Tau, APP, NCT and BACE1 in lymphocytes through cognitively normal ageing and neuropathology.

Although Alzheimer's disease is a brain disorder, a number of peripheral alterations have been found in these patients; however, little is known about how the key genes involved in the pathophysiology express in peripheral cells such as lymphocytes during normal compared to neuropathological ageing. We analysed the expression of tau, of the amyloid precursor protein, of nicastrin and of the ß-site APP cleaving enzyme genes by RT-PCR in lymphocytes from a small group of late-onset Alzheimer's disease patients, from aged patients suffering from neuropsychological conditions different from Alzheimer's and from cognitively healthy subjects divided in four groups by age. We also investigated correlations between gene expression and levels of blood pressure, glucose, total cholesterol and triglycerides as risk factors for Alzheimer's. Results show no tau expression in lymphocytes, a lack of detection of nicastrin expression in Alzheimer's patients and correlations between the medical conditions studied and gene expression in lymphocytes. We believe nicastrin gene expression in lymphocytes should be considered of interest for further analyses in a wider population to investigate whether it might represent a potential biomarker to differentiate Alzheimer's from other neuropsychological disorders.

[Osteoporosis treatment evaluation with desoxypiridinoline urine detection in postmenopause patients]. / Evaluación del tratamiento de osteoporosis con determinación urinaria de desoxipiridinolina en mujeres posmenopáusicas.

OBJECTIVE: to evaluate urinary desoxypiridinoline (Dpd) levels in postmenopause patients, with osteoporosis or osteopenia after treatment with sodium alendronate. METHODS: a quasiexperimental study was carried out in 118 patients, aged from 41 to 69 years. According to the densitometry results and treatment received, we formed five groups: group I, patients with osteoporosis, treated with 10 mg/day of alendronate; group IIA, patients with osteopenia treated with alendronate 5 mg/day; group IIB, patients with osteopenia treated with hormonal therapy replacement (HTR); group IIIA, patients with normal densitometry treated with change of life style habits; and group IIIB, patients with normal densitometry treated with HTR. Dpd urinary levels were measured in all patients at the beginning and 60 days after. The statistical analysis was t Student paired. RESULTS: the group I diminished 7.8 nmol Dpd/mmol Cr with a p = 0.001. In the other groups the reduction of the urinary Dpd level was not significant. CONCLUSIONS: in osteoporosis the urinary Dpd excretion diminishes after 60 days of treatment with 10 mg/day of sodium alendronate.

A study of the prostate, androgens and sexual activity of male rats.

BACKGROUND: The prostate is a sexual gland that produces important substances for the potency of sperm to fertilize eggs within the female reproductive tract, and is under complex endocrine control. Taking advantage of the peculiar behavioral pattern of copulating male rats, we developed experimental paradigms to determine the influence of sexual behavior on the level of serum testosterone, prostate androgen receptors, and mRNA for androgen receptors in male rats displaying up to four consecutive ejaculations. METHODS: The effect of four consecutive ejaculations was investigated by determining levels of (i) testosterone in serum by solid phase RIA, (ii) androgen receptors at the ventral prostate with Western Blots, and (iii) androgen receptors-mRNA with RT-PCR. Data were analyzed with a one-way ANOVA followed by a post hoc application of Dunnett's test if required. RESULTS: The constant execution of sexual behavior did not produce any change in the weight of the ventral prostate. Serum testosterone increased after the second ejaculation, and remained elevated even after four ejaculations. The androgen receptor at the ventral prostate was higher after the first to third ejaculations, but returned suddenly to baseline levels after the fourth ejaculation. The level of mRNA increased after the first ejaculation, continued to increase after the second, and reached the highest peak after the third ejaculation; however, it returned suddenly to baseline levels after the fourth ejaculation. CONCLUSION: Four consecutive ejaculations by sexually experienced male rats had important effects on the physiological responses of the ventral prostate. Fast responses were induced as a result of sexual behavior that involved an increase and decrease in androgen receptors after one and four ejaculations, respectively. However, a progressive response was observed in the elevation of mRNA for androgen receptors, which also showed a fast decrease after four ejaculations. All of these changes with the prostate gland occurred in the presence of a sustained elevation of testosterone in the serum that started after two ejaculations. A consideration of these fast-induced changes suggests that the nerve supply plays a key role in prostate physiology during the sexual behavior of male rats.

Characteristics of ejaculated rat semen after lesion of scrotal nerves.

