RESUMEN
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.
Asunto(s)
Listeria monocytogenes , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Frío , Cobre , Humanos , Listeria monocytogenes/genética , Temperatura , Vitamina B 12/genética , Vitamina B 12/metabolismoRESUMEN
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.
Asunto(s)
Diabetes Mellitus Tipo 2 , Hiperglucemia , Inhibidores del Cotransportador de Sodio-Glucosa 2 , Consenso , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Humanos , Hipoglucemiantes/uso terapéuticoRESUMEN
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.
RESUMEN
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.
Asunto(s)
Humanos , Listeria monocytogenes/genética , Temperatura , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Vitamina B 12/genética , Vitamina B 12/metabolismo , Frío , CobreRESUMEN
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.
Asunto(s)
Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/etnología , Hipoglucemiantes/uso terapéutico , Insulina Glargina/uso terapéutico , Péptidos/uso terapéutico , Anciano , Glucemia , Combinación de Medicamentos , Etnicidad , Femenino , Hemoglobina Glucada/metabolismo , Humanos , Masculino , Metformina/uso terapéutico , México , Persona de Mediana Edad , Resultado del TratamientoRESUMEN
Se presenta el caso de una paciente con antecedentes de ser fumadora de baja intensidad, con índice acumulado de tabaco menor de 5 paquetes/año y sin otros antecedentes personales de interés. Acudió en diversas ocasiones durante 2 meses a urgencias, refiriendo cefalea difusa, opresiva e intermitente y diplopía acompañada de visión borrosa ocasional, siendo diagnosticada de parálisis isquémica del IV par craneal del ojo izquierdo e iniciando tratamiento con antiagregante. A pesar del tratamiento, a la semana acudió de nuevo a urgencias, ya que progresivamente había ido presentado mareos, inestabilidad en la marcha, pérdida de visión con predominio en ojo izquierdo y mayor sensación de debilidad en miembros superiores, Finalmente, se decidió ingreso en Neurología ante la sospecha de meningoencefalitis subaguda tuberculosa, pero tras diversas pruebas diagnósticas se llegó a la conclusión de que se trataba de un adenocarcinoma pulmonar, que debutó en forma de carcinomatosis meníngea sin haber presentado sintomatología respiratoria asociada
A case is presented of a patient with a history of low-intensity smoking, with an accumulated tobacco index of less than 5 packs-year and without other personal history of interest. She went to the emergency room several times over 2 months, complaining of a diffuse, oppressive and intermittent headache and diplopia accompanied by occasional blurred vision, being diagnosed with ischemic paralysis of the fourth cranial nerve of the left eye and initiating treatment with antiplatelets. Despite treatment, she returned to the emergency room within a week, as she had been suffering from progressive dizziness, instability when walking, loss of vision mainly in the left eye and a greater feeling of weakness in the upper limbs. Finally, admission to Neurology was decided upon with the suspicion of subacute tuberculous meningoencephalitis. However, after various diagnostic tests, it was concluded that it was a pulmonary adenocarcinoma, which began as meningeal carcinomatosis without presenting associated respiratory symptoms
Asunto(s)
Humanos , Femenino , Persona de Mediana Edad , Carcinomatosis Meníngea/diagnóstico por imagen , Adenocarcinoma/complicaciones , Adenocarcinoma/diagnóstico por imagen , Radiografía Torácica/instrumentación , Neoplasias Pulmonares/tratamiento farmacológico , Carcinomatosis Meníngea/etiología , Diplopía/complicaciones , Parálisis , Punción Espinal/métodos , Electroencefalografía , Tomografía de Emisión de Positrones , Clorhidrato de Erlotinib , Genes erbB-1 , Genes erbB-1/genéticaRESUMEN
AIMS: To provide a review of the available data and practical use of insulin degludec with insulin aspart (IDegAsp). Premixed insulins provide basal and prandial glucose control; however, they have an intermediate-acting prandial insulin component and do not provide as effective basal coverage as true long-acting insulins, owing to the physicochemical incompatibility of their individual components, coupled with the inflexibility of adjustment. The molecular structure of the co-formulation of IDegAsp, a novel insulin preparation, allows these two molecules to coexist without affecting their individual pharmacodynamic profiles. METHODS: Clinical evidence in phase 2/3 trials of IDegAsp efficacy and safety in type 1 and type 2 diabetes mellitus (T1DM and T2DM) have been assessed and summarised. RESULTS: In people with T2DM, once- and twice-daily dosing provides similar overall glycaemic control (HbA1c ) to current modern insulins, but with lower risk of nocturnal hypoglycaemia. In prior insulin users, glycaemic control was achieved with lower or equal insulin doses vs. other basal+meal-time or premix insulin regimens. In insulin-naïve patients with T2DM, IDegAsp can be started once or twice-daily, based on individual need. People switching from more than once-daily basal or premix insulin therapy can be converted unit-to-unit to once-daily IDegAsp, although this strategy should be assessed by the physician on an individual basis. CONCLUSIONS: IDegAsp offers physicians and people with T2DM a simpler insulin regimen than other available basal-bolus or premix-based insulin regimens, with stable daytime basal coverage, a lower rate of hypoglycaemia and some flexibility in injection timing compared with premix insulins.
