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1.
Endocr Oncol ; 3(1): e220075, 2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-37434643

RESUMO

Curcumin has been ascribed with countless therapeutic effects, but its impact on testicular function has been scarcely researched. Leydig cells comprise the androgen-secreting population of the testis and may give rise to Leydig cell tumours (LCTs). Due to their steroid-secreting nature, LCTs entail endocrine, reproductive, and psychological disorders. Approximately 10% are malignant and do not respond to chemotherapy and radiotherapy. The aim of this study was to assess curcumin's impact on Leydig cells' functions and its potential effect on LCT growth. In vitro assays on MA-10 Leydig cells showed that curcumin (20-80 µmol/L) stimulates acute steroidogenesis, both in the presence and absence of db-cAMP. This effect is accompanied by an increase in StAR expression. Regarding curcumin's in vitro cytostatic capacity, we show that 40-80 µmol/L curcumin reduces MA-10 Leydig cells' proliferative capacity, which could be explained by the arrest in G2/M and the reduced viability due to the activation of the apoptotic pathway. Finally, CB6F1 mice were inoculated with MA-10 cells to generate ectopic LCT in both flanks. They received i.p. injections of 20 mg/kg curcumin or vehicle every other day for 15 days. We unveiled curcumin's capacity to inhibit LCT growth as evidenced by reduced tumour volume, weight, and area under the growth curves. No detrimental effects on general health parameters or testicular integrity were observed. These results provide novel evidence of curcumin's effects on the endocrine cell population of the testis and propose this natural compound as a therapeutic agent for LCT.

2.
Transl Androl Urol ; 11(8): 1096-1104, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-36092849

RESUMO

Background: There is a growing interest in reporting satisfaction levels of transgender women undergoing vaginoplasty surgery. The lack of information regarding satisfaction during the initial experience of the vaginoplasty technique, and the moderate morbidity related to the surgery, could discourage the immersion of new groups in initiating a program of this kind. Therefore, we aim to report patients' level of satisfaction during our initial experience in the penile inversion vaginoplasty technique. Methods: Retrospective study of patients who underwent penile inversion vaginoplasty in our center between September 2019 and August 2021. Surgery technique, demographic data, preoperative clinical variables, and short and long-term follow-up are described. Six months after surgery, a survey elaborated by the research team was conducted by phone. The score goes from 1 to 5, and it evaluates satisfaction on esthetics, functional, psychosocial, and global aspects. Results: Twenty patients underwent penile inversion vaginoplasty in our center during the described period. The average age was 35.6 years old, the mean body mass index (BMI) was 24.7 kg/m2, and they presented low comorbidity. Half of the patients presented at least one complication, most of which were minor. One patient was urgently reoperated due to bleeding, and three patients were reoperated on a scheduled basis from minor surgeries. 90% of the patients answered the questionnaire. The most common answers to all four areas covered (esthetics, functional, psychosocial, and global) were satisfied or very satisfied, resulting in a mean over four points in each one of the sections. Lastly, 94.4% of the patients reported being satisfied with their choice of having undergone surgery. Conclusions: Our initial experience in penile inversion vaginoplasty reveals good satisfaction results at short follow up.

3.
Appl Environ Microbiol ; 88(19): e0129722, 2022 10 11.
Artigo em Inglês | MEDLINE | ID: mdl-36102660

RESUMO

After the outbreak of COVID-19, additional protocols have been established to prevent the transmission of the SARS-CoV-2 from the patient to the health personnel and vice versa in health care settings. However, in the case of emergency surgeries, it is not always possible to ensure that the patient is not infected with SARS-CoV-2, assuming a potential source of transmission of the virus to health personnel. This work aimed to evaluate the presence of the SARS-CoV-2 and quantify the viral load in indoor air samples collected inside operating rooms, where emergency and scheduled operations take place. Samples were collected for 3 weeks inside two operating rooms for 24 h at 38 L/min in quartz filters. RNA was extracted from the filters and analyzed using RT-qPCR targeting SARS-CoV-2 genes E, N1 and N2 regions. SARS-CoV-2 RNA was detected in 11.3% of aerosol samples collected in operating rooms, despite with low concentrations (not detected at 13.5 cg/m3 and 10.5 cg/m3 in the scheduled and emergency operating rooms, respectively). Potential sources of airborne SARS-CoV-2 could be aerosolization of the virus during aerosol-generating procedures and in open surgery from patients that might have been recently infected with the virus, despite presenting a negative COVID-19 test. Another source could be related to health care workers unknowingly infected with the virus and exhaling SARS-CoV-2 virions into the air. These results highlight the importance of reinforcing preventive measures against COVID-19 in operating rooms, such as the correct use of protective equipment, screening programs for health care workers, and information campaigns. IMPORTANCE Operating rooms are critical environments in which asepsis must be ensured. The COVID-19 pandemic entailed the implementation of additional preventative measures in health care settings, including operating theaters. Although one of the measures is to operate only COVID-19 free patients, this measure cannot be always implemented, especially in emergency interventions. Therefore, a surveillance campaign was conducted during 3 weeks in two operating rooms to assess the level of SARS-CoV-2 genetic material detected in operating theaters with the aim to assess the risk of COVID-19 transmission during operating procedures. SARS-CoV-2 genetic material was detected in 11% of aerosol samples collected in operating rooms, despite with low concentrations. Plausible SARS-CoV-2 sources have been discussed, including patients and health care personnel infected with the virus. These results highlight the importance of reinforcing preventive measures against COVID-19 in operating rooms, such as the correct use of protective equipment, screening programs for health care workers and information campaigns.


