Immune dysregulation and pathophysiology of alcohol consumption and alcoholic liver disease.

Alcoholic liver disease (ALD) is a clinical-pathologic entity caused by the chronic excessive consumption of alcohol. The disease includes a broad spectrum of anomalies at the cellular and tissual level that can cause acute-on-chronic (alcoholic hepatitis) or chronic (fibrosis, cirrhosis, hepatocellular cancer) injury, having a great impact on morbidity and mortality worldwide. Alcohol is metabolized mainly in the liver. During alcohol metabolism, toxic metabolites, such as acetaldehyde and oxygen reactive species, are produced. At the intestinal level, alcohol consumption can cause dysbiosis and alter intestinal permeability, promoting the translocation of bacterial products and causing the production of inflammatory cytokines in the liver, perpetuating local inflammation during the progression of ALD. Different study groups have reported systemic inflammatory response disturbances, but reports containing a compendium of the cytokines and cells involved in the pathophysiology of the disease, from the early stages, are difficult to find. In the present review article, the role of the inflammatory mediators involved in ALD progression are described, from risky patterns of alcohol consumption to advanced stages of the disease, with the aim of understanding the involvement of immune dysregulation in the pathophysiology of ALD.

Maternal and postnatal high-fat diets with high ω6 : ω3 ratios affect the reproductive performance of male offspring in the mouse.

High-fat diets (HFDs) are an acknowledged risk factor for male subfertility, but the underlying mechanisms remain unclear. In the present study we compared the effects of two HFDs with different ω6:ω3 ratios, one enriched with soy oil (SOD; ω6:ω3=9.62) and another enriched with sunflower oil (SFOD; ω6:ω3=51.55), with those of a commercial diet (CD; ω6:ω3=19.87), supplied from pregnancy to adulthood, on morphometric parameters and reproductive performance in adult male mice (recommended ω6:ω3 for rodents=1-6). Bodyweight was significantly higher in the SFOD than CD group, and relative testicular weight was significantly lower in the SFOD than the other two groups. SFOD altered sperm performance: it reduced sperm viability (mean±s.e.m.; 76.00±1.35% vs 82.50±1.45% and 80.63±1.00% in the SFOD vs CD and SOD groups respectively; P<0.05) and increased the percentage of immature spermatozoa (71.88±7.17% vs 51.38±5.87% and 48.00±5.72% in the SFOD vs CD and SOD groups respectively; P<0.05). The epididymal ω6:ω3 ratio was higher in the SFOD versus CD and SOD groups, whereas the unsaturation index was higher in the SOD and SFOD groups than in CD group. Sperm membrane integrity was diminished in both the SOD and SFOD groups, but there was no difference in sperm reactive oxygen species production in these two groups compared with the CD group. The fertilisation rate was lower in the SFOD compared with the CD and SOD groups. In conclusion, although both HFDs affected sperm quality, the fertilising ability was more altered by the excessive dietary ω6:ω3 ratio than by the net ω6 content.

Dosis altas de corticoides sistémicos en pacientes ingresados por exacerbación de enfermedad pulmonar obstructiva crónica. Un estudio de cohortes / High doses of systemic corticosteroids in patients hospitalised for exacerbation of chronic obstructive pulmonary disease. A cohort study