The scrotum, representing the pouch surrounding the testes and their associated structures, plays a significant role in maintaining the gonad at a temperature lower than that of the body. Although thermoregulation of the testes has been ascribed as a main function of the scrotum, here we found that mechanical stimulation of the scrotum is important during mating to facilitate the appropriate expulsion of semen during ejaculation. Previously we showed that the scrotal skin area is innervated by two nerve branches, the proximal (Psb) and distal (Dsb) scrotal branches which supply the proximal or distal half of the scrotum, respectively. The sensory field of each nerve is testosterone-dependent. The decreased androgen levels following castration reduce the sensitive area to mechanical stimuli that can be restored following exogenous administration of the hormone. Here, we tested the effect of scrotal nerve transection on sexual parameters of experienced male rats. Data show that lesion of PSb or DSb alone or combined did not affect the execution of sexual behavior. However, these lesions significantly reduced the proportion of males that expelled semen during ejaculation, with that semen showing a reduced quantity of sperm. Thus, scrotal nerves are important in reproduction not for the appropriate display of sexual behavior, but for the expulsion of a normal quantity of semen and number of sperm during ejaculation. Our suggestion is that scrotal afferents trigger spinal reflexes to activate autonomic efferents supplying the male reproductive tract for the control of seminal emission.

Prostate response to prolactin in sexually active male rats.

BACKGROUND: The prostate is a key gland in the sexual physiology of male mammals. Its sensitivity to steroid hormones is widely known, but its response to prolactin is still poorly known. Previous studies have shown a correlation between sexual behaviour, prolactin release and prostate physiology. Thus, here we used the sexual behaviour of male rats as a model for studying this correlation. Hence, we developed experimental paradigms to determine the influence of prolactin on sexual behaviour and prostate organization of male rats. METHODS: In addition to sexual behaviour recordings, we developed the ELISA procedure to quantify the serum level of prolactin, and the hematoxilin-eosin technique for analysis of the histological organization of the prostate. Also, different experimental manipulations were carried out; they included pituitary grafts, and haloperidol and ovine prolactin treatments. Data were analyzed with a One way ANOVA followed by post hoc Dunnet test if required. RESULTS: Data showed that male prolactin has a basal level with two peaks at the light-dark-light transitions. Consecutive ejaculations increased serum prolactin after the first ejaculation, which reached the highest level after the second, and started to decrease after the third ejaculation. These normal levels of prolactin did not induce any change at the prostate tissue. However, treatments for constant elevations of serum prolactin decreased sexual potency and increased the weight of the gland, the alveoli area and the epithelial cell height. Treatments for transient elevation of serum prolactin did not affect the sexual behaviour of males, but triggered these significant effects mainly at the ventral prostate. CONCLUSION: The prostate is a sexual gland that responds to prolactin. Mating-induced prolactin release is required during sexual encounters to activate the epithelial cells in the gland. Here we saw a precise mechanism controlling the release of prolactin during ejaculations that avoid the detrimental effects produced by constant levels. However, we showed that minor elevations of prolactin which do not affect the sexual behaviour of males, produced significant changes at the prostate epithelium that could account for triggering the development of hyperplasia or cancer. Thus, it is suggested that minute elevations of serum prolactin in healthy subjects are at the etiology of prostate abnormal growth.

Signal transducers and activators of transcription 1 and 3 in prostate: effect of sexual activity.

The signal transducers and activators of transcription (Stat) are effector molecules downstream of cytokine receptors. Ligand occupancy of these receptors results in the tyrosine phosphorylation, dimerization and nuclear translocation of the Stat family of transcription factors and by these means regulate gene expression. Prolactin receptors as members of the cytokine-hematopoietin receptor superfamily, are linked to Stat activation. Sexual stimulation leads to an increase in prolactin secretion that might be involved in long-term changes in the protein repertoire associated to prostate hyperplasia. In order to gain insight into this phenomenon, we analyzed the tyrosine phosphorylation and DNA binding activity of two members of the Stat family in the prostate of sexual experienced rats after different number of ejaculations. A significant increase in Stat-1 and Stat-3 tyrosine phosphorylation was found after three ejaculations. Concomitantly an increase in Stat-1 and Stat-3 DNA-binding activity is detected after two and three ejaculation series. These results, favor the notion that ejaculation-induced prolactin secretion activates its prostate receptors resulting in Stat-1 and Stat-3 nuclear translocation, event likely to be associated to the so-called benign prostate hyperplasia.

Correlation of prolactin levels and PRL-receptor expression with Stat and Mapk cell signaling in the prostate of long-term sexually active rats.

