Influence of tidal volume on pulse pressure variation and stroke volume variation during experimental intra-abdominal hypertension.

BACKGROUND: Pulse pressure variation (PPV) and stroke volume variation (SVV) are frequently used to assess fluid responsiveness in critically ill patients on mechanical ventilation (MV). There are many factors, in addition to preload that influence the magnitude of these cyclic variations. We sought to investigate the effect of tidal volume (V(T)) on PPV and SVV, and prediction of fluid responsiveness in a model of intra-abdominal hypertension (IAH). METHODS: Twelve anesthetized and mechanically ventilated piglets on continuous pulse contour cardiac output monitoring. Hypovolemia was ruled out with 2 consecutive fluid boluses after instrumentation. IAH was induced by intraperitoneal instillation of colloid solution with a goal of reducing respiratory system compliance by 50 %. Subjects were classified as fluid responders if stroke volume increased >15 % after each fluid challenge. SVV and PPV were recorded with tidal volumes (VT) of 6, 12 and 18 ml/kg before IAH after IAH induction and after a fluid challenge during IAH. RESULTS: V(T) influenced PPV and SVV at baseline and during IAH, being significantly larger with higher V(T). These differences were attenuated after fluid administration in both conditions. After IAH induction, there was a significant increase in SVV with the three-tested V(T), but the magnitude of that change was larger with high V(T): with 6 ml/kg from 3 % (3, 4) to 5 % (4, 6.25) (p = 0.05), with 12 ml/kg from 5 % (4, 6) to 11 % (8.75, 17) (p = 0.02) and 18 ml/kg from 5 % (4,7.5) to 15 % (8.75, 19.5) (p = 0.02). Similarly, PPV increased with all the tested VT after IAH induction, being this increase larger with high VT: with 6 ml/kg from 3 % (2, 4.25) to 6 % (4.75, 7) (p = 0.05), with 12 ml/kg from 5 % (4, 6) to 13.5 % (10.25, 15.5) (p = 0.02) and 18 ml/kg from 7 % (5.5, 8.5) to 24 % (13.5, 30.25) (p = 0.02). One third of subjects responded to fluid administration after IAH, but neither SVV nor PPV were able to identify the fluid responders with the tested V(T). CONCLUSION: IAH induction in non-hypovolemic subjects significantly increased SVV and PPV with the three tested V(T), but the magnitude of that change was higher with larger V(T). This observation reveals the dependence of functional hemodynamic markers on intrathoracic as well intra-abdominal pressures, in addition to volemic status. Also, PPV and SVV were unable to predict fluid responsiveness after IAH induction. Future studies should take into consideration these findings when exploring relationships between dynamic preload indicators and fluid responsiveness during IAH.

Characteristics of Medically Transported Critically Ill Children with Respiratory Failure in Latin America: Implications for Outcomes.

Several challenges exist for referral and transport of critically ill children in resource-limited regions such as Latin America; however, little is known about factors associated with clinical outcomes. Thus, we aimed to describe the characteristics of critically ill children in Latin America transferred to pediatric intensive care units for acute respiratory failure to identify risk factors for mortality. We analyzed data from 2,692 patients admitted to 28 centers in the Pediatric Collaborative Network of Latin America Acute Respiratory Failure Registry. Among patients referred from another facility (773, 28%), nonurban transports were independently associated with mortality (adjusted odds ratio = 9.4; 95% confidence interval: 2.4-36.3).

Divergent molecular and growth responses of young "Cabernet Sauvignon" (Vitis vinifera) plants to simple and mixed infections with Grapevine rupestris stem pitting-associated virus.

