[Glycation and protein crosslinking in the diabetes and ageing pathogenesis]. / Glicación y entrecruzamiento de proteínas en la patogénesis de la diabetes y el envejecimiento.

Long exposition to hyperglycemia is associated with development of vascular diseases in diabetic patients. Many of these effects are mediated by non-enzymatic glycosylation (glycation) of proteins and formation of advanced glycation end-products (AGEs). This phenomenon is accelerated in conditions where glucose concentration is chronically high, as it happens in diabetes mellitus. AGE formation is associated with structure-function alterations of proteins such as collagen, and particularly in tissues where these products are accumulated. A number of studies have demonstrated that AGEs can act as mediators, not only for the development of chronic complications of diabetes, but also in those related to ageing, nephropathy, Alzheimer's disease and erectile dysfunction, among others. In this paper, information generated about formation and accumulation of AGEs, including its biological effects and their participation in the development of complications in diabetes mellitus and other process such as ageing is revised. In addition, therapeutic strategies and a new methodology to measure glycation products are also considered.

Differential expression of steroidogenic factors 1 and 2, cytochrome p450scc, and steroidogenic acute regulatory protein in human pancreas.

OBJECTIVES: The aim of this study was to investigate the expression of the 4 gene transcripts, steroidogenic factors 1 (SF-1) and 2 (SF-2), steroidogenic acute regulatory (StAR), and cytochrome P450 11A1, involved in the synthesis of steroid hormones in normal human pancreas. METHODS: Total RNA was extracted from normal male (n = 5) and female (n = 5) samples, obtained from the organ donor program. The expression levels of SF-1, SF-2, StAR protein, and P450scc were assessed by reverse transcription-polymerase chain reaction and complemented with immunohistochemistry analysis. RESULTS: Polymerase chain reaction products amplification for all genes was present in both male and female samples, although differential expression was observed. The signals detected were much more evident in male than in female messenger RNA isolates for SF-1, SF-2, and StAR protein. The expression for P450scc was more intense in female samples. A similar pattern was observed in the immunohistochemical studies. CONCLUSIONS: Normal human pancreas expresses 4 gene transcripts involved in steroid synthesis similarly to steroidogenic organs. A distinctive characteristic is the sexually dimorphic expression of these factors. These data provide further evidence to support that the pancreas is a truly steroidogenic tissue, highlighting the presence of sex- and location-related differences in the expression of steroidogenic factors.

Endocrine gland-derived vascular endothelial growth factor in rat pancreas: genetic expression and testosterone regulation.

Endocrine gland-derived vascular endothelial growth factor (EG-VEGF) is an endothelial cell mitogen, expressed essentially in steroidogenic cells. Recently, the expression of EG-VEGF in normal human pancreas and pancreatic adenocarcinoma has been demonstrated. Epidemiologically, pancreatic carcinogenesis is more frequent in males than females, and given that androgen receptors and testosterone biotransformation have been described in pancreas, we hypothesized that testosterone could participate in the regulation of EG-VEGF expression. In this study, we investigated the regulation of EG-VEGF gene expression by testosterone in normal rat pancreatic tissue and rat insulinoma cells (RINm5F). Total RNA was extracted from rat pancreas and cultured cells. Gene expression was studied by real-time PCR and protein detection by immunohistochemistry. Serum testosterone was quantified by RIA. Results showed that EG-VEGF is expressed predominantly in pancreatic islets and vascular endothelium, as well as in RINm5F cells. EG-VEGF gene expression was lower in the pancreas of rats with higher testosterone serum levels. A similar effect that was reverted by flutamide was observed in testosterone-treated RINm5F cells. In summary, testosterone down-regulated EG-VEGF gene expression in rat pancreatic tissue and RINm5F cells. This effect could be mediated by the androgen receptor. To our knowledge, this is the first time that a direct effect of testosterone on EG-VEGF gene expression in rat pancreas and RINm5F cells is demonstrated.

Expression and localization of endocrine gland-derived vascular endothelial growth factor (EG-VEGF) in human pancreas and pancreatic adenocarcinoma.