Objetivos. Evaluar el efecto de las dosis altas de corticoides en pacientes ingresados por exacerbación de una enfermedad pulmonar obstructiva crónica (EPOC). Pacientes y métodos. Estudio de cohortes prospectivo de enfermos hospitalizados con EPOC entre enero y marzo de 2015, agrupados en función de la dosis de glucocorticoides recibida (punto de corte: 40mg de prednisona/día). Se compararon los resultados de estancia hospitalaria, y de reingreso y mortalidad a los 3 meses del alta. Resultados. Se analizaron 87 pacientes. La mediana de la dosis diaria recibida fue de 60mg de prednisona/día (rango intercuartílico: 46,67-82,33mg/día); la vía de administración fue endovenosa en el 96,6% de los casos. Se estableció un riesgo relativo (RR) de estancia superior a 8 días de 1,095 [intervalo de confianza (IC) 95%: 0,597-2,007; p=0,765] cuando se usaban dosis de esteroides superiores a 40mg/día. Además, en estos pacientes la hazard ratio (HR) para el reingreso durante los 3 meses siguientes al alta fue de 0,903 [IC 95%: 0,392-2,082; p=0,811] y la mortalidad de 1,832 (IC 95%: 0,229-16,645; p=0,568]. Ni el RR ni las HR observadas variaron de forma estadísticamente significativa tras el ajuste por factores de confusión. Conclusiones. Una dosis superior a 40mg diarios de prednisona en pacientes ingresados por exacerbación de EPOC no se asocia a una menor estancia hospitalaria ni a una disminución del reingreso y de la mortalidad a los 3 meses (AU)

Objectives. To assess the effect of high doses of corticosteroids in patients hospitalised for exacerbation of chronic obstructive pulmonary disease (COPD). Patients and methods. A prospective cohort study was conducted on patients hospitalized with COPD between January and March 2015, grouped according to the glucocorticoid dosage administered (cutoff, 40mg of prednisone/day). We compared the results of hospital stay, readmission and mortality at 3 months of discharge. Results. We analysed 87 patients. The median daily dose was 60mg of prednisone (interquartile range, 46.67-82.33mg/day), and the administration route was intravenous in 96.6% of the cases. We established a relative risk (RR) for hospital stays longer than 8 days of 1.095 (95% CI 0.597-2.007; P=.765) when steroid dosages greater than 40mg/day were employed. In these patients, the hazard ratio (HR) for readmission in the 3 months after discharge was 0.903 (95% CI 0.392-2.082; P=.811), and the mortality was 1.832 (95% CI 0.229-16.645; P=.568). Neither the RR nor the HR varied in a statistically significant manner after adjusting for confounding factors. Conclusions. A daily dose greater than 40mg of prednisone in patients hospitalised for COPD exacerbation was not associated with a shorter hospital stay or a reduction in readmissions or mortality at 3 months (AU)

High doses of systemic corticosteroids in patients hospitalised for exacerbation of chronic obstructive pulmonary disease. A cohort study. / Dosis altas de corticoides sistémicos en pacientes ingresados por exacerbación de enfermedad pulmonar obstructiva crónica. Un estudio de cohortes.

OBJECTIVES: To assess the effect of high doses of corticosteroids in patients hospitalised for exacerbation of chronic obstructive pulmonary disease (COPD). PATIENTS AND METHODS: A prospective cohort study was conducted on patients hospitalized with COPD between January and March 2015, grouped according to the glucocorticoid dosage administered (cutoff, 40mg of prednisone/day). We compared the results of hospital stay, readmission and mortality at 3 months of discharge. RESULTS: We analysed 87 patients. The median daily dose was 60mg of prednisone (interquartile range, 46.67-82.33mg/day), and the administration route was intravenous in 96.6% of the cases. We established a relative risk (RR) for hospital stays longer than 8 days of 1.095 (95% CI 0.597-2.007; P=.765) when steroid dosages greater than 40mg/day were employed. In these patients, the hazard ratio (HR) for readmission in the 3 months after discharge was 0.903 (95% CI 0.392-2.082; P=.811), and the mortality was 1.832 (95% CI 0.229-16.645; P=.568). Neither the RR nor the HR varied in a statistically significant manner after adjusting for confounding factors. CONCLUSIONS: A daily dose greater than 40mg of prednisone in patients hospitalised for COPD exacerbation was not associated with a shorter hospital stay or a reduction in readmissions or mortality at 3 months.

Local-stability analysis of a low-dissipation heat engine working at maximum power output.

