Behavioral effects of the combined use of alcohol and energy drinks on alcohol hangover in an experimental mice model.

In last few years it has been a significant increase in the consumption of alcohol combined with energy drink. The aim of this work was to study the effect of this mixture in motor and affective behaviors during an alcohol hangover episode. Male Swiss mice received one of the following treatments: saline + sucrose; saline + energy drink; ethanol + sucrose; ethanol + energy drink. Ethanol dose was 3.8 g/kg BW (i.p.) and energy drink dose was 18 ml/kg BW (gavage) at ZT1 (8 am) (ZT: Zeitgeber time; ZT0: 7 am; lights on). The behavioral tests used were tight rope test to determine motor coordination; hanging wire test to study muscular strength; elevated plus maze and open field tests to evaluate anxiety like-behavior and locomotor activity. Tests were carried out at basal point that matched with lights onset and every 6 h up to 18 h after treatments. Hangover onset was established at ZT7 when blood alcohol concentration (BAC) was almost zero. Our results showed that the mixture of alcohol and energy drink altered significantly motor skills. Specifically, a significant decrease was observed in the performance of the animals in the tightrope and hanging wire tests in groups treated with the mixture of alcohol and energy drink. A significant impairment in the anxiety-like behavior was observed mainly at the beginning of alcohol hangover. These findings suggest that energy drink added to alcohol extends motor disabilities observed during an alcohol hangover episode in comparison with animals that received alcohol alone.

Influence of conformity on the wear of total knee replacement: An experimental study.

Wear of total knee replacement continues to be a significant factor influencing the clinical longevity of implants. Historically, failure due to delamination and fatigue directed design towards more conforming inserts to reduce contact stress. As new generations of more oxidatively stable polyethylene have been developed, more flexibility in bearing design has been introduced. The aim of this study was to investigate the effect of insert conformity on the wear performance of a fixed bearing total knee replacement through experimental simulation. Two geometries of insert were studied under standard gait conditions. There was a significant reduction in wear with reducing implant conformity. This study has demonstrated that bearing conformity has a significant impact on the wear performance of a fixed bearing total knee replacement, providing opportunities to improve clinical performance through enhanced material and design selection.

PEEK and CFR-PEEK as alternative bearing materials to UHMWPE in a fixed bearing total knee replacement: An experimental wear study.

New bearing materials for total joint replacement have been explored as the need to improve longevity and enhance performance is driven by the changing demands of the patient demographic. Carbon-reinforced PEEK has demonstrated good wear characteristics in experimental wear simulation in both simple geometry pin-on-plate studies and in total hip joint replacement. Carbon reinforced PEEK CFR-PEEK has the potential to reduce tibial insert thickness and preserve bone in the knee. This study investigated the wear performance of PEEK and CFR-PEEK in a low conformity total knee replacement configuration. Custom-made flat inserts were tested against cobalt-chromium femoral bearings in a knee wear simulation for a period of three million cycles. Wear was assessed gravimetrically at intervals throughout the study. The wear rates of both PEEK and CFR-PEEK were very high and almost two orders of magnitude higher than the wear rate of UHMWPE under comparable conditions. Evidence of mechanical failure of the materials, including surface cracking and delamination was observed in both materials. This study highlights that these materials may not be suitable alternatives for UHMWPE in low-conformity designs.

Wear of composite ceramics in mixed-material combinations in total hip replacement under adverse edge loading conditions.

