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Simple Summary Lobesia botrana, also known as the European grapevine moth, is one of the main pests that affect grapes. In Chile, this type of moth is classified as a quarantine pest, which requires fumigating the fruit with methyl bromide to prevent the immature stages of the pest from being strained and reaching the export-destination countries. In the fields, the larvae of this moth feed on grapes, which can introduce diseases such as Botrytis cinerea, thereby increasing the costs of managing the crop. One way to control this pest is to use entomopathogenic fungi on the winter pupae to reduce moth populations in the spring. In the present study, six fungi were characterized, formulated, and evaluated. The selected strains RGM 2184 and RGM 678 were evaluated in two regions of Chile during two seasons. These strains reached maximum efficiencies of 80% and 88%, respectively. Therefore, the use of entomopathogenic fungi is an environmentally friendly alternative to control L. botrana and reduce the use of chemical pesticides. Abstract Lobesia botrana (Denis and Shiffermüller) (Lepidoptera: Tortricidae) is one of the main pests that affect the production and export of table grapes in Chile. Because this pest has quarantine status, the fruit must be fumigated with methyl bromide, which reduces the fruit’s export competitiveness in the destination market. In the present study, to help resolve this issue, six native entomopathogenic fungi were identified through multilocus analysis, including three Beauveria pseudobassiana and three Metarhizium robertsii. These fungi were evaluated in the laboratory to control L. botrana in its pupal stage in a silk cocoon and compared against a biological control product. Formulations with additional carbon sources improved the performance of the fungi. The treatments with outstanding performance contained the fungal strains B. pseudobassiana RGM 2184 and M. robertsii RGM 678. These strains were evaluated in the field during the winter season in two different regions of the country; the strains reached maximum efficacies of 80% and 88%, respectively, at 21 days post first application. Therefore, entomopathogenic fungi can contribute to reducing pupal populations in winter, thereby decreasing the moth population in spring–summer.

BACKGROUND: Perturbations in the timing of puberty, with potential adverse consequences in later health, are increasingly common. The underlying neurohormonal mechanisms are unfolded, but nutritional alterations are key contributors. Efforts to unveil the basis of normal puberty and its metabolic control have focused on mechanisms controlling expression of Kiss1, the gene encoding the puberty-activating neuropeptide, kisspeptin. However, other regulatory phenomena remain ill-defined. Here, we address the putative role of the G protein-coupled-receptor kinase-2, GRK2, in GnRH neurons, as modulator of pubertal timing via repression of the actions of kisspeptin, in normal maturation and conditions of nutritional deficiency. METHODS: Hypothalamic RNA and protein expression analyses were conducted in maturing female rats. Pharmacological studies involved central administration of GRK2 inhibitor, βARK1-I, and assessment of gonadotropin responses to kisspeptin or phenotypic and hormonal markers of puberty, under normal nutrition or early subnutrition in female rats. In addition, a mouse line with selective ablation of GRK2 in GnRH neurons, aka G-GRKO, was generated, in which hormonal responses to kisspeptin and puberty onset were monitored, in normal conditions and after nutritional deprivation. RESULTS: Hypothalamic GRK2 expression increased along postnatal maturation in female rats, especially in the preoptic area, where most GnRH neurons reside, but decreased during the juvenile-to-pubertal transition. Blockade of GRK2 activity enhanced Ca(+2) responses to kisspeptin in vitro, while central inhibition of GRK2 in vivo augmented gonadotropin responses to kisspeptin and advanced puberty onset. Postnatal undernutrition increased hypothalamic GRK2 expression and delayed puberty onset, the latter being partially reversed by central GRK2 inhibition. Conditional ablation of GRK2 in GnRH neurons enhanced gonadotropin responses to kisspeptin, accelerated puberty onset, and increased LH pulse frequency, while partially prevented the negative impact of subnutrition on pubertal timing and LH pulsatility in mice. CONCLUSIONS: Our data disclose a novel pathway whereby GRK2 negatively regulates kisspeptin actions in GnRH neurons, as major regulatory mechanism for tuning pubertal timing in nutritionally-compromised conditions.

