ER Oxidative Stress Promotes Glutathione-Dependent Oxidation of Collagen-1A1 and Promotes Lung Fibroblast Activation.

Changes in the oxidative (redox) environment accompany idiopathic pulmonary fibrosis (IPF). S-glutathionylation of reactive protein cysteines is a post-translational event that transduces oxidant signals into biological responses. We recently demonstrated that increases in S-glutathionylation promote pulmonary fibrosis, which was mitigated by the deglutathionylating enzyme glutaredoxin (GLRX). However, the protein targets of S-glutathionylation that promote fibrogenesis remain unknown. In the present study we addressed whether the extracellular matrix is a target for S-glutathionylation. We discovered increases in collagen 1A1 S-glutathionylation (COL1A1-SSG) in lung tissues from IPF subjects compared to control subjects in association with increases in ER oxidoreductin 1 (ERO1A) and enhanced oxidation of ER-localized peroxiredoxin 4 (PRDX4) reflecting an increased oxidative environment of the endoplasmic reticulum (ER). Human lung fibroblasts exposed to transforming growth factor beta 1 (TGFB1) show increased secretion of COL1A1-SSG. Pharmacologic inhibition of ERO1A diminished oxidation of PRDX4, attenuated COL1A1-SSG and total COL1A1 levels and dampened fibroblast activation. Absence of Glrx enhanced COL1A1-SSG and overall COL1A1 secretion and promoted activation of mechanosensing pathways. Remarkably, COL1A1-SSG resulted in marked resistance to collagenase degradation. Compared to COL1, lung fibroblasts plated on COL1-SSG proliferated more rapidly, and increased expression of genes encoding extracellular matrix crosslinking enzymes and genes linked to mechanosensing pathways. Overall, these findings suggest that glutathione-dependent oxidation of COL1A1 occurs in settings of IPF in association with enhanced ER oxidative stress and may promote fibrotic remodeling due to increased resistance to collagenase-mediated degradation and fibroblast activation.

Neurolysis of the distal segment of the long thoracic nerve for the treatment of scapular winging due to serratus anterior palsy: a continuous series of 73 cases.

BACKGROUND: Serratus anterior (SA) palsy following mechanical injury to the long thoracic nerve (LTN) is the most common cause of scapular winging. This study aimed to identify the factors influencing the outcome of neurolysis of the distal segment of the LTN. We hypothesized that poor results are due to duration before surgery and to persistent scapulothoracic dysfunction. METHODS: A retrospective study was conducted. The inclusion criteria were partial or complete isolated noniatrogenic SA paralysis of at least 4-month duration with preoperative electrophysiologic assessment confirming the neurogenic origin without signs of reinnervation. RESULTS: Seventy-three patients were assessed at 45 days, 6 months, and 24 months after neurolysis of the distal segment of the LTN. At the last follow-up, improvement was excellent in 38 (52%), good in 22 cases (30%), moderate in 6 (8%), and poor in 7 (10%). No patient showed deterioration in outcomes since the beginning of follow-up. Scapular winging was no longer present in 46 cases (63%), while it was minimal in 23 (31.5%). In 4 cases (5.5%), winging was similar to the preoperative condition. DISCUSSION: The best outcomes occurred in patients who presented without compensatory muscle pain and who were treated within 12 months of paralysis. Beyond this time frame, neurolysis can still provide useful functional improvement and avoid palliative surgery. CONCLUSION: Neurolysis of the distal segment of the LTN is a safe and reliable procedure. This technique allows treatment of SA muscle palsy and corrects scapular winging with excellent or good outcomes in 82% of cases.

Hydroxyapatite deposits of the hand and wrist: a diagnosis not to be ignored.

Hydroxyapatite crystal deposition disease (HADD) of the hand and wrist is rare but can cause acute inflammatory syndromes that mimic infectious arthritis. These symptoms, which rapidly resolve with systemic anti-inflammatory drugs, are a source of diagnostic errors and inappropriate treatment. It is of crucial importance to make the diagnosis in order to avoid iatrogenic surgical management. The aim of this study was to determine the clinical and radiographic signs and the key features on which diagnosis depends. Treatment effectiveness and the course of the disease were also examined. Between 1992 and 2008, 12 patients consulted for an isolated acute local inflammatory syndrome of the hand or wrist, which was accompanied by a unique radiographic picture of calcific density. All patients were reassessed clinically and radiographically with a minimum follow-up of 2 years. All patients had presented with acute local inflammatory syndromes. Nine patients had edema and 8 had swelling and erythema. No patient had fever. The course was favorable in 11 patients and one patient required surgery. No patient had a recurrence at the mean final follow-up of 90 ± 64 months. The symptoms associated with hydroxyapatite crystal deposits suggest septic arthritis with acute joint inflammation. The radiological appearance is characteristic and corrects the diagnosis. Oral anti-inflammatory treatment gives more rapid spontaneous improvement, with complete and long-lasting resolution.

Overall Quality and Sanitation Evaluation of Fish Stores at Local Markets in Ibagué, Tolima, Colombia.

HIGHLIGHTS: Results indicated ineffective cleaning and sanitation of surfaces and utensils. High incidence of coliforms indicated inadequate product handling. The low compliance with regulations was corroborated by luminometry results. Deficiencies in hygiene practices could be indicative of potential food safety problems.