Overproduction of cyclo-oxygenase-2 (COX-2) is involved in the resistance to apoptosis in vascular smooth muscle cells from diabetic patients: a link between inflammation and apoptosis.

AIMS/HYPOTHESIS: Inflammation is a common feature in cardiovascular diseases, including diabetes mellitus. In addition to the well-known inflammatory role of cyclo-oxygenase-2 (COX-2), this protein has also been implicated in apoptosis resistance in tumour cells. Vascular smooth muscle cells (VSMC) from diabetic patients are also resistant to apoptosis because of an increased abundance of B cell lymphoma 2 protein (BCL2). In this work, we investigated whether overproduction of COX-2 was involved in the resistance to apoptosis in VSMC from diabetic patients. METHODS: VSMC were obtained from internal mammary arteries from patients who had undergone coronary artery bypass graft surgery. Apoptosis was measured by DNA fragmentation, BCL2 degradation and cytochrome c release. RESULTS: Apoptosis induced by C-reactive protein in cells from non-diabetic patients was mediated by COX-2. VSMC from diabetic patients showed higher basal levels of COX-2 compared with those from non-diabetic patients. Transfection of VSMC from non-diabetic patients with a plasmid containing COX-2 (also known as PTGS2) increased basal production of COX-2 and BCL2 and mimicked the resistance to apoptosis that occurs in diabetic patients. We also found a significant correlation (R = 0.846, p = 0.016) between COX-2 and BCL2 production in arterial rings from diabetic patients measured by confocal microscopy. However, inhibition of COX-2 production by small interfering RNA proved unable to reverse BCL2 production in diabetic VSMC. CONCLUSIONS/INTERPRETATION: These results suggest a link between inflammation (COX-2) and apoptosis resistance (BCL2) in the arteries of diabetic patients. This relationship is not causative and the common production of these two proteins may be co-regulated by shared regulatory elements in diabetes.

Use of statins for the treatment of spontaneous intracerebral hemorrhage: results of a pilot study.

BACKGROUND AND STUDY AIMS: Spontaneous intracerebral hemorrhage (ICH) represents the most fatal kind of stroke, and there is still no treatment available that improves the outcome. Statins are cholesterol reducers, and during the last few years many additional effects have been demonstrated that might be neuroprotective. We designed a pilot clinical study in order to evaluate whether the administration of statins is associated with a better outcome. PATIENTS AND METHODS: From August to December 2006 we carried out a prospective/retrospective non-randomized clinical study. The prospective group was treated with rosuvastatin (20 mg) and the retrospective control group was taken from our clinical records with a relation of 1:3. We included patients of both sexes, aged > or =15 years with proven ICH in CT-scan. Exclusion criteria were a history of neoplasm, head injury four weeks before admission, non-hypertensive reasons, brainstem hemorrhage, steroid administration, cranial surgery, initial hydrocephalus, and NIHSS > or =30. RESULTS: We analyzed 18 patients treated with rosuvastatin and 57 controls with similar basic characteristics. The mortality rate during hospitalization was 1 (5.6%) patient in the statin group and 9 (15.8%) in the control group; the hazard ratio adjusted by the initial Glasgow Coma Scale (GCS), intubation, admission in intensive care unit, disruption into the subarachnoid space was 0.20 (95% CI 0.02-1.67). The odds ratio for NIHSS > or =15 at release was 0.04 (95% CI 0.003-0.93). CONCLUSIONS: The use of statins during the acute phase of ICH could be associated with a better outcome. Further clinical trials are necessary to confirm a possible therapeutic effect and evaluate the toxicity of statins.

[A clinical-epidemiological approximation to intracerebral hemorrhage in a Mexican hospital: analysis of factors associated to mortality]. / Aproximacion clinicoepidemiológica de la hemorragia intracerebral en un hospital mexicano: analisis de factores asociados a la mortalidad.

INTRODUCTION: Intracerebral hemorrhage (ICH) is the most lethal type of stroke. There are some clinical and radiological factors related to mortality. The time for obtaining medical care could be related with poor prognosis, but there are not available studies in Hispanics that evaluated this one. AIM: To determinate the association between epidemiological factors, time to obtain medical care, origin, and clinical characteristics with hospital mortality due to ICH. SUBJECTS AND METHODS: Study of cases and controls in a regional third level center, between January 2000 and December 2006 with patients of both sexes, older than 15 years with tomographic diagnosis of ICH. We excluded patients with NIHSS undetermined or traumatic head injury 4 weeks before. We studied demographic variables, time between beginning of symptoms and medical care, origin in kilometers until hospital, clinical characteristics at admission, including Glasgow and NIHSS. RESULTS: We analyzed 74 men and 101 women with mean age of 65 years. The etiology was hypertension in 77.4% and localization lobar in 39.4%. Eighty-five percent receipt medical care after 3 hours and 75.4% came from a radius < 100 km. Mortality in hospital was 16.6% with an explicative model of regression that included blood pressure < 130/80 mmHg, intubation, Glasgow < 9 at admission or NIHSS > 15, and hospitalization days. CONCLUSIONS: Demographic characteristics, causes, and localization are similar to previously informed series. The time for obtaining medical care is far from ideal, this could delay treatment; allow progression of disease, and then worse prognosis.

