Interposition grafting of popliteal artery cystic adventitial disease: case report

Cystic adventitial disease of the popliteal artery is a rare cause of leg claudication occurring primarily in young adults. We report a case of a 41-year-old athletic man who presented with rapidly progressive left leg claudication. Using duplex ultrasound and magnetic resonance angiography, a diagnosis of popliteal artery cystic adventitial disease was made. The cystic popliteal artery was resected and replaced using a prosthetic interposition graft. At the 1.5-year follow-up, the cysts have recurred; however, the related symptoms have not. This is in contrast to a previously reported case of interposition saphenous vein grafting requiring resection due to invasion by recurrent cysts within 6 months.     

Prosurvival function of the granulin-epithelin precursor is important in tumor progression and chemoresponse

The granulin-epithelin precursor (GEP/PCDGF), a 68-88 kDa secreted glycoprotein, has been shown to be an important growth and survival factor for ovarian cancer cells. Furthermore, GEP expression is a predictor of patient survival in metastatic ovarian cancer cells. Up to this point, however, the molecular mechanisms and clinical relevance of a GEP-mediated prosurvival phenotype remain poorly characterized. We hypothesize that the prosurvival function of GEP is important in ovarian cancer tumor progression and chemoresponse. To explore this hypothesis, we examined the effects of GEP overexpression on migration, invasion and cisplatin (CDDP) chemosensitivity in the ovarian cancer cell line A2780. Full length GEP transfectants demonstrated an increased capacity to migrate and invade their substratum when compared to empty vector controls. In addition, GEP overexpression was associated with CDDP chemoresistance. Finally, GEP overexpression increased tumor formation and protected cells from tumor regression in response to CDDP treatment in vivo. Taken together, these data support a role for GEP in tumor progression and development of drug resistance.     

R-Spondin1 regulates Wnt signaling by inhibiting internalization of LRP6

The R-Spondin (RSpo) family of secreted proteins act as potent activators of the Wnt/beta-catenin signaling pathway. We have previously shown that RSpo proteins can induce proliferative effects on the gastrointestinal epithelium in mice. Here we provide a mechanism whereby RSpo1 regulates cellular responsiveness to Wnt ligands by modulating the cell-surface levels of the coreceptor LRP6. We show that RSpo1 activity critically depends on the presence of canonical Wnt ligands and LRP6. Although RSpo1 does not directly activate LRP6, it interferes with DKK1/Kremen-mediated internalization of LRP6 through an interaction with Kremen, resulting in increased LRP6 levels on the cell surface. Our results support a model in which RSpo1 relieves the inhibition DKK1 imposes on the Wnt pathway.     

Neuromedin U partially mediates leptin-induced hypothalamo-pituitary adrenal (HPA) stimulation and has a physiological role in the regulation of the HPA axis in the rat

Intracerebroventricular (ICV) administration of the hypothalamic neuropeptide neuromedin U (NMU) or the adipostat hormone leptin increases plasma ACTH and corticosterone. The relationship between leptin and NMU in the regulation of the hypothalamo-pituitary adrenal (HPA) axis is currently unknown. In this study, leptin (1 nm) significantly increased the release of CRH from ex vivo hypothalamic explants by 207 +/- 8.4% (P < 0.05 vs. basal), an effect blocked by the administration of anti-NMU IgG. The ICV administration of leptin (10 mug, 0.625 nmol) increased plasma ACTH and corticosterone 20 min after injection [plasma ACTH (picograms per milliliter): vehicle, 63 +/- 20, leptin, 135 +/- 36, P < 0.05; plasma corticosterone (nanograms per milliliter): vehicle, 285 +/- 39, leptin, 452 +/- 44, P < 0.01]. These effects were partially attenuated by the prior administration of anti-NMU IgG. Peripheral leptin also stimulated ACTH release, an effect attenuated by prior ICV administration of anti-NMU IgG. We examined the diurnal pattern of hypothalamic NMU mRNA expression and peptide content, plasma leptin, and plasma corticosterone. The diurnal changes in hypothalamic NMU mRNA expression were positively correlated with hypothalamic NMU peptide content, plasma corticosterone, and plasma leptin. The ICV administration of anti-NMU IgG significantly attenuated the dark phase rise in corticosterone [corticosterone (nanograms per milliliter): vehicle, 493 +/- 38; NMU IgG, 342 +/- 47 (P < 0.05)]. These studies suggest that NMU may play a role in the regulation of the HPA axis and partially mediate leptin-induced HPA stimulation.     

Bisphenol A and estradiol are equipotent in antagonizing cisplatin-induced cytotoxicity in breast cancer cells

Resistance to chemotherapy is a major problem facing breast cancer patients. Cisplatin, a highly effective DNA-damaging drug, has shown only little success in breast cancer treatment. We are reporting that low nanomolar doses of bisphenol A (BPA) or estradiol antagonize cisplatin cytotoxicity in breast cancer cells, with their effects not mediated via classical estrogen receptors. Although both compounds increase the expression of Bcl-2, a Bcl-2 inhibitor completely blocked the protective effects of BPA while only partially affecting those of estradiol. Blockade of BPA and E2 actions should sensitize ER-negative breast tumors to anti-cancer drugs and allow for the inclusion of cisplatin in treatment regimens.     

Acute Dacryocystitis Causing Orbital Cellulitis and Abscess

Purpose: Acute dacryocystitis commonly presents as preseptal cellulitis as lacrimal sac lies anterior to the orbital septum and hence infection localizes in the preseptal space. The purpose of this study is to describe presentation and management of cases of acute dacryocystitis presenting as orbital cellilitis and abscess secondary to acute dacryocystitis. Method: This retrospective, non-comparative, interventional case series included 6 patients presenting with orbital cellulitis and abscess secondary to acute dacryocystitis. All patients underwent drainage of abscess under general anesthesia. External dcaryocystorhinostomy was advised as the definitive treatment for all pateints. Result: Abscess was localized in the extraconal space in 4 patients and in the intraconal space in 2 patients. Patients with intraconal abscess had visual loss on presentation while vision could be preserved in patients with abscess in extraconal space. Both patients with intraconal abscess had history of acute dacryocystitis. Conclusion: Acute dacryocystitis is an ophthalmic emergency that can cause orbital cellulitis with abscess formation, and even vision loss, if left untreated.