No abstract available.

No abstract available.
Asian Continental Ancestry Group* ; Female ; Humans

The expression of inducible nitric oxide synthase (iNOS) is a critical factor in both normal physiological functions and the pathogenesis of disease. This study was undertaken to determine the molecular mechanism by which nitric oxide (NO) exerts negative feedback regulation on iNOS gene expression. Isolated rat hepatocytes stimulated with cytokines exhibited a marked increase in NO production as well as iNOS mRNA and protein levels, which were significantly reduced by pretreatment of the NO donors S-nitroso-N-acetyl-D, L-penicillamine (SNAP) and V-PYRRO/NO. This effect of SNAP was inhibited when NO was scavenged using red blood cells. Pretreatment with oxidized SNAP, 8-Br-cGMP, NO2-, or NO3- did not suppress the cytokine-induced NO production. Moreover, LPS/ IFN-gamma-stimulated RAW264.7 cells, which produce endogenous NO, expressed lower levels of iNOS, IL-1beta, IL-6 and TNF-alpha mRNAs, without changes in their mRNA half-lives, than those in the presence of the iNOS inhibitor NG-monomethyl- L-arginine. The iNOS gene transcription rate exhibited an 18-fold increase after cytokine stimulation, which was significantly inhibited by SNAP pretreatment. SNAP also blocked cytokine- induced increase in NF-kappa B activation, iNOS promoter activity, nuclear translocation of cytosolic NF-kappa B p65 subunit, and I kappa B alpha degradation, which correlated with its inhibitory effect on phosphorylation and ubiquitination of I kappa B. These data indicate that NO down-regulates iNOS gene expression and NO production by inhibiting the post-translational processes of I kappa B alpha thereby preventing NF-kappa B activation. These results identify a novel negative feedback mechanism whereby NO down-regulates iNOS gene expression.
Animals ; Cell Line ; Cell Nucleus/metabolism ; Cyclic GMP/*analogs & derivatives/pharmacology ; Cytokines/genetics/metabolism ; *Down-Regulation ; Hepatocytes/metabolism ; I-kappa B/*metabolism ; Lipopolysaccharides/pharmacology ; Nitric Oxide/biosynthesis/*physiology ; Nitric-Oxide Synthase/biosynthesis/*genetics ; Penicillamine/*analogs & derivatives/pharmacology ; Phosphorylation ; Promoter Regions (Genetics)/genetics ; *Protein Processing, Post-Translational ; Protein Transport ; Rats ; Research Support, Non-U.S. Gov't

Background: Occupational injuries and diseases are life events that significantly impact an individuals’ identity. In this study, we examined the trajectories of self-esteem among victims of occupational injury and disease and their relation to health. Methods: The Panel Study of Workers’ Compensation Insurance conducted annual followups on workers who had experienced occupational injury or disease. A total of 2,000 participants, who had completed medical care, were followed from 2013 to 2017. Growth mixture modeling was utilized to identify latent classes in the self-esteem trajectory.Additionally, logistic regressions were conducted to explore the association between trajectory membership, baseline predictors, and outcomes. Results: Three distinct trajectory classes were identified. Total 65.8% of the samples (n = 1,316) followed an increasing self-esteem trajectory, while 31.1% (n = 623) exhibited a constant trajectory, and 3.1% (n = 61) showed a decreasing trajectory. Individuals with an increasing trajectory were more likely to have a higher educational attainment (odds ratio [OR], 1.86; 95% confidence interval [CI], 1.20–2.88), an absence of a moderate-to-severe disability rating (OR, 0.49; 95% CI, 0.25–0.96), no difficulty in daily living activities (OR, 0.81; 95% CI, 0.75–0.88), and were economically active (re-employed: OR, 2.46; 95% CI, 1.52–3.98; returned to original work: OR, 4.46; 9% CI, 2.65–7.50). Those with a decreasing self-esteem trajectory exhibited an increased risk of poor subjective health (OR, 1.89; 95% CI, 0.85–4.85 in 2013 to OR, 3.17; 95% CI, 1.04–13.81 in 2017), whereas individuals with an increasing trajectory showed a decreased risk (OR, 0.54; 95% CI, 0.43–0.68 in 2013 to OR, 0.44; 95% CI, 0.33–0.57 in 2017). Conclusion Our findings emphasize the diversity of psychological responses to occupational injury or disease. Policymakers should implement interventions to enhance the self-esteem of victims.

