Development of a rapid, sensitive, and selective LC-MS/MS method for quantifying curcumin levels in healthy human urine: Effect of pepper on curcumin bioavailability.

Curcumin (CCM), a culinary spice, is widely consumed for its health benefits for managing oxidative and inflammatory conditions, metabolic syndrome, arthritis, and hyperlipidemia. However, due to its extensive metabolism, the oral bioavailability of CCM is very low. In this study, we developed a rapid, sensitive, and selective assay to examine the hypothesis that piperine improves CCM bioavailability after piperine co-ingestion. We developed a selective, sensitive, and robust LC-MS/MS method to quantify CCM in human urine. The method was linear over a concentration range 0.625-40 ng/mL with LLOQ and LLOD of 0.625 ng/mL and 0.312 ng/mL, respectively. Healthy volunteers have consumed test meals of CCM as turmeric powder with and without black pepper with 1 week wash out. Urine samples were collected for 24 hours and analyzed for CCM excretion. Black pepper increased CCM half-life from 2.2 ± 0.79 h (CCM alone) to 4.5 ± 0.80 h (CCM + pepper). The CCM 24-h urinary excreted amount was higher in individuals consuming CCM + pepper (218.14 ± 94.98 µg) than those who received CCM only (49.45 ± 12.94 µg). This preliminary study indicates that piperine significantly increased CCM oral absorption, reduced systemic clearance, and improved bioavailability.

Circadian Modulation of the Antioxidant Effect of Grape Consumption: A Randomized Controlled Trial.

Grape consumption acts on the immune system to produce antioxidant and anti-inflammatory effects. Since immune activity demonstrates circadian rhythmicity, with peak activity occurring during waking hours, the timing of grape intake may influence the magnitude of its antioxidant effect. This study followed a 2 × 2 factorial randomized, controlled design wherein healthy men and women (n = 32) consumed either a grape or placebo drink with a high-fat meal in the morning or evening. Urine was collected for measurements of biomarkers of oxidative stress and grape metabolites at baseline and post-meal at hour 1 and hours 1-6. F-2 isoprostane levels showed main effects of time period (baseline < hour 1 < hours 1-6, p < 0.0001), time (a.m. > p.m., p = 0.008) and treatment (placebo > grape, p = 0.05). Total F2-isoprostane excretion expressed as % baseline was higher in the a.m. vs. p.m. (p = 0.004) and in the a.m. placebo vs. all other groups (p < 0.05). Tartaric acid and resveratrol excretion levels were higher in the grape vs. placebo group (p < 0.05) but were not correlated with F-2 isoprostane levels. The findings support a protective effect of grape consumption against morning sensitivity to oxidative stress.

The Effect of Berry Consumption on Oxidative Stress Biomarkers: A Systematic Review of Randomized Controlled Trials in Humans.

Bioactive compounds in berries may scavenge reactive oxygen and nitrogen species by donating electrons to free radicals, thereby protecting DNA, proteins, and lipids from oxidative damage. Evidence shows that berry consumption has beneficial health effects, though it remains unclear whether berries exert a significant impact on oxidative stress in humans. Thus, we performed a systematic review of randomized controlled trials (RCT) to examine the effects of non-acute (more than a single dose and ≥7 days) berry consumption on biomarkers of oxidative stress. Searches were conducted in PubMed, Cochrane Library, and Scopus; results were imported into Covidence for screening and data extraction. The literature search identified 622 studies that were screened, and 131 full-text studies assessed for eligibility. Ultimately, 28 RCTs met the eligibility criteria. Common biomarkers of oxidative stress (antioxidants, DNA damage, isoprostanes, malondialdehyde, and oxidized LDL) were systematically reviewed, and results were reported narratively. Of the approximate 56 oxidative stress biomarkers evaluated in the 28 RCTs, 32% of the biomarkers were reported to have statistically significant beneficial results and 68% of the biomarkers were reported as having no statistically significant differences. More well-designed and longer-term berry RCTs are needed to evaluate biomarkers of oxidative stress.