Ceramic composites have performed very well under adverse edge loading conditions when used in like-on-like configurations, where the femoral head and acetabular cup are of the same material. The aim of this study was to determine the wear of pure alumina (Al2 O3 ), alumina toughened zirconia (ATZ) and zirconia toughened alumina (ZTA) when used in mixed bearing combinations, under edge loading conditions due to translational mal-positioning. The head-on-cup configurations of three ceramic materials were ATZ-on-ZTA, ZTA-on-ATZ, Al2 O3 -on-ATZ, ATZ-on-Al2 O3 , Al2 O3 -on-ZTA, and ZTA-on-Al2 O3 . They were tested on the Leeds II hip simulator under microseparation conditions. The bedding in and steady state wear rates of ATZ-on-ZTA were 1.16mm3 /million cycles and 0.18mm3 /million, respectively, and for ATZ-on-Al2 O3 were 0.66 mm3 /million cycles and 0.20 mm3 /million, respectively. The wear rates of the other bearing combinations under these adverse microseparation conditions, Al2 O3 -on-ATZ, Al2 O3 -on-ZTA, ZTA-on-ATZ and ZTA-on-Al2 O3 were very low with no clear bedding in and steady state phases, and with steady state wear rates lower than 0.11 mm3 /million. The mixed material combinations tested in this study have shown slightly higher wear rates when compared to ATZ in like-on-like configuration reported previously, but superior wear resistance when compared to alumina-on-alumina bearings tested previously under the same adverse microseparation conditions. © 2016 The Authors Journal of Biomedical Materials Research Part B: Applied Biomaterials Published by Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 1361-1368, 2017.

Influence of third-body particles originating from bone void fillers on the wear of ultra-high-molecular-weight polyethylene.

Calcium sulfate bone void fillers are increasingly being used for dead space management in infected arthroplasty revision surgery. The presence of these materials as loose beads close to the bearing surfaces of joint replacements gives the potential for them to enter the joint becoming trapped between the articulating surfaces; the resulting damage to cobalt chrome counterfaces and the subsequent wear of ultra-high-molecular-weight polyethylene is unknown. In this study, third-body damage to cobalt chrome counterfaces was simulated using particles of the calcium sulfate bone void fillers Stimulan(®) (Biocomposites Ltd., Keele, UK) and Osteoset(®) (Wright Medical Technology, TN, USA) using a bespoke rig. Scratches on the cobalt chrome plates were quantified in terms of their density and mean lip height, and the damage caused by the bone void fillers was compared to that caused by particles of SmartSet GMV PMMA bone cement (DePuy Synthes, IN, USA). The surface damage from Stimulan(®) was below the resolution of the analysis technique used; SmartSet GMV caused 0.19 scratches/mm with a mean lip height of 0.03 µm; Osteoset(®) led to a significantly higher number (1.62 scratches/mm) of scratches with a higher mean lip height (0.04 µm). Wear tests of ultra-high-molecular-weight polyethylene were carried out in a six-station multi-axial pin on plate reciprocating rig against the damaged plates and compared to negative (highly polished) and positive control plates damaged with a diamond stylus (2 µm lip height). The wear of ultra-high-molecular-weight polyethylene was shown to be similar against the negative control plates and those damaged with third-body particles; there was a significantly higher (p < 0.001) rate of ultra-high-molecular-weight polyethylene wear against the positive control plates. This study showed that bone void fillers of similar composition can cause varying damage to cobalt chrome counterfaces. However, the lip heights of the scratches were not of sufficient magnitude to increase the wear of ultra-high-molecular-weight polyethylene above that of the negative controls.

Psychiatric Worker and Family Members: Pathways Towards Co-Operation Networks within Psychiatric Assistance Services.

The family's role in patient care was greatly altered by Law 180. This law, introduced in Italy in 1978, led to a gradual phasing out of custodial treatment for psychiatric patients. This different mindset, which views the family as an alternative to institutionalization, leads to it being seen as an essential entity in the setting up of community service dynamics. We interviewed health professionals in order to understand obstacles of collaboration between family members and mental health care workers. The goal was to uncover actions that promote collaboration and help build alliances between families and psychiatric workers. Results showed that health professionals view the family as a therapeutic resource. Despite this view, family members were rarely included in patient treatment. The reasons is: the structures have a theoretical orientation of collaboration with the family but, for nurses not are organized a few meeting spaces with family members. Services should create moments, such as multi-family groups or groups of information, managed by nurses and not only by doctors. These occasions it might facilitate the knowledge between professionals and family members.

