Virulence Genes of Helicobacter pylori Increase the Risk of Premalignant Gastric Lesions in a Colombian Population.

Background: Genetic variability of Helicobacter pylori is associated with various gastrointestinal diseases; however, little is known about interaction with sociodemographic in the development of premalignant lesions in Colombian patients. Methods: An analytical study was conducted including cases (patients with gastric atrophy, intestinal metaplasia, and gastric dysplasia) and controls (patients with nonatrophic gastritis). Sociodemographic information was obtained using a questionnaire. Histopathological diagnosis was performed according to the Sydney System. The cagA and vacA genotypes were established using polymerase chain reaction in paraffin blocks. The effect of each variable on the study outcome (premalignant lesion) is presented as odds ratio (OR) and 95% CI. A p value of <0.05 was considered as statistically significant. Results: The vacA/s1m1 genotype increases the risk of developing premalignant lesions of the stomach (OR: 3.05, 95% IC: 1.57-5.91, p=0.001). Age and educational level showed a positive interaction with the s1m1 genotype (adjusted OR: 3.68, 95% CI: 1.73-7.82, p=0.001). The cagA genotype was not correlated to the development of premalignant lesions of the stomach (OR: 1.32, 95% CI: 0.90-1.94, p=0.151). Conclusions: The vacA genotype, age, and educational level are indicators of the risk of developing premalignant lesions of the stomach in the study population. Significance Statement. Genetic variability of H. pylori and sociodemographic information could be used to predict the risk of premalignant lesions in stomach in Colombian population.

Helicobacter pylori genotypes associated with gastric cancer and dysplasia in Colombian patients.

INTRODUCTION AND AIMS: Colombia has high incidence levels of gastric cancer that can be explained by the genetic variability of Helicobacter pylori (H. pylori). Our aim was to establish the relation of the H. pylori CagA and VacA genotypes to dysplasia and gastric cancer, in a high-risk population. MATERIAL AND METHODS: A case-control study was conducted on 202 patients from a high-risk cancer zone. Patients with dysplasia and gastric cancer (cases) and patients with nonatrophic gastritis (controls) were included. Endoscopic sampling and histologic classification were carried out according to the Sydney system and the Lauren classification. Genetic information was obtained through polymerase chain reaction on paraffin blocks. The measures of association of the variables of interest were evaluated in bivariate and multivariate models. A P<0.05 was considered statistically significant and the SPSS version 25 program was employed. RESULTS: Age above 50 years (OR: 23.76; CI: 8.40-67.17; P=0.000) and the VacA s1m1 genotype (OR: 6.18; CI: 1.25-30.51; P=0.025) were associated with higher risk for developing dysplasia and gastric cancer. The CagA+ genotype was not found to be a risk factor for developing those pathologies (OR: 1.02; CI: 0.39-2.62; P=0.965). CONCLUSIONS: The H. pylori VacA genotypes are markers for the development of gastric cancer. That information could be used to create a risk index in a predictive model to optimize the healthcare of higher-risk patients.

Helicobacter pylori genotypes associated with gastric cancer and dysplasia in Colombian patients. / Genotipos de Helicobacter pylori asociados con cáncer gástrico y displasia en pacientes de Colombia.

INTRODUCTION AND AIMS: Colombia has high incidence levels of gastric cancer that can be explained by the genetic variability of Helicobacter pylori (H. pylori). Our aim was to establish the relation of the H. pylori CagA and VacA genotypes to dysplasia and gastric cancer, in a high-risk population. MATERIAL AND METHODS: A case-control study was conducted on 202 patients from a high-risk cancer zone. Patients with dysplasia and gastric cancer (cases) and patients with nonatrophic gastritis (controls) were included. Endoscopic sampling and histologic classification were carried out according to the Sydney system and the Lauren classification. Genetic information was obtained through polymerase chain reaction on paraffin blocks. The measures of association of the variables of interest were evaluated in bivariate and multivariate models. A P<0.05 was considered statistically significant and the SPSS version 25 program was employed. RESULTS: Age above 50 years (OR: 23.76; CI: 8.40-67.17; P=0.000) and the VacA s1m1 genotype (OR: 6.18; CI: 1.25-30.51; P=0.025) were associated with higher risk for developing dysplasia and gastric cancer. The CagA+ genotype was not found to be a risk factor for developing those pathologies (OR: 1.02; CI: 0.39-2.62; P=0.965). CONCLUSIONS: The H. pylori VacA genotypes are markers for the development of gastric cancer. That information could be used to create a risk index in a predictive model to optimize the healthcare of higher-risk patients.