Endocrine gland-derived vascular endothelial growth factor (EG-VEGF) was recently identified as the first tissue-specific angiogenic molecule. EG-VEGF (the gene product of PROK-1) appears to be expressed exclusively in steroid-producing organs such as the ovary, testis, adrenals and placenta. Since the human pancreatic cells retain steroidogenic activity, in the present study we ascertained whether this angiogenic factor is expressed in normal pancreas and pancreatic adenocarcinoma. Tissue samples from normal males (n=5), normal females (n=5) and from surgically resected adenocarcinomas (n=2) were processed for RT-PCR and immunohistochemical studies. Results from semi-quantitative analysis by RT-PCR suggest a distinct expression level for EG-VEGF in the different tissue samples. The relative amount of EG-VEGF mRNA in pancreas was more abundant in female adenocarcinoma (0.89) followed by male adenocarcinoma (0.71), than normal female (0.64) and normal male (0.38). The expression of mRNA for EG-VEGF in normal tissue was significantly higher in females than in males. All samples examined showed specific immunostaining for EG-VEGF. In male preparations, the positive labeling was localized predominantly within the pancreatic islets while in female preparations the main staining was detected towards the exocrine portion. Specific immunolabeling was also observed in endothelial cells of pancreatic blood vessels. Our data provide evidence that the human pancreas expresses the EG-VEGF, a highly specific mitogen which regulates proliferation and differentiation of the vascular endothelium. The significance of this finding could be interpreted as either, EG-VEGF is not exclusive of endocrine organs, or the pancreas should be considered as a functional steroidogenic tissue. The extent of the expression of EG-VEGF appears to have a dimorphic pattern in normal and tumoral pancreatic tissue.

[Steroid hormones and pancreas: a new paradigm]. / Las hormonas esteroides y el páncreas: un nuevo paradigma.

The relation between steroid hormones and pancreatic function has been poorly discussed and not very well understood. In general, there is a lack of recognition among the scientific community about the importance of steroids in pancreatic function (current paradigm). In the present article we present basic, as well as clinic and epidemiologic data that demonstrate steroid synthesis and steroid biotransformation by pancreatic tissue, how exocrine and endocrine functions are modulated by steroids, the gender specific frequency and behavior of some tumors and the use of synthetic steroids and steroid action antagonists as therapeutic agents. With the available information it is possible to establish that: 1. Pancreatic tissue synthesize and transform steroid hormones. 2. Pancreatic tissue respond to steroid hormones and express steroid specific receptor molecules. 3. Some endocrine functions such as insulin synthesis and release are modulated by steroids. 4. Tumor growth is modulated by steroids and anti-steroid drugs. This set of data creates a new paradigm for the holistic study of pancreas and opens new research fields. The application of this new paradigm might result in an increase in the knowledge of pancreatic physiology, in the design of new and better diagnostic methods and eventually in the design of more effective medical treatments for the pancreatic cancers.

Las hormonas esteroides y el páncreas: Un nuevo paradigma / Steroid hormones and pancreas: A new paradigm

The relation between steroid hormones and pancreatic function has been poorly discussed and not very well understood. In general, there is a lack of recognition among the scientific community about the importance of steroids in pancreatic function (current paradigm). In the present article we present basic, as well as clinic and epidemiologic data that demonstrate steroid synthesis and steroid biotransformation by pancreatic tissue, how exocrine and endocrine functions are modulated by steroids, the gender specific frequency and behavior of some tumors and the use of synthetic steroids and steroid action antagonists as therapeutic agents. With the available information it is possible to establish that: 1. Pancreatic tissue synthesize and transform steroid hormones. 2. Pancreatic tissue respond to steroid hormones and express steroid specific receptor molecules. 3. Some endocrine functions such as insulin synthesis and release are modulated by steroids. 4. Tumor growth is modulated by steroids and anti-steroid drugs. This set of data creates a new paradigm for the holistic study of pancreas and opens new research fields. The application of this new paradigm might result in an increase in the knowledge of pancreatic physiology, in the design of new and better diagnostic methods and eventually in the design of more effective medical treatments for the pancreatic cancers.

