This study indicates that: (i) asymptomatic and symptomatic GS patients have a benign natural history; (ii) the majority of GS patients with severe or mild symptoms will no longer experience biliary pain; and (iii) a significant proportion of cholecystectomies are performed in asymptomatic patients. Expectant management still represents a valid therapeutic approach in the majority of patients.

The present study was designed to evaluate the clinical outcome of cell-based therapy with cultured adiposederived stromal cells (ASCs) for the treatment of cutaneous manifestations in patients affected by systemic sclerosis (SSc). ASCs have an extraordinary developmental plasticity, including the ability to undergo multilineage differentiation and self-renewal. Moreover, ASCs can be easily harvested from small volumes of liposuction aspirate, showing great in vitro viability and proliferation rate. Here we isolated, characterized, and expanded ASCs, assessing both their mesenchymal origin and their capability to differentiate towards the adipogenic, osteogenic, and chondrogenic lineage. We developed an effective method for ASCs transplantation into sclerodermic patients by means of a hyaluronic acid (HA) solution, which allowed us to achieve precise structural modifications. ASCs were isolated from subcutaneous adipose tissue of six sclerodermic patients and cultured in a chemical-defined medium before autologous transplantation to restore skin sequelae. The results indicated that transplantation of a combination of ASCs in HA solution determined a significant improvement in tightening of the skin without complications such as anechoic areas, fat necrosis, or infections, thus suggesting that ASCs are a potentially valuable source of cells for skin therapy in rare diseases such as SSc and generally in skin disorders.

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Cultured rat hepatocytes and human hepatoma HepG2 cells were used to evaluate the hepatoprotective properties of polyphenolic extracts from the edible part of artichoke (AE). The hepatocytes were exposed to H2O2generated in situ by glucose oxidase and were treated with either AE, or pure chlorogenic acid (ChA) or with the well known antioxidant, N, N'-diphenyl-p-phenilenediamine (DPPD). Addition of glucose oxidase to the culture medium caused depletion of intracellular glutathione (GSH) content, accumulation of malondialdehyde (MDA) in the cultures, as a lipid peroxidation indicator, and cell death. These results demonstrated that AE protected cells from the oxidative stress caused by glucose oxidase, comparable to DPPD. Furthermore, AE, as well as ChA, prevented the loss of total GSH and the accumulation of MDA. Treatment of HepG2 cells for 24 h with AE reduced cell viability in a dose-dependent manner, however, ChA had no prominent effects on the cell death rate. Similarly, AE rather than ChA induced apoptosis, measured by flow cytometric analysis of annexin and by activation of caspase-3, in HepG2 cells. Our findings indicate that AE had a marked antioxidative potential that protects hepatocytes from an oxidative stress. Furthermore, AE reduced cell viability and had an apoptotic activity on a human liver cancer cell line.

Hyperglycemia has been causally linked to vascular and glomerular dysfunction by a variety of biochemical mechanisms, including a glucose-dependent abnormality in nitric oxide (NO) production and action. NO is a candidate for mediating hyperfiltration and the increased vascular permeability induced by diabetes. Serum nitrite and nitrate (NO 2 -+ NO 3 -) concentrations were assessed as an index of NO production in 30 adolescents and young adults with type 1 diabetes, 15 with and 15 without microalbuminuria (albumin excretion rate [AER] between 20 and 200 µg/min), compared with a well-balanced group of healthy control subjects. In all subjects, glomerular filtration rate (GFR) was determined by radionuclide imaging. Our study showed that NO 2 -+ NO 3 -serum content and GFR values were significantly higher in microalbuminuric diabetic patients than in the other 2 groups. GFR was significantly and positively related to AER levels (r 2 = 0.75, P < 0.0001), whereas NO 2 -+ NO 3 -serum content was independently associated with both AER and GFR values (␤ = 2.086, P = 0.05, ␤ = 1.273, P = 0.0085, respectively), suggesting a strong link between circulating NO, glomerular hyperfiltration, and microalbuminuria in young type 1 diabetic patients with early nephropathy. Interestingly, mean HbA 1c serum concentration was significantly higher in microalbuminuric than in normoalbuminuric diabetic subjects (P < 0.05) and was independently associated with AER values, suggesting a role for chronic hyperglycemia in the genesis of diabetic nephropathy. Moreover, HbA 1c serum concentration was significantly and positively related to NO 2 + NO 3 serum content (r 2 = 0.45, P = 0.0063) and GFR values (r 2 = 0.57, P = 0.0011), suggesting that chronic hyperglycemia may act through a mechanism that involves increased NO generation and/or action. In conclusion, we suggest that in young type 1 diabetic patients with early nephropathy, chronic hyperglycemia is associated with an increased NO biosynthesis and action that contributes to generating glomerular hyperfiltration and persistent microalbuminuria. Diabetes 49:1258-1263, 2000 E arly diabetic nephropathy in children and adolescents is caused predominantly by microangiopathy, representing functional and structural abnormalities in the microvascular system leading to microalbuminuria (1-3). Microvascular disease carries a substantive morbidity in young patients with type 1 diabetes (3,4). Long duration of diabetes and poor glycemic control have been shown to be the most important risk factors for the development of microvascular disease in these patients (5). A considerable body of evidence in humans indicates that microalbuminuria is strictly associated with a generalized endothelial vascular dysfunction (2,6). In this regard, a glucosedependent abnormality in nitric oxide (NO) production and action has become an attractive hypothesis for the pathogenesis of early diabetic nephropathy (7-11). In fact, vasodilation due to increased NO generation or action has recently been implicated in the ...

