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In-vivo and in-vitro effects of ethanol on mouse preimplantation embryos.

In Exp. 1A, hybrid mice (N = 10) were provided with food and 25% (v/v) ethanol as the only source of liquid for 72 h, beginning at the detection of the copulatory plug (08:00 h, Day 1). Control mice received food and tap water. Food consumption (P less than 0.001) but not total caloric intake (P greater than 0.05) was less for the alcohol-treated mice than the controls. Ethanol-derived calories averaged 35% of caloric intake during the 72 h of treatment. Alcohol-treated animals showed a dramatic weight loss until Day 5 while controls gained weight (P less than 0.05). Ethanol consumption did not influence pregnancy rate, litter size or litter weight. In Exp. 1B, animals were treated as in Exp. 1A, but were killed at various times between 24:00 h, Day 1, and 08:00 h, Day 4. Trunk blood was used to determine haematocrit and serum to determine alcohol concentration. Haematocrit was greater (P less than 0.05) for all alcohol-treated mice than for controls at all time periods sampled except one. Dehydration was therefore probably responsible for the weight loss seen in Exps 1A and 1B. Average blood alcohol concentrations fluctuated with time of day and day of treatment. Average maximum concentration was 91.4 mg ethanol/100 ml serum. In Exp. 2, hybrid mouse 2-cell embryos were cultured in vitro in 0 or 0.1% ethanol (Exp. 2A) and 0 or 1.0% ethanol (Exp. 2B) for 8 days.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

[Nutrition and cancer patients].

Nutritional therapy for cancer patients includes various objectives such as improvement of cachexia, elucidation of the mechanism of malnutrition, development of therapy for anorexia, nutrition support during chemotherapy or radiotherapy, and inhibition of tumor growth under controlled caloric intake. This review describes recent remarkable developments in nutritional therapy for cancer patients. Cytokines such as interleukin (IL)-1, IL-6, and tumor necrosis factor which induce proteolysis and lipolysis are involved in the cause of malnutrition and cachexia in cancer patients. IL-1 also plays a significant role in the development of cancer anorexia via direct action in the brain. For anorexia therapy, progestogens have been shown to improve appetite and food intake in cancer patients. Moreover, glutamine supplementation improves the host protein metabolism without enhancement of tumor growth during chemotherapy. Among the effects of caloric intake on anticancer therapy, AO-90, a methionine-free intravenous amino acid solution, has been shown to increase the antitumor effect of 5-fluorouracil in clinical studies. From these observations, recent progress in nutritional therapy for cancer patients has been remarkable. Further study of nutritional therapy is required in order to maintain or improve the quality of life of cancer patients in the future.

Humans↗

The modifying effect of nutritional intake of the posttraumatic depletion in hepatic glycogen in rats.

Hepatic glycogen levels were measured in rats both on oral food ad libitum and where intravenous nutrition was supplied at 0.1, 0.2, and 0.35 Kcal/gm of body weigh/day at 24 and 72 hours after injury. While on oral food rats with a closed femoral fracture had a lower level (25 +/- 6.5 mg/gm of liver) than normal (66 +/- 9.1 mg/gm of liver, P less than 0.005), 24 hours after injury. There was a corresponding rise in blood sugar (161 +/- 20 leads to 240 +/- 23 mg/100 ml, P less than 0.005) at 24 hours. However the food intake fell (23.8 +/- 1.5 leads to 16.6 +/- 2.4 gm/day, P less than 0.01) during the first 24 hours after the injury. When intravenous nutrition was given at a caloric level of 0.35 Kcal/gm/day, hepatic glycogen levels were above normal and there was no difference between injured and noninjured animals. At 0.2 Kcal/gm/day there was also no difference between injured and noninjured animals, but glycogen levels fell from norman levels (78 +/- 12.9 mg/gm) to lower levels (33 +/- 11.9 mg/gm, P less than 0.01) over the 24-hour to 72-hour period. Low levels of caloric intake (0.1 Kcal/gm/day) resulted in a fall in glycogen level in both injured and noninjured animals, with the decrease being significantly greater in the injured animals. It is concluded that maintenance of the caloric intake of rats at normal or high levels via the intravenous route can prevent the depletion of hepatic glycogen produced by a femoral fracture.

