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

     

Aging disrupts the temporal organization of antioxidant defenses in the heart of male rats and phase shifts circadian rhythms of systolic blood pressure

Biogerontology - Aging is one of the main risk factors for cardiovascular diseases, and oxidative stress is a key element responsible for the development of age-related pathologies. In addition,...     

Small-molecule XIAP inhibitors derepress downstream effector caspases and induce apoptosis of acute myeloid leukemia cells

We tested the effects of small-molecule XIAP antagonists based on a polyphenylurea pharmacophore on cultured acute myelogenous leukemia (AML) cell lines and primary patient samples. X-linked inhibitor of apoptosis protein (XIAP) antagonist N-[(5R)-6-[(anilinocarbonyl)amino]-5-((anilinocarbonyl){[(2R)-1-(4-cyclohexylbutyl)pyrrolidin-2-yl]methyl}amino)hexyl]-N-methyl-N'-phenylurea (1396-12), but not a structurally related control compound, induced apoptosis of primary leukemia samples with a lethal dose (LD50) of less than 10 microM in 16 of 27 (60%) samples. In contrast, XIAP antagonist 1396-12 was not lethal to the normal hematopoietic cells in short-term cytotoxicity assays. Response of primary AML specimens to XIAP inhibitor correlated with XIAP protein levels, with higher levels of XIAP associated with sensitivity. The XIAP antagonist 1396-12 induced activation of downstream caspases 3 and 7 prior to the activation of upstream caspase 8 and caspase 9. Apoptosis induction was also independent of B-cell lymphoma protein-2 (Bcl-2) or caspase 8, indicative of a downstream effect on apoptotic pathways. Thus, polyphenylurea-based XIAP antagonsists directly induce apoptosis of leukemia cells and AML patient samples at low micromolar concentrations through a mechanism of action distinct from conventional chemotherapeutic agents.     

CD63 tetraspanin slows down cell migration and translocates to the endosomal-lysosomal-MIICs route after extracellular stimuli in human immature dendritic cells

We analyzed herein whether members of the tetraspanin superfamily are involved in human immature dendritic cell (DC) functions such as foreign antigen internalization, phagocytosis, and cell migration. We show that CD63, CD9, CD81, CD82, and CD151 are present in immature DCs. Whereas CD9 and CD81 are mostly expressed at the cell surface, CD63 and CD82 are also located in intracellular organelles. Complexes of monoclonal antibody (Mab) FC-5.01-CD63 or Fab-5.01-CD63 were rapidly translocated "outside-in" and followed the endocytic pathway through early endosomes and lysosomes, reaching major histocompatibility complex (MHC) class II-enriched compartments (MIICs) in less than one hour. Internalization of CD63 was also observed during Saccharomyces cerevisiae phagocytosis. Moreover, an association of CD63 with the beta-glycan receptor dectin-1 was observed. Mabs against CD9, CD63, CD81, and CD82 enhanced by 50% the migration induced by the chemokines macrophage inflammatory protein-5 (MIP-5) and MIP-1alpha. Concomitantly, Mabs against CD63 and CD82 diminished the surface expression of CD29, CD11b, CD18, and alpha5 integrins. By immunoprecipitation experiments we found that CD63 associated with integrins CD11b and CD18. These results suggest that CD9, CD63, CD81, and CD82 could play a role in modulating the interactions between immature DCs and their environment, slowing their migratory ability. However, only CD63 would intervene in the internalization of complex antigens.     

Gastric emptying before and after cholecystectomy in patients with cholecystolithiasis

BACKGROUND/AIMS: The objective of the present study was to measure gastric emptying time of solids and semisolids in dyspeptic individuals with cholecystolithiasis before and 6 months after cholecystectomy in order to determine whether cholecystectomy interferes with gastric emptying. METHODOLOGY: A prospective, self-pairing study was conducted on 29 patients selected according to appropriate inclusion and exclusion criteria. Gastric emptying time of solids and semisolids was determined before and six months after laparoscopic cholecystectomy by the 13C-octanoic acid and 13C-acetate breath tests, respectively. The samples were analyzed by infrared spectrometry. The gastric retention time (lag phase) and gastric emptying half-time of solid and semisolid were determined and the results obtained before and after surgery were compared in the same patient. In addition, the effects of surgery on dyspeptic symptoms were assessed. RESULTS: No significant differences (p>0.05) in gastric retention time and gastric emptying half-time of solid and semisolid test meals were observed before and after cholecystectomy. Dyspeptic symptoms (pain, upper abdominal gases, early satiety, nausea and vomiting) improved after surgery. CONCLUSIONS: Laparoscopic cholecystectomy does not interfere with the gastric emptying time of solids or semisolids in dyspeptic individuals with cholecystolithiasis.     

CNS cryptococcoma in an HIV-positive patient

This is the first case of brain cryptococcoma in an AIDS patient reported in Argentina. The patient was a 28-year-old white heterosexual man with AIDS who presented with altered mental status, seizures, visual hallucinations, headache, and fever without significant focal neurological deficit. He had a lumbar puncture, and was treated for cryptococcal meningitis. Subsequent brain CT scanning and MRI disclosed a mass lesion in the occipital lobe. Histopathological examination of biopsy was compatible with cryptococcoma, and tissue culture revealed Cryptococcus neoformans. Resolution of the mass and edema resulted after treatment with intravenous amphotericin B for six weeks, which was followed with maintenance oral fluconazole. Intracranial mass is an uncommon complication in AIDS patients with cryptococcosis, and cryptococcoma should be considered as differential diagnosis of brain mass lesion in these patients. The etiologic diagnosis is necessary because central nervous system (CNS) toxoplasmosis, lymphoma, and tuberculoma can produce similar clinical syndromes and MRI or CT findings to cryptococcoma. Also, these pathologies may coexist with meningeal cryptococcosis.     

Low bone mineral density is associated to poor glycemic control and increased OPG expression in children and adolescents with type 1 diabetes

Aims

To investigate early alterations on bone mineral density (BMD) and RANK, RANKL and OPG mRNA expression in peripheral blood leukocytes (PBL) in children and adolescents with type 1 diabetes (T1D) and the relationship with glycemic control and bone biomarkers.

Methods

This cross-sectional study included 75 children and adolescents with T1D and 100 individuals without diabetes (normoglycemic–NG) aged 6–20 years old. T1D individuals were considered to have good (T1DG) or poor (T1DP) glycemic control according to the values of HbA1c. Phosphorus, magnesium, total and ionized calcium, osteocalcin, alkaline phosphatase and tartaric-resistant acid phosphatase (TRAP) values were determined in blood samples. BMD was measured by DEXA. RANK, RANKL and OPG mRNA expression was measured in PBL by real-time PCR.

Results

Osteocalcin values were decreased in diabetic groups in comparison to NG group (p < 0.05), and a negative correlation with both serum glucose (r = −0.265, p < 0.01) and Hb1Ac (r = −0.252, p < 0.01) in T1D group was found. BMD was lower in diabetic groups in comparison with NG group (p < 0.05) and a negative correlation was observed between BMD and both serum glucose (r = −0.357, p < 0.01) and HbA1c (r = −0.351, p < 0.01) in T1D group. OPG mRNA expression was significantly increased in T1D and T1DP groups in comparison with NG group (p < 0.05). In conclusion, children and adolescents with early onset T1D presented low bone mineral density associated to unsatisfactory glycemic control, increased OPG mRNA expression and low osteocalcin concentration.