AIM: To determine the plasma and saliva levels of IL-6 in patients with bisphosphonate-related osteonecrosis of the jaws (BRONJ) and to investigate whether there is a correlation between more advanced stages of BRONJ and levels of IL-6.MATERIAL AND METHODS: We studied three groups: group 1 consisted of 30 patients with BRONJ due to intravenous bisphosphonates (ivBP), group 2 consisted of 25 patients treated with ivBP but without BRONJ, and group 3 consisted of 15 healthy controls. In each case, we assayed plasma and saliva IL-6 samples using an ELISA test.RESULTS: Significantly, higher IL-6 values were found in both saliva and plasma in group 1 vs groups 2 and 3 (P < 0.01). Group 1 showed no differences in plasma or saliva IL-6 according to patient gender (P > 0.05), type of tumor, BRONJ location, etiology of BRONJ, or disease stage (P > 0.05). We found higher plasma and saliva IL-6 values in the more advances stages of BRONJ, although the differences were not statistically significant.CONCLUSIONS: Plasma and saliva IL-6 values were higher in our patients with BRONJ than in controls and therefore might be a useful tool for monitoring the severity of BRONJ.

Non-alcoholic steatohepatitis (NASH) is a chronic liver disease characterized by hepatic lipid accumulation, inflammation, and progressive fibrosis. Acetyl-CoA carboxylase (ACC) catalyzes the rate-limiting step of de novo lipogenesis and regulates fatty acid β-oxidation in hepatocytes. ACC inhibition reduces hepatic fat content and markers of liver injury in patients with NASH; however, the effect of ACC inhibition on liver fibrosis has not been reported.A direct role for ACC in fibrosis was evaluated by measuring de novo lipogenesis, procollagen production, gene expression, glycolysis, and mitochondrial respiration in hepatic stellate cells (HSCs) in the absence or presence of small molecule inhibitors of ACC. ACC inhibitors were evaluated in rodent models of liver fibrosis induced by diet or the hepatotoxin, diethylnitrosamine. Fibrosis and hepatic steatosis were evaluated by histological and biochemical assessments.Inhibition of ACC reduced the activation of TGF-β-stimulated HSCs, as measured by both α-SMA expression and collagen production. ACC inhibition prevented a metabolic switch necessary for induction of glycolysis and oxidative phosphorylation during HSC activation. While the molecular mechanism by which inhibition of de novo lipogenesis blocks glycolysis and oxidative phosphorylation is unknown, we definitively show that HSCs require de novo lipogenesis for activation. Consistent with this direct antifibrotic mechanism in HSCs, ACC inhibition reduced liver fibrosis in a rat choline-deficient, high-fat diet model and in response to chronic diethylnitrosamine-induced liver injury (in the absence of hepatic lipid accumulation).In addition to reducing lipid accumulation in hepatocytes, ACC inhibition also directly impairs the profibrogenic activity of HSCs. Thus, small molecule inhibitors of ACC may lessen fibrosis by reducing lipotoxicity in hepatocytes and by preventing HSC activation, providing a mechanistic rationale for the treatment of patients with advanced liver fibrosis due to NASH.Hepatic fibrosis is the most important predictor of liver-related outcomes in patients with non-alcoholic steatohepatitis (NASH). Small molecule inhibitors of acetyl-CoA carboxylase (ACC) reduce hepatic fat content and markers of liver injury in patients with NASH. Herein, we report that inhibition of ACC and de novo lipogenesis also directly suppress the activation of hepatic stellate cells – the primary cell responsible for generating fibrotic scar in the liver – and thus fibrosis. These data provide further evidence for the use of ACC inhibitors to treat patients with NASH and advanced fibrosis.

Crataegus laevigata is a medicinal plant most commonly used for the treatment of heart failure and psychosomatic disorders. Based on previous experimental findings, this double-blind placebo-controlled study was aimed at finding beneficial effects of C. laevigata on biomarkers of coronary heart disease (CHD). The study included 49 diabetic subjects with chronic CHD who were randomly assigned to the treatment for 6 months with either a micronized flower and leaf preparation of C. laevigata (400 mg three times a day) or a matching placebo. Blood cell count, lipid profile, C-reactive protein, neutrophil elastase (NE) and malondialdehyde were analyzed in plasma at baseline, at one month and six months. The main results were that NE decreased in the C. laevigata group compared to the placebo group. In the C. laevigata group, baseline figures (median and interquartile range) were 35.8 (4.5) and in the placebo group 31 (5.9). At the end of the study, values were 33.2 (4.7) ng/ml and 36.7 (2.2) ng/ml, respectively; p<0.0001. C. laevigata, added to statins, decreased LDL cholesterol (LDL-C) (mean±SD) from 105±28.5 mg/dl at baseline to 92.7±25.1 mg/dl at 6 months (p=0.03), and non-HDL cholesterol from 131±37.5 mg/dl to 119.6±33 mg/dl (p<0.001). Differences between groups did not reach statistical significance at 6 months. No significant changes were observed in the rest of parameters. In conclusion, C. laevigata decreased NE and showed a trend to lower LDL-C compared to placebo as add-on-treatment for diabetic subjects with chronic CHD.