The current growing interest for natural antioxidants has led to a renewed scientific attention for artichoke, due not only to its nutritional value, but, overall, to its polyphenolic content, showing strong antioxidant properties. The major constituents of artichoke extracts are hydroxycinnamic acids such as chlorogenic acid, dicaffeoylquinic acids caffeic acid and ferulic acid, and flavonoids such as luteolin and apigenin glycosides. In vitro studies, using cultured rat hepatocytes, have shown its hepatoprotective functions and in vivo studies have shown the inhibition of cholesterol biosynthesis in human subjects. Several studies have shown the effect on animal models of artichoke extracts, while information on human bioavailability and metabolism of hydroxycinnamates derivatives is still lacking. Results showed a plasma maximum concentration of 6·4 (SD 1.8) ng/ml for chlorogenic acid after 1 h and its disappearance within 2 h (P, 0·05). Peak plasma concentrations of 19·5 (SD6·9) ng/ml for total caffeic acid were reached within 1 h, while ferulic acid plasma concentrations showed a biphasic profile with 6·4 (SD1·5) ng/ml and 8·4 (SD4·6) ng/ml within 1 h and after 8 h respectively. We observed a significant increase of dihydrocaffeic acid and dihydroferulic acid total levels after 8 h (P,0·05). No circulating plasma levels of luteolin and apigenin were present. Our study confirms the bioavailability of metabolites of hydroxycinnamic acids after ingestion of cooked edible Cynara scolymus L. (cultivar Violetto di Provenza).

The aim of this study was to describe the prevalence and distribution, by gender, of occlusal traits in a sample of Italian students aged 11-14 years (mean 13 +/- 1 years). Using standardized and validated recording criteria, a single operator measured the overjet, overbite, open bite, anterior and posterior crossbites, crowding, coincidence of the upper and lower midlines, and diastema, in 810 secondary school students (53.6 per cent males). Chi-square, t-test statistics, and odds ratios (ORs) with 95 per cent confidence intervals (CI) were used to investigate the relationship between gender and malocclusion characteristic. Logistic regression was used to further analyse the independent association between gender and each outcome measure. Ninety-three per cent of the subjects showed at least one occlusal trait, with one or two anomalies recorded in 63 per cent of children. The prevalence of occlusal traits ranged from 1.1 (negative overjet) to 54 per cent (upper and lower midlines not coincident). Males were more likely than females to show both an increased overbite and an increased overjet, although the latter result was not confirmed by logistic regression (P = 0.05). Multivariate analysis showed a negative association between overbite and misalignment of the lower incisors and lack of coincidence of the upper and lower midlines, whereas subjects with an increased overbite were more likely to have an increased overjet (all P < 0.01). Further studies are required in order to further clarify these findings and to provide accurate estimates of the orthodontic treatment need in Italian adolescents.

Background: In Italy, the loss of confidence towards vaccination resulted in low vaccine coverage, also among healthcare workers (HCWs). Indeed, low vaccination coverage among HCWs can lead to dangerous outbreaks of disease, reduce productivity, and increase absenteeism. The aim of this study was to investigate the vaccine coverage and attitudes toward vaccination among HCWs. Methods: A multicenter cross-sectional study was conducted among HCWs referred to all hospitals of the Local Health Authority 02 of Abruzzo Region, Italy. The survey was based on the questionnaire proposed by the H-ProImmune Project. Results: A total of 347 HCWs were enrolled in the study. Of these, 57.3% reported missing diphtheritis-tetanus-pertussis (DTP) vaccination, 50.1% reported missing measles-mumps-rubella (MMR) vaccination, and 62.5% reported missing flu vaccination. Regarding attitudes, other healthcare professionals reported to believe more in natural immunization compared to vaccination (26.5%; p < 0.001), and they were worried about long-term effects of vaccination (10.2%; p = 0.044). Conclusions: This survey showed all vaccination coverage considered resulted below the 95% threshold. Training on vaccination and mandatory measures may be needed in order to achieve better coverage.