Cobalamin cbiP mutant shows decreased tolerance to low temperature and copper stress in Listeria monocytogenes.

BACKGROUND: Listeria monocytogenes is a foodborne pathogen that causes listeriosis in humans. This pathogen activates multiple regulatory mechanisms in response to stress, and cobalamin biosynthesis might have a potential role in bacterial protection. Low temperature is a strategy used in the food industry to control bacteria proliferation; however, L. monocytogenes can grow in cold temperatures and overcome different stress conditions. In this study we selected L. monocytogenes List2-2, a strain with high tolerance to the combination of low temperature + copper, to understand whether the cobalamin biosynthesis pathway is part of the tolerance mechanism to this stress condition. For this, we characterized the transcription level of three cobalamin biosynthesis-related genes (cbiP, cbiB, and cysG) and the eutV gene, a transcriptional regulator encoding gene involved in ethanolamine metabolism, in L. monocytogenes strain List2-2 growing simultaneously under two environmental stressors: low temperature (8 °C) + copper (0.5 mM of CuSO4 × 5H2O). In addition, the gene cbiP, which encodes an essential cobyric acid synthase required in the cobalamin pathway, was deleted by homologous recombination to evaluate the impact of this gene in L. monocytogenes tolerance to a low temperature (8 °C) + different copper concentrations. RESULTS: By analyzing the KEGG pathway database, twenty-two genes were involved in the cobalamin biosynthesis pathway in L. monocytogenes List2-2. The expression of genes cbiP, cbiB, and cysG, and eutV increased 6 h after the exposure to low temperature + copper. The cobalamin cbiP mutant strain List2-2ΔcbiP showed less tolerance to low temperature + copper (3 mM) than the wild-type L. monocytogenes List2-2. The addition of cyanocobalamin (5 nM) to the medium reverted the phenotype observed in List2-2ΔcbiP. CONCLUSION: These results indicate that cobalamin biosynthesis is necessary for L. monocytogenes growth under stress and that the cbiP gene may play a role in the survival and growth of L. monocytogenes List2-2 at low temperature + copper.

[Consensus on the use of iSGLT2 in the treatment of patients with type 2 diabetes mellitus]. / Documento de consenso sobre el uso de los iSGLT2 en el tratamiento de pacientes con diabetes mellitus tipo 2.

Although in recent years in Mexico the quality of diabetes mellitus (DM) care has improved and access to health services and medications has increased, there is a lack of adherence to the recommendations of the clinical guidelines, which could explain the poor glycemic control in many of the patients with DM. Sodium-glucose cotransporter type 2 (iSGLT2) inhibitors have been the last class of antidiabetic agents to receive approval from the Food and Drug Administration (FDA) and COFEPRIS (Mexico). In order to improve the use of SGLT2i in clinical practice in Mexico, this paper presents the recommendations issued by a panel of eleven Mexican experts based on the new published evidence for the treatment of patients with DM2.

Aunque en los últimos años en México ha mejorado la calidad de la atención de la diabetes mellitus (DM) y ha aumentado el acceso a servicios de salud y medicamentos, existe una falta de apego a las recomendaciones de las guías de práctica clínica, que podría explicar la falta de un control glucémico adecuado en muchos de los pacientes con DM. Los inhibidores del cotransportador de sodio-glucosa tipo 2 (iSGLT2) han sido la última clase de agentes antidiabéticos en recibir la aprobación de la Food and Drug Administration (FDA) y de la Comisión Federal para la Protección contra Riesgos Sanitarios de México (COFEPRIS). Con el fin de mejorar el uso de los iSGLT2 en la práctica clínica en México, en este documento se presentan las recomendaciones emitidas por un panel de 11 expertos mexicanos con base en las nuevas evidencias publicadas para el tratamiento de los pacientes con DM2.

