The effects of ad libitum overfeeding and moderate and marked dietary restriction on age-related spontaneous pituitary gland pathology in Sprague-Dawley rats

This study compared the effects of ad libitum (AL) overfeeding and moderate or marked dietary restriction (DR) on the pathogenesis of aged-related pituitary gland changes in Sprague-Dawley (SD) rats. SD rats were fed Purina Certified Rodent Diet AL (group 1), DR at 72-79% of AL (group 2), DR at 68-72% of AL (group 3) or DR at 47-48% of AL (group 4) for 106 weeks. Interim necropsies were performed at 13, 26, and 53 weeks, after a 7-day 5-bromo-2-deoxyuridine (BrdU)-filled minipump implantation. Body weights, organ weights and insulin-like growth factor 1 (IGF-1) serum levels were measured at interim and final necropsies. Serum levels of prolactin (PRL), progesterone, estradiol, luteinizing hormone (LH) and follicle stimulating hormone (FSH) were measured at 53 and/or 106 weeks. In addition to the routine histopathologic examination, determination of 7 stereologic parameters after pituitary immunohistochemistry of PRL, growth hormone (GH) and BrdU was done in both sexes at 13, 26, and 53 weeks. Body and pituitary weights were proportional to the food intake. In AL-fed rats, hyperplastic and neoplastic changes developed early and progressed with age, affecting almost all animals by 106 weeks. These changes were associated with high PRL serum levels. Pituitary adenomas were the most common cause of death in both sexes. In DR rats, a delayed onset and a decreased incidence of pituitary tumors were observed in association with decreased serum IGF-1, PRL, estradiol, and LH levels. The results of the stereological analysis demonstrated that, compared to AL-fed rats, pituitary glands from DR rats contained lower PRL and GH secreting cell volumes, and a lower epithelial cell BrdU labeling index, which correlated with a lower incidence of pituitary tumors at study termination. Moderate and marked degrees of DR delayed the onset of pituitary tumors in a temporal- and dose-related manner. In contrast to marked DR, which dramatically reduced the incidence of hyperplastic and neoplastic pituitary gland changes, moderate DR delayed the onset but did not prevent the development of pituitary tumors.     

The effects of ad libitum overfeeding and moderate and marked dietary restriction on age-related spontaneous pancreatic islet pathology in Sprague-Dawley rats.

This study compared the effects of ad libitum (AL) overfeeding and moderate or marked dietary restriction (DR) on aged-related degenerative and proliferative changes of the endocrine pancreas in Sprague-Dawley (SD) rats. SD rats were fed Purina Certified Rodent Diet AL (group 1), DR at 72-79% of AL (group 2), DR at 68-72% of AL (group 3) or DR at 47-48% of AL (group 4) for 106 weeks. Interim necropsies were performed at 13, 26, and 53 weeks, after a 7-day 5-bromo-2-deoxyuridine (BrdU)-filled minipump implantation. Before each necropsy, glucose and serum insulin levels were measured. In addition to the routine histopathologic examination performed in both sexes, determination of 9 pancreatic islet stereologic parameters was done in males at 13, 26, and 53 weeks. In AL-fed rats, early changes in the islet morphology occurred, which resulted in a high incidence of islet fibrosis, focal hyperplasias and adenomas by two years. DR was dose-proportionally associated with decreased glucose and serum insulin levels, and delayed the onset, and decreased the incidence and severity of islet fibrosis and hyperplasia. Results of the stereology supported the histopathologic and clinical chemistry findings. It demonstrated that, compared to AL-fed rats, DR-fed rats had smaller pancreas, smaller pancreatic islets, smaller insulin secreting cell volumes, a lower degree of islet fibrosis and a lower islet cell BrdU labeling index, which correlated with a lower incidence of islet adenoma and carcinoma at study termination. Moderate and marked degrees of DR delayed the onset and severity of islet hyperplasia and fibrosis in a temporal- and dose-related manner. In contrast to marked DR, which dramatically prevented these changes, moderate DR delayed but not prevented onset of islet tumors. These findings support the concept that moderate DR results in a better-controlled animal model with a lower incidence or delayed onset of chronic spontaneous endocrine diseases in the rat bioassay.     

