Studies on the use of dietary n-3 fatty acids supplementation in patients with rheumatoid arthritis started to appear in the scientific literature in the early 1980's. Interest in n-3 fatty acid-modified diets developed further when it was observed that such diets in animal models partly alleviated autoimmune-induced inflammatory disease. Human studies indicate that n-3 fatty acids may reduce inflammation; however, the mechanism of these effects have not been fully elucidated. Inflammatory stimuli result in cytokine production and free radical release, which may enhance the production of tissue necrosis factor (TNF) and cytokines other than those produced through the cyclo-oxygenase and 5-lipoxygenase enzyme systems and the platelet-activating factor (PAF) system. Clinical manifestations of rheumatoid arthritis have been established by the American College of Rheumatology. The diagnostic criteria most commonly used in the clinical management of rheumatoid arthritis include prolonged morning stiffness, swelling and pain in more than one joint, commonly involving the hands, wrists, knees, and feet in a symmetrical pattern, and an ESR (erythrocyte sedimentation rate) of at least 28mm/h. Systemic symptoms associated with active disease include low-grade fever, weakness, and extra articular manifestations such as vasculitis, neuropathy, and pleuritis. There are inconsistencies reported in the literature regarding the effects of n-3 fatty acid supplementation on these clinical parameters. Controversies associated with n-3 fatty acids and rheumatoid arthritis studies may be associated with the crossover design protocol which is not appropriate because of the long carry over effects of fish oils. Also, a study length of less than 12 weeks is insufficient for alteration of cellular lipid levels. Another source of confusion is that the level of supplementation with n-3 fatty acids has not been dose related, and there has not been any control of linoleic acid levels in the background diet. The purpose of this article is to review the recent studies utilizing n-3 fatty acids in clinical investigations of patients with rheumatoid arthritis and to suggest directions for future research efforts.
The effects of Lupinus angustifolius L. (sweet lupin), cv. Unicrop seed meal and five of its fractions on different parameters of blood, plasma/serum and liver were studied in two experiments. Groups of four growing rats were pair-fed for 10 days on diets that contained the same amounts of energy and protein and were supplemented with amino acids and minerals to target requirements for growing rats. In addition to the lactalbumin (LACT) and raw lupin seed meal, which was fully supplemented (LMFS), five fractions were tested: four protein fractions (aqueous fractions that were soluble [LPAD] and insoluble [LPADI] after dialysis at pH 7.0, and phosphate-citrate buffer extracted ones that were soluble [BUSOL] and insoluble [BUDI] after dialysis at pH 7.0) and dialyzed residue (LMR) containing the material from the meal insoluble in water and buffer. The cellular components and parameters of blood plasma and serum were subjected to detailed studies. Cellular elements were, in fact, little affected by the seed meal and its fractions when compared with those obtained from the control. Significant changes, however, were found in plasma urea (p<0.05), albumin (p<0.05), alkaline phosphatase (p<0.05), total cholesterol (p<0.01) triglycerides, and liver lipid and cholesterol. A significant lowering effect on total plasma cholesterol was observed in growing rats fed the seed meal and its fractions compared with that value obtained from the lactalbumin control. The buffer-dialyzed insoluble (BUDI) fraction, which resembled γ-conglutin and was found to be in an almost pure form, lowered total plasma cholesterol by 34% compared with that value for the lactalbumin fed group. Liver lipid and cholesterol were also found to be decreased in rats fed L. angustifolius seed meal and its fractions. The observed hypocholesterolemic effects were greater than any values previously reported for such a short feeding period. The underlying mechanism(s) of the cholesterol lowering effects is not clear. However, the disproportionate value for arginine: lysine and/or cystine: methionine in the proteins may be a modulating factor(s). In addition, other biochemical changes were dependent on the involvement of general N metabolism and/or parenchymatous degeneration of the liver tissues by some unknown modulating factor.
This study was aimed at determining the basic biochemical changes induced by the toxicity of copper sulphate (CuSO4) and analyzing the detoxifying effects of Ocimum sanctum, a medicinal plant commonly used in India. CuSO4 dissolved in saline was injected into rats for 30 days. Determinations of serum or tissue level of copper, lipid peroxides, iron, ferritin and antiperoxidative enzymes like SOD, CAT, GSH, GST, GPx, and ceruloplasmin were then carried out. CuSO4 toxicity manifested itself as significantly increased production of lipid peroxides from lipid products by a free-radical mechanism involving hydroxyl free radicals. The anti-oxidant enzyme levels were also notably increased in CuSO4 toxicity, but not to the extent of substantially reducing the hydroxyl free radicals produced by CuSO4. Ocimum sanctum administration restored the various parameters to near their normal values.