Documento de consenso sobre el uso de los iSGLT2 en el tratamiento de pacientes con diabetes mellitus tipo 2 / Consensus on the use of iSGLT2 in the treatment of patients with type 2 diabetes mellitus

Resumen Aunque en los últimos años en México ha mejorado la calidad de la atención de la diabetes mellitus (DM) y ha aumentado el acceso a servicios de salud y medicamentos, existe una falta de apego a las recomendaciones de las guías de práctica clínica, que podría explicar la falta de un control glucémico adecuado en muchos de los pacientes con DM. Los inhibidores del cotransportador de sodio-glucosa tipo 2 (iSGLT2) han sido la última clase de agentes antidiabéticos en recibir la aprobación de la Food and Drug Administration (FDA) y de la Comisión Federal para la Protección contra Riesgos Sanitarios de México (COFEPRIS). Con el fin de mejorar el uso de los iSGLT2 en la práctica clínica en México, en este documento se presentan las recomendaciones emitidas por un panel de 11 expertos mexicanos con base en las nuevas evidencias publicadas para el tratamiento de los pacientes con DM2.

Abstract Although in recent years in Mexico the quality of diabetes mellitus (DM) care has improved and access to health services and medications has increased, there is a lack of adherence to the recommendations of the clinical guidelines, which could explain the poor glycemic control in many of the patients with DM. Sodium-glucose cotransporter type 2 (iSGLT2) inhibitors have been the last class of antidiabetic agents to receive approval from the Food and Drug Administration (FDA) and COFEPRIS (Mexico). In order to improve the use of SGLT2i in clinical practice in Mexico, this paper presents the recommendations issued by a panel of eleven Mexican experts based on the new published evidence for the treatment of patients with DM2.

Cobalamin cbiP mutant shows decreased tolerance to low temperature and copper stress in Listeria monocytogenes

BACKGROUND: Listeria monocytogenes is a foodborne pathogen that causes listeriosis in humans. This pathogen activates multiple regulatory mechanisms in response to stress, and cobalamin biosynthesis might have a potential role in bacterial protection. Low temperature is a strategy used in the food industry to control bacteria proliferation; however, L. monocytogenes can grow in cold temperatures and overcome different stress conditions. In this study we selected L. monocytogenes List2-2, a strain with high tolerance to the combination of low temperature +copper, to understand whether the cobalamin biosynthesis pathway is part of the tolerance mechanism to this stress condition. For this, we characterized the transcription level of three cobalamin biosynthesis related genes ( cbiP , cbiB, and cysG ) and the eutV gene, a transcriptional regulator encoding gene involved in ethanolamine metabolism, in L. monocytogenes strain List2-2 growing simultaneously under two environmental stressors: low temperature (8 °C) +copper (0.5 mM of CuSO4 ×5H2O). In addition, the gene cbiP , which encodes an essential cobyric acid synthase required in the cobalamin pathway, was deleted by homologous recombination to evaluate the impact of this gene in L. monocytogenes tolerance to a low temperature (8 °C) +different copper concentrations. RESULTS: By analyzing the KEGG pathway database, twenty-two genes were involved in the cobalamin biosynthesis pathway in L. monocytogenes List2-2. The expression of genes cbiP , cbiB, and cysG, and eutV increased 6 h after the exposure to low temperature +copper. The cobalamin cbiP mutant strain List2-2Δ cbiP showed less tolerance to low temperature +copper (3 mM) than the wild type L. monocytogenes List2-2. The addition of cyanocobalamin (5 nM) to the medium reverted the phenotype observed in List2-2Δ cbiP . CONCLUSION: These results indicate that cobalamin biosynthesis is necessary for L. monocytogenes growth under stress and that the cbiP gene may play a role in the survival and growth of L. monocytogenes List2-2 at low temperature +copper.

Mexican population sub-analysis of the lixilan clinical program with the fixed ratio combination of insulin glargine and lixisenatide (iGlarLixi).