In this paper we address the stability of a low-dissipation (LD) heat engine (HE) under maximum power conditions. The LD system dynamics are analyzed in terms of the contact times between the engine and the external heat reservoirs, which determine the amount of heat exchanged by the system. We study two different scenarios that secure the existence of a single stable steady state. In these scenarios, contact times dynamics are governed by restitutive forces that are linear functions of either the heat amounts exchanged per cycle, or the corresponding heat fluxes. In the first case, according to our results, preferably locating the system irreversibility sources at the hot-reservoir coupling improves the system stability and increases its efficiency. On the other hand, reducing the thermal gradient increases the system efficiency but deteriorates its stability properties, because the restitutive forces are smaller. Additionally, it is possible to compare the relaxation times with the total cycle time and obtain some constraints upon the system dynamics. In the second case, where the restitutive forces are assumed to be linear functions of the heat fluxes, we find that although the partial contact time presents a locally stable stationary value, the total cycle time does not; instead, there exists an infinite collection of steady values located in the neighborhood of the fixed point, along a one-dimensional manifold. Finally, the role of dissipation asymmetries on the efficiency, the stability, and the ratio of the total cycle time to the relaxation time is emphasized.

Malaria en Chile: importancia de diagnóstico oportuno a propósito de un caso / Malaria in Chile: Timely diagnosis importance of a case

La Malaria es una parasitosis producida por un protozoo del género Plasmodium, trasmitida por el mosquito Anopheles, existiendo 4 especies capaces de infectar a humanos. El P.falciparum es el agente causal más prevalente, presentando alta resistencia a antimaláricos y mayor probabilidad de complicación y muerte que las otras especies. Se presenta el caso de un paciente proveniente de Nigeria que consulta por fiebre, escalofríos, astenia, adinamia, anorexia, cefalea, trombocitopenia y leucopenia, que posteriormente evoluciona con diarrea y oliguria. Dado el cuadro clínico y el antecedente de residencia en Nigeria, país edénico de Malaria, se hicieron los estudios pertinentes, donde se confirmó la presencia de P.falciparum en el frotis (+++). Por el alto riesgo de complicaciones relacionadas a esta especie, tales como falla renal, anemia severa, hemorragia severa, convulsiones, shock y muerte; se hospitaliza en Cuidados Intermedios, donde evoluciona con deterioro de la función renal, disminución del hematocrito y del recuento plaquetario fuera de rango de severidad, con ictericia y hiperparasitemia en rango de severidad. Se manejo con Mefloquina, Malarone y medidas de soporte vital, logrando rápidamente mejoría clínica y de laboratorio, con disminución de carga parasitaria. Finalmente es dado de alta con tratamiento completo y sin complicaciones. Chile es un país libre de Malaria, pero por la globalización actual es importante considerar esta enfermedad en el diagnóstico diferencial de cualquier cuadro de fiebre inexplicada en pacientes que han estado en países endémicos, determinando de manera oportuna el diagnóstico e iniciar tratamiento precoz para evitar complicaciones potencialmente mortales.

Malaria is a parasitosis produced by a protozoa of the plasmodium gendre , transmited by the anopheles mosquito existing four species capable of infecting humans. The p. Falciparum is the most prevalent causal agent, presenting a high resistance to antimalaric treatment and mayor probability of complications and death than other species. We present a case of a patient provienent from Nigeria that consults with fever , chills , asthenia, adinamia, anorexia, headache, thrombocytopenia, leucopenia that later develops diarrhoea and oliguria. Given the clinical presentation and the history of residence in Nigeria, endemic country of Malaria, pertinent tests were performed confirming the presence of p. Falciporum in the smear (+++). Because of the high risk of complications related to this specie such as renal faliure, severe anemia, severe bleeding, seizures, shock and death the patient was hospitalized in intermediate care unit were he evolves with impairment of the renal function , the hematocrit and the platelet count out of the severity range , with jaundice and hiperparasitemia in severe range. He was treated with mefluoquina , malarone and vital care support quickly achieving clinical and laboratory improvement and lowering the parasite load. Finally he is discharged with a completed treatment and no complications. Chile is a malaria free country but with actual world globalization it is important to consider this desease in the differential diagnosis in any case of unexplained fever in patients that have been in endemic countries determining in an opportune way the diagnosis and giving a rapid treatment in order to prevent the potencially mortal complications.

