Aims: Spinal cord injury (SCI) above the sacral level causes bladder dysfunction and remodeling with fibrosis. This study examined the antifibrotic effects using nintedanib, an inhibitor of vascular endothelial growth factor, fibroblast growth factor, and platelet-derived growth factor receptors, on detrusor overactivity (DO) and bladder fibrosis, as well as the modulation mechanisms of C-fiber afferent pathways. Methods: Thirty female C57BL/6 mice were divided into group A (spinal intact), group B (SCI with vehicle), and group C (SCI with nintedanib). At 2 weeks after SCI, vehicle or 50 mg/kg nintedanib was administered subcutaneously for 2 weeks. Then, cystometry was conducted, followed by RT-PCR measurements of fibrosis-related molecules, muscarinic, β-adrenergic, TRP and purinergic receptors in the bladder or L6-S1 dorsal root ganglia (DRG). Trichrome stain and Western blot analysis of transforming growth factor-beta and fibronectin were performed in the bladder. TRPV1 expression in L6 DRG was measured by immunohistochemistry. Results: In cystometry, intercontraction intervals, nonvoiding contractions, voided volume, and voiding efficiency were significantly improved in group C versus group B. RT-PCR, Western blotting, and trichrome staining revealed the fibrotic changes in the bladder of group B, which was improved in group C. Increased messenger RNA levels of TRPV1, TRPA1, P2X 2 , and P2X 3 in DRG of group B were significantly decreased in group C. TRPV1 immunoreactivity in DRG was increased in group B, but decreased in group C. Conclusions:Nintedanib improves storage and voiding dysfunctions and bladder fibrosis in SCI mice. Also, nintedanib-induced improvement of DO is associated with reduced expression of C-fiber afferent markers, suggesting the modulation of bladder C-fiber afferent activity.
The effects of estradiol-17beta, methyltestosterone, tributyltin, bisphenol A and 2,4-dinitrophenol on sex differentiation were investigated in the Korean rockfish, Sebastes schlegeli. The 51 day-old fry with undifferentiated gonads were fed with food containing the chemicals at 0.05, 0.5, 5, 50 and 100 micro/g diet for 29 days. Sex ratio and gonadal abnormality after the chemical treatment were determined by histological examination of gonads. In control group, the sex ratio of fry was 1:1.3 (female:male), and more males than females appeared. The sex of fry fed with estradiol-17beta at 5, 50 and 100 micro/g diet was all females. Feminization of the fry was induced by exogenic estradiol-17beta. In the methyltestosterone group, sex ratio of fry was 1:10.2 in 0.05 micro/g diet, 1:2.4 in 0.5 micro/g diet, 1:3.1 in 5 micro/g diet, 1:1.2 in 50 micro/g diet and 1:2.3 in 100 micro/g diet. Masculinization of the fry was induced by methyltestosterone at the lowest concentration. Furthermore, intersex of the fry was observed. The number of intersex fry was 23.3, 25.0 and 35.3 at 0.5, 5 and 50 micro/g diet of methyltestosterone, respectively. Sex ratio of bisphenol A group showed no difference with that of the control. The sex of fry fed with 2,4-dinitrophenol at 5, 50 and 100 micro/g diet was all females. 2,4-dinitrophenol should be considered as a new member of endocrine disruptors. In tributyltin group, the sex ratio of fry at 100 micro/g diet of tributyltin was 5.4:1. Tributyltin induced the feminization of the fry at the highest dose. Tributyltin showed an estrogenic effect in the Korean rockfish in contrast to an androgenic effect in gastropods.
We experienced a rare case of an endobronchial primitive neuroectodermal tumor of the left main bronchus. Initially we suspected pneumothorax caused by a collapsed left upper lobe and an air-entrapped lower lobe. After tube thoracostomy, the pneumothorax persisted without air leakage. A tumor was detected at the left main bronchus on computed tomography and bronchoscopy, and diagnosed pathologically as small cell lung cancer. Under the presumed diagnosis of limited-stage small cell lung cancer, we performed a left pneumonectomy. The tumor was eventually identified pathologically as a primitive neuroectodermal tumor. Although adjuvant chemoradiotherapy was not performed, no recurrence was observed.
Schwannoma is a slow-growing, benign tumor of the nerve sheath. It rarely presents in the nasal cavity or the paranasal sinuses. Although schwannomas in the nasal septum have been reported previously, cases of this tumor in the nasal columella are rare in the literature. Here, we report on a 67-year-old woman with a schwannoma in the nasal columella that was successfully removed using a sublabial approach, along with a review of relevant literature.
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