The effects of aerobic exercise intensity and duration on levels of brain-derived neurotrophic factor in healthy men.

This study examined the combined effects of aerobic exercise intensity and duration on serum brain-derived neurotrophic factor (sBDNF) levels in healthy human adult males aged 18-25 years. Forty five participants were randomly assigned to one of six exercise conditions based on varying intensity (80% or 60% of heart rate reserve, or control) and duration (20 or 40 min). Vigorous (80% heart rate reserve, "Vig") and moderate (60% heart rate reserve, "Mod") exercise was carried out on cycle ergometers. Control subjects remained seated and at rest during the exercise period. Pre- and post-exercise blood draws were conducted and sBDNF measured. Physical exercise caused an average ~ 32% increase in sBDNF levels relative to baseline that resulted in concentrations that were 45% higher than control conditions. Comparing the six conditions, sBDNF levels rose consistently among the four exercise conditions (Vig20 = 26.38 ± 34.89%, Vig40 = 28.48 ± 19.11%, Mod20 = 41.23 ± 59.65%, Mod40 = 30.16 ± 72.11%) and decreased consistently among the controls (Con20 = -14.48 ± 16.50, Con40 = -10.51 ± 26.78). Vig conditions had the highest proportion of subjects that experienced a significant (? 10%) increase in sBDNF levels, followed by Mod and control conditions. An analysis of modeled sBDNF integrals (area under the curve) demonstrated substantially greater values for Vig40 and Mod40 conditions compared to Vig20 and Mod20 conditions. Collectively, these results demonstrate that neither duration (20 vs. 40 min) nor intensity (60 vs. 80% HR reserve) significantly affects the benefits of exercise if only the sBDNF increase at a single post-exercise time point is considered. However, when comparing either the probability of achieving a significant BDNF gain or the integral (i.e. the volume of circulating BDNF over time) the Vig40 condition offers maximal benefits. Thus, we conclude that the future study of aerobic exercise effects on BDNF-mediated neuroprotection should take the volume of BDNF release over time into account. Key PointsAerobic exercise caused a ~32% increase in serum BDNF in adult human males while serum BDNF decreased 13% in sedentary control subjects.Vigorous intensity (80% heart rate reserve), long duration (40 min) exercise offered the greatest probability of a significant BDNF elevation.Long duration exercise offered the greatest numerical benefits in terms of BDNF integral.Neither intensity nor duration affected the mean elevation in BDNF amplitude caused by exercise.

Menhaden oil administration to dogs treated with radiation for nasal tumors demonstrates lower levels of tissue eicosanoids.

Docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) or menhaden oil may reduce inflammatory eicosanoids (prostaglandin E2, thromboxane B2, leukotriene B4, and 11-dehydro thromboxane B2), matrix metalloproteinases (MMPs), and blood lactate in dogs with nasal carcinomas receiving radiation therapy. We hypothesized that menhaden oil would reduce inflammation from radiation damage and lower blood lactate levels in dogs with nasal carcinoma. In a randomized, double-blind, placebo-controlled clinical study, 12 dogs with malignant carcinomas of the nasal cavity were given dietary menhaden oil (DHA and EPA) or soybean oil (control) and then received radiation therapy. Megavoltage radiation was delivered in 18 fractions to a total dose of 56 Gy. Blood levels of DHA, EPA, insulin, glucose, lactic acid, and MMPs 2 and 9; resting energy expenditure; and inflammatory eicosanoids from nasal biopsies were measured throughout radiation therapy. Samples were obtained from each patient 1 week before the start of radiation therapy, at start of radiation, and 7, 18 (end of radiation therapy), and 42 days after radiation was initiated. Dogs that are fed with menhaden oil had significantly (P < .05) higher plasma concentration of DHA by 500% and EPA by 200% and had significantly lower tissue inflammatory eicosanoids and decreased resting energy expenditure by 20% when compared with controls. Increased plasma DHA was significantly associated (P < .05) with decreased plasma lactic acid and MMPs. These data may suggest that dietary fish oil could reduce some detrimental inflammatory eicosanoids and metabolic consequences of radiation therapy.

Fish oil decreases matrix metalloproteinases in knee synovia of dogs with inflammatory joint disease.

This study was designed to determine whether dietary fish oil affects the expression and activity of matrix metalloproteinases (MMP), tissue inhibitors of MMP-2 (TIMP-2) and urokinase plasminogen activator (uPA) in synovial fluid from dogs with spontaneously occurring stifle (knee) instability in a single hind limb resulting from acute cranial cruciate ligament (CCL) injury. Two groups of 12 dogs were fed diets from 1 week prior to surgery on the affected knee to 56 days post-surgery. The fish oil and control diets provided 90 and 4.5 mg, respectively, of combined eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)/kg body weight per day. Plasma and synovial fluid, from both surgical and nonsurgical knee joints, were obtained at start of the diet (-7), surgery day (0) and 7, 14, 28 and 56 days post-surgery. Plasma total EPA and DHA were significantly increased, and plasma total arachidonic acid (AA) was significantly decreased by the fish oil diet. In synovial fluid from the nonsurgical knee, fish oil treatment significantly decreased proMMP-2 expression at Days 7 and 14, and proMMP-9 expression at Day 56, and uPA activity at 28 days and significantly increased TIMP-2 expression at Days 7 and 28. There were no differences in MMP expression or activity, TIMP-2 expression and uPA activity in the surgical joint synovial fluid at any time throughout the study. These results suggest that dietary fish oil may exert beneficial effects on synovial fluid MMP and TIMP-2 equilibrium in the uninjured stifle of dogs with unilateral CCL injury.

