RESUMEN
Portal vein thrombosis (PVT) still remains a major challenge in managing liver transplant recipients. The aim of this study was to describe PVT prevalence in our health district and identify potential risk factors involved. Although further research is needed to make some general appointments, we identified anticoagulation therapy before transplant as a potential protective factor against PVT.
Asunto(s)
Trasplante de Hígado , Trombosis de la Vena , Humanos , Cirrosis Hepática/patología , Vena Porta/diagnóstico por imagen , Vena Porta/patología , Estudios Retrospectivos , Trombosis de la Vena/etiología , Trombosis de la Vena/patologíaRESUMEN
In addition to its essential role in the physiological control of longitudinal growth, growth-hormone (GH) is endowed with relevant metabolic functions, including anabolic actions in muscle, lipolysis in adipose-tissue and glycemic modulation. Adult obesity is known to negatively impact GH-axis, thereby promoting a vicious circle that may contribute to the exacerbation of the metabolic complications of overweight. Yet, to what extent early-overnutrition sensitizes the somatotropic-axis to the deleterious effects of obesity remains largely unexplored. Using a rat-model of sequential exposure to obesogenic insults, namely postnatal-overfeeding during lactation and high-fat diet (HFD) after weaning, we evaluated in both sexes the individual and combined impact of these nutritional challenges upon key elements of the somatotropic-axis. While feeding HFD per se had a modest impact on the adult GH-axis, early overnutrition had durable effects on key elements of the somatotropic-system, which were sexually different, with a significant inhibition of pituitary gene expression of GH-releasing hormone-receptor (GHRH-R) and somatostatin receptor-5 (SST5) in males, but an increase in pituitary GHRH-R, SST2, SST5, GH secretagogue-receptor (GHS-R) and ghrelin expression in females. Notably, early-overnutrition sensitized the GH-axis to the deleterious impact of HFD, with a significant suppression of pituitary GH expression in both sexes and lowering of circulating GH levels in females. Yet, despite their similar metabolic perturbations, males and females displayed rather distinct alterations of key somatotropic-regulators/ mediators. Our data document a synergistic effect of postnatal-overnutrition on the detrimental impact of HFD-induced obesity on key elements of the adult GH-axis, which is conducted via mechanisms that are sexually-divergent.
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Dieta Alta en Grasa , Hormona del Crecimiento/metabolismo , Obesidad/etiología , Hipernutrición/complicaciones , Caracteres Sexuales , Animales , Peso Corporal , Femenino , Factor I del Crecimiento Similar a la Insulina/genética , Factor I del Crecimiento Similar a la Insulina/metabolismo , Masculino , Modelos Biológicos , Obesidad/genética , Especificidad de Órganos , Hipernutrición/metabolismo , ARN Mensajero/genética , ARN Mensajero/metabolismo , Ratas Wistar , Receptores de Somatotropina/genética , Receptores de Somatotropina/metabolismoRESUMEN
STUDY QUESTION: Can kisspeptin treatment induce gonadotrophin responses and ovulation in preclinical models and anovulatory women with polycystic ovary syndrome (PCOS)? SUMMARY ANSWER: Kisspeptin administration in some anovulatory preclinical models and women with PCOS can stimulate reproductive hormone secretion and ovulation, albeit with incomplete efficacy. WHAT IS KNOWN ALREADY: PCOS is a prevalent, heterogeneous endocrine disorder, characterized by ovulatory dysfunction, hyperandrogenism and deregulated gonadotrophin secretion, in need of improved therapeutic options. Kisspeptins (encoded by Kiss1) are master regulators of the reproductive axis, acting mainly at GnRH neurons, with kisspeptins being an essential drive for gonadotrophin-driven ovarian follicular maturation and ovulation. Altered Kiss1 expression has been found in rodent models of PCOS, although the eventual pathophysiological role of kisspeptins in PCOS remains unknown. STUDY DESIGN, SIZE, DURATION: Gonadotrophin and ovarian/ovulatory responses to kisspeptin-54 (KP-54) were evaluated in three preclinical models of PCOS, generated by androgen exposures at different developmental windows, and a pilot exploratory cohort of anovulatory women with PCOS. PARTICIPANTS/MATERIALS, SETTING, METHODS: Three models of PCOS were generated by exposure of female rats to androgens at different periods of development: PNA (prenatal androgenization; N = 20), NeNA (neonatal androgenization; N = 20) and PWA (post-weaning androgenization; N = 20). At adulthood (postnatal day 100), rats were subjected to daily treatments with a bolus of KP-54 (100 µg/kg, s.c.) or vehicle for 11 days (N = 10 per model and treatment). On Days 1, 4, 7 and 11, LH and FSH responses were assessed at different time-points within 4 h after KP-54 injection, while ovarian responses, in terms of follicular maturation and ovulation, were measured at the end of the treatment. In addition, hormonal (gonadotrophin, estrogen and inhibin B) and ovulatory responses to repeated KP-54 administration, at doses of 6.4-12.8 nmol/kg, s.c. bd