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Beneficial effects of fluvastatin on myocardial blood flow at two time-points in hypercholesterolemic patients with coronary artery disease.

Hypercholesterolemia is a major risk factor initiating and accelerating atherosclerosis and leading to severe stages of coronary artery disease (CAD) with a high risk of cardiovascular events. We investigated the impact of lipid lowering in patients with hypercholesterolemia and evident CAD on clinically relevant parameters like myocardial perfusion. Myocardial imaging was performed with thallium-201 single photon-emission computed tomography at rest and after maximal bicycle exercise in 22 patients after a 4-week lead-in period, and after 12 and 24 weeks of therapy with fluvastatin. Perfusion defects occurred in all patients, indicating stress-induced myocardial ischemia. After 12 weeks of therapy, the perfusion of the ischemic segments increased by 26% (277+/-99 to 349+/-96 cpm; p < 0.001), whereas the value of the normal segments was augmented only by 4% (478+/-44 to 497+/-28 cpm; p < 0.05). The results slightly improved further after 24 weeks. Moreover, a subgroup analysis elucidated a more pronounced effect in patients without lipid-lowering premedication. This nonpretreated group (n = 11) revealed an improvement of ischemic segments at stress by 42% at week 24. In contrast, pretreated patients had an increase of only 18% (between groups, p < 0.05), indicating a carryover effect of premedication. In conclusion, short-term therapy with fluvastatin acts beneficially on impaired vascular function in hypercholesterolemic patients with CAD.

Adult↗

Lymphocyte responses to influenza and tetanus toxoid in vitro following intensive exercise and carbohydrate ingestion on consecutive days.

The effect of carbohydrate (CHO) ingestion on antigen- (rather than mitogen-) stimulated T-cell responses to prolonged, intensive exercise may give a more realistic insight into the effect of CHO on T-cell functional capacity and subsequent infection risk. This study investigated the effect of CHO ingestion during prolonged, intensive exercise on influenza- and tetanus toxoid-stimulated T-cell cytokine mRNA expression and proliferation. Mitogen- [phytohemagglutinin (PHA)] stimulated proliferation was assessed for comparison. Responses were assessed following exercise on consecutive mornings to determine any carryover effect. Fifteen male games players performed two exercise trials in a double-blind, randomized, crossover design. Each trial comprised 90 min of intensive, intermittent running on consecutive mornings, with either CHO (6.4% wt/vol) or placebo (PLA) beverage ingestion before, during, and after each bout of exercise. Postexercise CD3(+) cell counts were higher in PLA than CHO on both days (P < 0.05). Antigen-stimulated T-cell cytokine mRNA expression was unaffected by exercise or CHO ingestion. Before exercise on day 2, T-cell proliferative responses to PHA, influenza, and tetanus toxoid were higher in CHO than PLA by 99, 80, and 58%, respectively (P < 0.01 for PHA, P < 0.05 for influenza and tetanus toxoid). At 1 h postexercise on day 2, PHA-induced proliferation was 70% higher in CHO than PLA (P < 0.05), yet there were no differences between trials for antigen-induced proliferative responses. Therefore, mitogen-induced T-cell proliferation following strenuous exercise and CHO does not necessarily reflect responses to specific antigens and, consequently, may not provide a good model for the situation in vivo.

Adult↗

A double-blind placebo-controlled trial of antioxidant therapy in limited cutaneous systemic sclerosis.