Dietary docosahexaenoic acid alters pregnant rat reproductive tissue prostaglandin and matrix metalloproteinase production.

Shortened gestation is a major cause of infant mortality and morbidity. Evidence from both human and animal studies suggests that essential fatty acids of the n-6 and n-3 series play important and modifiable roles in gestational duration. We examined the influence of linolenic acid (LnA) vs. docosahexaenoic acid (DHA) on rat reproductive tissue prostaglandin (PG) and matrix metalloproteinase (MMP) indices of gestational duration. By varying the oil source of the diet, AIN-93G diets were constructed to provide either 0.7 energy % (en%) LnA, the current US intake of n-3 fatty acids, or 0.7 en% DHA. In addition, enhanced levels of 2.0 en% LnA or 2.0 e% DHA diets were also constructed. All diets contained approximately 6.0 en% linoleic acid (LA), the current US intake of LA. Four groups of 10 female rats were time-mated and fed the respective diets from conception through Day 20 of gestation. Day 20 uterus and placenta DHA were significantly increased by 160-180% by the 0.7 en% DHA diet, and by 250-350% by the 2.0 en% DHA diets in comparison to 0.7 en% LnA diet. DHA diets also significantly reduced uterus and placenta arachidonic acid content. Day 20 placenta and uterus PGE(2) and placenta PGF(2alpha) production rates were significantly reduced by 27-47% in the 0.7 en% DHA group in comparison to 0.7 en% LnA. Increasing LnA to 2.0 en% was without effect. Providing DHA at the enhanced 2.0 en% did not significantly enhance the suppression of PG production. Placenta active MMP-2 and active MMP-9 (gelatinase) production was suppressed significantly by 30-43% in the 0.7 en% DHA group in comparison to the 0.7 en% LnA group, and 2.0 en% DHA did not enhance this suppression. Placenta collagenase activity comprising the sum of MMP-1, MMP-8 and MMP-13 was also suppressed by 60% in the 0.7 en% DHA diet group with no additional effect with 2.0 en% DHA provision. These results suggest that substituting DHA for LnA even at the current US n-3 fatty acid intake of 0.7 en% is effective in suppressing indices of premature delivery and shortened gestation. Increasing LnA intake by 3-fold to 2.0 en% is not effective. The form of dietary n-3 fatty acid, DHA vs. LnA, appears to be more important than the amount.

Evaluation of the effects of dietary n-3 fatty acid supplementation on the pharmacokinetics of doxorubicin in dogs with lymphoma.

OBJECTIVE: To determine the effect of dietary n-3 fatty acids on the pharmacokinetics of doxorubicin in dogs with lymphoma. ANIMALS: 23 dogs with lymphoma in stages IIIa, IVa, and Va. PROCEDURE: Dogs receiving doxorubicin chemotherapy were randomly allocated to receive food with a high (test group) or low (control group) content of n-3 fatty acids. Serum doxorubicin and doxorubicinol concentrations were measured via high-performance liquid chromatography before and 6 to 9 weeks after initiation of the diets. Lymph node concentrations of doxorubicin were assessed 6 hours after the initial treatment. Dogs' body composition was assessed by means of dual-energy x-ray absorptiometry scans. RESULTS: No significant differences in doxorubicin pharmacokinetics were detected between treatment groups. Significant differences existed between the first and second sampling times among all dogs for area under the curve, maximum serum concentration, and clearance. Differences in body composition did not affect measured pharmacokinetic variables. The terminal elimination half-life was longer in dogs in which a long-term remission was achieved than in dogs that did not have remission. CONCLUSIONS AND CLINICAL RELEVANCE: Dietary supplementation of n-3 fatty acids is common in veterinary patients with neoplasia, but supplementation did not affect doxorubicin pharmacokinetics in this population of dogs. Explanations for the beneficial effects of n-3 fatty acids other than alterations in the pharmacokinetics of chemotherapy drugs should be investigated. Dogs may metabolize drugs differently prior to remission of lymphoma than when in remission. The pharmacokinetics of doxorubicin at the time of the first administration may predict response to treatment.

Plasma and skin concentrations of polyunsaturated fatty acids before and after supplementation with n-3 fatty acids in dogs with atopic dermatitis.