Animals↗

Minireview: the role of oxidative stress in relation to caloric restriction and longevity.

Reduction of caloric intake without malnutrition is one of the most consistent experimental interventions that increases mean and maximum life spans in different species. For over 70 yr, caloric restriction has been studied, and during the last years the number of investigations on such nutritional intervention and aging has dramatically increased. Because caloric restriction decreases the aging rate, it constitutes an excellent approach to better understand the mechanisms underlying the aging process. Various investigations have reported reductions in steady-state oxidative damage to proteins, lipids, and DNA in animals subjected to restricted caloric intake. Most interestingly, several investigations have reported that these decreases in oxidative damage are related to a lowering of mitochondrial free radical generation rate in various tissues of the restricted animals. Thus, similar to what has been described for long-lived animals in comparative studies, a decrease in mitochondrial free radical generation has been suggested to be one of the main determinants of the extended life span observed in restricted animals. In this study we review recent reports of caloric restriction and longevity, focusing on mitochondrial oxidative stress and the proposed mechanisms leading to an extended longevity in calorie-restricted animals.

Animals↗

A population-based case-control study of dietary factors and endometrial cancer in Shanghai, People's Republic of China.

The relation between diet and endometrial cancer was examined in a population-based case-control study conducted in Shanghai, People's Republic of China, between 1988 and 1990, involving interviews with 268 cases and 268 controls aged 18-74 years. The subjects' usual dietary intake of 63 major foods during the previous 10 years (disregarding any recent changes) was measured by means of a structured quantitative food questionnaire. Although women in the highest quartile of total caloric intake had a 2.1-fold increased risk of endometrial cancer, risk varied according to the source of calories. The highest quartiles of caloric intake from fat and protein were associated with odds ratios of 3.9 and 3.1, respectively, while calories from carbohydrates, the major contributor of total calories in this population, were not related to risk. The association of fat and protein with endometrial cancer risk was confined to foods of animal origin in the diet. After adjustment for age, body mass index (weight (kg)/height (m)2), and number of pregnancies, odds ratios were 3.5 (95% confidence interval (CI) 2.0-6.0) and 3.0 (95% CI 1.7-5.1) for women in the highest quartiles of intake of animal fat and animal protein, respectively. Food group analyses showed a similar pattern, with high consumption of meat, eggs, and fresh fish being associated with elevated risks. After adjustment for total calories, no significant association of risk was found with intake of vegetables or dark green/yellow vegetables, or with estimated carotene intake, although fruit and allium vegetables were associated with some reduction in risk. These results suggest that diets rich in animal fat and animal protein may play an important role in the etiology of endometrial cancer.

Adolescent↗

Individual differences in physical activity are closely associated with changes in body weight in adult female rhesus monkeys (Macaca mulatta).

The increased prevalence of overweight adults has serious health consequences. Epidemiological studies suggest an association between low activity and being overweight; however, few studies have objectively measured activity during a period of weight gain, so it is unknown whether low activity is a cause or consequence of being overweight. To determine whether individual differences in adult weight gain are linked to an individual's activity level, we measured activity, via accelerometry, over a prolonged period (9 mo) in 18 adult female rhesus monkeys. Weight, food intake, metabolic rate, and activity were first monitored over a 3-mo period. During this period, there was mild but significant weight gain (5.5 +/- 0.88%; t =-6.3, df = 17, P < 0.0001), whereas caloric intake and activity remained stable. Metabolic rate increased, as expected, with weight gain. Activity level correlated with weight gain (r = -0.52, P = 0.04), and the most active monkeys gained less weight than the least active monkeys (t = -2.74, df = 8, P = 0.03). Moreover, there was an eightfold difference in activity between the most and least active monkeys, and initial activity of each monkey was highly correlated with their activity after 9 mo (r = 0.85, P < 0.0001). In contrast, food intake did not correlate with weight gain, and there was no difference in weight gain between monkeys with the highest vs. lowest caloric intake, total metabolic rate, or basal metabolic rate. We conclude that physical activity is a particularly important factor contributing to weight change in adulthood and that there are large, but stable, differences in physical activity among individuals.

