Caffeic Acid Derivatives: In Vitro and In Vivo Anti-inflammatory Properties

Objective: This study examined whether, daily fruit (blueberries) consumption (250 g) for three weeks or acute fruit ingestion (250 g) would attenuate angiotensin converting enzyme (ACE) activity and reduce oxidative stress in chronic cigarette smokers.

Methods: Twenty subjects were recruited and randomized into fruit or control groups. Blood samples and blood pressure were obtained at baseline and then pre and one hour post when subjects returned to the lab three weeks later. To examine acute effects, the fruit group immediately ingested 250 g of blueberries after returning and at least one hour prior to the post blood draw. Plasma samples were analyzed for ACE activity, F₂- isoprostanes and lipid hydroperoxides (LH) as measures of oxidative stress, and ferric reducing ability of plasma (FRAP) as a measure of antioxidant potential. A 2 (treatment) × 3 (time) repeated measures ANOVA was used for statistical analysis. If interaction was significant, then Student's t-tests were used to further examine this relationship. For these comparisons, a Bonferroni adjustment was made with statistical significance set at P < 0.025.

Results: The pattern of change between treatments was not significant for any variable except LH (P < 0.001).

Conclusion: This study indicates that LH are significantly reduced by daily fruit consumption, but not affected by acute ingestion. This finding could be one way in which fruit consumption contributes to prevention of cardiovascular disease.     

The effects of substrate utilization, manipulated by caffeine, on post-exercise oxygen consumption in untrained female subjects

The effect of substrate utilization manipulated by caffeine on post-exercise oxygen consumption was investigated in five untrained females (age = 21 +/- 1.5 years), following 90 min of treadmill walking at 55% maximal oxygen consumption. Each subject participated in the two trials (control and experimental) within 2 weeks of each other. Immediately following the measurement of resting oxygen consumption, subjects consumed one of the two test beverages 60 min prior to exercise: 5 mg of caffeine per kg of body-weight in 200 ml of orange juice (CA) or 200 ml of orange juice (C). Assignment of CA and C was made in a random, double blind fashion. Immediately prior to the exercise phase (0 min) resting oxygen consumption was again measured. Following exercise, subjects returned to the same pre-exercise sitting position where respiratory data was collected over 1 h. No significant differences were found in resting oxygen consumption and respiratory exchange ratio (R) prior to caffeine ingestion (-60 min). One hour after caffeine ingestion (0 min) oxygen consumption and free fatty acid (FFA) levels increased significantly compared to C. During and 1 h following exercise, oxygen consumption and FFA levels were significantly greater, with R values being significantly lower in CA compared to C. These findings provide further evidence that metabolic substrate is somehow implicated in elevating oxygen consumption following exercise cessation.     

Feeding blueberry diets inhibits angiotensin II-converting enzyme (ACE) activity in spontaneously hypertensive stroke-prone rats

Feeding flavonoid-rich blueberries to spontaneously hypertensive stroke-prone rats (SHRSP) lowers blood pressure. To determine whether this is due to inhibition of angiotensin-converting enzyme (ACE) activity, as seen with other flavanoid-rich foods, we fed blueberries to SHRSP and normotensive rats and analyzed ACE activity in blood and tissues. After 2 weeks on a control diet, the hypertensive rats showed 56% higher levels of ACE activity in blood as compared with the normotensive rats (p < 0.05). Feeding a 3% blueberry diet for 2 weeks lowered ACE activity in the SHRSP (p < 0.05) but not the normotensive rats. ACE activity in plasma of SHRSP was no longer elevated at weeks 4 and 6, but blueberry feeding inhibited ACE in SHRSP after 6 weeks. Blueberry diets had no effect on ACE activity in lung, testis, kidney, or aorta. Our results suggest that dietary blueberries may be effective in managing early stages of hypertension, partially due to an inhibition of soluble ACE activity.     

The effects of high-dose glutamine ingestion on weightlifting performance

The purpose of this study was to determine if high-dose glutamine ingestion affected weightlifting performance. In a double-blind, placebo-controlled, crossover study, 6 resistance-trained men (mean +/- SE: age, 21.5 +/- 0.3 years; weight, 76.5 +/- 2.8 kg(-1)) performed weightlifting exercises after the ingestion of glutamine or glycine (0.3 g x kg(-1)) mixed with calorie-free fruit juice or placebo (calorie-free fruit juice only). Each subject underwent each of the 3 treatments in a randomized order. One hour after ingestion, subjects performed 4 total sets of exercise to momentary muscular failure (2 sets of leg presses at 200% of body weight, 2 sets of bench presses at 100% of body weight). There were no differences in the average number of maximal repetitions performed in the leg press or bench press exercises among the 3 groups. These data indicate that the short-term ingestion of glutamine does not enhance weightlifting performance in resistance-trained men.     

