RESUMEN
AIM: Mitochondrial function and the ensuing ATP synthesis are central to the functioning of the brain and contribute to neuronal physiology. Most studies on neurodegenerative diseases have highlighted that mitochondrial dysfunction is an important event contributing to pathology. However, studies on the human brain mitochondria in various neurodegenerative disorders heavily rely on post mortem samples. As post mortem tissues are influenced by pre- and post mortem factors, we investigated the effect of these variables on mitochondrial function. METHODS: We examined whether the mitochondrial function (represented by mitochondrial enzymes and antioxidant activities) in post mortem human brains (n=45) was affected by increased storage time (11.8-104.1 months), age of the donor (2 days to 80 years), post mortem interval (2.5-26 h), gender difference and agonal state [based on Glasgow Coma Scale: range=3-15] in the frontal cortex, as a prototype. RESULTS: We observed that the activities of citrate synthase, succinate dehydrogenase and mitochondrial reductase (MTT) were significantly affected only by gender difference (citrate synthase: P=0.005; succinate dehydrogenase: P=0.01; mitochondrial reductase: P=0.006), being higher in females, but not by any other factor. Mitochondrial complex I activity was significantly inhibited by increasing age (r=-0.40; P=0.05). On the other hand, the mitochondrial antioxidant enzyme glutathione reductase decreased with severe agonal state (P=0.003), while the activity of glutathione-S-transferase declined with increased storage time (P=0.005) and severe agonal state (P=0.02). CONCLUSION: Our data highlight the influence of pre- and post mortem factors on preservation of mitochondrial function with implications for studies on brain pathology employing stored human samples.
Asunto(s)
Encéfalo/metabolismo , Mitocondrias/metabolismo , Patología Clínica , Cambios Post Mortem , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Preescolar , Proteínas del Complejo de Cadena de Transporte de Electrón/análisis , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
Oxidative stress and mitochondrial damage are implicated in the evolution of neurodegenerative diseases. Increased oxidative damage in specific brain regions during aging might render the brain susceptible to degeneration. Previously, we demonstrated increased oxidative damage and lowered antioxidant function in substantia nigra during aging making it vulnerable to degeneration associated with Parkinson's disease. To understand whether aging contributes to the vulnerability of brain regions in Alzheimer's disease, we assessed the oxidant and antioxidant markers, glutathione (GSH) metabolic enzymes, glial fibrillary acidic protein (GFAP) expression and mitochondrial complex I (CI) activity in hippocampus (HC) and frontal cortex (FC) compared with cerebellum (CB) in human brains with increasing age (0.01-80 years). We observed significant increase in protein oxidation (HC: p = 0.01; FC: p = 0.0002) and protein nitration (HC: p = 0.001; FC: p = 0.02) and increased GFAP expression (HC: p = 0.03; FC: p = 0.001) with a decreasing trend in CI activity in HC and FC compared to CB with increasing age. These changes were associated with a decrease in antioxidant enzyme activities, such as superoxide dismutase (HC: p = 0.005), catalase (HC: p = 0.02), thioredoxin reductase (FC: p = 0.04), GSH reductase (GR) (HC: p = 0.005), glutathione-s-transferase (HC: p = 0.0001; FC: p = 0.03) and GSH (HC: p = 0.01) with age. However, these parameters were relatively unaltered in CB. We suggest that the regions HC and FC are subjected to widespread oxidative stress, loss of antioxidant function and enhanced GFAP expression during aging which might make them more susceptible to deranged physiology and selective neuronal degeneration.