El presente proyecto ha consistido en la implantación de un sistema de gamificación de preguntas y respuestas en clase con el objetivo de mejorar la motivación y el compromiso de los alumnos con el aprendizaje en las asignaturas del área de Fisiología: Fisiología General (Grado de Medicina, 180 alumnos), Fisiología (Grado de Enfermería: 170 alumnos) y Fisiología Especial (Grado de Fisioterapia: 70 alumnos). Como sistema de gamificación se empleó la aplicación web Kahoot!, que permite registrar en tiempo real, mediante el uso de dispositivos remotos individuales (p.ej. teléfonos móviles), la participación de los estudiantes en las diferentes tareas propuestas (p.ej. preguntas tipo test, evaluaciones). Los datos registrados nos permiten concluir que los alumnos han conseguido un grado de motivación significativamente superior al observado en cursos anteriores, en los que este sistema aún no se había implantado. Además, consideramos que dicha motivación viene dada por el papel protagonista que han adquirido los estudiantes tras la implantación de este nuevo sistema. En resumen, estos resultados sugieren que la gamificación es una herramienta muy útil para estimular la motivación de los estudiantes y abre la posibilidad de su implantación en otros contextos educativos, especialmente en aquellos en los que los estudiantes no se sientan motivados.

Tubul-Raqui, in the Lafkenche territory of Arauco, southern Chile, is a wetland for conservation scientists and state officials, but a bude for Lafkenche people. Wetland and bude sometimes coincide, but they are also radically divergent. This paper, a collaboration between two scholars and a Lafkenche longko, is about the existential and political consequences of this disjuncture for Lafkenche life projects and struggles for self-determination. By chronicling two recent events in Tubul-Raqui – the implementation of a sustainable plan for wetland conservation and the 2010 tsunami – we argue that liberal conservation programs under the rubric of “sustainability,” or what we call convivial conservation, only reinforce Indigenous disspossesion and extenuates Lafkenche lives. We show, as well, that the decolonization of conservation entails accounting for the plural meanings, practices, and temporalities of extinction – since death in Tubul-Raqui was not brought by the tsunami but by the extreme latency of extractivism, or what we call extractivist endings. We conclude by reflecting on the political trap faced by Lafkenche communities in Tubul-Raqui – the impossibilty to save the bude without converting it into a wetland – and to what extent this situation demands for a mode of politics that inhabits at the intersection between the plausible and the unconceivable – or what we call an unthinkable politics.

Background RF-amide-related peptide-3 (RFRP-3), the mammalian ortholog of gonadotropin-inhibiting hormone, operates as inhibitory signal for the reproductive axis. Recently, RFRP-3 has been also suggested to stimulate feeding, and therefore might contribute to the control of body weight and its alterations. Yet, characterization of the metabolic actions of RFRP-3 has been so far superficial and mostly pharmacological. Here, we aim to investigate the physiological roles of RFRP-3 signaling in the control of feeding and metabolic homeostasis using a novel mouse model of genetic ablation of its canonical receptor, NPFF1R. Methods Food intake, body weight gain and composition, and key metabolic parameters, including glucose tolerance and insulin sensitivity, were monitored in mice with constitutive inactivation of NPFF1R. Results Congenital elimination of NPFF1R in male mice resulted in changes in feeding patterns, with a decrease in spontaneous food intake and altered responses to leptin and ghrelin: leptin-induced feeding suppression was exaggerated in NPFF1R null mice, whereas orexigenic responses to ghrelin were partially blunted. Concordant with this pro-anorectic phenotype, hypothalamic expression of Pomc was increased in NPFF1R null mice. In contrast, spontaneous feeding and neuropeptide expression remained unaltered in NPFF1R KO female mice. Despite propensity for reduced feeding, ablation of NPFF1R signaling in male mice did not cause overt alterations in body weight (BW) gain or composition, neither it affected BW responses to high fat diet (HFD), total energy expenditure or RQ ratios. Yet, NPFF1R KO males showed a decrease in locomotor activity. Conversely, NPFF1R null female mice tended to be heavier and displayed exaggerated BW increases in response to obesogenic insults, such as HFD or ovariectomy. These were associated to increased fat mass, decreased total energy expenditure in HFD, and unaltered RQ ratios or spontaneous locomotor activity. Finally, lack of NPFF1R signaling worsened the metabolic impact of HFD on glycemic homeostasis in males, as revealed by impaired glucose tolerance and insulin sensitivity, while female mice remained unaffected. Conclusion Our data support a discernible orexigenic role of NPFF1R signaling selectively in males, which might modulate the effects of leptin and ghrelin on food intake. In addition, our study is the first to disclose the sex-biased, deleterious impact of the lack of NPFF1R signaling on body weight and fat composition, energy expenditure, locomotor activity and glucose balance, which exaggerates some of the metabolic consequences of concurrent obesogenic insults, such as HFD, in a sexually dimorphic manner. Summary of Translational Relevance Our data are the first to document the nature and magnitude of the regulatory actions of RFRP-3/NPFF1R signaling in the control of feeding and metabolic homeostasis in a physiological setting. Our results not only suggest an orexigenic action of endogenous RFRP-3, specifically in males, but reveal also the detrimental impact of ablation of NPFF1R signaling on body composition, energy expenditure, locomotor activity or glucose balance, especially when concurrent with other obesogenic insults, as HFD, thereby providing the first evidence for additional metabolic effects of RFRP-3, other that the mere control of feeding. Interestingly, alterations of such key metabolic parameters occurred in a sex-biased manner, with males being more sensitive to deregulation of locomotor activity and glycemic control, while females displayed clearer obesogenic responses and deregulated energy expenditure. While our study cannot discard the possibility of RFRP-3 actions via alternative pathways, such as NPFF2R, our data pave the way for future analyses addressing the eventual contribution of altered RFRP-3/NPFF1R signaling in the development of metabolic alterations (including obesity and its comorbidities), especially in conditions associated to reproductive dysfunction.