La relación de las hormonas esteroides con el páncreas ha sido muy poco explorada y comprendida y no se concede en general que exista una interacción relevante entre su función y los esteroides endógenos o exógenos (paradigma actual). En esta revisión se presentan datos de modelos experimentales y de estudios clínicos y epidemiológicos que demuestran que existe una clara relación entre la biotransformación y el efecto de las hormonas esteroides y la fisiopatología del páncreas. Con la información disponible se puede establecer que: 1. El páncreas es un órgano que sintetiza y transforma hormonas esteroides. 2. Que expresa receptores específicos para este tipo de substancias. 3. Que algunas de sus funciones como la síntesis y liberación de la insulina pueden ser modulados por la acción de esteroides gonadales. 4. Que el crecimiento tumoral puede ser inducido o frenado por la acción de esteroides y antiesteroides. Estas relaciones establecen un nuevo paradigma en el estudio de la fisiopatología del páncreas y abren nuevas líneas de investigación para el avance del conocimiento y su eventual aplicación clínica.

Gonadotrophin levels and morphological testicular features in rats after different doses of the phytoestrogen coumestrol.

INTRODUCTION: Phytoestrogens are a wide variety of chemical compounds, mainly isoflavonoids, from a vegetable source. Their name makes reference to their ability to induce estrogenic responses in mammals. Coumestrol is a phytoestrogen that can be found in high concentrations in the dietary elements of cattle. Some endocrine alterations have been reported for cows and ewes after ingestion of vegetables with high concentrations of coumestrol. However, these studies have been made mainly in females. OBJECTIVE: To analyze some features of the masculine endocrine response in rats after several doses of the phytoestrogen coumestrol. DESIGN: Adult male rats were injected with several doses of coumestrol. Plasma gonadotrophins (LH/FSH) and testosterone levels were assessed. In addition, morphology of the testicles was analyzed. SETTING: Experiments were done in the facilities of the neurosciences area at the University. RESULTS: No significant changes were observed in gonadotrophin levels after the administration of coumestrol. Testosterone levels showed a significant decrease with the higher doses. Morphological analysis showed an inhibitory effect on spermatogenesis expressed mainly in the right testicle. Testicular volume decreased and the tubular area increased significantly after coumestrol treatment. CONCLUSIONS: These results suggest that the endocrine effect of coumestrol is mainly expressed in peripheral targets in male rats. In addition, the possible mediation of estrogen beta receptors is discussed.

Expression of steroidogenic factors 1 and 2 in normal human pancreas.

Orphan nuclear receptor steroidogenic factor-1 (SF-1) is crucial for development and function of steroidogenic organs. The steroidogenic factor-2 (SF-2) is an essential factor involved in cholesterol transfer and activation of promoters of steroidogenic enzymes CYP11A1, CYP17 and Steroidogenic Acute Regulatory Protein (StAR). We have previously demonstrated steroidogenic activity in pancreatic tissue. The aim of this study was to investigate the presence of SF-1 and SF-2 in human pancreas. Total RNA was extracted from normal male (five) and female (five) samples, obtained from the organs donor program. RT-PCR approach was used to analyze the expression of SF-1 and SF-2. Immunohistochemical analysis was performed for SF-1. The bands of expression were present in both male and female samples, although differential expression was observed. For both factors, the signal detected was more evident in males than in females. A similar pattern was present in the immunohistochemical study. Normal human pancreas expresses SF-1 and SF-2 factors similarly to ovary and adrenals. A distinctive characteristic is the sexually dimorphic expression of these factors. Our data provide evidence suggesting that the pancreas achieves steroidogenic activity supporting the presence of gender- and location-related differences in the expression of these steroidogenic factors.

[Strengthening family planning efforts to reduce abortion]. / Acceso a servicios de planificación familiar como un medio para prevenir el aborto inducido.

Of the half million annual maternal deaths, complications from unsafe abortion account for 13% of all deaths. In Latin America and the Caribbean region there are 3.7 million induced abortions and it is estimated that 17% of all maternal deaths are due to unsafe abortions. Preventing unintended pregnancies has brought renewed focus on the role family planning and reproductive health services play in preventing unwanted pregnancies. Improving access to universal reproductive health services is one of the main strategies to reduce maternal mortality particularly due to unsafe abortions. Contraceptives are in high demand and short supply. Demand and population are increasing, yet contributions from donors and developing countries themselves are not keeping pace. Ensuring that all individuals and couples are able to exercise their rights to make free and informed choices about their sexual and reproductive health, and have access to universal sexual and reproductive health services are conditions to human development and freedom.

Nonoccupational determinants of plasma DDT and p,p'-DDE in men from Chiapas, Mexico.

