Mechanism of the endothelium-dependent vasodilator effect of an alcohol-free extract obtained from a vinifera grape skin.

An alcohol-free grape-skin extract (GSE) obtained from skins of Vitis labrusca has significant anti-hypertensive, antioxidant and vasodilator effects. According to our previous results, the vasodilator effect of GSE in the isolated mesenteric vascular bed (MVB) of the rat is dependent on endothelium and partially dependent on nitric oxide (NO). In the MVB of the rat pre-contracted with norepinephrine (NE), bolus injections of GSE induced a long-lasting dose-dependent vasodilation that is significantly reduced after the treatment with 1H-[1,2,3] oxadiazolo [4,4-a] quinoxalin-1-one (ODQ). Additionally, in vessels pre-contracted with norepinephrine and depolarized with KCl (25 mM) or treated with Ca(2+)-dependent K(+)-channel blockers charybdotoxin (ChTx) plus apamin, the vasodilator effect of GSE was significantly reduced and almost abolished by ChTx plus apamin plus L-NAME. However, the vasodilator effect of GSE was unaffected by D-Arg[Hyp(3),Thi(5),D-Tic(7),Oic(8)]bradykinin (HOE-140), atropine, yohimbine, pyrilamine and 4-aminopyridine (4-AP). The vasoconstriction response elicited by bolus injection of KCl was not affected by GSE, whereas the vasoconstrictor response induced by NE was dose-dependently and completed inhibited by GSE in the presence but not in the absence of endothelium. However, NE-induced vasoconstriction in calcium-free condition or without endothelium was not reduced by GSE. The present results demonstrate that GSE induces a vasodilator effect in the rat MVB, which is dependent on NO in combination with endothelium-derived hyperpolarizing factor (EDHF). Additionally, our results indicated that extracellular Ca(2+) has an important role on the endothelium-dependent vasodilator effect induced by GSE.     

Clinical and biological aspects of sentinel node biopsy in malignant melanoma — an update

The diagnostic usefulness of sentinel lymph node biopsy (SLNB) has been well established, but its therapeutic value remains unproven. First introduced by Morton and colleagues, the SLNB procedure is now widely available, and markedly enhances our ability to pathologically stage the regional nodes. Although the SLN status is acknowledged as the most powerful indicator of prognosis in melanoma, there is no evidence to-date, of survival advantage for complete lymphadenectomy in SLN-positive patients. Also, there is no effective adjuvant therapy that could benefit these sentinel node-positive patients, as yet. Additionally, new data have emerged indicating a possible increase in local/in-transit recurrence following complete lymphadenectomy in sentinel node-positive patients. To understand fully and to evaluate these observations we need information from randomized controlled trials. Major changes have occurred following the latest revision of melanoma staging system (AJCC, 6th edition). Concerning N category, these include the incorporation of the number of metastatic lymph nodes, the tumour burden of nodal metastases, and the ulceration of the primary tumour. The data obtained from the new staging system will reflect differences in prognosis that were not previously emphasized and which, we hope, will serve as a guide to more accurate analysis of metastatic pathways in cutaneous melanoma as well as a rationale for new forms of treatment.     

Assessment of drug addiction. The experience of the Medico Legal Institute of Oporto

Since 1993 in Portugal, it is possible, by legal enforcement, to request forensic examination to study possible conditions of drug addiction. On the basis of examinations carried out in the Medico Legal Institute of Oporto, we present a study of 494 cases involving the relation to the demographic data of the examined individuals, their family background, legal situation, age at which drug consumption began, consumption profile at the beginning and at time of forensic examination and our conclusions.     

Recirculant hyperthermic IntraVEsical chemotherapy (HIVEC) in intermediate–high-risk non-muscle-invasive bladder cancer