Low dose of bisphenol A impairs the reproductive axis of prepuberal male rats

The objective of the present work was to study the effect of a low dose of bisphenol A (BPA), on the reproductive axis of prepuberal male rats exposed to the endocrine disruptor (ED) during gestation and lactation period. Wistar-mated rats were treated with either 0.1 % ethanol or BPA in their drinking water until their offspring were weaned at the age of 21 days. The estimated average dose of exposure to dams was approximately 3 ìg/kg/day of BPA. The pups were sacrificed on the 35th day of life. Body weight was measured during the development and at the moment of the sacrifice; testicular and seminal vesicles weight and their respective relative weights were also measured. LH, FSH and testosterone were determined and histological studies of testicular tissue were also performed. Body weight at the moment of the sacrifice was significantly higher in the group exposed to BPA; testicular weight decreased significantly; seminal vesicles weight and relative weights of testes and seminal vesicles were not modified by treatment. LH and FSH serum levels increased significantly after treatment, meanwhile testosterone showed no significant changes. Histological studies showed the lumen of seminal tubes reduced by the presence of immature cells of the spermatic lineage. Our results suggest that pre- and early postnatal exposure to a low dose of BPA disrupts the normal function of the reproductive axis in prepuberal male rats. The effects of the ED may be exerted at different levels of the axis and may be dependent on the dose, manner of administration, and the moment of exposure to the disruptor

Low dose of bisphenol A impairs the reproductive axis of prepuberal male rats.

The objective of the present work was to study the effect of a low dose of bisphenol A (BPA), on the reproductive axis of prepuberal male rats exposed to the endocrine disruptor (ED) during gestation and lactation period. Wistar-mated rats were treated with either 0.1 % ethanol or BPA in their drinking water until their offspring were weaned at the age of 21 days. The estimated average dose of exposure to dams was approximately 3 µg/kg/day of BPA. The pups were sacrificed on the 35th day of life. Body weight was measured during the development and at the moment of the sacrifice; testicular and seminal vesicles weight and their respective relative weights were also measured. LH, FSH and testosterone were determined and histological studies of testicular tissue were also performed. Body weight at the moment of the sacrifice was significantly higher in the group exposed to BPA; testicular weight decreased significantly; seminal vesicles weight and relative weights of testes and seminal vesicles were not modified by treatment. LH and FSH serum levels increased significantly after treatment, meanwhile testosterone showed no significant changes. Histological studies showed the lumen of seminal tubes reduced by the presence of immature cells of the spermatic lineage. Our results suggest that pre- and early postnatal exposure to a low dose of BPA disrupts the normal function of the reproductive axis in prepuberal male rats. The effects of the ED may be exerted at different levels of the axis and may be dependent on the dose, manner of administration, and the moment of exposure to the disruptor.

Leptin inhibits the reproductive axis in adult male Syrian hamsters exposed to long and short photoperiod.

The aim of the study was to investigate the effects of acute leptin treatment of adult Syrian hamsters exposed to a long (LP, eugonadal males) and short photoperiod (SP, hypogonadal males). Animals were exposed to LP (L:D 14:10) or SP (L:D 10:14) for 10 weeks. Afterwards, both LP and SP hamsters were allocated to a control (SP-C, LP-C) or leptin-treated group (SP 3, SP 10, SP 30 or LP3, LP 10, LP 30). One hour before sacrifice, a single dose of leptin (3, 10 or 30 µg/kg) or vehicle was administered (i.p.) to the males. Testis weight, serum and pituitary luteinizing hormone (LH) concentrations, as well as the hypothalamic concentration of gonadotropin-releasing hormone (GnRH) were recorded. Histological analysis of the testis was performed and GnRH concentration in the culture medium of hypothalamic explants was examined. A dramatic regression of testicular weight and histological atrophy of seminiferous tubules, as well as a decrease in serum and pituitary LH concentrations were found in SP males. All doses of leptin significantly reduced serum LH levels and medium GnRH concentrations in both photoperiod groups. Pituitary LH and hypothalamic GnRH concentrations were not affected by leptin. In conclusion, we demonstrated that leptin inhibited the reproductive axis of Syrian male hamsters exposed to LP and SP and fed ad libitum.