Asunto(s)
Enfermedad de Alzheimer/fisiopatología , Antioxidantes/metabolismo , Lóbulo Frontal/metabolismo , Hipocampo/metabolismo , Estrés Oxidativo , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Envejecimiento/fisiología , Cerebelo/metabolismo , Niño , Preescolar , Complejo I de Transporte de Electrón/metabolismo , Femenino , Proteína Ácida Fibrilar de la Glía/metabolismo , Glutatión/metabolismo , Glutatión Transferasa , Humanos , Lactante , Masculino , Persona de Mediana Edad , Mitocondrias/metabolismo , Enfermedades Neurodegenerativas/metabolismoRESUMEN
The human brain displays oxidant and antioxidant markers with regional specificity that directly impinges on neuronal function in aging and in disease states. Similarly, the antioxidant activities might exhibit differential intracellular distribution rendering subcellular structures differentially vulnerable to toxic insults. To investigate the subcellular distribution of antioxidant activities in the human postmortem brain, we assayed superoxide dismutase (SOD), glutathione (GSH), glutathione peroxidase (GPx), glutathione reductase (GR), and glutathione-S-transferase (GST) in the cytosol and synaptosomal fraction from the frontal cortex (FC) of 45 postmortem human brains. We also tested whether these activities were altered by premortem and postmortem factors, including increasing storage time (11.8-104.1 months), postmortem interval (PMI) (2.5-26 h), age and gender differences, and agonal state [based on Glasgow coma scale (GCS): range: 3-15]. Overall, the antioxidant activities were found to be several folds lower in the synaptosomes compared to cytosol, which could make it more susceptible to degeneration. The activities were significantly affected mainly by age (SOD increased in synaptosomes, p=0.01; GSH decreased in cytosol, p=0.03; GPx decreased in cytosol and increased in synaptosomes, p=0.05; GST decreased in synaptosomes, p=0.05) and to a lesser extent by other premortem (GST decreased with GCS in synaptosomes, p=0.02) and postmortem factors (GSH decreased with PMI in cytosol, p=0.04). Increasing storage time or gender difference did not affect the antioxidant activities. We infer that premortem and postmortem factors in general, and increasing age in particular, significantly alter the antioxidant activities in subcellular fractions of postmortem brain with implications for studies on brain pathology employing stored human samples.
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Citosol/enzimología , Lóbulo Frontal/citología , Glutatión/metabolismo , Sinaptosomas/enzimología , Adolescente , Adulto , Factores de Edad , Anciano , Niño , Preescolar , Lóbulo Frontal/enzimología , Glutatión Peroxidasa/metabolismo , Glutatión Reductasa/metabolismo , Glutatión Transferasa/metabolismo , Humanos , Masculino , Preservación Biológica , Factores Sexuales , Superóxido Dismutasa/metabolismo , Adulto JovenRESUMEN
Parkinson's disease (PD) is characterized by selective degeneration and loss of dopaminergic neurons in the substantia nigra (SN) of the ventral mid brain leading to dopamine depletion in the striatum. Oxidative stress and mitochondrial damage have been implicated in the death of SN neurons during the evolution of PD. In our previous study on human PD brains, we observed that compared to SN, striatum was significantly protected against oxidative damage and mitochondrial dysfunction. To understand whether brain aging contributes to the vulnerability of midbrain to neurodegeneration in PD compared to striatum, we assessed the status of oxidant and antioxidant markers, glutathione metabolic enzymes, glial fibrillary acidic protein (GFAP) expression and mitochondrial complex I(CI) activity in SN (n = 23) and caudate nucleus (n = 24) during physiological aging in human brains. We observed a significant increase in protein oxidation (P < 0.001), loss of CI activity (P = 0.04) and increased astrocytic proliferation indicated by GFAP expression (P < 0.001) in SN compared to CD with increasing age. These changes were attributed to significant decrease in antioxidant function represented by superoxide dismutase (SOD) (P = 0.03), glutathione (GSH) peroxidase (GPx) (P = 0.02) and GSH reductase (GR) (P = 0.03) and a decreasing trend in total GSH and catalase with increasing age. However, these parameters were relatively unaltered in CD. We propose that SN undergoes extensive oxidative damage, loss of antioxidant and mitochondrial function and increased GFAP expression during physiological aging which might make it more vulnerable to neurotoxic insults thus contributing to selective degeneration during evolution of PD.