Involvement of Ad4BP/SF-1, DAX-1, and COUP-TFII transcription factor on steroid production and luteinization in ovarian theca cells

The link between chronic alcohol consumption and cardiovascular injury including hypertension is well known. However, molecular mediators implicated with alcohol-induced elevation in blood pressure (BP) remain elusive. The aim of this study was to investigate the relationship of chronic ethanol-induced endothelial injury and elevation in BP with angiotensin II levels in rats. Male Fisher rats were divided into two groups of seven animals each and treated as follows: (1) Control (5% sucrose, orally) daily for 12 weeks and (2) ethanol (4 g kg⁻¹, orally) daily for 12 weeks. The BP (systolic, diastolic, and mean) was recorded every week. The animals were anesthetized with pentobarbital after 12 weeks; blood and thoracic aorta were isolated and analyzed for aortic reactivity response, angiotensin II levels, and oxidative endothelial injury. The results show that the systolic, diastolic, and mean BP were significantly elevated 12 weeks after ethanol ingestion. The increased BP was related to elevated angiotensin II levels in the plasma and aorta of alcohol treated group compared to control. The aortic NADPH oxidase activity, ratio of oxidized to reduced glutathione (GSSG/GSH) and lipid peroxidation significantly increased, whereas nitric oxide (NO), endothelial NO synthase (eNOS), and vascular endothelial growth factor (VEGF) protein expressions were depressed in alcohol group compared to control. The phenylephrine-mediated vasoconstriction response was not altered, while acetylcholine-mediated vasorelaxation response was depressed in the aorta of ethanol treated rats compared to control. It is concluded that chronic ethanol ingestion induces hypertension which is correlated with elevated tissue angiotensin II levels, activation of NADPH oxidase activity causing endothelial injury, depletion of endothelial NO generating system, and impaired vascular relaxation in rats.     

Opioidergic, dopaminergic and adrenergic regulation of LH secretion in prepubertal heifers

Studies have shown inhibitory effects of endogenous opioids on LH secretion in early post-natal heifers. However, it is not clear whether these effects change during the rest of the prepubertal period or whether the inhibitory influences on the GnRH neurones are direct or by way of other neuronal systems. Two experiments were performed in heifer calves to study the developmental patterns of opioidergic, dopaminergic and adrenergic regulation of LH and the possible interactions between opioids and dopaminergic and adrenergic neuronal systems, in the regulation of LH secretion. In Expt 1 four groups each of five heifer calves were used. Blood samples were taken every 15 min for 10 h and each calf received one of the following treatments as a single injection at 4, 14, 24, 36 and 48 weeks of age: (i) naloxone (opioid antagonist, 1 mg kg(-1), i. v.); (ii) sulpiride (dopamine D2 antagonist, 0.59 mg kg(-1), s.c.); (iii) naloxone and sulpiride combined; or (iv) vehicle (control group). Treatments began after the first blood sample was taken. The design of Expt 2 was similar; a separate group of heifer calves was assigned to receive one of the following treatments as a single injection at 4, 14, 24, 36 and 48 weeks of age: (i) naloxone; (ii) phenoxybenzamine (an alpha-adrenoreceptor blocker, 0.8 mg kg(-1), i. v.); (iii) naloxone and phenoxybenzamine; (iv) or vehicle. Results from Expt 1 showed that the maximum concentration of LH and the number of calves responding to treatments with an LH pulse was higher in the first hour after treatments at 36 and 48 weeks of age in the naloxone group compared with the control or sulpiride groups (P < 0.05). These values in the naloxone group also increased over time and were greatest at 48 weeks of age (P < 0.05). In heifers given naloxone + sulpiride treatment at 36 and 48 weeks of age, maximum concentrations of LH in the first hour after treatment did not differ from the naloxone and control groups. In Expt 2, at 36 and 48 weeks of age, treatment with naloxone with or without phenoxybenzamine resulted in higher concentrations of LH than in the controls (P < 0.05). No pulses were seen over the first hour of treatment at 36 and 48 weeks of age in heifers treated with phenoxybenzamine. The 10 h periods of blood sampling at 48 weeks of age revealed that phenoxybenzamine alone suppressed LH pulse frequency and mean serum concentrations of LH compared with the control group (P < 0.05). It was concluded that a strong or more acute inhibition of LH secretion by endogenous opioids developed in mid- to late prepubertal heifers, or alternatively, that removal of opioidergic inhibition at the GnRH neurone unmasked stimulatory inputs that were greater in heifers close to first ovulation. Since sulpiride appeared to negate in part the effects of naloxone on LH release, the suppressive effects of opioids could be exerted in part through the inhibition or blocking of a stimulatory dopaminergic system. alpha-Adrenergic neuronal systems have stimulatory effects on LH release, especially during the late prepubertal period, but do not appear to mediate opioidergic inhibition of LH secretion in prepubertal heifer calves.     

