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PubMed2002

Plasma concentrations of insulin-like growth factors among healthy adult men and postmenopausal women: associations with body composition, lifestyle, and reproductive factors.

As evidence builds for cancer risk associated with insulin-like growth factors (IGFs) and their binding proteins (BPs), capitalizing on such associations for cancer prevention requires identifying the determinants of IGF levels. We measured plasma IGF-I, IGF-II, and IGF BP-3 in a cross-section of 210 men and 171 postmenopausal women enrolled in research as healthy controls. Using linear regression adjusted for age and ethnicity, we evaluated associations between IGF and IGF BP levels and gender, height, body mass index (BMI), smoking, caloric intake, physical activity, and reproductive factors. As expected, women using hormone replacement therapy (HRT) recently had significantly lower IGF-I levels than nonusers. Overall, IGF-I and IGF BP-3 levels did not differ by gender, although men had significantly higher molar ratios of IGF-I to IGF BP-3 and lower plasma IGF-II than women without recent HRT use. For men, BMI was a better predictor of IGF-I levels than height, whereas for women, height was more important. Lower IGF-II levels for both genders were associated with higher BMI and lower physical activity. Lower physical activity was associated with lower IGF BP-3 levels among men. Miscarriage number and menopausal age were positively associated with IGF BP-3 levels. HRT use strongly depressed IGF-I levels among smokers, and additional analysis revealed no remarkable associations. Caloric intake was negatively associated with IGF-I levels among men. Results for ratios of IGF-I and IGF-II to IGF BP-3 generally reflected those for IGF-I and IGF-II levels, respectively. In conclusion, whereas some traditional cancer risk factors were associated with IGF levels, altogether, they accounted for <15% of the total variability in plasma levels for each IGF, suggesting that other factors influence IGF levels.

Adult↗
PubMed1982

Continuous insulin infusion in hyperglycemic, very low birth weight infants.

Continuous insulin infusion (CII) was used to increase intravenous glucose tolerance in 10 extremely premature (26.2 +/- 0.04 weeks, means +/- SEM) very low birth weight (819 +/- 53 g) hyperglycemic infants. CII was continued for 3-36 days. Over the first 72 h of insulin administration the mean amount of glucose tolerated rose from 0.35 +/- 0.06 to 0.67 +/- 0.06 g/kg/h and caloric intake derived from intravenous glucose increased from 29 to 56 kcal/kg/day. Insulin doses required to maintain normoglycemia ranged from 0.005-0.052 U/kg/h initially to 0.002-0.086 U/kg/h after 72 h of CII. Plasma insulin levels were significantly higher during insulin infusion. The low insulin doses required to maintain normoglycemia were consistent with a state of relative insulin deficiency, rather than insulin resistance. Mean plasma insulin/glucose ratios were significantly higher in normoglycemic versus hyperglycemic infants (0.40 +/- 0.08 vs. 0.14 +/- 0.05). Less than 1% of all blood glucose estimations were less than 25 mg/dl. Seventy-eight percent were within the normal range (greater than 45, less than 130 mg/dl). The rate of weight gain increased during CII in 8 of the 10 infants. CII may be useful in extremely premature, very-low-birth-weight infants in whom glucose intolerance persists despite conservative treatment, and either severely limits caloric intake, or results in life-threatening hyperglycemia.

Blood Glucose↗
PubMed1985

Compensatory growth in infants with severe failure to thrive.

We studied compensatory growth and caloric intake during an accelerated growth period of ten infants with severe failure to thrive (FTT). The mean age at diagnosis was 7.1 months (range 1.5 to 16.0 months). The average percentage of normal weight for age in this group was 54.9%, mean length was 58 cm (86% normal for age), and the mean head circumference was 39.7 cm (92% normal for age). Compensatory growth rebound was completed after 6.2 months (range 3.5 to 9.0 months). Minimal calorie counts during peak rate of growth averaged 187 kcal/kg/day (range 147 to 213). The final group average percentage of normal weight for age was 95.5%, an increase of 40%. The group of rebounding infants gained 31 gm/day. The group's length increased to 94% of that expected for age and head circumference to 98% of that expected for age. Like malnourished infants, these with FTT had compensatory growth when managed with ad libitum caloric intake equal to twice the expected intake.

