Predictors of Australian consumers' intentions to consume conventional and novel sources of long-chain omega-3 fatty acids.

OBJECTIVES: To elicit predictors of variation in likelihood to purchase foods rich in long-chain omega-3 fatty acids. DESIGN, SETTING AND SUBJECTS: Responses from a community sample (n = 220) were elicited using a computer-administered questionnaire based on an adaptation of Protection Motivation Theory including measures of perceived risk and vulnerability to coronary heart disease (CHD). Other measures included health status, body mass index (BMI), perceived risk/benefits of novel technologies and sociodemographics. Descriptions of model products were presented, including farmed fish fed fishmeal (FFFF); farmed fish fed genetically modified (GM) oilseed (FFFGM); bread, milk and supplements containing fish oil (SFO) or GM oilseed. It was hypothesised that perceived vulnerability to CHD would enhance acceptance of GM products (H1). Furthermore, information describing the benefits of LCO3FA, limitations to fish supply and potential alternatives was given to a treatment group (50%) and hypothesised to have a positive effect on the acceptance of GM products (H2). RESULTS: No evidence was found to support H1 or H2. FFFF was most likely to be purchased (P < 0.01), followed by SFO and FFFGM. Multivariate regression analysis identified significant (P < 0.05) predictors (standardised beta) for likelihood to purchase FFFF: self-efficacy 0.56; behaviour (product) efficacy 0.19; belief that fishmeal is unnatural -0.14 (R2 = 0.44) and for FFFGM: self-efficacy 0.65; perceived severity of CHD 0.15; BMI -0.13; significant other has/had arthritis 0.11; belief that GM oilseed is unnatural 0.11 (R2 = 0.49). CONCLUSIONS: Self-efficacy (confidence to consume) was the most important predictor of likelihood to purchase all products.

Predicting intentions to consume functional foods and supplements to offset memory loss using an adaptation of protection motivation theory.

The widespread use of dietary supplements and so-called 'functional foods' is thought to be partially motivated by self-control of health. However, whilst consumers want foods associated with well-being or disease prevention, they are unlikely to be willing to compromise on taste or technology. This presents a dilemma for promoters of functional foods. Middle-aged consumers' intentions to consume functional foods or supplements that may improve memory were tested within an adaptation of Protection Motivation theory (PMT). Participants evaluated text descriptions of four products described as: having an unpleasant bitter taste (Natural-FF); having 'additives' to reduce bitterness (Sweetened-FF); being genetically modified to enhance function (GM-FF) and Supplements. Participants were recruited as being of high and low perceived vulnerability to memory failure. In total, 290 middle-aged consumers (aged 40-60 years) participated in the study. Motivations to consume the GM-FF were the lowest. There were gender differences between intention to consume the supplements, Natural-FF and Sweetened-FF and product differences within genders. Women were less favourable than men in their attitudes towards genetic modification in general. Regression analyses indicated that PM predictors of intention to consume functional foods or supplements explained 59-63% of the variance (R2). Overall, perceived 'efficacy' (of the behaviour) and self-efficacy were the most important predictors of intentions to consume.

Immunotoxicity of a standardized citrus polymethoxylated flavone extract.

Polymethoxylated flavones (PMFs) from citrus inhibit production of TNF-alpha and other pro-inflammatory cytokines. As TNF-alpha also modulates NK cell activity, the current studies were conducted to assess the potential for a standardized citrus PMF mixture to suppress humoral and innate immune functions. PMFs were isolated from orange peel oil using a procedure that obtained a consistent mixture of PMFs both in identity and proportion. The mixture consisted of nobiletin (30.7%), 3,3',4',5,6,7,8-heptamethoxyflavone (27.9%), trimethylscutellarein (14.5%), tangeretin (10.4%), sinensetin (5.8%), 5-demethyl-nobiletin (2.0%), hexa-O-methylquercetagetin (1.3%), 5-demethyl-tetramethylscutellarein (0.6%), and other flavonoids (2.7%). To assess the effect of the PMF mixture on humoral immune responses, female B(6)C(3)F(1) mice (n=8) were exposed to the PMF by gavage at 5, 50, 150 and 500 mg/kg/day for 28 days. On day 25, mice were sensitized to sRBC by tail vein injection and AFC response determined 4 days later. Humoral immunity was insensitive to suppression following exposure to all concentrations of the PMF mixture. Suppression of NK cell activity was observed only following 500 mg/kg/day for 28 days. Body weights were not affected by exposure to any concentration of the PMF mixture in sRBC immunized or non-immunized mice. However, in sRBC-immunized mice, higher concentrations of PMF were associated with a statistically insignificant increase in spleen weight (P>0.05). No change in spleen weight was observed in non-immunized mice. As anticipated, based on previously published in vitro observations, long-term, high-dose exposure to a standardized mixture of citrus PMFs caused a mild suppression of NK cell activity; however, humoral immunity was not sensitive to suppression at the same exposure levels.