Influence of Sibutramine on Energy Expenditure in African American Women

Objective: African American women have a high prevalence of obesity, which partially may be explained by their lower rates of resting energy expenditure (REE). The aim of this study was to examine the influence of acute sibutramine administration on REE and post‐exercise energy expenditure in African American women. Research Methods and Procedures: A total of 15 premenopausal, African American women (age, 29 ± 5 years; body fat, 38 ± 7%) completed a randomized, double‐blind cross‐over design with a 30‐mg ingestion of sibutramine or a placebo. Each trial was completed a month apart in the follicular phase and included a 30‐minute measurement of REE 2.5 hours after sibutramine or placebo administration. This was followed by 40 minutes of cycling at ～70% of peak aerobic capacity and a subsequent 2‐hour measurement of post‐cycling energy expenditure. Results: There was no difference (p > 0.05) in REE (23.70 ± 2.81 vs. 23.69 ± 2.95 kcal/30 min), exercise oxygen consumption (1.22 ± 0.15 vs. 1.25 ± 0.15 liter/min), and post‐cycling energy expenditure (104.2 ± 12.7 vs. 104.9 ± 11.4 kcal/120 min) between the sibutramine and placebo trials, respectively. Cycling heart rate was significantly higher (p = 0.01) during the sibutramine (158 ± 14 beats/min) vs. placebo (150 ± 12 beats/min) trials. Discussion: These data demonstrate that acute sibutramine ingestion does not increase REE or post‐exercise energy expenditures but does increase exercising heart rate in overweight African American women. Sibutramine may, therefore, impact weight loss through energy intake and not energy expenditure mechanisms.     

Fruit juice consumption modulates antioxidative status,immune status and DNA damage

Polyphenolic compounds exert a variety of physiological effects in vitro including antioxidative, immunomodulatory and antigenotoxic effects. In a randomized crossover study in healthy men on a low-polyphenol diet, we determined the effects of 2 polyphenol-rich juices (330 ml/d) supplemented for 2 weeks on bioavailability of polyphenols, markers of antioxidative and immune status, and reduction of DNA damage. Juices provided 236 mg (A) and 226 mg (B) polyphenols with cyanidin glycosides (A) and epigallocatechin gallate (B) as major polyphenolic ingredients. There was no accumulation of plasma polyphenols after two weeks of juice supplementation. In contrast, plasma malondialdehyde decreased with time during juice interventions. Moreover, juice consumption also increased lymphocyte proliferative responsiveness, with no difference between the two juices. Interleukin-2 secretion by activated lymphocytes and the lytic activity of natural killer cells were significantly increased by both juices. Juice intervention had no effect on single DNA strand breaks, but significantly reduced oxidative DNA damage in lymphocytes. A time-delay was observed between the intake of fruit juice and the reduction of oxidative DNA damage and the increase in interleukin-2 secretion. We conclude that consumption of either juice enhanced antioxidant status, reduced oxidative DNA damage and stimulated immune cell functions. However, fruit juice consumption for 2 weeks did not result in elevated plasma polyphenols in subjects after overnight fasting. Further studies should focus on the time-delay between juice intake and changes in measured physiological functions, as well as on active polyphenolic metabolites mediating the observed effects.     

Chronic corticosterone treatment impairs Leydig cell 11beta-hydroxysteroid dehydrogenase activity and LH-stimulated testosterone production.