Assuntos
COVID-19 , SARS-CoV-2 , COVID-19/prevenção & controle , Carga Genética , Humanos , Salas Cirúrgicas , Pandemias/prevenção & controle , Quartzo , RNA Viral/genética , Aerossóis e Gotículas Respiratórios , SARS-CoV-2/genética
4.
Oncol Rep ; 45(1): 317-328, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33416183

RESUMO

Adipocytes are the main stromal cells in the mammary microenvironment, and crosstalk between adipocytes and breast cancer cells may play a critical and important role in cancer maintenance and progression. Tumor­induced differentiation to beige/brown adipose tissue is an important contribution to the hypermetabolic state of breast cancer. However, the effect of epithelial cell­beige adipocyte communication on tumor progression remains unclear. To contribute to the understanding of this phenomenon, we characterized components present in conditioned media (CM) from beige adipocytes (BAs) or white adipocytes (WAs), and evaluated the effects of BA­ and WA­CM on both adhesion and migration of tumor (LM3, 4T1 and MC4­L1) and non­tumor (NMuMG) mouse mammary epithelial cell lines. Additionally, we analyzed the expression of ObR, CD44, vimentin, MMP­9, MCT1 and LDH in tumor and non­tumor mouse mammary epithelial cell lines incubated with BA­CM, WA­CM or Ctrol­CM (control conditioned media). 3T3­L1 preadipocytes differentiated into beige adipocytes upon PPARγ activation (rosiglitazone) displaying characteristics that morphologically resembled brown/beige adipocytes. Levels of UCP1, CIDEA, GLUT4, leptin, MCT4 and FABP4 were increased, while adiponectin, caveolin 1 and perilipin 1 levels were decreased in BAs with respect to WAs. Tumor cell lines revealed lower cell adhesion and increased cell migration after incubation with BA­ and WA­CM vs. Ctrol­CM. ObR and MMP­9 in MC4­L1 cells were significantly increased after incubation with BA­CM vs. WA­ and Ctrol­CM. In addition, MC4­L1 and LM3 cells significantly increased their migration in the presence of BAs, suggesting that new signals originating from the crosstalk between BAs and tumor cells, could be responsible for this change. Our results indicate that beige adipocytes are able to regulate the behavior of both tumor and non­tumor mouse mammary epithelial cells, favoring tumor progression.


Assuntos
Adipócitos Bege/metabolismo , Neoplasias da Mama/patologia , Neoplasias Mamárias Experimentais/patologia , Células 3T3-L1 , Adipócitos Bege/efeitos dos fármacos , Adipócitos Brancos/efeitos dos fármacos , Adipócitos Brancos/metabolismo , Animais , Adesão Celular/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Meios de Cultivo Condicionados/metabolismo , Progressão da Doença , Feminino , Humanos , Glândulas Mamárias Animais , Camundongos , PPAR gama/agonistas , PPAR gama/metabolismo , Rosiglitazona/farmacologia , Microambiente Tumoral/efeitos dos fármacos
5.
Am J Otolaryngol ; 42(2): 102865, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33450479

RESUMO

OBJECTIVES: To analyze the characteristics of the visits attended to in an ENT Emergency Department (ENT-ED) during the first wave of COVID-19, comparing them with the emergencies attended to during the same period of time in 2019. METHODS: Descriptive and analytical observational retrospective study of all emergency consultations between March 1, 2020, and May 21, 2020, carried out by the Otorhinolaryngology-Head and Neck Surgery Department of a tertiary university hospital. The adequacy of consultations was assessed with the Hospital Emergency Suitability Protocol (HESP). The correlation between the emergencies and the SARS-CoV-2 confirmed cases was assessed with a generalized linear model. RESULTS: Although there was a decrease of almost 50% in ENT-ED visits during the first wave of COVID-19, the pattern of most cases remained similar to the pre-COVID-19 era: non-urgent consultations, not previously assessed by Primary Care (PC), being considered inadequate by the HESP. The three main reasons for consultation were otalgia, odynophagia, and epistaxis. The number of ENT-ED visits and the total number of confirmed cases of SARS-CoV-2 in the health area were correlated. CONCLUSIONS: SARS-CoV-2 pandemic was a challenge for the Spanish health system. The critical epidemiological situation experienced during March, April, and May explains the reduction in the number of visits to the ENT-ED. However, this condition did not affect the predominant pattern of visits with respect to the pre-COVID-19 era, which were mostly inadequate. A strengthening of PC and an improvement in the population's health education is essential.