for 21 days, were evaluated in a pilot cohort of anovulatory women (N = 12) diagnosed with PCOS, according to the Rotterdam criteria. MAIN RESULTS AND THE ROLE OF CHANCE: Deregulated reproductive indices were detected in all PCOS models: PNA, NeNA and PWA. Yet, anovulation was observed only in NeNA and PWA rats. However, while anovulatory NeNA rats displayed significant LH and FSH responses to KP-54 (P < 0.05), which rescued ovulation, PWA rats showed blunted LH secretion after repeated KP-54 injection and failed to ovulate. In women with PCOS, KP-54 resulted in a small rise in LH (P < 0.05), with an equivalent elevation in serum estradiol levels (P < 0.05). Two women showed growth of a dominant follicle with subsequent ovulation, one woman displayed follicle growth but not ovulation and desensitization was observed in another patient. No follicular response was detected in the other women. LIMITATIONS, REASONS FOR CAUTION: While three different preclinical PCOS models were used in order to capture the heterogeneity of clinical presentations of the syndrome, it must be noted that rat models recapitulate many but not all the features of this condition. Additionally, our pilot study was intended as proof of principle, and the number of participants is low, but the convergent findings in preclinical and clinical studies reinforce the validity of our conclusions. WIDER IMPLICATIONS OF THE FINDINGS: Our first-in-rodent and -human studies demonstrate that KP-54 administration in anovulatory preclinical models and women with PCOS can stimulate reproductive hormone secretion and ovulation, albeit with incomplete efficacy. As our rat models likely reflect the diversity of PCOS phenotypes, our results argue for the need of personalized management of anovulatory dysfunction in women with PCOS, some of whom may benefit from kisspeptin-based treatments. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by research agreements between Ferring Research Institute and the Universities of Cordoba and Edinburgh. K.S. was supported by the Wellcome Trust Scottish Translational Medicine and Therapeutics Initiative (STMTI). Some of this work was undertaken in the MRC Centre for Reproductive Health which is funded by the MRC Centre grant MR/N022556/1. M.T.-S. is a member of CIBER Fisiopatología de la Obesidad y Nutrición, which is an initiative of Instituto de Salud Carlos III. Dr Mannaerts is an employee of Ferring International PharmaScience Center (Copenhagen, Denmark), and Drs Qi, van Duin and Kohout are employees of the Ferring Research Institute (San Diego, USA). Dr Anderson and Dr Tena-Sempere were recipients of a grant support from the Ferring Research Institute, and Dr Anderson has undertaken consultancy work and received speaker fees outside this study from Merck, IBSA, Roche Diagnostics, NeRRe Therapeutics and Sojournix Inc. Dr Skorupskaite was supported by the Wellcome Trust through the Scottish Translational Medicine and Therapeutics Initiative 102419/Z/13/A. The other authors have no competing interest.
Asunto(s)
Kisspeptinas/uso terapéutico , Ovulación/efectos de los fármacos , Síndrome del Ovario Poliquístico/tratamiento farmacológico , Adulto , Animales , Modelos Animales de Enfermedad , Femenino , Hormona Folículo Estimulante/sangre , Humanos , Kisspeptinas/farmacología , Hormona Luteinizante/sangre , Proyectos Piloto , Síndrome del Ovario Poliquístico/sangre , Ratas Wistar , Adulto JovenRESUMEN
INTRODUCTION: The current imbalance between available donors and potential recipients for orthotopic liver transplantation (OLT) has led to a liberalization of organ acceptance criteria, increasing the risk of post-transplant complications such as early allograft dysfunction (EAD). Consequently, we need accurate criteria to detect patients with early poor graft function to guide the strategies of management. We evaluated the usefulness of two frequently used criteria: the definition from Olthoff et al and the Model for Early Allograft Function (MEAF) scoring. PATIENTS AND METHODS: Unicentric cohort study of patients undergoing OLT between January 1, 2010, and November 20, 2016. We performed a univariate study to detect donor, recipient, and transplant factors favoring EAD, defined both by Olthoff criteria and a MEAF score higher than 7. Finally, we developed a comparative survival analysis for cases having or not EAD. RESULTS: In all, 201 transplants met inclusion criteria. According to the stated cutoff for MEAF score, the frequency of EAD was 9.3%, with a significant association to low recipient body mass index and prolonged total graft ischemia time, resulting in lower patient 3-month postoperative survival. According to Olthoff criteria, EAD incidence was 22.1% and was associated with younger donor and recipient ages and higher Model for End-stage Liver Disease and Child-Pugh recipient scores. Its development resulted in lower graft and recipient survival at 3 months after OLT. CONCLUSION: MEAF score and Olthoff criteria are useful tools for detection of EAD. The latter could select more appropriately patients at risk, but its calculation cannot be done until the seventh day after OLT, unlike MEAF score, available on third day.