Body Height↗
PubMed1993

Feed restriction in prepubertal lambs: effect on puberty onset and on in vivo release of luteinizing-hormone-releasing hormone, neuropeptide Y and beta-endorphin from the posterior-lateral median eminence.

The exact nature of the interaction between energy balance and reproduction is still elusive. Theoretically, nutrition-related variables must reach the hypothalamic luteinizing-hormone-releasing hormone (LHRH) network and/or its neuronal inputs, to alter plasma luteinizing hormone (LH) and therefore reproductive activity. In an attempt to assess the potential mechanism of such interaction at the median eminence (ME) level, the area of hypophysiotropic LHRH neuronal terminals and release, we used a decreased caloric intake lamb model which delays the onset of puberty. Thus, we determined the in vivo release of neuropeptides, by push-pull cannula (PPC) sampling from the posterior-lateral ME, in feed-restricted (FR) ewe lambs and in full-fed (FF), age-matched, contemporary control animals. Specifically, we assessed: (1) serum LH and ME in vivo release of LHRH, beta-endorphin (beta-END) and neuropeptide Y (NPY); beta-END and NPY are two putative neuronal inputs to LHRH neuronal terminals at the ME, reported to be involved in the control of both reproduction and feed intake; (2) the effect that exogenous infusion of beta-END through the PPC might have on the release of ME LHRH and NPY, and on plasma LH. In contrast to other works, the present results were obtained in lambs with intact ovaries. Furthermore, FR lambs were always compared statistically with FF contemporary paired controls that had attained puberty. Feed restriction decreased ME LHRH release, lowered plasma LH and prevented the onset of puberty. The changes induced by feed restriction in both LHRH and LH release were associated predominantly with decreases in pulse amplitude, rather than alterations in pulse frequency. The decreased LHRH and LH release occurred in the presence of a decreased beta-END but unchanged NPY release from the ME. Exogenous infusion of beta-END into the posterior-lateral ME decreased both LHRH and NPY release from this site and decreased plasma LH. In conclusion, decreased caloric intake lowers LH release and prevents puberty onset by decreasing the amplitude of the LHRH output from the hypothalamic hypophysiotropic network. A compensatory but unsuccessful mechanism for the FR status might be a lower beta-END-inhibitory tone on ME LHRH neuronal terminals. The unchanged release of NPY at this site supports the specificity of the changes induced by feed restriction on LHRH and beta-END in vivo release.

Animals↗
PubMed1994

Megestrol acetate in patients with AIDS-related cachexia.

OBJECTIVES: To compare the effects of oral suspensions of megestrol acetate, 800 mg/d, and placebo on body weight in patients with acquired immunodeficiency syndrome (AIDS)-related weight loss. DESIGN: Randomized, double-blind, placebo-controlled trial. SETTING: Outpatient community and university patient care setting. PATIENTS: Consecutive patients with AIDS who had substantial weight loss and anorexia were enrolled. Of 271 patients, 270 and 195 were evaluable for safety and efficacy, respectively. INTERVENTIONS: Patients were randomly assigned to receive placebo or megestrol acetate (100 mg, 400 mg, or 800 mg) daily for 12 weeks. MAIN OUTCOME MEASURES: The primary efficacy criterion was weight gain. Patients were evaluated at 4-week intervals for changes in weight and body composition, caloric intake, sense of well-being, toxic effects, and appetite. RESULTS: For evaluable patients receiving 800 mg of megestrol acetate per day, 64.2% gained 2.27 kg (5 pounds) or more compared with 21.4% of patients receiving placebo (P < 0.001). An intent-to-treat analysis showed significant differences (P = 0.002) between those receiving placebo and those receiving 800 mg of megestrol acetate for the number of patients who gained 2.27 kg (5 pounds) or more (8 of 32 [25%] compared with 38 of 61 [62.3%], respectively). Compared with patients receiving placebo at the time of maximum weight change, evaluable patients receiving megestrol acetate, 800 mg/d, reported improvement in overall well-being and had an increase in mean weight gain (-0.725 compared with 3.54 kg [-1.6 compared with +7.8 pounds]; P < 0.001), lean body mass (-0.772 compared with +1.14 kg [-1.7 compared with +2.5 pounds]; P < 0.001), appetite grade (P < 0.001), and caloric intake (-107 compared with +645.6 calories/d; P = 0.001). CONCLUSIONS: In patients with AIDS-related weight loss, megestrol acetate can stimulate appetite, food intake, and statistically significant weight gain that is associated with a patient-reported improvement in an overall sense of well-being.

