ABSTRACT
Lupus nephritis (LN) is a severe complication of systemic lupus erythematosus (SLE) and is considered one of the leading causes of mortality. Multiple immunological pathways are involved in the pathogenesis of SLE, which makes it imperative to deepen our knowledge about this disease's immune-pathological complexity and explore new therapeutic targets. Since an altered redox state contributes to immune system dysregulation, this document briefly addresses the roles of oxidative stress (OS), oxidative DNA damage, antioxidant enzymes, mitochondrial function, and mitophagy in SLE and LN. Although adaptive immunity's participation in the development of autoimmunity is undeniable, increasing data emphasize the importance of innate immunity elements, particularly the Toll-like receptors (TLRs) that recognize nucleic acid ligands, in inflammatory and autoimmune diseases. Here, we discuss the intriguing roles of TLR7 and TLR9 in developing SLE and LN. Also included are the essential characteristics of conventional treatments and some other novel and little-explored alternatives that offer options to improve renal function in LN.
Subject(s)
Lupus Erythematosus, Systemic , Lupus Nephritis , Humans , Lupus Nephritis/metabolism , Toll-Like Receptor 9/metabolism , Toll-Like Receptor 7/genetics , Immunity, Innate , Oxidation-ReductionABSTRACT
Obesity and hypertension are health problems of increasing prevalence in developed countries. The link between obesity and hypertension is not yet fully determined. Oxidative stress (OS) and mitochondrial function may play a role in obesity-associated hypertension. A cross-sectional study with 175 subjects with normal weight, overweight, or obese who attended a medical check-up was included. The subjects were divided according to the body mass index (BMI) into normal-weight (n-53), overweight (n-84), and obesity (n-38). Hypertension was also evaluated. To measure mitochondrial function, ATP hydrolysis and ATP synthesis in platelets and serum, respectively, were determined. Superoxide dismutase (SOD), catalase, lipohydroperoxides, 8-isoprostanes, carbonyl groups in proteins, nitric oxide (NO) metabolites, 8-hydroxy-2'-deoxyguanosine (8-OHG), 8-oxoguanine glycosylase (hOGG1), tumor necrosis factor-alpha (TNF-α) and interleukin 6 (IL-6) were measured by standard colorimetric or immunoassay methods. Obese subjects showed lower ATP hydrolysis activity than normal weight and overweight subjects (p < 0.01). No differences between those groups were found in ATP synthase and catalase activities, lipid hydroperoxides, carbonyl groups in proteins, 8-isoprostanes, and NO metabolites. In the obesity group, SOD activity (p < 0.01) was decreased while 8-OHG (p < 0.01) was increased. Subjects with hypertension showed increased 8-OHG (p < 0.01) and less reparative enzyme (hOGG1 p = 0.04) than subjects with normal weight. Moreover, we found a decrease of SOD (p < 0.01), catalase activities (p = 0.04), NO metabolites (p < 0.01), and increases of carbonyl groups in proteins (p = 0.01), TNF-α (p < 0.01) and IL-6 (p < 0.01 in hypertensive subjects. Obese subjects show a decrease in ATP hydrolysis. The decrease in ATP hydrolysis rate and ATP synthesis and an increase in OS and inflammation markers were associated with the hypertensive state.
ABSTRACT
BACKGROUND: We undertook this study to evaluate the results of surgical treatment of symptomatic cholelithiasis through laparoscopic cholecystectomy in a series of 47 consecutive pediatric patients. METHODS: During a 5-year period (2001-2005) we performed laparoscopic cholecystectomy in 47 patients <18 years old in one institution by the same surgical team. The population was comprised of 41 girls and 6 boys (age range: 6-18 years). All had symptomatic cholelithiasis confirmed at ultrasound examination. Associated pathology was studied in each case. The surgical procedure consisted of a four-port laparoscopic cholecystectomy under CO(2) pneumoperitoneum. No other concomitant procedure was performed in any case. RESULTS: Median age was 14.6 years old. The youngest patient of the series had a hematological disease. In girls we identified obesity in 62.5% of patients, with a body mass index (BMI) of 26.6 kg/m(2) (SD 3.0) vs. 21.5 kg/m(2) (SD 3.0) in boys (p <0.05), 30% of the girls had a positive medical history for pregnancies (range 1-3) and 15% regularly used oral contraceptives. All cases were symptomatic and 13% suffered from acute biliary pancreatitis. Average surgical time was 59.8 min, the conversion rate was 2.1% and the most frequent surgical complication was gallbladder rupture. No major morbidity was observed as well as no mortality. Postoperatively, all patients were asymptomatic, with a minimum follow-up time of 6 months. CONCLUSIONS: Laparoscopic cholecystectomy was highly effective in cases of symptomatic cholelithiasis. Etiologically, females showed risk factors for cholelithiasis similar to those usually observed in adults. Probably in the near future the incidence of cholelithiasis will increase in this age group. Pediatric surgeons should be familiarized with the minimal access technique to treat this disease.