Animals↗

Regulation of metabolic rate and substrate utilization by zinc deficiency.

The trace metal zinc (Zn) is essential for the catalytic activity of many enzymes involved in energy nutrient metabolism and appears to regulate hormones, such as insulin, leptin, and thyroid hormone that play key roles in metabolism. Thus, this study used the continuous monitoring of oxygen consumption, carbon dioxide production, locomotion, and food intake to determine the effect of dietary Zn restriction on metabolic rate (MR), basal metabolic rate (BMR), and respiratory quotient (RQ). Rats were fed a Zn-adequate (ZA, 28 ppm) or Zn-deficient (ZD, <1 ppm) diet for 8 days, followed by a 4-day refeeding period. To control for reductions in food intake that characteristically occur in ZD rats, an additional group was pair-fed (PF) the same amount ZA food eaten by ZD rats. The mean caloric intake of ZD rats was significantly lower than ZA rats by day 3. By day 8, ZD and PF rats weighed 64% and 67% of ZA rats, respectively, (P <.01). Pair feeding resulted in increased locomotor activity, such that the distance traveled for PF rats (316 +/- 43 m) was 6 times that of ZA (53 +/- 6 m). Despite the fact that PF and ZD rats had the same food intake, there was no increase in locomotor activity in ZD rats suggesting that the mechanisms responsible for increased physical activity in food restricted animals may be Zn dependent. Furthermore, differences in activity between PF and ZD animals were not reflected in differences in MR. Both ZD and PF significantly reduced MR compared with ZA rats beginning on day 4. There was a significant relationship between RQ and caloric intake (r = 0.708, P <.01), but no specific effect of Zn status. Thus, while there may be an effect of Zn on locomotion and the energetic cost of activity, it appears that the most profound effect of Zn status on MR and substrate utilization is the result of Zn deficiency-induced anorexia.

Animal Feed↗

Does the ingestion of alcohol influence the development of arteriosclerosis in fowls?

The effect of alcohol ingestion upon the development of naturally occurring and stilbestrol-induced arteriosclerosis was studied in the domestic fowl. In two experiments, a 15 per cent ethyl alcohol solution was used for drinking purposes, and in a third experiment wine containing 12 per cent of it was administered. The caloric intake of both food and alcohol was carefully controlled by pair-feeding, a glucose solution being used for drinking purposes to equalize the caloric intakes of the control birds with those of the alcohol-treated birds. A total of 224 cockrels was studied, and the period of observation for each experiment lasted 12 months. The degree of arteriosclerosis in the thoracic and abdominal aortas was determined in the gross and microscopically, and the degree of lipide infiltration was determined microscopically. The gross grading of arteriosclerotic lesions agreed closely with the microscopic analysis of intimal thickening and lipide infiltration of the arterial wall. The gross gradings were subjected to a critical statistical analysis which allowed precise statements to be made on the probability that a real effect would be overlooked. This analysis yielded no evidence that alcohol or the wine used had affected the degree of gross arteriosclerosis or lipide infiltration.

Alcohol Drinking↗

Nasoduodenal feeding in high risk newborns.

