Alpha-linolenic acid in rapeseed oil partly compensates for the effect of fish restriction on plasma long chain n-3 fatty acids

Injuries sustained in schools account for 20-30% of all accident and emergency attendances in school age children. Little information has been available on the epidemiology of school accidents in the United Kingdom. Two years of routine school incident reports were analysed from Renfrew Sub-Region, an area with a school roll of 55,521 children attending 135 schools. Schools returned 1,660 report forms in the two year period, of which 1,440 referred to injuries to school children. The peak incidence of injuries was in the 10-12 year age group. The male:female ratio was 1.37:1. Cuts/ laceration and fractures were the commonest diagnoses reported for both Primary and Secondary Schools. Injuries to face and features were commonest in Primary, and upper limb injuries in Secondary Schools. Uncontrolled areas, e.g. playgrounds, stairways and corridors were the most frequent places of occurrence in Primary Schools (Relative Risk 5.24, 95% C.I. 3.28-8.35). Report accuracy was assessed by comparing one year of school reports in a Local Government District to records in the local District General Hospital. This identified 156 children who had attended hospital as the result of a school accident. Schools overestimated the number of fractures by 27%, but where schools had not provided a diagnosis, 15.4% were identified as fractures in hospital records. Each child seen at the hospital received an average of 2.1 X-rays. Nine children underwent manipulations under general anaesthetic. Seventeen children were admitted to hospital, and the group required 103 outpatient follow-up appointments.     

Immunoregulatory and anti-inflammatory effects of n-3 polyunsaturated fatty acids

1. Fish oils are rich in the long-chain n-3 polyunsaturated fatty acids (PUFAs), eicosapentaenoic (20:5n-3) and docosahexaenoic (22:6n-3) acids. Linseed oil and green plant tissues are rich in the precursor fatty acid, alpha-linolenic acid (18:3n-3). Most vegetable oils are rich in the n-6 PUFA linoleic acid (18:2n-6), the precursor of arachidonic acid (20:4n-6). 2. Arachidonic acid-derived eicosanoids such as prostaglandin E2 are pro-inflammatory and regulate the functions of cells of the immune system. Consumption of fish oils leads to replacement of arachidonic acid in cell membranes by eicosapentaenoic acid. This changes the amount and alters the balance of eicosanoids produced. 3. Consumption of fish oils diminishes lymphocyte proliferation, T-cell-mediated cytotoxicity, natural killer cell activity, macrophage-mediated cytotoxicity, monocyte and neutrophil chemotaxis, major histocompatibility class II expression and antigen presentation, production of pro-inflammatory cytokines (interleukins 1 and 6, tumour necrosis factor) and adhesion molecule expression. 4. Feeding laboratory animals fish oil reduces acute and chronic inflammatory responses, improves survival to endotoxin and in models of autoimmunity and prolongs the survival of grafted organs. 5. Feeding fish oil reduces cell-mediated immune responses. 6. Fish oil supplementation may be clinically useful in acute and chronic inflammatory conditions and following transplantation. 7. n-3 PUFAs may exert their effects by modulating signal transduction and/or gene expression within inflammatory and immune cells.     

Dietary (n-3) and (n-6) polyunsaturated fatty acids rapidly modify fatty acid composition and insulin effects in rat adipocytes

