B. De Luca

Plasma Concentrations of Amino Acids in Chronic Schizophrenics Treated with Clozapine

Peripheral amino acid changes have been reported in schizophrenia, but results are not consistent. We measured serum levels of different amino acids in 11 neuroleptic-resistant schizophrenic patients before and after clozapine treatment and in 11 age- and sex-matched healthy subjects. The schizophrenic patients exhibited significantly higher levels of serum aspartate, glutamate, isoleucine, histidine and tyrosine and significantly lower concentrations of serum asparagine, tryptophan and serine. In patients, the ratio between tryptophan and large neutral amino acids (LNAA) was significantly lower than in matched controls, whereas the tyrosine/LNAA ratio did not differ significantly. Moreover, 12 weeks of clozapine administration significantly reduced serum levels of glutamate but did not restore the values observed in normal controls, nor did it affect other amino acid concentrations. These data show changes in serum amino acids that may influence central serotonergic, dopaminergic and glutamatergic transmission in neuroleptic-resistant schizophrenics.

Enhanced parasympathetic activity of sportive women is paradoxically associated to enhanced resting energy expenditure

The resting energy expenditure and the adaptation of the autonomic nervous system induced by sport activities in sedentary women and in female professional basketball players have been studied. Resting energy expenditure, body composition and the level of activity of the autonomic nervous system were measured before and after a period of six months. The physical activity induced an increase in resting energy expenditure and free fat mass without variations in body weight. Basketball players showed a significant increase in the parasympathetic activity, measured by the power spectral analysis of the heart rate variability. These findings demonstrate that resting energy expenditure is higher in the athletes than in sedentary women, despite the augmented parasympathetic activity that is usually related to lower energy expenditure.

Activity of autonomic nervous system is related to body weight in pre-menopausal, but not in post-menopausal women

Abstract This study analyzed vegetative modulation, expressed as heart rate variability (HRV) power spectral analysis, in lean and obese women at pre-menopausal or post-menopausal age to reveal possible differences in menopause-related autonomic activity in lean and obese subjects. Sedentary women (n = 40) were divided in four groups: pre-menopausal lean and obese women, post-menopausal lean and obese subjects. The HRV-power spectrum was evaluated on a 5-min long ECG recording. The absolute values of the spectrum were summed in the following frequencies: a low-frequency (0.04–0.15 Hz; LF) and high-frequency (0.15–0.40; HF) range. LF and HF were values used to estimate the sympathetic and parasympathetic activity. LF and HF values of pre-menopausal obese women are lower than values of lean women. The menopause induced a same decrease in LF and HF values in lean and obese subjects, so that no difference was found in post-menopausal groups. This experiment indicates that modifications of autonomic modulation can be included among factors related to obesity in pre-menopausal, but not post-menopausal women.

Resting energy expenditure and fat-free mass do not decline during aging in severely obese women

BACKGROUND & AIMS Few studies have investigated the age-related modification of resting energy expenditure (REE) and free fat mass (FFM) in severe obesity. This cross-sectional study analyzed REE and FFM in severely and moderately obese women and in lean subjects at different ages to find the possible differences between obese and lean subjects during aging. METHODS Sedentary women (n=261) were divided into three groups with different body mass indexes (BMIs): 20.0-24.9; 30-34.9; >40 kg/m(2). Each group was then divided into five subgroups: 20-29; 30-39; 40-49; 50-59; 60-69 years. REE was measured with an indirect calorimetric device. The FFM was calculated by bioelectric impedance. RESULTS The REE in severely obese women was higher than the REE in lean or moderately obese women. The FFM of severely obese women was lower than that of moderately obese or lean women. The aging induced reductions of the REE and FFM in lean and moderately obese subjects, but not in women with severe obesity. CONCLUSIONS This experiment indicates that REE and FFM do not decline during aging in women with BMI>40, suggesting that the severe obesity induces different age-related adaptations of metabolism and body composition.

Injection of muscimol in the posterior hypothalamus reduces the PGE1-hyperthermia in the rat.

The firing rate of the nerves innervating interscapular brown adipose tissue (IBAT), IBAT and colonic temperatures (TIBAT and Tc), heart rate, and oxygen (O2) consumption were monitored in urethane-anesthetized male Sprague-Dawley rats. These variables were measured for 40 min before (baseline values) and 40 min after a 56 ng muscimol injection in the posterior hypothalamus and an intracerebroventricular administration of 500 ng prostaglandin E1 (PGE1). The same variables were monitored in other rats with muscimol injection or PGE1 administration alone. No drug was injected in control rats. The results show that muscimol injection reduces the increases in firing rate, TIBAT, Tc, heart rate, O2 consumption induced by PGE1. These findings suggest that GABAergic tone in the posterior hypothalamus is important in the control of thermogenic changes induced by PGE1.

