insulin secretion in Walker 256 tumor cachexia.

The effect of cachexia on insulin secretion was examined in adult male rats. Isolated islets of Langerhans from Walker 256 tumor-bearing rats secreted less insulin by glucose stimuli as compared with the control group; this was accompanied by significant change in 45Ca2+ outflow rate. Reduced insulin secretion to glucose stimuli in tumor-bearing rats probably led to low insulinemia (one-third). These findings indicate that reduced insulin secretion is probably an important factor for the development of cachexia in Walker 256 tumor-bearing rats.

Animals↗