Asunto(s)
Antioxidantes/metabolismo , Estrés Oxidativo , Enfermedad de Parkinson/metabolismo , Sustancia Negra/metabolismo , Adulto , Anciano , Niño , Preescolar , Femenino , Proteína Ácida Fibrilar de la Glía/metabolismo , Humanos , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
The equilibrium between antioxidant function and oxidative stress is implicated in brain pathology. However, human studies on oxidant and antioxidant markers rely on postmortem tissue that might be affected by pre and postmortem factors. To evaluate the effect of these variables, we tested whether antioxidant enzymes [superoxide dismutase (SOD), catalase] glutathione (GSH) and related enzymes [gamma glutamylcysteine ligase (GCL), GSH peroxidase (GPx), GSH reductase (GR), GSH-S-transferase (GST)] and malondialdehyde (MDA, marker of lipid peroxidation) are affected in postmortem human brains (n=50) by increase in postmortem interval (2.5-26 h), gender difference and agonal state [based on Glasgow coma scale (GCS): range: 3-15] in different anatomical regions-frontal cortex (FC), cerebellum (CB) medulla oblongata (MO), substantia nigra (SN) and hippocampus (HC). While SOD and catalase activities were relatively unaltered, GR and GPx activities were affected by agonal state (GR in CB, p<0.05; GPx in MO, p<0.05) indicating altered GSH dynamics during the secondary events following neuronal injury. MO, SN and HC displayed low GSH compared to FC and CB. Total GSH level was decreased with PMI (MO, p=0.02) which could be partly attributed to increase in MDA levels with increasing PMI in MO (p<0.05). Total GSH level was higher in CB (p<0.017) and MO (p<0.04) in female brains compared to males. Interestingly, HC and SN regions showed significant stability in most of the markers tested. We suggest that while SOD and catalase were relatively unaffected by the pre and postmortem factors, GSH and its metabolic enzymes were significantly altered and this was more pronounced in MO of postmortem human brains. These data highlight the influence of pre and postmortem factors on GSH dynamics and the inherent differences in brain regions, with implications for studies on brain pathophysiology employing human samples.
Asunto(s)
Encéfalo/metabolismo , Glutatión/metabolismo , Factores Sexuales , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Encéfalo/enzimología , Encéfalo/patología , Enzimas/metabolismo , Femenino , Humanos , Masculino , Malondialdehído/metabolismo , Persona de Mediana Edad , Adulto JovenRESUMEN
Dopaminergic neurons die in Parkinson's disease (PD) due to oxidative stress and mitochondrial dysfunction in the substantia nigra (SN). We evaluated if oxidative stress occurs in other brain regions like the caudate nucleus (CD), putamen (Put) and frontal cortex (FC) in human postmortem PD brains (n = 6). While protein oxidation was elevated only in CD (P < 0.05), lipid peroxidation was increased only in FC (P < 0.05) and protein nitration was unchanged in PD compared to controls. Interestingly, mitochondrial complex I (CI) activity was unaffected in PD compared to controls. There was a 3-5 fold increase in the total glutathione (GSH) levels in the three regions (P < 0.01 in FC and CD; P < 0.05 in Put) but activities of antioxidant enzymes catalase, superoxide dismutase, glutathione reductase and glutathione-s-tranferase were not increased. Total GSH levels were elevated in these areas because of decreased activity of gamma glutamyl transpeptidase (γ-GT) (P < 0.05) activity suggesting a decreased breakdown of GSH. There was an increase in expression of glial fibrillary acidic protein (GFAP) (P < 0.001 in FC; P < 0.05 in CD) and glutathione peroxidase (P < 0.05 in CD and Put) activity due to proliferation of astrocytes. We suggest that increased GSH and astrocytic proliferation protects non-SN brain regions from oxidative and mitochondrial damage in PD.