Acquired Immunodeficiency Syndrome↗
PubMed2001

Adiposity indices in German children and adolescents with genetically confirmed Prader-Willi syndrome (PWS).

BACKGROUND: Morbid obesity develops as a result of hyperphagia and compulsive eating behavior in patients with Prader-Willi syndrome (PWS), if caloric intake is not rigorously controlled. PWS-specific centile curves for adiposity indices constructed in the past were based on clinically diagnosed patients. With the advent of molecular genetic methods, allowing for an unequivocal diagnosis, new PWS curves based exclusively on molecularly diagnosed patients are becoming available, eliminating a potential diagnostic bias. OBJECTIVE: To compare fat distribution in molecularly confirmed German PWS patients to that of clinically diagnosed American PWS patients and a healthy reference population. DESIGN: Cross-sectional anthropometric study. SUBJECTS: One hundred German patients (49 F) with molecularly confirmed PWS (age: <30 y). MEASUREMENTS: Triceps (subscapular) skinfold thickness, waist and hip circumference. RESULTS: Skinfold thickness was massively elevated in the majority of the molecularly confirmed German PWS patients compared to a healthy reference population. Whereas triceps skinfold thickness was in good agreement with American PWS patients, subscapular skinfold thickness in German girls rose earlier than in American PWS girls, indicating possible differences between caloric intake or the proportion of patients entering puberty spontaneously. Waist circumference and waist-hip ratio (n=89) were elevated in a relative small proportion of patients only and did not reflect lower abdominal fat. This may be due to the peculiar shape of many patients with a typical fat accumulation around the buttocks. CONCLUSIONS: In addition to body mass index, use of skinfold thickness is recommended for follow-up of dietary interventions in PWS.

Adolescent↗
PubMed2004

Silent acetaminophen-induced hepatotoxicity in febrile children: does this entity exist?

UNLABELLED: Several descriptions of acetaminophen-associated liver injury caused by therapeutic or a dosage slightly above the recommended dosage have been described. Our hypothesis is that in sick febrile infants and children, who may also be calorie depleted, there might be an increased hepatic vulnerability to acetaminophen. AIM: (1) To correlate serum acetaminophen levels in febrile infants and children with the following parameters: aspartate aminotransferase (AST) levels, fever, vomiting and/or decreased caloric intake; and (2) to assess parental knowledge regarding the medication dosage and hazards of acetaminophen. METHODS: Healthy children with an acute febrile illness, who had received acetaminophen, were eligible to participate in the study. AST and acetaminophen levels were drawn, and a detailed questionnaire was completed for every child. RESULTS: 107 children participated in the study; 50 girls and 57 boys with ages ranging from 1 mo to 16 y (mean 33 mo). All serum acetaminophen levels were within the safety range. Although 32% of parents administered a single acetaminophen dose above 15 mg/kg and 46% gave a daily dose above 60 mg/kg/d, no significant differences were observed in the serum acetaminophen and AST levels compared to those who received the appropriate dose. In about 60% of cases, the high doses were recommended by a physician. Young age and high fever were associated with significantly higher acetaminophen levels. We could not find an association between acetaminophen levels and vomiting, decreased caloric intake and AST levels. Only 24 parents (22%) were aware of the possible toxicity of acetaminophen. CONCLUSIONS: No evidence of increased hepatic vulnerability to acetaminophen was noted in a cohort of febrile infants and children. Furthermore, significant numbers of parents and physicians were unaware of acetaminophen dangers.

Acetaminophen↗
PubMed2000

Accumulation of advanced glycation endproducts in aging male Fischer 344 rats during long-term feeding of various dietary carbohydrates.