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Supervivencia de Injerto/fisiología , Disfunción Primaria del Injerto/diagnóstico , Disfunción Primaria del Injerto/epidemiología , Índice de Severidad de la Enfermedad , Adulto , Aloinjertos/fisiopatología , Estudios de Cohortes , Femenino , Humanos , Incidencia , Trasplante de Hígado/efectos adversos , Masculino , Persona de Mediana Edad , Disfunción Primaria del Injerto/fisiopatología , Factores de Riesgo , Factores de Tiempo , Donantes de Tejidos , Trasplante Homólogo/efectos adversosRESUMEN
INTRODUCTION: The aim of this study was to understand the prevalence of comorbidities and the usefulness of the PROFUND index for the prognostic stratification of patients with comorbidities in a hospital cardiology unit. PATIENTS AND METHODS: We consecutively analysed all patients hospitalized in 2012 in the department of cardiology. We recorded the comorbidities, length of stay, hospital mortality, Charlson indices and PROFUND indices. In the patients with comorbidities, we also recorded the readmissions and mortality during a 1-year follow-up. RESULTS: The study included 1,033 patients (mean age, 67±13.1 years; 35% women), 381 (36.9%) of whom had comorbidities, with a mean Charlson index of 6.4±1.7 and a mean PROFUND index of 2.5±2.5. Compared with the other patients, the patients with comorbidities were older (72 vs. 64 years, p<.001), had a higher mortality rate (2.9% vs. 1.1%, p=.046) and longer hospital stays (8±5.5 vs. 6±5.7 days, p<.001) and were more often admitted for heart failure (42.3% vs. 15.8%, p<.001). The PROFUND index was independently associated with overall mortality (hazard ratio [HR], 1.13; 95% CI: 1.01-1.27; p=.034) and with the presence of major adverse events during the 12-month follow-up (HR, 1.09; 95% CI: 1.01-1.18; p=.026). CONCLUSIONS: A high percentage of patients hospitalized in the department of cardiology had comorbidities. These patients had a higher prevalence of cardiovascular risk factors, longer stays and greater hospital mortality. The PROFUND index independently predicted mortality and adverse events during the follow-up.
RESUMEN
Kisspeptin/neurokinin B/dynorphin (KNDy) neurons, which coexpress kisspeptins (Kps), neurokinin B (NKB), and dynorphin (Dyn), regulate gonadotropin secretion. The KNDy model proposes that NKB (a stimulator, through NK3R) and Dyn (an inhibitor, through κ-opioid receptor) shape Kp secretion onto GnRH neurons. However, some aspects of this paradigm remain ill defined. Here we aimed to characterize the following: 1) the effects of NKB signaling on FSH secretion and 2) the role of Dyn in gonadotropin secretion after NK3R activation; 3) additionally, we explored the roles of other tachykinin receptors, NK1R and NK2R, on gonadotropin release. Thus, the effects of the NK3R agonist, senktide, on FSH release were explored across postnatal development in male and female rats; gonadotropin responses to agonists of NK1R substance P and NK2R [neurokinin A (NKA)] were also monitored. Moreover, the effects of senktide on gonadotropin secretion were assessed after antagonizing Dyn actions by nor-binaltorphimine didydrochloride. Before puberty, rats of both sexes showed increased FSH secretion to senktide (and Kp-10). Conversely, adult female rats were irresponsive to senktide in terms of FSH, despite proven LH responses, whereas the adult males did not display FSH or LH responses to senktide, even at high doses. In turn, substance P and NKA stimulated gonadotropin secretion in prepubertal rats, whereas in adults modest gonadotropin responses to NKA were detected. By pretreatment with a Dyn antagonist, adult males became responsive to senktide in terms of LH secretion and displayed elevated basal LH and FSH levels; nor-binaltorphimine didydrochloride treatment uncovered FSH responses to senktide in adult females. Furthermore, the expression of Pdyn and Opkr1 (encoding Dyn and κ-opioid receptor, respectively) in the mediobasal hypothalamus was greater in males than in females at prepubertal ages. Overall, our data contribute to refining our understanding on how the elements of the KNDy node and related factors (ie, other tachykinins) differentially participate in the control of gonadotropins at different stages of rat postnatal maturation.