Assuntos
COVID-19/epidemiologia , Serviço Hospitalar de Emergência , Otorrinolaringopatias/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Pandemias , Encaminhamento e Consulta , Estudos Retrospectivos , Espanha/epidemiologia , Adulto Jovem
6.
Bol. méd. postgrado ; 36(2): 26-30, dic.2020. tab
Artigo em Espanhol | LILACS, LIVECS | ID: biblio-1117896

RESUMO

Este estudio se sustentó en el paradigma cuantitativo orientado bajo una investigación de tipo descriptivo cuyo propósito fue describir el conocimiento sobre saberes populares del personal sanitario que labora en el Servicio de Atención Médica Inmediata del Servicio Desconcentrado Hospital Universitario Pediátrico Dr. Agustín Zubillaga. La muestra estuvo conformada por 10 médicos y 8 enfermeras a quienes se les aplicó una encuesta a través de un cuestionario con escala tipo Likert el cual fue validado por la técnica de juicio de expertos. Los resultados indican que los encuestados manifiestan una tendencia positiva en cuanto a que a la consulta llegan pacientes cuyas madres usan las creencias y costumbres de sus ancestros para tratar las enfermedades que padecen, respetando y reconociendo el saber popular que poseen las madres de los pacientes. Existe una tendencia negativa en la utilización de los saberes populares en la práctica médica, así como en la combinación del saber popular y el saber científico para tratar la enfermedad y en la posibilidad de integrar de manera pedagógica los saberes populares en la educación para la salud. Por otra parte expresan una marcada tendencia positiva en cuanto a que las madres utilizan los saberes populares por sus condiciones socioeconómicas y en el hecho de que la educación o valores recibidos por ellas influyen en el uso de dichas creencias; de igual forma, la mayoría expresa una tendencia positiva en que las creencias y costumbres maternales puedan generar intoxicaciones en los pacientes y una tendencia negativa en su habilidad para curar la enfermedad(AU)


This study was based on a quantitative paradigm oriented under descriptive field research. The purpose of this study was to describe knowledge on popular beliefs of patient's parents of the medical staff who work in the Servicio de Atención Médica Inmediata of the Servicio Desconcentrado Hospital Universitario Pediátrico Dr. Agustín Zubillaga. The sample consisted of 10 doctors and 8 nurses who were given a Likert-scale questionnaire which was validated by the expert judgment technique. The results demonstrate that respondents show a positive view in regards to the fact that patients mothers with beliefs and customs of their ancestors attend the consult, respecting and recognizing their popular belief system; there is a negative view in the use of popular beliefs in medical practice, combination of popular and scientific knowledge and the possibility of integration of popular beliefs into health education. On the other hand, they express a marked positive view in regards to the use of popular belief based on socioeconomic conditions and that the education or values received by them influence the use of these beliefs; similarly, most respondents express a positive view in relation to beliefs and customs leading to poisoning in patients and a negative view in the possibility that these beliefs cure disease(AU)


Assuntos
Humanos , Masculino , Feminino , Pessoal de Saúde , Educação , Capacitação Profissional , Cultura Popular , Mudança Social , Participação da Comunidade
7.
Rev. med. vet. (Bogota) ; (40): 35-44, ene.-jun. 2020. graf
Artigo em Espanhol | LILACS-Express | LILACS | ID: biblio-1139283