Background: Kisspeptins, encoded by Kiss1, have emerged as essential regulators of puberty and reproduction by primarily acting on GnRH neurons, via their canonical receptor, Gpr54. Mounting, as yet fragmentary, evidence strongly suggests that kisspeptin signaling may also participate in the control of key aspects of body energy and metabolic homeostasis. However, characterization of such metabolic dimension of kisspeptins remains uncomplete, without an unambiguous discrimination between the primary metabolic actions of kisspeptins vs. those derived from their ability to stimulate the secretion of gonadal hormones, which have distinct metabolic actions on their own. In this work, we aimed to tease apart primary vs. secondary effects of kisspeptins in the control of key aspects of metabolic homeostasis using genetic models of impaired kisspeptin signaling and/or gonadal hormone status. Methods: Body weight (BW) gain and composition, food intake and key metabolic parameters, including glucose tolerance, were comparatively analyzed, in lean and obesogenic conditions, in mice lacking kisspeptin signaling due to global inactivation of Gpr54 (displaying profound hypogonadism; Gpr54−/−) vs. Gpr54 null mice with selective re-introduction of Gpr54 expression only in GnRH cells (Gpr54−/−Tg), where kisspeptin signaling elsewhere than in GnRH neurons is ablated but gonadal function is preserved. Results: In male mice, global elimination of kisspeptin signaling resulted in decreased BW, feeding suppression and increased adiposity, without overt changes in glucose tolerance, whereas Gpr54−/− female mice displayed enhanced BW gain at adulthood, increased adiposity and perturbed glucose tolerance, despite reduced food intake. Gpr54−/−Tg rescued mice showed altered postnatal BW gain in males and mildly perturbed glucose tolerance in females, with intermediate phenotypes between control and global KO animals. Yet, body composition and leptin levels were similar to controls in gonadal-rescued mice. Exposure to obesogenic insults, such as high fat diet (HFD), resulted in exaggerated BW gain and adiposity in global Gpr54−/− mice of both sexes, and worsening of glucose tolerance, especially in females. Yet, while rescued Gpr54−/−Tg males displayed intermediate BW gain and feeding profiles and impaired glucose tolerance, rescued Gpr54−/−Tg females behaved as controls, except for a modest deterioration of glucose tolerance after ovariectomy. Conclusion: Our data support a global role of kisspeptin signaling in the control of body weight and metabolic homeostasis, with a dominant contribution of gonadal hormone-dependent actions. However, our results document also discernible primary effects of kisspeptin signaling in the regulation of body weight gain, feeding and responses to obesogenic insults, which occur in a sexually-dimorphic manner. Summary of translational relevance: Kisspeptins, master regulators of reproduction, may also participate in the control of key aspects of body energy and metabolic homeostasis; yet, the nature of such metabolic actions remains debatable, due in part to the fact that kisspeptins modulate gonadal hormones, which have metabolic actions on their own. By comparing the metabolic profiles of two mouse models with genetic inactivation of kisspeptin signaling but different gonadal status (hypogonadal vs. preserved gonadal function), we provide herein a systematic dissection of gonadal-dependent vs. -independent metabolic actions of kisspeptins. Our data support a global role of kisspeptin signaling in the control of body weight and metabolic homeostasis, with a dominant contribution of gonadal hormone-dependent actions. However, our results document also discernible primary effects of kisspeptin signaling in the regulation of body weight gain, feeding and responses to obesogenic insults, which occur in a sexually-dimorphic manner. These data pave the way for future analyses addressing the eventual contribution of altered kisspeptin signaling in the development of metabolic alterations, especially in conditions linked to reproductive dysfunction.