Probable gamma-aminobutyric acid involvement in bisphenol A effect at the hypothalamic level in adult male rats

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The aim of the present study was to investigate the effects of bisphenol A (BPA) on the neuroendocrine mechanism of control of the reproductive axis in adult male rats exposed to it during pre- and early postnatal periods. Wistar mated rats were treated with either 0.1% ethanol or BPA in their drinking water until their offspring were weaned at the age of 21 days. The estimated average dose of exposure to dams was approximately 2.5 mg/kg body weight per day of BPA. After 21 days, the pups were separated from the mother and sacrificed on 70 day of life. Gn-RH and gamma-aminobutyric acid (GABA) release from hypothalamic fragments was measured. LH, FSH, and testosterone concentrations were determined, and histological and morphometrical studies of testis were performed. Gn-RH release decreased significantly, while GABA serum levels were markedly increased by treatment. LH serum levels showed no changes, and FSH and testosterone levels decreased significantly. Histological studies showed abnormalities in the tubular organization of the germinal epithelium. The cytoarchitecture of germinal cells was apparently normal, and a reduction of the nuclear area of Leydig cells but not their number was observed. Taken all together, these results provide evidence of the effect caused by BPA on the adult male reproductive axis when exposed during pre- and postnatal period. Moreover, our findings suggest a probable GABA involvement in its effect at the hypothalamic level (AU)

Probable gamma-aminobutyric acid involvement in bisphenol A effect at the hypothalamic level in adult male rats.

The aim of the present study was to investigate the effects of bisphenol A (BPA) on the neuroendocrine mechanism of control of the reproductive axis in adult male rats exposed to it during pre- and early postnatal periods. Wistar mated rats were treated with either 0.1% ethanol or BPA in their drinking water until their offspring were weaned at the age of 21 days. The estimated average dose of exposure to dams was approximately 2.5 mg/kg body weight per day of BPA. After 21 days, the pups were separated from the mother and sacrificed on 70 day of life. Gn-RH and gamma-aminobutyric acid (GABA) release from hypothalamic fragments was measured. LH, FSH, and testosterone concentrations were determined, and histological and morphometrical studies of testis were performed. Gn-RH release decreased significantly, while GABA serum levels were markedly increased by treatment. LH serum levels showed no changes, and FSH and testosterone levels decreased significantly. Histological studies showed abnormalities in the tubular organization of the germinal epithelium. The cytoarchitecture of germinal cells was apparently normal, and a reduction of the nuclear area of Leydig cells but not their number was observed. Taken all together, these results provide evidence of the effect caused by BPA on the adult male reproductive axis when exposed during pre- and postnatal period. Moreover, our findings suggest a probable GABA involvement in its effect at the hypothalamic level.

Reproductive axis response to repeated lipopolysaccharide administration in peripubertal female rats

