Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0851184 (thinning)
 11,252 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Rupture of the ovarian follicle releases the oocyte at ovulation, a timed event that is critical for fertilization. It is not understood how the protease activity required for rupture is directed with precise timing and localization to the outer surface, or apex, of the follicle. We hypothesized that vasoconstriction at the apex is essential for rupture. The diameter and blood flow of individual vessels and the thickness of the apical follicle wall were examined over time to expected ovulation using intravital multiphoton microscopy. Vasoconstriction of apical vessels occurred within hours preceding follicle rupture in wild-type mice, but vasoconstriction and rupture were absent in Amhr2(cre/+)SmoM2 mice in which follicle vessels lack the normal association with vascular smooth muscle. Vasoconstriction is not simply a response to reduced thickness of the follicle wall; vasoconstriction persisted in wild-type mice when thinning of the follicle wall was prevented by infusion of protease inhibitors into the ovarian bursa. Ovulation was inhibited by preventing the periovulatory rise in the expression of the vasoconstrictor endothelin 2 by follicle cells of wild-type mice. In these mice, infusion of vasoconstrictors (either endothelin 2 or angiotensin 2) into the bursa restored the vasoconstriction of apical vessels and ovulation. Additionally, infusion of endothelin receptor antagonists into the bursa of wild-type mice prevented vasoconstriction and follicle rupture. Processing tissue to allow imaging at increased depth through the follicle and transabdominal ultrasonography in vivo showed that decreased blood flow is restricted to the apex. These results demonstrate that vasoconstriction at the apex of the follicle is essential for ovulation.
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PMID:In vivo imaging reveals an essential role of vasoconstriction in rupture of the ovarian follicle at ovulation. 2684 36

Digital ulcers (DUs) are among the most frequent and disabling vascular complications in patients with systemic sclerosis (SSc). The etiology and pathogenesis of DUs differs depending on the lesion localization. For this reason the underlying etiologic and pathogenetic factors will guide the therapeutic decision. The main pathogenic mechanism that contributes to the development of fingertip DUs is ischemia owing to SSc-related vasculopathy. DUs over bony prominences are mainly a result of skin fibrosis, epidermal thinning and mechanical friction. At the areas of subcutaneous calcinosis DUs can develop as a result of mechanical friction and inflammation. Thus, in cases of DUs over bony prominences and calcinosis, avoidance of trauma and skin care are main measures of primary prophylaxis. In pure ischemic DUs, a combination of vasodilators (calcium channel blockers (CCBs), intravenous prostanoid, phosphodiesterase inhibitors) and antiplatelet drugs should be applied. Despite the lack of controlled trials addressing the administration of antiplatelet agents and anticoagulants in DUs in the context of SSc, the current knowledge about the platelet and coagulation dysfunction leads to their frequent administration from the leading experts in the field of SSc. In our opinion, as more powerful agents, anticoagulants should be considered in severe cases of development of digital gangrenes. Analgetics and antibiotics may be indicated and local treatment is a mandatory care. Currently, the EUSTAR recommendations for the treatment of RP and DUs in SSc include CCBs, intravenous prostanoids and endothelin receptor antagonists. Although for the inclusion of other options in the official recommendations, their efficacy should be confirmed by controlled clinical trials, they are routinely used in the leading scleroderma-centers based on the current knowledge about the pathogenesis of development of DUs in SSc.
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PMID:Digital Ulcers in Systemic Sclerosis - How to Manage in 2013? 2693 93