Gold nanoparticles phytoreduced with Cornus mas extract mitigate some of gliadin effects on Caco-2 cells.

Celiac disease (CD) is an autoimmune condition that occurs in genetically predisposed people where the ingestion of gluten produces damage in the small intestine. The treatment accepted until now is a strict gluten free diet. This implies the need for novel or adjuvant treatments, in addition to the standard of care. The present study aimed to assess the effect of gold nanoparticles phytosynthesized with Cornus mas extract (AuCM) compared to Cornus mas extract (CM) and luteolin (LT) on Caco-2 cells, exposed or not to gliadin. Ultraviolet-visible spectroscopy and transmission electron microscopy were used for the characterization of AuCM. Measured cellular outcomes included oxidative stress markers (malondialdehyde level, catalase and superoxide dismutase activities), inflammatory response and cellular signaling and transcription factors involved in apoptosis (NFκB, pNFκB, NOS2, TNF-α, TRAIL, Bax, Bcl-2, p53). The internalization of gold nanoparticles in cells was evidenced by transmission electron microscopy (TEM). The gliadin administration induced oxidative stress, improved the activity of antioxidants enzymes, increased NOS2 and NFκB expressions and reduced pNFκB/NFκB ratio. In addition, gliadin enhanced TRAIL and Bcl-2 levels and reduced p53 expression in Caco-2 cells. The pretreatment with AuCM, CM extract and LT diminished oxidative stress and reduced NOS2 activity. AuCM and CM treatment amplified the expression of p53 and pNFκB/NFκB ratio and diminished Bcl-2, NFκB and pNFκB, especially AuCM. The results obtained confirmed that AuCM mitigate some of gliadin effects on Caco-2 cells through modulation of oxidative stress and inflammation.

Cardiac Changes in Overweight and Obese Patients.

BACKGROUND: Obesity and overweight are two pathologies that are more and more frequent in the XXIst century diagnosis and are causing high morbidity and mortality rates in the general population, especially through cardiovascular complications. AIMS: Identification and early diagnosis of cardiac changes in overweight and obese patients. MATERIAL AND METHOD: We carried out a sectional, analytical and observational study on 111 subjects: 27 normal weight subjects and 84 overweight and obese patients, which were submitted to a clinical exam, biochemical exams and 2D ultrasound. RESULTS: The presence of diastolic dysfunction is twice more frequent in overweight patients in comparison to normal weight ones (30% vs 15%) and 5 times more frequent in obese patients than normal weight ones (75% vs 15%). The size increase of the interventricular septum is correlated with the body mass index, there being statistically significant differences between normal weight vs overweight vs obese patients, as well as between overweight and obese ones. Within the whole group and within the groups, both the left ventricle mass (g) as well as the left ventricle mass to body surface ratio (g/m²) are statistically significantly higher in patients with present diastolic dysfunction (E/A < 1). This indicates a relation between the presence of diastolic dysfunction, increased left ventricle mass and body mass index (p < 0.05). CONCLUSIONS: Overweight and obese patients, unlike normal weight ones, present early cardiac changes, such as: a decrease of left ventricle ejection fraction, diastolic dysfunction, thickening of the interventricular septum, increase of the left ventricle mass both per se as well as in ratio to body surface.

Two different types of diabetes mellitus in pancreatic cancer population. Comparative study between new onset and long standing diabetes mellitus on 76 patients with pancreatic cancer.

BACKGROUND: There are some studies which have reported a higher diagnosis probability for PC if the DM occurred within the past 2-3 years. Information on the clinical profile of pancreatic cancer (PC) associated with diabetes mellitus (DM) is limited. The aim of the study was to compare clinic-morphological features in patients with new onset DM and PC and long lasting DM and PC, in order to detect new factors or markers which can help in early diagnosis of PC. METHODS: This study included 76 patients with pancreatic cancer admitted between 2000-2009 in the 4th Medical Clinic Cluj-Napoca; in group A 56 patients with PC and new onset of DM (< 24 months duration) were included and in group B 20 patients with PC and long standing diabetes (> 60 months duration) were included. We compared the demographic, clinical, biochemical and morphological characteristics of new onset or long lasting DM and pancreatic cancer. RESULTS: New onset DM was more prevalent (74% vs. 26%, p < .05) than long lasting DM among patients with PC. The patients with long lasting DM had a greater frequency of urban environment (100% vs. 55.6% p = .02), a higher body mass index (BMI)(32.1 SD 8.4 vs. 29.9 SD 6.7 kg/m2, p = .05), higher fasting blood glucose levels (182 mg/dL vs. 134 mg/dL, p = .008) and urinary ketone bodies (60% vs. 10.7%, p = .002) compared with those with new-onset DM and PC. There was no statistical difference regarding gender, median age, blood group, location and staging of tumours, long and hard alcohol and cigarettes consumption, between group A and B. CONCLUSIONS: New onset DM was more significantly frequent than long lasting DM in patients with PC. New onset diabetes DM associated with PC is frequent, mild and non-decompensated. In patients with PC and long lasting DM, the metabolic status and diabetes are imbalanced.

Endothelial dysfunction in metabolic syndrome.