The observation of accelerated collagen glycation in association with enhanced progression of many age-associated diseases in hyperglycemic subjects has led researchers to propose a role of glycation in the aging process. Although short-term studies in healthy animals suggest that feeding a diet high in fructose may increase serum glucose concentrations and increase glycemic stress, the effects of a long-term feeding, i.e., life span, are unknown. This study was designed to evaluate the long-term effects of dietary carbohydrates on serum and tissue markers of glycemic stress. Three-month-old male Fischer 344 rats were given free access to or restricted to 60% caloric intake of one of five isocaloric diets that contained as their carbohydrate source either cornstarch, glucose, sucrose, fructose or equimolar amounts of fructose and glucose. Rats were killed at 9-, 18- or 26-mo of age. Glycated hemoglobin, serum glucose and fructosamine levels were measured as markers of serum glycemic stress. Collagen-associated fluorescence and pentosidine concentrations were measured in skin, aortic, tracheal and tail tendon collagen as markers of advanced glycation endproducts (AGE). The source of dietary carbohydrate had little effect on markers of glycemic stress and the accumulation of AGE. Restricting the amount of calories consumed resulted in lower serum glucose concentrations, glycated hemoglobin levels and pentosidine concentrations in tail tendon collagen. Our data suggest that the rate of collagen glycation is tissue-specific. These results suggest that long-term feeding of specific dietary carbohydrates does not alter serum glucose concentrations or the rate of collagen glycation. Rather, age-related accumulation of AGE is more closely related to caloric intake.

Aging↗
PubMed2003

Effect of fish oil on appetite and other symptoms in patients with advanced cancer and anorexia/cachexia: a double-blind, placebo-controlled study.

PURPOSE: To determine whether high doses of fish oil, administered over 2 weeks, improve symptoms in patients with advanced cancer and decreased weight and appetite. PATIENTS AND METHODS: Sixty patients were randomly assigned to fish oil capsules or placebo. Appetite, tiredness, nausea, well-being, caloric intake, nutritional status, and function were prospectively assessed at days 1 and 14. RESULTS: The baseline weight loss was 16 +/- 11 and 16 +/- 8 kg in the fish oil (n = 30) and placebo (n = 30) group respectively, whereas the baseline appetite (0 mm = best and 10 mm = worst) was 58 +/- 24 mm and 67 +/- 19 mm, respectively (P = not significant). The mean daily dose was 10 +/- 4 (fish oil group) and 9 +/- 3 (placebo group) capsules, which provided 1.8 g of eicosapentaenoic acid and 1.2 g of docosahexaenoic acid in the fish oil group. No significant differences in symptomatic or nutritional parameters were found (P <.05), and there was no correlation between changes in different variables between days 1 and 14 and the fish oil doses. Finally, the majority of the patients were not able to swallow more than 10 fish oil capsules per day, mainly because of burping and aftertaste. CONCLUSION: Fish oil did not significantly influence appetite, tiredness, nausea, well-being, caloric intake, nutritional status, or function after 2 weeks compared with placebo in patients with advanced cancer and loss of both weight and appetite.

Anorexia↗
PubMedDate not supplied

Continuous compared with intermittent tube feeding in the elderly.

The methods of continuous (C) and intermittent (I) nasogastric tube feedings in 60 patients, 54 men and 6 women, with a mean age of 72 +/- 9 years were compared in terms of number of complications, staff time used, and caloric intake. Patients were randomly assigned between these two methods and followed for 7 days. Diarrhea, aspiration pneumonia, clogged tubes, and self-extubation were observed in both groups. Diarrhea was significantly more frequent (96% of 30 patients) in the I group than the C group (66% of 30 patients) (p < .008). Furthermore, diarrhea was more prolonged (4 days or more) in 64% of 30 patients in the I group than the C group (4 days or more) in 58% of 30 patients (p < .02). However, clogged tubes occurred 3 times more often in the C group (p < .01). Self-extubation and aspiration pneumonia tend to be more frequent in the I group but the difference was not significant. The average time used by staff nurses in the maintenance of NGT feedings was not significantly longer in the I group (48.45 +/- 11 min/patient per day) than the C group (46.46 +/- 11 min/patient per day). In the C group the mean calories recommended were 2248 +/- 36 kcal/day but the actual caloric intake was only 1465 +/- 281 kcal/day, a deficiency of 783 +/- 291 kcal/day. The recommended calorie count for the I group was 2021 +/- 5 kcal/day but the amount delivered was only 1226 +/- 254 kcal/day, which resulted in a deficit of 795 +/- 259 kcal/day.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1987

Composition of diet modifies toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in cold-adapted rats.