Diabesity: a polygenic model of dietary-induced obesity from ad libitum overfeeding of Sprague-Dawley rats and its modulation by moderate and marked dietary restriction

This study compared the effects of ad libitum (AL) overfeeding and moderate or marked dietary restriction (DR) on the pathogenesis of a metabolic syndrome of diabesity comprised of age-related degenerative diseases and obesity in a outbred stock of Sprague-Dawley (SD) rats [Crl:CD (SD) IGS BR]. SD rats were fed Purina Certified Rodent Diet AL (group 1), DR at 72-79% of AL (group 2), DR at 68-72% of AL (group 3) or DR at 47-48% of AL (group 4) for 106 weeks. Interim necropsies were performed at 13, 26, and 53 weeks, after a 7-day 5-bromo-2-deoxyuridine (BrdU)-filled minipump implantation. Body weights, organ weights, carcass analysis, in-life data including estrous cyclicity, and histopathology were determined. At 6-7 weeks of age SD rats had 6% body fat. AL-feeding resulted in hypertriglyceridemia, hypercholesterolemia, and dietary-induced obesity (DIO) by study week 14, with 25% body fat that progressed to 36-42% body fat by 106 weeks. As early as 14 weeks, key biomarkers developed for spontaneous nephropathy, cardiomyopathy, and degenerative changes in multiple organ systems. Early endocrine disruption was indicated by changes in metabolic and endocrine profiles and the early development and progression of lesions in the pituitary, pancreatic islets, adrenals, thyroids, parathyroids, liver, kidneys, and other tissues. Reproductive senescence was seen by 9 months with declines in estrous cyclicity and pathological changes in the reproductive organs of both sexes fed AL or moderate DR, but not marked DR. The diabesity syndrome in AL-fed, DIO SD rats was readily modulated or prevented by moderate to marked DR. Moderate DR of balanced diets resulted in a better toxicology model by significantly improving survival, controlling adult body weight and obesity, reducing the onset, severity, and morbidity of age-related renal, endocrine, metabolic, and cardiac diseases. Moderate DR feeding reduces study-to-study variability, increases treatment exposure time, and increases the ability to distinguish true treatment effects from spontaneous aging. The structural and metabolic differences between the phenotypes of DIO and DR SD rats indicated changes of polygenic expression over time in this outbred stock. AL-overfeeding of SD rats produces a needed model of DIO and diabesity that needs further study of its patterns of polygenic expression and phenotype.     

The relative protective effects of moderate dietary restriction versus dietary modification on spontaneous cardiomyopathy in male Sprague-Dawley rats

The relative protective effects of modifying dietary protein, fat, fiber, and energy content vs moderate food or dietary restriction (DR) on spontaneous cardiomyopathy of Charles River male Sprague-Dawley (SD) rats was evaluated at 1 and 2 years. For 2 years, SD rats were fed Purina Rodent Chow 5002 (21.4% protein, 5.7% fat, 4.1% fiber, 3.1 kcal/g) or a modified rodent chow 5002-9 (13.6% protein, 4.6% fat, 15.7% crude fiber, 2.4 kcal/g) ad libitum (AL) or by moderate DR at approximately 65% of the caloric intake of the AL group fed the 5002 diet. Serum lipids, carcass composition, and organ weights were evaluated and hearts were qualitatively and quantitatively examined microscopically for male SD rats at 1 and 2 years. Cardiomyopathy was characterized by the colocalization of myocardial degeneration, the development of subepicardial, perivascular, subendocardial, and interstitial fibrosis, and mononuclear inflammatory cell infiltration that increased by incidence and severity in an age-dependent manner from 1 to 2 years. SD rats fed the 5002 diet AL had the greatest heart weights and the most severe cardiomyopathy, with the highest myocardial fibrotic index. These parameters were relatively decreased in the AL 5002-9 diet, the DR 5002 diet, and the DR 5002-9 diet rats at 1 and 2 years. Regardless of the type of diet fed, both AL groups had the most severe cardiomyopathy by 2 years. Moderate DR allowed isocaloric comparisons of the relative effects of modified diets on survival, obesity, and heart disease. Only slight improvements in the severity and progression of spontaneous cardiomyopathy were seen by modification of the protein, fiber, fat, and energy content of the diet if fed AL. However, moderate DR with either diet was more effective than changing the diet composition in preventing and controlling the progression of cardiomyopathy in male SD rats.     

