RESUMO
This study defines retinal phosphatic metabolites and their adjustment to illumination in rat retinas under conditions that preserve retinal function. Metabolic data are measured using high-performance liquid chromatography (HPLC) and 31P nuclear magnetic resonance (31P NMR) spectroscopy after 10 min of light exposure in vivo compared with retinas from dark-adapted rats. Multiple high-energy and low-energy phosphatic metabolites of intermediary metabolism were quantified. The concentration of the high-energy phosphate adenosine triphosphate (ATP) remained unchanged from dark- to light-adaptation. Under the same conditions the concentrations of the high-energy phosphates guanosine triphosphate (GTP) and creatine phosphate increased, whereas the inorganic phosphate decreased. Comparing dark-adapted controls with retinas light-adapted either in vitro or in vivo, the evidence is consistent with a light-dependent increase in GTP and a decrease in cyclic guanosine monophosphate. Although cyclic adenosine monophosphate (cAMP) levels were lower in retinas light-adapted in vivo than in the dark-adapted controls, this did not seem to be an effect of light, as cAMP levels decreased similarly after 10 min incubation in dark or light in parallel with recovery of ATP/adenosine diphosphate ratios. This study: (1) reports on retinal metabolic changes with adjustment in illumination, (2) provides baseline measurements of retinal phosphatic metabolites in whole retinas, and (3) reports on the validity of chromatographic and spectroscopic methods used for studying retinal metabolism establishing a high correlation among measurements made using HPLC and 31P NMR.
Assuntos
Trifosfato de Adenosina , Retina , Adaptação Ocular , Trifosfato de Adenosina/metabolismo , Animais , Adaptação à Escuridão , Metabolismo Energético , Guanosina Trifosfato/metabolismo , Fosfatos/metabolismo , Ratos , Retina/metabolismoRESUMO
BACKGROUND: Conflicts can lead to significant disruption in the care of endstage kidney disease (ESKD) patients. The purpose of this paper is to review the available literature on the care of ESKD patients in times of armed conflict and make recommendations for action. METHOD: A review of all PubMed-published reports between 1965 and 2015 about the care of ESKD patients at the time of conflict. We excluded articles that reported on acute kidney injury and natural disasters. RESULTS: We found a total of 12 reports on dialysis care and/or kidney transplant care from five armed conflicts and resulting refugee crises. These conflicts led to significant shortage of staff and resources and caused several obstacles in providing adequate dialysis to ESKD patients. In one study, the mortality rate of patients on automated peritoneal dialysis was as high as 95%. The kidney transplantation rate decreased in all but one of the reports about kidney transplant care and patients had difficulties securing their immunosuppressive medications. CONCLUSIONS: ESKD patients, especially dialysis patients, comprise a severely vulnerable population during conflicts. Their care can be disrupted and altered leading to a substantial increase in their mortality rate. Efforts to improve their care during conflicts are needed.
Assuntos
Conflitos Armados , Atenção à Saúde , Falência Renal Crônica/terapia , Transplante de Rim , Diálise Renal , Feminino , Política de Saúde , Humanos , Transplante de Rim/efeitos adversos , Populações VulneráveisRESUMO
BACKGROUND/AIMS: Reactive oxygen species, and especially superoxide (O2*),have been implicated in diabetic nephropathy. O2* accumulation in cells is dependent on O2* production (by NADH/NADPH oxidase) as well as scavenging by superoxide dismutase (SOD) activity. This study was designed to investigate the effects of high glucose (HG) on O2* accumulation and SOD activity in human mesangial cells (HMC) and to determine if these effects are mediated by angiotensin II (Ang II). METHODS: HMC were incubated in media containing 10 mM glucose (control, C), 30 mM glucose (HG), 10 mM glucose + either 20 mM 2-deoxy-D-glucose (2-DG) or 20 mM mannitol (high mannitol, HM) (osmotic controls), or Ang II (10(-5) M). Ang II action was antagonized by employing 10(-4) M of Ang II receptor antagonists (losartan or irbesartan) or 10(-4) M of NADH/NADPH oxidase inhibitors [diphenyleneiodonium chloride (DPI) or apocynin]. Superoxide and total SOD activity were assayed using chemiluminescence of lucigenin. RESULTS: Incubation of HMC in HG resulted in a 1.6-fold increase in Ang I (p < 0.05) and a 1.4-fold increase in Ang II levels (p < 0.05) in cell lysates. These changes were accompanied by a >2-fold increase in O2* accumulation (p < 0.01), which was inhibited by losartan and irbesartan. Exogenous Ang II increased net O2* accumulation by 2.7-fold (p < 0.01), which was normalized by losartan and irbesartan. DPI and apocynin blocked the HG and Ang II-induced increases in O2* (p < 0.01). HG but not exogenous Ang II inhibited total SOD activity by 30%, which was not affected by losartan. CONCLUSION: High glucose increases O2* accumulation in HMC primarily by increasing its production via the Ang II-NADH/NADPH oxidase system.
Assuntos
Angiotensina II/fisiologia , Nefropatias Diabéticas/fisiopatologia , Glucose/fisiologia , Glomérulos Renais/fisiologia , Oxidantes/análise , Superóxido Dismutase/metabolismo , Superóxidos/análise , Bloqueadores do Receptor Tipo 1 de Angiotensina II/farmacologia , Compostos de Bifenilo/farmacologia , Técnicas de Cultura de Células , Humanos , Irbesartana , Glomérulos Renais/citologia , Losartan/farmacologia , Tetrazóis/farmacologiaRESUMO
BACKGROUND: The risk factors for progression of chronic kidney disease (CKD) in type 2 diabetes mellitus (DM) have not been fully elucidated. Although uncontrolled blood pressure (BP) is known to be deleterious, other factors may become more important once BP is treated. METHODS: All patients seen in the outpatient clinics of our hospital between January 1993 and September 2002 with type 2 DM and clinical evidence of CKD were evaluated. Progression of kidney disease was evaluated by rate of decline of glomerular filtration rate (GFR) as estimated from the simplified MDRD formula. Variables associated with progression in univariate analyses were examined by multivariate analysis to determine the factors independently associated with kidney disease progression. RESULTS: 343 patients (mean age 69 years; all male; 77% Caucasian) were studied. Mean BP, glycated hemoglobin, and serum cholesterol during the study period were 138/72 mmHg, 8.1%, and 4.8 mmol/L, respectively. Mean decline of GFR was 4.5 ml min-1 1.73 m2-1 yr-1 (range -14 to +32). Low initial serum albumin (p < 0.001), black race (p < 0.001), and degree of proteinuria (p = 0.002), but not blood pressure, glycated hemoglobin, or serum cholesterol, were independently associated with progression. CONCLUSION: In a cohort of diabetic patients with CKD in whom mean BP was < 140/80 mmHg, the potentially remediable factors hypoalbuminemia and proteinuria but not blood pressure were independently associated with progression of kidney disease. Further understanding of the relationship between these factors and kidney disease progression may lead to beneficial therapies in such patients.