First report of frequencies of Y chromosome microdeletions at a reproductive medicine center in Peru.

Objective: Y chromosome Microdeletions are the second genetic cause of infertility in men. Despite its importance for infertility treatment, there is no previous research in Peru. The aim of this study was to determine the frequencies and characteristics of Y chromosome microdeletions in a group of men who sought infertility consultation at a specialized reproductive medicine center in Peru. Methods: In this study, 201 semen samples were analyzed. The samples were obtained from Niu Vida's fertility program. Each seminal sample was analyzed according to the recommendations of the Laboratory Manual of the World Health Organization (WHO) 2010. A buccal swab and a 500 µL aliquot of seminal sample were used for the molecular study of Y chromosome microdeletions in each patient. The frequencies and the type of Y chromosome microdeletion in the AZFa, AZFb and AZFc regions were evaluated. Results: The prevalence of Y chromosome microdeletions in the AZF region was 6.45% in oligozoospermic and azoospermic patients, and a prevalence of 20% was observed specifically in azoospermic patients. No microdeletions of AZFb type were detected. A partial region microdeletion of AZFa was detected in a teratozoospermic patient with a normal sperm count. Conclusions: The study represents the first report on the incidence of Y chromosome microdeletions in Peru. Our results indicate a high prevalence of microdeletions in azoospermic patients compared to similar studies. It is suggested to assess the presence of AZFa microdeletions and to evaluate additional genetic markers in this region to identify specific mutations that may cause impaired sperm production and male infertility in the Peruvian male population.

Colitis ulcerosa con afectación gástrica y duodenal / Ulcerative colitis with gastric and duodenal involvement

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Age-related differences in the dynamics of hippocampal proteasome recovery.

Regulation of proteasome abundance to meet cell needs under stress conditions is critical for maintaining cellular homeostasis. However, the effects of aging on this homeostatic response remain unknown. In this report, we analyzed in young and aged rat hippocampus, the dynamics of proteasome recovery induced by proteasome stress. Proteasome inhibition in young rats leads to an early and coordinate transcriptional and translational up-regulation of both the catalytic subunits of constitutive proteasome and the proteasome maturation protein. By contrast, aged rats up-regulated the inducible catalytic subunits and showed a lower and shorter expression of proteasome maturation protein. This resulted in a faster recovery of proteasome activity in young rats. Importantly, proteasome inhibition highly affected pyramidal cells, leading to the accumulation of ubiquitinated proteins in perinuclear regions of aged, but not young pyramidal neurons. These data strongly suggest that age-dependent differences in proteasome level and composition could contribute to neurodegeneration induced by proteasome dysfunction in normal and pathological aging.

Age-related increase in the immunoproteasome content in rat hippocampus: molecular and functional aspects.

Alterations in the proteasome activity in the CNS have been described during aging. However, a detailed study of all proteasome subunits is actually lacking. We have analyzed, in vivo, the age-related modifications in the molecular composition of hippocampal proteasomes. We found that the immunoproteasome/proteasome ratio was increased in aged hippocampus. The processing of the low-molecular-mass protein (LMP)7/beta(5i) subunit, practically absent in young hippocampus, was increased in aged animals. Among the potential factors underlying these modifications we evaluated the neuroinflammation and the transcription factor Zif268. Lipopolysaccharide (LPS)-induced neuroinflammation in young rats, up-regulated the expression of immunoproteasome subunits and increased the processing of the LMP7/beta(5i) protein. Moreover, the hydrophobicity of cellular peptides, analyzed by liquid chromatography, increased in both, young LPS-injected animals and aged rats, suggesting that immunoproteasomes including the LMP7/beta(5i) subunit could, at least in part, account for this modification. Also, the mRNA expression of the transcription factor Zif268, which down-regulates the immunoproteasome subunit LMP7/beta(5i) by binding to sequences within the promoter regions, was decreased in both, aged hippocampus and young LPS-injected animals. Finally, we found that spatial memory training in young animals, a situation in which the expression of Zif268 is increased, modified the mRNA expression of the constitutive and catalytic subunits in an opposite manner. Based on present data, we propose that the age-related increases in the content of hippocampal immunoproteasome is mostly because of neuroinflammatory processes associated to aging.