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Immune system disorders are often accompanied by alterations in the reproductive axis. Several reports have shown that administration of bacterial lipopolysaccharide (LPS) has central inflammatory effects and activates cytokine release in the hypothalamus where the luteinizing hormone releasing hormone (Gn-RH) neurons are located. The present study was designed to investigate the effect of repeated LPS administration on the neuroendocrine mechanisms of control of the reproductive axis in peripubertal female rats (30-day-old rats). With this aim, LPS (50 ìg/kg weight) was administered to the animals during 25, 27 and 29 days of age and sacrificed on 30 day of life. Gn-RH, ã−amino butyric acid (GABA) and glutamic acid (GLU), two amino acids involved in the regulation of Gn-RH secretion, hypothalamic content were measured. LH and estradiol serum levels were also determined and the day of vaginal opening examined. The results showed a significant increase in Gn-RH and GLU content (p < 0.0001), shared by a reduction of GABA one (p < 0.0001). LH and estradiol serum levels were decreased (p < 0.01, p < 0.001) and delay in the day of vaginal opening was also observed in treated animals. Present results show that repeated LPSadministration impaired reproductive function, modifying the neuroendocrine mechanisms of control of the axis in peripubertal female rats (AU)

Evidence to suggest glutamic acid involvement in Bisphenol A effect at the hypothalamic level in prepubertal male rats.

OBJECTIVES: The aim of present paper was to study the probable role of glutamic acid (GLU) as a mediator of bisphenol A (BPA) effect at the hypothalamic level and its effects on the reproductive axis of prepubertal male rats. METHODS: Mated Wistar rats were treated with either 0.1% ethanol (control group, n=10) or BPA (BPA group, n=10) in their drinking water until their offspring were weaned at the age of 21 days. The estimated average dose of exposure to dams was approximately 2.5 mg/kg body weight/day of BPA. At the prepubertal stage (35 days of age), the male rats were sacrificed and Gn-RH and glutamic acid (GLU) release, an amino acid involved in Gn-RH secretion, were measured in hypothalamic samples containing medio basal and anterior preoptic area (MBH-APOA), by RIA and HPLC respectively. LH, FSH serum levels were measured by RIA and testosterone by EQLIA. RESULTS: Gn-RH and GLU release decreased significantly in animals exposed to BPA (p<0.001, p<0.01). LH, FSH and testosterone serum levels were also decreased by treatment (p<0.0001). CONCLUSION: Present results provide evidence that BPA may act at the hypothalamic level to decrease GLU release which in turn may modify Gn-RH secretion altering the normal function of the axis.

Impact of gestational and lactational phthalate exposure on hypothalamic content of amino acid neurotransmitters and FSH secretion in peripubertal male rats.

This study investigated the effect of the pre- and perinatal exposure to di-(2-ethylhexyl) phthalate (DEHP) on the neuroendocrine parameters that regulate reproduction in peripubertal male rats. DEHP at dose of 3 and 30mg/kg bw/day was administered orally to female rat since pregnancy onset until weaning. The male litters were sacrificed at 30 days of age to determine gonadotropin serum level and the hypothalamic contents of the amino acids aspartate and gamma-aminobutyric acid. No changes in gonadotropin, aspartate and gamma-aminobutyric acid levels were detected at the low dose. DEHP 30mg/kg bw/day reduced testis weight and serum FSH, in correlation with a significant increase in the inhibitory GABAergic tone and a reduction in the stimulatory effect of aspartate on gonadotropin level. This study provides unknown data regarding changes in the hypothalamic contents of the amino acid neurotransmitters, which are involved in the neuroendocrine regulation of reproductive axis, in peripubertal male rat offspring from dams exposed to DEHP during gestational and lactational periods. This could be related with the gonadotropin modifications also here described.

Reproductive axis response to repeated lipopolysaccharide administration in peripubertal female rats.