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Antioxidantes/metabolismo , Astrocitos/fisiología , Biomarcadores/metabolismo , Cuerpo Estriado , Lóbulo Frontal , Estrés Oxidativo , Enfermedad de Parkinson , Anciano , Anciano de 80 o más Años , Astrocitos/citología , Cuerpo Estriado/citología , Cuerpo Estriado/metabolismo , Cuerpo Estriado/patología , Neuronas Dopaminérgicas/metabolismo , Neuronas Dopaminérgicas/patología , Femenino , Lóbulo Frontal/citología , Lóbulo Frontal/metabolismo , Lóbulo Frontal/patología , Humanos , Masculino , Persona de Mediana Edad , Mitocondrias/metabolismo , Enfermedad de Parkinson/metabolismo , Enfermedad de Parkinson/patologíaRESUMEN
Biochemical analyses of many brain diseases have highlighted that oxidative damage of proteins and astrogliosis are important events associated with pathology. However, human studies on the status of protein oxidation/nitration and astrogliosis [indicated by expression of glial fibrillary acidic protein (GFAP)] heavily depend on postmortem tissues that might be altered by pre and postmortem factors. To evaluate the effect of these variables, we tested whether the status of GFAP expression, oxidized proteins, and nitrated proteins (by protein 3-nitrotyrosine or 3-NT) were affected in postmortem human brains (n=48) by increased storage time (11.8-104.1 months), postmortem interval (PMI) (2.5-26 h), gender difference, and agonal state (based on Glasgow coma scale: range: 3-15) in different anatomical regions-frontal cortex (FC), cerebellum (CB) and medulla oblongata (MD). We observed that increasing storage time significantly decreased the stability of all 3 markers in MD (oxyblot: P=0.003; 3-NT: P=0.01; GFAP: P=0.03) and that of oxidized proteins in CB (P=0.04), whereas the status of all markers was not significantly altered in FC. On the other hand, PMI and agonal state did not influence the status of all the markers tested in any of the regions. Similarly, except for the decreased protein 3-NT among women in CB compared with men (P=0.04), there was no effect due to gender differences in other brain regions for other markers. These data highlight the influence of storage time on preservation of markers of protein damage and astrogliosis and the inherent differences in brain regions, with implications for studies on brain pathology employing stored human samples.
RESUMEN
Oxidative stress is implicated in mitochondrial dysfunction associated with neurodegeneration in Parkinson's disease (PD). Depletion of the cellular antioxidant glutathione (GSH) resulting in oxidative stress is considered as an early event in neurodegeneration. We previously showed that curcumin, a dietary polyphenol from turmeric induced GSH synthesis in experimental models and protected against oxidative stress. Here we tested the effect of three bioconjugates of curcumin (involving diesters of demethylenated piperic acid, valine and glutamic acid) against GSH depletion mediated oxidative stress in dopaminergic neuronal cells and found that the glutamic acid derivative displayed improved neuroprotection compared to curcumin.
Asunto(s)
Antioxidantes/síntesis química , Curcumina/análogos & derivados , Curcumina/química , Dopamina/fisiología , Glutatión/metabolismo , Neuronas/metabolismo , Fármacos Neuroprotectores/síntesis química , Estrés Oxidativo/efectos de los fármacos , Enfermedad de Parkinson/tratamiento farmacológico , Antioxidantes/farmacología , Disponibilidad Biológica , Línea Celular , Curcumina/farmacología , Glutatión Transferasa/metabolismo , Humanos , Peróxido de Hidrógeno/metabolismo , Indicadores y Reactivos , Peroxidación de Lípido/efectos de los fármacos , Modelos Moleculares , Neuronas/efectos de los fármacos , Fármacos Neuroprotectores/farmacología , Oxidantes/metabolismo , Especies Reactivas de Oxígeno/metabolismoRESUMEN
Earlier we have reported the effect of arecoline thiazolidinone and morpholino arecoline derivatives as muscarinic receptor 1 agonists in Alzheimer's presenile dementia models. To elucidate further our Structure-Activity Relationship (SAR) studies on the chemistry and muscarinic receptor 1 binding efficacy, a series of novel carboxamide derivatives of 2-(1-methyl-1,2,5,6-tetrahydropyridin-3-yl)morpholine molecule have been designed and synthesized as a new class of M1 receptor agonists with a low toxicity effect profile that enhances memory function in animal models of Alzheimer's presenile dementia and also modulates the APP secretion from rat brain cerebrocortical slices by activating M1 receptor in vitro. Results suggest that compound 9b having methyl group at the para position of the aryl group attached to the carboxamide of morpholino arecoline could emerge as a potent molecule having antidementia activity.