The effects of excess corticosterone on luteinizing hormone (LH)-stimulated Leydig cell testosterone production and activity of 11beta-HSD was studied. Adult male rats (200-250 g body weight) were treated with corticosterone-21-acetate (2 mg/100 g body weight, i.m., twice daily) for 15 days. Another set of rats was treated with corticosterone (dose as above) plus LH (ovine LH 100 microg/kg body weight, s.c., daily) for 15 days. Corticosterone administration significantly increased serum and testicular interstitial fluid (TIF) corticosterone but decreased testosterone levels. Administration of LH with corticosterone partially prevented the decrease in serum and TIF testosterone. The oxidative activity of 11beta-hydroxysteroid dehydrogenase (11beta-HSD) was significantly decreased in Leydig cells of rats treated with corticosterone alone and in combination with LH. The direct effect of corticosterone on Leydig cell steroidogenic potency was also studied in vitro. Addition of corticosterone to Leydig cell culture showed a dose dependent effect on LH-stimulated testosterone production. Corticosterone at 50 and 100 ng/ml did not alter LH-stimulated testosterone production, but at high doses (200-400 ng/ml), decreased basal and LH-stimulated testosterone production. Basal and LH-stimulated cAMP production was not altered by corticosterone in vitro. It is concluded from the present study that elevated levels of corticosterone decreased the oxidative activity of 11beta-HSD and thus resulting in impaired Leydig cell steroidogenesis and the inhibitory effects of corticosterone on testosterone production appear to be mediated through inhibition of LH signal transduction at post-cAMP level.     

Dietary habits and mortality in 11,000 vegetarians and health conscious people: results of a 17 year follow up.

OBJECTIVE: To investigate the association of dietary habits with mortality in a cohort of vegetarians and other health conscious people. DESIGN: Observational study. SETTING: United Kingdom. SUBJECTS: 4336 men and 6435 women recruited through health food shops, vegetarian societies, and magazines. MAIN OUTCOME MEASURES: Mortality ratios for vegetarianism and for daily versus less than daily consumption of wholemeal bread, bran cereals, nuts or dried fruit, fresh fruit, and raw salad in relation to all cause mortality and mortality from ischaemic heart disease, cerebrovascular disease, all malignant neoplasms, lung cancer, colorectal cancer, and breast cancer. RESULTS: 2064 (19%) subjects smoked, 4627 (43%) were vegetarian, 6699 (62%) ate wholemeal bread daily, 2948 (27%) ate bran cereals daily, 4091 (38%) ate nuts or dried fruit daily, 8304 (77%) ate fresh fruit daily, and 4105 (38%) ate raw salad daily. After a mean of 16.8 years follow up there were 1343 deaths before age 80. Overall the cohort had a mortality about half that of the general population. Within the cohort, daily consumption of fresh fruit was associated with significantly reduced mortality from ischaemic heart disease (rate ratio adjusted for smoking 0.76 (95% confidence interval 0.60 to 0.97)), cerebrovascular disease (0.68 (0.47 to 0.98)), and for all causes combined (0.79 (0.70 to 0.90)). CONCLUSIONS: In this cohort of health conscious individuals, daily consumption of fresh fruit is associated with a reduced mortality from ischaemic heart disease, cerebrovascular disease, and all causes combined.     

Total antioxidant power in sled dogs supplemented with blueberries and the comparison of blood parameters associated with exercise

Oxidative damage from free radicals plays an important role in several diseases such as cancer, Alzheimer's disease, and heart disease. Research indicates that exercise contributes to oxidative stress. Fruits, such as blueberries, are good antioxidants because they contain phenolics that preferentially react with free radicals. Maintaining antioxidant levels by supplementing the diet with blueberries may prevent exercise-induced oxidative damage. The goal of our study was to compare antioxidant levels in sled dogs supplemented with blueberries on blood parameters within 48 h post-exercise. Though the exercise protocol did not cause unusual muscle damage as reflected in plasma creatine kinase and isoprostane levels, blueberry supplementation did elicit significantly elevated antioxidant status in sled dogs post exercise. This suggests that dogs fed blueberries while exercising as compared to dogs fed a control diet while exercising, may be better protected against oxidative damage.     