Aproximación clinicoepidemiológica de la hemorragia intracerebral en un hospital mexicano: análisis de factores asociados a la mortalidad / Clinical-epidemiological approximation to intracerebral hemorrhage in a Mexican hospital: analysis of factors associated to mortality

La hemorragia intracerebral (HIC) espontánea es la forma más letal de enfermedad cerebrovascular.Existen factores clínicos y radiológicos descritos asociados a mortalidad. El tiempo en recibir atención podría relacionarse con peor pronóstico; sin embargo, no existen estudios en la población latina que hayan analizado esta asociación. Objetivo.Determinar la asociación entre factores epidemiológicos, el tiempo de atención, la procedencia y características clínicas con la mortalidad hospitalaria por HIC. Sujetos y métodos. Es un estudio de casos y controles en un centro regional de tercer nivel,entre enero de 2000 y diciembre de 2006, con pacientes de ambos sexos, mayores de 15 años, con diagnóstico tomográfico de HIC. Se excluyeron aquéllos con la escala del Instituto Nacional de Salud para enfermedades cardiovasculares (NIHSS) basal indeterminada o traumatismo craneal en las cuatro semanas previas. Se estudiaron variables demográficas, tiempo entre inicio de síntomas y atención médica, lugar de procedencia en kilómetros y características clínicas en el momento del ingreso, incluyendo la puntuación de Glasgow y NIHSS. Resultados. Analizamos 74 hombres y 101 mujeres con edad promediode 65 años. La etiología fue hipertensión arterial en el 77,3% y localización lobar en el 39,4%. El 84,5% recibió atención despuésde tres horas y el 75,4% procedía de un radio menor de 100 km. La mortalidad hospitalaria fue del 16,6%, con un modeloexplicativo de regresión logística que incluyó: tensión arterial < 130/80 mmHg, intubación, Glasgow < 9 o NIHSS >15en el momento del ingreso y los días de hospitalización. Conclusiones. Las características demográficas, causas y localizaciónse asemejan a lo descrito en la bibliografía. El tiempo de atención dista de lo ideal, lo que puede retrasar el tratamiento,permitir la progresión de la enfermedad y empeorar el pronóstico

Intracerebral hemorrhage (ICH) is the most lethal type of stroke. There are some clinical andradiological factors related to mortality. The time for obtaining medical care could be related with poor prognosis, but there are not available studies in Hispanics that evaluated this one. Aim. To determinate the association between epidemiologicalfactors, time to obtain medical care, origin, and clinical characteristics with hospital mortality due to ICH. Subjects and methods. Study of cases and controls in a regional third level center, between January 2000 and December 2006 with patients of both sexes, older than 15 years with tomographic diagnosis of ICH. We excluded patients with NIHSS undetermined or traumatic head injury 4 weeks before. We studied demographic variables, time between beginning of symptoms and medicalcare, origin in kilometers until hospital, clinical characteristics at admission, including Glasgow and NIHSS. Results. We analyzed 74 men and 101 women with mean age of 65 years. The etiology was hypertension in 77.4% and localization lobar in 39.4%. Eighty-five percent receipt medical care after 3 hours and 75.4% came from a radius < 100 km. Mortality inhospital was 16.6% with an explicative model of regression that included blood pressure < 130/80 mmHg, intubation, Glasgow < 9 at admission or NIHSS > 15, and hospitalization days. Conclusions. Demographic characteristics, causes, and localization are similar to previously informed series. The time for obtaining medical care is far from ideal, this could delaytreatment; allow progression of disease, and then worse prognosis

Efficacy of nitroglycerine infusion versus sublingual nifedipine in severe pre-eclampsia: a randomized, triple-blind, controlled trial.

1. Information regarding the use of continuous i.v. administration of nitroglycerine as an antihypertensive agent in the management of pre-eclampsia is scarce. In the present study, i.v. nitroglycerine or sublingual nifedipine were administered to 32 women with severe pre-eclampsia who were being managed with controlled plasma volume expansion and MgSO(4) loading and maintenance doses. Maternal blood pressure and heart rate responses, fetal heart rate responses and perinatal fetal-maternal adverse effects were evaluated using classical parametric and non-parametric data analysis and data modelling by mixed models. 2. An important hypotensive response was observed in both groups, although this reponse was greater, faster and exhibited less variability (more precision) in the nitroglycerine-treated group. Heart rate also increased in both the nitroglycerine- and nifedipine-treated groups (4.6 +/- 4.4 vs 8.6 +/- 5.3 b.p.m., respectively), although the increase in the nifedipine-treated group was almost twofold that in the nitroglycerine-treated group. There were no significant changes in fetal heart rate in response to vasodilator therapy. The frequency of perinatal fetal-maternal adverse effects was similar in both groups at 40% and the adverse effects observed included flushing, headache, palpitations and nausea. 3. In conclusion, i.v. infusion of nitroglycerine is an effective, safe and alternative therapy for severe pre-eclampsia.

Fuzzy-based controller for glucose regulation in type-1 diabetic patients by subcutaneous route.

This paper presents an advisory/control algorithm for a type-1 diabetes mellitus (TIDM) patient under an intensive insulin treatment based on a multiple daily injections regimen (MDIR). The advisory/control algorithm incorporates expert knowledge about the treatment of this disease by using Mamdani-type fuzzy logic controllers to regulate the blood glucose level (BGL). The overall control strategy is based on a two-loop feedback strategy to overcome the variability in the glucose-insulin dynamics from patient to patient. An inner-loop provides the amount of both rapid/short and intermediate/long acting insulin (RSAI and ILAI) formulations that are programmed in a three-shots daily basis before meals. The combined preparation is then injected by the patient through a subcutaneous route. Meanwhile, an outer-loop adjusts the maximum amounts of insulin provided to the patient in a time-scale of days. The outer-loop controller aims to work as a supervisor of the inner-loop controller. Extensive closed-loop simulations are illustrated, using a detailed compartmental model of the insulin-glucose dynamics in a TIDM patient with meal intake.