Association of the Helicobacter pylori cagA, vacA, and iceA genotypes with chronic follicular gastritis in a Colombian population at high risk for gastric cancer. / Asociación de los genotipos cagA, vacA e IceA de H. pylori con la gastritis crónica y folicular en una población colombiana con alto riesgo de cáncer gástrico.

INTRODUCTION AND OBJECTIVE: Follicular gastritis is associated with Helicobacter pylori infection, but little is known of its relation to bacterial genotypes. Our aim was to establish the relation between follicular gastritis and different H. pylori strains. MATERIALS AND METHODS: An analytic case-control study was conducted that included 36 patients with follicular gastritis (cases) and 83 with nonatrophic gastritis (controls). The sociodemographic information was obtained through a questionnaire. Biopsies were evaluated according to the Sydney System and the Wotherspoon scoring system. Helicobacter pylori genotyping was performed using the polymerase chain reaction technique. The quantitative variables were presented as mean and standard deviation and the qualitative variables as proportions and absolute frequency. The effect of each variable on outcome (follicular gastritis) was evaluated through the odds ratio and its 95% confidence interval. Statistical significance was set at a P<0.05. RESULTS: Follicular gastritis was associated with Helicobacter pylori infection (OR: 13.41, CI: 1.7-103, P=0.01). The CagA+ genotype was present in 56.5% of the cases and 58% of the controls. The cytotoxic VacAs1m1strain was present in 82% of the isolates in both groups. IceA1 frequency was 34.8% in the cases and 26% in the controls and the difference was not statistically significant. CONCLUSIONS: The population studied had elevated frequencies of cytotoxic Helicobacter pylori strains and the iceA1 genotype was more frequent in follicular gastritis.

Novel consortium of Klebsiella variicola and Lactobacillus species enhances the functional potential of fermented dairy products by increasing the availability of branched-chain amino acids and the amount of distinctive volatiles.

AIMS: Identify novel bacterial taxa that could increase the availability of branched-chain amino acids and the amount of distinctive volatiles during skim milk fermentation. METHODS AND RESULTS: We recovered 344 bacterial isolates from stool samples of healthy and breastfed infants. Five were selected based on their ability to produce branched-chain amino acids. Three strains were identified as Escherichia coli, one as Klebsiella pneumoniae and other as Klebsiella variicola by molecular and biochemical methods. HPLC and solid-phase microextraction with GC-MS were used for the determination of free amino acids and volatile compounds respectively. The consortium formed by K. variicola and four Lactobacillus species showed the highest production of Leu and Ile in skim milk fermentation. In addition, the production of volatile compounds, such as acetoin, ethanol, 2-nonanone, and acetic, hexanoic and octanoic acids, increased in comparison to commercial yogurt, Emmental and Gouda cheese. Also, distinctive volatiles, such as 2,3-butanediol, 4-methyl-2- hexanone and octanol, were identified. CONCLUSION: The use of K. variicola in combination with probiotic Lactobacillus species enhances the availability of Leu and Ile and the amount of distinctive volatiles during skim milk fermentation. SIGNIFICANCE AND IMPACT OF THE STUDY: The identified consortium increases the functional potential of fermented dairy products.

RNA-sequencing of the brain transcriptome implicates dysregulation of neuroplasticity, circadian rhythms and GTPase binding in bipolar disorder.