The effect of serotonin (5-HT) on the electrical excitability of GnRH neurons was examined using gramicidin perforated-patch electrophysiology in transgenic GnRH-green fluorescent protein mice. In diestrous female, the predominant effect of 5-HT was inhibition (70%) with 50% of these cells also exhibiting a late-onset excitation. Responses were dose dependent (EC50 = 1.2μM) and persisted in the presence of amino acid receptor antagonists and tetrodotoxin, indicating a predominant postsynaptic action of 5-HT. Studies in neonatal, juvenile, peripubertal, and adult mice revealed that 5-HT exerted less potent responses from GnRH neurons with advancing postnatal age in both sexes. In adult male mice, 5-HT exerted less potent hyperpolarizing responses with more excitations compared with females. In addition, adult proestrous female GnRH neurons exhibited reduced inhibition and a complete absence of biphasic hyperpolarization-excitation responses. Studies using 5-HT receptor antagonists demonstrated that the activation of 5-HT1A receptors mediated the inhibitory responses, whereas the excitation was mediated by the activation of 5-HT2A receptors. The 5-HT-mediated hyperpolarization involved both potassium channels and adenylate cyclase activation, whereas the 5-HT excitation was dependent on protein kinase C. The effects of exogenous 5-HT were replicated using fluoxetine, which enhances endogenous 5-HT levels. These studies demonstrate that 5-HT exerts a biphasic action on most GnRH neurons whereby a fast 5HT1A-mediated inhibition occurs alongside a slow 5-HT2A excitation. The balance of 5-HT-evoked inhibition vs excitation is developmentally regulated, sexually differentiated, and variable across the estrous cycle and may play a role in regulation of hypothalamic-pituitary-gonadal axis throughout postnatal development.

Hypothalamic neuropeptide Y (NPY) and proopiomelanocortin (POMC) neurons act to sense and coordinate the brain's responses to metabolic cues. One neuronal network that is very sensitive to metabolic status is that controlling fertility. In this study, we investigated the impact of neuropeptides released by NPY and POMC neurons on the cellular excitability of GnRH neurons, the final output cells of the brain controlling fertility. The majority (∼70%) of GnRH neurons were activated by α-melanocyte-stimulating hormone, and this resulted from the direct postsynaptic activation of melanocortin receptor 3 and melanocortin receptor 4. A small population of GnRH neurons (∼15%) was excited by cocaine and amphetamine-regulated transcript or inhibited by β-endorphin. Agouti-related peptide, released by NPY neurons, was found to have variable inhibitory (∼10%) and stimulatory (∼25%) effects upon subpopulations of GnRH neurons. A variety of NPY and pancreatic polypeptide analogs was used to examine potential NPY interactions with GnRH neurons. Although porcine NPY (Y1/Y2/Y5 agonist) directly inhibited the firing of approximately 45% of GnRH neurons, [Leu(31),Pro(34)]-NPY (Y1/Y4/Y5 agonist) could excite (56%) or inhibit (19%). Experiments with further agonists indicated that Y1 receptors were responsible for suppressing GnRH neuron activity, whereas postsynaptic Y4 receptors were stimulatory. These results show that the activity of GnRH neurons is regulated in a complex manner by neuropeptides released by POMC and NPY neurons. This provides a direct route through which different metabolic cues can regulate fertility.