The influence of dietary (n-3) compared with (n-6) polyunsatured fatty acids (PUFA) on the lipid composition and metabolism of adipocytes was evaluated in rats over a period of 1 week. Isocaloric diets comprised 16.3 g/100 g protein, 53.8 g/100 g carbohydrate and 21.4 g/100 g lipids, the latter containing either (n-3) PUFA (32.4 mol/100 mol) or (n-6) PUFA (37.8 mol/100 mol) but having identical contents of saturated, monounsaturated and total unsaturated fatty acids and identical polyunsaturated to saturated fatty acid ratios and double bond indexes. Despite comparable food intake, significantly smaller body weight increments and adipocyte size were observed in rats of the (n-3) diet group after feeding for 1 wk. Rats fed the (n-3) diet also had significantly lower concentrations of serum triglycerides, cholesterol and insulin compared with those fed the (n-6) diet, although levels of serum glucose and free fatty acids did not differ in the two dietary groups. In the (n-6) diet group, the (n-6) and (n-3) PUFA contents of plasma triglycerides, free fatty acids and phospholipids were 30-60% higher and 60-80% lower, respectively, than in the (n-3) diet group, whereas adipocyte plasma membrane phospholipids showed a significantly higher unsaturated to saturated fatty acid ratio and greater fluidity. Glycerol release in response to noradrenaline was significantly higher in the adipocytes of rats fed the (n-3) diet, whereas the antilipolytic effect of insulin generally did not differ in the two groups. Finally, insulin stimulated the transport of glucose and its incorporation into fatty acids to a lesser extent in adipocytes of (n-3) diet fed rats compared with (n-6) diet fed rats. This reduction in the metabolic effects of insulin in rats fed a (n-3) diet for 1 wk could be related to smaller numbers and a lower binding capacity of the insulin receptors on adipocytes and/or to a lesser degree of phosphorylation of the 95 kDa beta subunit of the receptor. In conclusion, dietary intake for 1 wk of (n-3) rather than (n-6) PUFA is sufficient to induce significant differences in the lipid composition and metabolic responses to insulin of rat adipocytes.     

Enrichment of hen eggs with n-3 long-chain fatty acids and evaluation of enriched eggs in humans

Eggs enriched with n-3 polyunsaturated fatty acids (PUFAs) were produced by hens fed diets containing fish oil or a combination of fish and vegetable oils. In a sensory evaluation, 78 untrained volunteers could not distinguish between ordinary and enriched eggs. Storage life was also not significantly different between egg types. A food intake survey of 4 groups of 14 subjects each who consumed 7 eggs/wk for 24 wk showed that intakes of the major dietary components were not significantly different for 4 different egg types. Mean (n = 56) plasma cholesterol and triacylglycerol concentrations were not significantly different at the start and finish of the study. Body weight and HDL concentrations increased during the study (P < 0.05). For the last 2 wk of the experiment (weeks 23-24), mean egg consumption was increased from a total of 14 to a total of 21 eggs, resulting in a small increase in plasma triacylglycerols only. There were no significant differences (P > 0.05) in body weight, blood pressure, or plasma lipid components among treatment groups consuming the 4 different egg types. Blood samples taken after 16 and 22 wk from fasted subjects showed significant increases in eicosapentaenoic acid, docosahexaenoic acid, and total n-3 PUFAs in subjects consuming enriched eggs compared with controls. In addition, the ratio of n-6 to n-3 PUFAs in plasma was significantly reduced from 12.2:1 to 6.5-7.7:1 in subjects consuming enriched eggs compared with controls. Consumption of only one enriched egg daily can contribute substantially to the recommended daily intake of n-3 PUFAs.     

Dietary monounsaturated n-3 and n-6 long-chain polyunsaturated fatty acids affect cellular antioxidant defense system in rats with experimental ulcerative colitis induced by trinitrobenzene sulfonic acid

The intrarectal administration of trinitrobenzene sulfonic acid in rats induces ulcerative colitis, which results in histological alterations of colonic mucosa, severe modification of the cellular antioxidant defense system, and enhanced production of inflammatory eicosanoids. This study evaluated the influence of different dietary fatty acids, i.e., monounsaturated, n-3, and n-3 + n-6 polyunsaturated fatty acids, on the recovery of the colonic mucosa histological pattern, the cellular antioxidant defense system of colon, and PGE2 and LTB4 colonic mucosa contents in a model of ulcerative colitis induced by intrarectal administration of trinitrobenzene sulfonic acid. Administration of dietary n-3 polyunsaturated fatty acids led to a minimum stenosis score, a higher histological recovery, lower colon alkaline phosphatase and gamma-glutamyltranspeptidase activities, and lower mucosal levels of PGE2 and LTB4 compared with the other two experimental groups. However, glutathione transferase, glutathione reductase, glutathione peroxidase, and catalase activities were lower in the group treated with n-3 polyunsaturated fatty acids than in the groups fed with either the monounsaturated or the n-6 + n-3 polyunsaturated enriched diet. We conclude that n-3 polyunsaturated fatty acids can be administered to prevent inflammation in ulcerative colitis, but they cause a decrease in the colonic antioxidant defense system, promoting oxidative injury at the site of inflammation.     