RNA-sequencing (RNA-seq) is a powerful technique to investigate the complexity of gene expression in the human brain. We used RNA-seq to survey the brain transcriptome in high-quality postmortem dorsolateral prefrontal cortex from 11 individuals diagnosed with bipolar disorder (BD) and from 11 age- and gender-matched controls. Deep sequencing was performed, with over 350 million reads per specimen. At a false discovery rate of <5%, we detected five differentially expressed (DE) genes and 12 DE transcripts, most of which have not been previously implicated in BD. Among these, Prominin 1/CD133 and ATP-binding cassette-sub-family G-member2 (ABCG2) have important roles in neuroplasticity. We also show for the first time differential expression of long noncoding RNAs (lncRNAs) in BD. DE transcripts include those of serine/arginine-rich splicing factor 5 (SRSF5) and regulatory factor X4 (RFX4), which along with lncRNAs have a role in mammalian circadian rhythms. The DE genes were significantly enriched for several Gene Ontology categories. Of these, genes involved with GTPase binding were also enriched for BD-associated SNPs from previous genome-wide association studies, suggesting that differential expression of these genes is not simply a consequence of BD or its treatment. Many of these findings were replicated by microarray in an independent sample of 60 cases and controls. These results highlight common pathways for inherited and non-inherited influences on disease risk that may constitute good targets for novel therapies.

Colectomía parcial laparoscópica electiva por enfermedad diverticular / Elective laparoscopic colectomy for diverticular disease

Background: Colorectal colectomy is a less invasive technique that can be used for the treatment of diverticular disease, recently in younger patients. Aim: To report the experience with laparoscopic colectomy for diverticular disease. Material and Methods: All patients with indication for elective surgical resolution for diverticular disease were subjected to laparoscopic surgery from 1997 to 2009. The surgical protocols of these patients were analyzed. Results: Sixty patients with average age 53,8 (31 males) were operated in the period. Forty six were subjected to a sigmoidectomy and 14 to left hemicolectomy. Operative average time was 173 minutes and hospital stay 4,16 days. Three patients had to be converted to open surgery and three had complications that were managed without need of reoperation. During a median follow up of 38 months, the disease relapsed in two patients, which did not require a new intervention. Conclusions: Elective laparoscopic colectomy for diverticular disease is feasible and safe.

La cirugía laparoscópica colorrectal, aunque de desarrollo lento, ha presentado en los últimos años ventajas con respecto a la cirugía abierta. Hay escasas publicaciones nacionales sobre esta técnica en enfermedad diverticular. Objetivo: Presentar nuestra experiencia en enfermedad diverticular en una serie consecutiva de pacientes con indicación quirúrgica electiva resueltos por vía laparoscópica. Material y Método: Se analizan los protocolos prospectivos de cirugía laparoscópica de colon con diagnóstico de enfermedad diverticular para resolución electiva, desde junio de 1997, hasta diciembre de 2009. Todo paciente con indicación quirúrgica electiva por esta patología fue resuelto por vía laparoscópica. Se estudian edad, sexo, tipo de resección, evolución postoperatoria inmediata y tardía. Resultados: Se operaron 60 pacientes, con edad promedio de 53,8 años. De éstos 46 fueron sigmoidectomías y 14 hemicolectomías izquierdas. El tiempo operatorio promedio fue de 173 minutos y la hospitalización de 4,16 días. Se convirtieron 3 pacientes (5 por ciento) y hubo 3 complicaciones (5 por ciento), que fueron manejadas médicamente. Hubo 1 estenosis de anastomosis tratada endoscópicamente como complicación tardía. Seguimiento promedio de 37,9 meses. Hubo 2 recidivas (3,3 por ciento), tratadas médicamente y no hubo mortalidad en esta serie. Conclusión: La cirugía laparoscópica para la enfermedad diverticular electiva es factible de realizar en la gran mayoría de los pacientes, con baja morbilidad y rápida recuperación.

