Association between COX-2 rs 6681231 Genotype and Interleukin-6 in Periodontal Connective Tissue. A Pilot Study

This study was partially undertaken at the UCL Eastman Dental Institute, which received a proportion of funding from the Department of Health’s National Institute of Health Research (NIHR) Biomedical Research Centres funding scheme

Sarcomas primarios de hueso: estudio por citometría estática mediante análisis digital de imagen

Se presenta un estudio morfométrico y densitométrico mediante análisis digital de imagen de una serie de 50 tumores óseos malignos (32 osteosarcomas, 12 condrosarcomas y 6 histiocitomas fibrosos malignos de hueso), con el fin de evaluar la utilidad de la técnica para establecer el grado y el pronóstico de estas neoplasias. Las variables morfométricas y la disposición de la cromatina guardan una estrecha relación con el grado histológico (Spearman; p < 0,05) y muestran diferencias estadísticamente significativas entre los tumores considerados de alto y bajo grado en base a su presentación y evolución clínica. La ploidía estimada por densitometría óptica se comporta como un factor pronóstico independiente en el análisis multivariante de la serie de tumores de alto grado (COX; p < 0,001). La citometría estática, aunque más lenta e imprecisa que la citometría de flujo en la determinación de los picos de ploidía, permite analizar el modelo de cromatina y contribuye objetivamente al establecimiento del grado biológico de los tumores óseos.A densitometry and morphometric assessment by static image cytometry of 50 malignant bone tumors (32 osteosarcomas, 12 chondrosarcomas, and 6 malignant fibrous histiocytomas of bone) was performed in order to assess the validity of the technic in the pathobiological and prognostic evaluation of these neoplasms. A strong correlation between the morphometric features, cromatine distribution and histologic grade was found (Spearman; p < 0.05). These parameters are also statistically different for hight and low grade tumors in clinical staging. The stimation of DNA ploidy by optic densitometry is a significant prognostic factor in the multivariant analysis for the high grade tumors (COX; p < 0.001). Although Flow cytometry is a better procedure to evaluate DNA ploidy peaks, our study reveals static image cytometry as a useful technic for determine the cromatine model and objective assessment of the biological grade of bone neoplasms

Heat-shock protein 60 kDa and atherogenic dyslipidemia in patients with untreated mild periodontitis: a pilot study.

Identification of predictors of cardiovascular risk can help in the prevention of pathologic episodes and the management of patients at all stages of illness. Here, we investigated the relationships between serum levels of Hsp60 and dyslipidemia in patients with periodontitis by performing a cross-sectional study of 22 patients with mild periodontitis without any prior treatment for it (i.e., drug naïve) and 22 healthy controls, matched for age and body mass index (BMI). All subjects were evaluated for periodontal status, gingival inflammation, and oral hygiene. Levels of circulating Hsp60, C-reactive protein (CRP), and plasma lipids were measured, and small, dense low-density lipoproteins (LDL) were indirectly assessed by determining the triglycerides/high-density lipoproteins (HDL) cholesterol ratio. We also assessed by immunohistochemistry Hsp60 levels in oral mucosa of patients and controls. No difference was found in CRP levels or plasma lipids between the two groups, but subjects with periodontitis showed, in comparison to controls, higher levels of small, dense LDL (p  = 0.0355) and circulating Hsp60 concentrations (p < 0.0001). However, levels of mucosal Hsp60 did not change significantly between groups. Correlation analysis revealed that circulating Hsp60 inversely correlated with HDL-cholesterol (r  = -0.589, p  = 0.0039), and positively with triglycerides (r  = +0.877, p < 0.0001), and small, dense LDL (r  = +0.925, p < 0.0001). Serum Hsp60 significantly correlated with the degree of periodontal disease (r  = +0.403, p  = 0.0434). In brief, untreated patients with mild periodontitis had increased small, dense LDL and serum Hsp60 concentrations, in comparison to age- and BMI-matched controls and both parameters showed a strong positive correlation. Our data indicate that atherogenic dyslipidemia and elevated circulating Hsp60 tend to be linked and associated to periodontal pathology. Thus, the road is open to investigate the potential value of elevated levels of circulating Hsp60 as predictor of risk for cardiovascular disease when associated to dyslipidemia in periodontitis patients