Asunto(s)
Envejecimiento/metabolismo , Hormona Folículo Estimulante/metabolismo , Kisspeptinas/metabolismo , Hormona Luteinizante/metabolismo , Neuroquinina B/metabolismo , Animales , Dinorfinas/antagonistas & inhibidores , Dinorfinas/metabolismo , Encefalinas/metabolismo , Femenino , Hipotálamo/metabolismo , Masculino , Neuroquinina B/agonistas , Fragmentos de Péptidos , Precursores de Proteínas/metabolismo , Ratas Wistar , Receptores de Neuroquinina-1/agonistas , Receptores de Neuroquinina-2/agonistas , Sustancia P/análogos & derivadosRESUMEN
Body energy stores and metabolic cues influence the onset of puberty. However, the pubertal impact of early nutritional challenges has been only fragmentarily addressed. We evaluated here the consequences, in terms of pubertal timing and hormonal markers, of various nutritional manipulations during pre- or postnatal maturation in rats of both sexes. Males and females were submitted to gestational undernutrition (UNG) or peripubertal (SUB) subnutrition or were raised in large (LL; underfeeding) or small (SL; overfeeding) litters. In addition, groups of UNG, LL, and SL rats were fed on a high-fat diet (HFD) after weaning. Postnatal overfeeding resulted in higher body weights (BWs) during pubertal transition in both sexes, but only SL males displayed overtly advanced external signs of puberty. Postnatal underfeeding persistently decreased BW gain during puberty, yet the magnitude of pubertal delay was greater in LL males. In contrast, regardless of postnatal nutrition, HFD tended to advance the onset of puberty in females but did not alter pubertal timing in males. Likewise, SUB females displayed a marked delay in BW gain and puberty onset, whereas despite similar reduction in BW, SUB males showed normal timing of puberty. These sex divergences were also detected in various hormonal and metabolic indices so that postnatal overnutrition consistently increased LH, FSH, leptin, and insulin levels only in pubertal females, whereas HFD decreased gonadotropin levels in SL females but increased them in SL males. Notably, UNG rats did not show signs of delayed puberty but displayed a striking sex dimorphism in serum insulin/glucose levels, regardless of the diet, so that only UNG males had signs of presumable insulin resistance. Our data disclose important sex differences in the impact of various early nutritional challenges on the timing of puberty, which may help to explain the different trends of altered puberty and related comorbidities between sexes.
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Desarrollo Fetal , Trastornos Gonadales/etiología , Lactancia , Desnutrición/fisiopatología , Fenómenos Fisiologicos Nutricionales Maternos , Hipernutrición/fisiopatología , Maduración Sexual , Factores de Edad , Animales , Biomarcadores/sangre , Peso Corporal , Dieta Alta en Grasa/efectos adversos , Femenino , Trastornos Gonadales/sangre , Gonadotropinas/sangre , Resistencia a la Insulina , Masculino , Embarazo , Ratas , Ratas Wistar , Caracteres SexualesRESUMEN
Lin28 and Lin28b are related RNA-binding proteins that inhibit the maturation of miRNAs of the let-7 family and participate in the control of cellular stemness and early embryonic development. Considerable interest has arisen recently concerning other physiological roles of the Lin28/let-7 axis, including its potential involvement in the control of puberty, as suggested by genome-wide association studies and functional genomics. We report herein the expression profiles of Lin28 and let-7 members in the rat hypothalamus during postnatal maturation and in selected models of altered puberty. The expression patterns of c-Myc (upstream positive regulator of Lin28), mir-145 (negative regulator of c-Myc), and mir-132 and mir-9 (putative miRNA repressors of Lin28, predicted by bioinformatic algorithms) were also explored. In male and female rats, Lin28, Lin28b, and c-Myc mRNAs displayed very high hypothalamic expression during the neonatal period, markedly decreased during the infantile-to-juvenile transition and reached minimal levels before/around puberty. A similar puberty-related decline was observed for Lin28b in monkey hypothalamus but not in the rat cortex, suggesting species conservation and tissue specificity. Conversely, let-7a, let-7b, mir-132, and mir-145, but not mir-9, showed opposite expression profiles. Perturbation of brain sex differentiation and puberty, by neonatal treatment with estrogen or androgen, altered the expression ratios of Lin28/let-7 at the time of puberty. Changes in the c-Myc/Lin28b/let-7 pathway were also detected in models of delayed puberty linked to early photoperiod manipulation and, to a lesser extent, postnatal underfeeding or chronic subnutrition. Altogether, our data are the first to document dramatic changes in the expression of the Lin28/let-7 axis in the rat hypothalamus during the postnatal maturation and after different manipulations that disturb puberty, thus suggesting the potential involvement of developmental changes in hypothalamic Lin28/let-7 expression in the mechanisms permitting/leading to puberty onset.
