Diagnosis and risk stratification in patients with anti-RNP autoimmunity.

INTRODUCTION: Anti-RNP autoantibodies occur either in mixed connective tissue disease (MCTD) (with a frequently favorable prognosis), or in systemic lupus erythematosus (SLE) cases with aggressive major organ disease. It is uncertain how to assess for the risk of severe disease in anti-RNP + patients. METHODS: Following institutional review board-approved protocols, clinical data and blood were collected from patients with known or suspected anti-RNP autoimmunity and normal controls in a cohort study. Samples were screened for parameters of immune activation. Groups were compared based on clinical diagnoses, disease classification criteria, disease activity and specific end-organ clinical manifestations. RESULTS: Ninety-seven per cent of patients satisfying Alarcon-Segovia MCTD criteria also met Systemic Lupus International Collaborating Clinic (SLICC) SLE criteria, while 47% of the anti-RNP + SLE patients also met MCTD criteria. Among SLICC SLE patients, MCTD criteria were associated with reduced rates of renal disease (odds ratio (OR) 4.3, 95% confidence interval (CI) 1.3-14.0), increased rates of Raynaud's phenomenon (OR 3.5, 95% CI 1.3-9.5) and increased serum B-cell maturation antigen, transmembrane activator and CAML interactor and TNFα levels. Circulating immune markers and markers of type I interferon activation were not effective at distinguishing clinical subgroups. CONCLUSIONS: Among anti-RNP patients, the question of MCTD versus SLE is not either/or: most MCTD patients also have lupus. MCTD classification criteria (but not a broad set of immune markers) distinguish a subset of SLE patients at reduced risk for renal disease.

Salivary gland metabolism in an animal model of chronic kidney disease.

OBJECTIVE: The aim of this study was to determine the effects of experimental CKD into the metabolism of parotid and submandibular glands of rats. CKD was induced by 5/6 nephrectomy. DESIGN: Serum analyses of BUN (Blood Urea Nitrogen) and creatinine concentrations were performed. Major salivary glands metabolism was investigated in vivo, both at rest and during salivary stimulation conditions by NMR isotopomer analysis, using [U-13C]glucose as metabolic tracer. RESULTS: CKD increases BUN and serum creatinine concentrations (p < 0.001). Multiple metabolic alterations were detected in the parotid glands of this animal model, including decreased concentrations of alanine (p < 0.05) and creatine (p < 0.05) and increased lactate/alanine ratios (p < 0.05). The salivary stimulus fostered accumulations of acetate at both analyzed glands of the CKD model (p < 0.05), indicative of disruption of the oxidative metabolic process. CONCLUSIONS: Experimental CKD induced by 5/6 nephrectomy altered the parotid salivary gland function, since glucose metabolism is clearly affected after stimulation for salivation in this gland.

Adhesion and reliability of interfaces in cemented total joint arthroplasties.

Debonding of the prosthetic/polymethylmethacrylate interface has been implicated in the initial failure process of cemented total hip arthroplasties. However, little quantitative understanding of the debonding process, as well as of the optimum interface morphology for enhanced resistance to debonding, exists. Accordingly, a fracture-mechanics approach has been used in which adhesion at the interface is characterized in terms of the interface fracture energy, G (J/m2), and shown to be a strong function of the morphology, debonding length, and loading mode of the interface. Double-cantilever-beam and four-point-flexure fracture-mechanics samples containing four clinically relevant prosthetic surface preparations were prepared to survey a range of interface roughness and loading modes. Adhesion at the interface could not be characterized with a single-valued material property but was found to exhibit resistance-curve behavior in which resistance to debonding increased with both the initial debond extension and the roughness of the interface. Values of debonding initiation, Go, were relatively insensitive to the roughness of the surface and the loading mode, whereas steady-state fracture resistance of the interface, Gss, increased significantly with the roughness and shear loading of the interface. These quantitative results suggest that debonding of the prosthetic/polymethylmethacrylate interface may be primarily attributed to surface interactions such as interlocking and the pullout of rough asperities that occur behind the debond tip. A simple mechanics analysis of such interactions was performed and revealed increases in the fracture resistance of the interface that were consistent with experimentally measured values.

