Prostaglandins, leukotrienes, and essential fatty acids最新文献

A 25-day dietary restriction (50% of the normal diet) produce a fall in the production of 14CO2 from 14C-glucose in rats isolated uteri. The addition of 10 or 20 ngml(-1) interleukin 1alpha (IL-1alpha) or interleukin 2(IL-2) to the Krebs-Ringer bicarbonate solution medium stimulates glucose metabolism in uteri from underfed rats. Such concentrations are not effective in control rats. The addition of Nomega-nitro-L arginine methyl ester--an inhibitor of both the constitutive and inducible forms of nitric oxide synthase (NOS)--and of aminoguadinine--a preferential inhibitor of the inducible form of NOS--block such stimulation. In other experiments, the addition to the medium of arginine-a substrate for the formation of nitric oxide-increases interleukin stimulation of glucose metabolism, which is blocked by NOS inhibitor. At the same time, NS-398--a selective inhibitor of inducible cyclooxygenase (COX)--eliminates the interleukin metabolism stimulation. We conclude that IL-1alpha and IL-2 produce an increase of glucose metabolism in uteri isolated from underfed rats. Nitric oxide produced by the inducible form of NOS mediates the interleukins-induced glucose metabolism stimulation with the participation of inducible COX.

2-arachidonoylglycerol (2-AG) is a putative endogenous ligand for cannabinoid receptors and was suggested to play an important role in both physiological and pathological events in the central nervous system (CNS) as well as in peripheral organs. The sequential hydrolysis of arachidonic acid (20:4n-6, AA)-containing phospholipids has been proposed as a major biosynthetic route of 2-AG. On the other hand, the manipulation of the dietary n-3 polyunsaturated fatty acid (PUFA) status changes the AA level in tissue phospholipids. We, therefore, conducted two separate experiments to confirm whether the dietary n-3 PUFA status influences the 2-AG level in the mouse brain. In the first experiment, we fed mice with n-3 PUFA-deficient diet, which resulted in a marked decrease in the docosahexaenoic acid (22:6n-3, DHA) levels without a change in the AA level in brain phospholipids as compared with the mice fed with an n-3 PUFA-sufficient diet. The brain 2-AG level in the n-3 PUFA-deficient group was significantly higher than in the n-3 PUFA sufficient group. In the second experiment, we found that short-term supplementation of DHA-rich fish oil reduced brain 2-AG level as compared with the supplementation with low n-3 PUFA. The decrease in the AA level and the increase in the DHA level in the major phospholipids occurred in the brains of the mice fed the fish oil diet compared with those fed the low n-3 PUFA diet. Our results indicate that the n-3 PUFA deficiency elevates and n-3 PUFA enrichment reduces the brain 2-AG level in mice, suggesting that physiological and pathological events mediated by 2-AG through cannabinoid receptor in the CNS could be modified by the manipulation of the dietary n-3 PUFA status.

Prickly pear is traditionally used by Pima Indians as a dietary nutrient against diabetes mellitus. We examined the effect of daily consumption of 250 g in 8 healthy volunteers and 8 patients with mild familial heterozygous hypercholesterolemia on various parameters of platelet function. Beside its action on lipids and lipoproteins, prickly pear consumption significantly reduced the platelet proteins (platelet factor 4 and beta-thromboglobulin), ADP-induced platelet aggregation and improved platelet sensitivity (against PGI2 and PGE1) in volunteers as well as in patients. Also plasma 11-DH-TXB2 and the WU-test showed a significant improvement in both patients and volunteers. In contrast, collagen-induced platelet aggregation and the number of circulating endothelial cells showed a significant response in patients only. No influence of prickly pear ingestion on peripheral platelet count was monitored. The dietary run-in period did not influence any of the parameters of haemostasis examined. No sex difference was seen. Prickly pear may induce at least part of its beneficial actions on the cardiovascular system via decreasing platelet activity and thereby improving haemostatic balance.

Hypoxic-ischemic encephalopathy (HIE) remains one of the most important neurologic complications in the newborn. Several experimental and clinical studies have shown that hypothermia is the most effective means known for protecting the brain against hypoxic-ischemic brain damage. Furthermore, recent data have suggested that platelet-activating factor (PAF) could play a pathophysiologically important role in the progression of hypoxic-ischemic brain injury. The aim of the present study was to investigate the role of head cooling combined with minimal hypothermia in short-term outcome of infants with perinatal asphyxia. In addition, we have examined the effect of head cooling combined with minimal hypothermia on PAF concentrations in cerebrospinal fluid (CSF) after hypoxic-ischemic brain injury. The group of asphyxiated infants (Group 1) consisted of 21 full-term (gestational age >37 weeks). These infants were randomized and divided into either a standard therapy group (Group 1a; n=10) or cooling group (Group 1b; n=11). Head cooling combined with minimal hypothermia (rectal temperature 36.5-36 degrees C) was started as soon as practicable after birth. The infants were cooled for 72h and then were rewarmed at 0.5 degrees C/h. The control group (Group 2) consisted of seven full-term infants and none of these infants showed any sign of asphyxia. To measure PAF concentration in CSF, CSF with lumbar puncture was collected into tubes immediately before the cooling (1-3h after birth) and again after 36h. We had no evidence of severe adverse events related to hypothermia. In Group 1a, two infants died after 72h of life; however, all newborn infants in Group 1b survived. Convulsion required treatment in three infants of standard therapy group (1a); none of the infants in Group 1b had clinical seizure activity. Abnormal EEG patterns were found in four infants of Group 1a; no EEG abnormalities were noted in Group 1b (P<0.05). On admission (before cooling), PAF concentration in CSF of asphyxiated infants was found to be significantly higher when compared with that of control (P<0.001). Mean PAF concentration before initiation of the study was similar in the two asphyxiated groups (Group 1a vs. 1b) (P>0.05). Obtained PAF level in CSF after 36h, showed a profound decline in cooling group of infants compared to Group 1a infants (P<0.01). In conclusion, the present study suggests that cerebral cooling with minimal hypothermia started soon after birth has no severe adverse effects during 72-h cooling period and that short-term outcome of infants are encouraging. Our results also support the hypothesis PAF an important mediator in hypoxic-ischemic brain injury and demonstrate that head cooling combined with minimal hypothermia reduces the normal increase in PAF following hypoxic-ischemic brain injury in full-term infants.