A cross-sectional study was conducted to evaluate nonoccupational biological exposure to 1,1,1-trichloro-2,2-bis(4-chlorophenyl)ethane (DDT) compounds and to identify the main factors associated with such exposure in a malaria endemic region in Mexico. Capillary gas column chromatography was used to determine levels of p,p'-DDT and its metabolites in plasma. The mean age of the 144 male participants was 28 yr. Mean p,p'-DDE (1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene) and p,p'-DDT levels were 203.5 microg/l and 67.4 microg/l, respectively. Those whose houses had been sprayed for malaria control had much higher p,p'-DDE levels (p < 0.001). High levels of chlorinated pesticides were found despite being banned in Mexico for agricultural and public health use. Findings demonstrate the role of antimalarial campaigns as a major contributing factor for high DDT plasma levels.

The beta form of the estrogen receptor is predominantly expressed in the papillary cystic neoplasm of the pancreas.

INTRODUCTION: Papillary cystic neoplasm (PCN) of the pancreas is a low-malignancy tumor affecting predominantly young females. Sex steroid hormones have been involved in its development and/or growth. Estrogen receptor (ER) has been scarcely found in this tumor, although there is some evidence suggesting expression of the beta-isoform. Unlike ER, progesterone receptor (PR) expression has been consistently observed. Immunohistochemical analysis of the two isoforms of ER has not been performed in this tumor. AIM: To characterize expression of ER isoforms with an immunohistochemical method. METHODOLOGY: Expression of ER-alpha, ER-beta, and PR was analyzed by immunohistochemistry using isoform-specific ER and PR antibodies in paraffin-embedded tissue blocks from seven cases of PCN of the pancreas. RESULTS: Most patients were young females. ER-alpha and ER-beta were present in two and six tumors, respectively. PR was identified in six tumors. CONCLUSIONS: ER-beta expression predominates over the alpha-isoform in PCN of the pancreas. This finding supports the idea that previous negative results on ER expression were a consequence of the use of antibodies with no anti-beta activity. The role of ER-beta in the milieu of factors promoting the development and aggressiveness of PCN needs to be elucidated to address novel diagnostic and therapeutic approaches.

Sperm quality differences between the rainy and dry seasons in captive black-handed spider monkeys (Ateles geoffroyi).

The present work provides an assessment of sperm measures (concentration, motility, viability, etc.) of three black-handed spider monkeys (Ateles geoffroyi) during the rainy and dry seasons in Mexico City, as well as an evaluation of the between-subjects variability of sperm quality. Twenty samples obtained by rectal electroejaculation and digested with trypsin were evaluated. The results showed that during the dry season (n = 9) the semen samples were of better quality than those obtained during the rainy season (n = 11). The individual animals showed differences in sperm concentration, although there were no differences in sperm quality.

Comunicación química en primates / Chemical communication in primates

El sistema olfatorio de los mamíferos se ha especializado en la percepción de componentes químicos que regulan una gran diversidad de funciones. Uno de los componentes químicos que más utilizan las distintas especies es la feromona, cuyos efectos se pueden encontrar en el ámbito fisiológico o conductual, dependiendo del mensaje que se emita y del contexto en el cual se perciba.El uso de las feromonas en la comunicación química de los mamíferos tiene importantes funciones reguladoras de procesos reproducticos, que pueden afectar las interacciones sociales dentro de las poblaciones. Las feromonas que más emplean los mamíferos se encuentran en la orina y en las secreciones vaginales. La percepción de estos componentes químicos se lleva a cabo por el epitelio olfatorio y el órgano vomeronasal, que establecen conexiones neurales con diferentes núcleos cerebrales vinculados con la regulación del proceso reproductivo y las emociones. Sin embargo, hay controversia sobre la presencia de las feromonas en los antropoides del Viejo Mundo y en los seres humanos. En los primates, como los prosimios y los monos del Nuevo Mundo, se acepta su función en las conductas de marcaje territorial, en el reconocimiento entre conespecíficos y en la conducta sociosexual. En los primates catarrinos, en los póngidos y en los seres humanos se ha generado controversia sobre la participación de las feromonas en la atracción sexual. En primer lugar, debido a que esos grupos de primates muestran una disminucion de la región olfatoria, tanto nasal como cerebral, en comparación con el resto de los mamíferos. En segundo lugar, porque hasta ahora no se ha demostrado la funcionalidad del órgano vomeronasal, supuestamente especializado en la percepción de las feromonas en los demás mamíferos, que se considera como vestigial en los monos catarrinos y en los simios. Hay algunos trabajos sobre los seres humanos que muestran que dicho órgano no es completamente vestigial, como se consideraba, sino que es una estructura especializada en la percepción de feromonas, capaz de promover cambios fisiológicos dependientes del sexo.

