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Biomedical subjects

G Fernandes

Publications and source records attributed to G Fernandes.

At least 55 records · Page 3Linked to original sources
PubMed1994

Increased TGF-beta and decreased oncogene expression by omega-3 fatty acids in the spleen delays onset of autoimmune disease in B/W mice.

This study was designed to investigate the mechanisms by which marine lipids rich in long chain omega-3 fatty acids inhibit autoimmune disease and prolong the survival rate in female (NZB/NZW) F1 (B/W) mice, an animal model for human SLE. Nutritionally adequate semipurified diets containing at 10% either corn oil (CO) or fish oil (FO) were fed from 1 mo of age and were monitored for proteinuria and survival. Proteinuria was detected earlier and became progressively severe in CO-fed mice. The average life span was significantly shortened by the CO diet (266.7 days +/- 12.5), whereas FO extended the survival significantly (402.1 days +/- 26.1; p < 0.001). A cross-sectional study at 6.5 mo of age revealed an increased proliferative response to T cell mitogens including bacterial superantigens and decreased serum anti-dsDNA Ab titers in the FO group compared with the CO group. Furthermore, splenocytes from the FO group when stimulated with Con A had higher IL-2 and lower IL-4 production similar to that of young (3.5 mo) mice. Flow cytometric analyses of splenocytes revealed lower Ig+, higher lymphocyte endothelial cell adhesion molecule-1, and lower Pgp-1+ cells within CD4+ and CD8+ subsets in FO-fed mice. Also, elevated IL-2 and IL-4 and significantly higher TGF-beta 1 and lower c-myc and c-ras mRNA expression and higher TGF-beta 1 and significantly lower c-Myc and c-Ha-Ras proteins were detected in spleens of FO-fed mice. Fatty acid analysis revealed significantly higher linoleic (18:2 omega-6) and arachidonic (20:4 omega-6) acid levels in splenocytes of the CO-fed group and higher eicosapentaenoic (20:5 omega-3) and docosahexanoic (22:6 omega-3) acid levels in the FO-fed group, indicating that changes in membrane fatty acid composition may contribute to the altered immune function and gene expression during the development of murine SLE.

Animals↗
PubMed1994

Decreased pro-inflammatory cytokines and increased antioxidant enzyme gene expression by omega-3 lipids in murine lupus nephritis.

Enrichment of diet with omega-3 lipid rich-menhaden fish oil (FO) when fed ad libitum to autoimmune lupus-prone NZB/NZW F1 (B/W) female mice delayed the onset and slowed progression of renal disease while significantly extending life-span compared to omega-6 lipid rich-corn oil (CO)-fed mice. Northern blot analysis of kidneys from FO-fed mice revealed no detectable levels of IL-1 beta, IL-6 and TNF alpha mRNA contrasted to levels that were easily detected in CO-fed mice. In contrast to the cytokines, FO-fed mice showed higher renal levels of the antioxidant enzymes-catalase, glutathione peroxidase (GSH-Px), superoxide dismutase (SOD)-mRNAs compared to CO-fed mice. The results suggest that dietary supplementation with FO, as compared to CO, inhibits the production of pro-inflammatory cytokines and ameliorates immune-complex-mediated kidney injury possibly by enhancing the ability of cells to dispose of harmful reactive oxygen intermediates.

Animals↗
PubMed1994

Dietary lipids and risk of autoimmune disease.

In summary, it is well established that moderate calorie restriction or reduction in overall high calorie food intake prevents or forestalls the development of age-associated disease incidence such as breast cancer and renal disease in rodents. A similar approach could also readily be applied in humans for preventing the risk and rise of life-shortening diseases. Many age-associated diseases, particularly autoimmune diseases with viral etiology, appear to be exacerbated in the presence of adverse lipid intake such as an increased level of vegetable oils or trans-fatty acids from the usage of hydrogenated dietary oils. At present, nearly 35-40% of the total calories are from dietary fats and/or of lipid origin. Although usage of saturated fat, which increases cardiovascular disease, has been reduced to a large extent in the United States, consumption of both monounsaturated and polyunsaturated fats of omega-6 origin has either increased or simply been substituted in place of saturated fats. Further, for the past 50 years, a significant reduction in highly polyunsaturated fat consumption such as marine oil has also occurred specifically in the United States. The reduction in omega-3 lipids of marine or vegetable source occurs primarily because of short shelf life due to rancidity. However, the increased consumption of omega-6 or a vegetable source of oils and decreased omega-3 intake may increase in vivo the production of free radicals and higher proinflammatory cytokines. Our ongoing studies reveal that proinflammatory vegetable oil could increase autoimmune disease by increasing the free radical formation by decreasing the antioxidant enzyme mRNA levels, thereby further decreasing immune function, particularly the production of anti-inflammatory cytokines such as IL-2 and TGF beta mRNA levels. In contrast, omega-3 lipid intake in the presence of an antioxidant supplement appears to exert protection against autoimmunity by enhancing antioxidant enzymes and TGF beta mRNA levels and by preventing the rise in oncogene expression. However, detailed studies are required to establish the protective and deleterious role of different commonly consumed lipids or dietary oils by the general population, particularly during middle and aging years. Further, we also propose that combining nonsteroidal drug therapy along with moderate calorie reduction in the presence of more protective omega-3 dietary lipids of either marine or vegetable source and decreasing the levels of mono- and polyunsaturated lipids may provide additional protection against the age-associated rise in malignancy and autoimmune disorders.