Grapevine rupestris stem pitting associated virus (GRSPaV) is one of the most widely distributed viruses; even so, little is known about its effect on Vitis vinifera. To provide new insights, the effects of single and mixed GRSPaV infections on the V. vinifera cultivar "Cabernet Sauvignon" were studied by evaluating growth parameters, such as measurements of the total plant length, the number and distance of internodes and the number of leaves per shoot. In addition, parameters relating to gas exchange, i.e., the stomatal conductance, net photosynthetic rate, internal CO2 concentration and leaf transpiration, were also assessed. All the measurements were performed in one- and two-year-old plants with a single GRSPaV infection or mixed infections of GRSPaV and Grapevine fanleaf virus (GFLV). The results show that the plant phytosanitary status did not significantly alter the growth and gas exchange parameters in one-year-old plants. However, in two-year-old plants, single GRSPaV infections increased shoot elongation, which was accompanied by the overexpression of genes associated with the gibberellic acid response pathway. The gas exchange parameters of these plants were negatively affected, despite exhibiting higher LHCII gene expression. Plants with mixed infections did not have modified growth parameters, although they presented a greater reduction in the primary photosynthetic parameters evaluated with no change in LHCII expression. The results presented here confirm the co-evolution hypothesis for V. vinifera and GRSPaV during the early stages of plant development, and they provide new evidence about the effects of GRSPaV and GFLV co-infections on the "Cabernet Sauvignon" cultivar.

Scale to measure medical, nursing and midwifery students' engagement in an e-learning histology course / Escala para medir la participación de estudiantes de medicina, enfermería y obstetricia en un curso de histología e-learning

SUMMARY: E-learning courses become increasingly important and relevant in medicine and health sciences over the last decade. However, there are few teaching experiences of e-learning histology courses published in the literature worldwide. Moreover, most of these studies focus on the didactic aspects of the course without exploring student participation. The study presented below aimed to validate a scale to measure student participation in an e-learning histology course. We provide evidence of validity of the instrument based on its internal structure for use with medical, nursing, and midwifery students. The participants in this study were a group of 426 Chilean medical, nursing and midwifery students from a public university who completed the questionnaire in two consecutive semesters (2020-2021). Data from the first group of students were used to perform an exploratory factor analysis (EFA), while data from the second group of participants were used to perform a confirmatory factor analysis (CFA). The three factors identified according to the CFA were: "Habits of online," "Motivation for online learning," and "Interaction of online". After eliminating one of the initial items of the instrument, the scale showed acceptable psychometric properties suggesting that it is a useful instrument to measure students' perception of their participation in e-learning histology courses. The factors identified through the validation of the instrument provide relevant information for teachers and curriculum developers to create and implement different ways of encouraging student participation in e- learning histology courses to support online learning.

Los cursos e-learning han tomado mayor importancia y relevancia durante la ultima década en carreras de medicina y ciencias de la salud. No obstante, existen escasas experiencias docentes de cursos de histologia e-learning publicadas en la literatura mundial. Además, la mayoría de estos estudios se centran en los aspectos didácticos del curso sin explorar la participación de los estudiantes. El estudio que presentamos a continuación tuvo por objetivo validar una escala para medir la participación de los estudiantes en un curso de histología e-learning. Aportamos evidencia de validez del instrumento basada en su estructura interna para su uso con estudiantes de medicina, enfermería y obstetricia. Los participantes de este estudio fueron un grupo de 426 estudiantes chilenos de medicina, enfermería y obstetricia de una universidad pública quienes completaron el cuestionario en dos semestres consecutivos (año 2020-2021). Los datos del primer grupo de estudiantes se utilizaron para realizar un análisis factorial exploratorio (AFE), mientras que los datos del segundo grupo de participantes se utilizaron para realizar un análisis factorial confirmatorio (AFC). Los tres factores identificados según el AFC fueron: "Hábitos de los estudiantes en línea", "Motivación por el aprendizaje en línea", "Interacción de los estudiantes en línea". Luego de la eliminación de uno de los ítems iniciales del instrumento, la escala mostró propiedades psicométricas aceptables sugiriendo que es un instrumento útil para medir la percepción de los estudiantes sobre su participación en cursos de histología en formato e-learning. Los factores identificados mediante la validación del instrumento entregan información relevante para que los profesores y curriculistas desarrollen e implementen diferentes formas de estimular la participación de los estudiantes en cursos de histología e- learning y así apoyar el aprendizaje en formato online.

