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.     

RESOLUTION OF CUTANEOUS LEISHMANIASIS AFTER ACUTE ECZEMA DUE TO INTRALESIONAL MEGLUMINE ANTIMONIATE

We report a case of a 42 year-old female, who came to a leishmaniasis reference center in Rio de Janeiro, Brazil, presenting a cutaneous leishmaniasis lesion in the right forearm. Treatment with low-dose intramuscular meglumine antimoniate (MA) (5 mg Sb⁵⁺/kg/day) was initiated, with improvement after 28 days, although with the development of generalized eczema. After 87 days, the lesion worsened. Patient refused treatment with amphotericin B. MA was then infiltrated in the lesion, in two sessions, resulting in local eczema, with bullae formation; however, twenty days after, both the ulcer and eczema receded. Intralesional administration of MA should be used carefully when previous cutaneous hypersensitivity is detected.     

Vertebral Fracture Assessment in Acromegaly

Most vertebral fractures (VFs) are asymptomatic and incidentally found on X-rays. The effects of acromegaly on bone mineral density (BMD) are still controversial, and the prevalence of VFs in this specific population remains uncertain. The objective of this study was to assess VFs in acromegaly through vertebral fracture assessment (VFA) by dual-energy X-ray absorptiometry (DXA). Seventy-five acromegalic patients from the same center (53 female; age: 48.9 ± 14.5 yr) were enrolled in this study. None of them referred previous fragility fracture. They were divided according to the presence or absence of moderate or severe VFs on VFA, a densitometric spine imaging. Age, gender, estimated duration of disease, insulin-like growth factor I levels, disease control and gonadal status, as well as BMD and body composition (analyzed by DXA) were compared between these 2 groups. A prevalence of 10.6% of clinically unapparent VFs was observed. Eight patients had 13 moderate or severe VFs, and only one of them had osteoporosis at densitometry. There was a trend to longer duration of acromegaly before diagnosis, higher prevalence of hypogonadism, and higher BMD Z-score at lumbar spine and femoral neck in fractured patients, without reaching statistical significance. There is a significant prevalence of moderate and severe VFs in acromegalic patients, independently of BMD. More longitudinal and controlled studies are needed to recommend the use of VFA in all acromegalic patients submitted to DXA scan. VFA is simple, practical, uses low radiation, and may provide important information in the management of acromegaly.     

Unsafe Drug Use and Arrhythmic Events in Brugada Patients with ICD: Results of a Long-Term Follow-Up

Purpose

Brugada syndrome is a hereditary disease linked with an increased risk of sudden death that may require an implantable cardioverter-defibrillator (ICD) in order to halt the arrhythmic events. The aim of this study was to identify possible triggers for appropriate ICD therapies in patients with Brugada syndrome, focusing on their past and current therapeutic profiles.

Methods

Thirty patients with high-risk Brugada syndrome, with ICD implanted at the Coimbra Hospital and University Center, were enrolled. Patients were questioned about their Brugada syndrome history, previous cardiac events, comorbidities, present and past medications, and physical activity. Patients were followed up during 5.8?±?5.3 years. The ICD was interrogated, and arrhythmic events and device therapies were recorded. The cohort who received appropriate ICD therapies was compared with the remaining patients to determine the potential link between clinical variables and potentially fatal arrhythmic events.

Results

More than half of the patients (53.3%) took at least one non-recommended drug, and 16.7% received appropriate ICD therapies, with a long-term rate of 4.0%/year. There was a tendency for more appropriate ICD therapies in patients who took unsafe drugs (85.7 versus 45.5%, p?=?0.062), and the mean time between unsafe drug intake and appropriate ICD therapies was 3.8?±?7.5 days.

Conclusions

This study revealed that the medical community is still unaware of the pharmacological restrictions imposed by Brugada syndrome. Patients who took non-recommended drugs seem to have a higher risk of ventricular arrhythmic events.

     

Predicting retinal pigment epithelium remodelling and its functional impact

Graefe's Archive for Clinical and Experimental Ophthalmology - To identify predictive factors for RPE tear remodelling and its correlation with functional and morphological outcomes....     

MyD88 is essential for alveolar bone loss induced by Aggregatibacter actinomycetemcomitans lipopolysaccharide in mice

Aggregatibacter actinomycetemcomitans is a Gram‐negative bacteria highly associated with localized aggressive periodontitis. The recognition of microbial factors, such as lipopolysaccharide from A. actinomycetemcomitans (_AaLPS), in the oral environment is made mainly by surface receptors known as Toll‐like receptors (TLR). TLR4 is the major LPS receptor. This interaction leads to the production of inflammatory cytokines by myeloid differentiation primary‐response protein 88 (MyD88) ‐dependent and ‐independent pathways, which may involve the adaptor Toll/interleukin‐1 receptor‐domain‐containing adaptor inducing interferon‐β (TRIF). The aim of this study was to assess the involvement of MyD88 in alveolar bone loss induced by _AaLPS in mice. C57BL6/J wild‐type (WT) mice, MyD88, TRIF or TRIF/MyD88 knockout mice received 10 injections of _AaLPS strain FDC Y4 (5 μg in 3 μl), in the palatal gingival tissue of the right first molar, every 48 h. Phosphate‐buffered saline was injected in the opposite side and used as control. Animals were sacrificed 24 h after the 10th injection and the maxillae were removed for macroscopic and biochemical analyses. The injections of _AaLPS induced significant alveolar bone loss in WT mice. In the absence of MyD88 or TRIF/MyD88 no bone loss induced by _AaLPS was observed. In contrast, responses in TRIF^?/? mice were similar to those in WT mice. Diminished bone loss in the absence of MyD88 was associated with fewer TRAP‐positive cells and increased expression of osteoblast markers, RUNX2 and osteopontin. There was also reduced tumor necrosis factor‐α production in MyD88^?/? mice. There was less osteoclast differentiation of hematopoietic bone marrow cells from MyD88^?/? mice after _AaLPS stimulation. Hence, the signaling through MyD88 is pivotal for _AaLPS‐induced osteoclast formation and alveolar bone loss.     

Customized Root-Analogue Implants: A Review on Outcomes from Clinical Trials and Case Reports

(1) It is estimated that 10% of the world’s population will need a dental implant in their lifetime. Despite all the advances in the comprehension of dental implant designs, materials and techniques, traditional implants still have many limitations. Customized root-analogue implants are, therefore, gaining increased interest in dental rehabilitation and are expected to not only preserve more hard and soft tissues but also avoid a second surgery and improve patient overall satisfaction. In this sense, the aim of this review was to collect and analyse the clinical trials and case reports on customized root-analogue implants available in the literature; (2) This review was carried out according to the PRISMA Statement. An electronic database search was performed using five databases: PubMed, Google Scholar, Medline, Science Direct, and Scopus. The following keywords were used for gathering data: custom-made, dental implants, root-analogue, anatomical, customized and tooth-like; (3) 15 articles meeting the inclusion criteria—articles reporting clinical trials, case reports or animal studies and articles with root-analogue implants and articles with totally customized implant geometries—were selected for the qualitative synthesis. The design and manufacturing techniques, implant material and surface treatments were assessed and discussed; (4) The performance of some root-analogue implants with specific features (i.e., macro-retentions) was successful, with no signs of infection, periodontitis nor bleeding during the follow-up periods.