Animals↗
PubMed1994

Effects of n-3 and n-6 fatty acids on the activities and expression of hepatic antioxidant enzymes in autoimmune-prone NZBxNZW F1 mice.

Menhaden fish oil (FO) containing n-3 fatty acids dramatically extends the life span and delays the onset and progression of autoimmune disease in (NZBxNZW)F1 (B/W) female mice as compared to those fed corn oil (CO) rich in n-6 lipids. As an inefficient antioxidant defense system has been linked to autoimmune diseases, the present study was undertaken to determine whether the protective action of n-3 lipids is mediated through their antioxidant defense system. Weanling B/W mice were fed a nutritionally adequate, semipurified diet containing CO or krill oil (KO) or FO at 10% level (w/w) ad libitum until the mice were 6.5 months old. All diets contained the same level of vitamin E (21.5 mg/100 g diet). We compared the effects of feeding n-6 and n-3 lipids on survival, kidney disease, hepatic microsomal lipid composition, peroxidation, and on the activity and mRNA expression of the antioxidant enzymes catalase, glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) in 6.5-month-old B/W mice. The results showed that when compared to livers from CO-fed mice, livers from KO- and FO-fed mice showed: (i) significantly higher (P < 0.001) activities and expression of CAT, GSH-Px and SOD; (ii) significantly lower (P < 0.001) arachidonic acid (20:4n-6) and linoleic acid (18:2n-6) and higher (P < 0.001) eicosapentaenoic acid (20:5n-3) and docosahexaenoic acid (22:6n-3) levels in hepatic microsomes; and (iii) significantly lower (P < 0.001) estimated peroxidation indices and thiobarbituric acid reactive substances generation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Modulation of age-related alterations in membrane composition and receptor-associated immune functions by food restriction in Fischer 344 rats.

Food restriction is known to modulate aging and age-associated immune functions in rodents. In an attempt to understand the mechanism(s) through which food restriction delays age-associated loss of certain immune functions, lipid composition of spleen cells as well as binding of spleen cells to interleukin-2 (IL-2) and insulin were analyzed in four month-old and 19-month-old ad libitum fed (AL) and food-restricted (FR) Fischer-344 male rats. The results revealed that although AL-fed rats did not show a difference in age-related changes for IL-2 and insulin binding, the number of binding sites were significantly increased in the spleen cells of 19-month-old FR animals when compared with those of the 19-month-old AL group. When spleen cell phospholipid fractions were analyzed for fatty acid composition, the spleen cells from FR animals consistently revealed higher linoleic acid (18:2) levels and significantly lower arachidonic acid (20:4) and long chain fatty acid, docosatetraenoic acid (22:4) levels in the phosphatidylcholine and phosphatidylethanolamine fractions than the spleen cells of the AL rats. Further, spleen cell plasma membranes of FR rats also exhibited similar changes showing higher 18:2 and lower 20:4 and 22:4 levels than the AL animals. Finally, spleen cells obtained from 19-month-old FR animals produced higher levels of IL-2 and lesser prostaglandin E2 when compared to 19-month-old AL animals. The above observations suggest that one of the mechanisms through which food restriction may delay the loss of age-associated immune functions is through modulation of the fatty acyl composition of phospholipid fractions of spleen cell membranes. This modification may facilitate binding of IL-2 and insulin to their receptors and thus may improve T cell proliferation and prevent or delay age-related loss in immune functions.

Aging↗
PubMed1992

The effect of elevated levels of thromboxane on host response to tumor.