Metformin prevents vascular prostanoid release alterations induced by a high-fat diet in rats.

Perivascular adipose tissue dysfunction induced by high-fat feeding leads to alterations in the modulation of inflammation, contractile activity of the vascular smooth muscle and endothelial function, all risk factors in the development of hypertension. Metformin, an activator of AMP-activated protein kinase (AMPK), is currently the first-line drug treatment for type 2 diabetes (T2DM) and metabolic syndrome. Besides its glucose-lowering effect, there is an interest in actions of this drug with potential relevance in cardiovascular diseases. The high-fat (HF) diet is an experimental model that resembles human metabolic syndrome. We have previously reported an altered pattern of prostanoid release in mesenteric vessels in this model. The aim of this study was to analyse the effects of metformin on mesenteric vascular bed prostanoid release, adiposity index and its relation to blood pressure in Sprague-Dawley rats fed a HF diet for 8 and 12 weeks. Eight groups were used: control (C8, C1), HF diet (HF8, HF12, 50% w/w bovine fat), metformin-treated (CMf8, CMf12, 500 mg/kg/day) and metformin-treated HF diet (HFMf8, HFMf12, both treatments). HF diet increased mesenteric vascular bed adiposity index (%, HF8: 1.7±0.1 vs C8: 0.9±0.04 and HF12: 1.8±0.1 vs C12: 0.8±0.1, P<.001); systolic blood pressure (SBP, mm Hg, HF8: 145±6 vs C8: 118±4, P<.01 and HF12: 151±1 vs C12: 121±3, P<.001). We found a positive correlation between these two parameters. Moreover HF diet increased the release of vasoconstrictor prostanoids such as thromboxane (TX) B2 (ng PR/mg of tissue, HF8: 117±6 vs C8: 66±2 and HF12: 123±6 vs C12: 62±5, P<.001) and prostaglandin (PG) F2α (ng/mg, HF8: 153±9 vs C8: 88±3 and HF12: 160±11 vs C12: 83±5, P<.001). We also found that this increase in the release of vasoconstrictor prostanoids positively correlates with the elevation of SBP. In addition, HF diet increases the release of PGE2 and decreases the prostacyclin (PGI2 )/TXA2 release ratio at 8 and 12 weeks of treatment compared to control groups. In the HFMf group, metformin treatment prevented all these increases in mesenteric vascular bed adiposity index (%, HFMf8: 1.3±0.2 vs HF8 and HFMf12: 1.3±0.1 vs HF12, P<.05); SBP (mm Hg, HFMf8: 127±2 vs HF8 and HFMf12: 132±1 vs HF12, P<.001); TXB2 release (ng PR/mg of tissue, HFMf8: 65±12 vs HF8, P<.05 and HFMf12: 53±3 vs HF12, P<.001) and PGF2 α (ng PR/mg of tissue, HFMf8: 99±13 vs HF8, P<.01 and HFMf12: 77±8 vs HF12, P<.001). Meanwhile metformin prevented the increment in PGE2 release only at 12 weeks. On the other hand, metformin improved the PGI2 /TXA2 ratio in both periods studied. In conclusion, metformin could exert beneficial effects on adipose tissue and the vascular system by improving endothelial dysfunction induced by an imbalance of vasoactive substances in mesenteric perivascular adipose tissue in this model.

[Intraoperative high frequency oscillatory ventilation in 2 children undergoing lung surgery]. / Uso intraoperatorio de ventilación de alta frecuencia oscilatoria en dos casos pediátricos de cirugía pulmonar.