Asunto(s)
Enfermedad de Alzheimer/tratamiento farmacológico , Arecolina/química , Morfolinas/química , Agonistas Muscarínicos/química , Agonistas Muscarínicos/uso terapéutico , Receptor Muscarínico M1/metabolismo , Precursor de Proteína beta-Amiloide/metabolismo , Animales , Arecolina/síntesis química , Arecolina/farmacología , Arecolina/uso terapéutico , Corteza Cerebral/efectos de los fármacos , Corteza Cerebral/metabolismo , Relación Dosis-Respuesta a Droga , Humanos , Inositol 1,4,5-Trifosfato/metabolismo , Masculino , Aprendizaje por Laberinto/efectos de los fármacos , Trastornos de la Memoria/inducido químicamente , Trastornos de la Memoria/tratamiento farmacológico , Morfolinas/síntesis química , Morfolinas/farmacología , Morfolinas/uso terapéutico , Agonistas Muscarínicos/síntesis química , Agonistas Muscarínicos/farmacología , Unión Proteica , Ratas , Ratas Wistar , Receptor Muscarínico M1/agonistas , Relación Estructura-ActividadRESUMEN
Efficacy and safety of antibiotic 'locks', in prevention of thrombotic and infectious complication-related morbidity and mortality, among diabetics dialyzed through tunneled-cuffed catheters (TCCs) has not been effectively investigated. This trial was designed to investigate the outcome of TCCs (n = 109), inserted among 96 diabetic end-stage renal disease patients (March 2002-February 2003), by comparing the catheter thrombosis, catheter-related bloodstream infections (CRBSI), catheter survival, and mortality rates, between the cohorts of 49 patients who had TCCs (n = 51) 'locked' with cefotaxime/heparin (group I) and 47 patients with TCCs (n = 58) filled with standard heparin (group II). Thrombosis was defined as the inability to use catheter at a blood flow of 200 ml/min despite intraluminal thrombolysis. Primary end points were catheter thrombosis and CRBSI; elective catheter removal and CRBSI-related death led to sensor of TCCs follow-up. Patients with intraluminal cefotaxime/heparin lock, on cumulative survival analysis, showed a superior thrombosis-free (86.3 vs 63.8%, P = 0.023, log rank), infection-free (72.9 vs 27.1%, P = 0.004, log rank), and thrombosis- and infection-free TCC survival (78.4 vs 37.9%, P = 0.001, log rank) at 365 days, besides having significantly lower incidence of CRBSI (1.56 vs 3.68 episodes/1000 catheter days, P < 0.0001) and CRBSI-related mortality (9.8 vs 23.4%, P = 0.015), compared with the heparin-alone group. Deployment of cefotaxime-heparin 'lock' enhances catheter survival; reduces thrombotic and infectious complications and ensuing mortality, among diabetics on dialysis. However, further studies are needed to define the long-term implications of antibiotic locks in terms of the risk of emergence of antimicrobial resistance.