Previous studies have demonstrated that human malignancies can synthesize large amounts of thromboxane. It has also been reported that thromboxane can significantly alter multiple components of physiologic and immunologic function. We investigated the effect of elevated levels of thromboxane on host response to tumor using multiple rat models, and the long acting thromboxane analogue U-46619. Administration of the thromboxane analogue was not found to significantly alter the growth of primary tumors or peritoneal metastases. The analogue was found to significantly decrease mean survival time with a pulmonary metastases model. The thromboxane analogue failed to alter macrophage cytotoxicity, lymphocyte cytotoxicity, T lymphocyte subset numbers, or lymphocyte blastogenic response. Administration of the thromboxane analogue decreased the rate of lymphocyte metabolism of glucose and decreased lymphocyte intracellular adenosine deaminase activity. In conclusion, elevated thromboxane levels do not appear to alter primary tumor growth or host immune function, but do decrease resistance to pulmonary metastases.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1992

Effects of exercise and food restriction on rat skeletal muscles.

Studies were undertaken to compare the effects of exercise and food restriction on body weight (BW), muscle weight (MW), muscle fiber size, and proportion of muscle fiber types. 20 male Fischer 344 rats were randomly assigned to four equal groups: ad libitum-fed control (AC), ad libitum-fed exercise (AE), food restricted control (RC) and food restricted exercise (RE). From 6 weeks of age, RC and RE rats received 60% of the daily food intake of AC and AE rats, respectively. At 7 months of age, AE and RE rats began 40-50 min of daily treadmill exercise. Running speed increased from 1.2 to 1.6 miles/hour and the grade increased to 15% during the first 2 weeks of training. After 10 weeks of training, rats were weighed, sacrificed, and the soleus (SOL), plantaris (PLN) and extensor digitorum longus (EDL) muscles were removed at in situ rest length, weighed, and quick-frozen. Standard histochemical assays were performed, and muscle fiber cross-sectional area was determined planimetrically. Training had little effect on MW or BW, but food restriction greatly reduced BW. This resulted in greater MW/BW ratio in RC and RE than AC and AE rats, respectively. Exercise also increased SOL muscle fiber area in ad libitum-fed but not food restricted rats resulting in smaller fibers in SOL of RE than AE. No changes in percentage of SOL fiber types occurred with food restriction or exercise. In PLN, the percentage of fast-twitch oxidative fibers of AE and RE was greater than in AC and RC, but there was no effect of food restriction or exercise on fiber area.(ABSTRACT TRUNCATED AT 250 WORDS)

Animal Nutritional Physiological Phenomena↗
PubMed1992

Ultrastructural morphometry of matrical changes induced by exercise and food restriction in the rat calcaneal tendon.

The ultrastructural morphometry of collagen fibril populations in 24 calcaneal tendons obtained from 12 Fischer 344 rats were studied to elucidate matrical changes induced by food restriction and/or endurance exercise. Rats were randomly assigned to four equal groups: ad libitum control (AC), ad libitum exercise (AE), restricted diet control (RC) and restricted diet exercise (RE) groups. Beginning from 6 weeks of age, animals in the two food restriction groups were fed 60% of the mean food consumption of ad libitum fed rats. Then, starting from 6-7 months of age, the rats in the two exercise groups performed 40-50 min of treadmill running at 1.2-1.6 miles h-1 every day for a total of 10 weeks. Endurance training did not significantly alter body weight, but food restriction with or without exercise resulted in a significant loss of body weight. In ad libitum fed controls, food restriction alone did not significantly alter the mean collagen fibril CSA, but predisposed a preponderance of small-sized collagen fibrils. Endurance training per se induced a significant (32%) increase in mean fibril CSA (P less than 0.05), but this adaptive response to exercise was prevented by food restriction, as indicated by a 33% decline in fibril CSA (P less than 0.05). These findings demonstrate that dietary restriction modifies the adaptation of tendon collagen morphometry in response to endurance training, and that weight loss is better achieved with food restriction than endurance exercise.

Animal Nutritional Physiological Phenomena↗
PubMed1992

Potential of diet therapy on murine AIDS.