Recent reports indicate that nasoduodenal feeding is a suitable technique for high risk newborns, in particular those with a low birth weight. In the period between February 1975 and June 1976, 100 high risk newborns, divided into four cohorts on the basis of birth weight in 500 g divisions, were fed by nasoduodenal tube. The effect of nasoduodenal feeding has been measured in several ways, but particularly consideration has been given to weight gain, its caloric cost, the mortality rates observed in the Unit before and after the introduction of this nutritional regime and complications. The use of nasoduodenal feeding abolished the physiological loss of weight which normally occurs during the first week of life and was associated with a subsequent rate of weight gain equal to or better than that observed in infants fed by other routes. The mean caloric intake was greater in smaller infants than in larger ones and it was accompanied by a steady decrease in weight gain per unit of caloric intake with increasing birth weight. In 1974 the overall mortality rate in the Unit was 18% and in 1975 following the introduction of nasoduodenal feeding fell to 11.4%. No serious complications were observed associated with nasoduodenal feeding. The conclusion is that this form of feeding is particularly suitable for infants with a birth weight of 1 500 g or less.

Body Weight↗

Serotonin (5-HT) drugs: effects on appetite expression and use for the treatment of obesity.

The pivotal role of 5-HT in the control of appetite was formally proposed nearly 30 years ago. In particular endogenous hypothalamic 5-HT has been implicated in the processes of within meal satiation and the end state of post meal satiety. Of the numerous 5-HT receptor subtypes currently identified, 5-HT(1B) and 5-HT(2C) receptors are believed to mediate the 5-HT induced satiety. 5-HT drugs such as d-fenfluramine, selective serotoninergic reuptake inhibitor (SSRIs) and 5-HT(2C) receptor agonists have all been shown to significantly attenuate rodent body weight gain, an effect strongly associated with marked hypophagia. D-Fenfluramine, sibutramine, fluoxetine and the 5-HT(2C) receptor agonist mCPP have also all been shown to reduce caloric intake by modifying appetite in both lean and obese humans. Specifically, 5-HT drugs reduce appetite prior to and after the consumption of fixed caloric loads, and reduce pre meal appetite and caloric intake at ad libitum meals. Clinically significant weight loss over a year or more can be produced by both d-fenfluramine and sibutramine treatment, but apparently not by the SSRI fluoxetine. Treatment with the preferential 5-HT(2C) receptor agonist mCPP and the serotonin precursor 5-HTP has also been shown to produce weight loss in the obese. Issues around the actual and possible side effects of these compounds, and in the case of d-fenfluramine toxicity, have led to a search for drugs that act selectively on the CNS 5-HT receptors critical to the satiety response. Currently, a new generation of 5-HT(2C) selective agonists have been developed (including Ro 60-0175, Org 12962, VER-3323, BVT-933 and YM348) and at least one, ADP356, is currently undergoing clinical trials. Hopefully, such drugs will be as or even more effective at regulating appetite and controlling body weight, and will also be free of their predecessors' side effect.

Animals↗

A case-control study of dietary and nondietary risk factors for breast cancer in Shanghai.

A case-control study of breast cancer (186 cases, 186 population, and 186 hospital controls) was conducted in Shanghai, China, between 1982 and 1984. This population has a high daily caloric intake (population control mean, 2394 kcal) and low percentage of calories from fat (22.7%) compared to Western populations. Cases have a significantly greater daily caloric intake than controls, primarily because of increased consumption of monounsaturated fat for which the relative risk is 1.89 for the highest compared to the lowest quintile (P = 0.02). This finding requires cautious interpretation but seems worthy of further study in populations with similar dietary practices.

Breast Neoplasms↗

Toxic psychosis due to cyproheptadine in a child on hemodialysis: a case report.

In 1971 Simmons et al. presented evidence that children receiving regular dialysis therapy required approximately seventy percent of recommended caloric intake to achieve normal growth. Since that time, pediatric nephrologists and dietitians have strived to meet that requirement. In an effort to attain adequate caloric intake, cyproheptadine, a known appetite stimulant, was prescribed to a child on chronic hemodialysis. The following reports the unexpected complication of toxic psychosis that resulted.