Prolactin (PRL) is a key hormone for prostate function, with a basal level in serum and associated with two characteristic circadian peaks. In the male rat, the execution of one bout of sexual behavior with consecutive ejaculations produces a significant transient increase in PRL. However, the impact of a constant sexual life on both PRL levels and prostate function is unknown. Thus, by using constantly copulating males we analyzed the levels of serum PRL, the effect on prostate PRL receptors, and activation of pStat3, pStat5 and Mapk signaling pathways. Sexually experienced Wistar male rats were used, which underwent periodic sessions of sexual behavior tests. Males were subjected to a session of sexual behavior to achieve at least one and up to four ejaculations. Of these, a blood sample was collected from randomly selected males and the ventral prostate was removed for analysis. Serum PRL was quantified, the mRNA for PRL receptors was determined, and signaling pathways were analyzed. Data show that a constant sexual life produced a constant elevation of PRL in serum during four consecutive ejaculations. The ventral prostate showed a different mRNA expression profile for the long and short isoform of the PRL receptor, and both mRNA levels increased. Although the gland did not show modification of the activation of the pStat5 signaling pathway, the levels of pStat3 increased, and the Mapk pathway showed one significant elevation after the third ejaculation. Thus, we showed that an active and constant sexual life produces a sustained increase in serum PRL, its receptors, and the pStat3 signaling pathway. These responses seem to underlie the required physiological need to produce the quantity and quality of prostatic semen to ensure the appropriate environment for sperm to reach and fertilize the ovum.

Glutamate-dependent transcriptional regulation in bergmann glia cells: involvement of p38 MAP kinase.

Glutamate (Glu) is the major excitatory neurotransmitter in the Central Nervous System (CNS). Ionotropic and metabotropic glutamate receptors (GluRs) are present in neurons and glial cells and are involved in gene expression regulation. Mitogen-activated proteins kinases (MAPK) are critical for all the membrane to nuclei signaling pathways described so far. In cerebellar Bergmann glial cells, glutamate-dependent transcriptional regulation is partially dependent on p42/44 MAPK activity. Another member of this kinase family, p38 MAPK is activated by non-mitogenic stimuli through its Thr180/Tyr182 phosphorylation and phosphorylates cytoplasmic and nuclear protein targets involved in translational and transcriptional events. Taking into consideration that the role of p38MAPK in glial cells is not well understood, we demonstrate here that glutamate increases p38 MAPK phosphorylation in a time and dose dependent manner in cultured chick cerebellar Bergmann glial cells (BGC). Moreover, p38 MAPK is involved in the glutamate-induced transcriptional activation in these cells. Ionotropic as well as metabotropic glutamate receptors participate in p38 MAPK activation. The present findings demonstrate the involvement of p38 MAPK in glutamate-dependent gene expression regulation in glial cells.

Factores, causas y perspectivas de la obesidad Infantil en México / Factors, causes and perspective of childhood obesity in Mexico

Este escrito comprende una revisión bibliográfica sobre la obesidad infantil en México desde el año 2000 a 2012. La obesidad constituye un problema de salud pública la cual recientemente ha alcanzado proporciones de epidemia en algunos países. Esta patología constituye el principal problema de malnutrición en el adulto y es una enfermedad que ha aumentado notoriamente en la población infantil, ya que se calcula que más de 40 millones de niños padecen sobrepeso u obesidad. Es un trastorno multifactorial en cuya etiopatogenia están implicados factores genéticos, metabólicos, psicosociales y ambientales, por lo que es difícil distinguir en cada caso en particular la importancia relativa de estos factores. La obesidad infantil es uno de los factores de riesgo vinculados al aumento de enfermedad cardiovascular en el adulto, junto con la hipertensión, hipercolesterolemia y diabetes tipo II; se ha identificado que un factor importante en el desarrollo de la obesidad infantil es la influencia de los medios electrónicos que promueven un estilo de vida básicamente sedentario...

This work is a review of the information about childhood obesity in Mexico from 2000 to 2012. Obesity is a public health problem, which has recently reached epidemic proportions in some countries. This pathology is the main problem of adult malnutrition and has dramatically increased in children, since it is estimated that over 40 million children have overweight or obesity. It involves several factors such as genetic, metabolic, psychosocial and environmental ones. As a result, it is difficult to distinguish their influence in different cases. However, a well-recognized factor in the development of childhood obesity is the media, which promotes a sedentary lifestyle. Childhood obesity is a risk factor associated with cardiovascular disease in adults, hypertension, hypercholesterolemia and diabetes Type II...