Over the past 10 years, the application of high frequency oscillatory ventilation (HFOV) has been extended beyond the neonatal period. The technique is now used in various respiratory disease settings when conventional mechanical ventilation fails. Even though HFOV has become increasingly routine in some pediatric intensive care units, familiarity with it is still limited among anesthesiologists and surgeons and it is not often applied during surgery. We report our experience using HFOV during thoracic surgery on 2 pediatric patients, one aged 5 years and the other aged 1 month. The respective surgical procedures were to close a bronchopleural fistula and to obtain a lung biopsy in order to provide guidance for limiting therapeutic intervention. In both cases the procedure was performed without adverse effects and allowed medical interventions to be carried out. We conclude that it is possible to perform thoracic surgery in pediatric patients undergoing HFOV. This ventilation mode can be useful during surgery and teams that care for critically ill children should be familiar with the equipment.

Adaptación e implementación del modelo de prevención de consumo de sustancias Planet Youth en Chile / Adaptation and implementation of the Planet Youth substance use prevention model in Chile

Resumen El consumo de sustancias en adolescentes es altamente prevalente en varias regiones del mundo, y especialmente en Chile, siendo su prevención un importante desafío para la salud pública. Este artículo describe el modelo islandés de prevención del consumo de sustancias en adolescentes "Planet Youth", su adaptación y factibilidad de implementación en Chile, como primera experiencia en Latinoamérica. Este modelo comunitario está enfocado en la prevención ambiental y en la promoción de la salud de niños, niñas y adolescentes, basado en un diagnóstico local y oportuno de factores protectores y de riesgo, con colaboración de la autoridad local y la academia. Seis comunas de la región metropolitana en colaboración con la Universidad de Chile y el Icelandic Centre for Social Research and Analysis inician su implementación en 2018. Se tradujo y adaptó la encuesta islandesa que fue aplicada a 7354 estudiantes de 2° medio, cuyos resultados se retroalimentaron a colegios y municipalidades para trabajar en la modificación de los principales factores de riesgo y protección. En 2020, el proceso ha requerido algunas adaptaciones debido a la pandemia por COVID-19. Se discute acerca de factores socioculturales relevantes en la adaptación de estrategias basadas en evidencia internacional que se transfieren a un país diferente. La implementación del modelo Planet Youth es factible en Chile y ofrece una importante oportunidad para prevenir el consumo de sustancias en jóvenes de manera efectiva en Latinoamérica.

The prevalence of substance use is high among adolescents in several region around the world, specifically in Chile, and its prevention is an important public health challenge. We describe the adaptation and the feasibility to implement the Icelandic model of substance use prevention in adolescents "Planet Youth" in Chile as first experience in Latin America. This community prevention model focuses on the environment, culture and the promotion of health in adolescents, informed by local risk and protective factors. Implementation requires collaboration between academia and municipal authorities. Six municipalities of the Metropolitan Region, the University of Chile and the Icelandic Centre for Social Research and Analysis collaborated in the implementation of the Planet Youth model since 2018 in Chile. A substance use survey was translated, adapted, and applied to 7354 tenth grade students. The results were informed to schools and municipalities in order to work on modifications of the main risk and protective factors in their own community. In 2020, the prevention process has required some adaptation due to COVID-19 pandemic. We discuss sociocultural factors in the adaptation of this international prevention model transferred to Latin America. The implementation of the Planet Youth model is feasible in Chile and offers an opportunity to effectively prevent the substance use behaviors of adolescents in Latin America.

A high-fat plus fructose diet produces a vascular prostanoid alterations in the rat.

In the rat, a high-fat (HF) plus fructose (F) diet produces cardiovascular and metabolic alterations that resemble human metabolic syndrome. Prostanoids (PR), cyclo-oxygenase-derived arachidonic acid metabolites, have vasoactive properties and mediate inflammation. The aim of this study was to analyse the effect of a HF+F diet on blood pressure (BP), metabolic parameters and mesenteric vascular bed PR production in male Sprague-Dawley rats. Four groups were studied over 9 weeks (n = 6 each): control (C), standard diet (SD) and tap water to drink; F+SD and 10% w/v F solution to drink; HF 50% (w/w) bovine fat added to SD and tap water; and HFF, both treatments. PR were determined by HPLC. Blood pressure was elevated in all experimental groups. Triglyceridaemia, insulinaemia and HOMA-IR were increased in the F and HF groups. HF+F animals showed elevated glycaemia, insulinaemia, HOMA-IR and triglyceridaemia. F decreased the vasodilator prostanoids PGI2 and PGE2 in the mesenteric vascular bed. Body weight was not significantly altered. In HFF, production of PGE2 , PGF2 alpha and TXB2 was elevated. The increased BP in HF and HFF could be partly attributed to the imbalance in vascular PR production towards vasoconstrictors. On the other hand, this dietary modification could induce inflammation, which would explain the elevation of PGE2 . In the F group, hypertension could be related to decreased vasodilator PRs. The simultaneous administration of HF and F in the rat produces deleterious effects greater than observed when treatments are applied separately.