Review of the treatment literature for encopresis, functional constipation, and stool-toileting refusal.

This review summarizes the literature on randomized, controlled, published studies involving medical, behavioral, psychological, and biofeedback treatments for encopresis/functional constipation and stool-toileting refusal in preschool-age and school-age children. Nine such studies were located in the literature involving school-age children. No randomized, controlled treatment studies involving preschool-age children have been published. This review revealed no evidence to support the routine use of psychotherapy or anal sphincter biofeedback in the treatment of pediatric fecal elimination dysfunctions, beyond those benefits derived from a comprehensive medical-behavioral intervention. Further, this review indicated that paradoxical constriction of the External Anal Sphincter does not influence the treatment outcome of either biofeedback or medical-behavioral interventions. There are remarkably few controlled treatment outcome studies in this most important clinical area. More research is needed that employs standard treatment outcome variables.

Functional characterization of missense mutations in ATP7B: Wilson disease mutation or normal variant?

Wilson disease is an autosomal recessive disorder of copper transport that causes hepatic and/or neurological disease resulting from copper accumulation in the liver and brain. The protein defective in this disorder is a putative copper-transporting P-type ATPase, ATP7B. More than 100 mutations have been identified in the ATP7B gene of patients with Wilson disease. To determine the effect of Wilson disease missense mutations on ATP7B function, we have developed a yeast complementation assay based on the ability of ATP7B to complement the high-affinity iron-uptake deficiency of the yeast mutant ccc2. We characterized missense mutations found in the predicted membrane-spanning segments of ATP7B. Ten mutations have been made in the ATP7B cDNA by site-directed mutagenesis: five Wilson disease missense mutations, two mutations originally classified as possible disease-causing mutations, two putative ATP7B normal variants, and mutation of the cysteine-proline-cysteine (CPC) motif conserved in heavy-metal-transporting P-type ATPases. All seven putative Wilson disease mutants tested were able to at least partially complement ccc2 mutant yeast, indicating that they retain some ability to transport copper. One mutation was a temperature-sensitive mutation that was able to complement ccc2 mutant yeast at 30 degreesC but was unable to complement at 37 degreesC. Mutation of the CPC motif resulted in a nonfunctional protein, which demonstrates that this motif is essential for copper transport by ATP7B. Of the two putative ATP7B normal variants tested, one resulted in a nonfunctional protein, which suggests that it is a disease-causing mutation.

Contribution of behavior therapy and biofeedback to laxative therapy in the treatment of pediatric encopresis.

A model incorporating physiological, behavioral, and psychological parameters are presented to explain the maintenance and consequences of pediatric encopresis. It was hypothesized that the more comprehensive a treatment in addressing these parameters, the more efficacious it would be and the more children it would benefit. Eighty-seven children between the ages of 6 and 15 with the primary complaint of encopresis were randomly assigned to one of three treatments: (a) Intensive Medical Care (IMC), receiving enemas for disimpaction and laxatives to promote frequent bowel movements; (b) Enhanced Toilet Training (ETT), using reinforcement and scheduling to promote response to defecation urges and instruction and modeling to promote appropriate straining, along with laxatives and enemas; or (c) Biofeedback (BF), directed at relaxing the external anal sphincter during attempted defecation, along with toilet training, laxatives, and enemas. Three months following initiation of treatment, ETT and BF produced similar reductions in soiling/child (76% and 65%) that were superior (p's < .04) to IMC (21%). ETT significantly benefited more children than the other two treatments, employing fewer laxatives and fewer treatment sessions at a lower cost. Consistent with the presented model, reduction in soiling was associated with an increase in bowel movements in the toilet, reduction in parental prompting to use the toilet, and defecation pain. These results demonstrate that ETT should be used routinely with laxative therapy in the treatment of chronic encopresis.

The effect of dietary lipid on polyunsaturated fatty acid metabolism in Atlantic salmon (Salmo salar) undergoing parr-smolt transformation.