Asunto(s)
Diabetes Mellitus Tipo 1/tratamiento farmacológico , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Hipoglucemiantes/uso terapéutico , Insulina Aspart/administración & dosificación , Insulina de Acción Prolongada/administración & dosificación , Glucemia , Ensayos Clínicos Fase II como Asunto , Ensayos Clínicos Fase III como Asunto , Esquema de Medicación , Sustitución de Medicamentos , Humanos , Hipoglucemiantes/efectos adversos , Hipoglucemiantes/farmacología , Insulina Aspart/efectos adversos , Insulina Aspart/farmacología , Insulina de Acción Prolongada/efectos adversos , Insulina de Acción Prolongada/farmacología , Resultado del TratamientoRESUMEN
No disponible
Asunto(s)
Femenino , Humanos , Masculino , Enfermedad Pulmonar Obstructiva Crónica/epidemiología , Enfermedad Pulmonar Obstructiva Crónica/prevención & control , Productos de Tabaco/normas , Productos de Tabaco , Fenómenos Fisiológicos Respiratorios , Enfermedad Pulmonar Obstructiva Crónica/terapia , Productos de Tabaco/provisión & distribuciónRESUMEN
We applied thermography to investigate the cognitive neuropsychology of emotions, using it as a somatic marker of subjective experience during emotional tasks. We obtained results that showed significant correlations between changes in facial temperature and mental set. The main result was the change in the temperature of the nose, which tended to decrease with negative valence stimuli but to increase with positive emotions and arousal patterns. However, temperature change was identified not only in the nose, but also in the forehead, the oro-facial area, the cheeks and in the face taken as a whole. Nevertheless, thermic facial changes, mostly nasal temperature changes, correlated positively with participants' empathy scores and their performance. We found that temperature changes in the face may reveal maps of bodily sensations associated with different emotions and feelings like love.
Asunto(s)
Nivel de Alerta/fisiología , Temperatura Corporal/fisiología , Emociones/fisiología , Empatía/fisiología , Cara/fisiología , Termografía/métodos , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
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.
Asunto(s)
Humanos , Masculino , Femenino , Persona de Mediana Edad , Cuidados Críticos , Enfermedad Crítica , Unidades de Cuidados Intensivos , Terapia Ocupacional , Estudios ProspectivosRESUMEN
The interstitial cells of Cajal (ICC) have been reported to regulate gastrointestinal motility. We investigated the distribution and the morphological and morphometric characteristics of the immunohistochemical reaction against c-kit in the forestomachs of fetal, newborn and adult cows. The anti-c-kit reaction revealed different populations of ICC among age groups and organs. ICC were more numerous and smaller in fetuses. Larger ICC were identified in newborns, except for those in the rumen. During the earliest stages of development, ICC were abundant in the inner layer of the muscularis and were consistently associated with this layer. In all samples, ICC were found in the outer layer of the tunica muscularis. ICC were found between the two muscle layers in the omasum at all ages; however, they were identified only in the rumen of the adult. Our study demonstrated that ICC are present in the forestomach of bovines.