Pancreatitis aguda grave por hipertrigliceridemia: Reporte de un caso / Acute severe pancreatitis induced by Hypertriglyceridemia: Case report

La hipertrigliceridemia es la causa del 1-4 % de las Pancreatitis Agudas (PA).Clínicamente se presenta en forma similar a otras etiologías de PA, pero suelen tener una evolución más tórpida.Varios estudios han planteado que esto se debe a la lipotoxicidad producida tras la hidrólisis de los triglicéridos (TG) en el tejido pancreático. Suele presentarse con niveles de TG por sobre los 1000 mg/dL, aumentando el riesgo a medida que se incrementan. Trastornos en el metabolismo de las lipoproteínas pueden desencadenar cuadros de PA graves. Estos desórdenes se clasifican en trastornos primarios (defectos genéticos) y secundarios a otras causas,dentro de las que se encuentran: presencia de patologías subyacentes (obesidad, diabetes), secundarias al uso de fármacos (tratamientos hormonales) o alteraciones de condiciones fisiológicas (embarazo); todas estas condiciones favorecenla acumulación de TG en la circulación periférica. Para el tratamiento de las hipertrigliceridemias severas, se recomienda el uso de bombas de insulina y aféresis, con el objetivo de disminuir los valores de TG en forma precoz, lo que mejora los resultados y aumenta la sobrevida. En este contexto, se presenta el caso de una mujer de 22 años que desarrolla una PA grave por hipertrigliceridemia de más de 4000 mg/dL.

Hypertriglyceridemia is the etiology of 1-4% of Acute Pancreatitis (PA). The clinical presentation is similar to other causes of PA, but often has worst outcomes.Several studies have suggested that this is due to the lipotoxicity produced after hydrolysis of triglycerides (TG) in pancreatic tissue. It often is presented with TG levels above 1000 mg/dL, increasing the risk while it gets higher. Abnormality of lipoprotein metabolism can trigger severe cases of PA. These disorders are conventionally classified into primary disorders (genetic defects) and secondary to other causes, in which we can find: underlying pathologies, (obesity, diabetes), secondary to drug use (hormonal treatment) or disruption of physiological conditions (pregnancy). All these conditions favor accumulation of TG in peripheral circulation. For the treatment of severe hypertrigliridemia, the use of insulin bombs and aphaeresis is recommended, in order to reduce levels of TG precociously, which produces better results and enhances survival. It is in this context, that a case of a woman of 22 years old that develops severe PA with hypertriglyderidemia over 4000 mg/dl is presented.

New hosts for the mite Ornithonyssus bursa in Argentina.

The mite Ornithonyssus bursa (Berlese) (Mesostigmata: Macronyssidae) is considered a poultry pest causing important infestations in chickens and it is considered a potential vector of arbovirus. Despite being considered a common parasite in wild birds, there is scarce published information about its potential hosts and effects on them. Here we present new bird hosts for O. bursa, assess the presence of Alphavirus, Flavivirus and Bunyavirus in mites from three host species, and discuss its potential impact on wild bird populations. We found O. bursa infecting five raptor and six passerine wild bird species. For nine of these species, this is the first record of infection by O. bursa. Although all analysed mites were negative for the examined arboviruses, the small sample size of mites does not allow further conclusions at the present moment. Because of the general nature of this ectoparasite, its presence in migratory long dispersal and endangered bird species, and the seropositivity for arboviruses in some of the species studied here, we consider it critical to assess the role of O. bursa and other ectoparasites as vectors and reservoirs of pathogens and as potential deleterious agents in wild bird populations.

