ABSTRACT
The probability of acute kidney injury (AKI) is higher in septic diabetic patients, which is associated with, among other factors, proximal tubular cell (PTC) injury induced by the hypoxic/hyperglycemic/inflammatory microenvironment that surrounds PTCs in these patients. Here, we exposed human PTCs (HK-2 cells) to 1% O2/25 mM glucose/inflammatory cytokines with the aim of studying the role of prostaglandin uptake transporter (PGT) and dipeptidyl peptidase-4 (DPP-4, a target of anti-hyperglycemic agents) as pharmacological targets to prevent AKI in septic diabetic patients. Our model reproduced two pathologically relevant mechanisms: (i) pro-inflammatory PTC activation, as demonstrated by the increased secretion of chemokines IL-8 and MCP-1 and the enhanced expression of DPP-4, intercellular leukocyte adhesion molecule-1 and cyclo-oxygenase-2 (COX-2), the latter resulting in a PGT-dependent increase in intracellular prostaglandin E2 (iPGE2); and (ii) epithelial monolayer injury and the consequent disturbance of paracellular permeability, which was related to cell detachment from collagen IV and the alteration of the cell cytoskeleton. Most of these changes were prevented by the antagonism of PGE2 receptors or the inhibition of COX-2, PGT or DPP-4, and further studies suggested that a COX-2/iPGE2/DPP-4 pathway mediates the pathogenic effects of the hypoxic/hyperglycemic/inflammatory conditions on PTCs. Therefore, inhibitors of PGT or DPP-4 ought to undergo testing as a novel therapeutic avenue to prevent proximal tubular damage in diabetic patients at risk of AKI.
Subject(s)
Acute Kidney Injury , Diabetes Mellitus , Dipeptidyl-Peptidase IV Inhibitors , Humans , Cyclooxygenase 2/metabolism , Diabetes Mellitus/drug therapy , Acute Kidney Injury/drug therapy , Acute Kidney Injury/etiology , Acute Kidney Injury/prevention & control , Dipeptidyl-Peptidases and Tripeptidyl-Peptidases , Prostaglandins , Dipeptidyl-Peptidase IV Inhibitors/pharmacology , Dipeptidyl-Peptidase IV Inhibitors/therapeutic use , Dipeptidyl Peptidase 4ABSTRACT
Resumen El artículo pretende aportar en el debate sobre por qué algunos grupos guerrilleros latinoamericanos han sido exitosos en su proceso de adaptación partidista y otros en cambio no han logrado configurarse como una alternativa de poder real en sus respectivos sistemas políticos. Para tal fin se explora la relación entre la cultura política y el desempeño electoral del M-19, el FMLN, el FSLN, la URNG y el MLN-Tupamaros.
Abstract The article aims to contribute to the debate on why some Latin American guerrilla movements have been successful in their partisan adaptation process and others by contrast have not configured as an alternative to real power in their respective political systems. For this purpose, the relationship between the political culture and the electoral performance of the M-19, the FMLN, FSLN, the URNG and the MLN-Tupamaros is explored.
ABSTRACT
No disponible
Subject(s)
Humans , Accidents, Traffic/statistics & numerical data , Alcohol Drinking/adverse effects , Law Enforcement , Prisons/statistics & numerical dataABSTRACT
Introducción. El consumo de alcohol es la causa de un elevado número de accidentes de tráfico, por lo que se han endurecido las leyes para evitarlo. A pesar de ello hay personas que las infringen e ingresan en prisión por conducir bajo los efectos del alcohol. Se investiga si estas personas son bebedores ocasionales o bien son enfermos alcohólicos. Material y Método. Estudio transversal de 50 internos penitenciarios por delitos contra la seguridad vial, entrevistados acerca de su consumo alcohólico, antecedentes psicopatológicos y delictivos. Resultados. El 88% presenta indicadores de alcoholismo y la mayoría consume otras drogas. Sólo en el 10% se ha detectado psicopatología previa. El 72% tiene antecedentes penitenciarios, la mitad por delitos con violencia. Socialmente están adaptados, 39 años de edad media, son españoles (86%), tienen familia y trabajo regular (76%). Conclusiones. La mayoría de internos por delitos contrala seguridad vial son alcohólicos, pero pocos son detectados. Su enfermedad genera otras conductas delictivas, siendo necesario su tratamiento para evitar la reincidencia y un proceso de exclusión social (AU)
Introduction. Alcohol consumption is a major cause of traffic accidents, so that stricter laws have been enacted to avoid it. Despite this, there are still persons who break the law and go to prison because of driving under the effects of alcohol. We have investigated if these persons are occasionally alcohol drinkers or if they are alcoholics with difficult to modify alcohol patterns. Material and methods. A cross-sectional study including 50 inmates from two prisons who had committed traffic crimes were interviewed about their alcohol consumption habits and their criminal and psychopathological backgrounds. Results. 88% had indicators of alcoholism and most consumed other drugs. Previous psychopathology signs were only detected in 10% of the sample. A total of 72% had previous criminal records, half because of violent offences. They were socially adapted, with mean age 39 years, Spanish (86%), had a stable job and family (76%). Conclusions. Most of the inmates due to traffic rimes are alcoholic, but very few are detected. Their alcohol consumption generates other criminal conduct, treatment being necessary in order to avoid relapse and social exclusion (AU)
Subject(s)
Male , Adult , Middle Aged , Humans , Alcoholism/diagnosis , Alcoholism/psychology , Automobile Driving/statistics & numerical data , Accidents, Traffic/prevention & control , Accidents, Traffic/statistics & numerical data , Substance-Related Disorders/diagnosis , Substance-Related Disorders/psychology , Alcohol-Related Disorders/complications , Alcohol-Related Disorders/diagnosis , Alcohol-Related Disorders/psychology , Alcoholism/complications , Alcoholism/mortality , National Institute on Alcohol Abuse and Alcoholism (U.S.)/trends , National Institute on Alcohol Abuse and Alcoholism (U.S.) , Accidents, Traffic/economics , Alcoholism/etiology , Automobile Driving/education , Automobile Driving/legislation & jurisprudence , Accidents, Traffic/trendsABSTRACT
INTRODUCTION: Alcohol consumption is a major cause of traffic accidents, so that stricter laws have been enacted to avoid it. Despite this, there are still persons who break the law and go to prison because of driving under the effects of alcohol. We have investigated if these persons are occasionally alcohol drinkers or if they are alcoholics with difficult to modify alcohol patterns. MATERIAL AND METHODS: A cross-sectional study including 50 inmates from two prisons who had committed traffic crimes were interviewed about their alcohol consumption habits and their criminal and psychopathological backgrounds. RESULTS: 88% had indicators of alcoholism and most consumed other drugs. Previous psychopathology signs were only detected in 10% of the sample. A total of 72% had previous criminal records, half because of violent offences. They were socially adapted, with mean age 39 years, Spanish (86%), had a stable job and family (76%). CONCLUSIONS: Most of the inmates due to traffic crimes are alcoholic, but very few are detected. Their alcohol consumption generates other criminal conduct, treatment being necessary in order to avoid relapse and social exclusion.