RESUMO

Resumen Históricamente, la especie bovina ha sido de vital importancia para el hombre como animal de abasto, por lo que el cuidado y protección a esta especie es muy importante. A nivel mundial existen diversas enfermedades que atacan el ganado bovino, entre las cuales se encuentra anaplasmosis bovina. La presente investigación no experimental de campo tiene como objetivo evaluar la dinámica de anticuerpos anti-Anaplasma y determinar en qué momento el animal presenta infección activa. Para ello, se escogió una población de 35 becerras ubicadas en la unidad de producción del municipio Crespo, en el estado de Lara, Venezuela. A las becerras, de 0 a 7 días de nacidas, se le extrajo la sangre en tubos con anticoagulante, para realizar frotis de capa blanca y determinación del hematocrito, y sin anticoagulante, para la inmunofluorescencia indirecta. Posteriormente, fueron muestreadas cada 15 días hasta obtener un total de 12 muestras por cada becerra. Para analizar los datos, fue utilizada la prueba estadística X2 del programa estadístico Epi Info versión 3.5.4. Se obtuvo un 79,05 % de positividad y 100 % de seropositividad para Anaplasma marginale. Se concluyó que los altos valores obtenidos con las pruebas serológicas son indicativos de animales con memoria inmunológica, lo que quiere decir que no necesariamente estarían infectados al momento del muestreo. Asimismo, se confirma la capacidad de la especie bovina de crear un estado de premunición ante la anaplasmosis a edades tempranas y mantenerla por un periodo prolongado, de modo que se encuentra una estabilidad enzoótica en la unidad de producción.


Abstract Bovine species has been historically of high importance to the human beings as a provision animal. Therefore, it is highly important to care and protect this species. There are different diseases attacking the bovines around the world, such as the bovine anaplasmosis. This non-experimental research in the field aims to evaluate the dynamics of anti-Anaplasma antibodies and to determine when the animal has an active infection. To do so, a population of 35 female calves was used from the production unit in the town Crespo, Lara State, Venezuela. Female calves, from 0 to 7 days born, were taken blood samples in test tubes with anticoagulant. Then a white smear test was carried out and the hematocrit was determined. Samples without anticoagulant were taken to do an indirect immunofluorescence test. The calves were taken blood samples every 15 days in order to complete 12 samples from each individual calf. For the data analysis, the statistical test X2 from the software Epi Info v.3.5.4 was used. Positive tests accounted for 79.05 % of the samples and seropositiveness for Anaplasma marginale reached 100%. It is concluded that the high values resulting from the serologic tests indicate that these animals have an immune memory, which means, in turn, that they were not necessarily infected at the time of being taken the samples. Likewise, this study confirms that this species is able to create a pre-immunity condition to the anaplasmosis at an early age and to keep it for a long term. This way, they reach an enzootic balance in the production unit.

8.
Biochem Biophys Res Commun ; 502(4): 508-514, 2018 08 25.
Artigo em Inglês | MEDLINE | ID: mdl-29859192

RESUMO

The final number of Sertoli cells reached during the proliferative periods determines sperm production capacity in adulthood. It is well known that FSH increases the rate of proliferation of Sertoli cells; however, little is known about the transcription factors that are activated by the hormone in order to regulate Sertoli cell proliferation. On the other hand, Hypoxia Inducible Factors (HIFs) are master regulators of cell growth. HIFs are dimers of HIF-ß and HIF-α subunits. Considering that HIF-ß is constitutively expressed, HIF transcriptional activity is regulated through the abundance of HIF-α subunits. To date, three HIF-α isoforms have been described. The association of the different HIF-α subunits with HIF-ß subunit constitutes three active transcription factors -HIF-1, HIF-2 and HIF-3- which interact with consensus hypoxia-response elements in the promoter region of target genes. Hypoxia has been classically considered the main stimulus that increases HIF transcriptional activity, however, regulation by hormones under normoxic conditions was also demonstrated. The aim of this work has been to investigate whether HIFs participate in the regulation of rat Sertoli cell proliferation by FSH. Sertoli cells obtained from 8-day old rats were cultured in the absence or presence of FSH. It has been observed that FSH increases HIF transcriptional activity and HIF-2α mRNA levels without modifying either HIF-1α or HIF-3α expression. Incubations with FSH have been also performed in the absence or presence of a pharmacological agent that promotes HIF-α subunit degradation, LW6. It has been observed that LW6 inhibits the FSH effect on proliferation, CCND1 expression and c-Myc transcriptional activity. Altogether, these results suggest that HIFs might be involved in the regulation of Sertoli cell proliferation by FSH.


Assuntos
Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Hormônio Foliculoestimulante/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Células de Sertoli/citologia , Células de Sertoli/metabolismo , Animais , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Hormônio Foliculoestimulante/farmacologia , Genes bcl-1/efeitos dos fármacos , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Masculino , Proteínas Proto-Oncogênicas c-myc/metabolismo , Ratos , Células de Sertoli/efeitos dos fármacos , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Regulação para Cima/efeitos dos fármacos
9.
Methods Mol Biol ; 1748: 129-155, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29453570