A 53-year old man who had a left hemiparesis from head injury of traffic accident 20 years ago visited an emergency room with suddenly developed semi-comatose mental status. Brain CT showed 8.6-cm sized solid and cystic mass on right temporal lobe that was associated with hemorrhage. Solid lesion showed a strong enhancement after an administration of contrast media. Because of severe mass effect, emergency operation was performed. The mass was an intraparenchymal lesion with yellowish cystic fluid and the firm reddish-brown solid lesion was hemorrhagic. The lesion was totally resected. Pathologically, anaplastic solitary fibrous tumor/hemangiopericytoma was diagnosed with 70/10 high power fields. Postoperative radiotherapy of 50 Gy was done. Postoperative 2 months later, the patient was recovered to alert mental state. We report this unusual case of non-dural based intraparenchymal solitary fibrous tumor/hemangiopericytoma with high mitotic index and acute massive hemorrhage. Rapid tumor growth of hypervascular tumor might have a chance of bleeding.
Accidents, Traffic ; Brain ; Brain Neoplasms ; Central Nervous System ; Cerebral Hemorrhage ; Contrast Media ; Craniocerebral Trauma ; Emergencies ; Emergency Service, Hospital ; Hemangiopericytoma ; Hemorrhage ; Humans ; Mitotic Index ; Paresis ; Radiotherapy ; Solitary Fibrous Tumors ; Temporal Lobe

Methods: To operationalize precarious employment, we utilized data from the Korean Working Conditions Survey and focused on three distinct dimensions: employment insecurity, income inadequacy, and a lack of rights and protections. By constructing a summative scale ranging from -16 to 2, with lower scores indicating higher precariousness, we measured employment precariousness among Korean wage workers. To compare employment precariousness according to survey participant characteristics, we employed the Wilcoxon Rank Sum Test. Results: We analyzed a weighted number of 38,432 workers. The overall sample showed a median (Q1, Q3) summative scale score of -3 (-6, -1). The median summative score was lower for women compared to men (men: -2; women: -5; p < 0.001), as well as for young or older workers compared to middle-aged workers (young: -4; middle-aged: -2; older: -5; p < 0.001). Similarly, workers with lower educational levels (middle school or below: -8; high school: -5; college or above: -2; p < 0.001) and non-white collar workers (blue collar: -5; service/sales worker: -6; white collar: -2; p < 0.001) experienced higher levels of employment precariousness. Conclusion Our findings indicate that certain vulnerable groups, such as women, young or older adults, workers with low educational attainment, and caregiving or low-skilled elementary workers, are disproportionately exposed to high employment precariousness. Active policy interventions are needed to improve the employment quality of vulnerable groups.

Background: Although Gamma Knife radiosurgery (GKRS) has been widely used for intracranial meningiomas as an alternative or adjuvant treatment, guidelines have not been established for the selection of patients with petroclival meningioma (PCM) for GKRS. In this study, we reported the factors related to tumor progression and postoperative complications in PCM patients treated by GKRS, with a review of the literatures. Methods: Between 2004 and 2019, 64 patients (52 patients for alternative and 12 patients for adjuvant treatment) with PCM underwent GKRS in our institution. The clinical and radiological factors were retrospectively analyzed. The mean radiologic follow-up duration was 58.4 months (range, 6-164 months). The mean tumor volume and diameter before GKRS were 13.4㎤ and 2.9 cm, respectively.The median marginal dose was 12 Gy (range, 10-14 Gy) with a 50% median isodose line. Fractionation was used in 19 cases (29%, two fractionations in 5 cases & three fractionations in 14 cases). Results: Progression was noted in 7 cases (10.9%) and the progression-free survival rates were 91.1% at 5 years and 69.6% at 10 years. Although large in volume, moderate to severe peritumoral edema and male gender were somewhat related to progression, they did not reach statistical significance. Ten patients (15.6%) developed complications after GKRS. The most common complication was cranial nerve deficit (n=8), followed by hemiparesis, cognitive dysfunction, and hydrocephalus. Large size (maximal diameter ≥5 cm) [hazard ratio (HR) 0.091, 95% confidence interval (CI) 0.014-0.608;p=0.013] and multiplicity (HR 0.102, 95% CI 0.018-0.573; p=0.009) were independent factors for developing complications after GKRS. Conclusion GKRS can be considered an effective and safe treatment for large-volume PCM. However, for patients with large size or multiple masses, the treatment method should be determined with caution because the probability of complications after GKRS may increase.

BACKGROUNDCentral blood pressure (BP) is pathophysiologically more important than peripheral BP for the pathogenesis of cardiovascular disease. Arterial stiffness is also a good predictor of cardiovascular morbidity and mortality. The effects of benidipine, a unique dual L-/T-type calcium channel blocker, on central BP have not been reported. This study aimed to compare the effect of benidipine and losartan on the central BP and arterial stiffness in mild to moderate essential hypertensives.

METHODSThis 24 weeks, multi-center, open label, randomized, active drug comparative, parallel group study was designed as a non-inferiority study. The eligible patients (n = 200) were randomly assigned to receive benidipine (n = 101) or losartan (n = 99). Radial artery applanation tonometry and pulse wave analysis were used to measure the central BP, pulse wave velocity (PWV) and augmentation index (AIx). We also measured the metabolic and inflammatory markers.

RESULTSAfter 24 weeks, the central BP decreased significantly from baseline by (16.8 ± 14.0/10.5 ± 9.2) mmHg (1 mmHg = 0.133 kPa) (systolic/diastolic BP; P < 0.001) in benidipine group and (18.9 ± 14.7/12.1 ± 10.2) mmHg (P < 0.001) in losartan group respectively. Both benidipine and losartan groups significantly lowered peripheral BP (P < 0.001) and AIx (P < 0.05), but there were no significant differences between the two groups. The mean aortic, brachial and femoral PWV did not change in both groups after 24-week treatment. There were no significant changes of the blood metabolic and inflammatory biomarkers in each group.