Polycystic ovary syndrome (PCOS) may be loosely defined as unexplained hyperandrogenism, with variable degrees of cutaneous symptoms, anovulatory symptoms, and obesity. The vast majority of patients with the full-blown Stein-Leventhal syndrome have functional ovarian hyperandrogenism (FOH). However, FOH often occurs without the LH excess or polycystic ovaries of classic PCOS. Functional adrenal hyperandrogenism (FAH) is often found in the syndrome, but it is less closely associated with anovulatory symptoms than is FOH. The vast majority of FOH seems to arise from abnormal regulation (dysregulation) of ovarian androgen secretion. This typically is due to escape from desensitization to luteinizing hormone (LH); this appears to occur because of a breakdown in the processes that normally coordinate ovarian androgen and oestrogen secretion so as to prevent hyperoestrogenism. Similar dysregulation of adrenal androgen secretion in response to ACTH seems to account for most FAH. Dysregulation of androgen secretion may affect the ovary alone (isolated FOH), the adrenal alone (isolated FAH), or both together. Modest insulin resistance is common in PCOS/FOH, and the resultant hyperinsulinaemia is a major candidate as the cause of the dysregulation. The hyperinsulinaemia may arise from either ‘nature’ (genetic defects) or ‘nurture’ (exogenous obesity). Although hyperinsulinaemia alone does not have an obvious effect on steroidogenesis, it may act in genetically predisposed women as a ‘second hit’ to unmask latent abnormalities in steroidogenesis. The ovary, the adrenal cortex, and several other organs paradoxically function as if responding to the hyperinsulinaemic state in spite of resistance to the effects of insulin on glucose metabolism.PCOS should be viewed as an early manifestation of a hyperinsulinaemic condition that will predispose to cardiovascular and metabolic complications later in life. A subset of PCOS patients appear to have not only insulin resistance but also β-cell secretory dysfunction, which may indicate a relationship of the disorder to NIDDM. The fundamental genetic defects remain to be elucidated.

BACKGROUND:Cardiovascular disease remains the single most common cause of excess morbidity and mortality in end-stage renal disease (ESRD) patients and the traditional risk factors can't explain the high incidence of these events. New "non-traditional" risk factors are analysed in uremic patients and the increased oxidative stress is postulated to be an important contributor to uremic cardiovascular risk.METHODS:In order to evaluate the effects of the hemodialysis treatment, a complete oxidative stress study was performed in fifteen uremic patients. Representative antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx), together with oxidized/reduced glutathione ratio (GSSG/GSH) and other oxidation indicators including malondialdehyde (MDA) and 8-oxo-2'-deoxyguanosine (8-oxo-dG), were analysed to assess oxidative stress status in normal control volunteers and in uremic patients treated with hemodialysis (HD). In the latter group blood samples were taken prior and after HD to evaluate the effect of the session of HD over the oxidative markers.RESULTS:Low levels of antioxidant enzyme activities were observed in the uremic patients as compared with normal control subjects. HD treatment results in a significant recovery of these enzyme activities but remain lower as compared with control values. Levels of GSSG and GSH concentrations were increased and reduced respectively in uremic patients. These differences were even higher before the HD and were reduced upon treatment to levels closer to those observed in controls. MDA levels and 8-oxo-dG levels were also increased in uremic patients with the highest values observed in the pre-treated HD group. Even though HD treatment decreases the levels of oxidation products in mononuclear cells of uremic patients the values of the control group are not reached.CONCLUSIONS:Our results suggest that hemodialysis by itself could correct the oxidative status in these patients. The possible mechanisms involved in the oxidative stress changes with the hemodialysis treatment will be discussed below.

The objective was to study the relationship between left ventricular mass (LVM) and ventricular remodeling (RWT) with oxidative stress in mononuclear peripherals cells in essential hypertension.

Interest in xanthin oxidase complex (XOR) has grown because of its ability to generate reactive oxygen species (ROS). The potential influence in hypertension- or diabetes-associated endothelial dysfunction has been claimed in several studies. The objective of the present study was to assess the influence of frequent polymorphisms (–337GA and 565+64CT) of the xanthin oxidase gene in the blood pressure levels and in the oxidative stress of untreated essential hypertension subjects.