Abstract

Purpose To examine the effectiveness of hyperthermic intravesical chemotherapy (HIVEC?) with mitomycin-C (MMC) for patients with intermediate–high-risk non-muscle invasive bladder cancer (NMIBC). Materials and methods From November 2010 to April 2015, 40 patients with intermediate–high-risk NMIBC received HIVEC? treatment with a Combat BRS system. Of these patients, 24 received neoadjuvant HIVEC? treatment (eight weekly instillations) before a transurethral resection of the bladder (TURBT) and 16 received adjuvant HIVEC? treatment post-TURBT (four instillations weekly?+?six monthly). The pathological response of each tumour was evaluated after the neoadjuvant treatment. Recurrence rates and adverse effects were evaluated in both groups. Results A total of 40 patients completed the induction therapy: 24 patients received the Neoadjuvant HIVEC? treatment. Of these patients, 15 (62.5%) showed a complete response. Eight patients (33.3%) showed a partial response, and one patient (4.1%) showed no response at all. The 4-year cumulative incidence of recurrence was 20.8%. The adjuvant HIVEC? treatment was given to 16 patients. The 2-year cumulative incidence of recurrence was 12.5% for this group. The incidence and severity of side effects were slightly lower in the adjuvant group than in the neoadjuvant group. However, the difference was not statistically significant (p?<?0.3). Most of the side effects were low grade and had virtually no effect on the treatment plan, and 97% of patients completed all of the HIVEC? instillations scheduled. Conclusions The recirculation of hyperthermic MMC using Combat’s HIVEC? treatment is safe and effective and is capable of achieving good success rates in both neoadjuvant and adjuvant settings. This treatment seems to be appropriate for NMIBC intermediate–high-risk patients who cannot tolerate or have contraindications for standard BCG therapy or in cases in which there are supply issues or shortages of BCG.     

Excessive Dental Bleaching with 22% Carbamide Peroxide Combined with Erosive and Abrasive Challenges: New Insights into the Morphology and Surface Properties of Enamel

This study aimed to evaluate the effects of 22% carbamide peroxide combined with an erosive challenge and simulated brushing on enamel. Bovine incisor teeth were divided into G1, tooth bleaching; G2, tooth bleaching + erosive challenge; and G3, tooth bleaching + erosive challenge + simulated brushing, and evaluated at T0, before any intervention; T1, 14 days after the proposed treatments; and T2, 28 days after the proposed treatments. Tooth bleaching was performed daily for 1 h for 28 days. The microhardness, surface roughness, mass variation, and ultrastructure were analyzed at T0, T1, and T2. Two-way analysis of variance for repeated measures was performed and Tukey’s post hoc test (α = 5%) was used. The surface roughness increased in groups G2 and G3 as a function of time, whereas microhardness and mass measurements demonstrated a significant reduction for groups associated with challenges. Ultrastructural evaluation indicated a loss of the aprismatic layer and exposure of the enamel prisms in all groups after 14 days of bleaching, with more pronounced results in G2 and G3 after 28 days. In conclusion, abrasive and erosive challenges potentiated the deleterious effects of tooth whitening on microhardness, ultramorphology, and mass, without affecting the roughness of dental enamel.     

Evolution of infant feeding practices in children from 9 to 24 months,considering complementary feeding indicators and food processing: Results from the Brazilian cohort of the MAL‐ED study

Infant feeding practices impact children''s nutritional and health status, influencing growth and development. This study aimed to analyse the evolution of infant feeding practices from 9 to 24 months of age, considering infant and young child feeding (IYCF) indicators and food processing. The infant feeding practices in children from the Brazilian site of the MAL‐ED study were evaluated at 9 (n = 193), 15 (n = 182) and 24 months (n = 164) using 24‐h dietary recalls. IYCF indicators were evaluated, and the extent of food processing was evaluated, using the NOVA classification. Breastfeeding declined significantly over time, from 77.6% at 9 months to 45.1% at 24 months. Although dietary diversity did not significantly change during the study period (80.5% at 24 months), the minimum acceptable diet significantly increased from 67.9% to 76.1% at 24 months (p < 0.0005). All the studied children consumed sweetened beverages from 9 months. Unhealthy food consumption and zero vegetable or fruit consumption significantly increased over time (p < 0.0005). Unprocessed food consumption decreased from 9 to 24 months of age (p < 0.0005), while ultra‐processed food consumption increased (p < 0.0005) during the study period. Logistic regressions showed that, at 9 months, breastfed children presented a lower risk for ultra‐processed food consumption (odds ratio [OR] = 0.31; 95% confidence interval [CI] = 0.13–0.77); and children reaching the minimum acceptable diet presented more risk for ultra‐processed food consumption (OR = 2.31; 95% CI = 1.01–5.27). In conclusion, data showed a reduction in the quality of infant feeding practices over the first 2 years of life, with a decrease in breastfeeding and an increase in the consumption of unhealthy and ultra‐processed foods.