An acute increase in serum prolactin does not modify gonadotropin release in female rats

Attempts were made to find out whether hyperprolactinemia has an effect on the hypothalamo-pituitary response to estrogen feedback and LHRH stimulation. Adult female rats of Wistar strain were ovariectomized and received subcutaneous injection of 20 micrograms estradiol benzoate (EB) 3-4 weeks later (day-0). A second injection of 20 micrograms EB, when administered at noon on day-3, induced a highly significant increase in serum LH (p less than 0.001 vs. basal values), but not FSH, estimated at 1800 h on the same day. This EB-promoted LH release was not altered by pretreatment with rat PRL (5 micrograms/day), which was administered subcutaneously daily in the morning (1100 h) between day-1 and day-3. No statistical difference in the serum LH concentration was found when compared with the values for the control animals pretreated with 0.9% saline alone. Serum gonadotropins 15 min after LHRH administration (100 ng/100 g BW) in 32-day-old female rats were not statistically different between the animals pretreated with 5 micrograms PRL, which was given subcutaneously daily (at 0800 h) for 3 days, and the controls pretreated with 0.9% saline. These results suggest that an acute increase in serum PRL may not exert a negative effect on the gonadotropin release induced by estrogen feedback and LHRH stimulation.     

Kaolin affects blueberry maggot behavior on fruit

This study assessed the effects of Surround (kaolin) on several behavioral parameters of female blueberry maggot, Rhagoletis mendax Curran (Diptera: Tephritidae). First fruit visited, walking, cleaning, and oviposition behavior were quantified in two-choice and no-choice assays where females encountered Surround-treated and untreated fruit of highbush blueberries (Vaccinium spp.). In two-choice assays, females had a propensity (68%) to first visit untreated blueberries. In two-choice and no-choice tests, number of walking bouts and duration of walking bouts were significantly shorter on the Surround-treated than on untreated fruit. Few oviposition attempts on fruit were observed, irrespective of treatments and assays. Chromameter measurements showed significant modification of the blueberry skin color parameters lightness, hue, and saturation between untreated fruit compared with fruit dipped once or twice in a suspension of Surround. Oviposition trials with field-treated fruit showed that blueberries treated with Surround had fewer oviposition scars than the control, and this was more pronounced with weekly applications of Surround. Uneven coating of the fruit by Surround in field applications may have resulted in higher acceptance rates by flies than in blueberries individually dipped and used in laboratory trials.     

Effect of non aromatizable androgens on LHRH and TRH responses in primary testicular failure

We have assessed the gonadotropin, TSH and PRL responses to the non aromatizable androgens, mesterolone and fluoxymestrone, in 27 patients with primary testicular failure. All patients were given a bolus of LHRH (100 micrograms) and TRH (200 micrograms) at zero time. Nine subjects received a further bolus of TRH at 30 mins. The latter were then given mesterolone 150 mg daily for 6 weeks. The remaining subjects received fluoxymesterone 5 mg daily for 4 weeks and 10 mg daily for 2 weeks. On the last day of the androgen administration, the subjects were re-challenged with LHRH and TRH according to the identical protocol. When compared to controls, the patients had normal circulating levels of testosterone, estradiol, PRL and thyroid hormones. However, basal LH, FSH and TSH levels, as well as gonadotropin responses to LHRH and TSH and PRL responses to TRH, were increased. Mesterolone administration produced no changes in steroids, thyroid hormones, gonadotropins nor PRL. There was, however, a reduction in the integrated and incremental TSH secretion after TRH. Fluoxymesterone administration was accompanied by a reduction in thyroid binding globulin (with associated decreases in T3 and increases in T3 resin uptake). The free T4 index was unaltered, which implies that thyroid function was unchanged. In addition, during fluoxymesterone administration, there was a reduction in testosterone, gonadotropins and LH response to LHRH. Basal TSH did not vary, but there was a reduction in the peak and integrated TSH response to TRH. PRL levels were unaltered during fluoxymesterone treatment.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of Two Conjugated Linoleic Acid Isomers on Body Fat Mass in Overweight Humans

