Effect of new thiazolidine derivatives LPSF/GQ-02 and LPSF/GQ-16 on atherosclerotic lesions in LDL receptor-deficient mice (LDLR−/−)

BackgroundAtherosclerotic cardiovascular disease is a chronic inflammatory condition. Thiazolidinediones (TZDs) are used to enhance sensitivity to insulin and have demonstrated a protective effect over a variety of cardiovascular markers and risk factors. Controversially, the TZDs are associated with the development of heart failure. Thus, lines of research have invested in the search for new molecules in order to obtain more selective and less harmful treatment alternatives for the pathogenesis of atherosclerosis and its risk factors.MethodsAnimals were fed a diet rich in fat for 10 weeks. In the last 2 weeks, animals received either pioglitazone, LPSF/GQ-02, or LPSF/GQ-16 daily through gavage. At the end of the treatment, blood was collected for biochemical analysis and the aortas were dissected for subsequent analyses.ResultsNo changes in the blood lipid profile were found following the use of the drugs in comparison to the control. However, the new thiazolidine derivatives were more efficient in improving insulin resistance in comparison to pioglitazone and the control group. Morphometric analyses revealed that neither pioglitazone nor LPSF/GQ16 led to satisfactory effects over atherosclerosis. However, LPSF/GQ-02 led to a reduction in area of the atherosclerotic lesions. Ultrastructural analyses revealed extensive degeneration of the endothelium and an increase in apoptotic cells in the subendothelial space following the use of pioglitazone and LPSF/GQ-16. However, LPSF/GQ-02 caused minimal cell alterations in the aortic endothelium. Regarding markers, endothelial nitric oxide synthase (eNOS) and matrix metalloproteinase 9 (MMP-9), LPSF/GQ-16, and pioglitazone exerted similar effects, increasing the expression of MMP-9, and had no effect on the expression of eNOS compared with the control group. On the other hand, LPSF/GQ-02 was effective in reducing the expression of MMP-9 and increased eNOS significantly.ConclusionsThe results suggest that the new thiazolidine derivative LPSF/GQ-02 is a promising candidate for the treatment of atherosclerosis.     

Effect of green tea-loaded chitosan nanoparticles on leathery dentin microhardness

The purpose of this study was to assess the effect of a chitosan-based nanoformulation containing green tea on leathery (remaining) dentin subsurface microhardness. Size distribution, polydispersity index (PDI) and zeta potential (mV) of nanoformulations were previously determined by dynamic light scattering (DLS). Human dentin specimens were exposed to Streptococcus mutans for 14 d. Soft dentin were selectively removed by Er:YAG laser (n?=?30) or bur (n?=?30). Remaining dentin was biomodified with chitosan nanoparticles (Nchi, n?=?10) or green tea-loaded chitosan nanoparticles (Gt?+?Nchi, n?=?10) for 1 min. Control group (n?=?10) did not receive any treatment. Subsurface microhardness (Knoop) was evaluated in hard (sound) and soft dentin, and then, in leathery dentin and after its biomodification, at depths of 30, 60 and 90 μm from the surface. Nchi reached an average size of?≤?300 nm, PDI varied between 0.311 and 0.422, and zeta potential around?+?30 mV. Gt?+?Nchi reached an average size of?≤?350 nm, PDI?<?0.45, and zeta potential around?+?40 mV. Soft dentin showed significantly reduced microhardness at all depths (p?>?0.05). The subsurface microhardness was independent of choice of excavation method (p?>?0.05). At 30 µm from the surface, Gt?+?Nchi increased the leathery dentin microhardness compared to untreated group (p?<?0.05). Nchi promoted intermediate values (p?>?0.05). Both nanoformulations showed an average size less than 350 nm with nanoparticles of different sizes and stability along the 90-day period evaluated. Subsurface microhardness of bur-treated and laser-irradiated dentin was similar. At 30 µm, the biomodification with Gt?+?Nchi improved the microhardness of leathery dentin, independently of caries excavation method used.

     

Improving bonding to eroded dentin by using collagen cross-linking agents: 2 years of water storage

Clinical Oral Investigations - The aim of this study was to investigate the effects of collagen cross-linking agents on nanomechanical and bonding properties of eroded dentin (ED), 24&nbsp;h...     

Transcranial direct current stimulation in psychiatric disorders

The interest in non-invasive brain stimulation techniques is increasing in recent years. Among these techniques, transcranial direct current stimulation (tDCS) has been the subject of great interest among researchers because of its easiness to use, low cost, benign profile of side effects and encouraging results of research in the field. This interest has generated several studies and randomized clinical trials, particularly in psychiatry. In this review, we provide a summary of the development of the technique and its mechanism of action as well as a review of the methodological aspects of randomized clinical trials in psychiatry, including studies in affective disorders, schizophrenia, obsessive compulsive disorder, child psychiatry and substance use disorder. Finally, we provide an overview of tDCS use in cognitive enhancement as well as a discussion regarding its clinical use and regulatory and ethical issues. Although many promising results regarding tDCS efficacy were described, the total number of studies is still low, highlighting the need of further studies aiming to replicate these findings in larger samples as to provide a definite picture regarding tDCS efficacy in psychiatry.     

How to use ECG for decision support in the catheterization laboratory. Cases with inferior ST elevation myocardial infarction

Treatment of acute myocardial infarction has changed considerably during the last few years with the introduction of primary coronary angioplasty. In the acute phase risk stratification is largely based on simple clinical parameters, laboratory markers of myocardial injury and 12-lead electrocardiography. The electrocardiogram is of crucial importance especially during the first few hours after initiation of chest pain when important therapeutic decisions are made. Biochemical markers of myocardial injury are usually not elevated at that time point. Cases with inferior ST-elevation myocardial infarction from our hospital are presented to show how anatomical interpretation of ECG recorded during chest pain helps to risk stratify patients.     

Immune reconstitution syndrome in patients treated for HIV and tuberculosis in Rio de Janeiro.

We made a retrospective longitudinal study from January 2000 to January 2003 to examine cases of immune reconstitution syndrome (IRS) and its incidence rate in tuberculosis (TB)-human immunodeficiency virus (HIV) co-infected patients. The incidence rate (IR) was calculated using a Poisson regression. The confidence interval (CI) that was stipulated was 95%. IRS occurred in 10/84 HIV and TB-positive patients; nine of them were on highly active anti-retroviral therapy (HAART) during a mean of 61.7 (+/- 59) days following the introduction of antiretrovirals. Lymph-node enlargement was the sole clinical manifestation. CD4 counts were <100 cells/mm(3)in 50% of the patients, at the time of TB diagnosis. All but two patients were treated with prednisone, and recovered from TB within a mean of 91 days (+/- 30 days). One relapse of TB was observed, but there were no IRS-related deaths. The incidence rate was higher (IR=11.18; CI, 1.41-88.76) in patients that had superficial lymph node enlargement at the moment of TB diagnosis (not associated with TB), extrapulmonary TB (IR=1.97; CI, 0.44-8.79), were antiretroviral naive (IR=1.85; CI, 0.48-7.16), and CD4 counts <100 cells/mm(3) (IR=1.50; CI, 0.40-5.59), although with a wide CI. IRS was frequent in our sample, occurred more frequently in HIV-naive patients with lymph-node enlargement and extrapulmonary TB. No cases of new pulmonary lesions or worsening of pulmonary infiltrates were observed.