Modification of milk formula to enhance accretion of long-chain n-6 and n-3 polyunsaturated fatty acids in artificially reared infant rats

Background spike activity of 235 cells of the integrative subcortical motor center, i.e., the ventrolateral nucleus of the thalamus, were analyzed in nonanesthetized human brains during stereotaxic surgery in patients with various forms of Parkinson's disease. Previous data on the existence of two major types of neurons with convergent properties in the ventrolateral nucleus were confirmed. These cell types are: 1) cells with irregular occasional activity, with a tendency for spikes to group into the frequency ranges 5 +/- 1 and 10-30 Hz (type A cells, 74%), and 2) cells with constant rhythmic (3-6 Hz) generation of short volleys of discharges, with an interval structure similar to that of low-threshold Ca(2+)-dependent volley activity (type B, 26%). This is the first report demonstrating that changes in the functional state of the brain (after repeated movement trials, in transient anesthesia) are accompanied by transiently occurring transformations of the initial irregular activity of A cells into a rhythmic, volley-like pattern whose interval structure was in some cases similar to the spike activity of B cells. Differences in the localizations of A and B neurons in the ventrolateral nucleus are described, along with differences in the correlation characteristics of their background spike activity with the pathological features of Parkinson's disease (tremor, rigidity). The nature of the two types of convergent neurons in the ventrolateral nucleus is discussed, and a basis is laid for the importance of the functional factor in understanding the transformation of their background spike activity, due to the properties of cell membranes and intercellular and interstructure interactions in conditions of the living nonanesthetized human brain.     

Health aspects of fish and n-3 polyunsaturated fatty acids from plant and marine origin

An expert workshop reviewed the health effects of n-3 polyunsaturated fatty acids (PUFA), and came to the following conclusions. 1. Consumption of fish may reduce the risk of coronary heart disease (CHD). People at risk for CHD are therefore advised to eat fish once a week. The n-3 PUFA in fish are probably the active agents. People who do not eat fish should consider obtaining 200 mg of very long chain n-3 PUFA daily from other sources. 2. Marine n-3 PUFA somewhat alleviate the symptoms of rheumatoid arthritis. 3. There is incomplete but growing evidence that consumption of the plant n-3 PUFA, alpha-linolenic acid, reduces the risk of CHD. An intake of 2 g/d or 1% of energy of alpha-linolenic acid appears prudent. 4. The ratio of total n-3 over n-6 PUFA (linoleic acid) is not useful for characterising foods or diets because plant and marine n-3 PUFA show different effects, and because a decrease in n-6 PUFA intake does not produce the same effects as an increase in n-3 PUFA intake. Separate recommendations for alpha-linolenic acid, marine n-3 PUFA and linoleic acid are preferred.     

Differential accumulation and release of long-chain n-3 fatty acids from liver, muscle, and adipose tissue triacylglycerols