The effect of branched-chain amino acid supplementation on cancer treatment.

Background: Anticancer therapies are associated with significant adverse side effects and few treatments that alleviate symptoms exist. Branched-chain amino acids (BCAAs) have been investigated as an intervention for reducing anticancer therapy side effects, although a review of the literature results has yet to be published. Aim: The current review summarizes evidence surrounding this topic and suggests both support and caution in using BCAAs as a treatment for patients receiving anticancer therapies. Methods: In this review, two literature searches were completed. Google Scholar, PubMed, EBSCOhost, and Cochrane databases were searched using the terms "branched-chain amino acids and cancer" and "BCAA and cancer." Results: Two bodies of evidence emerged: One supporting beneficial effects and the other showing adverse outcomes of BCAA supplementation in patients with cancer. Evidence of benefit was a decrease in malnourishment and unintentional weight loss during and after chemotherapy. Potential harms included the idea cancer cells may utilize BCAAs as a source of energy for growth. Conclusions: Supplementation of BCAAs in individuals with cancer should be implemented cautiously. Those who are severely malnourished due to anticancer therapy may benefit the most. BCAA supplementation may also be provided once cancer has been destroyed from the individual's body to aid with recovery.

Dietary Hempseed Decreases Femur Maximum Load in a Young Female C57BL/6 Mouse Model but Does Not Influence Bone Mineral Density or Micro-Architecture.

Numerous seed and seed extract diets have been investigated as a means of combating age-related bone loss, with many findings suggesting that the seeds/extracts confer positive effects on bone. Recently, there has been rising interest in the use of dietary hempseed in human and animal diets due to a perceived health benefit from the seed. Despite this, there has been a lack of research investigating the physiologic effects of dietary hempseed on bone. Previous studies have suggested that hempseed may enhance bone strength. However, a complete understanding of the effects of hempseed on bone mineralization, bone micro-architecture, and bone biomechanical properties is lacking. Using a young and developing female C57BL/6 mouse model, we aimed to fill these gaps in knowledge. From five to twenty-nine weeks of age, the mice were raised on either a control (0%), 50 g/kg (5%), or 150 g/kg (15%) hempseed diet (n = 8 per group). It was found that the diet did not influence the bone mineral density or micro-architecture of either the right femur or L5 vertebrae. Furthermore, it did not influence the stiffness, yield load, post-yield displacement, or work-to-fracture of the right femur. Interestingly, it reduced the maximum load of the right femur in the 15% hempseed group compared to the control group. This finding suggests that a hempseed-enriched diet provides no benefit to bone in young, developing C57BL/6 mice and may even reduce bone strength.

Anti-Inflammatory Diet for Women with Interstitial Cystitis/Bladder Pain Syndrome: The AID-IC Pilot Study.

Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic condition characterized by pelvic pain coupled with urinary frequency and urgency. The underlying cause of IC/BPS is unknown; there is no cure. Dietary components exacerbate symptoms. The Anti-Inflammatory Diet for Interstitial Cystitis (AID-IC) employs a randomized, crossover design to evaluate the effect of a plant-based, low saturated fat diet on the quality of life of women with IC/BPS. Insights on the implementation of the protocol and reflections on the facilitators and barriers experienced during the pilot study follow. The logistics of the protocol proved time-consuming; however, the barriers were surmountable. Quantitative and qualitative findings suggest that the AID-IC therapeutic diet may have lessened symptoms and improved the quality of life for many of the women in the study.

The Effects of Berry Polyphenols on the Gut Microbiota and Blood Pressure: A Systematic Review of Randomized Clinical Trials in Humans.