Poly[ADP-Ribose] Polymerase-1 Expression Is Related To Cold Ischemia, Acute Tubular Necrosis, and Delayed Renal Function In Kidney Transplantation

Cold ischemia time especially impacts on outcomes of expanded-criteria donor (ECD) transplantation. Ischemia-reperfusion (IR) injury produces excessive poly[ADP-Ribose] Polymerase-1 (PARP-1) activation. The present study explored the hypothesis that increased tubular expression of PARP-1 contributes to delayed renal function in suboptimal ECD kidney allografts and in non-ECD allografts that develop posttransplant acute tubular necrosis (ATN)

Therapeutic Effect of a Poly(ADP-Ribose) Polymerase-1 Inhibitor on Experimental Arthritis by Downregulating Inflammation and Th1 Response

Poly(ADP-ribose) polymerase-1 (PARP-1) synthesizes and transfers ADP ribose polymers to target proteins, and regulates DNA repair and genomic integrity maintenance. PARP-1 also plays a crucial role in the progression of the inflammatory response, and its inhibition confers protection in several models of inflammatory disorders. Here, we investigate the impact of a selective PARP-1 inhibitor in experimental arthritis. PARP-1 inhibition with 5-aminoisoquinolinone (AIQ) significantly reduces incidence and severity of established collagen-induced arthritis, completely abrogating joint swelling and destruction of cartilage and bone. The therapeutic effect of AIQ is associated with a striking reduction of the two deleterious components of the disease, i.e. the Th1-driven autoimmune and inflammatory responses. AIQ downregulates the production of various inflammatory cytokines and chemokines, decreases the antigen-specific Th1-cell expansion, and induces the production of the anti-inflammatory cytokine IL-10. Our results provide evidence of the contribution of PARP-1 to the progression of arthritis and identify this protein as a potential therapeutic target for the treatment of rheumatoid arthritis

Urinary Aminopeptidase Activities as Early and Predictive Biomarkers of Renal Dysfunction in Cisplatin-Treated Rats

This study analyzes the fluorimetric determination of alanyl- (Ala), glutamyl- (Glu), leucyl-cystinyl- (Cys) and aspartyl-aminopeptidase (AspAp) urinary enzymatic activities as early and predictive biomarkers of renal dysfunction in cisplatin-treated rats. Male Wistar rats (n = 8 each group) received a single subcutaneous injection of either saline or cisplatin 3.5 or 7 mg/kg, and urine samples were taken at 0, 1, 2, 3 and 14 days after treatment. In urine samples we determined Ala, Glu, Cys and AspAp activities, proteinuria, N-acetyl-β-D-glucosaminidase (NAG), albumin, and neutrophil gelatinase-associated lipocalin (NGAL). Plasma creatinine, creatinine clearance and renal morphological variables were measured at the end of the experiment. CysAp, NAG and albumin were increased 48 hours after treatment in the cisplatin 3.5 mg/kg treated group. At 24 hours, all urinary aminopeptidase activities and albuminuria were significantly increased in the cisplatin 7 mg/kg treated group. Aminopeptidase urinary activities correlated (p0.259) with plasma creatinine, creatinine clearance and/or kidney weight/body weight ratio at the end of the experiment and they could be considered as predictive biomarkers of renal injury severity. ROC-AUC analysis was made to study their sensitivity and specificity to distinguish between treated and untreated rats at day 1. All aminopeptidase activities showed an AUC>0.633. We conclude that Ala, Cys, Glu and AspAp enzymatic activities are early and predictive urinary biomarkers of the renal dysfunction induced by cisplatin. These determinations can be very useful in the prognostic and diagnostic of renal dysfunction in preclinical research and clinical practice.This study was supported by a grant (R1/12/2010/66) from the University of Jaén with the participation of Caja Rural of Jaén, and from the Carlos III Health Institute of the Spanish Ministry of Health and Consumer Affairs (Red de Investigación Renal, REDinREN RD06/0016/0017 and RD07/0016/2008), “FEDER una manera de hacer Europa.