OBJECTIVE: To evaluate the effects of a combination of micronutrient antioxidants (selenium, beta-carotene, vitamin C, vitamin E and methionine) with allopurinol in patients with limited cutaneous systemic sclerosis (SSc). METHODS: The study was designed as a placebo-controlled double-blind crossover study. A carryover effect was detected retrospectively for some of the prescribed antioxidants, and so the data were analysed as: (a) a between group comparison of the first 10 week treatment period; and (b) a within group comparison of the first and second 10-week periods in those who received placebo treatment first. Study end-points were plasma von Willebrand factor (vWF), thermographic response to a standard cold challenge, frequency and duration of Raynaud's attacks, patient opinion, and specialised biochemical parameters (fatty acid profiles, antioxidants and markers of free radical injury). RESULTS: Thirty-three patients were recruited. The median duration of Raynaud's phenomenon was 10 years (range 2 to 50 years) in the active-first group and 10 years (range 4 to 53 years) in the placebo-first group. In the 10-week study, there were no differences between the active and placebo groups in the change from baseline for vWF, for the parameters of the rewarming curve, or for patients' symptoms. Despite a rise in circulating antioxidant levels, there was no fall in markers of free radical mediated injury. In the 20-week cross-over study, patients did not experience any clinical benefit from active treatment compared to placebo. CONCLUSION: No clinical benefit could be demonstrated from active treatment. There are several possible explanations for this negative result, including the short duration of therapy. It is possible that antioxidant therapy, to be effective, needs to be given early in the SSc disease process, before the onset of irreversible tissue damage.

Adult↗

[Sequence in prescribing neuroleptics: a therapeutic alternative in refractory schizophrenia?].

Although clozapine (CLZ) is effective in resistant schizophrenia, it fails in some cases leading to a therapeutic problem. Authors report a case of schizophrenia which resists several neuroleptic trials (including haloperidol, chlorpromazine and thioproperazine) and responds to a sequence of CLZ and amisulpride. These two atypical neuroleptics have the same main target (mesolimbic system) but have different and complementary affinities to neuromediator receptors: CLZ has strong serotoninergic and anticholinergic action, noradrenergic alpha 1 affinity and moderately active dopaminergic antagonism; amisulpride has a high and specific dopaminergic D2 antagonism when used at high posology. This clinical improvement can be related to "second treatment effect", described by Goldman in 1966: his study included two groups of refractory schizophrenic patients who received successively during two 6 months periods, 2 neuroleptics (fluphenazine and trifluperazine). Without initial therapeutic response, he noted a significant improvement only after change of neuroleptic medication. Tricyclic antidepressants may turn to be effective, after an initial failure, when they are given after an uneffective ECT trial. The same model may be applied and the clozapine-amisulpride sequence is proposed as an alternative treatment in resistant schizophrenia: even if CLZ is uneffective, it may produce carryover effects which ease the action of amisulpride. The hypothesis of an action on 5HT2-D2 antagonism is advanced. It leads to the general question of the opportunity of neuroleptic sequential prescription in resistant schizophrenia as a therapeutic option.

Adult↗

Spatial working memory and the brainstem cholinergic innervation to the anterior thalamus.

The anteroventral thalamic nucleus (AV) has a role in spatial memory, but the influence of the prominent brainstem cholinergic projection to this region is unknown. Here, spatial memory in a 12-arm radial maze was examined after 0.15 microl bilateral AV infusions of scopolamine. In part one, rats visited six arms singly (the phase 1 arms) and, after a 10 min delay, were allowed free choice to both phase 1 arms and the remaining six baited arms (phase 2 arms). Scopolamine (10 microg) administered during the delay increased errors to both phase 1 and phase 2 arms, whereas PBS infusions increased phase 1 arm errors only. The PBS effect was the result of inserting the internal cannulas alone and not the infusion. The same dose of scopolamine (10 microg) infused before maze testing (part two: no phase 1 arms, no delay) also impaired spatial memory over and above the effects of both PBS and no-infusion, which did not differ markedly. Part two also showed that choice latency and choice strategies were unaffected by PBS and scopolamine. Cannulation and infusion procedures in both parts one and two did not produce any negative carryover effects across multiple control (no internal cannula) sessions, and a trypan blue manipulation indicated that infusions were restricted to the AV region. This study provides the first direct evidence that the brainstem cholinergic innervation to the limbic thalamus influences learning and memory, which may have important implications for human neurological conditions such as alcohol-related disorders and schizophrenia.

Animals↗

Effects of interstimulus interval on slow phase velocity to ipsilateral warm air caloric stimulation in normal subjects.