Child↗

Weight gain associated with decreases in smoking rate and nicotine intake.

The mechanisms involved in the weight gain associated with smoking cessation are not well known. This study employed a single-subject design to investigate changes in weight following systematic reductions in smoking rate and cigarette nicotine content. Although there were no changes in the subject's caloric intake or physical activity, a weight gain of 3.6 kg was observed after 4 months of reduced rate and nicotine intake. These results suggest that weight change during smoking reduction and cessation may be primarily due to changes in factors other than caloric intake or activity.

Body Weight↗

Dietary risk factors for the incidence and recurrence of colorectal adenomatous polyps. A case-control study.

OBJECTIVE: To investigate the association of dietary factors with the incidence and recurrence of colorectal adenomatous polyps. DESIGN: Two case-control studies. SETTING: Three university-based colonoscopy practices in New York City. PATIENTS: For the incidence study, 286 patients with pathologically confirmed incident adenomatous polyps (162 men and 124 women) were compared with 480 controls (210 men and 270 women) with no current or previous neoplasia. For the recurrence study, 186 patients with recurrent polyps (130 men and 56 women) were compared with 330 controls (187 men and 143 women). These patients had a history of polyps but no current neoplasia. MEASUREMENTS: Structured interviews using the Block food frequency questionnaire were conducted on all participants and were compared over quartiles of crude nutrient intake of total and saturated fat; fiber; protein; carbohydrates; carotene; vitamins A, C, and E; and various food groups. Data were adjusted for age, Quetelet index, and caloric intake by multiple logistic regression for men and women separately. RESULTS: For incident polyps, elevated adjusted odds ratios (high to low quartile) for women were found for saturated fat (odds ratio, 2.3; 95% CI, 0.9 to 5.8) and the ratio of red meat to chicken and fish intake (odds ratio, 1.9; CI, 1.0 to 3.6). Protective associations were observed for fish and chicken (odds ratio, 0.6; CI, 0.3 to 1.2) and vitamin A intake (odds ratio, 0.4; CI, 0.2 to 0.9). Among women, recurrent polyps showed an association with total dietary fat (odds ratio, 4.4; CI, 1.0 to 19.5), saturated fat (odds ratio, 3.8; CI, 1.0 to 14.9; P = 0.15 for the trend), and total fiber (odds ratio, 0.2; CI, 0.1 to 0.5; P = 0.01) and a borderline association with carbohydrates (odds ratio, 0.3; CI, 0.1 to 1.3; P = 0.10). No consistent relations were observed for men, although increased caloric intake increased the risk for incidence and recurrence in both men and women. CONCLUSIONS: These findings are consistent with previously described relations between diet and the incidence of colon cancer and suggest that, at least in women, dietary modification may be warranted in patients diagnosed with polyps.

Adult↗

The endogenous cannabinoid system affects energy balance via central orexigenic drive and peripheral lipogenesis.

The cannabinoid receptor type 1 (CB1) and its endogenous ligands, the endocannabinoids, are involved in the regulation of food intake. Here we show that the lack of CB1 in mice with a disrupted CB1 gene causes hypophagia and leanness. As compared with WT (CB1+/+) littermates, mice lacking CB1 (CB1-/-) exhibited reduced spontaneous caloric intake and, as a consequence of reduced total fat mass, decreased body weight. In young CB1-/- mice, the lean phenotype is predominantly caused by decreased caloric intake, whereas in adult CB1-/- mice, metabolic factors appear to contribute to the lean phenotype. No significant differences between genotypes were detected regarding locomotor activity, body temperature, or energy expenditure. Hypothalamic CB1 mRNA was found to be coexpressed with neuropeptides known to modulate food intake, such as corticotropin-releasing hormone (CRH), cocaine-amphetamine-regulated transcript (CART), melanin-concentrating hormone (MCH), and preproorexin, indicating a possible role for endocannabinoid receptors within central networks governing appetite. CB1-/- mice showed significantly increased CRH mRNA levels in the paraventricular nucleus and reduced CART mRNA levels in the dorsomedial and lateral hypothalamic areas. CB1 was also detected in epidydimal mouse adipocytes, and CB1-specific activation enhanced lipogenesis in primary adipocyte cultures. Our results indicate that the cannabinoid system is an essential endogenous regulator of energy homeostasis via central orexigenic as well as peripheral lipogenic mechanisms and might therefore represent a promising target to treat diseases characterized by impaired energy balance.