Recently, a murine retrovirus (LpBM5 MuLV), which induces immunodeficiency syndrome in mice, termed MAIDS, has been found to have several features similar to those seen in human acquired immunodeficiency syndrome (AIDS). The present study was undertaken to compare the effects of 40% energy restriction (R) and/or ad libitum (AL) diets with vegetable [corn oil, (CO) (n-6)] or marine oil [menhaden fish oil (FO), (n-3)] as a source of dietary fats on the immune function and survival rate of C57BL/6 mice injected with the LpBM5 MuLV virus. Weanling mice were fed, throughout the study, either a 5% CO-, 5% CO(R)-, 20% CO- or 20% FO-based diet and 8 wk later the mice were injected with the LpBM5 MuLV (5 x 10(5) plaque-forming units). The results revealed a significantly prolonged postinjected survival rate in the mice fed 20% FO and 5% CO(R) diets [5% CO = 131 +/- 7 d; 5% CO(R) = 161 +/- 13 d; 20% CO = 125 +/- 6 d; 20% FO = 164 +/- 14 d]. Immunological studies conducted 4 wk after injection revealed decline in both interleukin-2 production and proliferative response to mitogens in spleen cells of mice in all four dietary groups. However, this decline was less apparent in mice fed 5% CO(R) and 20% FO diets.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Aging reduces the mRNA of alpha 1 GABAA receptor subunit in rat cerebral cortex.

The effect of aging on the binding of ligands to the GABA, benzodiazepine and picrotoxin binding sites as well as alpha subunit mRNA level of GABAA receptor was investigated in cerebral cortex of male Fischer F-344 rats. In aged (730- to 770-day-old) rats, the binding of [35S]t-butylbicyclophosphorothionate (TBPS) was significantly reduced. Also, alpha 1 mRNA level was markedly decreased (86% suppression). In contrast, alpha 1 mRNA remained unchanged in cerebellum. These findings indicate a selective age-related structural change in GABAA receptor in rat cerebral cortex.

Aging↗
PubMed1991

Aspirin-like drugs prime human T cells. Modulation of intracellular calcium concentrations.

Aspirin-like drugs (ALD) enhance T cell proliferation by suppressing PG production in monocytes. Normal human T cells do not produce any eicosanoids. Therefore we studied whether ALD would affect purified T cells directly. We found that ALD enhanced the proliferation and IL-2 production of T cells in the absence of monocytes. This effect did not depend on arachidonic acid metabolism as no lipoxygenase products and only nonsuppressive levels of cyclooxygenase products were detected in T cell cultures. Several possible mechanisms of the ALD effect were ruled out including 1) enhanced mitogen binding, 2) induction of activation markers (IL-2R, transferrin receptor, HLA-DR) on the cell surface, 3) down-regulation of suppressor cells. ALD caused a rise in [Ca2+]i which appeared to reflect an influx of Ca2+ from the extracellular milieu and was more pronounced in CD4+ cells. The rise in intracellular levels of Ca2+, that is considered a necessary second messenger for T cell activation, may prime these cells for an enhanced response to mitogens. In addition, ALD increased T cell membrane fluidity but only at higher concentrations than those found to enhance proliferation. The pharmacologic effect of ALD on T cells presents a possible new immunoenhancing potential of these drugs and may have therapeutic use in immunosuppressed individuals.

Adult↗
PubMed1991

Alterations in host defense associated with anesthesia and blood transfusions. II. Effect on response to endotoxin.

The effect of blood transfusions and anesthesia on host response to endotoxin was evaluated in multiple Lewis rat models. The rats were randomized to receive A'Sogaloff Cancer Institute rat blood, pentobarbital sodium, or lactated Ringer's solution and, at either 2 or 7 days following administration of these agents, were challenged with intravenous endotoxin. Neither blood transfusions nor anesthesia altered mortality when administered 2 days before endotoxin challenge. However, blood transfusions administered 7 days before endotoxin challenge were found to prolong survival, to prevent endotoxin-induced alterations in T-lymphocyte subsets, and to decrease plasma tumor necrosis factor levels. In conclusion, blood transfusions appear to depress immune function in a beneficial manner in endotoxin shock.

Anesthesia, General↗
PubMed1991

Effect of prostaglandin E in multiple experimental models. VIII. Effect on host response to metastatic tumor.

Prostaglandin E (PGE) is produced by certain tumors and is reported to decrease primary tumor growth. We evaluated its effect in multiple tumor models utilizing a 1 week course of the long acting PGE derivative dimethyl-PGE (dPGE) at a dosage of 100 micrograms/kg/day vs. a lactated Ringers control. For all tumor models, a suspension of 1 x 10(6) colon carcinoma cells were injected into Wistar-Furth rats. When the suspension was injected subcutaneously and the drug was begun at the time of tumor challenge, there was no effect on survival. When the tumor was injected intraperitoneally or intravenously and the drug begun at the time of tumor challenge, dPGE decreased survival time. When the tumor was administered intravenously but dPGE was delayed for 5 days, there was no effect on survival time. When rats were given a 1 week course of dPGE or saline, dPGE was found not to alter natural killer (NK) cell cytotoxicity, macrophage cytotoxicity, spontaneous lymphocyte blastogenesis, or mitogen stimulated blastogenesis. dPGE failed to alter lymphocyte metabolism of glucose in nonstimulated lymphocytes, but decreased the rate of glucose metabolism and adenosine deaminase activity in mitogen stimulated lymphocytes. In conclusion, PGE appears to enhance metastatic growth of tumor lines where it does not alter primary tumor growth. This effect does not appear immunologically mediated.