The aim of this study was to measure the changes in lipid metabolism which occur during smoltification and seawater transfer in Atlantic salmon (Salmo salar). Duplicate groups of Atlantic salmon parr were fed diets containing either fish oil (FO) or a blend of linseed and rapeseed oils, vegetable oil (VO), from October (week 0) to seawater transfer in May (week 26). From May to August (weeks 26-43), all fish were fed a fish oil-containing diet. Fatty acyl desaturation and elongation activity were followed in isolated hepatocytes incubated with radioactive 18:3n-3 and 18:2n-6. Metabolism of 18:3n-3 was consistently around 5-fold greater than metabolism of 18:2n-6, and total metabolism of both substrate polyunsaturated fatty acids (PUFA) was increased in fish fed both VO and FO up to seawater transfer after which desaturation activities were reduced. Desaturation activities with both 18:3n-3 and 18:2n-6 were significantly greater in fish fed VO, compared to fish fed FO, at 22 and 26 wk. Arachidonic acid (20:4n-6; AA) in liver polar lipids (PL) of fish fed VO increased consistently from weeks 0-22 but varied after seawater transfer. In fish fed FO, AA in liver PL remained constant up to week 17 before increasing at seawater transfer and leveling off thereafter. Eicosapentaenoic acid (20:5n-3; EPA) in liver PL of fish fed VO decreased significantly from week 0-22 before rising at seawater transfer and increasing rapidly posttransfer. EPA in liver PL of fish fed FO showed a similar trend except EPA was always greater in the freshwater phase compared to fish fed VO. Docosahexaenoic acid (DHA) levels in liver PL of fish fed VO remained constant in the seawater phase before increasing following seawater transfer. In fish fed FO, DHA in liver PL increased from weeks 0-17 reducing and leveling off postseawater transfer. The levels of PGF(2 alpha) and PGF(3 alpha) were measured in isolated gill cells stimulated with calcium ionophore A23187. PGF(2 alpha) production in fish fed VO increased significantly between 0-7 wk before decreasing toward seawater transfer. After transfer, PGF(2 alpha), production increased to a peak at 35 wk. PGF(2 alpha) production in fish fed FO was not significantly altered during the trial period. The changes in PGF(3 alpha) production were broadly similar to those occurring with PGF(2 alpha), but the latter was always in excess of the former (2- to 4-fold). Plasma chloride concentrations in fish subjected to seawater challenge at 20 wk were significantly lower in fish fed VO compared to those fed FO. This study has provided new information on the changes in lipid metabolism which accompany parr-smolt transformation and suggests that diets which have a fatty acid composition more similar to that in aquatic invertebrates may be beneficial in effecting successful seawater adaptation.

Biomonitoring of possible human exposure to environmental genotoxic chemicals: lessons from a study following the wreck of the oil tanker Braer.

In January 1993 the oil tanker Braer ran aground in the Shetland Islands, Scotland. Approximately 80,000 tons of crude oil were released. Exceptionally high winds caused extensive pollution and exposure of the local population to crude oil. We describe the study which was immediately set in place to examine the exposed population for evidence of genotoxic exposure. Blood samples were taken and primary DNA damage was measured in the mononuclear cell fraction by the butanol modification of the 32P-postlabelling method. Mutation was measured at the hprt locus in T lymphocytes. No evidence of genotoxicity was obtained for either end point, but nevertheless, we believe that useful lessons were learnt, which should be incorporated into the design of future studies: (1) A rapid response is essential, and even if sufficient funds are not immediately available, it is still worth attempting to obtain samples quickly and use cryopreservation, also to attempt to estimate exposure. (2) Adequate numbers of volunteers must be sought, together with enough controls, not just to allow meaningful analysis but to overcome loss of samples and failure of things to go according to plan. (3) Points concerning laboratory practice include: (i) samples should be coded, (ii) clearly defined and proven protocols should be used, (iii) irreplaceable samples should not be used for method development, (iv) should a problem become apparent during the study, work on such samples should cease immediately until the problem is solved, (v) all critical experimental components should be pretested against a laboratory standard. (4) The study design should include replicate experiments to monitor experimental variability and reproducibility, as well as internal standards and cryopreserved "in house" samples. Care must be taken that samples from any one exposure group are spread between a number of independent experiments and that each experiment includes samples from a number of exposure groups. (5) A computerised data base should be maintained with full details of experimental variables, donor attributes, and raw data so that any contribution of experimental artefacts to "outlier" results can be monitored. (6) Because of the nature of the statistical variation for many environmental genotoxicity end points, only a large-scale study is likely to be capable of yielding useful information.