This study investigated the effects of interstimulus interval on slow phase velocity (SPV) to ipsilateral warm air caloric stimulation in normal subjects. Results suggest that about 3 minutes should intervene between the offset of one irrigation and the onset of the second irrigation. This finding supports the hypothesis that carryover effects are likely only when nystagmus from the preceding irrigation overlaps the subsequent irrigation. If correct, clinicians do not have to wait a fixed time period between stimuli, but can initiate caloric stimulation as soon as nystagmus has ceased from the preceding irrigation. This recommendation compensates for individual and procedural differences. Test-retest reliability also was investigated. Findings suggest that when immediate test-retest differences exceed approximately 6 degrees/second (95% confidence interval), the examiner should administer additional trials until stability is ascertained. Moreover, unusual or significant findings should be verified with repeat testing.

Adult↗

Use of crossover trials to obtain antihypertensive dose-response curves and to study combination therapy during the development of benazepril.

When a new drug is developed, one of the first requirements is to establish the correct dose. Unfortunately, in dose-determination studies, not enough lessons have been learned from the past. Pilot studies are often planned without sufficient statistical power, due to an insufficient number of patients and highly variable blood pressure measurements. In the development of the new angiotensin converting enzyme (ACE) inhibitor benazepril, crossover trials were used to obtain useful information. At the end of phase II of the benazepril development, a double-blind crossover study was carried out with 25 patients, and the results made it possible to redefine the 12- and 24-h effects of benazepril in comparison with placebo. Moreover, the crossover trial allowed an investigation of the biological effects of the treatment. In further work, the efficacy of 10 mg benazepril, administered once a day, was confirmed in comparison with captopril and enalapril, with a beta-risk of less than 20%. Since this crossover study yielded reliable data, and there was no carryover effect, a similar crossover design was used to study the interaction between benazepril and nifedipine. In the past, mistakes were made and many antihypertensive drugs were administered in high doses, with no further beneficial effect on blood pressure and an increased risk of side effects. Work described in this paper shows that fewer but better designed and implemented studies can improve the efficiency and value of dose-finding studies for antihypertensive drugs.

Antihypertensive Agents↗

Studies of women eating diets with different fatty acid composition. I. Plasma lipoproteins and steroid excretion.

Moderate changes in dietary fat composition have been recommended to improve plasma cholesterol status. Such changes have not been studied extensively in women. This research evaluates plasma lipoprotein and steroid excretion changes in young women who consumed a diet similar to US average consumption in 1974 [40 en% fat, polyunsaturated (P) to saturated fatty acid (S) ratio, P/S = 0.3, US74] or a diet modified to contain 30 en% fat, P/S = 1.0 (MOD). Following a preexperimental period of self-selected diets, young women were fed the diets for 28-day periods in a crossover design with 10 women at the University of Nebraska, Lincoln, and 10 at Iowa State University, Ames. Plasma lipoproteins and steroid excretion were quantitated and the compositions determined. Data were analyzed for race (five Chinese, 14 Caucasians) and for diet carryover effects, as well as for primary diet effects. In the Chinese women, the US74 diet raised total and very-low-density lipoprotein (VLDL) cholesterol compared to prior self-selected or modified diets; in the Caucasian women the MOD diet lowered total, low-density lipoprotein (LDL), and VLDL cholesterol. The diet carryover was evident in total high-density lipoprotein (HDL) and HDL3 cholesterol. Total HDL and HDL3 cholesterol in response to the US74 diet were unchanged from the MOD diet when the US74 diet followed the MOD diet, but were lower than modified when the US74 diet followed self-selected diets. The US74 diet resulted in greater neutral sterol excretion than the MOD diet; this response was more marked in the self-selected, US74, MOD sequence than in the self-selected, MOD, US74 sequence.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Duration of opioid antagonism by nalmefene and naloxone in the dog: an integrated pharmacokinetic/pharmacodynamic comparison.