Attainment of reproductive capacity at puberty relies on a complex series of maturational events that include sexual differentiation of the brain; a hormonally driven phenomenon that takes place at early stages of development (critical period). Alterations of sex steroid milieu during such critical period disrupt pubertal maturation and gonadotropic function later in life, through mechanisms that remain partially unknown. Kisspeptins, products of the KiSS-1 gene acting via G protein-coupled receptor 54, have recently emerged as essential gatekeepers of puberty onset and reproductive function. By using rat models of neonatal administration of estrogenic compounds, we provide herein compelling evidence for the functional impairment of the hypothalamic KiSS-1 system at the time preceding puberty after early inappropriate exposures during brain sex differentiation. Neonatal injection of estradiol benzoate to male and female rats resulted in a dose-dependent decrease in hypothalamic KiSS-1 mRNA levels at the prepubertal stage, linked to lowering of serum LH concentrations. Yet, despite persistently decreased basal gonadotropin levels in estrogenized animals, intracerebral injection of kisspeptin evoked potent LH and FSH secretory responses, similar in magnitude to those of control animals. Estrogenized rats also showed defective levels of hypothalamic KiSS-1 mRNA and circulating gonadotropins in response to gonadectomy, whereas exogenous kisspeptin was capable to enhance further LH and FSH secretion in this model. Finally, protocols of neonatal exposure to high doses of an environmentally relevant estrogen, bisphenol-A, mimicked the effects of estradiol benzoate in terms of hypothalamic expression of KiSS-1 gene at the prepubertal period. Altogether, our data document the sensitivity of the hypothalamic KiSS-1 system to alterations in sex steroid milieu during critical periods of brain sex differentiation, and suggest that lowering of endogenous kisspeptin tone induced by early exposures to xeno-estrogens might be mechanistically relevant for disruption of gonadotropin secretion and puberty onset later in life.

It is well established that pubertal activation of the reproductive axis and maintenance of fertility are critically dependent on the magnitude of body energy reserves and the metabolic state of the organism. Hence, conditions of impaired energy homeostasis often result in deregulation of puberty and reproduction, whereas gonadal dysfunction can be associated with the worsening of the metabolic profile and, eventually, changes in body weight. While much progress has taken place in our knowledge about the neuroendocrine mechanisms linking metabolism and reproduction, our understanding of how such dynamic interplay happens is still incomplete. As paradigmatic example, much has been learned in the last two decades on the reproductive roles of key metabolic hormones (such as leptin, insulin and ghrelin), their brain targets and the major transmitters and neuropeptides involved. Yet, the molecular mechanisms whereby metabolic information is translated and engages into the reproductive circuits remain largely unsolved. In this work, we will summarize recent developments in the characterization of the putative central roles of key cellular energy sensors, such as mTOR, in this phenomenon, and will relate these with other molecular mechanisms likely contributing to the brain coupling of energy balance and fertility. In doing so, we aim to provide an updated view of an area that, despite still underdeveloped, may be critically important to fully understand how reproduction and metabolism are tightly connected in health and disease.

Signaling between kisspeptin and its receptor, G-protein-coupled receptor 54 (Gpr54), is now recognized as being essential for normal fertility. However, the key cellular location of kisspeptin-Gpr54 signaling is unknown. Here we create a mouse with a GnRH neuron-specific deletion of Gpr54 to assess the role of gonadotropin-releasing hormone (GnRH) neurons. Mutant mice are infertile, fail to go through puberty and exhibit markedly reduced gonadal size and follicle-stimulating hormone levels alongside GnRH neurons that are unresponsive to kisspeptin. In an attempt to rescue the infertile phenotype of global Gpr54⁻/⁻ mutants, we use BAC transgenesis to target Gpr54 to the GnRH neurons. This results in mice with normal puberty onset, estrous cyclicity, fecundity and a recovery of kisspeptin's stimulatory action upon GnRH neurons. Using complimentary cell-specific knockout and knockin approaches we demonstrate here that the GnRH neuron is the key site of kisspeptin-Gpr54 signaling for fertility.