Evidence is accumulating that dietary lipids play an important role in bone health. Most of the data supporting the effects of lipids on bones have been collected in young adult and/or developing animals. Based upon this work, mechanisms have been proposed to explain how lipids act to enhance or inhibit bone resorption and deposition. Little work, however, has been done in older models. Since osteoporosis primarily afflicts the elderly, such work is needed in order to determine if mechanisms relevant to the young differ in advanced age, and to develop effective interventions for this especially vulnerable segment of the population. This article reviews evidence that dietary lipids are important to bone health in older individuals, and describes possible mechanisms that may be of particular relevance to the elderly. Specifically, studies supporting the influence of dietary lipids on calcium excretion, growth hormone secretion, fatty acid metabolism, and osteoblast formation are reviewed.

Recent investigations indicate that the type and amount of polyunsaturated fatty acids (PUFA) influence bone formation in animal models and osteoblastic cell functions in culture. In growing rats, supplementing the diet with omega-3 PUFA results in greater bone formation rates and moderates ex vivo prostaglandin E(2) production in bone organ cultures. A protective effect of omega-3 PUFA on minimizing bone mineral loss in ovariectomized rats has also been reported. The actions of omega-3 fatty acids on bone formation appear to be linked to altering osteoblast functions. Herein we describe experiments with MC3T3-E1 osteoblast-like cells that support findings in vivo where omega-3 PUFA modulated COX-2 protein expression, reduced prostaglandin E(2) production, and increased alkaline phosphatase activity. Other studies indicate that the dietary source of PUFA may affect protein expression of Cbfa1 and nodule formation in fetal rat calvarial cells.

It is well established that bone loss due to estrogen deficiency after menopause is greater in women consuming higher quantities of animal protein than in women consuming vegetable protein, particularly soy protein. Besides the dietary protein source altering bone loss, it has also been postulated recently that the source of a higher n-6/n-3 ratio in dietary oils is implicated in causing osteoporosis. Both animal and human studies have indicated that an increased intake of n-6 fatty acids from vegetable oils elevates prostaglandin E(2) levels as well as pro-inflammatory cytokines such as IL-1, IL-6 and TNF-alpha. Interestingly, it has been found that lack of estrogen also increases the production of these cytokines by immune cells and thereby activates osteoclasts during the peri-menopausal period. We speculated that the use of n-3 fatty acids and soy protein, which are known to act as anti-inflammatory and down regulate pro-inflammatory cytokines, may also protect against bone loss by decreasing osteoclast activation and bone resorption. Similar to the results of others, our ongoing studies indeed show that the bone loss in ovariectomized mice is significantly attenuated by feeding diets enriched with either fish oil or soy protein when compared to corn oil and casein-fed mice. One of the mechanisms appears to be decreasing the activation of receptor activator of NF-kappaB ligand (RANKL) on T cells, which has been found to increase osteoclast activation along with increasing pro-inflammatory cytokines in OVX mice. Since hormone replacement therapy has been found to cause adverse effects, further both animal and human studies are required with moderate soy protein and fish oil supplements in understanding the mechanisms involved in altering immune function and bone loss during menopause in women and aging in men.

Eicosanoids derived from the n-6 fatty acid, arachidonic acid, and the cytokines interleukin-1beta and tumour necrosis factor-alpha are involved in the signs and symptoms of inflammatory joint disease, as well as the cartilage degradation seen in established rheumatoid arthritis (RA). Then n-3 fatty acids in fish and fish oil can inhibit production of both eicosanoid and cytokine inflammatory mediators and therefore, have the potential to modify RA pathology. Epidemiological studies suggest that fish intake may be preventive for RA and double-blind placebo-controlled studies demonstrate that dietary fish oil can alleviate the signs and symptoms of RA. The implementation of these findings will require among other things, a range of n-3 fat enriched foods, as well as physician awareness of the possibilities for dietary n-3 fat increases to be used as adjunctive therapy in RA.

The study objective was to determine if male and female rats fed a diet rich in fish oil had femurs and vertebrae that were stronger and more resistant to fracture than rats not fed omega-3 long chain polyunsaturated fatty acids. Weanling rats were randomized to a control or a fish oil diet for 5 weeks. Feeding fish oil to males had no effect on biomechanical strength properties of femurs and vertebrae as measured by three point bending and compression, respectively. In contrast, females fed fish oil had reduced length growth and a lower vertebral peak load. These effects may have been partly mediated by a lower food intake but were not associated with differences in serum IGF-I, estradiol or urinary calcium. The effect of consuming a fish oil diet into later adulthood should be investigated to determine if femur strength is also affected among females.