The effect of a high carbohydrate, high fat or high protein diet was studied on the acute toxicity of TCDD (125 micrograms/kg) in cold-adapted (4 +/- 1 degrees C) rats. Within 10 days after dosing, TCDD-treated rats fed a high carbohydrate or a high protein diet reduced their caloric intake by 25% whereas those fed a high fat diet consumed only 15% fewer kcal/MBS (metabolic body size). TCDD-treated rats fed a high protein diet lost body weight at the same rate as their pair-fed controls, whereas body weight loss in high fat-fed rats was significantly higher than in their pair-fed controls. In contrast, TCDD-treated rats fed a high carbohydrate diet effectively maintained their body weight in the 4 days immediately after TCDD dosage, whereas their pair-fed controls lost weight. Mortality in TCDD-treated animals was 100% irrespective of the diet; all pair-fed control rats (except one fed a high protein diet) were terminated on days corresponding to the spontaneous death of their TCDD-treated pairs. Mean time to 50% mortality and mean time to death were significantly longer in TCDD-treated rats fed a high carbohydrate diet in comparison with the other two TCDD-treated groups (p less than 0.05), although caloric intake was comparable. Serum triiodothyronine (T3) was reduced in TCDD-treated animals fed a high fat or a high carbohydrate diet but not in those fed a high protein diet; serum thyroxine (T4) was reduced in all the treated groups, irrespective of diet.(ABSTRACT TRUNCATED AT 250 WORDS)

Acclimatization↗
PubMedDate not supplied

[The nasogastric feeding of preterm newborns].

The aim of this study is to investigate if nasogastric feeding may provide an adequate caloric intake and a good growth in preterm infants. One hundred and thirty-one newborns with gestational age less than or equal to 33 weeks, admitted to the Neonatal Unit of the Catholic University of Rome over a period of three years, were included in the study. Infants were divided according to birth weight in four groups: the first includes 22 neonates weighing less than or equal to 1000 g; the second 60 newborns with birth weight of 1001-1500 g; the third includes 36 prematures weighing 1501-2000 g; the fourth group 19 neonates with birth weight greater than 2000 grams. Body weight was measured daily and head circumference weekly for all the study period (60-90 days). Mean postnatal weight loss was greater in the lowest birth weight group (13.2% of the birth weight) as compared to the other three groups (8%-9%). Birth weight was regained at 18th day of age in the newborns of the first group and in the second week of age in the other three groups. A caloric intake greater than 100 Kcal/Kg/day was achieved in the second week, ranging between the 8th day (forth group) and 14th day (first group). The achievement of full enteral feeding was inversely related to the birth weight.(ABSTRACT TRUNCATED AT 250 WORDS)

Enteral Nutrition↗
PubMed1993

Variation in total energy expenditure in young healthy free-living men.

Interindividual and intraindividual variation in total energy expenditure (TEE) were examined in 17 healthy, free-living men (weight, 56.4 to 82.4 kg; age, 18 to 30 years). TEE over 14 days, resting metabolic rate (RMR), and body composition were measured two or three times during 77 days of fixed caloric intake using doubly labeled water, respiratory gas analysis, and isotope dilution, respectively. When individual data were averaged, TEE was most significantly related to fat-free mass ([FFM] r = .73, P = .001), body mass (r = .70, P = .002), and RMR (r = .63, P = .006). After adjusting TEE for BM, a significant inverse relation with age was found (partial r = -.52, P = .032). Stepwise regression analysis showed that 69% of individual variation in TEE was explained by BM, age, and fasting respiratory exchange ratio (RER). TEE/RMR averaged 1.73 +/- 0.25 (range, 1.38 to 2.32), and was independent of age and body composition. In 10 subjects in whom triplicate observations of TEE were performed, the average experimental variation for TEE was +/- 11.9% (range, 6.1% to 19.6%) compared with a theoretical estimate of precision of +/- 5.9% based on the reported isotope dose and analytical uncertainty. The difference between theoretical estimates of precision and observed experimental variation suggests that inherent random variation in free-living TEE is +/- 10% (ie, square root of 12(2)-6(2)) in subjects maintained on fixed caloric intake. We conclude that in young free living men (1) BM, age, and RER are important determinants of TEE; and (2) intraindividual variation in TEE is approximately +/- 10% due to fluctuations in physical activity levels within individuals over time.