Hyperthyroidism is characterized in rats by increased energy expenditure and marked hyperphagia. Alterations of thermogenesis linked to hyperthyroidism are associated with dysregulation of hypothalamic AMPK and fatty acid metabolism; however, the central mechanisms mediating hyperthyroidism-induced hyperphagia remain largely unclear. Here, we demonstrate that hyperthyroid rats exhibit marked up-regulation of the hypothalamic mammalian target of rapamycin (mTOR) signalling pathway associated with increased mRNA levels of agouti-related protein (AgRP) and neuropeptide Y (NPY), and decreased mRNA levels of pro-opiomelanocortin (POMC) in the arcuate nucleus of the hypothalamus (ARC), an area where mTOR co-localizes with thyroid hormone receptor-α (TRα). Central administration of thyroid hormone (T3) or genetic activation of thyroid hormone signalling in the ARC recapitulated hyperthyroidism effects on feeding and the mTOR pathway. In turn, central inhibition of mTOR signalling with rapamycin in hyperthyroid rats reversed hyperphagia and normalized the expression of ARC-derived neuropeptides, resulting in substantial body weight loss. The data indicate that in the hyperthyroid state, increased feeding is associated with thyroid hormone-induced up-regulation of mTOR signalling. Furthermore, our findings that different neuronal modulations influence food intake and energy expenditure in hyperthyroidism pave the way for a more rational design of specific and selective therapeutic compounds aimed at reversing the metabolic consequences of this disease.

Kisspeptins, a family of neuropeptides encoded by the Kiss1 gene that are mainly expressed in discrete neuronal populations of the hypothalamus, have recently emerged as essential upstream regulatory elements of GnRH (gonadotropin-releasing hormone) neurons and, thereby, potent elicitors of gonadotropin secretion. Indeed, kisspeptins are now recognized as important regulators of key aspects of the maturation and function of the reproductive axis, including the sexual differentiation of the brain, the timing of puberty, the adult regulation of gonadotropin secretion by gonadal hormones, and the control of fertility by metabolic and environmental (e.g., photoperiod) cues. Appreciation of these fundamental biological features has led to the contention that kisspeptins are indispensable elements of the reproductive brain whose relevance goes beyond their crucial physiological roles and may pose potential pathophysiological and therapeutic interest. In spite of such a consensus, recent developments in the field have helped to expand, and somewhat challenged, our current understanding of the neuroendocrine and molecular mechanisms whereby some of the effects of kisspeptins are conducted. This review aims to provide a synoptic and balanced account of the consensus knowledge and recent findings in the field of kisspeptin physiology, which we predict will be crucial in shaping the progress of our understanding of the roles played by this family of neuropeptides in reproductive biology.

The hormone leptin modulates a diverse range of biological functions, including energy homeostasis and reproduction. Leptin promotes GnRH function via an indirect action on forebrain neurons. We tested whether leptin deficiency or leptin resistance due to a high-fat diet (HFD) can regulate the potent reproductive neuropeptide kisspeptin. In mice with normalized levels of estradiol, leptin deficiency markedly reduced kisspeptin gene expression, particularly in the arcuate nucleus (ARC), and kisspeptin immunoreactive cell numbers in the rostral periventricular region of the third ventricle (RP3V). The HFD model was used to determine the effects of diet-induced obesity and central leptin resistance on kisspeptin cell number and gene expression. DBA/2J mice, which are prone to HFD-induced infertility, showed a marked decrease in kisspeptin expression in both the RP3V and ARC and cell numbers in the RP3V after HFD. This is the first evidence that kisspeptin can be regulated by HFD and/or increased body weight. Next we demonstrated that leptin does not signal (via signal transducer and activator of transcription 3 or 5, or mammalian target of rapamycin) directly on kisspeptin-expressing neurons in the RP3V. Lastly, in leptin receptor-deficient mice, neither GnRH nor kisspeptin neurons were activated during a preovulatory-like GnRH/LH surge induction regime, indicating that leptin's actions on GnRH may be upstream of kisspeptin neurons. These data provide evidence that leptin's effects on reproductive function are regulated by kisspeptin neurons in both the ARC and RP3V, although in the latter site the effects are likely to be indirect.