Animals↗
PubMed1991

Study on the lipid composition of aging Fischer-344 rat lymphoid cells: effect of long-term calorie restriction.

Long-term calorie restriction (LCR) is widely known to increase the survival rate of laboratory rodents and appears to retard the aging and senescence process. The present study was undertaken in Fischer-344 male rats maintained on ad libitum (AL) or LCR (40% less food intake than AL starting at 6 weeks of age). Age-associated changes in the proliferative response of lymphoid cells to mitogenic stimuli were studied in relation to alterations in the fatty acid composition of adherent and non-adherent-enriched subpopulations of spleen cells. Increases in spleen cell long-chain highly unsaturated fatty acids (20:4, 22:4 and 22:5) were accompanied by decreases in linoleic acid (18:2) in aging AL-fed rats. However, LCR stabilized levels of 18:2 and prevented the rise in highly unsaturated fatty acids. In addition, LCR markedly modulated the fatty acid profiles of thymocytes and bone marrow cells. A 70% decline in concanavalin A (Con A) stimulated [3H]thymidine uptake of spleen cells from AL animals was normalized by LCR. Splenic reduced glutathione (GSH), a potential modulator of the mitogenic response, was unaffected by age and nutritional regimen. Thus, normalization of lymphoid cell fatty acid composition by LCR parallels the preservation of mitogenic responsiveness to Con A.

Aging↗
PubMed1991

Effect of fish oil diet on immune response and proteinuria in mice.

In this study, we examined the immune response and proteinuria caused by dietary polyunsaturated fatty acids in normal NZW/N and autoimmune NZB/NZW mice. Mice were maintained more than one year on five dietary groups: normal (5% corn oil), calorie-restricted, high fat (20% corn oil), high fat (20% fish oil), and Purina laboratory rodent chow. Normal mice fed with the fish oil diet had a more reduced anti-sheep red blood cells (SRBC) plaque-forming cell (PFC) response and less interleukin-2 (IL-2) enhancement of PFC than did the group with the restricted diet and the young control group. The corn oil (5 and 20%) diet animals also showed reduced PFC response and IL-2 utilization. NZB/NZW mice fed with the fish oil diet showed similar reduced PFC response but had a significantly lower response to IL-2 than did those on the corn oil diets and the restricted diet. The IL-2 production by macrophages from NZW/N mice was reduced in both the fish oil and corn oil diet groups. However, mice fed with the fish oil diet had less proteinuria and good survival rates, similar to the group with the restricted diet. These results suggest that the beneficial effect of the fish oil diet in these animals may be attributed in part to the immunosuppression mechanism.

Animals↗
PubMed1990

Studies on membrane lipid peroxidation in omega-3 fatty acid-fed autoimmune mice: effect of vitamin E supplementation.

Enzyme-dependent and non-enzymatic in vitro lipid peroxidation was studied in autoimmune prone B/W mice fed diets containing high levels of dietary corn oil (CO) or menhaden fish oil (FO) as lipid source since weaning. Lipid analysis revealed that FO-fed mouse liver mitochondrial and microsomal membrane fractions incorporated 20:5 omega 3 and 22:6 omega 3 in replacement of 18:2 omega 6 and 20:4 omega 6 found in corn oil (CO) fed control animals reflecting the composition of the dietary oils. Lower concentrations of vitamin E were found in the FO-fed mouse membranes and serum than those of CO-fed mice when diets were supplemented with a standard 75 I.U. alpha-tocopheryl acetate/kg diet. The rate and extent of membrane lipid peroxidation was greatly increased in FO-fed, vitamin-E-depleted membranes. Full repletion of membrane vitamin E levels by supplementation with 500 I.U./kg of FO diet for 30 days significantly decreased lipid peroxidation and showed that in FO-fed mice, membrane peroxidation is inversely proportional to vitamin E content. However, due to a lower ratio of vitamin E and highly unsaturated fatty acids, FO-fed mouse membranes were more sensitive to pro-oxidant stimulus than were those from CO-fed mice. These findings illustrate the action of vitamin E against membrane lipid peroxidation and stress the importance of adequate supplementation of antioxidant with high omega-3 fatty acids intake.

Animals↗