AIM: To evaluate the efficacy and safety of iGlarLixi in Mexican patients with type 2 diabetes who participated in the LixiLan clinical trials and compare results with the rest of the patients. METHODS: Data was collected for Mexican patients who participated in either of three studies: phase 2 trial LixiLan-POC, that compared iGlarLixi vs insulin glargine (iGlar) on inadequately controlled patients with metformin; phase 3 trial LixiLan-O, comparing iGlarLixi vs iGlar and lixisenatide on inadequately controlled patients with oral antidiabetic agents; and finally the phase 3 trial LixiLan-L, comparing iGlarLixi vs iGlar on inadequately controlled patients with basal insulin. The primary endpoint was the change in HbA1c from baseline to end of treatment. RESULTS: In the Mexican population, treatment with iGlarLixi significantly improved HbA1c compared with each component alone achieving an average of 6.5%; (6.17%, 6.63% and 6.73% for the LixiLan-POC, O and L studies respectively) and an average HbA1c reduction from baseline of 1.6%, for the three studies at end of treatment period. CONCLUSION: The efficacy and safety profile of iGlarLixi demonstrate a fair or better composite endpoint of HbA1c without hypoglycemia and no weight gain compared to overall trial population, which could help improve Mexican patients' outcomes.

Terapia ocupacional y paciente crítico / Occupational therapy and critical ill patients

El presente estudio fue realizado en la Unidad de Pacientes Críticos adultos, del Hospital Clínico de la Pontificia Universidad Católica de Chile (UPC-HCPUC), durante el año 2012, donde se exploraron las características del paciente crítico, para obtener un perfil de salud global durante su estadía en la UPC, con el fin de determinar si sería posible realizar una intervención desde la Terapia Ocupacional que fuese un aporte a esta unidad.Se realizó un estudio prospectivo, observacional en la UPC médico quirúrgica durante 25 días. Los resultados obtenidos permitieron caracterizar al paciente crítico de esta unidad, como un sujeto con alta probabilidad de presentar compromiso de conciencia, edema en mano, limitación de rango de movimiento articular (ROM) en muñeca y dedos, y carencia de estímulos que evoquen su realidad previa a la hospitalización. Finalmente, a partir del análisis del perfil del paciente crítico de la UPC HCPUC y del contexto al que se encuentra expuesto, se concluye que la intervención temprana de Terapia Ocupacional podría disminuir y prevenir la aparición de algunos signos asociados al paciente crítico, comprobándose la hipótesis, que dadas las características de este paciente, sería posible realizar una intervención desde la Terapia Ocupacional.

This study was conducted in The Unit Critics adult patients, Clinical Hospital of the Catholic University of Chile (UPC HCPUC), in 2012, where the characteristics of critical patients were explored to obtain a profile of global health while in the UPC, in order to determine whether it would be possible to make an intervention from occupational therapy to be a contribution to this unit.A prospective, observational study in medical UPC-surgery for 25 days. The results allowed to characterize critical patients of this unit, as a subject with high probability of impairment of consciousness, edema in hand, limitation of joint range of motion (ROM) in the wrist and fingers, and lack of stimuli that evoke your reality prior to hospitalization.Finally, from the analysis of the profile of critical patient - HCPUC UPC and the context to which it is exposed, it is concluded that early intervention occupational therapy could reduce and prevent the appearance of certain signs associated with critical patient, checking hypothesized that given the characteristics of this patient, it would be an intervention from Occupational Therapy.

[Ministry of Health Intensive Care Medicine Commission: proposals for the development of the discipline]. / Medicina intensiva en Chile: desafíos para su desarrollo. Documento de la Comisión Nacional de Medicina Intensiva del Ministerio de Salud.

Intensive care medicine in Chile is still in its dawn. It has experienced a progressive growth in the last decade, but continues to be weak. Although investments in the discipline have increased fivefold, there is still a severe deficiency of intensive care specialists. This issue will represent a serious problem in the near future. The Ministry of Health gathered an expert committee to study the problem and propose solutions for the future development of the discipline.