A continuous fentanyl infusion was administered to eight adult, male beagle dogs for a duration of approximately 400 min at a rate of 30 micrograms/kg/h. The extent of respiratory depression was quantified by continuous, noninvasive, transcutaneous pCO2 recordings. Upon reaching a pseudosteady-state of respiratory depression at approximately 120 min of fentanyl infusion, the animals then received, in a 2 x 2 crossover fashion separated by approximately 3 weeks, 30-minute equiefficacious infusions of nalmefene (12 micrograms/kg/h) or naloxone (48 micrograms/kg/h). Multiple venous blood samples were taken throughout the dosing regimen, and the resulting fentanyl, nalmefene, or naloxone plasma concentrations were determined. The concentration-time data were analyzed by noncompartmental methods and subsequently linked to the pharmacodynamic effect data by a competitive antagonism link model. Separately, the biophase concentrations were linked to the plasma concentration-time profiles through a single-exponential conduction function. The various pharmacokinetic/pharmacodynamic parameters resulting from this semiparametric analysis were analyzed by ANOVA, using a statistical model that considers carryover effects. The results of these analyses indicate that several pharmacokinetic/pharmacodynamic parameters of the two antagonists were comparable. However, nalmefene had a significantly more protracted terminal disposition and a significantly greater persistency in the biophase evaluated over the experimental time frame from 0 to 450 min.

Animals↗

Facilitative effects of the ampakine CX516 on short-term memory in rats: enhancement of delayed-nonmatch-to-sample performance.

Ampakines are a family of drugs that selectively increase AMPA receptor-gated currents and improve performance on several behavioral tasks. This report describes evidence that ampakines cause a cumulative enhancement of performance in a spatial short-term memory task (Deadwyler et al., 1996). Two groups of rats were trained on a spatial variant of the delayed-nonmatch-to-sample (DNMS) paradigm. One group (n = 12) received the ampakine CX516 (Cortex Pharmaceuticals) alternated with vehicle for 17 consecutive days and then only vehicle for an additional 7 d. The second group (n = 6) received only vehicle injections over the same number of days. CX516 improved performance within sessions, particularly on trials with delays of 6-35 sec. In 9 of 12 rats, the positive effect of the drug was also present on nondrug days between CX516 administration and after cessation of CX516 injections. The animals that received only vehicle injections showed no improvement in DNMS performance over the entire 32 d of testing. Three of the 12 animals given CX516 did not exhibit "carryover" effects of the drug to the intervening (vehicle only) test sessions, but nonetheless exhibited superior performance during the first half of the session on days in which the ampakine was administered. Evaluation of errors suggests that the ampakine eliminated the necessity for a shift in response strategy that produced proactive interference on the following trial. Hippocampal involvement in these ampakine effects is discussed as a prelude to the second article in the series (Hampson et al., 1998).

Animals↗

Effects of protein and amino acid level fed zero to forty-two days on response of broilers to protein and amino acid levels fed forty-two to forty-nine days of age.

Three studies were conducted to evaluate the effect of protein and amino acid (AA) levels fed 0 to 42 days posthatch on response of broiler chickens to levels of protein and AA fed during the finisher period. Birds were grown to 42 days on diets formulated to contain a minimum of 105 or 120% of recommended AA levels, and then randomly assigned to diets formulated to contain a minimum of 70, 80, 90, 100, 110, or 120% of recommended AA levels for 42 to 49 days. No minimum protein level was imposed on the diets. Body weight, feed intake, feed utilization, dressing percentage, abdominal fat content, and parts yield were determined. The protein and AA level fed 0 to 42 days had significant effects on 42- and 49-day body weight and 42- to 49-day feed intake of male but not female broilers. However, there was no interaction of protein and AA levels fed 0 to 42 days on response to protein and AA levels fed 42 to 49 days for these criteria. Weight gain, feed intake, and feed utilization of both males and females 42 to 49 days were significantly influenced by protein and AA levels fed during this time; protein and AA requirements of females during this time appeared to be equal to, or greater than, those of the male broiler. Although there were significant interactions of protein and AA levels 0 to 42 and 42 to 49 days on various carcass parameters for both male and female broilers, these followed no consistent pattern. Protein and amino acid levels fed 0 to 42 days had a significant influence on both quantity and percentage of abdominal fat in both male and female broilers processed at 49 days but not on any other carcass parameters. The protein and AA levels fed 42 to 49 days had a significant effect on both quantity and percentage of abdominal fat in male but not female broilers. The protein and AA levels fed 42 to 49 days significantly influenced quantity but not percentage of breast meat in male but not female broilers. The results of the current study indicate that there was minimal carryover effect of protein and AA levels fed 0 to 42 days on response to AA levels fed 42 to 49 days.