RESUMO

Sertoli cells play a central role in spermatogenesis. They maintain the blood-testis barrier, an essential feature of seminiferous tubules which creates the proper environment for the occurrence of the spermatogenesis. However, this confinement renders germ cells almost exclusively dependent on Sertoli cells' nursing function and support. Throughout spermatogenesis, differentiating sperm cells become more specialized, and their biochemical machinery is insufficient to meet their metabolic demands. Although the needs are not the same at all differentiation stages, Sertoli cells are able to satisfy their needs. In order to maintain the seminiferous tubule energetic homeostasis, Sertoli cells react in response to several metabolic stimuli, through signaling cascades. The AMP-activated kinase, sensitive to the global energetic status; the hypoxia-inducible factors, sensitive to oxygen concentration; and the peroxisome proliferator-activated receptors, sensitive to fatty acid availability, are pathways already described in Sertoli cells. These cells' metabolism also reflects the whole-body metabolic dynamics. Metabolic diseases, including obesity and type II diabetes mellitus, induce changes that, both directly and indirectly, affect Sertoli cell function and, ultimately, (dys)function in male reproductive health. Insulin resistance, increased estrogen synthesis, vascular disease, and pubic fat accumulation are examples of metabolic-related conditions that affect male fertility potential. On the other hand, malnutrition can also induce negative effects on male sexual function. In this chapter, we review the molecular mechanisms associated with the nutritional state and male sexual (dys)function and the central role played by the Sertoli cells.


Assuntos
Apoio Nutricional , Células de Sertoli/metabolismo , Transdução de Sinais , Espermatogênese , Diferenciação Celular , Células Cultivadas , Humanos , Masculino , Células de Sertoli/citologia
10.
Curr Drug Saf ; 11(2): 156-63, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27194037

RESUMO

AIM: Renal transplant patients are frequently subject to polypharmacy and drug-drug interactions. However, no previous study has systematically assessed the risk of drug interactions and Adverse Drug Reactions (ADRs) in this population. METHODS: A total of 138 consecutive adult kidney transplant recipients admitted to our hospital between August 2010 and February 2012 were prospectively and systematically assessed by our pharmacovigilance team, within 24 hours of admission, to identify potential drug-drug interactions and probable ADRs. RESULTS: As a consequence of the high number of medications per patient (7.8±0.2 drugs), a considerable number of drugdrug interactions were observed in this population, with an average of 5.6±0.4 drug interactions per patient. Moreover, a significant percentage of admissions (~10%) of kidney transplant patients were related to probable ADRs. Almost all these patients had at least one drug interaction that could have potentially contributed to the probable ADR. Of note, clinically significant (i.e. severe) drug interactions were more frequent among patients with ADRs (29% vs. 15%, p<0.01). Also, patients with ADRs were more likely to have started a medication 30 days before admission (38.5% vs. 10.4%, p < 0.01). Non-immunosuppressive drugs most commonly involved in severe interactions were omeprazole, magnesium sulphate, and statins. The most commonly observed interactions were: tacrolimus and omeprazole, mycophenolate and omeprazole, sirolimus and enalapril, mycophenolate and antivirals, and mycophenolate and magnesium sulphate. CONCLUSION: Drug interactions were extremely frequent among kidney transplant recipients, and responsible for potentially avoidable ADRs. They should be carefully considered when following kidney transplant recipients.


Assuntos
Interações Medicamentosas/fisiologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/diagnóstico , Transplante de Rim , Farmacovigilância , Polimedicação , Adulto , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Feminino , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/administração & dosagem , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Imunossupressores/administração & dosagem , Imunossupressores/efeitos adversos , Transplante de Rim/tendências , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Inibidores da Bomba de Prótons/administração & dosagem , Inibidores da Bomba de Prótons/efeitos adversos
11.
Gen Comp Endocrinol ; 222: 124-33, 2015 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-26315388

RESUMO

The purpose of this study was to investigate if FSH and bFGF regulate fatty acid (FA) metabolism and mitochondrial biogenesis in Sertoli cells (SC). SC cultures obtained from 20-day-old rats were incubated with 100ng/ml FSH or 30ng/ml bFGF for 6, 12, 24 and 48h. The expression of genes involved in transport and metabolism of FA such as: fatty acid transporter CD36 (FAT/CD36), carnitine-palmitoyltransferase 1 (CPT1), long- and medium-chain 3-hydroxyacyl-CoA dehydrogenases (LCAD, MCAD), and of genes involved in mitochondrial biogenesis such as: nuclear respiratory factors 1 and 2 (NRF1, NRF2) and transcription factor A (Tfam), was analyzed. FSH stimulated FAT/CD36, CPT1, MCAD, NRF1, NRF2 and Tfam mRNA levels while bFGF only stimulated CPT1 expression. A possible participation of PPARß/δ activation in the regulation of gene expression and lactate production was then evaluated. SC cultures were incubated with FSH or bFGF in the presence of the PPARß/δ antagonist GSK3787 (GSK; 20µM). bFGF stimulation of CPT1 expression and lactate production were inhibited by GSK. On the other hand, FSH effects were not inhibited by GSK indicating that FSH regulates the expression of genes involved in FA transport and metabolism and in mitochondrial biogenesis, independently of PPARß/δ activation. FA oxidation and mitochondrial biogenesis as well as lactate production are essential for the energetic metabolism of the seminiferous tubule. The fact that these processes are regulated by hormones in a different way reflects the multifarious regulation of molecular mechanisms involved in Sertoli cell function.