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Envejecimiento/genética , Encéfalo/crecimiento & desarrollo , MicroARNs/metabolismo , Proteínas de Unión al ARN/biosíntesis , Animales , Células Madre Embrionarias/citología , Femenino , Hipotálamo/crecimiento & desarrollo , Hipotálamo/metabolismo , Masculino , MicroARNs/biosíntesis , Proteínas Proto-Oncogénicas c-myc/biosíntesis , Pubertad/efectos de los fármacos , Ratas , Ratas Wistar , Distribución TisularRESUMEN
Neurokinin B (NKB), encoded by Tac2 in rodents, and its receptor, NK3R, have recently emerged as important regulators of reproduction; NKB has been proposed to stimulate kisspeptin output onto GnRH neurons. Accordingly, NKB has been shown to induce gonadotropin release in several species; yet, null or even inhibitory effects of NKB have been also reported. The basis for these discrepant findings, as well as other key aspects of NKB function, remains unknown. We report here that in the rat, LH responses to the NK3R agonist, senktide, display a salient sexual dimorphism, with persistent stimulation in females, regardless of the stage of postnatal development, and lack of LH responses in males from puberty onward. Such dimorphism was independent of the predominant sex steroid after puberty, because testosterone administration to adult females failed to prevent LH responses to senktide, and LH responsiveness was not restored in adult males treated with estradiol or the nonaromatizable androgen, dihydrotestosterone. Yet, removal of sex steroids by gonadectomy switched senktide effects to inhibitory, both in adult male and female rats. Sexual dimorphism was also evident in the numbers of NKB-positive neurons in the arcuate nucleus (ARC), which were higher in adult female rats. This is likely the result of differences in sex steroid milieu during early periods of brain differentiation, because neonatal exposures to high doses of estrogen decreased ARC NKB neurons at later developmental stages. Likewise, neonatal estrogenization resulted in lower serum LH levels that were normalized by senktide administration. Finally, we document that the ability of estrogen to inhibit hypothalamic Tac2 expression seems region specific, because estrogen administration decreased Tac2 levels in the ARC but increased them in the lateral hypothalamus. Altogether, our data provide a deeper insight into relevant aspects of NKB function as major regulator of the gonadotropic axis in the rat, including maturational changes, sexual dimorphism, and differential regulation by sex steroids.
Asunto(s)
Núcleo Arqueado del Hipotálamo/metabolismo , Hormona Luteinizante/sangre , Neuroquinina B/metabolismo , Fragmentos de Péptidos/farmacología , Receptores de Neuroquinina-3/metabolismo , Maduración Sexual/fisiología , Sustancia P/análogos & derivados , Andrógenos/metabolismo , Andrógenos/farmacología , Animales , Núcleo Arqueado del Hipotálamo/efectos de los fármacos , Dihidrotestosterona/farmacología , Estradiol/metabolismo , Estradiol/farmacología , Estrógenos/metabolismo , Estrógenos/farmacología , Femenino , Masculino , Neuronas/efectos de los fármacos , Neuronas/metabolismo , Ratas , Ratas Wistar , Receptores de Neuroquinina-3/agonistas , Caracteres Sexuales , Factores Sexuales , Maduración Sexual/efectos de los fármacos , Sustancia P/farmacología , Testosterona/metabolismo , Testosterona/farmacologíaRESUMEN
La histiocitosis pulmonar de células de Langerhans es una enfermedad rara de adultos jóvenes, generalmente fumadores, que se asocia con una significativa morbilidad. El curso de esta enfermedad es impredecible, oscilando desde formas benignas autolimitadas hasta formas malignas con evolución progresiva hacia la insuficiencia respiratoria y la muerte. Su causa es desconocida, pero la mayor parte de los autores creen que en estos pacientes hay una alteración en la regulación del sistema inmunológico. Presentamos el caso de un paciente con el diagnóstico de histiocitosis pulmonar de células de Langerhans y revisamos las características clínicas, diagnósticas y terapéuticas de esta enfermedad. Consideramos de interés este caso por la baja frecuencia de esta entidad (AU)
Pulmonary Langerhans cell histiocytosis is a rare disease of young adults, usually smokers, which is associated with significant morbidity. The course of the disease is unpredictable, ranging from benign self-limiting types with spontaneous regression, to malignant forms with progression to respiratory failure and death. Its cause is unknown, but most authors believe that there is an alteration in immune system regulation in these patients. We report a case of a patient with the diagnosis of pulmonary Langerhans cell histiocytosis and review the clinical characteristics, diagnosis and treatment of this disease. We consider this case of interest due by the low frequency of this disease (AU)
Asunto(s)
Humanos , Masculino , Adulto , Histiocitosis de Células de Langerhans/complicaciones , Histiocitosis de Células de Langerhans/diagnóstico , Histiocitosis de Células de Langerhans/terapia , Enfermedades Pulmonares Intersticiales/complicaciones , Enfermedades Pulmonares Intersticiales , Enfermedades Raras/epidemiología , Broncoscopía/métodos , Broncoscopía , Corticoesteroides/uso terapéutico , Histiocitosis de Células de Langerhans/fisiopatología , Histiocitosis de Células de Langerhans , Radiografía Torácica/métodos , Bronquitis/complicaciones , Bronquitis/diagnóstico , /métodosRESUMEN
PURPOSE: To compare the microhardness of several dual-cure, self-adhesive resin cements used to lute fiber posts at 24 hours and seven days after cementation. METHODS: Bovine incisors were selected to lute 15 fiber posts that were 12 mm long (FRC Postec Plus size 3, Ivoclar-Vivadent). Five resin cements were tested: Multilink Automix (Ivoclar-Vivadent), without light-curing, and the self-adhesive resin cements Maxcem Elite (Kerr), RelyX Unicem (3M ESPE), G-Cem (GC), and Smartcem 2 (Dentsply), which were light-cured for 40 seconds (LED Bluephase, Ivoclar-Vivadent). Each root was embedded in chemically cured acrylic resin and stored at 37°C for 24 hours. The roots were transversally sectioned into nine specimens that were each 1 mm thick, with three specimens corresponding to each root third. Indentations (100g, 30 seconds) were performed on each section in the resin cement, at 24 hours and seven days after cementation, using a Vickers digital microdurometer (Buehler). Data were analyzed by two-way analysis of variance, Student-Newman-Keuls test, and paired t-test (p<0.05). RESULTS: A significant influence was found (p<0.05) for the resin cement evaluated, the root third, and their interactions on microhardness values at 24 hours and seven days after post cementation. RelyX Unicem and G-Cem exhibited the highest microhardness values, whereas Multilink Automix presented the lowest. All resin cements suffered a decrease in microhardness according to root canal depth, with the exception of G-Cem and Multilink Automix at 24 hours and Smartcem 2 after seven days. After seven days, the evaluated resin cements showed a significant increase in microhardness values, with the exception of Maxcem Elite and Smartcem 2 at the coronal third. CONCLUSIONS: Microhardness of the self-adhesive resin cements when used to lute fiber posts was material-dependent and higher values were obtained in the coronal third, revealing their sensitivity to light irradiation. More information regarding the polymerization reaction of these cements is warranted. According to the current results, microhardness values were significantly higher one week after post luting.