Metabolic syndrome (MS) or insulin resistance syndrome is the result of multiple metabolic abnormalities associated with cardiovascular disease. Since 1988, when Reaven first described MS, many researches have been conducted in order to understand its pathophysiology, epidemiology, prognostic implications and therapeutic strategies. Numerous metabolic abnormalities found in the metabolic syndrome, including hyperglycemia, excessive fatty acids and insulin resistance, cause an endothelial cell dysfunction by affecting nitric oxide synthesis or degradation. Although the exact mechanism by which metabolic syndrome induces endothelial dysfunction remains to be clarified, there are many possibilities of vascular endothelial damage and increase in cardiovascular risk in these patients. The most frequent metabolic, hormonal, hemostatic abnormalities in patients with metabolic syndrome that may contribute to endothelial dysfunction are: hyperinsulinemia, hyperglycemia, increase in fatty acid levels, hypertriglyceridemia, decrease in HDL-cholesterol, increase in small dense LDL-cholesterol, increase in apolipoprotein B, increase in insulin-1 growth factor levels, increase in tissue angiotensin II levels, increase in plasminogen activator inhibitor-1, increase in C reactive protein, increase in oxidative stress.

Serological and histological correlations in celiac disease.

UNLABELLED: The aim of this study was to compare the sensitivity of the serological markers in patients with non-treated celiac disease by determination of antiendomysium and anti-tissue-transglutaminase autoantibodies separately and together. At the same time we examined the correlation between the serum levels of the two antibodies and the severity of the histological lesions. MATERIAL AND METHODS: The research included 26 persons (19 females, 7 males, age range 18-56 years) in whom the small bowel biopsy confirmed the villous atrophy. The sera of these patients were investigated by the determination of antiendomysium antibodies (AEA) and antitissue-transglutaminase antibodies (ATTG). For the morphological disorders we used the Marsh modified criteria. ATTG were determined by a sandwich-ELISA technique and AEA were dosed by indirect immunofluorescence technique. RESULTS: 6 patients presented with partial villous atrophy (PVA), 7 with subtotal villous atrophy (SVA) and 13 with total villous atrophy (TVA). 23 persons were seropositive, having at least one of the two antibodies tested. The sensitivity of the serological investigation increased at 88% using both AEA and ATTG determinations. In patients with TVA, the sensitivity of ATTG was 100% and of AEA was 92%. In patients with SVA and PVA, the sensitivity of these antibodies was lower. Among the patients with SVA, 43% were negative for AEA and 50% for ATTG. The determination of AEA and ATTG together reduced the seronegativity at 15% in patients with SVA and at 34% in patients with PVA. CONCLUSIONS: Antitissue-transglutaminase antibodies testing in patients with non-treated celiac disease is more sensitive than antiendomysium antibodies. The efficiency of the serological diagnosis improves when both AEA and ATTG are determined. Serum antibodies levels correlated very well with the severe histological alterations (TVA), but the correlation is not so good with SVA and PVA. So, we can tell that high levels of AEA and/or ATTG are suggestive for severe histological disorders in celiac disease.

The oxidative stress in the development of diabetes chronic complications in the elderly.

The diabetes mellitus occurs as an important disease at elderly people, to whom the micro- and macrovascular complications represent a major cause of morbidity and mortality. Experimental researches of the last years proved that the oxidative stress may be the common mechanisms that intervenes in the occurrence of the diabetes complications as well as in the aging process and is responsible for the increased prevalence of chronic complications at elderly diabetics. Starting from this information, we performed a comparative study where we followed the intensity of the oxidative stress at elderly diabetics as compared to adult diabetics and non-diabetic elderly people. At the same time, we have followed the involvement of oxidative stress in the occurrence of diabetic microangiopathy and atherosclerosis. 155 patients from the 4th Medical Clinic were studied during 2000-2003. These patients were divided into three lots: lot 1: elderly diabetics, lot 2: adult diabetics, lot 3: elderly non-diabetics. At these patients we have followed comparatively the intensity of the oxidant status by determining the plasma malondialdehyde (MDA) and the anti-oxidant status by determining the plasma ceruloplasmin, as well as the correlations of these two parameters with the chronic complications of diabetes. At elderly diabetics there is an increased oxidative stress underlined by an increased plasma level of MDA and ceruloplasmin as compared to the adult diabetics and non-diabetic elderly people and this increased oxidative stress is involved in the development of the chronic complications at this patients. In case of elderly diabetics, the age and the illness may induce the formation of oxygen-derived free radicals with synergic effect in injuring tissues and organs.

Rheological changes in diabetic microangiopathy.

OBJECTIVES: Evaluation of rheological changes in patients with diabetes mellitus. MATERIAL AND METHOD: Determination of plasma viscosity, erythrocyte deformability, erythrocyte adhesion, fibrinogen and hematocrit in a group of 56 patients with diabetes mellitus, of which 28 with diabetic microangiopathy. The group includes 20 patients with type 1 diabetes mellitus and 36 patients with type 2 diabetes mellitus. RESULTS: In patients with diabetes mellitus with microangiopathy, more important rheological changes are noted than in diabetes mellitus without microangiopathy; thrombocyte adhesion is increased in 25 patients with microangiopathy compared to those without microangiopathy (7), erythrocyte deformability is decreased in 23 patients with microangiopathy and only in 9 patients without microangiopathy, and increased plasma viscosity is found in 26 patients with microangiopathy compared to those without microangiopathy (3). CONCLUSIONS: In the study performed, a direct correlation is found between the decrease of erythrocyte deformability and the severity of diabetic microangiopathy; the decrease is more severe in patients with proliferative retinopathy or clinically manifest nephropathy. The increase of platelet adhesion in patients with diabetic microangiopathy suggests the hypothesis of the role of thrombocyte changes in the pathogenesis of microangiopathic complications of diabetes mellitus. Plasma viscosity contributes to the pathogenesis of diabetic nephropathy and diabetic polyneuropathy, its increase being noted in diabetic patients with microalbuminuria and peripheral neurological involvement.