Valores bioquímicos en sangre de la tortuga verde (Chelonia mydas) presentes en la Alta Guajira Venezuela / Blood biochemistry values of green turtle (Chelonia mydas) present in the Alta Guajira Venezuela

Las tortugas marinas han sido ampliamente investigadas y documentadas en las últimas décadas. La bioquímica sanguínea representa una valiosa herramienta diagnóstica para el monitoreo del estado de salud de la fauna silvestre El objetivo de este estudio fue determinar los valores bioquímicos en la sangre de la tortuga verde (Chelonia mydas) presente en la Alta Guajira, Venezuela. La extracción de las muestras sanguíneas se realizó de los senos cervicales dorsales en 28 ejemplares de tortugas verdes capturadas en redes y posteriormente liberadas. Fueron medidos el largo curvo del caparazón (LCC) y ancho curvo del caparazón (ACC) con una cinta métrica flexible. Se determinaron los valores bioquímicos de la sangre: proteínas totales, albúmina, fosfatasa alcalina, urea, creatinina, ácido úrico, colesterol, triglicéridos, glucosa y fósforo por colorimetría, utilizando kits comerciales; los minerales (calcio, hierro, magnesio, zinc) se determinaron por espectrofotometría de absorción y emisión (sodio, potasio). Los valores promedio fueron: 4,37 g/dL proteínas totales, 1,50 g/dL albúmina, 119,63 U/L fosfatasa alcalina, 27,60 mg/dL urea, 0,17 mg/dL creatinina, 3,36 mg/dL ácido úrico, 180,77 mg/dL colesterol, 32,24 mg/dL triglicéridos, 130,07 mg/dL glucosa, 5,20 mg/dL fósforo, 7,94 mg/dL calcio, 44,02 µg/dL hierro, 196,68 meq/L sodio, 4,75 meq/L potasio, 4,99 mg/dL magnesio y 2,11 mg/L zinc. Estos resultados se encuentran dentro de los intervalos de referencia documentados para la especie, a excepción de la fosfatasa alcalina, triglicéridos, colesterol y la urea, los cuales presentaron las mayores variaciones.

Sea turtles have been widely investigated and reviewed over the last decades. Blood biochemistry represents a valuable diagnostic tool for monitoring the health condition of wildlife. The aim of this study was to determine the blood biochemistry values of green turtles (Chelonia mydas) present in the Alta Guajira, Venezuela. Blood samples were collected of the dorsal cervical sinuses from 28 green turtles captured in gill nets. The turtles were released later. The curved carapace length (CCL) and curved carapace width (CCW) were measured with a flexible measuring tape. The following values were established using commercial kits: total proteins, albumin, alkaline phosphatase, urea, creatinine, uric acid, cholesterol, triglycerides, glucose, and phosphorus by colorimetry; the minerals were determined by emission (sodium, potassium) and absorption spectrometry (calcium, iron, magnesium, zinc). The mean values obtained were: total proteins (4.37 g/dL), albumin (1.50 g/dL), alkaline phosphatase (119.63 U/L), urea (27.60 mg/dL), creatinine (0.17 mg/dL), uric acid (3.36 mg/dL), cholesterol (180.77 mg/dL), triglycerids (32.24 mg/dL), glucose (130.07 mg/dL), phosphorus (5.20 mg/dL), calcium (7.94 mg/dL), iron (44.02 µg/dL), sodium (196.68 meq/L), potassium (4.75 meq/L), magnesium (4.99 mg/dL) and zinc (2.11 mg/L). These results fall within the reference intervals documented in this species, except for the alkaline phosphatase, triglycerides, cholesterol, and urea, which showed the largest variations.

Expresión de proteínas del choque térmico HSP72 y HSP73 en casos colombianos de Linfoma de Hodgkin positivos y negativos para virus de Epstein Barr / Expression of heat shock proteins HSP72 and HSP73 in Epstein-Barr positive or negative Hodgkin lymphoma