Chronic nephropathy in ad libitum overfed Sprague-Dawley rats and its early attenuation by increasing degrees of dietary (caloric) restriction to control growth

The early development and progression of chronic nephropathy and its amelioration by moderate and marked dietary restriction (DR) was determined in Sprague-Dawley (SD) rats at 20, 33, 60, and 113 weeks of age. Both sexes of SD rats were overfed ad libitum (AL) or DR-fed at 72-79%, 68-72%, or 47-48% of the adult AL intake. The AL-fed rats rapidly developed increased body and kidney size, increased glomerular area (GA) and urinary protein loss, followed by declining creatinine clearance. Early increased kidney growth and glomerular hypertrophy by 20 weeks preceded increases in glomerular sclerotic index (GSI), 7-day BrdU tubular labeling index (TLI), and the lesions associated with chronic nephropathy. The glomerular number (GN) or the number of nephrons did not differ between the groups over the course of the study. Moderate DR (68-79% of AL) prevented the increased kidney size and GA at 20 weeks and delayed increases in GSI and TLI until 60 weeks of age. Marked DR (47-48% of AL) prevented increases in kidney size, GA and TLI at 20 weeks, and GSI at 60 weeks of age. In AL-fed rats, the early increase in GA predicted the early onset of proteinuria and the later decrease in creatinine clearance, and increased GSI, TLI, and mortality from severe nephropathy. The temporal and dose-related effects of increasing degrees of DR demonstrated that while nephron numbers were unchanged with age, the early development of glomerular hypertrophy was the critical morphological biomarker predicting the progression and severity of chronic nephropathy. Caloric restriction by DR prevented or delayed the development of glomerulosclerosis, tubulointerstitial damage, functional changes, morbidity, and mortality associated with chronic nephropathy in AL-overfed SD rats by controlling initial body and kidney growth, glomerular size, and nephron hypertrophy. These results indicate that control of body and renal growth by DR may be essential to prevent the development and progression of glomerulosclerosis in spontaneous nephropathy of laboratory rats.     

Assessment of sustained attention in ad libitum fed Wistar rats: effects of MK-801

RATIONALE: Rodent models designed to assess cognitive function, such as sustained attention tasks, use food and/or fluid restriction in order to motivate responding. However, evidence indicates that dietary restriction can have profound effects on brain function and on the neurobehavioral effects of drugs. OBJECTIVE: The primary objective of this study was to demonstrate the feasibility of using ad libitum fed rats to assess sustained attention in an operant 2-choice reaction time (2-CRT) task. Because N-methyl-D-aspartate (NMDA) receptor function is critical for sustaining attention in animal models, the effects of the NMDA antagonist MK-801 on 2-CRT performance were also assessed. METHODS: Male Wistar rats (n = 20) rats were trained to perform an operant 2-CRT task. A 10% sucrose solution was used as the reinforcer. After performance levels stabilized, the effects of MK-801 (0.01-0.12 mg/kg, IP) were assessed. RESULTS: Stable levels of performance on the final version of the 2-CRT task was established after 2-3 months of training. Consistent with prior reports, correct trials varied as a function of stimulus light duration (1000 ms: 67 +/- 3%, 500 ms: 59 +/- 3%, 100 ms: 51 +/- 3%, 50 ms: 43 +/- 2%). Administration of 0.06 mg/kg MK-801 significantly increased choice accuracy. Administration of 0.12 mg/kg MK-801 significantly slowed reaction times and resulted in pronounced motor incoordination. CONCLUSIONS: This study demonstrates that ad libitum fed rats can be trained to perform a 2-CRT task. However, the levels of choice accuracy are lower than typically observed under conditions of dietary restriction. The increase in choice accuracy following MK-801 is consistent with the effects of psychomotor stimulants and may suggest sustained attention was slightly enhanced by MK-801.     