Asunto(s)
Profilaxis Antibiótica/instrumentación , Infecciones Bacterianas/etiología , Cateterismo/efectos adversos , Complicaciones de la Diabetes/microbiología , Nefropatías Diabéticas/terapia , Fallo Renal Crónico/terapia , Diálisis Renal/instrumentación , Adulto , Anciano , Anciano de 80 o más Años , Antibacterianos/uso terapéutico , Profilaxis Antibiótica/métodos , Infecciones Bacterianas/prevención & control , Cefalosporinas/uso terapéutico , Complicaciones de la Diabetes/prevención & control , Diabetes Mellitus/microbiología , Método Doble Ciego , Sistemas de Liberación de Medicamentos , Diseño de Equipo , Femenino , Gentamicinas/uso terapéutico , Humanos , Masculino , Persona de Mediana Edad , Diálisis Renal/métodos , Trombosis/prevención & control , Resultado del TratamientoRESUMEN
BACKGROUND: Infection with the hepatitis C virus (HCV) is endemic in hemodialysis (HD) units, especially in Middle Eastern countries. The meticulous isolation policy recommended for patients with the hepatitis B virus (HBV) in an HD unit resulted in a significant drop in HBV incidence globally. This study was developed to prospectively investigate the impact of an identical isolation policy on incidence of nosocomial HCV infection in this HD unit of the Middle East. METHODS: In phase I of the study, we retrospectively reviewed the records of 189 patients with a mean age of 47.5 +/- 11.4 years (range, 15-85 years) who were receiving maintenance HD from December 7, 1995, to December 6, 2000, for the mean duration of 73 +/- 6.3 months (range, 3-144 months) to record the prevalence of HCV. Factors such as blood transfusions and dialytic age (time span that patient has received dialysis since its initiation) implicated in transmission of HCV in the HD unit also were recorded. Phase II involved stringent isolation of anti-HCV positive patients detected during phase I through provision of dedicated space, dialysis equipment, and nursing staff from December 7, 2000, to December 6, 2001. Liver function and anti-HCV tests were repeated for all the 198 patients every 6 months to identify new HCV seroconversions. RESULTS: An HCV prevalence rate of 43.9% (83/189) and an annual HCV seroconversion rate of 6.8% were identified in this cohort. No significant association with blood tranfusion was observed. Eighty-three anti-HCV positive (43.9%) patients had a mean dialytic age of 48.5 +/- 14.2 months compared with 25.0 +/- 8.6 months among 106 (56.1%) anti-HCV negative patients (relative risk [RR], 1.89; 95% confidence interval [CI], 1.39-5.86; P <.001). Only 2 new HCV seroconversions (1.01% [2/198]) were identified. CONCLUSIONS: Evidently, the sharing of facilities in a high-risk HD environment for a prolonged dialytic age facilitates the nosocomial transmission of HCV infection. A significant decline of annual seroconversion rate from 6.8% to 1.01% (odds ratio [OR], 7.535; 95% CI, 1.598-48.89; P <.005) suggests that a comprehensive, strictly enforced isolation policy for HCV-positive patients may play a significant role in limiting HCV transmission in HD units, just as it has in drastically reducing HBV transmission in these settings.