Objective: To examine the effects of two different conjugated linoleic acid (CLA) isomers at two different intakes on body composition in overweight humans. Research Methods and Procedures: Eighty‐one middle‐aged, overweight, healthy men and women participated in this bicentric, placebo‐controlled, double‐blind, randomized study. For 6 weeks (run‐in period), all subjects consumed daily a drinkable dairy product containing 3 g of high oleic acid sunflower oil. Volunteers were then randomized over five groups receiving daily either 3 g of high oleic acid sunflower oil, 1.5 g of cis‐9, trans‐11 (c9t11) CLA, 3 g of c9t11 CLA, 1.5 g of trans‐10, cis‐12 (t10c12) CLA, or 3 g of t10c12 CLA administrated as triacylglycerol in a drinkable dairy product for 18 weeks. Percentage body fat mass and fat and lean body mass were assessed at the end of the run‐in and experimental periods by DXA. Dietary intake was also recorded. Results: Body fat mass changes averaged 0.1 ± 0.9 kg (mean ± SD) in the placebo group and ?0.3 ± 1.4, ?0.8 ± 2.1, 0.0 ± 2.3, and ?0.9 ± 1.7 kg in the 1.5‐g c9t11, 3‐g c9t11, 1.5‐g t10c12, and 3‐g t10c12 groups, respectively. Changes among the groups were not significantly different (p = 0.444). Also, lean body mass and dietary intake were not significantly different among the treatments. Discussion: A daily consumption of a drinkable dairy product containing up to 3 g of CLA isomers for 18 weeks had no statistically significant effect on body composition in overweight, middle‐aged men and women.     

Post partum patterns of circulating FSH, LH, prolactin, estradiol, and progesterone in nonsuckling cynomolgus monkeys.

Circulating levels of FSH, LH, prolactin (Prl), estradiol (E), and progesterone (P) were determined by RIA in four intact and four monkeys luteectomized (CLX) at parturition in order to a) characterize the patterns of these hormones during the puerperium, and b) examine a possible inhibitory role of the "rejuvenated" corpus luteum (CL) on the resumption of follicle growth post partum. In both groups during the first four weeks, FSH and LH were at tonic levels typical of ovulatory cycles. Recurrent puerperal "surges" of FSH, but not LH, unaccompanied by increments in serum E, were observed in both intact and CLX monkeys. No consistent pattern of serum Prl was apparent. CLX was followed by a prompt fall in serum P levels, which were elevated above typical follicular phase levels into the second week post partum in intact monkeys. Menstrual cycles resumed 2-4 months after delivery. Hormonal patterns during the first menstrual cycle post partum were indistinguishable from those observed in pregravidic ovulatory cycles. The findings indicate that in nonsuckling cynomolgus monkeys a) although it secretes progesterone, the puerperal CL does not inhibit the resumption of the ovarian cycle post partum, b) the puerperal ovary is not absolutely refractory to gonadotropins, since initial trials with Pergonal + hCG stimulated ovarian function, and c) ovarian activity during the puerperium may be limited by factors other than the tonic supply of gonadotropins.     

Studies of LDL oxidation following alpha-, gamma-, or delta-tocotrienyl acetate supplementation of hypercholesterolemic humans

In vitro tocotrienols (T3s) have potent vitamin E antioxidant activity, but unlike tocopherols can inhibit cholesterol synthesis by suppressing 3-hydroxy-3-methyl-glutarylCoA (HMG-CoA) reductase. Because hypercholesterolemia is a major risk factor for coronary artery disease and oxidative modification of low-density lipoprotein (LDL) may be involved in atherogenesis, we investigated whether daily supplements of placebo, or alpha-, gamma-, or delta- (alpha-, gamma-, or delta-) tocotrienyl acetates would alter serum cholesterol or LDL oxidative resistance in hypercholesterolemics in a double-blind placebo controlled study. Subjects were randomly assigned to receive placebo (n = 13), alpha- (n = 13), gamma- (n = 12), or delta- (n = 13) tocotrienyl acetate supplements (250 mg/d). All subjects followed a low-fat diet for 4 weeks, then took supplements with dinner for the following 8 weeks while still continuing diet restrictions. Plasma alpha- and gamma-tocopherols were unchanged by supplementation. Plasma T3s were undetectable initially and always in the placebo group. Following supplementation in the respective groups plasma concentrations were: alpha-T3 0.98 +/- 0.80 micromol/l, gamma-T3 0.54 +/- 0.45 micromol/l, and delta-T3 0.09 +/- 0.07 micromol/l. Alpha-T3 increased in vitro LDL oxidative resistance (+22%, p <.001) and decreased its rate of oxidation (p <. 01). Neither serum or LDL cholesterol nor apolipoprotein B were significantly decreased by tocotrienyl acetate supplements. This study demonstrates that: (i) tocotrienyl acetate supplements are hydrolyzed, absorbed, and detectable in human plasma; (ii) tocotrienyl acetate supplements do not lower cholesterol in hypercholesterolemic subjects on low-fat diets; and (iii) alpha-T3 may be potent in decreasing LDL oxidizability.     