Adipose Tissue↗

The effects of diet differing in fat, carbohydrate, and fiber on carbohydrate and lipid metabolism in type II diabetes.

This study was designed to determine the effects of varying the proportions of carbohydrate, fiber, and fat on metabolic control in Type II diabetes. Ten men, aged 50 to 69 years, with Type II diabetes participated. Four isocaloric diets were consumed for 2 weeks each, with a break of 6 to 14 weeks between diets to ensure no carryover effects. Two of the diets were high in carbohydrate (63% to 65% energy) and low in fat (10% to 12% energy) but differed in their fiber contents (20 vs. 45 gm/day). The other two diets were low in carbohydrate (23% to 27% energy) with either a low or a high fat content (15% vs. 55% energy) and a high or normal protein content (62% vs. 18% energy). The composition of the subjects' usual diets in the week before each of the experimental diets did not vary significantly: carbohydrate 47% to 50% energy, protein 22% to 25% energy, fat 27% to 31% energy, and fiber 24 to 25 gm/day. A 75-gm oral glucose tolerance test and a 12-hour metabolic profile in response to 3 meals typical of the particular diet were conducted before and at the conclusion of each 2-week dietary period. The most significant improvements in metabolic control (as assessed by the effects of the diets on fasting glucose and on lipids, and on the glucose and insulin responses to oral glucose and the mixed meals) were obtained with the high-fiber, high-carbohydrate, low-fat diet and with the low-carbohydrate, high-protein, low-fat diet. Metabolic control was not significantly affected by the low-fiber, high-carbohydrate, low-fat diet, but it deteriorated significantly on the low-carbohydrate, high-fat diet. The results of this study confirmed the importance of high fiber and low fat in improving metabolic control in Type II diabetes. In conclusion, if high-carbohydrate, low-fat diets are to be recommended to patients with diabetes, it is essential that the type of carbohydrate recommended be unrefined and high in fiber.

Blood Glucose↗

Preparation of novel solid-phase microextraction fibers by sol-gel technology for headspace solid-phase microextraction-gas chromatographic analysis of aroma compounds in beer.

3-(Trimethoxysilyl)propyl methacrylate (TMSPMA) was first used as precursor as well as selective stationary phase to prepare the sol-gel-derived TMSPMA-hydroxyl-terminated silicone oil (TMSPMA-OH-TSO) solid-phase mircroextraction (SPME) fibers for the analysis of aroma compounds in beer. TMSPMA-OH-TSO was a medium polarity coating, and was found to be very effective in carrying out simultaneous extraction of both polar alcohols and fatty acids and nonpolar esters in beer. The extraction temperature, extraction time, and ionic strength of the sample matrix were modified to allow for maximium sorption of the analytes onto the fiber. Desorption temperature and time were optimized to avoid the carryover effects. To check the matrix effects, several different matrices, including distilled water, 4% ethanol/water (v/v) solution, a concentrated synthetic beer, a "volatile-free" beer and a real beer were investigated. Matrix effects were compensated for by using 4-methyl-2-pentanol as internal standard and selecting the "volatile-free" beer as working standard. The method proposed in this study showed satisfactory linearity, precision and detection limits and accuracy. The established headspace SPME-gas chromatography (GC) method was then used for determination of volatile compounds in four beer varieties. The recoveries obtained ranged from 92.8 to 105.8%. The relative standard deviations (RSD, n = 5) for all analytes were below 10%. The major aroma contributing substances of each variety were identified via aroma indexes.

Beer↗

Influence of stocking rate and steroidal implants on growth rate of steers grazing toxic tall fescue and subsequent physiological responses.