Aspirin inhibits expression of sFLT1 from human cytotrophoblasts induced by hypoxia, via cyclo-oxygenase 1.

INTRODUCTION: Elevated circulating soluble FLT1 (sFLT1) levels seen in preeclampsia may play a role in its development. Aspirin is recommended for prevention of preeclampsia. We hypothesized that aspirin may inhibit the production of sFlt1. METHODS: Placentas from women with and without preeclampsia were collected. Primary cytotrophoblasts (CTBs) were cultured from normal placentas and treated with aspirin, sc-560, a COX1 inhibitor or celecoxib, a COX2 inhibitor. The expression of sFLT1, FLT1, COX1 and COX2 was studied. The effect of aspirin on sFlt1 expression was also studied in HEK293 cells and in HTR-8/SVNeo cells. RESULTS: The expression of sFLT1 was increased in preeclamptic placentas compared to control placentas and the expression and release of sFLT1 increased in CTBs exposed to 2% O2 compared to controls. Aspirin at 3 and 12 mM concentration reduced the expression and release of sFLT1 in CTBs. Aspirin also inhibited sFlt1 expression from HTR-8/SVNeo and HEK293 cells. Sc-560, but not celecoxib, reduced sFLT1 expression and release from CTBs. Aspirin and sc-560 also reduced hypoxia-induced FLT1 mRNA expression and inhibited COX1 mRNA in CTBs. DISCUSSION: This study confirms that sFLT1 expression is increased in preeclamptic placentas and in CTBs exposed to hypoxia. Aspirin inhibits the production sFLT1 in CTBs and in HTR-8/SVNeo. Sc-560 recapitulated the effects of aspirin on sFLT1 expression and release in CTBs suggesting that the aspirin effect may be mediated via inhibition of COX1. The study increases our understanding of the mechanisms regulating sFlt1 expression and provides a plausible explanation for the effect of aspirin to prevent preeclampsia.

Afectación vascular del sistema nervioso central en la arteritis de células gigantes: una forma de presentación infrecuente / Vascular involvement of the central nervous system in giant cell arteritis: an unusual form of presentation

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Mouse plasma progesterone levels are affected by different dietary ω6/ω3 ratios.

An imbalance in the dietary polyunsaturated fatty acids (PUFAs) ω6/ω3 ratio, could influence negatively the reproductive performance. The aim of the study was to assess the effects of chronic administration of diets enriched with soybean or sunflower oils with different ω6/ω3 ratios on the reproductive parameters of adult female mice. Mice were fed different diets for 90 days: a commercial diet (CD), a 5 or 10% soy oil-enriched diet (SOD5 and SOD10, respectively), and a 5 or 10% sunflower oil-enriched diet (SFOD5 and SFOD10, respectively). The parameters evaluated were: body weight and food intake, estrous cycle, plasma progesterone concentration, ovulation rate, and oocyte quality. Progesterone concentrations (ng/ml) were significantly higher in the SFOD10: 14.9±2.8 vs CD: 5.4±1.2; SOD5: 5.6±1.1 and SFOD5: 4.6±1.4. Additional parameters evaluated were not affected. However, metestrous and luteal phases were shorter in subjects receiving SOD and longer in those under SFOD diets. In SFOD, there was a trend towards a smaller number of recruited oocytes compared to CD and SOD and a higher percentage of cleaved oocytes were quantified in SOD diets. A 3-month supply of a diet with elevated LA ω6/ALA ω3 ratio to adult female mice affects their reproductive physiology, modifying progesterone production, ovulation rate, and/or oocyte quality. Although some differences in the response to diets have been observed in several mammalian species, the present findings must be taken into consideration when a diet for optimizing reproductive capability is indicated.

Understanding the relationship between Mycobacterium bovis spoligotypes from cattle in Latin American countries.