Endogenous excitatory amino acid neurotransmission regulates the estradiol-induced LH surge in ovariectomized rats.

The present study was designed to evaluate the relative contribution of endogenous excitatory amino acids to the control of the estradiol-induced LH surge using specific blockers for N-methyl-D-aspartic acid (NMDA) and non-NMDA receptor types. Adult female rats ovariectomized for 2-3 weeks were implanted with third ventricular cannulae one week before the experiments. Silastic capsules (3 cm active surface) containing estradiol benzoate (250 micrograms/ml dissolved in sesame oil) were implanted subcutaneously two days prior to bleeding. Blood samples were collected at hourly intervals (from 1300 to 2100 h) through indwelling atrial cannulae implanted the day before the bleeding. (+) 2-amino-7-phosphoheptanoic acid (AP-7), a NMDA receptor antagonist, and 6,7-dinitroquinoxaline-2,3-dione (DNQX), a non-NMDA receptor antagonist, were administered (10 and 20 nmole dissolved in 10 microliters 0.9% sodium chloride, respectively) at 1300 and 1400 h into the third ventricle. LH, FSH and PRL levels were assayed by RIA in plasma samples. AP-7 and DNQX administration completely blocked the estradiol-induced LH surge, whereas PRL and FSH secretion was not affected by the treatments. These results indicate that endogenous EAA play an important role in controlling LH secretion. Furthermore, the study reveals that both EAA receptor types; i.e. NMDA and non-NMDA, appear to be necessary for the physiological mechanism(s) triggering the estradiol-induced LH surge.

Endogenous excitatory amino acids and glutamate receptor subtypes involved in the control of hypothalamic luteinizing hormone-releasing hormone secretion.

These studies were designed to evaluate the actions and relative potencies of different endogenous and excitatory amino acid (EAA) selective analogs on EAA-induced neuropeptide secretion as well as to analyze the receptor subtypes involved. For this purpose, different glutamate agonists were tested for their ability to evoke release of the hypothalamic neuropeptide LHRH from arcuate nucleus-median eminence (AN-ME) fragments incubated in vitro. Different glutamate agonists, i.e. 3-amino-3-hydroxy-5-methyl-isoxazole-4-propionic (AMPA), kainic, quisqualic, homocysteic (HCA), quinolinic (QUIN), N-methyl-D-aspartic (NMDA), and pyroglutamic (PYR) acids, elicited LHRH release from AN-ME fragments in vitro. Further evaluation of the range of activity of several of these compounds, both in terms of the dose inducing a half-maximal response and the LHRH-releasing effect at that particular dose, indicated that AMPA greater than HCA greater than QUIN greater than PYR, suggesting that non-NMDA receptors are primarily involved in EAA-induced LHRH release at the level of the AN-ME. Evaluation of the receptor types involved using two specific antagonists for NMDA and non-NMDA receptors, D,L-2-amino-7-phosphoheptanoic acid and 6,7-cyanoquinoxaline-2,3-dione, respectively, showed that the effects of AMPA and HCA on LHRH release can be completely blocked by 6,7-cyanoquinoxaline-2,3-dione, whereas QUIN activity was blocked by D,L-2-amino-7-phosphoheptanoic acid. The effects of PYR on LHRH release were abolished by both receptor blockers. The metabotropic receptor agonist trans-1-amino-cyclopentyl-1,1,3-dicarboxylic acid was not active in eliciting LHRH secretion. The data indicate that endogenous substances active at EAA receptor sites, such as HCA, QUIN, and PYR, can significantly increase the secretion of the neuropeptide LHRH and, thus, may participate in the physiological regulation of the activity of this important neuroendocrine neuronal system. In addition, the results suggest that non-NMDA receptor sites may be preferentially activated at lower ligand concentrations, although NMDA receptors may also be involved in the response to certain endogenous agonists.