Síntomas psiquiátricos e insulinoma: reporte de caso / Psychiatric symptoms and insulinoma: a case report

Insulinomas are pancreatic endocrine neoplasms with a low incidence between 1-4 cases per million per year. Case description: A female 49 years-old with neurological and psychiatric symptoms were treated for two years as a psychiatric patient. Presented a glucose value, which reflects hypoglycemia. The patient was operated with resolution of symptoms. Conclusion: Assess all patients with psychiatric symptoms and perform a complete medical history and laboratory findings, being the most opportune glucose...

Medicina intensiva en Chile: desafíos para su desarrollo. Documento de la Comisión Nacional de Medicina Intensiva del Ministerio de Salud / Ministry of Health Intensive Care Medicine Commission: Proposals for the development of the discipline

Intensive care medicine in Chile is still in its dawn. It has experienced a progressive growth in the last decade, but continues to be weak. Although investments in the discipline have increased fivefold, there is still a severe deficiency of intensive care specialists. This issue will represent a serious problem in the near future. The Ministry of Health gathered an expert committee to study the problem and propose solutions for the future development of the discipline.

Strongyloides stercolaris: manifestaciones sistémicas de la parasitosis / Strongyloides stercolaris: systemic manifestations of parasitic diseases

Se describen tres casos de pacientes portadores crónicos de Strongyloidesstercolaris gastrointestinal oculto, con manifestaciones clínicas y de laboratorio que mimetizan patologías autoinmunes, en quienes el tratamiento inmunosupresor ocasionó empeoramiento de la sintomatología hasta el óbito en uno de los mismos.

Three clinic cases of patients with chronic hidden gastrointestinalStrongyloides stercolaris infection are described, with clinical manifestationsand analysis results pretending auto-immune diseases. In these patients, the immunosuppressive therapy made those manifestations got worse and even caused death in one of them.

Strongyloides stercolaris: manifestaciones sistémicas de la parasitosis / Strongyloides stercolaris: systemic manifestations of parasitic diseases

Se describen tres casos de pacientes portadores crónicos de Strongyloidesstercolaris gastrointestinal oculto, con manifestaciones clínicas y de laboratorio que mimetizan patologías autoinmunes, en quienes el tratamiento inmunosupresor ocasionó empeoramiento de la sintomatología hasta el óbito en uno de los mismos.(AU)

Three clinic cases of patients with chronic hidden gastrointestinalStrongyloides stercolaris infection are described, with clinical manifestationsand analysis results pretending auto-immune diseases. In these patients, the immunosuppressive therapy made those manifestations got worse and even caused death in one of them.(AU)

The dipeptidyl peptidase-4 inhibitor PHX1149 improves blood glucose control in patients with type 2 diabetes mellitus.

AIM: To determine the efficacy and tolerability of PHX1149, a novel dipeptidyl peptidase-4 (DPP4) inhibitor, in patients with type 2 diabetes. METHODS: This is a multicentre, randomized, double-blind, placebo-controlled, 4-week study in patients with type 2 diabetes with suboptimal metabolic control. Patients with a baseline haemoglobin A(1c) (HbA(1c)) of 7.3 to 11.0% were randomized 1 : 1 : 1 : 1 to receive once-daily oral therapy with either PHX1149 (100, 200 or 400 mg) or placebo; patients were on a constant background therapy of either metformin alone or metformin plus a glitazone. RESULTS: Treatment with 100, 200 or 400 mg of PHX1149 significantly decreased postprandial glucose area under the curve AUC(0-2 h) by approximately 20% (+0.11 +/- 0.50, -2.08 +/- 0.51, -1.73 +/- 0.49 and -1.88 +/- 0.48 mmol/l x h, respectively, for placebo and 100, 200 and 400 mg (p = 0.002, 0.008 and 0.004 vs. placebo). Postprandial AUC(0-2 h) of intact glucagon-like peptide-1, the principal mediator of the biological effects of DPP4 inhibitors, was increased by 3.90 +/- 2.83, 11.63 +/- 2.86, 16.42 +/- 2.72 and 15.75 +/- 2.71 pmol/l x h, respectively, for placebo and 100, 200 and 400 mg (p = 0.053, 0.001 and 0.002 vs. placebo). Mean HbA(1c) was lower in all dose groups; the placebo-corrected change in the groups receiving 400 mg PHX1149 was -0.28% (p = 0.02). DPP4 inhibition on day 28 was 53, 73 and 78% at 24 h postdose in the groups receiving 100, 200 and 400 mg PHX1149, respectively. There were no differences in adverse events between PHX1149-treated and placebo subjects. CONCLUSIONS: Addition of the DPP4 inhibitor PHX1149 to a stable regimen of metformin or metformin plus a glitazone in patients with type 2 diabetes was well tolerated and improved blood glucose control.