Background: The expression of heat shock proteins (HSP70) in tumor cells or virus infected cells is important for the induction of specific cellular immune response. They are implicated in transport of immunodominants peptides in the endoplasmic reticulum, activation of antigen presenting cells and cross priming of CD8 T cells. Aim: To analyze the expression of HSP70 protein in its constitutive (HSP73) and inducible forms (HSP72) in Hodgkin's lymphoma (HL), infected or not by Epstein Barr virus (EBV) and to assess its relationship with pathological subtype, clinical stages and treatment response. Material and methods: The analysis of HSP73 and HSP72 was done by immunoperoxidase on routinely processed paraffin sections with prior antigen retrieval. Results: Sixty seven cases were studied. The expression of HSP73 and HSP72 was detected in 19.4 and 17.9% of samples respectively. The infiltrating lymphocytes expressed HSP72 in 58% of cases. The pathological subtypes with the higher expression in lymphocytes were mixed cellularity and nodular sclerosis. No differences in HSP70 expression were observed, according to clinical stage, treatment response or the presence of EBV. Conclusions: The expression of HSP72 on lymphocytes suggests that this protein plays an important role in the induction and amplification of anti-tumor immune response (Rev Méd Chile 2003; 131: 1375-81).

Tuberomammillary nucleus activation anticipates feeding under a restricted schedule in rats.

We used FOS-immunoreactivity to map changes in the neuronal activity of brain nuclei related to the state of arousal, in rats under a restricted feeding schedule. Our main finding was the outstanding activation of the tuberomammillary nucleus 24h after a meal, and its steep deactivation, which was independent of actually having the meal. The time course of FOS activation and deactivation indicated a burst of tuberomammilary nucleus activity in close temporal relation with the increased locomotor activity shown by rats in anticipation of the next meal.

Antiaggresive and anxiolytic effects of gepirone in mice, and their attenuation by WAY 100635.

The purpose of the investigation was to ascertain whether (a) the antiaggressive effects of the 5-HT1A partial agonist, Gepirone, could be mediated via its anxiolytic action; (b) the selective 5-HT1A antagonist, WAY 100635, reversed these effects, and (c) the modulation of "stress hyperthermia" could be attributed to direct effects of the drugs. Isolated male mice were treated with WAY 100635 (0, 1.5, 2.5, and 5 mg/kg) given 15 min prior to Gepirone (0, 2.5, 5, and 7.5 mg/kg). Rectal temperature was taken before the first injection and again prior to the behavioral tests. In the first session only, subjects were tested for anxiety on the elevated plus-maze before the resident-intruder test. Gepirone reduced aggression in a dose-dependent manner. This effect was counteracted by all doses of WAY 100635. On the elevated plus maze, Gepirone increased open-arm entries and duration and reduced risk assessment. The largest dose of WAY 100635 had a mild direct anxiolytic action, but all doses reduced the anxiolytic action of the largest dose of Gepirone. Body temperature was decreased dose dependently by Gepirone, an effect prevented by WAY 100635. The results justify attributing the involvement of the 5-HT1A receptors in the modulation of aggression and anxiety.

Combined effects of Gepirone and (+)WAY 100135 on territorial aggression in mice.

The purpose of this investigation was to elucidate the involvement of the serotonergic 5-HT1A system in the control of aggression. The paradigm was the response of a resident mouse to an intruder into its territory. Three experiments were performed to assess the action of various doses of Gepirone (a partial agonist) and (+)WAY 100135 (a putative antagonist), separately and in combination, on aggression and on rectal body temperature. The most consistent action of Gepirone was an increase in the latency to attack. After initiation of fighting, rates of attack, chase, and tail rattling were reduced in a dose-dependent manner by i.p. administration of 2.5, 5, and 10 mg/kg of Gepirone. There was no evidence of sedation or motor impairment, but autogrooming was decreased. When doses of 2.5, 5, and 10 mg/kg of (+)WAY 100135 (WAY) were given, no effects whatsoever on aggressive or other behaviors were observed. In a third experiment, a two-factor design was followed in which injection of WAY (0, 2.5, and 5 mg/kg) was followed 15 min later by injection of Gepirone (0, 2.5, 5, and 10 mg/kg). WAY decreased attack latency, increased attack rate, and attenuated the marked dose-dependent aggression reducing properties of Gepirone. The test procedure resulted in "stress hyperthermia," which was reduced by Gepirone and increased by WAY. In both behavioral and temperature measures, the larger dose of WAY proved to be less effective than the smaller one. The results support the involvement of the 5-HT1A system in the modulation of some forms of aggression.