Asunto(s)
Infección Hospitalaria/prevención & control , Unidades de Hemodiálisis en Hospital/organización & administración , Hepatitis C/prevención & control , Control de Infecciones/métodos , Aislamiento de Pacientes , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Infección Hospitalaria/epidemiología , Infección Hospitalaria/virología , Desinfección/métodos , Femenino , Hepatitis C/epidemiología , Humanos , Masculino , Persona de Mediana Edad , Personal de Enfermería en Hospital/organización & administración , Prevalencia , Estudios Prospectivos , Diálisis Renal/efectos adversos , Diálisis Renal/métodos , Estudios Retrospectivos , Factores de Riesgo , Arabia Saudita/epidemiología , Estudios SeroepidemiológicosRESUMEN
BACKGROUND: Fairly higher nasal carriage rates among type-II diabetics place them at a greater risk of endogenous Staphylococcus aureus linked vascular access-related septicemia (VRS) that is also dependent on the type of vascular access used for hemodialysis (HD). The prevalence of nasal carriage of methicillin susceptible and methicillin-resistant S. aureus (MSSA and MRSA) and its impact on VRS was determined in order to identify most vulnerable group and plan potential prophylactic strategies, accordingly. METHODS: Five standardized nasal swab cultures were performed in 208 patients enrolled for long-term HD through July 1996 to July 1999. Persistent nasal carriage was defined by two or more positive cultures for MSSA or MRSA. Peripheral blood cultures were collected on clinical suspicion of septicemia. RESULTS: The prevalence of type-II diabetes of 28.0% with 72.4% of nasal carriage rate and three folds higher S. aureus related VRS (RR-3.19, p<0.0001) than diabetic non-carriers on HD, was observed. Type-II diabetics also had higher MSSA and MRSA nasal carriage rates (53.4% and 19.0%) than non-diabetic nasal carriers (18.6 and 6.0%) yet, carried a comparable (RR-4.0 vs. 4.5) risk of VRS between MSSA and MRSA nasal carriers. Among diabetic type-II S. aureus nasal carriers, central venous catheters (CVCs) carried 35 and 38 times higher collective risk of developing MSSA and MRSA nasal carriage-related VRS respectively than Arterio-venous fistula (AVF). The AVF recorded the lowest risk of developing MSSA and MRSA nasal carriage-related VRS (0.013 and 0.010 episodes/patient-year) in both diabetic type-II MSSA and MRSA nasal carrier groups. CONCLUSIONS: Diabetic type-II S. aureus nasal carriers on HD through CVCs make an extremely high-risk group for MSSA and MRSA nasal carriage-related VRS. The incidence of S. aureus nasal carriage-related VRS could reasonably be reduced through a challenging obligation of optimizing AVF prevalence in this high-risk group, while limiting the use of CVCs, at the same time.
Asunto(s)
Bacteriemia/etiología , Portador Sano/microbiología , Catéteres de Permanencia/efectos adversos , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/terapia , Fallo Renal Crónico/etiología , Fallo Renal Crónico/terapia , Resistencia a la Meticilina , Cavidad Nasal/microbiología , Diálisis Renal/efectos adversos , Staphylococcus aureus/aislamiento & purificación , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Bacteriemia/microbiología , Catéteres de Permanencia/microbiología , Diabetes Mellitus Tipo 2/microbiología , Femenino , Humanos , Fallo Renal Crónico/microbiología , Masculino , Persona de Mediana Edad , Factores de Riesgo , Staphylococcus aureus/efectos de los fármacosRESUMEN
BACKGROUND: AV fistula (AVF) is the safest of vascular accesses with lowest infection rates; yet only 23% patients used AVF during 1997 in USA. The lower prevalence of AVF among diabetics on hemodialysis (HD) places them at a higher risk of vascular-access-related septicemia (VRS) and ensuing mortality. In this study we assessed the outcome of VRS after maximizing the frequency of native AVF in this largest growing population on HD. METHODS: Study included 218 patients, 63 diabetics and 155 nondiabetics on HD, through July 1996 to July 2000 when National Kidney Foundation-Dialysis Outcome and Quality Initiative (NKF-DOQI) set goal was accomplished with overall 72% of functioning AVF (57.2% diabetics and 78.1% nondiabetics) through joint efforts of nephrologists and vascular surgeons. RESULTS: Overall, 10.6% patients per year developed VRS through 125 episodes, over 10,464 patient-months, recording 1.19 episodes per 100 patient-months. In the diabetic group, 13.87% patients per year had VRS during 44 episodes with 1.45 episodes per 100 patient-months while 1.08 episodes per 100 patient-months were recorded in nondiabetics with 9.35% per year having VRS during 81 episodes. Collectively, catheters recorded 1.5 folds higher VRS episodes in diabetic than in nondiabetic group. Mortality of 9.28% per year in diabetic group as compared to that of 6.45% per year in nondiabetic group [RR-1.436, 95% CI (0.778-2.651)] was observed, while overall mortality of 7.5% per year recorded is a good deal lower than 12-22% reported. CONCLUSION: The NKF-DOQI set aim of dialyzing over 50% patients through AVF is attainable in diabetics as well. Optimizing AVF is a viable approach to lessen VRS related mortality in diabetics on HD. Our continued dependence on vascular catheters is largely responsible for higher mortality in diabetics than nondiabetics on HD due to lack of cagily established pre-ESRD program for diabetics.