Additive benefits of laxative, toilet training, and biofeedback therapies in the treatment of pediatric encopresis.

Compared the additive benefits of laxative, behavior, and biofeedback treatments for encopresis, while attempting to identify treatment mechanisms and predictors of treatment outcome. 44 encopretic children, ages 6-15 years, were randomly assigned to either laxative therapy (LAX), LAX plus enhanced toilet training (ETT), or LAX + ETT + anal sphincter biofeedback (BF). Daily symptom diaries were completed 14 days before, upon initiation of and 3 months following treatment initiation. ETT and BF were superior to LAX in reducing encopresis. Outcome was significantly predicted by improvement during the initial 14 days of treatment. Reduction of soiling was associated with an increase in bowel movement frequency, and reductions in defecation pain and parental prompting to use the toilet. Because of its efficacy and minimal reliance on technology, ETT should be the initial treatment of choice.

The toxic milk mouse is a murine model of Wilson disease.

Wilson disease (WD) is an autosomal recessive defect of copper transport characterized by massive accumulation of copper in the liver, which can lead to liver failure. Mutations in a copper transporting ATPase (WND or ATP7B) have been shown to cause the disease. The toxic milk mouse mutant (tx) accumulates copper in the liver in a manner similar to that observed in patients with WD. However, some physiological differences between tx mice and human WD patients have cast doubts on whether this mutant mouse is a valid model for WD. In this paper we report the isolation of cDNA clones encoding the murine homologue of WND. The predicted amino acid sequence is 1462 amino acids and contains the same functional domains identified in human and rat WND. As in the rat, the fourth metal binding domain is apparently non-functional. Similar levels of a 7.5 kb WND mRNA were detected in liver and kidney from normal and tx mice, indicating that transcription of this gene was unaffected in the mutant mice. The coding sequence of WND cDNA from the tx mouse liver identified a single nucleotide difference between the normal DL mouse and the tx which is predicted to change methionine 1356 in the eighth transmembrane domain to valine. This methionine is conserved in all copper ATPases including those from bacteria and yeast. The conclusion that this is the causative mutation is supported by the recent mapping of tx and WND to the same region of mouse chromosome 8. Thus the tx mouse is presented as a valid model for studies of the role of WND in copper transport and for investigation of different treatment strategies for WD.

Long-term follow-up of medically treated childhood constipation.

We describe the long-term (mean 6.8 years) follow-up of 43 children treated medically for chronic constipation and encopresis. Overall outcome was quite good. Thirty children (70%) were entirely asymptomatic at follow-up. Intermittent mild constipation persisted in 13 patients; only two required persistent but infrequent laxative therapy. Encopresis persisted in three of 17 children who initially reported this symptom, and was associated with significant behavioral problems.

Cloning, expression, and tissue distribution of the rat nicotinamide adenine dinucleotide-dependent 11 beta-hydroxysteroid dehydrogenase.

A pcDNAI adult rat kidney complementary DNA (cDNA) library was screened using a sheep 11-hydroxysteroid dehydrogenase 2 (11 beta HSD-2) probe, and the isolated clones were sequenced. The 5'-end of the cDNA was determined by 5'-rapid amplification of cDNA ends. The rat 11 beta HSD-2 cDNA is 1864 base pair (bp) long. It consists of a 5'-untranslated region of 126 bp, an open reading frame of 1203 bp, and a 3'-untranslated region of 535 bp. The predicted protein contains 400 amino acid residues, with a calculated mol wt of 43,700. The rat 11 beta HSD-2 protein sequence is 85% homologous to human 11 beta HSD-2 and 76% to sheep 11 beta HSD-2. Expression of 11 beta HSD-2 messenger RNA by Northern blot and reverse transcription-polymerase chain reaction was high in kidney, distal colon, and adrenal and lower in the lung, hypothalamus, hippocampus, and midbrain. The rat 11 beta HSD-2 was transiently transfected into modified Chinese hamster ovary cells. Cells transfected with the 11 beta HSD-2 cDNA converted corticosterone into 11-dehydrocorticosterone. Conversion of corticosterone to 11-dehydrocorticosterone was NAD+ dependent and had a Km of 10.1 +/- 2.1 nM. In conclusion, we have cloned a rat NAD(+)-dependent 11 beta HSD with tissue distribution and kinetic characteristics suggesting that it could play a significant role in mineralocorticoid receptor selectivity.