NADPH-d positive neurons in the developing somatosensory cortex of the rat: effects of early and late environmental enrichment.

The effects of environmental enrichment upon the topographic arrangement of NADPH diaphorase-positive neurons (NADPH-d+ neurons) was studied in the somatosensory cortex of 56 Sprague-Dawley albino rats during early stages of development (18th, 24th, 30th and 60th postnatal days). This diaphorase is easily demonstrable, providing a convenient marker for quantitative studies. Environmental enrichment diminished the number of NADPH-d+ neurons and exerted its maximal influence during lactation, a time of exceptional cortical susceptibility. This implies that the magnitude of such effects on the density of NADPH-d+ neurons is age-dependent. Furthermore, it was found that the experience-dependent cortical changes persisted after a subsequent period without environmental stimulation. The effects of early environmental enrichment did not occur uniformly throughout the cerebral hemispheres but, instead, such effects were maximal in the latero-ventral sector of the cerebral cortex where a dramatic reduction in the number of NADPH-d+ neurons was observed. Particularly striking was the existence of a latero-medial sequence of NADPH-d+ neurons in the infragranular layer and a reversed distribution of labeled cells, in the supragranular layer. Both ontogenetic sequences of NADPH-d+ neurons remained unchanged during postnatal development in controls and enriched subjects (18th-60th postnatal days).

The gap effect during visual and auditory stimulation using manual responses.

Six experiments were conducted in naive human participants to examine any facilitation produced in manual reaction time (RT) by the interposition of a temporal gap between a warning signal and an imperative signal. Peripheral visual stimuli and monoaural auditory stimuli were used as targets. Participants showed a facilitation of RTs to the targets for both auditory and visual stimuli in the five experiments in which RTs were the dependent variable. In addition, the gap effect increased over successive blocks of trials, suggesting learning. RTs were facilitated only when the gap had predictive value and was salient. Using a variable temporal gap or visual warning stimulus did not change the facilitation in RTs. A further experiment demonstrated that the gap can be perceived by the participants. The dissociation between a learned and a non-learned component in the gap effect suggests that the temporal gap induces two independent processes: warning and disengagement of attention.

Expression of constitutively active IkappaB beta in T cells of transgenic mice: persistent NF-kappaB activity is required for T-cell immune responses.

The transcription factor NF-kappaB is normally sequestered in the cytoplasm by members of the IkappaB family, including IkappaB alpha, IkappaB beta, and the recently cloned IkappaB epsilon. Upon cellular activation, these inhibitors are rapidly phosphorylated on two amino-terminal serines, ubiquitinated, and degraded by the 26S proteasome, releasing a functional NF-kappaB. To determine the importance of IkappaB beta in NF-kappaB regulation in T cells, we generated transgenic mice expressing a constitutively active IkappaB beta mutant (mIkappaB beta) under the control of the lck promoter. The transgene contains the two critical N-terminal serine residues mutated to alanines and therefore no longer susceptible to degradation upon cell activation. mIkappaB beta is unable to totally displace IkappaB alpha from RelA-containing complexes, thus allowing a transient activation of NF-kappaB upon T-cell stimulation. However, mIkappaB beta completely blocks NF-kappaB activity after IkappaB alpha degradation. In addition, as a consequence of this inhibition, ikba expression is down regulated, along with that of other NF-kappaB-regulated genes. These transgenic mice have a significant reduction in the peripheral T-cell population, especially CD8+ cells. The remaining T cells have impaired proliferation in response to phorbol 12-myristate 13-acetate plus phytohemagglutinin or calcium ionophore but not to anti-CD3/anti-CD28 costimulation. As a result of these alterations, transgenic animals present defects in immune responses such as delayed-type hypersensitivity and the generation of specific antibodies against T-cell-dependent antigens. These results show that in nonstimulated T cells, IkappaB beta cannot efficiently displace IkappaB alpha bound to RelA-containing complexes and that persistent NF-kappaB activity is required for proper T-cell responses in vivo.