Spoligotyping is the most frequently used method for genotyping isolates of Mycobacterium bovis worldwide. In the current work, we compared spoligotypes from 1684 M. bovis isolates from Argentina (816), Brazil (412), Chile (66), Mexico (274) and Venezuela (116), obtained from cattle, humans, pigs, wild boars, farmed deer, goats, buffaloes, cats, and wild animals. A total of 269 different spoligotypes were found: 142 (8.4%) isolates presented orphan spoligotypes, whereas 1542 (91.6%) formed 113 different clusters. In cattle, SB0140 was the most representative spoligotype with 355 (24.6%) isolates, followed by SB0121 with 149 (10.3%) isolates. Clustering of spoligotypes ranged from 95.2% in Argentina to 85.3% in Mexico. Orphan spoligotypes were also variable, ranging from 23.7% in Mexico to 4.1% in Brazil. A large proportion of spoligotypes were common to the neighboring countries Argentina, Brazil and Chile. In conclusion, despite the diversity of spoligotypes found in the five countries studied, there are major patterns that predominate in these neighboring countries. These clusters may reflect a long-lasting active transmission of bovine tuberculosis or common historical origins of infection.

Rectal hyposensitivity for non-noxious stimuli, postprandial hypersensitivity and its correlation with symptoms in complete spinal cord injury with neurogenic bowel dysfunction.

STUDY DESIGN: Prospective clinical study. OBJECTIVES: To assess fasting and postprandial (PP) perception of rectal distension and its correlation with symptoms in patients with spinal cord injury (SCI) and neurogenic bowel dysfunction compared to ten healthy subjects (HS). SETTING: Experimental Medicine and Motility Unit, Mexico General Hospital and National Institute of Rehabilitation. METHODS: Twenty patients with complete SCI at cervical, thoracic and lumbar levels [American Spinal Injury Association (ASIA) A] were studied. Rectal sensitivity was evaluated with a barostat. RESULTS: In SCI patients, while lower the rectal tone more time was used for defecate (R=0.50, P=0.048) and more PP episodes of fecal incontinence occur (R=0.54, P=0.030). The thresholds for non-noxious stimuli of first (23.6 mmHg, CI 19.5-27.7) vs 14.0 (CI 10.9-17.1), P=0.004; gas (27.9 mmHg, CI 19.9-35.8) vs 17.9 mmHg (CI 14.25-21.69), P=0.02 and urge-to-defecate sensation (33.2 mmHg, CI 27.5-38.8) vs 22.4 mmHg (CI 17.9-26.9), P=0.01 were reported by SCI patients at higher pressure than HS, respectively. SCI patients reported PP pain sensation at a lower pressure than controls (27.8 mmHg, CI 21.5-34.2 vs 36.5 mmHg, CI 31.8-41.2), P=0.04. CONCLUSION: SCI patients preserve rectal sensation, present rectal hyposensitivity for non-noxious stimuli and PP hypersensitivity. Lower rectal tone was related to the time used for defecate and with fecal incontinence. The results suggest that an intact neural transmission between the spinal cord and higher centres is indispensable for noxious stimulus, but not for non-noxious stimuli. Also, barostat sensitivity studies can complement ASIA criteria to verify a complete injury.

Reproductive performance and fertility in male and female adult mice chronically treated with hexarelin.

Hexarelin (HEXr), a synthetic ghrelin analogue, has been associated with modifications of reproductive physiology. In previous studies of adult mice, we detected that HEXr induced significantly reduced ovulation rate and significant correlation coefficients between sexual maturation and corporal weight in offspring. In this study, we investigated the effects of chronic HEXr administration on sperm concentration and functional activity, oestrous cyclicity and pregnancy index, in addition to the number of fetuses and its correlation with the number of corpora lutea. Adult Albino swiss mice were injected (sc) daily with HEXr: 100 µgkg(-1) day(-1) (HEXr D1) or 200 µgkg(-1) day(-1) (HEXr D2) for 53 days in males and 30 days in females. We detected a significantly decreased ratio in the number of fetuses per corpora lutea in females treated with HEXr D2 for 30 days before mating and during the first 6 days of pregnancy, in addition to a downward trend in the pregnancy index and percentage of females impregnated by each male treated with both doses of the analogue. Although we did not find any significant effect on additional parameters evaluated in both genders, we propose certain effects of HEXr on the implantation process and/or early development of embryos and over the in vivo reproductive capability of males.