Molecular and cellular characterization of the age-related neuroinflammatory processes occurring in normal rat hippocampus: potential relation with the loss of somatostatin GABAergic neurons.

Increased neuroinflammatory reaction is frequently observed during normal brain aging. However, a direct link between neuroinflammation and neurodegeneration during aging has not yet been clearly shown. Here, we have characterized the age-related hippocampal inflammatory processes and the potential relation with hippocampal neurodegeneration. The mRNA expression of the pro-inflammatory cytokines IL-1beta and tumor necrosis factor-alpha (TNF-alpha), and the iNOs enzyme was significantly increased in aged hippocampus. Accordingly, numerous activated microglial cells were observed in aged rats. These cells were differentially distributed along the hippocampus, being more frequently located in the hilus and the CA3 area. The mRNA expression of somatostatin, a neuropeptide expressed by some GABAergic interneurons, and the number of somatostatin-immunopositive cells decreased in aged rats. However, the number of hippocampal parvalbumin-containing GABAergic interneurons was preserved. Interestingly, in aged rats, the mRNA expression of somatostatin and IL-1beta was inversely correlated and, the decrease in the number of somatostatin-immunopositive cells was higher in the hilus of dentate gyrus than in the CA1 region. Finally, intraperitoneal chronic lipopolysaccharide (LPS) injection in young animals mimicked the age-related hippocampal inflammation as well as the decrease of somatostatin mRNA expression. Present results strongly support the neuroinflammation as a potential factor involved in the age-related degeneration of somatostatin GABAergic cells.

Hypersensitivity to penicillin V with good tolerance to other beta-lactams.

A 24 year-old man developed an anaphylactic reaction within thirty minutes of an oral administration of penicillin V. He suffered from recurrent streptococal pharyngitis that was usually treated with penicillin V with good tolerance. Skin prick and intradermal tests with penicilloyl-polylysine, minor determinant mixture, amoxicillin, ampicillin and cefuroxima were negative. However, a skin prick test with penicillin V was positive in the patient and negative in 10 controls. Determination of specific (Immunogloblulin (Ig) E to penicillin V was 0.64 kU/L. Specific IgE to penicillin G, amoxicillin and ampicillin were all negative. Single blind controlled oral challenge with amoxicillin and cefuroxime were both negative. This is an exceptional case of an anaphylactic reaction induced by phenoxymethylpenicillin with positive allergologic study in vivo and in vitro tests and with negative allergological study to other beta-lactams.

Inter-individual variability in the expression of the mutated form of hPS1M146L determined the production of Abeta peptides in the PS1xAPP transgenic mice.

The detection of the early phenotypic modifications of Alzheimer's disease (AD) models is fundamental to understand the progression and identify pharmacologic targets of this pathology. However, a large variability within different models and between age-matched mice from the same model has been observed. This variability could be due to heterogeneity in the Abeta production. Present results showed the existence of a large variability in the Abeta deposition in both hippocampus and cortex in 6-month-old PS1xAPP mice. This variability was not due to the expression of hAPP751SL, however, linear relationship between hPS1M146L mRNA and Abeta production was identified. The Abeta content was related to the incorporation of the hPS1M146L into functional gamma-secretase complexes, detected by the presence of the corresponding human or endogenous PS1-CTFs. Animals expressing low amount of hPS1M146L mRNA, displayed low hPS1-CTF incorporation and produced a low amount of Abeta peptides. Conversely, mice with relatively high hPS1 mRNA expression displayed high hPS1-CTF and high Abeta deposition. Furthermore, the Abeta total and Abeta1-42 content was increased dramatically by the expression of hPS1M146L (as compared with transgenic APPsl littermates). Therefore, variations in the expression of transgenic form of hPS1M146L in this model, or even between different models, influenced strongly the incorporation of the mutated PS1 into functional gamma-secretase complexes, the production of Abeta peptides and, in consequence, the detrimental effects of Abeta peptides. These data might implicate an "apparent gain-of-function" of the gamma-secretase complex by the expression of the mutated PS1M146L.

Role of p38 and inducible nitric oxide synthase in the in vivo dopaminergic cells' degeneration induced by inflammatory processes after lipopolysaccharide injection.