Adolescent↗
PubMed1986

Weight loss causes neuroendocrine disturbances: experimental study in healthy starving subjects.

A variety of endocrine dysfunctions have been reported for anorexia nervosa, protein caloric malnutrition, and depression. The effect of reduced caloric intake and weight loss on endocrine functions was assessed in an experiment with five healthy female subjects during an initial baseline phase, a 3-week phase of complete food abstinence, weight gain to the original level, and a final baseline phase. During fasting, disturbances in hypothalamic-pituitary-adrenal function were observed, with elevated plasma cortisol levels, increase in the number of secretory episodes, increase in cortisol plasma half-life, and insufficient suppression following 1.5 mg dexamethasone. While all dexamethasone suppression tests (DSTs) were normal at baseline, 7 of 14 DSTs showed insufficient suppression in the fasting phase. During fasting, basal thyroid-stimulating hormone (TSH) values were lowered and the TSH response to thyrotropin-releasing hormone (TRH) was blunted. The plasma level of growth hormone (GH) over 24 hours was elevated during fasting and administration of the alpha 2-adrenergic receptor agonist clonidine resulted in a subnormal GH response after restoration of original body weight. One of the five subjects showed increased irritability, distress, anxiety, and depression as measured by various psychological scales. The results show that reduced caloric intake, weight loss, or catabolic state have powerful effects on several endocrine systems. The specificity of measures of endocrine disturbances (DST, TRH tests, and clonidine tests) as biological markers for certain types of depression must be questioned, and the metabolic state should be given more consideration in future studies.

Adult↗
PubMed1994

Oxidative damage, mitochondrial oxidant generation and antioxidant defenses during aging and in response to food restriction in the mouse.

This study was conducted in order to test the concept that oxidative damage is associated with aging and may be a factor in the modulation of life span in response to variations in caloric intake. Mice fed a diet that was 40% lower in calories (DR) than the ad libitum fed (AL) animals exhibited a 43% extension in average life span and a 61% prolongation in mortality rate doubling time. A comparison of AL and DR mice at 9, 17 and 23 months of age indicated that the protein carbonyl content in the brain, heart and kidney increased with age and was significantly greater in the AL than DR group in each organ at each of the three ages. Mitochondrial state 4 or resting respiratory rate increased with age in the AL, but not the DR group, and was also relatively higher in the former. The rates of mitochondrial superoxide and hydrogen peroxide generation increased with age and were higher in the AL than DR mice in all the three organs at each age. In contrast, there was no clear-cut overall pattern of age-related or dietary-related changes in antioxidant defenses provided by superoxide dismutase, catalase and glutathione peroxidase. Results suggest that mechanisms of aging and life span shortening by enhanced caloric intake are associated with oxidative damage arising from corresponding changes in mitochondrial oxidant production. Protein carbonyl content, and mitochondrial O2.- and H2O2 generation may act as indices of aging.

Aging↗
PubMed2002

Nutritional support via percutaneous endoscopic gastrostomy in children with cardiac disease experiencing difficulties with feeding.

Adequate nutrition is crucial to the management of children and infants with cardiac disease. Difficulties with feeding are extremely common, and maintaining an adequate caloric intake, in order to achieve sustained growth, is often not possible without nutritional support. We retrospectively reviewed our experience between 1995 and 1999 in treating 37 children with cardiac disease who underwent percutaneous endoscopic construction of a gastrostomy to augment nutritional needs. We stratified the patients into those with cyanotic heart disease, when saturations of oxygen were less than 95%; those with non-cyanotic heart disease with saturations greater than 95%, and those with minor cardiac disease associated with a systemic disorder. Each group was compared to control children matched for age, sex, and diagnosis. We evaluated, the variation in standard deviation score for body weight over a median period of follow-up of 295 days. Improvements in the standard deviation score for body weight occurred in each of the groups, whereas children in the control groups demonstrated a decrease in standard deviation score for body weight. The median change of the score for body weight was significantly higher in patients managed with gastrostomy compared to controls. We conclude that supplementation using a gastrostomy tube allows the safe delivery of the caloric intake needed to support malnourished children with cardiac disease.