Asunto(s)
Envejecimiento/metabolismo , Envejecimiento/patología , Mucosa Gástrica/metabolismo , Células Intersticiales de Cajal/citología , Células Intersticiales de Cajal/metabolismo , Proteínas Proto-Oncogénicas c-kit/metabolismo , Estómago/citología , Animales , Animales Recién Nacidos , Biomarcadores/metabolismo , Bovinos , Especificidad de Órganos , Distribución TisularRESUMEN
AIMS: Canagliflozin is a sodium glucose co-transporter 2 inhibitor developed for the treatment of type 2 diabetes mellitus (T2DM). This randomised, double-blind, placebo-controlled, Phase 3 study evaluated the efficacy and safety of canagliflozin as an add-on to metformin plus sulphonylurea in patients with T2DM. METHODS: Patients (N = 469) received canagliflozin 100 or 300 mg or placebo once daily during a 26-week core period and a 26-week extension. Prespecified primary end-point was change in HbA1c at 26 weeks. Secondary end-points included change in HbA1c at week 52 as well as proportion of patients achieving HbA1c < 7.0%, change in fasting plasma glucose (FPG) and systolic blood pressure, and per cent change in body weight, high-density lipoprotein cholesterol, and triglycerides (weeks 26 and 52). RESULTS: HbA1c was significantly reduced with canagliflozin 100 and 300 mg vs. placebo at week 26 (-0.85%, -1.06%, and -0.13%; p < 0.001); these reductions were maintained at week 52 (-0.74%, -0.96%, and 0.01%). Both canagliflozin doses reduced FPG and body weight vs. placebo at week 26 (p < 0.001) and week 52. Overall adverse event (AE) rates were similar across groups over 52 weeks, with higher rates of genital mycotic infections and osmotic diuresis-related AEs seen with canagliflozin vs. placebo; these led to few discontinuations. Increased incidence of documented, but not severe, hypoglycaemia episodes was seen with canagliflozin vs. placebo. CONCLUSIONS: Canagliflozin improved glycaemic control, reduced body weight, and was generally well tolerated in T2DM patients on metformin plus sulphonylurea over 52 weeks.
Asunto(s)
Diabetes Mellitus Tipo 2/tratamiento farmacológico , Glucósidos/administración & dosificación , Hipoglucemiantes/administración & dosificación , Tiofenos/administración & dosificación , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Glucemia/metabolismo , Presión Sanguínea/efectos de los fármacos , Canagliflozina , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/fisiopatología , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Esquema de Medicación , Femenino , Glucósidos/efectos adversos , Hemoglobina Glucada/metabolismo , Humanos , Hipoglucemiantes/efectos adversos , Células Secretoras de Insulina/fisiología , Metabolismo de los Lípidos/efectos de los fármacos , Masculino , Metformina/administración & dosificación , Metformina/efectos adversos , Persona de Mediana Edad , Compuestos de Sulfonilurea/administración & dosificación , Compuestos de Sulfonilurea/efectos adversos , Tiofenos/efectos adversos , Resultado del Tratamiento , Pérdida de Peso/efectos de los fármacos , Adulto JovenRESUMEN
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.
Asunto(s)
Cuidados Críticos , Educación de Postgrado en Medicina , Programas de Gobierno/educación , ChileRESUMEN
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...
Asunto(s)
Humanos , Femenino , Persona de Mediana Edad , Insulinoma/diagnóstico , Neoplasias Pancreáticas/diagnóstico , Trastornos Mentales/etiología , Hipoglucemia/etiología , Insulinoma/complicaciones , Neoplasias Pancreáticas/complicacionesRESUMEN
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.
Asunto(s)
Educación de Postgrado en Medicina , Programas de Gobierno/educación , Cuidados Críticos , ChileAsunto(s)
Células Madre Adultas/fisiología , Aorta/citología , Diferenciación Celular , Atrios Cardíacos/citología , Ventrículos Cardíacos/citología , Células Madre Adultas/metabolismo , Fosfatasa Alcalina/metabolismo , Animales , Antígenos CD/metabolismo , Biomarcadores/metabolismo , Proliferación Celular , Células Cultivadas , Técnicas de Cocultivo , Cariotipo , Ratas , Sus scrofaRESUMEN
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.
Asunto(s)
Anticuerpos , Infecciones , Parasitosis Hepáticas , Strongyloides stercoralisRESUMEN
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)
Asunto(s)
Strongyloides stercoralis , Anticuerpos , Infecciones , Parasitosis HepáticasRESUMEN
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.
Asunto(s)
Diabetes Mellitus Tipo 2/tratamiento farmacológico , Inhibidores de la Dipeptidil-Peptidasa IV/administración & dosificación , Hipoglucemiantes/uso terapéutico , Metformina/uso terapéutico , Tiazolidinedionas/uso terapéutico , Administración Oral , Adulto , Anciano , Área Bajo la Curva , Biomarcadores/sangre , Glucemia/análisis , Diabetes Mellitus Tipo 2/sangre , Inhibidores de la Dipeptidil-Peptidasa IV/uso terapéutico , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Esquema de Medicación , Quimioterapia Combinada , Femenino , Hemoglobina Glucada/análisis , Humanos , Masculino , Persona de Mediana Edad , Periodo Posprandial , Resultado del TratamientoRESUMEN
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.