Fas ligand-dependent inflammatory regulation in acute myocarditis induced by Trypanosoma cruzi infection

Fas/Fas ligand (Fas-L) engagement, a potent inducer of apoptosis, is also important for cellular activation, regulation of effector and chemotactic activity, and secretion of chemokines and cytokines. We evaluated the relevance of Fas/Fas-L in the regulation of myocarditis induced by Trypanosoma cruzi infection and observed that in Fas-L(-/-) mice (gld/gld), cardiac infiltration was significantly reduced, accordingly showing less cardiomyocyte destruction. Fluorescence-activated cell sorting analysis of cardiac inflammatory cells showed higher numbers of CD8(+) T cells in BALB/c compared with gld/gld mice but similar levels of lymphocyte function-associated antigen-1, intercellular adhesion molecule, CD2, and CD69 expression; MAC-1(+) myeloid cells and mast cells were increased in BALB/c mice, whereas gld/gld mice exhibited an enrichment of CD4(+/low) T cells. Intracellular labeling of cytokines revealed no clear cardiac skewing of Th1 or Th2 responses, but we found a higher number of interleukin-10(+) cells in gld/gld mice and a deficient expression of vascular cell adhesion molecule-1 on cardiac endothelial cells in gld/gld mice. Finally, we found a population of CD3(+) but CD4/CD8 double negative cardiac T cells in both groups of infected mice, but down-regulation of some adhesion molecules and surface receptors was only observed in gld/gld mice, indicating a targeted T-cell population mostly affected by the lack of Fas-L engagement. These results point to a role for myocarditis regulation by Fas/Fas-L beyond its possible direct relevance in cellular death.     

Enhancement of tioconazole ungual delivery: Combining nanocapsule formulation and nail poration approaches

This work investigated the impact of formulation including in vitro release profile, repeated dosing, and nail poration on the ex vivo nail delivery performance of antifungal formulations. Chitosan coated and uncoated tioconazole-loaded nanocapsules and a nano-based film-forming vehicle were assessed via in vitro release and in vitro permeation tests using an artificial membrane and human nail clippings, respectively. The later involved single and daily dosing experiments with intact and porated nails. Additional experiments with Nile Red-loaded formulations evaluated the depth of penetration of the fluorescent marker into the nail by laser scanning confocal microscopy. The nanocapsule formulations prolonged release of tioconazole for longer than the control solutions and this ability was related to an enhanced nail penetration of the drug. Further, the new film-forming formulation delivered its drug payload more efficiently than a marketed product. Daily dosing of the formulations doubled the amount of drug recovered from the nails. Porating the nails enhanced tioconazole delivery in single dose experiments only. The depth of penetration of Nile Red into the nails clippings ranged between 90–160?μm. This research suggests that ensuring prolonged release of a drug is fundamental to develop efficacious topical nail formulations.     

ASSOCIATION BETWEEN POLYMORPHISM IN THE PROMOTER REGION (G/C-915) OF PAX9 GENE AND THIRD MOLAR AGENESIS

Purpose:

Hypodontia is the congenital absence of one or more (up to six) permanent and/or deciduous teeth, being one of the most common alterations of the human dentition. Genetic polymorphisms are variations of DNA sequences occurring in a population. This study investigated whether G-915C single nucleotide polymorphism (SNPs) in the PAX9 gene promoter is associated with hypodontia in humans.

Material and Methods:

The polymorphism in region G/C-915 of PAX9 gene (NCBI ref SNP ID: rs 2073247) of 240 patients was analyzed, being 110 controls and 130 individuals with third molar agenesis. After DNA extraction, the region of interest was amplified by PCR technique using two different primers. The significance of the differences in observed frequencies of polymorphisms in both groups was assessed by odds-ratio and chi-squared test with 95% confidence interval.

Results:

Genotype CC was more frequent in patients with agenesis (11.5%) compared to the control (1.8%), while GG was more prevalent in the control group (39.1%) compared to the individuals with agenesis (26.2%).

Conclusion:

These data showed that the allele C could be associated with the third molar agenesis.     

Antioxidant treatment prevented late memory impairment in an animal model of sepsis