CONCLUSIONBenidipine is as effective as losartan in lowering the central and peripheral BP, and improving arterial stiffness.

Adolescent ; Adult ; Aged ; Angiotensin II Type 1 Receptor Blockers ; therapeutic use ; Blood Pressure ; drug effects ; Calcium Channel Blockers ; therapeutic use ; Dihydropyridines ; adverse effects ; therapeutic use ; Essential Hypertension ; Female ; Humans ; Hypertension ; drug therapy ; physiopathology ; Losartan ; adverse effects ; therapeutic use ; Male ; Middle Aged ; Vascular Stiffness ; drug effects

Prostaglandin E2(PGE2), a major product of cyclooxygenase, has been implicated in modulating angiogenesis, vascular function, and inflammatory processes, but the underlying mechanism is not clearly elucidated. We here investigated the molecular mechanism by which PGE 2 regulates angiogenesis. Treatment of human umbilical vein endothelial cells (HUVEC) with PGE 2 increased angiogenesis. PGE 2 increased phosphorylation of Akt and endothelial nitric oxide synthase (eNOS), eNOS activity, and nitric oxide (NO) production by the activation of cAMP-dependent protein kinase (PKA) and phosphatidylinositol 3-kinase (PI3K). Dibutyryl cAMP (DB-cAMP) mimicked the role of PGE 2 in angiogenesis and the signaling pathway, suggesting that cAMP is a down-stream mediator of PGE 2. Furthermore, PGE 2 increased endothelial cell sprouting from normal murine aortic segments, but not from eNOS-deficient ones, on Matrigel. The angiogenic effects of PGE 2 were inhibited by the inhibitors of PKA, PI3K, eNOS, and soluble guanylate cyclase, but not by phospholipase C inhibitor. These results clearly show that PGE 2 increased angiogenesis by activating the NO/cGMP signaling pathway through PKA/PI3K/Akt-dependent increase in eNOS activity.
1-Phosphatidylinositol 3-Kinase/antagonists & inhibitors ; Animals ; Aorta ; Cell Movement/drug effects ; Cell Proliferation/drug effects ; Cyclic AMP/metabolism/pharmacology ; Cyclic GMP/biosynthesis/*metabolism ; Dinoprostone/*pharmacology ; Endothelial Cells/*drug effects/metabolism ; Enzyme Inhibitors/pharmacology ; Humans ; Mice ; Mice, Knockout ; Neovascularization, Physiologic/*drug effects ; Nitric Oxide/biosynthesis/*metabolism ; Nitric Oxide Synthase Type III/deficiency/metabolism ; Phosphorylation/drug effects ; Proto-Oncogene Proteins c-akt/metabolism ; Rats ; Rats, Sprague-Dawley ; Research Support, Non-U.S. Gov't ; Signal Transduction/*drug effects ; Umbilical Veins/cytology/*drug effects/metabolism

Vascular endothelial growth factor (VEGF) plays a pivotal role in pathologic ocular neovascularization and vascular leakage via activation of VEGF receptor 2 (VEGFR2). This study was undertaken to evaluate the therapeutic mechanisms and effects of the tetrapeptide Arg-Leu-Tyr-Glu (RLYE), a VEGFR2 inhibitor, in the development of vascular permeability and choroidal neovascularization (CNV). In cultured human retinal microvascular endothelial cells (HRMECs), treatment with RLYE blocked VEGF-A-induced phosphorylation of VEGFR2, Akt, ERK, and endothelial nitric oxide synthase (eNOS), leading to suppression of VEGF-A-mediated hyper-production of NO. Treatment with RLYE also inhibited VEGF-A-stimulated angiogenic processes (migration, proliferation, and tube formation) and the hyperpermeability of HRMECs, in addition to attenuating VEGF-A-induced angiogenesis and vascular permeability in mice. The anti-vascular permeability activity of RLYE was correlated with enhanced stability and positioning of the junction proteins VE-cadherin, β-catenin, claudin-5, and ZO-1, critical components of the cortical actin ring structure and retinal endothelial barrier, at the boundary between HRMECs stimulated with VEGF-A. Furthermore, intravitreally injected RLYE bound to retinal microvascular endothelium and inhibited laser-induced CNV in mice. These findings suggest that RLYE has potential as a therapeutic drug for the treatment of CNV by preventing VEGFR2-mediated vascular leakage and angiogenesis.
Actins ; Animals ; Capillary Permeability ; Choroid ; Choroidal Neovascularization ; Claudin-5 ; Endothelial Cells ; Endothelium ; Humans ; Macular Degeneration ; Mice ; Nitric Oxide Synthase Type III ; Permeability ; Phosphorylation ; Receptors, Vascular Endothelial Growth Factor ; Retinaldehyde ; Vascular Endothelial Growth Factor A