Variación en la ingestión de energía y sus fuentes durante el ciclo mestrual / Variation in energy intake and sources during menstrual cycle

Diez mujeres mexicanas sanas (18-25 años), estudiantes de nutriología, registraron su ingestión de alimentos durante 2 ciclos mestruales consecutivos. Se midió la concentración de estradiol y progesterona de 16 muestras de sangre de cada voluntaria (8 por ciclo) y se dividió el ciclo en 5 fases. Se obtuvo el promedio de la ingestión de energía y sus fuentes por Kg de peso corporal para cada fase. El consumo de energía (31.5 ñ 1.4 y 31.6 * 1.6 kcal/kg) para ada ciclo fue significativamente menor (por < 0.05) en la fase ovulatoria comparado con las demás y coincidió con el pico mñaximo de estradiol observado (219.8 ñ 27.8 y 238.3 ñ 19.4 pg/ml en cada ciclo respectivamente); este resultado apoya la hipótesis derivada de modelos animales en que se plantea que losestrógenos son supresores del hambre, se concluye que las variaciones hormonales del ciclo menstrual influyen en la ingestión de alimentos.

Oclusión tubaria no quirurgica: uso del metilcianoacrilato (MCA) y el dispositivo FEMCEPT / Non surgical tubal occlusion: use of methylcianoacrilate and a blind delivery system (FEMCEPT)

En un estudio clínico de fase II se determinó en 26 mujeres voluntarias la efectividad y seguridad de un método para producir oclusión tubaria no quirúrgica. El procedimiento empleado consistió en la aplicación única de Metilcianoacrilato (MCA) a través del cuello uterino usando el dispositivo FEMCEPT. En todos los casos la maniobra se efectuó sin complicaciones. La efectividad del método fue evaluada por medio de Histerosalpingografía practicada 16 semanas después de la instilación del agente químico. En el 72% de los sujetos (18) se demostró la oclusión tubaria bilateral, en el 28% (7) hubo falla del método, y en el 3,3% (1) no se documentó. A tres años de seguimiento clínico no han ocurrido embarazos en los casos donde se documentó oclusión tubaria bilateral. Se demuestra que es posible ofrecer a la mujer que desea un método anticonceptivo definitivo una técnica simple, segura y efectiva que no requiere internamiento hospitalario, medicación anestésica ni la invasión de la cavidad abdominal

Eficacia de anticonceptivos inyectables en mujeres mexicanas / Efficacy of injectable contraceptives in Mexican women

De 1978 a 1981 se evaluó la eficacia de dos anticonceptivos inyectables, acetato de medroxiprogesterona de depósito (AMPD) y enantato de noretisterona (EN-NET), en una problación de 326 mujeres mexicanas cuyas edades fluctuaron entre los 18 y 40 años. Las participantes, sanas y de fecundidad comprobada, se dividieron en tres grupos a los que se administró por vía intramuscular 150 mg de AMPD cada 90 días, 200 mg de EN-NET cada 60 días primero y después cada 84 días, y 200 mg de EN-NET cada 60 días respectivamente. El índice de deserción acumulativo al final del ensayo fue de 78% y el motivo más frecuente de abandono fue primero la pérdida de seguimiento y, segundo, las alteraciones en el patrón de sangrado mentrual. Durante el estudio solo ocurrió un embarazo en los tres grupos en una mujer del grupo 2. Por otra parte el incremento promedio en el peso corporal fue moderado (4 kg) y en ningún caso se citó como causa para abandonar el tratamiento. Tampoco se observó un cambio significativo en la tensión arterial. Se concluyó que ambos anticonceptivos inyectables son muy eficaces en la regulación de la fecundidad en mujeres mexicanas aunque se señaló que es preciso controlar las alteraciones en el sangrado menstrual para que las mujeres sean más constantes en el tratamiento