Accumulating evidences suggest that neuroinflammation is involved in the progressive death of dopaminergic neurons in Parkinson's disease. Several studies have shown that intranigral injection of lipopolysaccharide induces inflammation in the substantia nigra leading to death of tyrosine hydroxylase-positive cells. To better understand how the inflammatory response gives rise to neurotoxicity we induced inflammation in substantia nigra by injecting lipopolysaccharide. The damage of substantia nigra dopaminergic neurons was evaluated by immunohistochemistry, reverse transcription-PCR and Western blot analysis of tyrosine hydroxylase. In parallel, activation of microglial cells, a hallmark of inflammation in CNS, was revealed by immunohistochemistry. Similarly the expression of molecules involved in the inflammatory response and apoptotic pathway was also tested, such as cytokines (tumor necrosis factor-alpha, interleukin-1beta, interleukin-6), inducible nitric oxide synthase and caspase-11. Tyrosine hydroxylase expression (both mRNA and protein) started to decrease around 3 days post-injection. At the mRNA level, our results showed that the cytokines expression peaked shortly (3-6 h) after lipopolysaccharide injection, followed by the induction of inducible nitric oxide synthase and caspase-11 (14 h). However, inducible nitric oxide synthase protein peaked at 24 h and lasted for 14 days. The lipopolysaccharide-induced loss of substantia nigra dopaminergic neurons was partially inhibited by co-injection of lipopolysaccharide with S-methylisothiourea, an inducible nitric oxide synthase inhibitor. Co-injections of lipopolysaccharide with SB203580, a p38 MAP kinase inhibitor, reduced inducible nitric oxide synthase and caspase-11 mRNA expression, and also rescued dopaminergic neurons in substantia nigra. In summary, this is the first report to describe in vivo the temporal profile of the expression of these inflammatory mediators and proteins involved in dopaminergic neuronal death after intranigral injection of lipopolysaccharide. Moreover data strongly support that lipopolysaccharide-induced dopaminergic cellular death in substantia nigra could be mediated, at least in part, by the p38 signal pathway leading to activation of inducible nitric oxide synthase and caspase-11.

Cellular environment facilitates protein accumulation in aged rat hippocampus.

Aging represents the main risk factor to develop Alzheimer disease (AD) and protein aggregation constitutes a pathological hallmark thought to be involved in the etiology of this disease. Here, we show that, in basal conditions, the expression of chaperones calnexin, protein disulfide isomerase (PDI) and Grp78 was decreased in aged hippocampus, whereas the protein ubiquitination increased, suggesting the existence of age-related deficits in the systems involved in the defense against unfolded proteins. Interestingly, when cellular stress was induced by intra-hippocampal lactacystin injection, the aged rats were less efficient than young animals in alleviating the protein accumulation and, as an important factor, did not induce the expression of chaperones as young animals. However, the expression of the pro-apoptotic factor CHOP/GADD153 was induced and caspase-12 was activated in stressed aged rats but not in young animals. Current results demonstrated that unfolding protein response (UPR) is not correctly activated in aged rat hippocampus. Consequently, the up-regulation of apoptotic pathway mediators is increased in aged rats. Results might provide further understanding of the pathogenic mechanisms of age-related neurodegenerative disorders.

Hyperhomocysteinemia correlates with insulin resistance and low-grade systemic inflammation in obese prepubertal children.

Obesity is an independent risk factor for the development of cardiovascular disease frequently associated with hypertension, dyslipemia, diabetes, and insulin resistance. Higher homocysteine (Hcy) levels are observed in the hyperinsulinemic obese adults and suggest that Hcy could play a role in the higher risk of cardiovascular disease in obesity. We analyzed total Hcy levels in obese prepubertal children and their possible association with both metabolic syndrome and various inflammatory biomarkers and leptin. We studied 43 obese children (aged 6-9 years) and an equal number of nonobese children, paired by age and sex. The obese subjects presented significantly elevated values for insulin (P = .003), C-reactive protein (P = .033), and leptin (P < .001). No significant differences were found in Hcy levels between the obese and nonobese children. However, Hcy concentration was significantly higher in the hyperinsulinemic obese children than in the normoinsulinemic group (P = .002). Using multivariant regression analysis, in the obese group, corrected for age and sex, the homeostasis model assessment for insulin resistance (P partial = .001) and leptin (P partial = .02) are independent predictive factors for Hcy. In the control group, corrected for age and sex, the homeostasis model assessment for insulin resistance (P partial = .005) and leptin (P partial = .031) also are independent predictive factor for Hcy. Increased plasma Hcy, particularly in hyperinsulinemic obese children, may be causally involved in the pathogenesis of atherosclerosis and/or cardiovascular disease, both of which are common in obesity.

