Myeloid-derived suppressor cells and associated events in urethane-induced lung cancer

OBJECTIVES:

Myeloid-derived suppressor cells contribute to the immunosuppressive microenvironment during tumor development and limit the efficacy of cancer immunotherapy. Identifying myeloid-derived suppressor cells and associated factors is the first step in creating strategies to reverse the suppressive effects of these cells on the immune system.

METHODS:

To induce lung cancer, we administered 2 doses of urethane to BALB/c mice and observed these animals for 120 days. After this period, we evaluated the percentage of myeloid-derived suppressor cells in the blood, lung and bone marrow. The expression of alpha-smooth muscle actin, transforming growth factor-β, Toll-like receptor 2, Toll-like receptor 4, and interleukin-6 was also determined in the lung tissue.

RESULTS:

Myeloid-derived suppressor cells were increased in all evaluated tissues after lung cancer development in association with increased Toll-like receptor 4 expression and decreased interleukin-6 expression in the lung. We observed alpha-smooth muscle actin and transforming growth factor-β expression in lung nodules.

CONCLUSIONS:

We believe that the early diagnosis of cancer through determining the blood levels of myeloid-derived suppressor cells followed by the depletion of these cells should be further investigated as a possible approach for cancer treatment.     

Measuring Adherence to Antiretroviral Treatment: The Role of Pharmacy Records of Drug Withdrawals

This study aimed to evaluate adherence to antiretroviral treatment (ART) among HIV + adults, assess its association with HIV viral load (VL) and identify factors associated to adherence. A survey involving a random sample of adults followed at a HIV/AIDS reference center in S?o Paulo city, Brazil, from 2007 to 2009 was done. A questionnaire was applied and data were retrieved from the pharmacy and medical records. The study involved 292 subjects: 70.2% men; median age: 43 years; median duration of ART: 8 years. 89.3% self-reported taken all prescribed pills in the last 3 days but only 39.3% picked up ≥95% of the prescribed ART from the pharmacy in the last 12 months. At the multivariate analysis having symptoms prior to ART, taking fewer ART pills, and not missing medical appointments were independently associated to higher adherence. Adherence was strongly associated with undetectable HIV VL. Rates of undetectable HIV VL did not differ from 80 to ≥95% of adherence.     

Late brain alterations in sepsis‐survivor rats

Central nervous system (CNS) dysfunction secondary to sepsis is characterized by long‐term cognitive impairment. It was observed that oxidative damage, energetic metabolism impairment, and cytokine level alteration seen in early times in an animal model of sepsis may persist for up to 10 days and might be associated with cognitive damage. In order to understand these mechanisms, at least in part, we evaluated the effects of sepsis on cytokine levels in the cerebrospinal fluid (CSF), oxidative parameters, and energetic metabolism in the brain of rats at both 30 and 60 days after sepsis induction by cecal ligation and perforation (CLP). To this aim, male Wistar rats underwent CLP with “basic support” or were sham‐operated. Both 30 and 60 days after surgery, the CSF was collected and the animals were killed by decapitation. Then, the prefrontal cortex, hippocampus, striatum, and cortex were collected. Thirty days after surgery, an increase of IL‐6 level in the CSF; an increase in the thiobarbituric acid‐reactive species (TBARS) in prefrontal cortex and a decrease in hippocampus, striatum, and cortex; a decrease of carbonyl protein formation only in prefrontal cortex and an increase in striatum; and an increase in the complex IV activity only in hippocampus were observed. Sixty days after sepsis, an increase of TNF‐α level in the CSF; a decrease of TBARS only in hippocampus; an increase of carbonyl protein formation in striatum; and a decrease of complex I activity in prefrontal cortex, hippocampus, and striatum were observed. These findings may contribute to understanding the role of late cognitive impairment. Further studies may address how these findings interact during sepsis development and contribute to CNS dysfunction. Synapse 67:786–793, 2013. © 2013 Wiley Periodicals, Inc.     

CO<Subscript>2</Subscript> laser irradiation enhances CaF<Subscript>2</Subscript> formation and inhibits lesion progression on demineralized dental enamel—in vitro study

This study evaluated if Carbon dioxide (CO₂) (λ 10.6 μm) laser irradiation combined with acidulated phosphate fluoride gel application (APF gel) enhances “CaF₂” uptake by demineralized enamel specimens (DES) and inhibits enamel lesion progression. Thus, two studies were conducted and DES were subjected to APF gel combined or not with CO₂ laser irradiation (11.3 or 20.0 J/cm², 0.4 or 0.7 W) performed before, during, or after APF gel application. In study 1, 165 DES were allocated to 11 groups. Fluoride as “CaF₂ like material” formed on enamel was determined in 100 DES (n?=?10/group), and the surface morphologies of 50 specimens were evaluated by scanning electron microscopy (SEM) before and after “CaF₂” extraction. In study 2, 165 DES (11 groups, n?=?15), subjected to the same treatments as in study 1, were further subjected to a pH-cycling model to simulate a high cariogenic challenge. The progression of demineralization in DES was evaluated by cross-sectional microhardness and polarized light microscopy analyses. Laser at 11.3 J/cm² applied during APF gel application increased “CaF₂” uptake on enamel surface. Laser irradiation and APF gel alone arrested the lesion progression compared with the control (p?<?0.05). Areas of melting, fusion, and cracks were observed. CO₂ laser irradiation, combined with a single APF application enhanced “CaF₂” uptake on enamel surface and a synergistic effect was found. However, regarding the inhibition of caries lesion progression, no synergistic effect could be demonstrated. In conclusion, the results have shown that irradiation with specific laser parameters significantly enhanced CaF₂ uptake by demineralized enamel and inhibited lesion progression.     