Thermal biofeedback in the treatment of intermittent claudication in diabetes: a case study.

The objective of the present case study was to examine the therapeutic effects of thermal biofeedback-assisted autogenic training on a patient with non-insulin-dependent diabetes mellitus (NIDDM), vascular disease, and symptoms of intermittent claudication. The patient received thermal biofeedback from the hand for five sessions, then from the foot for 16 sessions, while hand and foot skin temperature were monitored simultaneously. In addition, the patient was instructed in autogenic training and practiced daily at home. Follow-up measurements were taken at 12 and 48 months. Within-session foot temperature rose specifically in response to foot temperature biofeedback and starting foot temperature rose between sessions. Posttreatment blood pressure was reduced to a normal level. Attacks of intermittent claudication were reduced to zero after 12 sessions and walking distance increased by about a mile per day over the course of treatment. It would appear that thermal biofeedback and autogenic training are potentially promising therapies for persons with diabetes and peripheral vascular disease.

Behavioral treatment of phobic avoidance in multiple chemical sensitivity.

The clinical ecology model of environmental illness, or multiple chemical sensitivity (MCS), and particularly the theoretical assumptions, diagnostic procedures, and therapeutic recommendations promulgated by clinical ecologists are reviewed. No scientific evidence is found for their claims. MCS is conceptualized, instead, as a phobic disorder explicable in terms of the two-factor model of avoidance. Three cases of MCS are discussed in light of this model, and a comprehensive behavioral treatment package that includes biofeedback-assisted in vivo desensitization and cognitive restructuring is proposed.

Selenium kinetics, placental transfer, and neonatal exposure in cynomolgus macaques (Macaca fascicularis).

Forty pregnant cynomolgus macaques were treated daily from gestational day 20 to 50 by nasogastric intubation of 0, 25, 150, or 300 micrograms selenium as L-selenomethionine/kg body weight. In each group, 7-8 pregnancies were terminated by hysterotomy at gestational day 100 +/- 2 and the fetuses were examined, while 2-3 pregnancies in each group were allowed to proceed to term. Selenium and soluble glutathione peroxidase were measured in: maternal, neonatal, and fetal plasma and erythrocytes; fetal kidney, liver, muscle, and placenta; and maternal breast milk. The area under the multidose maternal plasma selenium concentration:time curve, the maximum maternal plasma selenium concentration, and the maternal urinary selenium excretion rates were proportional to the L-selenomethionine dose. Selenium concentrations in all fetal and neonatal, tissues were also proportional to maternal L-selenomethionine dose. Glutathione peroxidase was affected only in maternal erythrocytes, fetal kidney, and neonatal plasma. The selenium concentration in fetal plasma was an average 33% of that in maternal plasma. Although selenium concentrations in macaque milk were doubled by the highest dose, intrauterine selenium accumulation accounted for the majority of the neonatal selenium body burden. Despite the elevated selenium concentrations in fetal tissues, neonatal blood, and milk, no deleterious effects on neonates were observed. These results suggest that primate fetuses are well protected against selenium toxicity arising from high maternal L-selenomethionine intakes.

The LEC rat has a deletion in the copper transporting ATPase gene homologous to the Wilson disease gene.

The Long-Evans Cinnamon (LEC) rat shows similarity to Wilson disease in many clinical and biochemical features. We have cloned cDNAs for the rat gene (Atp7b) homologous to the human Wilson disease gene (ATP7B) and have used them to identify a partial deletion in the Atp7b gene in the LEC rat. The deletion removes at least 900 bp of the coding region at the 3' end, includes the crucial ATP binding domain and extends downstream of the gene. Our results provide convincing evidence for defining the LEC rat as an animal model for Wilson disease. This model will be important for studying liver pathophysiology, for developing therapy for Wilson disease and for studying the pathway of copper transport and its possible interaction with other heavy metals.

Simple electromyographic biofeedback treatment for chronic pediatric constipation/encopresis: preliminary report.

Pediatric constipation/encopresis is thought to be due, in part, to paradoxical constriction of the external anal sphincter (EAS) muscle during attempted defecation. This inappropriate contraction can lead to delayed, impacted, painful, and infrequent bowel movements. Standard Medical Care (SMC) involves disimpaction with enemas, followed by laxative therapy and diet modification, to maintain frequent soft stools. Using the case control method, the efficacy of SMC alone was compared with SMC plus EAS electromyographic biofeedback aimed at eliminating paradoxical contraction. Thirteen consecutive chronically constipated children received SMC plus biofeedback, and were compared with 13 age- and sex-matched children who received only SMC. Biofeedback subjects demonstrated post-treatment elimination of EAS paradoxical constriction. At 16 months follow-up parents of biofeedback children reported significantly greater improvement in constipation, encopresis, laxative use, and painful bowel movements compared to SMC.