Reissner's fiber formation depends on developmentally regulated factors extrinsic to the subcommissural organ.

Reissner's fiber (RF) is a threadlike structure present in the third and fourth ventricles and in the central canal of the spinal cord. RF develops by the assembly of glycoproteins released into the cerebrospinal fluid (CSF) by the subcommissural organ (SCO). SCO cells differentiate early during embryonic development. In chick embryos, the release into the CSF starts at embryonic day 7 (E7). However, RF does not form until E11, suggesting that a factor other than release is required for RF formation. The aim of the present investigation was to establish whether the factor(s) triggering RF formation is (are) intrinsic or extrinsic to the SCO itself. For this purpose, SCO explants from E13 chick embryos (a stage at which RF has formed) were grafted at two different developmental stages. After grafting, host embryos were allowed to survive for 6-7 days, reaching E 9 (group 1) and E13 (group 2). In experimental group 1, the secretion released by the grafted SCOs never formed a RF; instead, it aggregated as a flocculent material. In experimental group 2, grafted SCO explants were able to develop an RF-like structure, similar to a control RF. These results suggest that the factor triggering RF formation is not present in the SCO itself, since E13 SCO secretion forms an RF in E13 brains but never develops RF-like structures when placed in earlier developmental environments. Furthermore, the glycoproteins released by implanted SCOs bind specifically to several structures: the apical portion of the mesencephalic floor plate and the choroid plexus of the third and fourth ventricles.

El soporte de enfermería y la claudicación del cuidador informal / Nursing support and caregiver strain

Objetivo. Explorar la posible asociación entre la satisfacción sobre el soporte de enfermería y el riesgo de claudicación del cuidador informal, en 4 áreas básicas de salud de Barcelona, durante 2001 y 2002. Método. Estudio observacional, descriptivo y transversal. Los individuos de estudio han sido 65 cuidadores informales, de uno u otro sexo, de 65 o más años de edad, con una enfermedad crónica, terminal o demencia. Las variables estudiadas en relación con el cuidador informal han sido: la edad, el sexo, la relación de parentesco con el paciente, el grado de sobrecarga, el riesgo de claudicación y la satisfacción sobre el soporte de las enfermeras. Y las variables con relación al paciente: la edad, el sexo, el tipo de enfermedad y el nivel de dependencia. Para valorar el nivel de sobrecarga del cuidador informal se ha utilizado la escala de Zarit. Resultados. La media de edad de los cuidadores informales es de 60 años, y la mayoría son mujeres (56; 86%). El grado de sobrecarga del cuidador informal presenta una media de 61,20 puntos en la escala de Zarit (desviación estándar = 16,50; intervalo de confianza del 95%, 57,11-65,29). Los cuidadores informales con riesgo de claudicar fueron 42 (65%). No se han encontrado diferencias estadísticamente significativas entre la satisfacción del cuidador informal y el riesgo de claudicación. Conclusiones. El perfil del cuidador informal corresponde a mujeres con un elevado nivel de satisfacción sobre el soporte de enfermería, y un alto riesgo de claudicación

Objective. To examine the possible association between satisfaction with nursing support and the risk of caregiver strain in informal carers in four Basic Health Areas in Barcelona from 2001 to 2002. Method. An observational, descriptive, cross-sectional study was performed. Subjects were 65 informal carers of both sexes of individuals aged 65 years or older with chronic or terminal diseases, or dementia. Carer-related variables were: age, gender, family relationship with the patient, degree of burden, risk of abandonment, and satisfaction with nursing support. Patient-related variables were: age, gender, type the disease, and degree of dependency. To evaluate the degree of burden in the informal carer, the Zarit scale was used. Results. The mean age of informal carers was 60 years, and most were women (56; 86%). Informal carers had a mean score of 61.20 points on the Zarit scale (SD = 16.50; 95% confidence interval, 57.11-65.29). There were 42 (65%) informal carers at risk of caregiver strain (65%). No statistically significant differences were found between satisfaction of the informal carer and the risk of caregiver strain. Conclusions. The profile of the informal carer corresponds to women with a high level of satisfaction with nursing support and a high risk of caregiver strain

Structure of Anisakis simplex s.l. populations in a region sympatric for A. pegreffii and A. simplex s.s. Absence of reproductive isolation between both species.

