Curcumin prevents maleate-induced nephrotoxicity: relation to hemodynamic alterations, oxidative stress, mitochondrial oxygen consumption and activity of respiratory complex I.

The potential protective effect of the dietary antioxidant curcumin (120 mg/Kg/day for 6 days) against the renal injury induced by maleate was evaluated. Tubular proteinuria and oxidative stress were induced by a single injection of maleate (400 mg/kg) in rats. Maleate-induced renal injury included increase in renal vascular resistance and in the urinary excretion of total protein, glucose, sodium, neutrophil gelatinase-associated lipocalin (NGAL) and N-acetyl ß-D-glucosaminidase (NAG), upregulation of kidney injury molecule (KIM)-1, decrease in renal blood flow and claudin-2 expression besides of necrosis and apoptosis of tubular cells on 24 h. Oxidative stress was determined by measuring the oxidation of lipids and proteins and diminution in renal Nrf2 levels. Studies were also conducted in renal epithelial LLC-PK1 cells and in mitochondria isolated from kidneys of all the experimental groups. Maleate induced cell damage and reactive oxygen species (ROS) production in LLC-PK1 cells in culture. In addition, maleate treatment reduced oxygen consumption in ADP-stimulated mitochondria and diminished respiratory control index when using malate/glutamate as substrate. The activities of both complex I and aconitase were also diminished. All the above-described alterations were prevented by curcumin. It is concluded that curcumin is able to attenuate in vivo maleate-induced nephropathy and in vitro cell damage. The in vivo protection was associated to the prevention of oxidative stress and preservation of mitochondrial oxygen consumption and activity of respiratory complex I, and the in vitro protection was associated to the prevention of ROS production.

Low fructose and low salt diets increase mitochondrial DNA in white blood cells of overweight subjects.

OBJECTIVE: To evaluate the effect of sodium and fructose restriction on mitochondrial DNA (mtDNA) content and systemic oxidative stress in a sample of overweight and pre hypertensive subjects. MATERIAL/METHODS: Data and blood samples were collected from 36 overweight and pre hypertensive patients randomly assigned to either an isocaloric (with respect to baseline) low sodium-fructose diet or an isocaloric low sodium diet. Patients were followed for 8 weeks. We measured mitochondrial DNA (mtDNA) content from peripheral blood white cells by Real-time PCR and plasma malondialdehyde (MDA) and 2,4-dinitrophenylhydrazine (DNPH) as markers of reactive oxygen species (ROS). RESULTS: Compared to baseline, at week 8 there was a continued and significant increase in mtDNA in both the low sodium diet group [2.4 vs. 13.1 (relative copy number), p<0.05] and the low sodium diet-fructose group (1.9 vs. 147.2, p<0.05). By week 8 there was a continued decrease in plasma DNPH levels in the low sodium diet group (4.6 vs. 2.6, p<0.05) and in the low sodium diet-fructose group (5.8 vs. 2.2, p<0.05). No significant differences were found with MDA. CONCLUSION: Our studies suggest that simple dietary measures such as reducing salt with or without restricting fructose can increase mtDNA and improve markers of oxidative stress.

Characterization of IgE epitopes of Cuc m 2, the major melon allergen, and their role in cross-reactivity with pollen profilins.

BACKGROUND: Plant profilins are described as minor allergens, although with some exceptions in foods such as melon, watermelon or orange. In fact, they could be responsible for many cross-reactions among distantly related species. This is likely to be a consequence of the presence of common epitopes. OBJECTIVE: To characterize the B epitopes of Cuc m 2, a model of plant food profilin, using phage display techniques and to compare with other profilins, such as those of timothy grass and birch pollen, and human I profilin, to understand the mechanism of cross-reaction among members of this family. METHODS: IgE of melon-allergic patients was used to select clones from a phage display 12 mer peptide library. After two rounds of screening, Cuc m 2-specific clones were eluted and the DNA insertion sequenced. The residues of each clone were mapped on the Cuc m 2 surface to define a mimotope, which was also localized on the three-dimensional surfaces of other profilins. RESULTS: Seventeen melon-allergic patients were selected. Sera from each of them recognized the melon profilin, Cuc m 2, but the majority also recognized Phl p 12 or Bet v 2, timothy grass-, and birch-pollen profilins, respectively. A Cuc m 2 mimotope was defined and mapped onto its surface giving the following sequence: S(2)W(3)A(5)Y(6)D(9)H(10)T(111)P(112)G(113)Q(114)N(116)M(117)R(121)L(122). The homologous residues in Phl p 12 and Bet v 2 had almost identical sequences. By contrast, the homologous sequence in human profilin showed many differences. CONCLUSIONS: The identified mimotope could be involved in cross-reactions among food and pollen profilins. Many of these cross-reactions observed in the clinical realm could be explained by the presence of a common epitope found in food and pollen allergens. A new strategy of immunotherapy based on this IgE region could be used in alternative immunotherapy strategies.