Berry consumption has beneficial effects on blood pressure. Intestinal microbiota transform berry phytochemicals into more bioactive forms. Thus, we performed a systematic review of randomized clinical trials to determine whether berry polyphenols in foods, extracts or supplements have effects on both the profile of gut microbiota and systolic and diastolic blood pressure in humans. PubMed, Cochrane Library, Scopus, and CAB Abstracts (EBSCOhost) were searched for randomized clinical trials in humans published from 1 January 2011 to 29 October 2021. Search results were imported into Covidence for screening and data extraction by two blinded reviewers, who also performed bias assessment independently. The literature search identified 216 publications; after duplicates were removed, 168 publications were screened with 12 full-text publications assessed for eligibility. Ultimately three randomized clinical trials in humans met the eligibility criteria. One randomized clinical trial showed a low risk of bias while the other two randomized clinical trials included low, high or unclear risk of bias. Together the randomized clinical trials showed that berry consumption (Aronia berry, strawberries, raspberries, cloudberries and bilberries) for 8-12 weeks had no significant effect on both blood pressure and the gut microbiota. More randomized clinical trials are needed to determine the effects of berry consumption on the profile of gut microbiota and blood pressure in humans.

The Impact of Hempseed Consumption on Bone Parameters and Body Composition in Growing Female C57BL/6 Mice.

Optimizing peak bone mass is critical to healthy aging. Beyond the established roles of dietary minerals and protein on bone integrity, fatty acids and polyphenols modify bone structure. This study investigated the effect of a diet containing hempseeds (HS), which are rich in polyunsaturated fatty acids and polyphenols, on bone mineral density, bone cell populations and body composition. Groups (n = 8 each) of female C57BL/6 mice were fed one of three diets (15% HS by weight; 5% HS; 0% HS (control)) from age 5 to 30 weeks. In vivo whole-body composition and bone mineral density and content were measured every 4 weeks using dual-energy X-ray absorptiometry. Ex vivo humeri cell populations in the epiphyseal plate region were determined by sectioning the bone longitudinally, mounting the sections on slides and staining with tartrate-resistant acid phosphatase and alkaline phosphatase stain to identify osteoclasts and osteoblasts, respectively. Mixed models with repeated measures across experimental weeks showed that neither body weight nor body weight gain across weeks differed among groups yet mice fed the 15% HS diet consumed significantly more food and more kilocalories per g body weight gained than those fed the 5% HS and control diets (p < 0.0001). Across weeks, fat mass was significantly higher in the 5% HS versus the control group (p = 0.02). At the end point, whole-body bone mineral content was significantly higher in the control compared to the 5% HS group (p = 0.02). Humeri from both HS groups displayed significantly lower osteoblast densities compared to the control group (p < 0.0001). No relationship was seen between osteoblast density and body composition measurements. These data invite closer examination of bone cell activity and microarchitecture to determine the effect of habitual HS consumption on bone integrity.

Diet Quality and Mental Health Status among Division 1 Female Collegiate Athletes during the COVID-19 Pandemic.

The International Olympic Committee has identified mental health as a priority that significantly affects the physical health and safety of collegiate athletes. Interventions that improve diet quality have been shown to improve mental health in several populations. However, studies are needed to examine this relationship in female collegiate athletes, who have elevated risk of experiencing anxiety and depression symptoms, as well as dietary insufficiencies. In a quantitative, cross-sectional study, female student athletes at a U.S. university completed three mental health questionnaires: Depression Anxiety and Stress Scale (DASS-21), Athlete Psychological Strain Questionnaire (APSQ), and COVID Stress Scales (CSS). Each female athlete also completed a validated, web-based Diet History Questionnaire (DHQ-III) resulting in a Healthy Eating Index (HEI). Seventy-seven participants completed all survey information. HEI scores were consistently higher for athletes with poorer mental health. HEI scores were significantly positively associated with stress (p = 0.015), performance concerns (p = 0.048), CSS components of danger (p = 0.007), contamination (p = 0.006), and traumatic stress (p = 0.003). Although findings support statistically significant associations among dietary quality and mental health indicators, including broad symptom severity or stressors specific to athletics or COVID-19, these associations were in the opposite direction hypothesized. Possible reasons for results and suggestions for future research are discussed.

Effect of Morning vs. Evening Turmeric Consumption on Urine Oxidative Stress Biomarkers in Obese, Middle-Aged Adults: A Feasibility Study.