Hantavirus cardiopulmonary syndrome (HCPS) is an acute infectious disease characterized by sudden cardiorespiratory failure and high mortality, caused by a RNA virus of the genus Hantavirus, family Bunyaviridae, 15% of Chilean cases have been detected in the Araucania Region.To determine in fatal cases of HCPS, clinical and morphological characteristics.Descriptive-retrospective analysis of seven fatal cases with postmortem study of HCPS, attended between 1997 and 2009 at the Hospital of Temuco, Chile.Cases were young patients from rural areas, and presented as an illness of progressive respiratory failure, with leukocytosis, thrombocytopenia and bilateral interstitial pulmonary infiltrates. Main morphological findings were marked intersticial and intraalveolar pulmonary edema, with minimal epithelial injury and mononuclear cell intersticial infiltrate and mild edematous intersticial inflamatory process.Epidemiological, clinical and laboratory background allow to suspect HCPS. In fatal cases, the autopsy makes possible to discard other similar pathologies and provide tissue for confirmation of the disease.

The concomitant presence of a primary gastric adenocarcinoma and a gastrointestinal stromal tumor in the stomach is uncommon. We report a 68-year-old male with an advanced gastric adenocarcinoma. During gastrectomy, a nodular intramural lesion was found. The pathological study, revealed a gastrointestinal stromal tumor, positive form CD117. After six months of follow up, there is no evidence of recurrence of either tumor).

Thyroglossal duct cyst is the most common congenital anomaly of thyroid gland development. However, papillary carcinoma is described only in 1-2% of cases and the clinical appearance is indistinguishable from a benign thyroglossal duct cyst. We report two females aged 15 and 27 years consulting for a cervical mass. In both, a solid cystic lesion was found and excised using the Sistrunk procedure. The biopsy disclosed a papillary carcinoma in both. The postoperative evolution of both patients was uneventful.

Ovulation is triggered by the preovulatory rise of gonadotropins, which is in turn elicited by the preceding increase in circulating estrogen. Kisspeptins, ligands of G protein-coupled receptor 54 encoded by the KiSS-1 gene, have emerged as potent stimulators of GnRH/LH secretion, and KiSS-1 neurons at the anteroventral periventricular nucleus have been shown to be involved in the generation of preovulatory LH surge, estrogen being a potent elicitor of KiSS-1 gene expression selectively at the anteroventral periventricular nucleus. Whether, in addition to transcriptional effects, estrogen influences other aspects of kisspeptin-induced GnRH/LH release in the female remains unexplored. We provide herein evidence for the specific roles of estrogen receptor (ER)-alpha and ERbeta in the modulation of LH responses to kisspeptin and the generation of the preovulatory surge. Selective blockade of ERalpha in cyclic females blunted LH responses to kisspeptin, eliminated the endogenous preovulatory rise of LH, and blocked ovulation. In contrast, antagonism of ERbeta failed to cause major changes in terms of LH surge and ovulatory rate but significantly augmented acute LH responses to kisspeptin. Notably, defective LH secretion and ovulation after ERalpha blockade were not observed after GnRH stimulation, which elicited maximal acute (

The E-cadherin/catenin complex plays an essential role in the control of epithelial differentiation. Abnormal expression in tumors correlates with histological grade, advanced stage and poor prognosis.To evaluate the expression pattern of E-cadherin/catenin complex in gastric carcinoma and analyze their association with tumor clinicopathological features and patient survival.Inmunohistochemical staining of E-cadherin, alpha and ss-catenin was performed from paraffin specimens of 65 gastric carcinomas.Abnormal expression of E-cadherin, alpha and ss-catenin was demonstrated in 82%, 85% and 88% of gastric carcinomas, respectively. There was a significant correlation between abnormal expression and Lauren pathological classification and depth of infiltration, but not with tumor stage, positive lymph node metastases and survival.Abnormal expression of E-cadherin, alpha and ss-catenin occurs frequently in gastric carcinoma and correlates with histological grade.

Aneurysmal bone cysts are benign fibro osseous lesions, rarely present in maxillary region. We report the CT and morphological findings of aneurysmal bone cyst of the maxilla in a 15 years old female. The patient was subjected to a maxillectomy, preserving the orbit floor. The postoperative evolution has been uneventful. The tumor mainly involved the maxillary sinus with extension to the orbit wall and osseous palate. Very few cases of aneurysmal bone cysts of the maxilla have been reported in the literature.