Eicosapentaenoic acid (EPA, 20:5n-3) is less efficiently accumulated in tissue triacylglycerols (TAGs) during fish oil feeding than docosahexaneoic acid (DHA, 22:6n-3) or docosapentaenoic acid (DPA, 22:5n-3), and EPA is preferentially released from the TAG of isolated adipocytes in vitro and adipose tissue in vivo during fasting compared with DHA or DPA. It is not known if this preferential release occurs in vivo under nonfasting conditions or if it is limited to adipose tissue. Accordingly, we have carried out experiments to study the turnover of EPA, DHA, and DPA in the TAG of adipose tissue, liver, and skeletal muscle. Weanling rats were fed diets containing fish oil for 6 weeks and then switched to diets containing only corn oil as the dietary fat for 8 weeks. The fatty acid composition and mass in epididymal fat pads, omental fat, liver, and soleus muscle TAGs were determined weekly for the first 10 weeks and at weeks 12 and 14. Subsequent to the change to the corn oil diet, EPA (20:5n-3), DPA (22:5n-3), and DHA (22:6n-3), which had accumulated during fish oil feeding, were lost from the tissue TAG pools of each tissue examined. After 8 weeks on the corn oil diet, less than 10% of the accumulated EPA, DPA, and DHA remained in the liver and muscle. The loss of EPA, DPA, and DHA from epididymal fat pad was slower. In each tissue, EPA was lost more rapidly than DPA or DHA. This selective loss of EPA relative to DHA or DPA may explain the previously reported underrepresentation of EPA compared with DHA or DPA in tissue TAG.     

Strain and age effects on egg composition from hens fed diets rich in n-3 fatty acids

The objective of this study was to compare the analgesic effects of intra-articularly administered bupivacaine with bupivacaine/morphine during and after therapeutic knee arthroscopy. In a prospective, randomized study, 50 patients with clinical signs of medial meniscal injury were allocated to two groups, A and B. The patients in group A received 40 mL of 0.25% bupivacaine while the same dose of bupivacaine combined with 1 mg of morphine sulphate was administered in group B. Pain was estimated using the visual analogue scale (VAS) during surgery and at 2, 4, 6, and 24 hours after the operation was completed. Supplementary analgesic requirements were also registered, as well as the patients' overall rating of the entire procedure. The pain scores were significantly lower in Group B throughout the whole postoperative observation period. However, no significant differences were found between the two groups in terms of intraoperative pain scores, supplementary analgesic requirements, or the overall rating of the procedure. This study provides evidence that arthroscopic surgery can be performed in a safe manner after intra-articularly administered bupivacaine with or without low-dose morphine. The combination of low-dose morphine and bupivacaine did, however, produce a superior postoperative analgesic effect during the 24 hours following knee arthroscopy compared with bupivacaine alone.     

Effects of medium chain fatty acids (MCFA), myristic acid, and oleic acid on serum lipoproteins in healthy subjects

In this study we investigated the effects on lipoproteins of medium chain fatty acids (MCFA) and myristic acid relative to those of oleic acid. Thirty-seven women and 23 men consumed a 3-wk run-in diet enriched in oleic acid followed by a 6-wk test diet rich in MCFA (n = 21), myristic (n = 20), or oleic acid (n = 19). Experimental fats were incorporated into solid foods. Total fat intake was 40 En% fat. The dietary compositions were the same except for 10 En%, which was provided by MCFA, myristic, or oleic acids, respectively. With the myristic acid diet, low density lipoprotein (LDL) cholesterol was 0.37 mmol/L higher compared with the oleic acid diet (P = 0.0064 for difference in changes). The MCFA diet increased LDL cholesterol, though not significantly, with 0.23 mmol/L relative to the oleic acid diet (P = 0.0752). Compared with the oleic acid diet, HDL cholesterol concentrations increased with the myristic acid diet by 0.10 mmol/L (P = 0.0273) but not with the MCFA diet. The MCFA diet slightly elevated triacylglycerol concentrations, but responses did not significantly differ between the diets. The MCFA diet significantly decreased the apoA-I to apoB ratio compared with both other diets (P < 0.02). We conclude that MCFA raise LDL cholesterol concentrations slightly and affect the apoA-I to apoB ratio unfavorably compared with oleic acid. Myristic acid is hypercholesterolemic, although less than predicted earlier, and raises both LDL and HDL cholesterol concentrations compared with oleic acid.     