Body Weight↗
PubMed2000

Testicular regression in response to food restriction and short photoperiod in white-footed mice (Peromyscus leucopus) is mediated by apoptosis.

Short day lengths or reduced food availability are salient cues for small mammals that breed seasonally. Photoperiod-mediated gonadal regression in white-footed mice (Peromyscus leucopus) is a slow, orderly process that involves testicular apoptosis. Testicular regression in response to restricted caloric intake is relatively rapid, and it is generally reversed quickly by ad libitum (ad lib) feeding. To determine the contribution of apoptotic cell death during food restriction, and to examine possible interactions with photoperiod, mice housed in long (16L:8D) or short (8L:16D) photoperiods were fed either ad lib or 70% of their average ad lib intake. Testes were removed at 2, 4, 6, or 8 wk of experimental treatment. Apoptotic activity was determined by in situ TUNEL labeling and assessment of DNA laddering. Significant (P < 0.05) gonadal regression in response to short days was first detected at 8 weeks in mice fed ad lib. Food-restricted, long-day mice also showed significant testicular regression at 8 wk. Combined exposure to short day lengths and food restriction resulted in significant testicular regression at 6 wk (P < 0.05). TUNEL labeling was slightly, though significantly, elevated in germ cells at 2 and 4 wk in long-day food-restricted mice (P < 0.05). TUNEL labeling was also elevated in short-day food-restricted males at these early times but then increased nearly 5-fold at 6 and 8 wk in these mice (P < 0.001). DNA laddering confirmed elevated apoptosis. Overall apoptotic activity negatively correlated with paired testis mass, plasma testosterone, and spermatogenic index measurements in both ad lib and food-restricted males. Few histological markers of necrotic cell death were observed in any group. Taken together, these results suggest that testicular regression in response to limited caloric intake or short days is mediated by apoptosis.

Animals↗
PubMed1995

Who would have thought it? An operation proves to be the most effective therapy for adult-onset diabetes mellitus.

OBJECTIVE: This report documents that the gastric bypass operation provides long-term control for obesity and diabetes. SUMMARY BACKGROUND DATA: Obesity and diabetes, both notoriously resistant to medical therapy, continue to be two of our most common and serious diseases. METHODS: Over the last 14 years, 608 morbidly obese patients underwent gastric bypass, an operation that restricts caloric intake by (1) reducing the functional stomach to approximately 30 mL, (2) delaying gastric emptying with a c. 0.8 to 1.0 cm gastric outlet, and (3) excluding foregut with a 40 to 60 cm Roux-en-Y gastrojejunostomy. Even though many of the patients were seriously ill, the operation was performed with a perioperative mortality and complication rate of 1.5% and 8.5%, respectively. Seventeen of the 608 patients (< 3%) were lost to follow-up. RESULTS: Gastric bypass provides durable weight control. Weights fell from a preoperative mean of 304.4 lb (range, 198 to 615 lb) to 192.2 lb (range, 104 to 466) by 1 year and were maintained at 205.4 lb (range, 107 to 512 lb) at 5 years, 206.5 lb (130 to 388 lb) at 10 years, and 204.7 lb (158 to 270 lb) at 14 years. The operation provides long-term control of non-insulin-dependent diabetes mellitus (NIDDM). In those patients with adequate follow-up, 121 of 146 patients (82.9%) with NIDDM and 150 of 152 patients (98.7%) with glucose impairment maintained normal levels of plasma glucose, glycosylated hemoglobin, and insulin. These antidiabetic effects appear to be due primarily to a reduction in caloric intake, suggesting that insulin resistance is a secondary protective effect rather than the initial lesion. In addition to the control of weight and NIDDM, gastric bypass also corrected or alleviated a number of other comorbidities of obesity, including hypertension, sleep apnea, cardiopulmonary failure, arthritis, and infertility. Gastric bypass is now established as an effective and safe therapy for morbid obesity and its associated morbidities. No other therapy has produced such durable and complete control of diabetes mellitus.

Adolescent↗