Redon, J.1; Giner, V.1; Tormos, M. C.2; Espinosa, O.2; Lozano, J. V.1; Chaves, F. J.1; Saez, G.2 Author Information

Valorar el estatus oxidativo de las neoplasias ováricas mediante la determinación de las enzimas antioxidantes más importantes, los valores de glutatión reducido y oxidado, la formación de malondialdehído, como índice de peroxidación molecular, y el grado de oxidación del material genético mediante la cuantificación de la base mutagénica 8-oxo-deoxiguanosina Estudio prospectivo de 52 casos de neoplasia ovárica: 43 casos de cáncer de ovario epitelial, de los que nueve habían recibido quimioterapia previa a la cirugía, y otros nueve con tumoraciones benignas En el tejido tumoral, al compararlo con tejido sano de las mismas pacientes, se evidenció disminución de las enzimas antioxidantes catalasa y superóxido-dismutasa, así como un aumento del resto de los parámetros estudiados. La quimioterapia anuló las diferencias entre el ovario sano y el tumoral El metabolismo oxidativo se encuentra alterado en el tejido tumoral ovárico si se compara con el tejido sano de las mismas pacientes. La quimioterapia ejerce efecto sobre dicho metabolismo To evaluate the oxidative status of ovarian tumors by determining the most important antioxidant enzymes, oxidized and reduced glutathione levels, the formation of malondialdehyde as an index of molecular peroxidation, and the degree of genetic oxidation by quantification of the mutagenic base 8-oxodeoxiguanosine We performed a prospective study of 52 cases of ovarian tumors: 43 cases were epithelial ovarian carcinoma, 9 of which had been treated with chemotherapy prior to surgery, and 9 cases corresponded to benign tumors Catalase and superoxide-dismutase were decreased, and the remaining parameters evaluated were increased in tumoral tissue compared with non-tumoral tissue from the same patients. Chemotherapy annulled differences between tumoral and non-tumoral ovarian tissue Oxidative metabolism is altered in tumoral ovarian tissue compared with non-tumoral tissue from the same patients. Chemotherapy has an effect on oxidative metabolism

The objective was to evaluate the oxidative status, the extent of lipid and DNA oxidation and the activity of enzymatic antioxidants in essential hypertensive patients out of antihypertensive treatment. Forty-one essential hypertensive subjects (mean age 48 yr, 24 males, SBP 160±18 mmHg, DBP 97±12 mmHg), and 10 normotensive controls were included. According 24h ABP hypertensives were grouped in those with isolated clinic hypertension (ISCH) and true hypertensives (HTN). In whole blood and in lymphocites, oxidative stress status (GSSG/GSH), lipid-perodixation product (malondialdehyde), DNA-damage (8-oxo-2'-deoxyguanosine only in lymphocites) and the activity of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (Gpx) were measured in absence of antihypertensive treatment. All hypertensive subjects shown a significative increase in the GSSG/GSH index as well as in the levels of malondialdehyde or 8-oxo-2'-deoxyguanosine. Subjects with ISCH shown higher GSSG/GSH, malondialdehyde and 8-oxo-2'-deoxyguanosine than the controls did, but lower than those observed in HTN. A decreased activity of the three enzymatic systems, SOD, CAT and Gpx measured were observed in all hypertensive subjects, both ISCH and HTN. Conclusion: Essential hypertension is associated with greater than normal oxidative stress partially related to ambulatory BP levels. Furthermore an imbalance in anti-oxidant status was present in hypertensive subjects.

The objective was to evaluate the relationship between the oxidative status, the extent of DNA oxidation and markers of early organ damage in essential hypertensive patients. Forty-one essential hypertensive subjects (mean age 48 yr, 24 males, SBP 160±18 mmHg, DBP 97±12 mmHg) were included. In absence of antihypertensive treatment, 24-hour urinary albumin excretion (UAE mg/24h) and left ventricular mass index (LVMI g/m) were measured. In whole blood and in lymphocites, oxidative stress status (GSSG/GSH) and DNA-damage (8-oxo-2'-deoxyguanosine only in lymphocites) were assessed. When subjects were divided in tertiles of GSSG/GSH, in whole blood or in lymphocites, the highest tertiles shown higher values of UAE (17.6±6; 19.3±5 and 80.7±44 mg/24h) and higher LVMI (84.4±10; 62.7±4.4 and 104.0±16.3 g/m) than those observed in the two other tertiles. No differences among groups were observed in the 24-hour ambulatory MBP (102±12; 106±7 and 107±20 mmHg). Likewise, subjects in the highest tertile of 8-oxo-2'-deoxyguanosine shown the highest LVMI as compared to the two other tertiles (74±23; 71±23 and 106±51 g/m) in absence of differences in the 24-hour ambulatory MBP (108±11; 106±19 and 103±13 mmHg). Conclusion: Hypertension-induced early organ damage, in part independent to BP values, was related to the oxidative stress levels.