The clinical and morphological characterization of the subserous gallbladder carcinomas is controversial.To study the prognostic importance of DNA content of subserous gallbladder carcinoma.We studied 104 females aged 60+/-12 years old and 16 men aged 70+/-13 years old. In all of them diagnosis was established after mapping of cholecystectomy sample and had a complete clinical follow up. DNA content was measured by flow cytometry.All tumors were adenocarcinoma, and only 16% were well differentiated. Aneuploidy was observed in 29 cases (26%) with DNA index fluctuating between 1.1 and 1.8. Lymphatic vessel tumor involvement was present in 16 of 22 cases with aneuploidy and in 22 of 46 diploid tumors (p=0.05). Eighty nine percent of aneuploid tumors were detected macroscopically and 11% were unapparent. Five years survival was non significantly better among patients with diploid tumors than in patients with aneuploid tumors (45 and 28%, respectively, p=0.2). The histological differentiation was the only variable significantly associated with survival.Aneuploidy is present in 26% of subserous gallbladder carcinoma. It is not related with any of the morphological or clinical variables studied in this series of patients.

Chile has a high frequency of gallbladder cancer. Polyps are common lesions of gallbladder mucosa but there is little information about their morphological features.To report the clinical and pathological features of 219 gallbladder polyps.Cholecystectomites samples in which a polypoid lesion was diagnosed microscopically. In all cases, complete clinical information and digitalized images of the complete surgical specimens was reviewed.In a period of 10 years, 21,412 gall-bladders were processed. Among these, 884 carcinomas were diagnosed and in 219 cases (1%) a polyp was found. One hundred and eighty three patients were females (mean age 49.3 years) and 36 males (mean age 53.4 years). The preoperative diagnosis of gallbladder polyp wars done only in 26 cases (12%). Eighty five percent of polyps were non-neoplastic (metaplastic in 32%, cholesterol in 29%, hyperplastic in 22% and inflammatory in 2%). The remaining 15% were adenomas. Seventy five percent of non-neoplastic polyps were located in the proximal half of the gallbladder and 88% of adenomas in the distal half. Ninety five percent of non-neoplastic polyps measured less than 10 mm. Among adenomas, 47% measured less than 5 mm and 28% more than 10 mm. Smaller polyps were of cholesterol and larger polyps were adenomas. Eight adenomas were associated with an adenocarcinoma, two had less than 5 mm length. Mean age of patients with adenomas associated to cancer was higher than patients with pure adenomas (64.6 and 44.3 years respectively, p0.001).There are size and location differences between non neoplastic polyps and adenomas. Adenomas associated to cancer may measure less than 5 mm. Therefore the polyp size criteria to decide surgical behavior in symptomatic gallstone patients may be misleading.

Subserous gallbladder carcinoma is difficult to diagnose and treat. There are no tissue markers with prognostic value in this type of tumor.To study the immunohistochemical expression of E-cadherin alpha and beta catenin in subserous gallbladder carcinoma.One hundred seventeen subjects (103 women and 14 men aged 62 and 69 years as a mean, respectively), were studied. Thirty five gallbladder samples without evidence of cancer were used as controls. Expression of markers was studied with standard immunohistochemical techniques for formalin fixed and paraffin embedded tissue.Ninety seven percent of tumors were adenocarcinoma. A lower or absent expression of E-cadherin, alpha catenin and beta catenin was observed in 26, 33 and 29% of tumors, respectively. Actuarial five years survival was 37%. No association between macroscopic features of the tumor and survival was observed. Well differentiated tumors had a 73% survival, whereas less differentiated tumors had a 30% survival. Tumors with a normal expression of the markers had a slightly better survival, although not significant (p = 0.06).Approximately 30% of subserous gallbladder carcinoma have an abnormal expression of E-cadherin, alpha catenin and beta catenin. This abnormal expression has no relationship with prognosis and is probably secondary to the aberrant genic expression of the tumor.

Gallbladder cancer is frequent in Chile, but it is not uniformly mortal. The diagnosis is usually made after a cholecystectomy, indicated for a symptomatic cholelithiasis. Global survival of gallbladder cancer can be as high as 40% at five years. In 69% of women of less than 30 years old, the tumor is detected in early stages. In these cases, cholecystectomy is the curative procedure, with a 90% survival at five years. According to our experience, cholecystectomies should be performed between 40 and 50 years of age in men and between 30 and 40 years in women. The prognostic factors that should be considered are symptoms associated to lithiasis, age, parity, obesity, size of stones and the size of the gallbladder. If the tumor is detected in early stages, the survival is good. The natural history of the disease would change significantly if all women with symptomatic stones were operated.