Immune system disorders are often accompanied by alterations in the reproductive axis. Several reports have shown that administration of bacterial lipopolysaccharide (LPS) has central inflammatory effects and activates cytokine release in the hypothalamus where the luteinizing hormone releasing hormone (Gn-RH) neurons are located. The present study was designed to investigate the effect of repeated LPS administration on the neuroendocrine mechanisms of control of the reproductive axis in peripubertal female rats (30-day-old rats). With this aim, LPS (50 mug/kg weight) was administered to the animals during 25, 27 and 29 days of age and sacrificed on 30 day of life. Gn-RH, gamma-amino butyric acid (GABA) and glutamic acid (GLU), two amino acids involved in the regulation of Gn-RH secretion, hypothalamic content were measured. LH and estradiol serum levels were also determined and the day of vaginal opening examined. The results showed a significant increase in Gn-RH and GLU content (p < 0.0001), shared by a reduction of GABA one (p < 0.0001). LH and estradiol serum levels were decreased (p < 0.01, p < 0.001) and delay in the day of vaginal opening was also observed in treated animals. Present results show that repeated LPS administration impaired reproductive function, modifying the neuroendocrine mechanisms of control of the axis in peripubertal female rats.

Effect of bacterial lipopolysaccharide on the reproductive axis of prepubertal and peripubertal female rats. Ontogenic changes in the immune-neuroendocrine interactions.

The immune, endocrine and nervous systems are closely interrelated, which allows the organism to respond to different types of stress such as infection. Chronic infectious and inflammatory conditions are often accompanied by an impaired reproductive function. Leptin, a hormone produced by adipose tissue, exerts a regulatory function on the reproductive axis. It has homology with other proinflammatory cytokines and could be modified by lipopolysaccharide (LPS). Therefore, these studies were designed to investigate the effect of LPS administration on the neuroendocrine mechanisms involved in the regulation of the reproductive axis during sexual maturation. Fifteen- and 30-day-old female rats were injected with a single dose of LPS 250 microg/kg (i.p.) and then nitric oxide synthase (NOS) activity, hypothalamic excitatory/inhibitory amino acids and Gn-RH content, serum LH and leptin concentration were studied. In 15-day-old female rats LPS treatment did not modify hypothalamic inducible (iNOS) and constitutive (cNOS) NOS activity, Gn-RH, glutamate (GLU) and GABA content. Also serum LH and leptin levels were not modified. In 30-day-old rats LPS increased iNOS and cNOS activity (p < 0.001) and hypothalamic Gn-RH content (p < 0.001). At this age hypothalamic GABA content was significantly decreased (p < 0.001) without changes in GLU content, and serum LH (p < 0.001) and leptin (p < 0.0001) decreased significantly. In summary, current studies have demonstrated that LPS administration to 15- and 30-day-old female rats results in a different response of the hypothalamus-pituitary-gonadal axis and of the adipose tissue, demonstrating an ontogenic response of the immune-neuroendocrine system to LPS administration.

Low dose 4-MBC effect on neuroendocrine regulation of reproductive axis in adult male rats.

4-Methylbenzylidene camphor (4-MBC) is an ultraviolet absorbent. The objective of this paper was to evaluate the effect of 4-MBC low-dose exposure on the neuroendocrine reproductive regulation in male rats. Wistar male adult rats were injected sc. with 4-MBC during 5 days with a dose of 2 and 10mg/kg or during 2 days with a dose of 2 and 20mg/kg. In all rats serum prolactin, LH and FSH concentration were assayed. The hypothalamus of rats injected during 2 days were also dissected to study GnRH release. Rats that received 2 and 10mg/kg of 4-MBC during 5 days showed a decrease in the LH and FSH serum concentration. In rats injected during 2 days, serum LH decreased with 2 and 20mg/kg and FSH decreased with 2mg/kg of 4-MBC. In vitro hypothalamic GnRH release also decreased in these animals. These results show that low doses of 4-MBC inhibit the reproductive axis in adult male rats.

Leptin stimulates LH secretion in peripubertal male rats through NMDA receptors.