The circadian rhythm of biological systems is an important consideration in developing health interventions. The immune and oxidative defense systems exhibit circadian periodicity, with an anticipatory increase in activity coincident with the onset of the active period. Spice consumption is associated with enhanced oxidative defense. The objective of this study was to test the feasibility of a protocol, comparing the effects of morning vs. evening consumption of turmeric on urine markers of oxidative stress in obese, middle-aged adults. Using a within-sample design, participants received each of four clock time x treatment administrations, each separated by one week: morning turmeric; evening turmeric; morning control; evening control. Participants prepared for each lab visit by consuming a low-antioxidant diet for two days and fasting for 12 h. Urine was collected in the lab at baseline and one-hour post-meal and at home for the following five hours. The results showed that the processes were successful in executing the protocol and collecting the measurements and that participants understood and adhered to the instructions. The findings also revealed that the spice treatment did not elicit the expected antioxidant effect and that the six-hour post-treatment urine collection period did not detect differences in urine endpoints across treatments. This feasibility study revealed that modifications to the spice treatment and urine sampling timeline are needed before implementing a larger study.

Relative Validity of an Online Herb and Spice Consumption Questionnaire.

Culinary herbs and spices contribute bioactives to the diet, which act to reduce systemic inflammation and associated disease. Investigating the health effects of herb/spice consumption is hampered, however, by a scarcity of dietary assessment tools designed to collect herb/spice data. The objective of this study was to determine the relative validity of an online 28-item herb/spices intake questionnaire (HSQ). In randomized order, 62 volunteers residing in Idaho, USA, completed the online Diet History Questionnaire III + the HSQ followed one week later by one of two comparative methods: 7-day food records or three telephone-administered 24-h dietary recalls. Relative validity of the HSQ was tested two ways: (1) by comparing herb/spice intakes between the HSQ and comparator, and (2) by determining the correlation between herb/spice data and Healthy Eating Index 2015 score. The HSQ and both comparators identified black pepper, cinnamon and garlic powder as the three most commonly used herbs/spices. The HSQ captured significantly higher measures of the number and amount of herbs/spices consumed than the comparators. The number of herbs/spices consumed was significantly directly correlated with diet quality for the HSQ. These results support the ability of the HSQ to record general herb/spice use, yet suggest that further validation testing is needed.

Bone Response to Dietary Co-Enrichment with Powdered Whole Grape and Probiotics.

Nutrition is a primary modifiable determinant of chronic noncommunicable disease, including osteoporosis. An etiology of osteoporosis is the stimulation of bone-resorbing osteoclasts by reactive oxygen species (ROS). Dietary polyphenols and probiotics demonstrate protective effects on bone that are associated with reduced ROS formation and suppressed osteoclast activity. This study tested the effect of dietary enrichment with powdered whole grape and probiotics (composed of equal parts Bifidobacterium bifidum, B. breve, Lactobacillus casei, L. plantarum, and L. bulgaricus) on bone microarchitecture in a mouse model of age-related osteoporosis. Groups (n = 7 each) of 10-month-old male mice were fed one of six diets for 6 months: 10% grape powder with sugar corrected to 20%; 20% grape powder; 1% probiotic with sugar corrected to 20%; 10% grape powder + 1% probiotic with sugar corrected to 20%; 20% grape powder + 1% probiotic; 20% sugar control. Femur, tibia and 4th lumbar vertebrae from 10-month-old mice served as comparator baseline samples. Bone microarchitecture was measured by micro-computed tomography and compared across diet groups using analysis of variance. Aging exerted a significant effect on tibia metaphysis trabecular bone, with baseline 10-month-old mice having significantly higher bone volume/total volume (BV/TV) and trabecular number measurements and lower trabecular spacing measurements than all 16-month-old groups (p < 0.001). Neither grape nor probiotic enrichment significantly improved bone microarchitecture during aging compared to control diet. The combination of 20% grape + 1% probiotic exerted detrimental effects on tibia metaphysis BV/TV compared to 10% grape + 1% probiotic, and trabecular number and trabecular spacing compared to 10% grape + 1% probiotic, 1% probiotic and control groups (p < 0.05). Femur metaphysis trabecular bone displayed less pronounced aging effects than tibia bone, but also showed detrimental effects of the 20% grape + 1% probiotic vs. most other diets for BV/TV, trabecular number, trabecular spacing and trabecular pattern factor (p < 0.05). Tibia and femur diaphysis cortical bone (cortical wall thickness and medullary area) displayed neither aging nor diet effects (p > 0.05). Vertebrae bone showed age-related deterioration in trabecular thickness and trabecular spacing and a trend toward preservation of trabecular thickness by grape and/or probiotic enrichment (p < 0.05). These findings demonstrate no benefit to bone of combined compared to independent supplementation with probiotics or whole grape powder and even suggest an interference of co-ingestion.