Assuntos
Ácidos Graxos/metabolismo , Hormônio Foliculoestimulante/metabolismo , Oligopeptídeos/metabolismo , Túbulos Seminíferos/metabolismo , Células de Sertoli/metabolismo , Animais , Expressão Gênica , Humanos , Masculino , Oxirredução , Ratos , Ratos Sprague-Dawley
12.
Am J Physiol Endocrinol Metab ; 302(8): E914-23, 2012 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-22275758

RESUMO

The final number of Sertoli cells reached during the proliferative periods determines sperm production capacity in adulthood. It is well known that FSH is the major Sertoli cell mitogen; however, little is known about the signal transduction pathways that regulate the proliferation of Sertoli cells. The hypothesis of this investigation was that FSH regulates proliferation through a PI3K/Akt/mTORC1 pathway, and additionally, AMPK-dependent mechanisms counteract FSH proliferative effects. The present study was performed in 8-day-old rat Sertoli cell cultures. The results presented herein show that FSH, in addition to increasing p-Akt, p-mTOR, and p-p70S6K levels, increases p-PRAS40 levels, probably contributing to improving mTORC1 signaling. Furthermore, the decrease in FSH-stimulated p-Akt, p-mTOR, p-p70S6K, and p-PRAS40 levels in the presence of wortmannin emphasizes the participation of PI3K in FSH signaling. Additionally, the inhibition of FSH-stimulated Sertoli cell proliferation by the effect of wortmannin and rapamycin point to the relevance of the PI3K/Akt/mTORC1 signaling pathway in the mitotic activity of FSH. On the other hand, by activating AMPK, several interesting observations were made. Activation of AMPK produced an increase in Raptor phosphorylation, a decrease in p70S6K phosphorylation, and a decrease in FSH-stimulated Sertoli cell proliferation. The decrease in FSH-stimulated cell proliferation was accompanied by an increased expression of the cyclin-dependent kinase inhibitors (CDKIs) p19INK4d, p21Cip1, and p27Kip1. In summary, it is concluded that FSH regulates Sertoli cell proliferation with the participation of a PI3K/Akt/mTORC1 pathway and that AMPK activation may be involved in the detention of proliferation by, at least in part, a decrease in mTORC1 signaling and an increase in CDKI expression.


Assuntos
Proliferação de Células , Hormônio Foliculoestimulante/metabolismo , Fosfatidilinositol 3-Quinase/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Células de Sertoli/metabolismo , Transdução de Sinais , Serina-Treonina Quinases TOR/metabolismo , Proteínas Quinases Ativadas por AMP/química , Proteínas Quinases Ativadas por AMP/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Animais , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Proteínas Inibidoras de Quinase Dependente de Ciclina/metabolismo , Ativação Enzimática/efeitos dos fármacos , Inibidores Enzimáticos/farmacologia , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Masculino , Inibidores de Fosfoinositídeo-3 Quinase , Fosfoproteínas/metabolismo , Fosforilação/efeitos dos fármacos , Processamento de Proteína Pós-Traducional/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Proteína Regulatória Associada a mTOR , Proteínas Quinases S6 Ribossômicas 70-kDa/metabolismo , Células de Sertoli/citologia , Células de Sertoli/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Sus scrofa , Serina-Treonina Quinases TOR/antagonistas & inibidores
13.
Rev Esp Cardiol ; 64(6): 463-9, 2011 Jun.
Artigo em Espanhol | MEDLINE | ID: mdl-21497978