Leptin, a peptide hormone secreted by adipocytes that has been proposed as a metabolic signal in the reproductive system, appears to be linked to the different neuroendocrine processes involved in the onset of puberty. We studied the ontogenic effect of administration of leptin (30 mg/kg i.p.) on serum LH levels during different stages of sexual development (7, 30, and 45 days of age) in male rats and on the hypothalamic content of glutamate (GLU) and gamma-aminobutyric acid (GABA) in 30-day-old rats. Leptin induced a significant increase (p < 0.01) in LH levels in 30 days old rats. This hormone stimulatory effect was accompanied by a significant enhancement (p < 0.01) of the hypothalamic content of glutamate, the hypothalamic excitatory aminoacid involved in N-methyl-D-aspartate (NMDA) neurotransmission. No changes in the LH plasma levels were observed in 7- and 45-day-old male rats treated with leptin. MK 801 (0.1 and 0.3 mg/kg i.p.), an antagonist of NMDA receptors of excitatory amino acid system (EAAs), antagonized the stimulatory effect of leptin on LH secretion and on the hypothalamic content of GLU. These results demonstrate that leptin stimulates the reproductive axis in male rats during a determined period of sexual maturation and that NMDA receptors are involved in thefacilitatory action of leptin on the gonadal axis of male rats during sexual maturation.

Effect of leptin on LH levels and hypothalamic release of GnRH. Its relationship with the hypothalamic neurotransmitter amino acids system in adult male rats.

The objective of the present paper was to determine the effect of leptin on the reproductive axis in adult male rats, as well as the hypothalamic mechanisms involved in this effect. For this purpose, we studied the in vivo effect of leptin in adult male rats on serum LH levels, and the in vitro effect on hypothalamic GnRH and amino acid neurotrasmitter release. For in vivo experiments, animals were injected i.p. with leptin at a dose of 30, 100 and 300 microg/kg. In the in vitro experiments, hypothalamic samples were incubated for 60 min in Earle's medium with leptin: 10(-9), 10(-10) and 10(-12) M for GnRH determination, and 10(-10) M for amino acids evaluation. Finally, we studied the effect of the lowest effective leptin dose on plasma LH levels in peripubertal male rats to compare the effect between this group and adults. Leptin induces significant decreases of serum LH levels with the different studied doses (p < 0.01 vs. control) in adult male rats, while in peripubertal male rats, it induced a significant (p < 0.01 vs. control) increment in serum LH levels. On the other hand, in vitro leptin in adult male rats, significantly decreases GnRH release as well as the hypothalamic release of glutamate (GLU). In contrast, leptin increased the GABA release by this hypothalamus in these animals. These results indicate that leptin has an inhibitory effect on the GnRH-LH axis in adult male rats and this effect appears to be connected with an inhibition of hypothalamic release of GLU (the excitatory amino acid) and a stimulatory effect on GABA release (the inhibitory amino acid). On the other hand, in peripubertal male rats, leptin showed a stimulatory effect.

Hypothalamic nitric oxide synthase activity during sexual maturation in female rats. Effects of estrogens.

OBJECTIVES: To determine the hypothalamic activity of nitric oxide synthase (NOS, the enzyme involved in the synthesis of nitric oxide NO) during sexual maturation in prepubertal (15 days old) and peripubertal female rats (30 days old) as well as the effect of estradiol administration on this neurotransmitter system. METHODS: Hypothalamic samples containing the anterior preoptic and medial basal areas (APOA-MBH) were homogenized with HEPES 20 mM, pH = 7.4 and NOS activity was determined in APO-MBH after 10 minutes of incubation by the conversion of 14C arginine to 14C citrulline. RESULTS: The hypothalamic concentration of NOS is significantly higher in peripubertal than in prepubertal rats. Treatment with EB increased significantly the activity of the enzyme in both groups compared with control and the increases was similar at both ages. CONCLUSIONS: These results clearly demonstrated that the hypothalamic NOS activity increases in peripubertal rats as compared with prepubertal animals. Estradiol has a similar stimulatory effect on hypothalamic NOS activity at both ages of sexual maturation, indicating that the increase in NOS during sexual maturation is connected with the peripubertal increase of estradiol rather than an increase in the sensitivity of the enzyme to the ovarian hormone.