Dietary n-3 fatty acids alter angiotensin-induced contraction and 1,2-diacylglycerol fatty acid composition in thoracic aortas from diabetic rats

Height and weight of 6th year-grade children in primary schools and the 3rd year-grade children in junior high schools have been recorded in Sendai in every October since pre-World War II days, and the secular trends of the annual gains in the measures were compared among the latest three decades of 1965-74, 1975-84 and 1985-94. Acceleration and then reduction in acceleration in growth were observed in the first and the second decade, respectively, and such were followed by reacceleration in the latest 10 year-period. The three-phased changes were most evident in height and weight of primary school children of both sexes, whereas less clear or unclear among children in junior high schools.     

Generalized peroxisomal disorder in male twins: fatty acid composition of serum lipids and response to n-3 fatty acids

Ischemia leads to intracellular acidification which can be counteracted by the Na+/H+-exchange mechanism. A blockade of this exchanger has been hypothesized to cause stronger intracellular acidification in the course of ischemia thereby protecting the heart from ischemic damage. The aim of our study was to find out (1) whether in the course of ischemia areas become electrically silent, (2) whether this is enhanced by the Na+/H+-exchange inhibitor cariporide (4-Isopropyl-3-methylsulfonylbenzoyl-guanidine; Hoe 642) and whether cariporide has protective effects. Therefore, we submitted isolated rabbit hearts, perfused according to the Langendorff technique to regional ischemia (LAD occlusion) for 30 min followed by 30 min reperfusion with (n=7) or without (n=7) pre-treatment with 1 microM cariporide. Under these conditions 256-channel epicardial potential mapping was carried out. Under non-ischemic conditions cariporide did not alter any of the parameters under observation. We found that ischemia led to marked alterations of the activation pattern, to action potential shortening and a marked increase in the dispersion of refractoriness. In the ischemic region there was a significant ST deviation from the isoelectrical line (control 32+/-10; 30 min ischemia: 290+/-35 arbitrary units [a.u.]). This was markedly reduced by cariporide (control 39+/-10; 30 min ischemia: 170+/-25 a.u.). The increase in dispersion by ischemia (by 50+/-5 ms) was significantly counteracted by cariporide (increased dispersion by 20+/-4 ms). In a similar way the alteration of the activation pattern was antagonized. Under the influence of cariporide we found a lower increase in the left ventricular enddiastolic pressure, and a significantly slower recovery of the action potential duration. After 30 min of ischemia 24+/-5 (control series) 24.5+/-5 mm2 (cariporide) became electrically silent. In a second series of experiments the incidence of arrhythmia was assessed: we found ventricular fibrillation in 6/7 untreated control hearts and in 4/7 cariporide treated hearts. In a third series of experiments we determined the intracellular [ATP] after 30 min of LAD occlusion using a histochemical method. We observed a decrease in [ATP] in the ischemic region as compared to the non-ischemic right ventricular wall, which was less pronounced in cariporide-treated hearts. Thus, we conclude that (1) cariporide protects the heart from ischemic damage and (2) at least under these conditions an enlargement of the electrically silent area did not occur.     

Plasmatic and membrane lipid alterations in erythrocytes from diabetic rats fed either n-6 or n-3 fatty acids

We examined the effect of dietary n-6 and n-3 fatty acids on the lipid composition and physical properties of erythrocyte membranes together with cholesterol and triglyceride plasmatic levels in normal and experimental diabetic rats. Plasmatic total cholesterol and triglyceride did not change in normal rats under the dietary regime, but both parameters decreased significantly in the diabetic animals after the consumption of either n-6 or n-3 fatty acids. Lipid analyses of erythrocyte membranes revealed a significant decrease in the total cholesterol together with an increase in the phospholipid amount in the diabetics compared to the normal rats. As a consequence, cholesterol/phospholipid ratio decreased in these groups of animals and markedly in those fed n-3 fatty acids. These changes would be responsible for the lower fluorescent polarization of DPH observed in the latter group. We conclude that equivalent and adequate amounts of dietary either n-6 or n-3 fatty acids produce plasmatic and red cell membrane lipid changes in diabetic rats that may improve the evolution of the disease.     