Effects of chronic ICV leptin infusion on motor-activating effects of D-amphetamine in food-restricted and ad libitum fed rats

Recently, attention has turned to the possibility that endocrine adiposity hormones, such as leptin, may regulate appetitively motivated behavior by modulating brain dopamine function. By extension, it has been hypothesized that the increased behavioral sensitivity of food-restricted, underweight rats to psychostimulant challenge may be triggered by the accompanying hypoleptinemia. The purpose of the present study was to determine whether two weeks of continuous intracerebroventricular (ICV) infusion of leptin alters the motor-activating effect of D-amphetamine (0.75 mg/kg, IP) in food-restricted rats. Lateral ventricular infusion of leptin, using a regimen that decreases food intake and body weight in ad libitum fed rats (12 microg/day), had no effect on the locomotor response to D-amphetamine in food-restricted rats that were maintained at 80% of prerestriction body weight. This result may indicate that hypoleptinemia is not involved in the induction/maintenance of neuroadaptations that mediate enhanced behavioral sensitivity to psychostimulant challenge. Interestingly, ad libitum fed rats treated with leptin displayed an increased locomotor response to D-amphetamine that was most prominent 3-5 days after termination of the infusion. Body weights and D-amphetamine sensitivity of these subjects returned to control values by 8-10 days postinfusion. The enhanced behavioral sensitivity to D-amphetamine in leptin-treated ad libitum fed rats may be a by-product of adipose depletion and, if so, would further support involvement of a peripheral signal other than hypoleptinemia in the modulation of central sensitivity to psychostimulant challenge.     

Strain differences in drinking in inbred mice during ad libitum feeding and food deprivation

Water intakes were measured in 7 mouse strains under 3 conditions of food availability: (a) ad lib feeding, (b) $\text{1}\text{3}\text{-}\text{normal}$ food intake, and (c) total food deprivation. Under ad lib feeding strains were ranked according to magnitude of water intake. These ranks were similar, but not identical, when absolute water intakes (ml) and relative (ml/100 g body wt) water intakes were measured. Statistically reliable, positive correlations were found between food intake and body weight, water intake and food intake, and water intake and body weight. Under the $\text{1}\text{3}\text{-}\text{food}$ condition, mean water intakes decreased significantly from ad lib feeding conditions in the BALB/cJ, A/J and C57BL/6J strains, did not change significantly in the SWR/J, CBA/J and DBA/2J strains and increased (food-deprivation polydipsia) in the C3H/HeJ strains. Results in 2 replications of total food deprivation parallelled those of $\text{1}\text{3}$ normal intake except that in the former condition DBA/2J mice showed a significant decrease in water intake. Food-deprivation polydipsia was seen in some individual SWR/J and CBA/J mice, as well as in the C3H/HeJ strain but was very rare in the other four strains.     

Long-term dietary restriction causes negative effects on cognitive functions in rats

Long-term dietary restriction is reported to increase life span and improve age-related cognitive deficits. The present study shows that the restriction increases the life span of rats but decreases their cognitive ability. Thirty-two rats were divided into restricted and ad lib feeding groups at 2.5 months of age. The restricted rats were kept at a weight of 280g. The restricted rats were poor in performing the Morris water maze task at 7-12 months. At 17-18 months, they were poor in performing the delayed matching-to-place task. At 24-27 months, the surviving 13 restricted and 5 ad lib rats performed the spatial discrimination task. The restricted rats were also poor in performing this task. Injection of glucose prior to the discrimination task improved their performance to the level of the ad lib rats. These results suggest that dietary restriction is beneficial for longevity but has negative effects on the performance of cognitive tasks, and that the cause of the negative effects may be a reduced availability of glucose in the food-restricted aged rats.     