RESUMO

INTRODUCTION AND OBJECTIVES: Evaluating patient outcomes following cardiac surgery is a means of measuring the quality of that surgery. The present study analyzes survival and the risk factors associated with mid-term mortality of patients undergoing cardiac surgery in Son Dureta University Hospital (Palma, Balearic Islands, Spain). METHODS: From November 2002 thru December 2007, 1938 patients underwent interventions. Patients were stratified in 4 age groups. Of 1900 patients discharged from hospital, 1844 were followed until December 31, 2008. Following discharge, we constructed Kaplan-Meier survival curves and performed Cox regression analysis to determine which variables associated with mid-term mortality. RESULTS: In-hospital mortality of the 1,938 patients was 1.96% (CI 95%, 1.36%-2.6%). Survival probability at 1, 3 and 5 years follow-up was 98%, 94% and 90%, respectively. Mean follow-up was 3.2 (0.01-6.06) years. Patients aged ≥ 70 years showed a lower survival rate than those aged <70 (log rank test, P <.0001). At the end of follow-up, mortality was 6.5% (CI 95%, 5.4%-7.7%). Age ≥ 70 years, a history of severe ventricular dysfunction (ejection fraction < 30%), severe pulmonary hypertension, diabetes mellitus, preoperative anemia, postoperative stroke, and hospital stay were independently associated with mid-term mortality. CONCLUSIONS: Mid-term survival after discharge was highly satisfactory. Mid-term mortality varied with age and other pre- and postoperative factors.


Assuntos
Procedimentos Cirúrgicos Cardíacos/mortalidade , Cardiopatias/mortalidade , Cardiopatias/cirurgia , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Cardiopatias/complicações , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Probabilidade , Análise de Regressão , Fatores de Risco , Espanha/epidemiologia , Análise de Sobrevida , Adulto Jovem
14.
Am J Physiol Endocrinol Metab ; 297(4): E907-14, 2009 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-19638510

RESUMO

Sertoli cells provide the physical support and the necessary environment for germ cell development. Among the products secreted by Sertoli cells, lactate, the preferred energy substrate for spermatocytes and spermatids, is present. Considering the essential role of lactate on germ cell metabolism, it is supposed that Sertoli cells must ensure its production even in adverse conditions, such as those that would result from a decrease in glucose levels in the extracellular milieu. The aim of the present study was to investigate 1) a possible effect of glucose deprivation on glucose uptake and on the expression of glucose transporters in rat Sertoli cells and 2) the participation of different signal transduction pathways in the above-mentioned regulation. Results obtained show that decreasing glucose levels in Sertoli cell culture medium provokes 1) an increase in glucose uptake accompanied by only a slight decrease in lactate production, 2) an increase in GLUT1 and a decrease in GLUT3 expression, and 3) an activation of AMP-activated protein kinase (AMPK)-, phosphatidylinositol 3-kinase (PI3K)/PKB-, and p38 MAPK-dependent pathways. Additionally, by using specific inhibitors of these pathways, a possible participation of AMPK- and p38MAPK-dependent pathways in the regulation of glucose uptake and GLUT1 expression is shown. These results suggest that Sertoli cells adapt to conditions of glucose deprivation to ensure an adequate lactate concentration in the microenvironment where germ cell development occurs.


Assuntos
Glucose/deficiência , Células de Sertoli/fisiologia , Adaptação Fisiológica/fisiologia , Animais , Northern Blotting , Western Blotting , Células Cultivadas , Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , Desoxiglucose/metabolismo , Espaço Extracelular/metabolismo , Glucose/metabolismo , Proteínas Facilitadoras de Transporte de Glucose/biossíntese , Transportador de Glucose Tipo 1/biossíntese , Transportador de Glucose Tipo 1/metabolismo , Transportador de Glucose Tipo 3/biossíntese , Transportador de Glucose Tipo 3/metabolismo , Ácido Láctico/metabolismo , Masculino , Fosfatidilinositol 3-Quinases/metabolismo , Ratos , Ratos Sprague-Dawley , Células de Sertoli/metabolismo , Transdução de Sinais/fisiologia , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
15.
Interact Cardiovasc Thorac Surg ; 6(6): 748-52, 2007 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-17890235

RESUMO

The objective of this study was to investigate the effect of preoperative mild renal dysfunction (RD) not requiring dialysis on mortality and morbidity after valve cardiac surgery (VCS). We studied 681 consecutive patients (2002-2006) who underwent valve cardiac surgery with or without coronary artery bypass graft (CABG). Preoperative RD was calculated with the abbreviated Modification of Diet in Renal Disease formula and was defined as a glomerular filtration rate <60 ml/min/1.73 m(2). Logistic regression analysis was used to assess the effect of preoperative renal dysfunction on operative and adverse outcomes. Two hundred and seven patients (30%) had preoperative mild RD. Patients with preoperative RD were older, had a higher rate of preoperative anaemia (43% vs. 25%, P<0.001) and more comorbidities. Patients with preoperative RD had worse outcomes with more reoperation (6.8% vs. 2.3%, P<0.001). Preoperative RD was significantly and independently associated with more red blood cell transfusions and longer hospital stay (median 9 vs. 8 days, P<0.001). Mortality was similar in both groups (3.4% vs. 2.3%, P=0.43). Preoperative mild renal dysfunction in patients undergoing cardiac valve surgery is an independent marker of postoperative morbidity.