OBJECTIVE: Assess the effect of antioxidant treatment on late memory impairment and early hippocampus oxidative stress after cecal ligation and perforation. SUBJECTS: Male Wistar rats. INTERVENTIONS: Rats underwent sham operation or cecal ligation and perforation. Animals that underwent cecal ligation and perforation were divided into groups: 1) treated with basic support (50 mL/kg saline, 30 mg/kg ceftriaxone, and 25 mg/kg clindamycin every 6 hrs), 2) treated with basic support plus N-acetylcysteine (20 mg/kg N-acetylcysteine at 3, 6, 12, 18, and 24 hrs after cecal ligation and perforation), 3) treated with basic support plus deferoxamine (20 mg/kg deferoxamine at 3 and 24 hrs after cecal ligation and perforation), 4) treated with basic support plus N-acetylcysteine and deferoxamine, or 5) treated with N-acetylcysteine plus deferoxamine. MEASUREMENTS AND MAIN RESULTS: On days 10 and 30 after surgery, the animals underwent behavioral tasks: inhibitory avoidance task, habituation to an open field, and continuous multiple-trials step-down inhibitory avoidance task. The sepsis group showed significantly decreased performance in latency retention compared with the sham group in the inhibitory avoidance task. In the open-field task, the sepsis group presented memory impairment after sepsis. In the continuous multiple-trials step-down inhibitory avoidance task, the sepsis group showed a significant increase in the number of training trials required to reach the acquisition criterion. All these memory impairments were prevented by N-acetylcysteine plus deferoxamine treatment, but not its isolate use. In addition, the combined use of antioxidants attenuated oxidative damage in hippocampus 6 hrs after sepsis induction. CONCLUSIONS: Antioxidant treatment prevented the development of late cognitive deficits in an animal model of sepsis.     

Diagnosing COVID-19 in human serum using Raman spectroscopy

Lasers in Medical Science - This study proposed the diagnosis of COVID-19 by means of Raman spectroscopy. Samples of blood serum from 10 patients positive and 10 patients negative for...     

The effect of photobiomodulation using low-level laser therapy on tooth sensitivity after dental bleaching: a systematic review

Lasers in Medical Science - The authors aimed to conduct a systematic review to assess data from the current literature on the effectiveness of low-level laser therapy (LLLT) in preventing tooth...     

Toxicity of pamam‐coated gold nanoparticles in different unicellular models

Polyamidoamine (PAMAM) dendrimers are used for many pharmaceutical and biomedical applications. However, the toxicological risks of several PAMAM‐based compounds are still not fully evaluated, despite evidences of PAMAM deleterious effects on biological membranes, leading to toxicity. In this report, we investigated the toxicity of generation 0 PAMAM‐coated gold nanoparticles (AuG0 NPs) in four different models to determine how different cellular systems are affected by PAMAM‐coated NPs. Toxicity was evaluated in two mammalian cell lines, Neuro 2A and Vero, in the green alga Chlamydomonas reinhardtii and the bacteria Vibrio fischeri. AuG0 NP treatments reduced cell metabolic activity in algal and bacterial cells, measured by esterase enzymatic activity (C. reinhardtii) and luminescence emission (V. fischeri). EC50 value after 30 min of treatment was similar in both organisms, with 0.114 and 0.167 mg mL^?1 for C. reinhardtii and V. fischeri, respectively. On the other hand, AuG0 NPs induced no change of mitochondrial activity in mammalian cells after 24 h of treatment to up to 0.4 mg mL^?1 AuG0 NPs. Change in the absorption spectra of AuG0 NP in the mammalian cell culture media may indicate an alteration of NP properties that contributed to the low toxicity of AuG0 NPs in mammalian cells. For a safe development of PAMAM‐based nanomaterials, the difference of sensitivity between mammalian and microbial cells, as well as the modulation of NPs toxicity by medium properties, should be taken into account when designing PAMAM NPs for applications that may lead to their introduction in the environment. © 2012 Wiley Periodicals, Inc. Environ Toxicol 29: 328–336, 2014.     

Resistance exercise: a strategy to attenuate inflammation and protein-energy wasting in hemodialysis patients?

Purpose

Patients undergoing hemodialysis (HD) present persistent inflammation and protein-energy wasting (PEW), which contributes to high rates of mortality. This study aimed to assess the effects of a resistance exercise training program (RETP) on inflammation and PEW in HD patients.

Methods

Thirty-seven patients (56.7 % men, 45.9 ± 14.1 years, 23.5 ± 3.9 kg/m²) performed 6 months of intradialytic RETP. Plasma adhesion molecules levels (ICAM-1 and VCAM-1) were measured using the enzyme immunometric assay, and interleukin-6 (IL-6), C-reactive protein, and tumor necrosis factor-alpha by ELISA. Anthropometric, physical capacity, and PEW (simultaneously presence of: BMI <23 kg/m², serum albumin <3.8 g/dL, and reduced arm muscle area) were analyzed.

Results

There was a reduction of ICAM-1 [(1,934.1 pg/mL (1,031.8–2,875.0) vs. 1,571.1 pg/mL (447.1–2,985.5), p < 0.05], VCAM-1 [5,259.51 pg/mL (3,967.4–6,682.4) vs. 3,062.11 pg/mL (2,034.0–5,034.4), p < 0.05], and CRP levels (2.3 ± 0.9 to 1.6 ± 0.6 pg/mL, p < 0.001) after 6 months of RETP. Body composition improved, albumin increased (3.7 ± 0.3 to 3.9 ± 0.2, p < 0.05), and the number of patients presenting PEW was decreased (p = 0.005).

Conclusions

Resistance exercise program for 6 months seems to be effective in reducing inflammation and PEW of HD patients. The universal trial number of this study is U1111-1139-1326.