Cellular growth of skeletal muscle in weanling rats during dietary restrictions

The effects of feeding varying levels of a nutritionally balanced diet on the cellular growth of rat skeletal muscles were examined. Groups of male weanling rats were fed 50% (R-50), 40% (R-40), or 30% (R-30) of the intake of the ad libitum fed age-matched controls (C). An initial control group (IC) was killed at 25 days of age, and all other groups were sacrificed at 46 days. These chronic dietary restrictions slowed the rates of growth of each of the four skeletal muscles examined: the plantaris, soleus, extensor digitorum longus, and gastrocnemius. Longitudinal growth, as estimated from tibia length, was also significantly affected by the restrictions. DNA, protein, and RNA were examined in the plantaris. DNA content was the same in the IC and R-30 groups but increased significantly with each subsequent increase in food intake. The ratio of protein/DNA was the same for the C, R-50, and R-40 groups but was 15% lower for the R-30 group. Therefore, the restricted rats tended to maintain the normal ratio of protein/DNA even at the expense of halting DNA replication. While the transverse growth (cross-sectional area of muscle fibers) of the plantaris was significantly slowed by the chronic restrictions, muscle fiber number was the same for all groups at 46 days of age. These data indicate that in skeletal muscle, DNA content (nuclear number) does not equate with cell number, and the ratio of protein/DNA does not reflect cell size. Furthermore, nuclear number, not cell number, appears to be the major factor controlling postnatal skeletal muscle growth.     

高脂饮食喂养对大鼠骨骼肌细胞膜GLUT4含量的影响

目的:检测骨骼肌细胞膜GLUT4含量的改变,探讨高脂饮食喂养诱导胰岛素抵抗的受体后机制。方法:将动物分为3组:①正常对照组;②高脂饮食组;③高脂饮食+饮食控制组。通过8周高脂饮食喂养建立胰岛素抵抗大鼠模型,随后代以普通饮食继续喂养4周。用Westernblot方法检测骨骼肌细胞膜表面GLUT4蛋白表达。结果:在胰岛素刺激下,高脂饮食组大鼠骨骼肌细胞膜GLUT4蛋白表达显著少于正常对照组(减少约31%);饮食控制组骨骼肌细胞膜GLUT4蛋白表达明显高于高脂饮食组(约1.14倍)。结论:高脂喂养的方法可成功复制出胰岛素抵抗大鼠模型;高脂饮食可能通过影响胰岛素信号转导系统,使胰岛素刺激的GLUT4转位至细胞膜受阻,其在膜上的含量也降低,从而促进胰岛素抵抗的形成和发展。     

The effects of high-intensity exercise on skeletal muscle neutrophil myeloperoxidase in untrained and trained rats

The primary purpose of this study was to examine the effects of high-intensity acute exercise on neutrophil infiltration in different muscle fiber types of untrained rats and to compare postexercise neutrophil accumulation in muscles of untrained and trained animals. The effect of high-intensity acute exercise on blood neutrophil degranulation reaction in trained animals was also elucidated. Neutrophil enzyme myeloperoxidase (MPO) was determined as a measure of neutrophil migration into muscles and blood neutrophil degranulation. Male albino rats were subjected to acute exercise and 5 weeks of training. The used model of intensive acute exercise consisted of 5, 15, and 25 intermittent swimming bouts with the addition of weight (8% of total body mass) for 1-min each, followed by 1.5-min rest intervals. MPO was analyzed in quadriceps muscle (white and red portion) and in soleus muscle 24 h after acute exercise. MPO content in resting blood plasma and neutrophils was determined 48-h following the completion of a training process. In addition, MPO content in the trained rats was measured immediately (in blood plasma and neutrophils) after and 24 h (in muscles) following a single-bout of exercise to exhaustion. The remaining two-third of the trained animals were exposed to a single-bout of nonstop swimming with the addition of 6% body mass until exhaustion. These animals were sacrificed immediately and 24 h after loaded swimming to analyze leukocyte count, MPO content in blood plasma and neutrophils and in muscles, respectively. About 24 h after exercise MPO concentrations in the red portion of quadriceps muscle and in soleus muscle were 4–7-fold higher as compared to the white portion of m. quadriceps. There was an association between the quantity of repetitive bouts of swimming and MPO content in the muscles. The duration of swimming to exhaustion of trained rats was 3.8-fold longer than untrained sedentary control. At rest, plasma MPO concentration was found to be 40% higher in trained rats compared to untrained controls (P < 0.05). Postexercise plasma MPO concentrations were significantly higher both in untrained (+137%; P < 0.05) and trained (+81%; P < 0.05) rats compared to resting values. At rest neutrophil MPO concentration was found to be 33% lower in trained rats compared to untrained controls (P < 0.05). There were no significant differences in muscle MPO concentrations between untrained and trained rats at rest. A single-bout of exercise to exhaustion produced a greater increase in MPO content in untrained compared to trained rats. The data suggest that postexercise neutrophil infiltration is more intensive in red fibers types compared to white fiber types. A smaller neutrophil infiltration in muscles of trained animals after exhaustive exercise suggests a protective effect of previous training to muscle injury.Portions of this paper were presented by V. Morozov in 2003 at the 6th ISEI Symposium on Exercise Muscle Metabolism and Immune Function, Copenhagen.     