Sustained Release from Ionic-Gradient Liposomes Significantly Decreases ETIDOCAINE Cytotoxicity

Purpose

Etidocaine (EDC) is a long lasting local anesthetic, which alleged toxicity has restricted its clinical use. Liposomes can prolong the analgesia time and reduce the toxicity of local anesthetics. Ionic gradient liposomes (IGL) have been proposed to increase the upload and prolong the drug release, from liposomes.

Methods

First, a HPLC method for EDC quantification was validated. Then, large unilamellar vesicles composed of hydrogenated soy phosphatidylcholine:cholesterol with 250 mM (NH₄)₂SO₄ - inside gradient - were prepared for the encapsulation of 0.5% EDC. Dynamic light scattering, nanotracking analysis, transmission electron microscopy and electron paramagnetic resonance were used to characterize: nanoparticles size, polydispersity, zeta potential, concentration, morphology and membrane fluidity. Release kinetics and in vitro cytotoxicity tests were also performed.

Results

IGL_EDC showed average diameters of 172.3?±?2.6 nm, low PDI (0.12?±?0.01), mean particle concentration of 6.3?±?0.5?×?10¹²/mL and negative zeta values (?10.2?±?0.4 mV); parameters that remain stable during storage at 4°C. The formulation, with 40% encapsulation efficiency, induced the sustained release of EDC (ca. 24 h), while reducing its toxicity to human fibroblasts.

Conclusion

A novel formulation is proposed for etidocaine that promotes sustained release and reduces its cytotoxicity. IGL_EDC can come to be a tool to reintroduce etidocaine in clinical use.

     

Curcumin supplementation improves oxidative stress and inflammation biomarkers in patients undergoing hemodialysis: a secondary analysis of a randomized controlled trial

International Urology and Nephrology - Recent studies have shed light on the potential role of curcumin in mitigating inflammation in patients with chronic kidney disease (CKD). This study aimed to...     

Photobiomodulation via a cluster device associated with a physical exercise program in the level of pain and muscle strength in middle-aged and older women with knee osteoarthritis: a randomized placebo-controlled trial

Osteoarthritis (OA) is a chronic joint disease that leads to pain and functional incapacity. The aim of the study is to investigate the effects of the incorporation of photobiomodulation (PBM) (via cluster) into a physical exercise program on the level of pain, lower limb muscle strength, and physical capacity, in patients with knee OA. Sixty-two female volunteers with a diagnosis of knee OA were distributed in 4 groups: exercise associated with placebo PBM group, exercise associated with active PBM group, active PBM group, and placebo PBM group. Sixteen sessions of lower limb strength exercises and PBM via cluster (808 nm, 100 mW, 7 points each side, 56 J total) were performed. The level of pain, physical capacity, and lower limb muscle strength were evaluated with the use of the numeric pain rating scale (NPRS), 6-min walking test (6-MWT) and timed up and go (TUG), and maximal voluntary isometric torque (MVIT) before and after the interventions. Both groups presented a significant decrease in the level of pain when compared with the placebo-treated women. Furthermore, the 6-MWT showed that the trained groups (with or without PBM) demonstrated higher values in the distance walked comparing pre and post-treatment values. The same behavior was found for the MVIT load before and after intervention. TUG was higher for all the treated with exercise groups comparing the pre and post-treatment values. Physical exercise and PBM showed analgesic effects. However, PBM did not have any extra effect along with the effects of exercise in improving the distance walked, the TUG, and the muscle strength.

Trial registration: RBR-7t6nzr

     

Biocompatibility of Ricinus communis polymer with addition of calcium carbonate compared to titanium. Experimental study in guinea pigs

Objective

The aim of the present investigation was to determine whether the difference in inflammatory tissue reaction between the Riccinus communis (castor) polymer with calcium carbonate and the titanium implant is statistically significant.

Methods

Thirty-two Cavia porcellus were allocated into four groups of eight animals each. We implanted the two types of materials in the retroperitoneal space of all the animals. They were euthanized at 7, 20, 30 and 40 days after surgery, and an histological study of the samples was conducted.

Results

All implants showed characteristics of chronic inflammation regardless of the material and timepoint of evaluation. There was no statistically significant difference between Pm+CaCO₃ and Ti with regard to the presence of granulation tissue, tissue congestion, histiocytes, lymphocytes, neutrophils, giant cells, and fibrosis (P> 0.05).

Conclusion

The castor oil polymer plus calcium carbonate implant was not statistically different from the titanium implant regarding inflammatory tissue reaction.