Inhibition of icosanoid production in MC/9 mouse mast cells by n-3 polyunsaturated fatty acids isolated from edible marine algae

The effects of two polyunsaturated fatty acids, 18:4n-3 and 16:4n-3 purified from the marine algae, Undaria pinnatifida and Ulva pertusa, on icosanoid production in MC/9 mouse mast cells were assessed. Both fatty acids suppressed the production of leukotriene B4 (LTB4), leukotriene C4 (LTC4), and 5-hydroxyeicosatetraenoic acid (5-HETE). The order of the suppressive activity for the two marine algae-derived fatty acids and three other common polyunsaturated fatty acids was as follows; 22:6n-3 = 18:4n-3 = 18:3n-3 > 20:5n-3 = 16:4n-3 for LTB4; 22:6n-3 = 18:4n-3 = 18:3n-3 > 16:4n-3 > 20:5n-3 (no suppression) for LTC4; 22:6n-3 = 18:4n-3 > 18:3n-3 > 20:5n-3 = 16:4n-3 for 5-HETE.     

The effects of varying dietary n-6 to n-3 fatty acid ratios on platelet reactivity, coagulation screening assays, and antithrombin III activity in dogs

Thirty beagles were placed on diets containing ratios of n-6 to n-3 fatty acids ranging from 5:1 to 100:1 for 12 weeks to determine the effects of these diets on platelet reactivity, coagulation screening assays, and antithrombin III activity. Although small changes were observed in adenosine diphosphate (ADP)-, collagen-, and arachidonic acid-induced platelet aggregation and 14C-serotonin release, fibrinogen concentrations, and antithrombin III activities during the 12-week study, these changes were not of clinical significance and did not correlate with the varying ratios of n-6 to n-3 fatty acids.     

The effect of dietary oil containing (n-3) fatty acids on the fatty acid, physicochemical, and organoleptic characteristics of pig meat and fat

An investigation was made to alter the fatty acid composition of pork and a pork product in line with human dietary advice while not adversely affecting factors controlling consumer acceptability. Pigs (n = 150) were assigned to three dietary treatments with 25 intact male-female pairs per treatment. Diet A (control) contained 3% of a 4:1 (wt/ wt) tallow-soybean oil mixture. Diets B and C contained 2% rapeseed oil plus 1% fish oil. Diets A, B, and C were supplemented with 100, 100, and 250 mg of all-rac-alpha-tocopheryl acetate/kg of diet, respectively. Pigs were given ad libitum access to feed from 52 kg live weight until 95 kg (slaughter). Sausages were prepared from the resulting cuts. Tissues of pigs were evaluated in terms of fat firmness, color, fatty acid composition, and contents of alpha-tocopherol and thiobarbituric acid-reactive substances (TBARS). Organoleptic characteristics of chops and sausages were evaluated by a trained taste panel. Pigs fed Diets B and C had improved feed conversion ratios (P < .05) and ADG compared with control pigs. The levels of n-3 (omega-3) polyunsaturates were significantly increased in the tissues and sausage from pigs fed Diets B and C with associated alterations in n-6 to n-3 fatty acid ratios that accorded with contemporary human dietary recommendations. Levels of alpha-tocopherol and TBARS were significantly altered in the tissues. There were no appreciable differences between treatments in carcass characteristics, including color. The overall organoleptic acceptability of chops and sausages was not different between the treatments.     