Initial effects of the grounding of the tanker Braer on health in Shetland. The Shetland Health Study Group.

OBJECTIVE: To determine if the oil spillage from the tanker Braer had any immediate health effects on the exposed resident population. DESIGN: Cohort study with a comparison against controls, exposure status being assigned on the basis of geographical location. SETTING: Rural Shetland. SUBJECTS: All those resident on or after 5 January 1993 (day 0) within 4.5 km of the site of tanker's grounding. Controls matched for sex and age were drawn from a general practice list 95 km distant. OUTCOME MEASURES: Demographic details; smoking and alcohol consumption; perception of health and reported presence or absence of specific symptoms; peak expiratory flow; results of haematology, liver and renal function tests, and blood and urine toxicology. RESULTS: Of subjects contacted, 420 (66%) exposed people and 92 (68%) controls were studied; 56 non-attenders were surveyed. Principal health effects arose on days 1 and 2 and were headache, throat irritation, and itchy eyes. No significant differences between those exposed and controls were found for any of the biological markers. Toxicological studies did not show any exposures that are known to affect human health. CONCLUSIONS: The study confirmed the anecdotal reports of certain acute symptoms. No evidence of pulmonary, haematological, renal, or hepatic damage was detected at the population level. Toxicological samples from exposed people did not find levels known to affect human health. Further studies are required to ascertain whether there have been any long term effects on the population.

The effects of evening primrose oil on nerve function and capillarization in streptozotocin-diabetic rats: modulation by the cyclo-oxygenase inhibitor flurbiprofen.

1. The aims of this study were first, to examine whether deficits in nerve conduction in streptozotocin-diabetic rats could be reversed by a 10% dietary supplement of evening primrose oil. Second, to determine the time-course of reversal, and third, to assess whether the effects could be blocked by the cyclo-oxygenase inhibitor flurbiprofen (5 mg kg-1 day-1). 2. One-month diabetes produced 20% and 15% deficits in sciatic motor and saphenous sensory conduction velocity respectively, which were maintained over 2 months diabetes. 3. The effect of 1-month evening primrose oil treatment on abnormalities caused by an initial month of untreated diabetes was examined. Motor and sensory nerve conduction velocity were restored to the non-diabetic level. 4. Resistance to hypoxic conduction failure was investigated for sciatic nerve trunk in vitro. The 80% conduction failure times were 29% and 55% prolonged by 1- and 2-month diabetes respectively. Evening primrose oil did not reverse the increased hypoxic resistance following 1-month untreated diabetes. 5. Sciatic nerve endoneurial capillary density was not significantly affected by diabetes, but was 16% increased in diabetic rats with reversal by evening primrose oil treatment for 1 month compared to 2-month untreated diabetes. 6. Serial motor conduction velocity measurement after 3-month untreated diabetes revealed complete normalization by evening primrose oil within 4 days. Cessation of treatment resulted in a rapid decline in conduction velocity over 24 h. 7. In a preventive study of 2-month duration, 6 groups of rats were used. These comprised non-diabetic controls, diabetic rats, and evening primrose oil-treated diabetic rats, both with and without flurbiprofen treatment. Flurbiprofen had no significant effect in non-diabetic rats, but produced an 11% worsening of motor conduction velocity and a 21% reduction of sciatic capillary density in diabetic rats. Evening primrose oil prevented the decreases in conduction velocity and increased hypoxic resistance with diabetes, and caused a 23% increase in capillary density. Flurbiprofen completely blocked the effect of evening primrose oil on conduction velocity, resistance to hypoxia, and capillarization.8. Six main conclusions were reached. First, evening primrose oil rapidly reverses conduction deficits in diabetic rats. Second, the effects of treatment may be very short-lived, suggesting a primary metabolic action. Third, evening primrose oil cannot reverse established changes in hypoxic resistance over 1-month treatment. Fourth, long-term treatment causes angiogenesis, suggesting a vascular action. Fifth,products of cyclo-oxygenase-mediated metabolism are necessary for maintaining vasa nervorum integrity in diabetic rats. Sixth, evening primrose oil probably acts by providing substrate for vasodilator prostanoid synthesis by vasa nervorum.