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Cavidad Pulpar/anatomía & histología , Técnica de Perno Muñón/instrumentación , Cementos de Resina/química , Animales , Bovinos , Cementación/métodos , Resinas Compuestas/química , Cementos Dentales/química , Materiales Dentales/química , Vidrio/química , Dureza , Curación por Luz de Adhesivos Dentales/instrumentación , Curación por Luz de Adhesivos Dentales/métodos , Polimerizacion , Preparación del Conducto Radicular/métodos , Auto-Curación de Resinas Dentales/métodos , Silanos/química , Temperatura , Factores de TiempoRESUMEN
Nesfatin-1, product of the precursor NEFA/nucleobindin2 (NUCB2), was initially identified as anorectic hypothalamic neuropeptide, acting in a leptin-independent manner. In addition to its central role in the control of energy homeostasis, evidence has mounted recently that nesfatin-1 is also produced in peripheral metabolic tissues, such as pancreas, adipose, and gut. Moreover, nesfatin-1 has been shown to participate in the control of body functions gated by whole-body energy homeostasis, including puberty onset. Yet, whether, as is the case for other metabolic neuropeptides, NUCB2/nesfatin-1 participates in the direct control of gonadal function remains unexplored. We document here for the first time the expression of NUCB2 mRNA in rat, mouse, and human testes, where NUCB2/nesfatin-1 protein was identified in interstitial mature Leydig cells. Yet in rats, NUCB2/nesfatin-1 became expressed in Sertoli cells upon Leydig cell elimination and was also detected in Leydig cell progenitors. Although NUCB2 mRNA levels did not overtly change in rat testis during pubertal maturation and after short-term fasting, NUCB2/nesfatin-1 content significantly increased along the puberty-to-adult transition and was markedly suppressed after fasting. In addition, testicular NUCB2/nesfatin-1 expression was up-regulated by pituitary LH, because hypophysectomy decreased, whereas human choriogonadotropin (super-agonist of LH receptors) replacement enhanced, NUCB2/nesfatin-1 mRNA and peptide levels. Finally, nesfatin-1 increased human choriogonadotropin-stimulated testosterone secretion by rat testicular explants ex vivo. Our data are the first to disclose the presence and functional role of NUCB2/nesfatin-1 in the testis, where its expression is regulated by developmental, metabolic, and hormonal cues as well as by Leydig cell-derived factors. Our observations expand the reproductive dimension of nesfatin-1, which may operate directly at the testicular level to link energy homeostasis, puberty onset, and gonadal function.
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Proteínas de Unión al Calcio/metabolismo , Proteínas de Unión al ADN/metabolismo , Metabolismo Energético/fisiología , Proteínas del Tejido Nervioso/metabolismo , Maduración Sexual/fisiología , Testículo/metabolismo , Envejecimiento/metabolismo , Animales , Regulación de la Expresión Génica , Humanos , Células Intersticiales del Testículo/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Modelos Animales , Nucleobindinas , Ratas , Ratas Wistar , Testículo/citología , Testículo/crecimiento & desarrollo , Testosterona/metabolismoRESUMEN
Pulmonary Langerhans cell histiocytosis is a rare disease of young adults, usually smokers, which is associated with significant morbidity. The course of the disease is unpredictable, ranging from benign self-limiting types with spontaneous regression, to malignant forms with progression to respiratory failure and death. Its cause is unknown, but most authors believe that there is an alteration in immune system regulation in these patients. We report a case of a patient with the diagnosis of pulmonary Langerhans cell histiocytosis and review the clinical characteristics, diagnosis and treatment of this disease. We consider this case of interest due by the low frequency of this disease.
