Laura Di Renzo

Curcumin and the cellular stress response in free radical-related diseases

Free radicals play a main pathogenic role in several human diseases such as neurodegenerative disorders, diabetes, and cancer. Although there has been progress in treatment of these diseases, the development of important side effects may complicate the therapeutic course. Curcumin, a well known spice commonly used in India to make foods colored and flavored, is also used in traditional medicine to treat mild or moderate human diseases. In the recent years, a growing body of literature has unraveled the antioxidant, anticarcinogenic, and antinfectious activity of curcumin based on the ability of this compound to regulate a number of cellular signal transduction pathways. These promising data obtained in vitro are now being translated to the clinic and more than ten clinical trials are currently ongoing worldwide. This review outlines the biological activities of curcumin and discusses its potential use in the prevention and treatment of human diseases.

Oxidative Stress in Normal-Weight Obese Syndrome

The normal‐weight obese (NWO) syndrome was identified in women whose body weight (BW) and BMI are normal but whose fat mass (FM) is >30%. In these subjects, an early inflammatory status has been demonstrated. The aim was to verify whether oxidative stress occurs in NWO. Sixty age‐matched white Italian women were studied and subdivided as follows: 20 normal‐weight individuals (NW) (BMI <25 kg/m2; FM% <30%); 20 NWO (BMI <25 kg/m2; FM% >30%); 20 preobese‐obese (OB) (BMI >25 kg/m2; FM% >30%). Anthropometric, body composition (by dual‐energy X‐ray absorptiometry) variables, plasma levels of some cytokines, reduced glutathione (GSH), lipid hydroperoxide (LOOH), nitric oxide (NO) metabolites (NO2−/NO3−), antioxidant nonproteic capacity (ANPC) were measured and compared between groups. Glucose and lipid metabolism parameters were assessed. GSH and NO2−/NO3− levels resulted lower in OB and NWO compared to NW (P < 0.01). LOOH levels resulted higher in OB and NWO (P < 0.01). ANPC in NWO was lower than NW but higher with respect to OB (P < 0.01). Correlation analysis revealed strong associations between GSH levels and BW, BMI, FM% (R = −0.45, at least P < 0.05); waist circumference (W) (R = −0.33, P < 0.05); FFM% (R = 0.45, P < 0.01); IL‐1α, IL‐6, IL‐10, IL‐15 (R = −0.39, −0.33, −0.36 −0.34, respectively, P < 0.05); triglycerides (R = −0.416, P < 0.05). LOOH levels were negatively related to FFM% (R = −0.413, P < 0.05) and positively to FM%, IL‐15, TNF‐α, insulin, total cholesterol, low‐density lipoprotein cholesterol, and triglycerides (R = 0.408, R = 0.502, R = 0.341, R = 0.412, R = 0.4036, R = 0.405, R = 0.405, respectively, P < 0.05). The study clearly indicates that NWO, besides being in early inflammatory status, are contextually exposed to an oxidative stress related to metabolic abnormalities occurring in obesity.

Prospective assessment of body weight and body composition changes in patients with psoriasis receiving anti-TNF-α treatment

Tumor necrosis factor (TNF)‐α is a pro‐inflammatory cytokine associated with psoriasis pathogenesis. Anti‐TNF‐α therapies are effective in psoriasis. A significant weight gain has been reported in patients treated with anti‐TNF‐α agents. The aim of the present study was to evaluate the body composition changes in psoriatic patients receiving anti‐TNF‐α therapies according with disease phenotype. Forty patients affected with psoriasis were followed up for 24 weeks and divided into two groups: psoriasis vulgaris (PsO) and psoriatic arthritis (PsA). Anthropometric, blood biochemical, body composition parameters, resting metabolic rate, and disease activity indexes were measured at baseline and at week 24. After 24 weeks of anti‐TNF‐α administration, the disease activity indexes and concentration of inflammatory markers were significantly decreased. Seventy‐five percent of PsO and 60% of PsA patients had an increase in body weight. Weight changes correlated with fat mass gain in the PsO group, and with fat and lean mass gain in the PsA group. In the present study, we demonstrated that a blockage of TNF‐α bioactivity is related with fat and lean mass gain in both PsO and PsA subjects. The anti‐TNF‐α therapies could play a key role in the cross talk between adipose tissue and skeletal muscle, mediated by the reduction of TNF‐α and interleukin‐6 production.