Comparison of the Efficacy of Morning versus Evening Administration of Olmesartan in Uncomplicated Essential Hypertension

A total of 18 diurnally active subjects with uncomplicated, mild to moderate, essential hypertension were studied to compare the efficacy of the morning versus evening administration of an oral olmesartan medication. After a two‐week, wash‐out/placebo run‐in period, subjects with clinic diastolic blood pressure (DBP) ≥90 mm Hg and <110 mm Hg began 12 weeks of 20 mg olmesartan medoxomil tablet therapy at 08:00 h daily. Four of the 18 subjects required dose escalation to 40 mg at eight weeks because of clinic DBP≥90 mm Hg. After the 12‐week period of once‐a‐day 08:00 h treatment, subjects were immediately switched to an evening (20:00 h) drug‐ingestion schedule for another 12‐week period without change in dose. Subjects underwent 24 h ambulatory blood pressure monitoring (ABPM) before the initiation of morning treatment and at the end of both the 12‐week morning and evening treatment arms. Dosing time did not exert statistically significant differences on the efficacy of olmesartan: the reduction from baseline in the 24 h mean systolic (SBP) and DBP was, respectively, 18.8 and 14.6 mm Hg with morning dosing and 16.1 and 13.2 mm Hg with evening dosing (p>0.152 between groups). The amplitude of the BP 24 h pattern did not vary with dosing time, indicating full 24 h BP reduction no matter the clock hour of treatment. Although, the BP‐lowering effect was somewhat better with morning dosing, the results of this study suggest that the studied olmesartan medoxomil preparation efficiently reduces BP when ingested in the morning (08:00 h) or evening (20:00 h) in equivalent manner, based on statistical testing, throughout the 24 h.     

Captopril increased mitochondrial coenzyme Q10 level, improved respiratory chain function and energy production in the left ventricle in rabbits with smoke mitochondrial cardiomyopathy.

The aim of the study was to show whether the ACE inhibitor captopril is able to protect the heart against the deleterious effect of passive cigarette smoking on left ventricular mitochondria. Four groups of rabbits were investigated: control (C), passive smoking of three cigarettes twice daily/30 minutes (S), control + captopril (7.5 mg/kg body weight twice daily) (Cap), and smoking + captopril (SCap) as in group 2 and 3. Three weeks lasting passive smoking impaired oxidative phosphorylation, diminished cytochrome oxidase activity and increased the mitochondrial F1-ATPase protein concentration. Moreover, the level of coenzyme Q10 (CoQ10) and coenzyme Q9 were decreased. Simultaneous treatment with captopril prevented partly the decrease of CoQ10 level, deterioration of oxidative phosphorylation, diminution of cytochrome oxidase activity and enhancement of F1-ATPase level. We conclude that captopril protected the myocardium against the harmful effect of passive smoking in rabbits.     

Response of lutropin (LH) and follitropin (FSH) to the administration of gonadoliberin (GnRH) in pregnant and post-partum cattle including experiments with prolactin suppression

GnRH (250 μg) was administered intravenously in a total of 121 experiments carried out on 21 cows during the period from 180 days ante (ap) to 50 days post partum (pp). Additionally in one group of animals prolactin secretion was inhibited after parturition by means of 3 intramuscular injections of 150 mg Bromocryptine (CB-154) on days 1, 4 and 7 pp. LH response (peak height, area under the dose response curve) was about the same from 150 to 60 days ap, then decreased significantly towards parturition and was lowest during the first 6 days post partum. At a later time the Lh response was more pronounced than during pregnancy. The FSH response decreased significantly during the last 9 days ap, remained low during the frist 6 days pp and increased thereafter. There was no significant influence of prolactin inhibition on LH and FSH values (except for the total FSH released on day 50 pp). Whereas in all GnRH treated animals pronounced pituitary gonadotropin responsiveness was measurable (except during the period around parturition), the variation of the LH response pp was much higher than ap. The LH results gave some indication of the wide range of response pattern for this hormone after parturition which might be one reason for the individuality in the initiation of a new estrous cycle post partum in cattle.