Asunto(s)
Histiocitosis de Células de Langerhans/diagnóstico , Pulmón/patología , Adulto , Histiocitosis de Células de Langerhans/patología , Histiocitosis de Células de Langerhans/terapia , Humanos , Células de Langerhans/patología , Masculino , Tomografía Computarizada por Rayos XRESUMEN
Severe inflammatory challenges are frequently coupled to decreased food intake and disruption of reproductive function, the latter via deregulation of different signaling pathways that impinge onto GnRH neurons. Recently, the hypothalamic Kiss1 system, a major gatekeeper of GnRH function, was suggested as potential target for transmitting immune-mediated repression of the gonadotropic axis during acute inflammation, and yet key facets of such a phenomenon remain ill defined. Using lipopolysaccharide S (LPS)-treated male rats as model of inflammation, we document herein the pattern of hypothalamic kisspeptin immunoreactivity (IR) and hormonal responses to kisspeptin during the acute inflammatory phase. LPS injections induced a dramatic but transient drop of serum LH and testosterone levels. Suppression of gonadotropic function was associated with a significant decrease in kisspeptin-IR in the arcuate nucleus (ARC) that was not observed under conditions of metabolic stress induced by 48-h fasting. In addition, absolute responses to kisspeptin-10 (Kp-10), in terms of LH and testosterone secretion, were significantly attenuated in LPS-treated males that also displayed a decrease in food intake and body weight. Yet pair-fed males did not show similar alterations in LH and testosterone secretory responses to Kp-10, whose magnitude was preserved, if not augmented, during food restriction. In summary, our data document the impact of acute inflammation on kisspeptin content at the ARC as key center for the neuroendocrine control of reproduction. Our results also suggest that suppressed gonadotropic function following inflammatory challenges might involve a reduction in absolute responsiveness to kisspeptin that is independent of the anorectic effects of inflammation.
Asunto(s)
Núcleo Arqueado del Hipotálamo/fisiopatología , Hipogonadismo/fisiopatología , Inflamación/fisiopatología , Hormona Luteinizante/fisiología , Oligopéptidos/fisiología , Testosterona/fisiología , Animales , Área Bajo la Curva , Ingestión de Alimentos/fisiología , Inmunohistoquímica , Kisspeptinas , Hormona Luteinizante/sangre , Masculino , Ratas , Ratas Wistar , Testosterona/sangreRESUMEN
RF-amide related peptides (RFRP), as putative mammalian orthologs of the avian gonadotropin-inhibitory hormone (GnIH), have been proposed as key regulators of gonadotropin secretion in higher vertebrates. Yet considerable debate has arisen recently on their physiological relevance and potential mechanisms and sites of action. Present studies were undertaken to further characterize the effects of RFRP on LH and FSH secretion by a combination of in vivo and in vitro approaches in male and female rats. Initial screening via intracerebroventricular (icv) administration of different analogs of RFRP1 (RFRP1-12 and RFRP1-20) and RFRP3 (RFRP3-8 and RFRP3-17), as well as the related neuropeptide FF (NPFF8), to gonadectomized (GNX) female rats evidenced significant, albeit modest, inhibitory effects on LH secretion only for RFRP3-8 and RFRP3-17, which were detectable at the high dose rage (1 nmol for RFRP3-8, 5 nmol for RFRP3-17). This moderate inhibitory action was also documented after icv administration of RFRP3-8 to intact and GNX male rats. In addition, systemic (intravenous) administration of RFRP3-8 decreased the circulating levels of both gonadotropins in GNX male rats. Likewise, RFRP3-8 inhibited basal and GnRH-stimulated LH secretion by pituitaries from GNX males in vitro. This inhibitory effect was blocked by the antagonist of RFRP receptors, RF9. In summary, our results support a putative inhibitory role of RFRP3 as ortholog of GnIH in the regulation of gonadotropin secretion in mammals, which appears to involve direct pituitary actions as well as potential central (hypothalamic) effects.