Assuntos
Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Doenças das Valvas Cardíacas/mortalidade , Doenças das Valvas Cardíacas/cirurgia , Insuficiência Renal/complicações , Insuficiência Renal/mortalidade , Idoso , Anemia/etiologia , Anemia/mortalidade , Transfusão de Eritrócitos , Feminino , Taxa de Filtração Glomerular , Doenças das Valvas Cardíacas/complicações , Humanos , Incidência , Tempo de Internação , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Morbidade , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/mortalidade , Estudos Prospectivos , Insuficiência Renal/fisiopatologia , Reoperação , Medição de Risco , Fatores de Risco , Índice de Gravidade de Doença , Fatores de Tempo , Resultado do Tratamento
16.
Reproduction ; 133(4): 763-73, 2007 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-17504920

RESUMO

Interleukin-1beta (IL1beta ) belongs to a set of intratesticular regulators that provide the fine-tuning of cellular processes implicated in the maintenance of spermatogenesis. The aim of the present study was to analyze the signaling pathways that may participate in IL1beta regulation of Sertoli cell function. Sertoli cell cultures from 20-day-old rat were used. Stimulation of the cultures with IL1beta showed increments in phosphorylated protein kinase B (PKB), P70S6K, and ERK1/2 levels. A phosphatidyl inositol 3-kinase (PI3K) inhibitor (wortmannin (W)), a mammalian target of rapamycin inhibitor (rapamycin (R)), and a MEK inhibitor (PD98059 (PD)) were utilized to evaluate the participation of PI3K/PKB, P70S6K, and ERK1/2 pathways in the regulation of lactate production by IL1beta . PD and W, but not R, decreased IL1beta-stimulated lactate production. The participation of these pathways in the regulation of glucose uptake and lactate dehydrogenase (LDH) A mRNA levels by IL1beta was also analyzed. It was observed that W decreased IL1beta-stimulated glucose uptake, whereas PD and R did not modify it. On the other hand, PD decreased the stimulation of LDH A mRNA levels by IL1beta , whereas W and R did not modify it. In summary, results presented herein demonstrate that IL1beta stimulates PI3K/PKB-, P70S6K-, and ERK1/2-dependent pathways in rat Sertoli cells. Moreover, these results show that while IL1beta utilizes the PI3K/PKB pathway to regulate glucose transport, it utilizes the ERK1/2 pathway to regulate LDH A mRNA levels. This study reveals that IL1beta utilizes different signal transduction pathways to modify the biochemical steps that are important to regulate lactate production in rat Sertoli cells.


Assuntos
Interleucina-1beta/farmacologia , Lactatos/metabolismo , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Células de Sertoli/metabolismo , Androstadienos/farmacologia , Animais , Western Blotting/métodos , Butadienos/farmacologia , Células Cultivadas , Cromonas/farmacologia , Ativação Enzimática , Inibidores Enzimáticos/farmacologia , Flavonoides/farmacologia , Imunossupressores/farmacologia , L-Lactato Desidrogenase/análise , L-Lactato Desidrogenase/metabolismo , Masculino , Proteínas Quinases Ativadas por Mitógeno/antagonistas & inibidores , Morfolinas/farmacologia , Nitrilas/farmacologia , Inibidores de Fosfoinositídeo-3 Quinase , Ratos , Ratos Sprague-Dawley , Células de Sertoli/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Sirolimo/farmacologia , Estimulação Química , Transferrina/análise , Transferrina/metabolismo , Wortmanina
17.
Rev. bras. entomol ; 49(1): 159-161, mar. 2005. ilus
Artigo em Português | LILACS | ID: lil-400940

RESUMO

A ocorrência de Rhopalopsyllus lutzi lutzi (Baker) (Siphonaptera, Rhopalopsyllidae) foi assinalada em Canis familiaris (Linnaeus) de áreas rurais do município de Piraí, estado do Rio de Janeiro, Brasil. No período de junho 2001/novembro 2003, 51 sifonápteros foram capturados em oito cães procedentes de duas propriedades rurais do município de Piraí. Os exemplares coletados foram acondicionados em álcool etílico 70 por cento, levados ao Laboratório de Parasitologia Animal da Universidade Federal Rural do Rio de Janeiro para contagem e sexagem. Os exemplares foram identificados como Rhopalopsyllus lutzi lutzi Baker, 1904 (machos=18 e fêmeas=33). R. lutzi lutzi é, pela primeira vez, assinalada em cães domésticos naturalmente infestados em áreas rurais do estado do Rio de Janeiro.


Assuntos
Animais , Masculino , Feminino , Cães , Sifonápteros
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