Weight Bias in University Health Professions Students.

Negative attitudes toward people with high body weight have been documented in pre-professional health students, prompting concern that such feelings may manifest as poor patient care in professional practice. This study assessed weight bias in university students in the non-physician health professions. A convenience sample of 206 students completed an online survey composed of a validated 14-item scale (1-5 lowest to highest weight bias) and questions regarding personal experiences of weight bias. Respondents were grouped by discipline within graduate and undergraduate levels. Weight bias was present in a majority of respondents. Overall, the percentage of responses indicative of weight bias was 92.7%. The mean total score was 3.65. ± 0.52, and the rating exceeded 3 for all 14 scale descriptors of high-weight people. In graduate students, discipline had a significant main effect on total score (p=0.01), with lower scores in dietetics (3.17 ± 0.46) vs audiology/sign language/speech language pathology (3.84 ± 0.41) and physician assistant students (3.78 ± 0.51; p<0.05). These findings show that weight bias is prevalent in health professions students at a mountain west university. Well-controlled studies that track students into professional practice would help determine whether bias-reduction interventions in college improve provider behaviors and clinical outcomes.

Probiotics Blunt the Anti-Hypertensive Effect of Blueberry Feeding in Hypertensive Rats without Altering Hippuric Acid Production.

Previously we showed that feeding polyphenol-rich wild blueberries to hypertensive rats lowered systolic blood pressure. Since probiotic bacteria produce bioactive metabolites from berry polyphenols that enhance the health benefits of berry consumption, we hypothesized that adding probiotics to a blueberry-enriched diet would augment the anti-hypertensive effects of blueberry consumption. Groups (n = 8) of male spontaneously hypertensive rats were fed one of four AIN '93G-based diets for 8 weeks: Control (CON); 3% freeze-dried wild blueberry (BB); 1% probiotic bacteria (PRO); or 3% BB + 1% PRO (BB+PRO). Blood pressure was measured at weeks 0, 2, 4, 6, and 8 by the tail-cuff method, and urine was collected at weeks 4 and 8 to determine markers of oxidative stress (F2-isoprostanes), nitric oxide synthesis (nitrites), and polyphenol metabolism (hippuric acid). Data were analyzed using mixed models ANOVA with repeated measures. Diet had a significant main effect on diastolic blood pressure (p = 0.046), with significantly lower measurements in the BB- vs. CON-fed rats (p = 0.035). Systolic blood pressure showed a similar but less pronounced response to diet (p = 0.220), again with the largest difference between the BB and CON groups. Absolute increase in blood pressure between weeks 0 and 8 tended to be smaller in the BB and PRO vs. CON and BB+PRO groups (systolic increase, p = 0.074; diastolic increase, p = 0.185). Diet had a significant main effect on hippuric acid excretion (p<0.0001), with 2- and ~1.5-fold higher levels at weeks 4 and 8, respectively, in the BB and BB+PRO vs. PRO and CON groups. Diet did not have a significant main effect on F2-isoprostane (p = 0.159) or nitrite excretion (p = 0.670). Our findings show that adding probiotics to a blueberry-enriched diet does not enhance and actually may impair the anti-hypertensive effect of blueberry consumption. However, probiotic bacteria are not interfering with blueberry polyphenol metabolism into hippuric acid.