An 84-d grazing experiment was conducted in 2 growing seasons to evaluate interactions of stocking rate and steroidal implants with BW gain and symptoms of toxicosis in yearling steers grazing endemic endophyte-infected (E+) tall fescue (Festuca arundinacea Schreb.). A 4 x 2 factoral design was used to evaluate 4 stocking rates (3.0, 4.0, 5.0, and 6.0 steers/ ha) with or without steroidal implants (200 mg of progesterone + 20 mg of estradiol benzoate). Treatment combinations were randomly assigned to eight 1-ha pastures of E+ Kentucky-31 tall fescue (i.e., treatments were not replicated). Treatment effects were analyzed for ADG, total BW gain per hectare, forage availability, and hair coat ratings. At the conclusion of grazing in the second year (22 June), steers were placed on a bermudagrass [Cynodon dactylon (L.) Pers.] pasture, and rectal temperatures and serum prolactin concentrations were monitored for 10 d to assess carryover effects of stocking rate and steroidal implants on recovery from toxicosis-related heat stress. Forage availability differed (P < 0.001) between years, but there were no year x treatment interactions (P > 0.10). There was an implant x stocking rate interaction (P < 0.05) on ADG. Differences between the slopes in the regression equations indicated that ADG responded to implantation when stocking rates were low, but the response diminished as stocking rate increased. Stocking rate did not influence (P = 0.89) postgraze rectal temperature, but the regression intercept for implanted steers was 0.4 degrees C greater (P < 0.05) than for nonimplanted steers, and the difference was consistent across the entire 10-d fescue-free grazing period. Concentrations of prolactin increased during the 10-d fescue-free grazing period, but trends differed due to an implantation x stocking rate interaction (P < 0.05). Results indicate that implantation with progesterone + estradiol benzoate increases ADG with lower stocking rates, but the effect diminishes with increased grazing intensity. Implantation with steroid hormones increased rectal temperatures, but during a fescue-free grazing period rectal temperatures and serum prolactins for implanted and nonimplanted steers returned to values indicative of a stable and healthy status in a 192- to 240-h (i.e., an 8- to 10-d) period. However, because the treatments used in this study were not replicated, these observations need to be confirmed with replicated studies.

Absorbable Implants↗

Effects of supplementation with purified red clover (Trifolium pratense) isoflavones on plasma lipids and insulin resistance in healthy premenopausal women.

Consumption of isoflavone-rich soyabean protein is reported to reduce total and LDL-cholesterol, but the specific components responsible are undetermined. In a previous crossover trial we showed that purified isoflavones, derived from red clover (Trifolium pratense), raised HDL3-cholesterol in premenopausal women; however, these findings were inconclusive due to period and carryover effects. In an attempt to overcome this problem, we utilised a parallel study designed to re-examine the effects of purified isoflavones on plasma lipoproteins and markers of insulin resistance in premenopausal women. Twenty-five healthy premenopausal women participated in a double-blind, randomised, parallel study. The treatment group (n 12) consumed a placebo for the first menstrual cycle and an isoflavone supplement (86 mg/d, derived from red clover) for three cycles, while the placebo group (n 13) consumed a placebo supplement for four menstrual cycles. Blood samples were collected weekly during cycles 1, 3 and 4. Supplementation with isoflavones resulted in a 15-fold increase in urinary isoflavone excretion (P<0.0001). There were no significant effects on total cholesterol, LDL- and HDL-cholesterol, HDL subfractions, triacylglycerol, lipoprotein(a), glucose or insulin concentrations. Our present results indicate that purified isoflavones derived from red clover have no effect on cholesterol homeostasis or insulin resistance in premenopausal women, a group which is at low risk of CHD.

Adult↗

Sequential predator effects across three life stages of the African tree frog, Hyperolius spinigularis.

