Soluble vascular endothelial growth factor receptor-1 protects mice in sepsis

OBJECTIVE: To determine the putative role in the modulation of inflammation of a soluble form of Flt-1 (sFlt), a potent vascular endothelial growth factor antagonist, in experimental endotoxemia and sepsis. DESIGN: Randomized prospective experimental study. SETTING: University medical laboratory. SUBJECTS: Male C56BL/6 strain mice. INTERVENTIONS: We investigated the expression patterns and the effects of vascular endothelial growth factor and soluble Flt-1 in experimental endotoxic shock and sepsis. The possible anti-inflammatory mechanism of soluble Flt-1 was also evaluated. MEASUREMENTS AND MAIN RESULTS: Both vascular endothelial growth factor and sFlt-1 were rapidly released from macrophages activated in vitro by lipopolysaccharide and in the plasma of endotoxemic mice. Administration of vascular endothelial growth factor enhanced proinflammatory cytokine production and mediated a dramatic increase in mortality in endotoxemic mice. Treatment with sFlt-1 attenuated inflammatory responses, inhibited recruitment of inflammatory cells into the peritoneal cavity, and improved survival in a lethal endotoxemia and cecal ligation and puncture-induced sepsis model, even when administered as late as 24 hrs after the onset of sepsis. CONCLUSIONS: These findings support a critical protective role of sFlt-1 in endotoxic shock and sepsis. sFlt-1 may therefore have utility as an adjunctive agent for the treatment of sepsis syndrome.     

In vivo release and turnover of secreted platelet antiheparin proteins in rhesus monkey (Macaca mulatta)

Human and rhesus monkey platelets secrete at least two antiheparin proteins: platelet factor 4 (PF4) and low affinity platelet factor 4 (LA-PF4). Neither of these proteins showed species-related antigenic differences. As determined by radioimmunoassay, the levels of PF4 and LA-PF4 antigen per 10(9) monkey platelets amounted to 10.7 and 20.3 microgram, respectively. One milliliter of monkey plasma prepared from blood collected into an anticoagulant composed of EDTA, prostaglandin E1, and theophylline solution contained 22.4 ng LA-PF4 and 8.0 ng PF4. Concentrations of these two platelet-specific proteins in monkeys closely resembled levels found in human platelets and plasma. Infusion of prostacyclin (PGI2) (100 or 300 ng/kg/min) into monkeys for 15 min resulted in a significant decrease of plasma levels of LA-PF4 antigen and of PF4 by 40%--60% (p < 0.0001). This decrease was related to the inhibitory effect of PGI2 on the secretion of platelets stimulated by a catheter or by venipuncture. Longer infusion of PGI2 did not produce further significant change. The supernate obtained after aggregation of human platelets stimulated by thrombin was injected into monkeys receiving PGI2 infusion. The disappearance of LA-PF4 antigen in monkey plasma followed a biphasic exponential curve with half-lives for the fast and slow components of 8.4 and 63 min. PF4 disappeared faster but followed the same pattern (half-lives for the fast and slow component of 2.1 and 70 min). Analysis of the experimental data suggests that the low levels of secreted platelet proteins in monkey plasma are related to their minimal in vivo release and to their rapid clearance.     

Self-catheterization of urinary bladder complicated with extraperitoneal abscess that mimics an infected bladder diverticulum

For patients who are suffering from neurogenic lower urinary tract dysfunction, intermittent urinary catheterization is an efficient way to empty the bladder.¹ However, the method may result in various complications. Herein we present a rare complication of extraperitoneal abscess owing to intermittent urinary catheterization in a 62-year-old male who had cervical spine injury and was treated with intermittent urethral catheterization for neurogenic lower urinary tract dysfunction. Treatment and a literature review are also described.     

Electrodiagnostic features of true neurogenic thoracic outlet syndrome

Introduction: We report the electrodiagnostic (EDX) features of 32 patients with surgically verified true neurogenic thoracic outlet syndrome (TN‐TOS). Methods: Retrospective record review. Results: We found uniform EDX evidence of a chronic axon loss process that affected the lower portion of the brachial plexus and disproportionately involved the T1 more than the C8 sensory and motor fibers. Because of this relationship, the medial antebrachial cutaneous sensory nerve (T1) and median motor (T1 > C8) study combination was abnormal in 89%, whereas response combinations that primarily assessed the C8 fibers were less frequently affected. Conclusions: The characteristic EDX features of TN‐TOS are T1 > C8 nerve fiber involvement. A comprehensive EDX examination of the lower plexus with contralateral comparison studies is imperative to diagnose this disorder accurately. Muscle Nerve 49 : 724–727, 2014     

Overexpression of the proto-oncogene C-jun in association with low-risk type specific human papillomavirus infection in condyloma acuminata

Infection with different types of human papillomavirus (HPV) is associated with neoplasia at different anatomic sites. The “low-risk” HPVs (LR-HPV) are responsible for benign genital lesions such as condyloma acuminata. In order to clarify the tumorigenic mechanism of LR-HPV, the HPV infection status was investigated and the expression of the c-jun proto-oncogene in different HPV-related skin and genital lesions analyzed. Of the 17 condyloma specimens analyzed by Western blotting, 13 cases (76.5%) exhibited overexpression of the c-jun gene. All 13 cases harbored high copy numbers of the LR-HPV genome with an average of 926 copies per cell, whereas the other four cases had an average of 12 copies of LR-HPV per cell (P < 0.001). Further typing of HPV by Southern blotting revealed that HPV-6 and HPV-11 infections predominated in c-jun positive cases. The c-jun protein was detected much less frequently in cervical cancers (three of 29, or 10.3%) and skin warts (one of 10), and was not detected in five genital polyps or in five normal cervical tissues. These findings suggest a type 6/11-specific induction of c-jun gene expression in HPV-related neoplastic lesions. © 1996 Wiley-Liss, Inc.