Brown Tumour in a Patient with Secondary Hyperparathyroidism Resistant to Medical Therapy: Case Report on Successful Treatment after Subtotal Parathyroidectomy

Brown tumour represents a serious complication of hyperparathyroidism. Differential diagnosis, based on histological examination, is only presumptive and clinical, radiological and laboratory data are necessary for definitive diagnosis. Here we describe a case of a brown tumour localised in the maxilla due to secondary hyperparathyroidism in a young women with chronic renal failure. Hemodialysis and pharmacological treatment were unsuccessful in controlling secondary hyperparathyroidism making it necessary to proceed with a subtotal parathyroidectomy. The proper timing of the parathyroidectomy and its favourable effect on regression of the brown tumor made it possible to avoid a potentially disfiguring surgical removal of the brown tumor.

Metabolic aspects of adult patients with nonalcoholic fatty liver disease

Nonalcoholic fatty liver disease (NAFLD) is a major cause of chronic liver disease and it encompasses a spectrum from simple steatosis to steatohepatitis, fibrosis, or cirrhosis. The mechanisms involved in the occurrence of NAFLD and its progression are probably due to a metabolic profile expressed within the context of a genetic predisposition and is associated with a higher energy intake. The metabolic syndrome (MS) is a cluster of metabolic alterations associated with an increased risk for the development of cardiovascular diseases and diabetes. NAFLD patients have more than one feature of the MS, and now they are considered the hepatic components of the MS. Several scientific advances in understanding the association between NAFLD and MS have identified insulin resistance (IR) as the key aspect in the pathophysiology of both diseases. In the multi parallel hits theory of NAFLD pathogenesis, IR was described to be central in the predisposition of hepatocytes to be susceptible to other multiple pathogenetic factors. The recent knowledge gained from these advances can be applied clinically in the prevention and management of NAFLD and its associated metabolic changes. The present review analyses the current literature and highlights the new evidence on the metabolic aspects in the adult patients with NAFLD.

Levofloxacin/amoxicillin-based schemes vs quadruple therapy for Helicobacter pylori eradication in second-line

Worldwide prevalence of Helicobacter pylori (H. pylori) infection is approximately 50%, with the highest being in developing countries. We compared cure rates and tolerability (SE) of second-line anti-H. pylori levofloxacin/amoxicillin (LA)-based triple regimens vs standard quadruple therapy (QT). An English language literature search was performed up to October 2010. A meta-analysis was performed including randomized clinical trials comparing 7- or 10-d LA with 7-d QT. In total, 10 articles and four abstracts were identified. Overall eradication rate in LA was 76.5% (95% CI: 64.4%-97.6%). When only 7-d regimens were included, cure rate was 70.6% (95% CI: 40.2%-99.1%), whereas for 10-d combinations, cure rate was significantly higher (88.7%; 95% CI: 56.1%-109.9%; P < 0.05). Main eradication rate for QT was 67.4% (95% CI: 49.7%-67.9%). The 7-d LA and QT showed comparable efficacy [odds ratio (OR): 1.09; 95% CI: 0.63-1.87], whereas the 10-d LA regimen was significantly more effective than QT (OR: 5.05; 95% CI: 2.74-9.31; P < 0.001; I(2) = 75%). No differences were reported in QT eradication rates among Asian and European studies, whereas LA regimens were more effective in European populations (78.3% vs 67.7%; P = 0.05). Incidence of SE was lower in LA therapy than QT (OR: 0.39; 95% CI: 0.18-0.85; P = 0.02). A higher rate of side effects was reported in Asian patients who received QT. Our findings support the use of 10-d LA as a simple second-line treatment for H. pylori eradication with an excellent eradication rate and tolerability. The optimal second-line alternative scheme might differ among countries depending on quinolone resistance.

Intake of Red Wine in Different Meals Modulates Oxidized LDL Level, Oxidative and Inflammatory Gene Expression in Healthy People: A Randomized Crossover Trial

Several studies have found that adherence to the Mediterranean Diet, including consumption of red wine, is associated with beneficial effects on oxidative and inflammatory conditions. We evaluate the outcome of consumption of a McDonalds Meal (McD) and a Mediterranean Meal (MM), with and without the additive effect of red wine, in order to ascertain whether the addition of the latter has a positive impact on oxidized (ox-) LDL and on expression of oxidative and inflammatory genes. A total of 24 subjects were analyzed for ox-LDL, CAT, GPX1, SOD2, SIRT2, and CCL5 gene expression levels, before and after consumption of the 4 different meal combinations with washout intervals between each meal. When red wine is associated with McD or MM, values of ox-LDL are lowered (P < 0.05) and expression of antioxidant genes is increased, while CCL5 expression is decreased (P < 0.05). SIRT2 expression after MM and fasting with red wine is significantly correlated with downregulation of CCL5 and upregulation of CAT (P < 0.001). GPX1 increased significantly in the comparison between baseline and all conditions with red wine. We highlighted for the first time the positive effect of red wine intake combined with different but widely consumed meal types on ox-LDL and gene expression. Trial Registration. This trial is registered with ClinicalTrials.gov NCT01890070.