OBJECTIVE: To determine essential fatty acid concentrations in plasma and tissue before and after supplementation with n-3 fatty acids in dogs with atopic dermatitis. ANIMALS: 30 dogs with atopic dermatitis. PROCEDURE: Dogs received supplemental flaxseed oil (200 mg/kg/d), eicosapentaenoic acid (EPA; 50 mg/kg/d)-docosahexaenoic acid (DHA; 35 mg/kg/d), or mineral oil as a placebo in a double-blind, placebo-controlled, randomized trial. Clinical scores and plasma and cutaneous concentrations of linoleic acid, arachidonic acid, alpha-linolenic acid (alpha-LLA), EPA, DHA, prostaglandin E2, and leukotriene B4 were determined. RESULTS: Total plasma concentrations of alpha-LLA and EPA increased and those of arachidonic acid decreased significantly with administration of EPA-DHA, and concentrations of alpha-LLA increased with flaxseed oil supplementation; nevertheless, there was no significant change in the concentrations of these fatty acids or eicosanoids in the skin. There was no correlation between clinical scores and plasma or cutaneous concentrations for any of the measured fatty acids or eicosanoids. CONCLUSION AND CLINICAL RELEVANCE: Results indicated that at the dose used, neither the concentrations of fatty acids in skin or plasma nor a decrease in the production of inflammatory eicosanoids was a major factor involved in the mechanism of action in dogs with atopy that responded to fatty acid supplementation.

Effects of dietary flaxseed oil supplementation on equine plasma fatty acid concentrations and whole blood platelet aggregation.

An 18-week feeding trial was performed to investigate the effects of an omega-3 (n-3) fatty acid-enriched ration on plasma fatty acid concentrations and platelet aggregation in healthy horses. Flaxseed oil served as the source of the n-3 fatty acid alpha-linolenic acid (ALA). Twelve horses were fed dietary maintenance requirements using a complete pelleted ration (80%) and timothy grass hay (20%) for a 2-week acclimation period before being randomly assigned either to a treatment (group 1) or control (group 2) group. Group 2 horses (n = 6) were fed the diet described in the acclimation period, whereas group I horses (n = 6) were fed a 10% flaxseed oil-enriched complete pellet (80%) and grass hay (20%). Biological samples and physical measurements were collected at one point during the acclimation period (week 0) and every 4 weeks thereafter (weeks 4, 8, 12, and 16). Body weight, CBC (including platelet count), plasma fibrinogen. electrolyte (Na, K, and Cl) concentrations, and biochemical profile enzyme activities (aspartate aminotransferase, alkaline phosphatase, gamma-glutamyltransferase, and creatine kinase) did not change markedly with diet. Platelet aggregation was not altered by the supplementation of flaxseed oil in these healthy horses, although increases in plasma cis-polyunsaturated 18-carbon fatty acids C18:3; n-3 (ALA) and C18:2; n-6 (linoleic acid), biologically active C20:5; n-3 (eicosapentaenoic acid [EPA]), and malondialdehyde (MDA) were evident. There were no marked decreases in C20:4; n-6 (arachidonic acid [AA]) or increases in C22:6; n-3 (docosahexaenoic acid [DHA]), signifying that flaxseed oil may have had a high percentage of omega-6 (n-6) fatty acids as well as n-3 fatty acids, and this relatively high n-6: n-3 fatty acid ratio may have affected the biochemical effect of n-3 fatty acids. In healthy horses supplemented with flaxseed oil, platelet aggregation was not altered, which may have been due to the limited biologic effect in healthy subjects or the inability of flaxseed oil to induce the necessary biochemical effect of replacing n-6 fatty acids with n-3 types.

Matrix metalloproteinase activity in tumor, stromal tissue, and serum from cats with malignancies.

Matrix metalloproteinases (MMPs) are enzymes that play key roles in angiogenesis, tumor invasion, and metastasis in a wide variety of species. The purpose of this study was to evaluate pro and active MMP 2 and 9 concentrations in tumor, normal stromal tissue, and serum from tumor-bearing cats. We hypothesized that serum concentrations of pro and active forms of MMPs 2 and 9 would be predictive of MMP concentrations in tumor tissue and that these MMP concentrations would correlate with the histopathologic grade of the malignancies. Pro and active forms of MMPs 2 and 9 were determined by gelatin zymography and subsequent computerized densitometry from tumor and nearby stromal tissue and serum from 49 cats with various malignancies. The serum concentrations of MMPs from these tumor-bearing cats were compared with serum concentrations of MMPs from 44 normal cats of similar age and gender. Measurable concentrations of MMPs 2 and 9 were found within tumor, stromal, and serum samples. Mean concentrations of total pro and active MMPs 2 and 9 within tumor tissue were significantly higher (P values <.0001, .0031, <.001, and .0064, respectively) when compared with stromal tissue from the same animals. Serum MMP concentrations from tumor-bearing cats were higher than those from normal cats. Poor correlation was found between serum MMP concentrations and tissue MMP concentrations of increasing histologic grades of malignancies.