Cross-talk between excitatory and inhibitory amino acids in the regulation of luteinizing hormone-releasing hormone secretion.

Inhibitory (IAA) and excitatory amino acid (EAA) neurotransmitters appear to play an important role in regulating reproductive functions. L-Glutamic acid (GLU), the major representative of the EAA system, stimulates LHRH release from arcuate nucleus-median eminence (AN-ME) fragments in vitro. Several studies have provided evidence for considering gamma-aminobutyric acid (GABA), a major IAA neurotransmitter, as another regulator of LHRH secretion. Recent reports have indicated that a cross-talk between GABA and GLU participates in the regulation of synaptic transmission in the brain. In concert with this notion, we present evidence indicating that this cross-talk between GABA and GLU appears to be also involved in neuroendocrinological paradigms. In this respect, bicuculline, a GABA-A receptor antagonist, blocked GLU-evoked LHRH secretion from AN-ME fragments in vitro without affecting basal LHRH release. In addition, activation of GABA-A receptors by muscimol (MUS) stimulated basal LHRH secretion. Interestingly, when MUS and GLU were added together to the incubation medium, an additive, stimulatory effect was observed. These observations clearly indicate that a GABAergic mechanism participates, via GABA-A receptors, in GLU-induced LHRH secretion from terminals of the ME. Furthermore, GABA-B receptors appear to negatively modulate the effects of GLU. Activation of GABA-B receptors by baclofen (BAC) blocked GLU-induced LHRH secretion, while phaclofen, a GABA-B receptor antagonist, reversed this effect. In summary, our data provide evidence for a cross-talk between EAA and IAA systems in the regulation of LHRH release, and, therefore, in the control of gonadal function.

Glutamate receptors of the non-N-methyl-D-aspartic acid type mediate the increase in luteinizing hormone-releasing hormone release by excitatory amino acids in vitro.

The present study was designed to analyze in detail the effects of L-glutamate (L-Glu) and its agonists on the release of LHRH from arcuate nucleus-median eminence (AN-ME) fragments in vitro. Fragments from adult male rats were incubated in Krebs-Ringer bicarbonate buffer in the presence of different concentrations of L-Glu, kainate (KA), N-methyl-D-aspartic acid (NMDA), and quisqualate (QA). L-Glu at 10-20 mM evoked a significant increase in basal LHRH release, while D-glutamate at similar concentrations was ineffective. Partial depolarization with 14 mM K+ significantly augmented the release of LHRH induced by L-Glu. L-Glu-induced LHRH release was blunted in a dose-related manner by the specific KA/QA receptor antagonist 6,7-dinitroquinoxaline-2,3-dione. Exposure to KA or QA significantly increased LHRH release at concentrations (1 mM) much lower than those required for L-Glu. In the presence of 14 mM K+ the potencies of KA and QA (0.075 and 0.1 mM, respectively) were significantly enhanced. 6,7-Dinitroquinoxaline-2,3-dione blocked KA-induced LHRH release, while AP-7, a competitive NMDA receptor antagonist, was inactive in preventing L-Glu- and KA-induced LHRH release. LHRH secretion from AN-ME fragments was unaffected by NMDA at concentrations up to 10 mM in the different media tested. A significant stimulatory effect of NMDA at 20 mM was observed when fragments were incubated in Mg2+-free medium. These results show the stereoselectivity of L-Glu to enhance LHRH release from AN-ME fragments in vitro. Moreover, in view of the respective potencies of excitatory amino acid agonists (KA = QA greater than L-Glu greater than NMDA) and the selective antagonism of excitatory amino acid effects, they provide evidence that non-NMDA receptors primarily mediate the excitatory actions of L-Glu on LHRH release from nerve terminals in the AN-ME.