While theoretical studies of the timing of key switch points in complex life cycles such as hatching and metamorphosis have stressed the importance of considering multiple stages, most empirical work has focused on a single life stage. However, the relationship between the fitness components of different life stages may be complex. Ontogenetic switch points such as hatching and metamorphosis do not represent new beginnings--carryover effects across stages can arise when environmental effects on the density and/or traits of early ontogenetic stages subsequently alter mortality or growth in later stages. In this study, I examine the effects of egg- and larval-stage predators on larval performance, size at metamorphosis, and post-metamorphic predation in the African tree frog Hyperolius spinigularis. I monitored the density and survival of arboreal H. spinigularis clutches in the field to estimate how much egg-stage predation reduced the input of tadpoles into the pond. I then conducted experiments to determine: (1) how reductions in initial larval density due to egg predators affect larval survival and mass and age at metamorphosis in the presence and absence of aquatic larval predators, dragonfly larvae, and (2) how differences in mass or age at metamorphosis arising from predation in the embryonic and larval environments affect encounters with post-metamorphic predators, fishing spiders. Reduction in larval densities due to egg predation tended to increase per capita larval survival, decrease larval duration and increase mass at metamorphosis. Larval predators decreased larval survival and had density-dependent effects on larval duration and mass at metamorphosis. The combined effects of embryonic and larval-stage predators increased mass at metamorphosis of survivors by 91%. Larger mass at metamorphosis may have immediate fitness benefits, as larger metamorphs had higher survival in encounters with fishing spiders. Thus, the effects of predators early in ontogeny can alter predation risk even two life stages later.

Age Factors↗

Effects of nitrous oxide on psychological performance.

Thirty healthy volunteers took part in this double-blind crossover study comparing 15 percent nitrous oxide in oxygen with 100 percent oxygen. They received each treatment for 45 minutes, in counter-balanced order, with no break between treatments. Central nervous system (CNS) effects of nitrous oxide were assessed by a battery of performance tests and by the Visual Analog Scales. The Digit-symbol Substitution Test showed significant slowing with nitrous oxide as did Symbol-digit Substitution and Sentence Verification. Subjects rated themselves as more drowsy, dizzy, abnormal, drunk, and muzzy on nitrous oxide than on oxygen. Significant carryover effects were seen only for the Alert-Drowsy scale at 2.5 minutes after the start of treatment, and not at any later time point. These results show that the onset and offset of the CNS effects of 15 percent nitrous oxide are sufficiently rapid to permit the study of two treatment periods within a single experimental session.

Adult↗

The recruitment of ovarian follicles is enhanced by increased dietary intake in heifers.

The objective of this study was to determine whether dietary-induced changes in growth hormone (GH), insulin, and IGF-I alter the pattern of ovarian follicular development in heifers. Twenty-eight 2- to 3-yr-old Hereford-Friesian heifers were equally allocated (n = 7) to one of four dietary treatments: 1) Control (C) fed a maintenance diet as two meals per day; 2) twice maintenance (2M2) given as two meals per day; 3) twice maintenance (2M6) given as six meals per day; 4) feed-deprived (F) fed maintenance requirements as for C, changed to straw ad libitum for 3 d from a synchronized estrus. On d 4 (estrus = d 0) heifers were transferred to grass silage (ad libitum access) until the end of the experiment. Blood samples were collected hourly for 10 h on d 1 and 3 and daily for an additional 14 d. Follicular development was monitored daily by ultrasonography until d 14. The number of small follicles (< 4 mm) was increased (P < .05) by 37% on d 1 and 2 in 2M2 and 2M6 heifers, with no carryover effect of nutrition to the second follicular wave. Number of medium-sized (4 to 8 mm) and large (> 8 mm) follicles did not vary (P > .05) among treatments. The FSH concentrations were not different (P > .05) among treatments. Insulin concentrations were higher (P < .05) in 2M2 and 2M6 heifers than in C or F heifers, with no carryover after the diet was changed. Increase in number of small follicles was independent of changes in FSH and IGF-I, negatively associated with GH, but positively associated with circulating insulin. These results indicate that a short-term increase in nutritional plane can affect follicular recruitment in cycling heifers.

Animal Nutritional Physiological Phenomena↗