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

     

ASO Author Reflections: Undertreatment of Early-Stage Breast Cancer in Elderly Women Undergoing Lumpectomy Without Radiotherapy Increases the Risk of Locoregional Recurrence

Annals of Surgical Oncology -     

Simvastatin decreases nitric oxide overproduction and reverts the impaired vascular responsiveness induced by endotoxic shock in rats

Lipopolysaccharides (LPS) can be used to induce experimental endotoxic shock, which is characterized by a significant decrease in mean arterial pressure (MAP) and a decreased vasoconstrictor response that have been attributed to excessive nitric oxide production. Inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoA reductase), in addition to lowering serum cholesterol levels, exert many pleiotropic effects, including anti-inflammatory action. In the present study, we investigated the effect of simvastatin, an HMG-CoA reductase inhibitor, on the production of nitric oxide and the cardiovascular response to LPS. Male Wistar rats were pretreated with different doses of simvastatin (10, 20, 40, and 80 mg/kg, i.p.) or saline 20 min before i.v. injection of LPS (1.5 mg/kg) or saline (control). MAP was continuously recorded and nitrate plasma concentration was determined during the 6-h experimental session at 1-h intervals. The pressor response to phenylephrine (1 microg/kg) was evaluated before and 6 h after LPS administration. In the LPS-treated group, there was a time-dependent increase in nitrate plasma concentration (P<0.001), and this response was decreased in simvastatin pretreated rats (P<0.001). We also observed that LPS decreased the pressor response to phenylephrine (P<0.001), an effect that was reverted by simvastatin pretreatment (P<0.05). However, simvastatin did not modify the decrease of MAP induced by LPS. We concluded that simvastatin decreases nitrate plasma concentration in response to LPS and recovers vascular responsiveness during an experimental endotoxic shock. These data suggest the potential use of HMG-CoA reductase inhibitors as a coadjuvant in the treatment of septic shock.     

A homozygous missense mutation in human KLOTHO causes severe tumoral calcinosis

Familial tumoral calcinosis is characterized by ectopic calcifications and hyperphosphatemia due to inactivating mutations in FGF23 or UDP-N-acetyl-alpha-D-galactosamine:polypeptide N-acetylgalactosaminyltransferase 3 (GALNT3). Herein we report a homozygous missense mutation (H193R) in the KLOTHO (KL) gene of a 13-year-old girl who presented with severe tumoral calcinosis with dural and carotid artery calcifications. This patient exhibited defects in mineral ion homeostasis with marked hyperphosphatemia and hypercalcemia as well as elevated serum levels of parathyroid hormone and FGF23. Mapping of H193R mutation onto the crystal structure of myrosinase, a plant homolog of KL, revealed that this histidine residue was at the base of the deep catalytic cleft and mutation of this histidine to arginine should destabilize the putative glycosidase domain (KL1) of KL, thereby attenuating production of membrane-bound and secreted KL. Indeed, compared with wild-type KL, expression and secretion of H193R KL were markedly reduced in vitro, resulting in diminished ability of FGF23 to signal via its cognate FGF receptors. Taken together, our findings provide what we believe to be the first evidence that loss-of-function mutations in human KL impair FGF23 bioactivity, underscoring the essential role of KL in FGF23-mediated phosphate and vitamin D homeostasis in humans.