Chemically induced hepatocarcinogenesis in rats with partial hepatectomy was followed morphologically and enzymatically at 4, 6, 8, 12, and 16 weeks after injection of the inducer, diethylnitrosamine. The enzymes determined were plasma and liver γ-glutamyltranspeptidase (GGT), alkaline phosphatase (ALP), and glutathione S-transferase (GST), The livers of the treated rats killed after 8 weeks appeared to be rough, pale, and larger compared with the control ones. After 6 weeks, large nodules were observed on the treated liver. Staining of the liver sections histochemically and immunohistochemically revealed that the enzyme-positive foci increased with time (r=0.93, p<0.05, for the placental form of GST (PGST); not significantly for GGT). The number of enzyme-positive foci per tissue surface area did not correlate with time. GGT, ALP, and GST activities in the plasma and liver of the treated rats were higher than those in the controls. Blood glutathione levels were not affected during chemically induced hepatocarcinogenesis in the rat.
The protective effect of α-tocopherol pretreatment on antioxidant status in erythrocytes of isoproterenol-induced myocardially infarcted rats was studied. Isoproterenol-treated rats showed a significant decrease in the activity of erythrocyte antioxidant enzymes, resulting in increased lipid peroxides in serum and erythrocytes. The level of antioxidants such as vitamin E, ascorbate, and glutathione decreased on isoproterenol treatment. α-Tocopherol pretreatment prevented the inactivation of erythrocyte antioxidant enzymes and formation of lipid peroxides. The antioxidant levels were maintained near normal in α-tocopherol-pretreated, isoproterenol-administered rats. α-Tocopherol, being a potential antioxidant, reduces free radical-mediated reactions, thereby preventing erythrocyte damage.
Antibodies to glutamic acid decarboxylase (GAD Ab's) provide an important serologic marker for insulin-dependent diabetes mellitus (IDDM), but the diagnostic sensitivity and specificity of GAD antibodies have yet to be defined in assay systems suitable for screening a large number of samples. Therefore, using affinity purified GAD from rat brain we have developed a simple and sensitive solid-phase radioimmunoassay for measuring antibodies against the isoforms GAD65 and GAD67 and have examined a large number of serum samples from Japanese patients with IDDM of short-duration (less than 3 years) as well as from those with non-insulin-dependent diabetes mellitus (NIDDM). We detected GAD Ab in 62% (37 of 60) of the patients with IDDM, but only in 8% (4 of 51) of those with NIDDM. Almost all the patients with other autoimmune diseases and the healthy controls had no GAD Ab at all. Seventy-eight percent of the IDDM patients with GAD Ab concomitantly had islet cell cytoplasmic antibody (ICA), and there was a significant correlation between both autoantibody levels. This assay provides for rapid and simple screening for the early diagnosis of IDDM.
Serum fatty acid compositions and serum lipid concentrations in workers residing in five different metropolitan areas were compared by sex, age group, and region; and their correlations were studied. The proportion of C18:2 was the largest among polyunsaturated fatty acids (PUFA) in both males and females in any age group, and the proportion of n-3 PUFA was less than one fifth of that of n-6 PUFA. The proportion of C18:2 was significantly larger in females than males. On the other hand, the proportions of C20:5, C22:6, and n-3 PUFA increased in both sexes in their 20 to 40s, but showed no significant changes in the older groups. The P/S ratio was significantly higher in females than in males. The n-3/n-6 ratio was lowest in both sexes in their 20s (0.11-0.12), and increased with advancing age. There were no differences between the sexes in the mean serum total cholesterol (TC) concentration. The serum triglyceride (TG) concentration was higher in males than females. Serum TC showed weak positive Correlations with the proportion of n-3 PUFA and the n-3/n-6 ratio. In contrast, serum TG showed a strong positive correlation with C18:1 and negative correlations with the proportion of n-6 PUFA and the P/S ratio. The study suggests that, in healthy humans with normal serum TC and TG, TG concentration responded more strongly than TC concentration to n-6 PUFA, which is predominant in serum.
Effects of dietary composition (high fat, FAT; or high carbohydrate, CHO) and exercise timing (preprandial exercise, Ex-; or postprandial exercise, -Ex) on postprandial energy expenditure and substrate utilization were studied in seven women aged 19-20 years. The experimental protocol included four different sessions (Ex-FAT, Ex-CHO, FAT-Ex, and CHO-Ex). The FAT and CHO diets provided 48 and 5% as fat, respectively. On the experimental days, subjects were fed a meal containing the same caloric energy at lunch time and they exercised for 30min on a bicycle ergometer at an intensity of 60% VO2max at pre- or post-meal followed by rest for 3h. The values of oxygen consumption were 1, 559, 1, 628, 1, 526, and 1, 557ml·kg-1·4h-1 in Ex-FAT, Ex-CHO, FAT-Ex, and CHO-Ex groups, respectively. Total levels of serum insulin were 7.6, 13.7, 4.5, and 7.8μU·ml-1·min·10-3, respectively. These results suggest that preprandial exercise, especially before CHO diet intake, has an advantage for increasing oxygen consumption. This advantage might be related to rates of substrate (“futile”) cycling and insulinemic responses at rest and during exercise.