Effects of dietary supplementation with n-3 fatty acid ethyl esters on coccidiosis in chickens

The ethyl esters of eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids were added to a broiler starter diet singly or in combination [as bulk purified ethyl ester concentrate from menhaden oil (n3FAC)] in quantities similar to those found in a diet supplemented with 5% menhaden oil (MO). Diets were fed to chickens from 1 d of age through 3 wk of age. At 2 wk of age, the chickens were infected with Eimeria tenella, Eimeria acervulina, or Eimeria maxima. At 6 d postinfection (PI), the effects of the diets were assessed on weight gains, plasma carotenoids, gross lesion scores, and histological parasite scores in gut cross sections, or oocyst output. Significant ameliorating effects of diet on lesion scores and parasite scores were only seen in E. tenella infections and were only produced by the n3FAC and MO supplements. These two supplements, which contained higher molar concentrations of double bonds than the other supplements, also significantly reduced plasma carotenoids in uninfected chickens, indicating that they promoted a state of oxidative stress. These results are consistent with previous reports on the interaction of coccidiosis with dietary n-3 fatty acids and strengthen the hypotheses that dietary-induced oxidative stress is an effective deterrent against cecal coccidiosis in chickens.     

The effects of n-6 polyunsaturated fatty acids on the expression of nm-23 in human cancer cells

Over an interval of approximately six months beginning in October 1993, most haemophilia A patients in Canada were switched from a plasma-derived intermediate-purity factor VIII concentrate (i.p. VIII) to a recombinant factor VIII (rVIII). In order to determine the consequence of this change in therapy on progression of HIV infection, we gathered surveillance data on clinical status and CD4 and CD8 cell counts in those patients who were HIV seropositive at the time of switching concentrates. Data were recorded at the time of switchover, annually for 2 years thereafter, and retrospectively at a point 1 year prior to the switch. CD4 cells fell significantly over the study period. Multiple direct comparisons revealed that this decline was restricted to the time intervals which included the final year in which patients received intermediate-purity factor VIII concentrate (i.p. VIII). In the 2 year interval in which rVIII was used exclusively, there was a nonsignificant fall in CD4 cells. Changes in CD4 cells did not correlate with the intensity of exposure to either i.p.VIII or rVIII. CD8 cells did not fall significantly over the study period. There was no obvious reduction in the incidence of death or clinical progression over the 2 years in which rVIII was used. However, we are hopeful that the stabilizing trend in CD4 cell counts which followed the introduction of rVIII will be predictive of corresponding clinical stabilization over the coming years.     

Identical effects of indomethacin on renal function in healthy uninephrectomized subjects and in healthy control subjects

1. Animal studies have shown that prostaglandins are important for renal function after unilateral nephrectomy. In order to investigate the importance of prostaglandins for renal function in the fully adapted remnant kidney in healthy uninephrectomized subjects, the acute effects of indomethacin on renal haemodynamics, lithium clearance, urinary excretion rates of prostaglandin E2, sodium and water, and plasma levels of angiotensin II, aldosterone, atrial natriuretic peptide and arginine vasopressin were measured in 14 healthy uninephrectomized subjects (median time after nephrectomy 1.7 years) and in 14 matched healthy control subjects. In addition, nine healthy control subjects were studied without indomethacin and served as a time-control group. 2. Before indomethacin ingestion there was a significantly higher single-kidney urinary excretion rate of prostaglandin E2 in the uninephrectomized group (uninephrectomized group, 349.2 fmol/min; control group, 76.6 fmol/min; time-control group, 96.3 fmol/min). 3. Indomethacin ingestion resulted in equal changes in all parameters in both groups. These were significant decreases in glomerular filtration rate (-11.3% versus -14.6%), renal plasma flow (-6.5% versus -13.0%), urinary flow rate (-49.8% versus -49.4%), fractional sodium excretion (-44.5% versus -47.4%), lithium clearance (33.2% versus -23.8%) and urinary excretion rate of prostaglandin E2 (-93.8% versus -86.7%) (uninephrectomized versus control subjects, values are medians). In the time-control group no changes were observed in these parameters. 4. It is concluded that healthy uninephrectomized subjects with a fully adapted remnant kidney have a normal renal response to acute indomethacin-induced inhibition of prostaglandin synthesis.