Age decreased steady-state concentrations of genistein in plasma, liver, and skeletal muscle in Sprague-Dawley rats

Soy isoflavones are associated with low incidence of cardiovascular diseases (CVD) and hormone-dependent cancers, but no solid information is available on the relative deposition of isoflavones in the body as a function of age. One-year-old (adult) male Sprague-Dawley rats were fed control diet or one of three high-genistein isoflavone (HGI) diets at a dose of 62, 154, or 308 genistein mg/kg (ppm) diet for 5 weeks; 2-year-old (old) were fed a dose of 154 or 308 ppm. Steady-state genistein concentrations in plasma, liver, and gastrocnemius muscle of the adult rats after 12 h fast revealed a linear dose-dependent manner (P < or = 0.0001). However, there was no such relationship in the old rats. Nevertheless, old rats fed the 308 ppm genistein diet had significantly lower steady-state genistein concentrations in plasma and liver than the adult rats did (P < or = 0.05); but similar genistein concentration in muscle. The results of this study indicate that steady-state genistein concentrations in tissues of adult rats after 12 h fast exhibited a dose-dependent fashion and were diminished in specific tissues by age.     

Pattern of biphasic response to various noxious stimuli in rats ingesting sucrose ad libitum

Sucrose ingestion is reported to produce an initial (20-30 min) analgesia and late (<5 h) hyperalgesia. However, the influence of the characteristics of noxious stimuli and sweet substances on the pattern of transition from analgesia to hyperalgesia is not known. Therefore, we investigated the effect of sucrose (20%, sucrose fed group), saccharin (0.1%, saccharin fed group) and water ingestion (control group) on pain responses to various noxious stimuli for 5 h. Latency of motor response of tail (TFL), paws to noxious thermal stimuli, threshold for elicitation of motor responses to electrical stimulation of tail nociceptive afferents in 5 sessions (0, 0.25, 1, 3 and 5 h) and pain-related behavior to tonic noxious stimulus in 3 sessions at 1, 3 and 5 h were recorded. In sucrose fed rats as compared to controls, the TFL sequentially increased (9.29 ± 0.47 s from 8.41 ± 0.25; p < 0.01), recovered to base-line and decreased (6.61 ± 0.61 sec; p < 0.0001) in sessions II, III and V indicating analgesia, eualgesia and hyperalgesia, respectively. In saccharin fed rats the initial analgesia extended until session III followed by eualgesia and hyperalgesia in sessions IV and V. Pain related behaviour to tonic noxious stimulus also indicated an initial analgesia (0-5 min), intermediate eualgesia and late hyperalgesia (3-5 h) in sucrose fed rats, whereas only analgesia in saccharin fed rats. The results of our study suggest that sucrose ingestion for 5 h leads to a bi-phasic response to both phasic and tonic noxious stimuli, albeit there are variations in their durations. Therefore, the temporal relationship of the nociceptive responses to palatable food is a function of the stimulus quality of both.     