Nitric oxide reduces body temperature and sympathetic input to brown adipose tissue during PGE1-hyperthermia

The firing rate of the nerves innervating interscapular brown adipose tissue (IBAT) and IBAT and colonic temperatures (TIBAT and TC were monitored in urethane-anaesthetized male Sprague-Dawley rats. These variables were measured for 40 min before (baseline values) and 40 min after a 4 micromoles L-arginine (L-arg) or 400 nmoles nitroprusside (NP) injection in a lateral cerebral ventricle and an intracerebroventricular administration of 500 ng prostaglandin E1 (PGE1). The same variables were monitored in other rats with L-arg or NP or PGE1 administration alone. No drug was injected in control rats. The results show that L-arg or NP injection reduces the increases in firing rate, TIBAT, Tc induced by PGE1. These findings suggest that nitric oxide is important in the control of thermogenic changes during the PGE1 hyperthermia.

Lesions of the Ventromedial Hypothalamus Reduce Postingestional Thermogenesis

The aim of this experiment was to evaluate the effects of ventromedial hypothalamus lesions on the thermogenic changes that follow food intake. Four groups of six Sprague-Dawley male rats were used. Under anesthesia with pentobarbital, the animals in the first and second groups received lesions at the ventromedial hypothalamus, and animals in the third and fourth groups received sham lesions. Body weight and food intake were monitored daily until the experimental procedure began. Twenty days after lesion, oxygen consumption, firing rate of sympathetic nerves to interscapular brown adipose tissue (IBAT), and IBAT temperature were monitored for 45 min both before and after 5 g food intake in 24 h fasted rats from the first and third groups. The same variables were measured in the animals of the second and fourth groups 50 days after receiving the lesions. Lesion placements were histologically verified. The results showed that lesions produced hyperphagia and obesity. Firing rate of nerves to IBAT, IBAT temperature, and oxygen consumption increased after food intake in sham-lesioned rats. This increase was significantly reduced by the lesion at both the 20- and 50-day time points. These findings indicate that the ventromedial hypothalamus controls postingestional activation of sympathetic discharge to IBAT. The reduction of postingestional thermogenesis could be involved in the development of obesity induced by lesion of the ventromedial hypothalamus.

Alteration of the Bcl-2 : Bax Ratio in the Placenta as Pregnancy Proceeds

The placenta is the primary site of nutrient and gas exchange between mother and foetus. During human placental development, proliferation, differentiation and apoptosis occur at different stages. In order to clarify some of the molecular mechanisms underlying these events, we investigated the pattern of expression of two members of the Bcl-2 family in human placenta samples and compared them to the level of apoptosis detected by the TUNEL method.In particular, we evaluated the expression of Bcl-2 and Bax and their ratio during the first and third trimester. We found that Bcl-2 was generally expressed at low levels during the entire gestational period. On the other hand, Bax was low during the first trimester but increased towards the end of gestation. In accordance with the change of ratio of these two molecules, the increase of apoptotic cells was observable in the third trimester. These data indicate that Bcl-2 and Bax are spatio-temporally regulated during placental development and that the different expression of the above mentioned genes is at least in part responsible for the delicate balance between cell proliferation and programmed cell death in the human placenta during pregnancy.

The influence of exercise on energy balance changes induced by ventromedial hypothalamic lesion in the rat

The effects of a hypothalamic ventromedial area lesion on energy balance were tested in exercising rats and in sedentary rats to add further information about the type of obesity developed after ventromedial lesion. Four groups of six male Sprague-Dawley rats were used. Group 1: sham-lesioned and sedentary rats, which were utilized as control rats (C); group 2: sham-lesioned and exercising rats (E); group 3: lesioned and sedentary rats (L); group 4: lesioned and exercising rats (LE). The exercise consisted of daily swimming for 30 min. Resting oxygen consumption, food intake, and body weight were measured before any treatment and 3 weeks after the lesion or/and the exercise period. The results showed that the oxygen consumption increased in the E and LE groups but not in the C and L groups. Food intake increased more in E and LE groups than in L group. The increases in body weight were higher in L and LE than in the E and C groups. These findings suggest that exercise modifies resting oxygen consumption and food intake in lesioned rats, but does not influence the degree of obesity. Thus, the ventromedial syndrome can be considered a type of obesity not completely unregulated.

Non-shivering thermogenesis during prostaglandin E1 fever in rats: role of the cerebral cortex

We have tested the hypothesis that there is a role for the cerebral cortex in the control of non-shivering thermogenesis during fever induced by prostaglandin E1 (PGE1). While under urethan anesthesia, the firing rate of nerves innervating interscapular brown adipose tissue (IBAT), IBAT and colonic temperatures (TIBAT and Tc) and oxygen (O2) consumption were monitored during the fever from PGE1 injection (400 and 800 ng) in a lateral cerebral ventricle in controls and in functionally decorticated Sprague-Dawley rats. Rats were functionally decorticated by applying 3.3 M KCl solution on the frontal cortex which causes cortical spreading depression (CSD). Pyrogen injections caused dose-related increases in firing rate, TIBAT, Tc and O2 consumption and CSD reduced these enhancements. Our findings indicate that the cerebral cortex could be involved in the control of non-shivering thermogenesis during PGE1-induced febrile response.