Long-term outcomes in nondiabetic chronic kidney disease.

The Modification of Diet in Renal Disease (MDRD) Study examined the effects of strict blood pressure control and dietary protein restriction on the progression of kidney disease. Here, we retrospectively evaluated outcomes of nondiabetic participants with stages 2-4 chronic kidney disease (CKD) from randomized and nonrandomized cohorts of the MDRD Study. Kidney failure and survival status through December of 2000, were obtained from the US Renal Data System and the National Death Index. Event rates were calculated for kidney failure, death, and a composite outcome of death and kidney failure. In the 1666 patients, rates for kidney failure were four times higher than that for death. Kidney failure was a more likely event than death in subgroups based on baseline glomerular filtration rate, proteinuria, kidney disease etiology, gender, and race. It was only among those older than 65 that the rate for death approximated that for kidney failure. In contrast to other populations with CKD, our study of relatively young subjects with nondiabetic disease has found that the majority of the participants advanced to kidney failure with a low competing risk of death. In such patients, the primary emphasis should be on delaying progression of kidney disease.

Digestive hemorrhage caused by a Meckel's diverticulum in a metformin-treated patient: is there any connection?

An obese patient, not diabetic, treated with metformin for some weeks, was referred to us with severe inferior digestive hemorrhage, diagnosed with Meckel's diverticulum. Metformin is described as a glucose-lowering agent for treatment of type 2 diabetes mellitus and as antiobesity drug, though results achieved with this last indication are not conclusive. But metformin has fibrinolytic features by means of diminished plasminogen activator inhibitor 1 activity. Although no coagulation study was done and the Meckel's diverticulum is normally associated with bleeding, the particular intensity of the following hemorrhage may have been favored by metformin.

Activity indices in rheumatoid arthritis.

OBJECTIVE: To determine which activity indices better correlate with assessor's (AGA) and patient's (PGA) global assessment of disease activity and to compare the improvement with American College of Rheumatology (ACR) and European League Against Rheumatism (EULAR) criteria and their association with PGA and AGA of overall improvement. METHODS: Seventy-five patients with rheumatoid arthritis (RA) were studied. Swollen and tender joints, morning stiffness, grip strength, pain, AGA, PGA, Health Assessment Questionnaire (HAQ) score, erythrocyte sedimentation rate (ESR), C-reactive protein (CPR), and hemoglobin were determined before and 6 months after treatment. Several activity indices were calculated: Disease Activity Score (DAS), DAS 3, DAS 28, DAS '28,' ACR > or = 20%, Mallya, Riel, IDA, and a modification of the Stoke index. RESULTS: All indices correlated with PGA and AGA before and after treatment (r > 0.38, p < 0.01), but better results were obtained with AGA than PGA. DAS, DAS 3, DAS 28, and modified Stoke had the best correlation with AGA (r > or = 0.77, p < 0.01). The indices that better detected the differences after treatment for AGA were DAS, DAS 3, DAS 28, and modified Stoke (r > or = -0.42, p < 0.01). The level of agreement between EULAR and ACR improvement classifications with both reduced and extensive joint counts was comparable and its association with PGA and AGA overall improvement was significant (p < 0.01). CONCLUSION: All activity indices correlated with PGA and AGA, although the best results were obtained with AGA. Although indices' correlations were similar, the DAS group and the modified Stoke seemed to be the most useful indices to measure disease activity in RA. The discriminating potential between ACR and EULAR improvement classification was comparable, as was the association with PGA and AGA overall improvement.

[Hemodynamic course in relation to mechanical ventilation in the postoperative period of extracorporeal surgery in children]. / Evolución hemodinámica en relación con la ventilación mecánica durante el postoperatorio de cirugía extracorpórea en niños.

Hemodynamic evolution and its relationship with the factors that have an effect upon gaseous exchange, during the early phase after extracorporeal circulation in sixty nine children, are reviewed. They are divided into three groups: group I (APH), arterial pulmonary hypertension; group II (OF), overflow, and group III (C), control. Results in the three phases of mechanical ventilation (IPPV, IMV and CPAP), are compared. We found that only in group I (APH), the pulmonary mechanics was altered. The programmed hyperventilation (IPPV) in group III (C), underlie the results of correlation between ventilatory and hemodynamic parameters with the oxygenation. There are high pulmonary vascular resistance in group I (APH); this explains the positive correlation between diastolic pulmonary arterial pressure and cardiac output. There are a good right ventricle function in I (APH) and III (C) groups. The hemodynamic patterns in IPPV are not depending on the pulmonary state.