Effects of histamine implants in several brain regions on the release of prolactin in conscious adult male rats.

The levels of prolactin in the plasma of conscious male rats were determined at various times after an acute administration of histamine or a histamine releasing agent, compound 48/80, in three brain regions. The brain structures that were examined were, the caudal part of the preoptic area and anterior part of the anterior hypothalamic area (POA-AHA), the arcuate nucleus-ventromedial nucleus region (ARC-VMN) and the medial-basal amygdaloid nucleus of the limbic system (AME). A marked increase in plasma levels of prolactin was observed when implants of histamine were in the POA-AHA region. A more consistent increase was found when 1 microgram histamine was injected in the same region; values of prolactin were about 3.6 times greater than in their controls injected with 0.9% saline. Such increased hormone levels lasted up to 2 h. A similar rise in prolactin level was found when the implants of histamine were located in the ARC-VMN region. When compound 48/80 or empty cannulae were placed in those brain regions that were examined, no changes in plasma levels of prolactin were induced. Both histamine and compound 48/80 elicited a delayed and long-lasting decrease of the high plasma level of prolactin present in rats bearing cannulae in the AME region. The results suggest that in the male rat, histaminergic sites, located in rostral and mediobasal hypothalamus and in the central area of the amygdala, are involved in the mechanisms controlling prolactin secretion.

Blockade of the LH surge and ovulation by GABA-T inhibitory drugs that increase brain GABA levels in rats.

The present experiments were designed to evaluate the effects of GABA increase in the brain on the LH surge and ovulation in female rats. GABA-transaminase (GABA-T) inhibitory drugs were administered intraperitoneally in the early afternoon hours on the day before the expected ovulation. Gamma-acetylenic GABA (GAG) prevented the proestrus LH surge and ovulation in freely moving adult female rats. In a similar manner, GAG blunted the enhanced LH release found at 1800 h on the preovulatory day and the subsequent ovulation in PMSG-treated 32-day-old rats. LH secretion and ovulation in these animals was restored by administration of the selective GABA antagonist, bicuculline. The other GABA-T inhibitors, amino-oxyacetic acid and gamma-vinyl GABA, produced similar effects to GAG in the PMSG-treated rats. These results indicate that the increase of brain GABA levels during the preovulatory day alters LH release and prevents ovulation in rats.

Blockage of progesterone-induced release of luteinizing hormone and prolactin by d-amphetamine and fenfluramine in rats.

Subcutaneous administration of d-amphetamine at various doses (1.25, 2.5, and 5 mg/kg) decreased plasma luteinizing-hormone levels in ovariectomized rats primed with estradiol and injected with progesterone. In these animals prolactin levels decreased after injection of 0.6 and 1.25 mg/kg of d-amphetamine. No significant hormone modifications were detected in oavariectomized and ovariectomized estradiol-primed rats after injection of 2.5 mg/kg of d-amphetamine. Fenfluramine at doses of 25 mg/kg induced decreases of plasma LH and prolactin levels in ovariectomized estradiol- and progesterone-treated rats. A low dose of fenfluramine, 2.5 mg/kg, had no effect. It is concluded that d-amphetamine and fenfluramine are able to alter the facilitatory actions of progesterone on luteinizing hormone and prolactin release in ovariectomized estradiol-primed rats.

Effects of a histamine synthesis inhibitor and antihistamines on the sexual behavior of female rats.