Flagellar motility of Trypanosoma cruzi epimastigotes.

The hemoflagellate Trypanosoma cruzi is the causative agent of American trypanosomiasis. Despite the importance of motility in the parasite life cycle, little is known about T. cruzi motility, and there is no quantitative description of its flagellar beating. Using video microscopy and quantitative vectorial analysis of epimastigote trajectories, we find a forward parasite motility defined by tip-to-base symmetrical flagellar beats. This motion is occasionally interrupted by base-to-tip highly asymmetric beats, which represent the ciliary beat of trypanosomatid flagella. The switch between flagellar and ciliary beating facilitates the parasite's reorientation, which produces a large variability of movement and trajectories that results in different distance ranges traveled by the cells. An analysis of the distance, speed, and rotational angle indicates that epimastigote movement is not completely random, and the phenomenon is highly dependent on the parasite behavior and is characterized by directed and tumbling parasite motion as well as their combination, resulting in the alternation of rectilinear and intricate motility paths.

Inhibitory effects of ghrelin on sexual behavior: role of the peptide in the receptivity reduction induced by food restriction in mice.

Ghrelin (Ghr) is a gut/hypothalamus peptide with inhibitory actions on reproductive physiology; however, there are no previous reports of its role on estrous behavior. Under the hypothesis that the increase of plasma Ghr during food restriction (FR) is responsible for receptivity reduction, we intended to evaluate the receptivity percentage of female mice subjected to: exp. 1) acute and chronic FR and Ghr administration (3 nmol/animal/day, s. c.) and exp. 2) the co-administration of a ghrelin antagonist [ant=(d-Lys3)-GHRP-6; 6 nmol/animal/day s. c.]. All females were ovariectomized, primed with steroids, trained, and randomly subjected every week to each one of several protocols, followed by a behavioral test. Experiment 1 (n=8): basal, no treatment; acute FR (aFR), 24-h fasting; chronic FR (cFR), 50% FR for 5 days; acute ghrelin (aGhr), Ghr 30 min before test and chronic ghrelin (cGhr), Ghr for 5 days. Except for cGhr, all treatments significantly decreased the percentage of receptivity (mean±SEM): basal 61.9±6.0, aFR 33.1±8.1, cFR 18.8±7.7, aGhr 45.6±10.6, p<0.05 vs. basal. In exp. 2 (n=11), except for cFR+ant (55.0±6.4) the co-administration of the antagonist reversed the deleterious effects detected in exp. 1: basal 70.9±5.4; aFR+ant 72.3±7.6; aGhr+ant 73.6±4.7. As expected, the administration of vehicle or antagonist alone did not modify receptivity. Besides, we found a significant correlation between percentage of body weight loss and percentage of receptivity reduction (r=0.62, p=0.0004). This is the first study demonstrating that ghrelin is able to inhibit female mice sexual behavior and that is involved, at least in part, in receptivity reduction after food scarcity.

Numerical solution of the chemical master equation uniqueness and stability of the stationary distribution for chemical networks, and mRNA bursting in a gene network with negative feedback regulation.

In this work, we introduce a couple of algorithms to compute the stationary probability distribution for the chemical master equation (CME) of arbitrary chemical networks. We further find the conditions guaranteeing the algorithms' convergence and the unity and stability of the stationary distribution. Next, we employ these algorithms to study the mRNA and protein probability distributions in a gene regulatory network subject to negative feedback regulation. In particular, we analyze the influence of the promoter activation/deactivation speed on the shape of such distributions. We find that a reduction of the promoter activation/deactivation speed modifies the shape of those distributions in a way consistent with the phenomenon known as mRNA (or transcription) bursting.