The aim of this study was to determine the genetic structure of A. simplex s.l. populations. This was done by applying PCR-RFLP and RAPD-PCR to 42 specimens morphologically identified as third stage larvae of A. simplex s.l. Of these larvae, 59.26% of those of Mediterranean origin are identified by PCR-RFLP as A. pegreffii. In Atlantic waters, this percentage dropped to 20.00% while A. simplex s.s. represents 66.67%. However, findings seem to suggest that the taxonomic status of both species should be reconsidered owing to: (i) the high gene flow value that we detected between A. simplex s.s. and A. pegreffii; (ii) the short genetic distance between both members of the A. simplex complex; (iii) the fact that hybrid genotypes represent 16.67% of the parasites analyzed and are represented in all the populations studied, except for the Cantabrian one. When the genetic variation is estimated between the 42 individual A. simplex s.l. specimens studied these can be classified into four groups. The genetic distances and gene flow between three of them are compatible with the existence of three different genetic populations. The fourth is comprised of a single specimen of L3, identified both by PCR-RFLP and by RAPD-PCR as a new genotype.

Tratamiento de la preeclampsia grave con urapidil / Treatment of severe pre-eclampsia with urapidil

Estudio retrospectivo de 9 casos de pacientes con hipertensión en el contexto de una preeclampsia grave, tratadas con clorhidrato de urapidil. Analizamos una serie de variables: edad, semanas de gestación, dosis y número de ellas empleadas, tiempo transcurrido en controlar la presión arterial, efectos adversos maternofetales y test de Apgar al nacimiento. Los resultados demuestran la eficacia de dicho fármaco en el control de la hipertensión grave inducida por embarazo; normalizó en un tiempo relativamente corto tanto la presión arterial sistólica como la diastólica (11,6 ñ 7,50 min) y con dosis bajas (20,3 ñ 11,13) en 7 casos; sólo en un caso se requirieron tiempo y dosis mayores (40 min y 70 mg), y en otra gestante de 28 semanas no se pudo controlar y se tuvo que finalizar la gestación mediante cesárea. En cuanto a las reacciones adversas, tanto maternas como neonatales, a diferencia de los antihipertensivos habituales (hidralacina, labetalol o nifedipina), fueron irrelevantes (AU)

Diarrea de origen nosocomial en la población adulta / Nosocomial diarrhoea in the adult population

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Plasma level monitoring of oxcarbazepine in epileptic patients.

BACKGROUND: Despite the wide use of oxcarbazepine (OXC) there is little data concerning the usefulness of plasma level monitoring with this drug in Mexican patients with epilepsy. The purpose of the present study was to determine whether OXC levels correlate with dose, age, weight, or drugs used concomitantly. METHODS: Plasma levels of the antiepileptic drug OXC were evaluated in 214 patients with epilepsy. In each patient, plasma MHD (10-hydroxycarbazepine, the main metabolite of OXC) concentration was determined. Additionally, plasma protein binding was determined in 30 patients and affinity to red blood cells (RBCs) was evaluated in 50 patients. RESULTS: Our results showed that the mean plasma level of MHD was 15.34 microg/mL, mean protein binding ranged between 30-40%, and the mean RBC concentration was 18.38 microg/mL. A relationship between dose/weight and plasma concentration was found (r = 0.5149, p <0.001). In addition, a linear relationship between plasma and RBC concentration was established (r = 0.8806, p <0.0001). CONCLUSIONS: These results suggest that for OXC, routine RBC concentrations are not necessary to make drug adjustments.

Celulitis espontánea recidivante en un paciente con síndrome nefrótico / Recidivant spontaneous cellulitis in a patient with nephrotic syndrome

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