Intraventricular administration of alpha-hydrazinohistidine, a histamine synthesis inhibitor, at different doses and times before testing produced a significant decrease of lordotic responses and sexual receptivity in ovariectomized estrogen plus progesterone-primed female rats. The H1-antihistamines pyrilamine and chlorfeniramine and the H2-antihistamine metiamide, injected in the lateral ventricle, significantly decreased the lordosis quotient but did not modify receptivity; antihistamine-injected rats showed no soliciting behavior. Exploratory activity was decreased by both alpha-hydrazinohistidine and metiamide but not by the H1-antihistamines. It is concluded that treatments which either deplete histamine or block their receptors can alter female copulatory responsiveness. The mechanism of this antihistamine effect appears to be unrelated to that of other side effects, such as motor impairment, sedation, or local anesthesia.

Central natriuretic peptides regulation of peripheral atrial natriuretic factor release.

Atrial natriuretic factor (ANF) and C-type natriuretic peptide (CNP) receptors have been described in encephalic areas and nuclei related to the regulation of cardiovascular as well as sodium and water homeostasis. Stimulation of the anterior ventral third ventricular region of the brain modifies plasma ANF concentration, suggesting the participation of the central nervous system in the regulation of circulating ANF. The aim of this work was to study the effect of centrally applied ANF or CNP on plasma ANF. Normal and blood volume expanded rats (0.8 ml isotonic saline/100 g body weight) were intra cerebralventricularly injected with 1, 10 or 100 ng/microl/min ANF. Blood volume expanded animals were also centrally injected with the same doses of CNP. Blood samples were collected at 5 and 15 min. after intracerebralventricular administration of either ANF or CNP. Centrally applied ANF did not affect circulating ANF in normal blood volume rats. In blood volume expanded animals both ANF (1, 10 or 100 ng/microl/min) and CNP (1 ng/microl/min) decreased plasma ANF concentration after 15 min. Moreover, CNP (10 and 100 ng/microl/min) lowered circulating ANF levels not only at 15 min but also at 5 min. Neither ANF nor CNP elicited any change in mean arterial pressure and heart rate in normal and blood volume expanded rats. These results suggest the existence of a central regulation exerted by natriuretic peptides on circulating ANF levels. Furthermore, this is the first study reporting an effect on plasma ANF induced by centrally applied CNP.

NMDA receptor antagonists block stress-induced prolactin release in female rats at estrus.

In order to evaluate the role of glutamate in prolactin secretion, we examined the effects of N-methyl-D,L-aspartic acid (NMDA) receptor antagonists on serum prolactin levels at both resting and restraint-stress conditions in female rats at estrus. NMDA increased basal serum prolactin levels. Administration of the selective NMDA receptor antagonist, cis-4-phosphonomethyl-2-piperidine carboxylic acid (CGS 19755) (5 and 10 mg/kg i.p.), to rats under resting conditions enhanced basal prolactin levels. A low dose of CGS 19755 (3 mg/kg) was unable to modify the hormone serum level. Under stress conditions the pretreatment with CGS 19755 (3 and 5 mg/kg) prevented the increase in serum prolactin levels. This effect was reversed by NMDA (60 mg/kg s.c.). The NMDA receptor antagonist (5 mg/kg) decreased the median eminence concentration of the dopamine metabolite, 3,4-dihydroxyphenylacetic acid (DOPAC), without modifying dopamine content. To examine the probable link between serotonin (5-HT) and glutamate in prolactin release, the 5-HT2A/5-HT2C receptor antagonist, ritanserin, was used. Under resting conditions, a dose of 5 mg/kg s.c. blocked the NMDA-induced prolactin release. In rats submitted to restraint, ritanserin decreased the prolactin response and NMDA was unable to correct the stress serum prolactin levels. The 5-HT1A receptor agonist, 8-hidroxypropyl-amino tetralin (8-OH-DPAT) (3 mg/kg s.c.), increased basal serum prolactin levels and restored serum prolactin in stressed animals pretreated with CGS 19755 (5 mg/kg). The present data strongly suggest that the glutamatergic system participates in the regulation of prolactin secretion. A stimulation tone seems to be exerted via the tuberoinfundibular dopaminergic system, and the prolactin release evoked by restraint apparently involves glutamate/NMDA receptors linked to a serotoninergic pathway.