Protective effect of cyanidin 3- O -β- d -glucoside on ochratoxin A-mediated damage in the rat

The aim of the present study was to verify whether the oral administration of cyanidin 3-O-beta-D-glucoside (C3G) might counteract damage induced by chronic exposure (28 d) to ochratoxin A (OTA) in rats and if its effect may be mediated by haeme oxygenase-1 (HO-1). Forty male Sprague-Dawley rats, individually caged, were divided into four groups of ten animals. A control group received a commercial diet, group C3G received the control diet supplemented with C3G (1 g/kg feed), group OTA received the control diet supplemented with 200 parts per billion of OTA, and group OTA+C3G received the OTA group diet supplemented with C3G (1 g/kg feed). After 4 weeks of treatment animals were killed and the liver, kidneys and brain of each rat were collected and homogenised to evaluate non-proteic thiol groups (RSH), lipid hydroperoxide (LOOH) levels, HO-1 expression and DNA fragmentation. Rats of the OTA group showed a significant (P < 0.001) decrease in RSH content of kidney and liver and a significant (P < 0.001) increase of LOOH in all the examined tissues compared with the control group. In the OTA+C3G group both RSH content and LOOH levels were similar to those observed in the control group, demonstrating that C3G was able to counteract the effects of OTA. A significant (P < 0.001) induction of HO-1 was evident in kidney and liver of both OTA and C3G groups. DNA damage occurred in all the examined tissues of the OTA group, whereas C3G was able to prevent it. The present study confirmed that the effects of OTA are mediated by oxidative stress and demonstrated that C3G efficiently counteracted deleterious effects of OTA because of its antioxidant and HO-1-inducing properties.

Changes in LDL Oxidative Status and Oxidative and Inflammatory Gene Expression after Red Wine Intake in Healthy People: A Randomized Trial

Postprandial oxidative stress is characterized by an increased susceptibility of the organism towards oxidative damage after consumption of a meal rich in lipids and/or carbohydrates. Micronutrients modulate immune system and exert a protective action by reducing low density lipoproteins (LDL) oxidation via induction of antioxidant enzymes. We evaluated the gene expression of oxidative stress (HOSp), inflammasome (HIp), and human drug metabolism pathways (HDM) and ox-LDL level at baseline and after the intake of red wine naturally enriched with resveratrol (NPVRW), in association with or without a McDonalds meal (McDM). The ox-LDL levels significantly increase comparing baseline (B) versus McDM and decreased comparing McDM versus McDM + NPVRW (P ≤ 0.05). Percentages of significant genes expressed after each nutritional intervention were the following: (1) B versus McDM, 2.88% HOSp, 2.40% of HIp, and 3.37% of HDMp; (2) B versus McDM + NPVRW, 1.44% of HOSp, 4.81% of HIp, and 0.96% of HDMp; (3) McDM versus McDM + NPVRW, 2.40% of HOSp, 2.40% of HIp, and 5.77% of HDMp; (4) B versus NPVRW, 4.80% HOSp, 3.85% HIp, and 3.85% HDMp. NPVRW intake reduced postprandial ox-LDL and the expression of inflammation and oxidative stress related genes. Chronic studies on larger population are necessary before definitive conclusions.

Cocoa Bioactive Compounds: Significance and Potential for the Maintenance of Skin Health

Cocoa has a rich history in human use. Skin is prone to the development of several diseases, and the mechanisms in the pathogenesis of aged skin are still poorly understood. However, a growing body of evidence from clinical and bench research has begun to provide scientific validation for the use of cocoa-derived phytochemicals as an effective approach for skin protection. Although the specific molecular and cellular mechanisms of the beneficial actions of cocoa phytochemicals remain to be elucidated, this review will provide an overview of the current literature emphasizing potential cytoprotective pathways modulated by cocoa and its polyphenolic components. Moreover, we will summarize in vivo studies showing that bioactive compounds of cocoa may have a positive impact on skin health.