Asunto(s)
Derivación Arteriovenosa Quirúrgica , Catéteres de Permanencia/efectos adversos , Complicaciones de la Diabetes , Sepsis/etiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Diabetes Mellitus/microbiología , Diabetes Mellitus/mortalidad , Femenino , Humanos , Fallo Renal Crónico/complicaciones , Fallo Renal Crónico/mortalidad , Fallo Renal Crónico/terapia , Masculino , Persona de Mediana Edad , Arabia Saudita/epidemiología , Sepsis/microbiología , Sepsis/mortalidad , Resultado del TratamientoRESUMEN
BACKGROUND: Populations of elderly and type-II diabetics are increasing worldwide. Therefore elderly diabetics on hemodialysis (HD), known to have higher nasal carriage rates, are also increasing. These patients are more often dialyzed through central venous catheters (CVCs). They represent the high-risk groups for Staphylococcus aureus linked vascular access-related septicemia (VRS) and ensuing mortality. The outcome of VRS in terms of mortality was studied in the three high-risk groups: elderly; type-II diabetics; elderly diabetics, following optimization of arteriovenous fistula (AVF) prevalence to at least 50%. METHODS: Persistent nasal carriage was defined by two or more positive standardized nasal swab cultures performed on 187 ESRD patients undergoing HD from July 1997 to July 2000. Peripheral blood samples were collected for culture and sensitivity on clinical suspicion of septicemia. Overall, AVF prevalence of over 50% was achieved through joint efforts of nephrology and vascular surgery departments. RESULTS: A nasal carriage rate of 47.6% was observed in this HD cohort. This included nasal carriage rates of 16.4% in <65 years non-diabetic (reference) group, 55.8% in elderly and 70.7% among type-II diabetics along with that of 75.5% in elderly-diabetic group. We achieved an overall AVF prevalence of 72.7% inclusive of 66.17% in elderly, 65.5% in type-II diabetics and 86.8% in reference group along with 37.7% in elderly-diabetic group. We recorded a mortality due to S. aureus nasal carriage-related VRS of 6.86% in elderly (RR-1.50, p-NS), 10.91% in type-II diabetics (RR-1.52, p<0.02) and 13.20% in the elderly-diabetic group (RR-2.87, p<0.0004) as compared to that of 4.4% per year in the reference group (assigned RR of one) with overall mortality of 7.3% per year. CONCLUSIONS: AVF prevalence of over 50% is achievable in all the high-risk groups except among elderly-diabetics due to the predominance of peripheral vasculopathy. Optimizing AVF placement is a physiological and safer approach for achieving significant reductions in mortality associated with S. aureus nasal carriage-related VRS among high-risk groups.
RESUMEN
The prevalence of anti-HCV antibodies among hemodialysis (HD) patients was studied at King Fahad Hospital, Hofuf, Saudi Arabia. The records of 189 patients undergoing HD were reviewed. The overall prevalence of anti-HCV antibodies was 43.9%. Anti-HCV antibody prevalence was more common among female patients. There was no correlation between repeated blood transfusions and anti-HCV positivity as 4.8% of the patients who did not receive any blood transfusion during HD were positive for anti-HCV antibodies. A positive correlation was observed between the duration on dialysis and anti-HCV antibodies. An annual serocoversion rate of 6.8% was observed in this study.