Asunto(s)
Hormona Folículo Estimulante/fisiología , Hormona Luteinizante/fisiología , Neuropéptidos/fisiología , Hipófisis/fisiología , Animales , Área Bajo la Curva , Relación Dosis-Respuesta a Droga , Femenino , Hormona Folículo Estimulante/metabolismo , Hormona Luteinizante/metabolismo , Masculino , Hipófisis/metabolismo , Ratas , Ratas WistarAsunto(s)
Bacteriemia/microbiología , Infección Hospitalaria/microbiología , Infecciones por Enterobacteriaceae/microbiología , Trasplante de Hígado , Pantoea/aislamiento & purificación , Neumonía Bacteriana/microbiología , Complicaciones Posoperatorias/microbiología , Anciano , Bacteriemia/etiología , Carcinoma Hepatocelular/complicaciones , Carcinoma Hepatocelular/cirugía , Comorbilidad , Infección Hospitalaria/etiología , Diabetes Mellitus Tipo 1/complicaciones , Infecciones por Enterobacteriaceae/etiología , Hepatitis C Crónica/complicaciones , Humanos , Huésped Inmunocomprometido , Cirrosis Hepática/complicaciones , Cirrosis Hepática/cirugía , Neoplasias Hepáticas/complicaciones , Neoplasias Hepáticas/cirugía , Masculino , Neumonía Bacteriana/etiología , Complicaciones Posoperatorias/etiologíaRESUMEN
Identification of RF-amide-related peptides (RFRP), as putative mammalian orthologs of the avian gonadotropin-inhibitory hormone, has drawn considerable interest on its potential effects and mechanisms of action in the control of gonadotropin secretion in higher vertebrates. Yet, these analyses have so far relied mostly on indirect approaches, while direct assessment of their physiological roles has been hampered by the lack of suitable antagonists. RF9 was recently reported as a selective and potent antagonist of the receptors for RFRP (RFRPR) and the related neuropeptides, neuropeptide FF (NPFF) and neuropeptide AF (NPFF receptor). We show here that RF9 possesses very strong gonadotropin-releasing activities in vivo. Central administration of RF9 evoked a dose-dependent increase of LH and FSH levels in adult male and female rats. Similarly, male and female mice responded to intracerebroventricular injection of RF9 with robust LH secretory bursts. In rats, administration of RF9 further augmented the gonadotropin-releasing effects of kisspeptin, and its stimulatory effects were detected despite the prevailing suppression of gonadotropin secretion by testosterone or estradiol. In fact, blockade of estrogen receptor-alpha partially attenuated gonadotropin responses to RF9. Finally, systemic administration of RF9 modestly stimulated LH secretion in vivo, although no direct effects in terms of gonadotropin secretion were detected at the pituitary in vitro. Altogether, these data are the first to disclose the potent gonadotropin-releasing activity of RF9, a selective antagonist of RFRP (and NPFF) receptors. Our findings support a putative role of the RFRP/gonadotropin-inhibitory hormone system in the central control of gonadotropin secretion in mammals and have interesting implications concerning the potential therapeutic indications and pharmacological effects of RF9.
Asunto(s)
Adamantano/análogos & derivados , Dipéptidos/metabolismo , Dipéptidos/farmacología , Hormona Folículo Estimulante/metabolismo , Sistema Hipotálamo-Hipofisario/efectos de los fármacos , Hormona Luteinizante/metabolismo , Adamantano/metabolismo , Adamantano/farmacología , Análisis de Varianza , Animales , Relación Dosis-Respuesta a Droga , Estradiol/farmacología , Receptor alfa de Estrógeno/metabolismo , Ciclo Estral/efectos de los fármacos , Ciclo Estral/fisiología , Femenino , Sistema Hipotálamo-Hipofisario/metabolismo , Kisspeptinas , Masculino , Ratones , Hipófisis/efectos de los fármacos , Hipófisis/metabolismo , Proteínas/farmacología , Radioinmunoensayo , Ratas , Ratas Wistar , Factores de TiempoAsunto(s)
Humanos , Masculino , Persona de Mediana Edad , Bacteriemia/complicaciones , Bacteriemia/diagnóstico , Pantoea/aislamiento & purificación , Trasplante de Hígado/métodos , Trasplante de Hígado/patología , Radiografía Torácica , Inmunosupresores/uso terapéutico , Pantoea/patogenicidad , Colitis/complicaciones , Complicaciones de la Diabetes/diagnóstico , Encefalopatía Hepática/complicaciones , Encefalopatía Hepática/diagnósticoRESUMEN
Kisspeptins (Kp) have recently emerged as master regulators of the reproductive axis and among the most potent elicitors of GnRH-gonadotropin secretion. Despite their paramount importance in reproductive physiology and their potential therapeutic implications, development of Kp antagonists has remained elusive, and only recently has the first compound with the ability to block Kp actions in vitro and in vivo, namely p234, been reported. However, previous in vivo studies all used acute central injections, whereas characterization of the effects of the antagonist after continuous or systemic administration, which poses pharmacological challenges, is still pending. We report herein a comprehensive series of analyses on the impact of continuous intracerebroventricular infusion of p234 on puberty onset and the preovulatory surge of gonadotropins in the female rat. In addition, the effects of systemic (ip) administration of a tagged p234-penetratin, with a predicted higher permeability at the blood-brain barrier, on Kp-10 induced gonadotropin secretion were evaluated. Central infusion of p234 to pubertal females delayed vaginal opening and decreased uterine and ovarian weights at the expected time of puberty, without affecting body weight. Likewise, chronic intracerebroventricular administration of p234 for 4 d prevented the preovulatory surges of LH and FSH. In addition, systemic (ip) administration of p234-penetratin significantly attenuated acute LH and FSH responses to Kp-10, either after intracerebroventricular or ip injection of Kp. Our data document the validity of p234 for antagonizing Kp actions in vivo and provide direct experimental evidence for the important role of Kp signaling in the key events of female reproduction, such as puberty onset and the preovulatory surge of gonadotropins.