Body iron is associated with cognitive executive planning function in college women.

Evidence of the relationship between altered cognitive function and depleted Fe status is accumulating in women of reproductive age but the degree of Fe deficiency associated with negative neuropsychological outcomes needs to be delineated. Data are limited regarding this relationship in university women in whom optimal cognitive function is critical to academic success. The aim of the present study was to examine the relationship between body Fe, in the absence of Fe-deficiency anaemia, and neuropsychological function in young college women. Healthy, non-anaemic undergraduate women (n 42) provided a blood sample and completed a standardised cognitive test battery consisting of one manual (Tower of London (TOL), a measure of central executive function) and five computerised (Bakan vigilance task, mental rotation, simple reaction time, immediate word recall and two-finger tapping) tasks. Women's body Fe ranged from - 4·2 to 8·1 mg/kg. General linear model ANOVA revealed a significant effect of body Fe on TOL planning time (P= 0·002). Spearman's correlation coefficients showed a significant inverse relationship between body Fe and TOL planning time for move categories 4 (r - 0·39, P= 0·01) and 5 (r - 0·47, P= 0·002). Performance on the computerised cognitive tasks was not affected by body Fe level. These findings suggest that Fe status in the absence of anaemia is positively associated with central executive function in otherwise healthy college women.

Improvements in iron status and cognitive function in young women consuming beef or non-beef lunches.

Iron status is associated with cognitive performance and intervention trials show that iron supplementation improves mental function in iron-deficient adults. However, no studies have tested the efficacy of naturally iron-rich food in this context. This investigation measured the hematologic and cognitive responses to moderate beef consumption in young women. Participants (n=43; age 21.1±0.4 years) were randomly assigned to a beef or non-beef protein lunch group [3-oz (85 g), 3 times weekly] for 16 weeks. Blood was sampled at baseline, and weeks 8 and 16, and cognitive performance was measured at baseline and week 16. Body iron increased in both lunch groups (p<0.0001), with greater improvement demonstrated in women with lower baseline body iron (p<0.0001). Body iron had significant beneficial effects on spatial working memory and planning speed (p<0.05), and ferritin responders (n=17) vs. non-responders (n=26) showed significantly greater improvements in planning speed, spatial working memory strategy, and attention (p<0.05). Lunch group had neither significant interactions with iron status nor consistent main effects on test performance. These findings support a relationship between iron status and cognition, but do not show a particular benefit of beef over non-beef protein consumption on either measure in young women.

The USDA Automated Multiple-Pass Method accurately estimates group total energy and nutrient intake.

The imperative to address the national obesity epidemic has stimulated efforts to develop accurate dietary assessment methods suitable for large-scale applications. This study evaluated the performance of the USDA Automated Multiple-Pass Method (AMPM), the computerized dietary recall designed for the National Health and Nutrition Examination Survey dietary survey, and 2 epidemiological methods [the Block food-frequency questionnaire (Block) and National Cancer Institute's Diet History Questionnaire (DHQ)] using doubly labeled water (DLW) total energy expenditure (TEE) and 14-d estimated food record (FR) absolute nutrient intake as criterion measures. Twenty highly motivated, normal-weight-stable, premenopausal women participated in a free-living study that included 2 unannounced AMPM recalls and completion of the Block and DHQ. AMPM and FR total energy intake (TEI) did not differ significantly from DLW TEE [AMPM: 8982 +/- 2625 kJ; FR: 8416 +/- 2217; DLW: 8905 +/- 1881 (mean +/- SD)]. Conversely, the questionnaires underestimated TEI by approximately 28% (Block: 6365 +/- 2193; DHQ: 6215 +/- 1976; P < 0.0001 vs. DLW). Pearson correlation coefficients for DLW TEE with each dietary method TEI showed a stronger linear relation for AMPM (r = 0.53; P = 0.02) and FR (r = 0.41; P = 0.07) than for the Block (r = 0.25; P = 0.29) and DHQ (r = 0.15; P = 0.53). Most mean absolute FR nutrient intakes were closely approximated by the AMPM but were significantly underestimated by the questionnaires. In highly motivated premenopausal women, the AMPM provides valid measures of group total energy and nutrient intake whereas the Block and DHQ yield underestimations.