[Therapeutical targets for revert liver fibrosis]. / Blancos terapéuticos potenciales para revertir la cirrosis hepática.

Liver fibrosis is the common response to chronic liver injury, ultimately leading to cirrhosis and its complications: portal hypertension, liver failure, hepatic encephalopathy, and hepatocellular carcinoma and others. Efficient and well-tolerated antifibrotic drugs are still lacking, and current treatment of hepatic fibrosis is limited to withdrawal of the noxious agent. Efforts over the past decade have mainly focused on fibrogenic cells generating the scarring response, although promising data on inhibition of parenchymal injury or reduction of liver inflammation have also been obtained. A large number of approaches have been validated in culture studies and in animal models, and several clinical trials are underway or anticipated for a growing number of molecules. This review highlight recent advances in the molecular mechanisms of liver fibrosis and discusses mechanistically based strategies that have recently emerged.

Blancos terapéuticos potenciales para revertir la cirrosis hepática / Therapeutical targets for revert liver fibrosis

Liver fibrosis is the common response to chronic liver injury, ultimately leading to cirrhosis and its complications: portal hypertension, liver failure, hepatic encephalopathy, and hepatocellular carcinoma and others. Efficient and well-tolerated antifibrotic drugs are still lacking, and current treatment of hepatic fibrosis is limited to withdrawal of the noxious agent. Efforts over the past decade have mainly focused on fibrogenic cells generating the scarring response, although promising data on inhibition of parenchymal injury or reduction of liver inflammation have also been obtained. A large number of approaches have been validated in culture studies and in animal models, and several clinical trials are underway or anticipated for a growing number of molecules. This review highlight recent advances in the molecular mechanisms of liver fibrosis and discusses mechanistically based strategies that have recently emerged.

Oral aluminum administration to rats wih normal renal function. 1. Impairment of erythropoiesis.

Aluminum (Al) toxicity has been mainly investigated in uremic patients although healthy subjects and patients without renal insufficiency are not exempt from its potential deleterious effects. This experimental study aims to elucidate the action of different doses of Al citrate on in vivo erythropoiesis and find out whether the metal exerts a local toxic effect upon the bone marrow late erythroid progenitor cells. The groups in the first experimental series were: C1 (n=5) controls and TAl-1 (n=5) rats receiving 1 micromol Al citrate/g body weight/day by gavage. Colony-forming units-erythroid (CFU-E) development was inhibited in the TAl-1 group, but the median osmotic fragility (MOF) and hematocrit (Ht) values were similar to those of the C1 group. The groups in the second series were C2 (n=5) controls and TAl-2 (n=5) rats receiving Al citrate in drinking water (100 mmol/l). The TAl-2 group showed decreased Ht, hemoglobin concentration, MOF and red blood-cell life-span values (P<0.05), and a marked inhibition of the CFU-E development (P<0.01). Serum and bone Al concentrations were increased in both Al-treated groups (P < 0.01). There was a dose-dependent increase in bone Al levels (P < 0.01) and a dose-dependent decrease of CFU-E development (P<0.05). The CFU-E development was inversely correlated with the bone Al content (r=-0.79; P<0.05). The results demonstrate that even very low doses of Al citrate impair erythropoiesis in vivo and higher doses exert a deleterious action on both CFU-E and mature erythrocytes. This might show a local effect of Al on CFU-E caused by the bone sensitivity to the metal accumulation.