Control of feeding in aplysia with ad libitum access to food: presence of food increases the intervals between feeding bouts

The patterning of feeding and the quantity eaten in Aplysia californica with ad libitum food access cannot be explained by the effects of three variables previously shown to control the patterning of consummatory feeding responses and the quantity eaten in animals hand-fed individual meals. Feeding in ad libitum conditions is regulated primarily by varying the time between feeding bouts rather than by modulating bout lengths or the efficacy of consummatory movements within a bout. Aplysia with steady-state food access are in a newly characterized feeding state in which they are relatively unresponsive to food. They eat very little (1-4% of the time), and the quantity eaten is unrelated to the quantity of food in the anterior gut. The steady state can be maintained by the presence of food, even if animals do not contact food. The chemosensory rhinophores signal the presence of food that maintains the steady state. Up to 24 h without food is needed for animals to recover from the inhibition of feeding by steady-state presence of food. Recovery from the steady state is partially governed by postingestion stimuli as shown by a faster recovery in animals that have not been in contact with food. Inhibition of feeding during the steady-state is mediated in part via humoral factors because bathing the cerebral and buccal ganglia in hemolymph from animals in the steady state inhibits the ability to elicit buccal motor programs via a cholinomimetic thought to simulate stimulation of the lips with food. After food deprivation that is sufficiently long so that the steady-state decays, animals eat a large meal the size and dynamics of which are consistent with regulation via the three variables previously identified. This large meal is modulated by pheromones secreted by conspecifics even in sexually immature Aplysia.     

The effects of alcoholism on skeletal and cardiac muscle

To determine the prevalence of alcoholic myopathy and cardiomyopathy, we studied a group of 50 asymptomatic alcoholic men (mean age, 38.5 years) entering an outpatient treatment program. Studies performed included an assessment of muscle strength by electronic myometer, muscle biopsy, echocardiography, and radionuclide cardiac scanning, with comparison to healthy control subjects of similar age. The patients' mean (+/- SEM) daily alcohol consumption was 243 +/- 13 g over an average of 16 years. These patients had no clinical or laboratory signs of malnutrition or electrolyte imbalance. Forty-two percent of the patients, as compared with none of the controls, had strength of less than 20 kg as measured in the deltoid muscle. Muscle-biopsy specimens from 23 patients (46 percent) had histologic evidence of myopathy. In the cardiac studies, when the alcoholic patients were compared with 20 healthy controls, the patients had a significantly lower mean ejection fraction (59 vs. 67 percent), a lower mean shortening fraction (33 vs. 38 percent), a greater mean end-diastolic diameter (51 vs. 49 mm), and a greater mean left ventricular mass (123 vs. 106 g per square meter of body-surface area). One third of the alcoholics had an ejection fraction of 55 percent or less, as compared with none of the controls. Endomyocardial biopsy specimens from six patients with ejection fractions below 50 percent showed histologic changes of cardiomyopathy. The estimated total lifetime dose of ethanol correlated inversely with muscular strength (r = -0.65; P less than 0.001). In an analysis that also included six patients with symptomatic alcoholic cardiomyopathy, the estimated total lifetime dose of ethanol correlated inversely with the ejection fraction (r = -0.58; P less than 0.001) and directly with the left ventricular mass (r = 0.59; P less than 0.001). We conclude that myopathy of skeletal muscle and cardiomyopathy are common among persons with chronic alcoholism and that alcohol is toxic to striated muscle in a dose-dependent manner.     

Effects of oxytocin on the IGF-axis and some gastrointestinal hormones in ad libitum fed and food-restricted female rats

The aims of this study were to investigate if administration of oxytocin to ad libitum fed and food-restricted female rats affects weight gain, body fatness, the IGF-axis, and some vagally mediated gastrointestinal hormones, such as gastrin, cholecystokinin (CCK) and somatostatin. Ad libitum fed and food-restricted (receiving 70% of the food intake of the ad libitum fed group) female rats were injected subcutaneously, once a day, for 10 days, with saline (control) or oxytocin (1 mg kg^–1 bodyweight). The animals were killed 5 days after the last injection. Oxytocin-treated food-restricted females had more body fat and lower plasma levels of IGF-I, IGFBP-1 and IGFBP-3 compared with saline-treated counterparts. Oxytocin-treated ad libitum fed rats also had lower plasma levels of IGFBP-1 but contained less body fat, compared with saline-treated counterparts. There was no effect of oxytocin treatment on body weight or weight gain in either of the feeding groups. Except for gastrin, which was lower, there was no effect of oxytocin on the gastrointestinal hormones studied. The results indicate that oxytocin treatment influences fat deposition and the IGF-axis in female rats, but that the results are dependent on the nutritional status of the animal.