America's obesity epidemic: measuring physical activity to promote an active lifestyle.

The incidence of overweight and obesity in the United States and worldwide has reached epidemic proportions. To effectively intervene, dietetics professionals and other health care practitioners need to address both sides of the energy balance equation when counseling clients and patients. Often, the focus on energy intake supersedes the promotion of a physically active lifestyle. Incorporating appropriate and sufficient physical activity into one's life is an essential component of achieving and maintaining a healthful body weight. This review summarizes background knowledge on the benefits of physical activity for health and provides an overview of available tools for measuring physical activity and energy expenditure. The physical and mental health benefits of an active lifestyle, current physical activity recommendations for the US public, the prevalence of inactivity in the United States, and components of energy expenditure are reviewed. Additionally, tools for estimating total energy expenditure, resting metabolic rate, and physical activity are evaluated and suitable approaches for applying these tools are provided.

Prenatal ethanol exposure alters the responsiveness of the rat hypothalamic-pituitary-adrenal axis to nitric oxide.

BACKGROUND: Prenatal alcohol exposure is known to cause hyperactivity of the mature offspring's hypothalamic-pituitary-adrenal (HPA) axis. We have recently shown that hypothalamic neurons that produce corticotropin-releasing factor (CRF), the peptide that represents the major adrenocorticotropin hormone (ACTH) secretagogue, display increased responses to various stimuli in prenatal alcohol-exposed (E), compared to control (C) rats. CRF-producing perikarya are regulated, in part, by nitric oxide (NO), a signaling molecule whose function is also modified by prenatal alcohol exposure. The present investigation was therefore undertaken to test the hypothesis that prenatal alcohol exposure is associated with alterations in NO-stimulated ACTH secretion. METHODS: Adult male and female Sprague-Dawley rats exposed to alcohol in utero were injected intracerebroventricularly (icv) with the vehicle or the NO donor 3-morpholino-sydnonimine (SIN-1; 20 or 50 microg). ACTH levels were measured in blood samples collected from indwelling jugular cannulae at 15, 30 and 45 min following injection. Brains were obtained 45 and 90 min after SIN-1 injection and processed for in situ hybridization.RESULTS Compared to males, both C and E females exhibited a significantly (p < 0.01) larger ACTH response to SIN-1 (20 microg). Prenatal alcohol treatment enhanced SIN-1-induced ACTH release in all E animals, but this difference only reached statistical significance (p < 0.01) in males. This prenatal influence was also observed in the significantly (p < 0.01) larger SIN-1-induced increase in transcripts for the immediate early gene nerve growth factor induced protein B (NGFI-B) in the paraventricular nucleus (PVN) of the males', but not females' hypothalamus. CONCLUSIONS: The ability of increased brain NO levels to release ACTH and stimulate PVN neuronal activity is enhanced in adult male rats exposed to alcohol prenatally. These data support the hypothesis that alterations in HPA axis activity in adult offspring of alcohol-exposed dams may be related to changes in hypothalamic responsiveness to NO.

Physiologic determinants of the anorexia of aging: insights from animal studies.

The anorexia of aging is a syndrome characterized by unexplained losses in food intake and body weight that occur near the end of life. Proposed etiologies cover a wide range of biological and psychological conditions. The observation of this phenomenon in older laboratory animals suggests that physiological changes play a significant causal role. Research on the neurochemical control of energy balance has received much attention in recent years, and age-related alterations in the neuropeptidergic effectors of food intake have been implicated in the anorexia of aging. This review provides an update on putative mechanisms underlying this dysregulation of feeding during advanced age.