New insights into antioxidant strategies against paraquat toxicity.

Paraquat (PQ, 1,1'-dimethyl-4-4'-bipyridinium dichloride) is a highly toxic quaternary ammonium herbicide widely used in agriculture, it exerts its toxic effects mainly because of its redox cycle through the production of superoxide anions in organisms, leading to an imbalance in the redox state of the cell causing oxidative damage and finally cell death. The contribution of mitochondrial dysfunction including increased production of reactive oxygen species besides the reduction in oxygen consumption as well as in the activity of some respiratory complexes has emerged as a key component in the mechanisms through which PQ induces cell death. Although several aspects of PQ-mitochondria interaction remain to be clarified, recent advances have been conducted with reproducible results. Currently, there is no treatment for PQ poisoning; however, several studies taking into account oxidative stress as the main mechanism of PQ-induced toxicity suggest an antioxidant therapy as a viable alternative. In fact, it has been shown that the antioxidants naringin, sylimarin, edaravone, Bathysa cuspidata extracts, alpha-lipoic acid, pirfenidone, lysine acetylsalicylate, selenium, quercetin, C-phycocyanin, bacosides, and vitamin C may be useful in the treatment against PQ toxicity. The main mechanisms involved in the protective effect of these antioxidants include the reduction of oxidative stress and inflammation and the induction of antioxidant defenses. Interestingly, recent findings suggest that the induction of nuclear factor erythroid like-2 (Nrf2), a major regulator of the antioxidant response, by some of the above-mentioned antioxidants, has been involved in the protective effect against PQ-induced toxicity.

Analysis of DNA damage induced by aflatoxin B1 in Dunkin-Hartley guinea pigs.

Aflatoxin B1 (AFB1) is among the most potent naturally occurring carcinogens and classified as a group I carcinogen. Since the ingestion of aflatoxin-contaminated food is associated with several liver diseases, the aim of the present study was to evaluate the effect of 2, 20, and 200 ppb of AFB1 on DNA damage in peripheral blood lymphocytes and liver cells in Dunkin-Hartley guinea pigs. The animals were divided into four groups according to the given diet. After the treatment the lymphocytes and liver cells were isolated and DNA damage determined by Comet assay. The levels of DNA damage in lymphocytes were higher animals treated with 200 ppb of AFB1-enriched diet (P = 0.02). In the liver cells there were a relationship between the levels of DNA damage and the consumption of AFB1 in all studied groups. These results suggest that Comet assay performed on lymphocytes is a valuable genotoxic marker for high levels of exposure to AFB1 in guinea pig. Additionally our results indicate that the exposure to this toxin increases significantly and increases the level of DNA damage in liver cells, which is a key step on liver cancer development. We also suggest that the Comet assay is an useful tool for monitoring the genotoxicity of AFB1 in liver.

Sliding trochanteric osteotomy preserves favorable abductor biomechanics in revision total hip arthroplasty.

The outcome of sliding trochanteric osteotomy in revision total hip arthroplasty was assessed by comparing preoperative and postoperative static radiographic biomechanics and clinical hip abductor function of 22 consecutive operations (20 patients). Preoperative and postoperative pelvic radiographs were reviewed to quantify the biomechanical reconstruction of the hip abductor mechanism. Abductor muscle length and abductor moment arm were increased significantly (P <.05) by the operation. There was a significant (P <.05) increase in maximum degrees of active hip abduction from the preoperative to the postoperative state, an average of 32 months (range, 6-65 months) after surgery. The dysfunction index (a radiographic representation of hip torque) correlated positively (r =.63; P <.05) with active hip abduction. Sliding trochanteric osteotomy improves abductor biomechanics and may protect against trochanteric migration in revision total hip arthroplasty.