Neumonia nosocomial en pacientes en ventilación mecánica / Nosocomial pneumonia in patients in mechanical ventilation

Durante un período de 4 meses entre Septiembre de 1992 y Enero de 1993 se estudiaron prospectivamente a 21 pacientes que requirieron para su manejo intubación endotraqueal y conección a ventilación mecánica, sin infección respiratoria previa al ingreso a la Unidad de Cuidados Intensivos. Se realizó seguimiento con cultivo cuantitativo de aspirado endotraqueal diariamente y en el momento de sospecha de infección pulmonar se aplicaron los scores clínicos de Johanson (1) y Pugin (10), para diagnósticar neumonía nosocomial, la que se presento en promedio a los 8 días postingreso a la unidad. A todos los que presentaron neumonía y que su condición crítica lo permitió, se efectuó broncofibroscopía con lavado broncoalveolar. Los agentes etiológicos encontrados fueron: acinetobacter baumanii en un 62,5 por ciento, seguidos por pseudomona aeruginosa en un 37, 5 por ciento. Hubo coincidencia en los microorganismos aislados en el aspirado endotraqueal y en el lavado broncoalveolar, con un recuento de colonias en el cultivo cuantitativo de 10(5). De los scores utilizados el que demostró mayor especificidad, fue el propuesto por Pugin (10), con una puntuación mayor o igual a 8 puntos. Los criterios clínicos de Johanson (1) carecen de especificidad. En este trabajo se observó que el método de aspirado endotraqueal bien efectuado, con puntos de corte mayor o igual a 10(5) es confiable y seguro

Intoxicaciones graves por inhibidores de la acetilcolinesterasa / Serious intoxications by acetylcholine esterase inhibitors

Se analizan en forma retrospectiva 17 casos de intoxicaciones graves por inhibidores de la acetilcolinesterasa ingresadas a nuestra UCI entre los años 1985-92. Se observó una incidencia de 5 casos por cada 1000 ingresos. Siendo el 76 por ciento de ellos en edad de trabajo activo, provenientes de zonas rurales que intentaron suicidarse por este medio. Se analiza el tratamiento inicial recibido por ellos, a partir de lo cual se proponen algunas sugerencias para mejorar las condiciones de su traslado al hospital de referencia. La mortalidad específica fue mayor (29 por ciento) que la que presentan la globalidad de la intoxicaciones (13 por ciento). Dicha cifra puede estar sobreestimada debido a que el diagnóstico no se pudo realizar con certeza en 3 de los 5 pacientes fallecidos

Evaluación de gravedad en 1000 pacientes críticos / Evaluation of seriousness in 1.000 critical patients

Evaluamos 1000 pacientes críticos según la escala de gravedad APS-2 (2) descrita por William Knaus (desde 1988 a 1991) con elo objeto de conocer su capacidad para estimar la mortalidad en nuestro medio. La mortalidad global fue de un 28 por ciento en esta serie, superior a las series extranjeras de comparación, utilizadas (5,6). Se analizan los factores que explican estas diferencias, y se evaluó la utilización de el APS-2, como herramienta en la selección de las admisiones a la Unidad de Cuidados Intensivos (UCI)

Degeneración espongiforme en la biopsia cerebral de un caso esporádico de enfermedad de Alzheimer: estudio ultraestructural / Spongiform change in the brain biopsy from a sporadic case of Alzheimer's disease: ultrastructural study

Comunicamos el estudio histológico de la biopsia cerebral de un hombre de 53 años de edad con una demencia progresiva de 4 años asociada a parafasias como única manifestación neurológica. En la microscopía de luz, junto a numerosas placas neuríticas y degeneración neurofibrillar, hecho característico de la enfermedad de Aizheimer, se observó además leve despoblación neuronal, marcada gliosis mínima espongiosis. La microscopía electrónica mostró que las vacuolas estaban localizadas de preferencia en las dendritas neuronales. Se discute la posible coexistencia de la enfermedad de Alzheimer y de la enfermedad de Creutzfeldt-Jakob en el mismo paciente, situación que ha sido excepcionalmente observada por otros autores