Adipocytes↗

Maximum Nutrition, Minimum Calories.

There is more to losing weight, maintaining weight and choosing a healthy diet after gastric bypass than simply limiting food intake and avoiding sugars. Patients must learn to make food selections that have a high nutrient:energy ratio. Considerable research indicates that the dietary fat level, independent of total caloric intake, is a predictor of fat storage. A contributing factor is the difference in metabolic efficiency of converting dietary fats to body fat compared to the relative inefficiency of converting carbohydrates to body fat. The recommendation that no more than 25% of daily caloric intake come from fat is in keeping with good nutritional practices and may also lower the risk of heart disease and cancer. Patients should have nutrition counseling supplemented with written materials on label reading and recognizing high fat foods, types of fat and cholesterol, serving sizes, meal planning, low fat cooking and dining out. Choosing foods with a high nutrient:energy ratio allows the patient to eat an increased volume and thus a wider variety of foods to meet their nutrient and energy requirements.

Journal Article↗

Caloric and exercise requirements of space flight: biostereometric results from skylab.

The biostereometric study of the Skylab astronauts used stereophotogrammetry to make accurate three-dimensional measurement of body form, from which regional and total body volumes were derived. Volume changes in the thighs and calves, over the course of the flight, showed a high correlation with inflight exercise on the bicycle ergometer, and suggested that an exercise level of 80-100 W-min/d/kg lean body mass would be necessary to prevent inflight muscle atrophy. The bicycle ergometer is thus a relatively inefficient means of preventing leg muscle atrophy. Inflight caloric intake showed a high correlation with the change in volume of the buttocks, the abdomen, and the body as a whole, and suggested that a caloric intake of 47-51 kcal/d/kg lean body mass would be necessary to prevent a change in body fat. Only one of the astronauts exceeded this range and gained body fat; the group as a whole showed a mean fat loss of 1.2 kg.

Adult↗

Mitochondrial and nuclear DNA base excision repair are affected differently by caloric restriction.

Aging is strongly correlated with the accumulation of oxidative damage in DNA, particularly in mitochondria. Oxidative damage to both mitochondrial and nuclear DNA is repaired by the base excision repair (BER) pathway. The "mitochondrial theory of aging" suggests that aging results from declining mitochondrial function, due to high loads of damage and mutation in mitochondrial DNA (mtDNA). Restriction of caloric intake is the only intervention so far proven to slow the aging rate. However, the molecular mechanisms underlying such effects are still unclear. We used caloric-restricted (CR) mice to investigate whether lifespan extension is associated with changes in mitochondrial BER activities. Mice were divided into two groups, receiving 100% (PF) or 60% (CR) of normal caloric intake, a regime that extends mean lifespan by approximately 40% in CR mice. Mitochondria isolated from CR mice had slightly higher uracil (UDG) and oxoguanine DNA glycosylase (OGG1) activities but marginally lower abasic endonuclease and polymerase gamma gap-filling activities, although these differences were tissue-specific. Uracil-initiated BER synthesis incorporation activities were significantly lower in brain and kidney from CR mice but marginally enhanced in liver. However, nuclear repair synthesis activities were increased by CR, indicating differential regulation of BER in the two compartments. The results indicate that a general up-regulation of mitochondrial BER does not occur in CR.

Aging↗