CD81-Receptor Associations — Impact for Hepatitis C Virus Entry and Antiviral Therapies

Tetraspanins are integral transmembrane proteins organized in microdomains displaying specific and direct interactions with other tetraspanins and molecular partners. Among them, CD81 has been implicated in a variety of physiological and pathological processes. CD81 also plays a crucial role in pathogen entry into host cells, including hepatitis C virus (HCV) entry into hepatocytes. HCV is a major cause of liver cirrhosis and hepatocellular carcinoma. HCV entry into hepatocytes is a complex process that requires the coordinated interaction of viral and host factors for the initiation of infection, including CD81, scavenger receptor BI, claudin-1, occludin, membrane-bound host cell kinases, Niemann-Pick C1 Like 1, Harvey rat sarcoma viral oncogene homolog (HRas), CD63 and transferrin receptor 1. Furthermore, recent data in HCV model systems have demonstrated that targeting critical components of tetraspanins and associated cell membrane proteins open new avenues to prevent and treat viral infection.     

A murine model of mild traumatic brain injury exhibiting cognitive and motor deficits

Background

Mild traumatic brain injury (TBI) is a serious public health concern affecting more than 1.7 million people in the United States annually. Mild TBI is difficult to diagnose and is clinically associated with impaired motor coordination and cognition.

Methods

We subjected mice to a mild TBI (mTBI-1 or mTBI-2) induced by a weight drop model. We assessed brain injury histologically and biochemically, the latter by serum neuron-specific enolase and glial fibrillary acidic protein. Systemic and brain inflammation were measured by cytokine array. We determined blood–brain barrier integrity by cerebral vascular leakage of micromolecular and macromolecular fluorescent molecules. We evaluated mice using a rotarod device and novel object recognition to measure motor coordination and cognition, respectively.

Results

Mice undergoing mTBI-1 or mTBI-2 had significant deficits in motor coordination and cognition for several days after injury compared with controls. Furthermore, both mTBI-1 and mTBI-2 caused micromolecular leakage in the blood–brain barrier, whereas only mTBI-2 caused macromolecular leakage. Serum neuron-specific enolase and glial fibrillary acidic protein were elevated acutely and corresponded to the degree of injury, but returned to baseline within 24 h. Serum cytokines interleukin-6 and keratinocyte-derived chemokine were significantly increased within 90 min of TBI. Interleukin-6 levels correlated with the degree of injury.

Conclusions

The current study provides a reproducible model of mild TBI in mice that exhibits pathologic features of mild TBI in humans. Furthermore, our data suggest that serum cytokines, such as IL-6, may be effective biomarkers for severity of head injury.     

Association of midregional proadrenomedullin with coronary artery stenoses, soft atherosclerotic plaques and coronary artery calcium

Midregional proadrenomedullin (MR-proADM) is elevated in patients with heart failure and myocardial infarction. The aim of this study was to evaluate the association of MR-proADM with the grade of coronary artery stenosis, presence of coronary artery soft plaques and coronary artery calcification score (CACS), determined by 64-multislice computed tomography (MSCT) in patients without known prior cardiovascular disease. This retrospective study included 107 patients undergoing MSCT for confirmation (or exclusion) of coronary artery disease. MR-proADM levels were measured in all patients. The assessment of coronary artery stenoses, CACS and soft coronary plaques was made by MSCT using known criteria. The MR-proADM [median (25th–75th percentiles)] level was 0.33 (0.21–0.43)?nmol/l. The MR-proADM level was 0.28 (0.22–0.40)?nmol/l in patients with coronary stenoses ≥50% (n?=?23) versus 0.33 (0.27–0.40)?nmol/l in patients with coronary stenoses <50% (n?=?83, P?=?0.59), 0.33 (0.26–0.40)?nmol/l in patients with soft plaques (n?=?56) versus 0.33 (0.25–0.41)?nmol/l in patients without soft plaques (n?=?50, P?=?0.73) and 0.33 (0.25–0.39)?nmol/l in patients with CACS?<200 (n?=?81) versus 0.32 (0.26–0.44)?nmol/l in patients with CACS?≥200 (n?=?26, P?=?0.77). In multivariate analysis, the MR-proADM level was a significant correlate of coronary artery stenoses [odds ratio (OR)?=?0.93; 95% confidence interval (CI) 0.86–0.99; P?=?0.026] and soft plaques (OR?=?0.94; 95% CI 0.90–0.99; P?=?0.015) but not of CACS (OR?=?0.98; 95% CI 0.93–1.03; P?=?0.36). A decreased MR-proADM level is an independent correlate of the presence of coronary artery disease and of soft atherosclerotic plaques. Patients with decreased MR-proADM levels may need invasive examinations to diagnose more severe forms of coronary artery disease.     

Inter-eye relationship of intraocular pressure change after unilateral trabeculectomy,filtering canaloplasty,or PreserFlo™ microshunt implantation

Graefe's Archive for Clinical and Experimental Ophthalmology - This study assesses short-term intraocular pressure (IOP) change in the fellow eye of glaucoma patients after mitomycin...     

The Role of EC-IC in the Treatment of Giant Intracranial Aneurysms

Abstract

Extracranial to intracranial bypass surgery was used in 27 cases of intracranial giant aneurysm to prevent ischemic complications. In 19 of 21 patients the aneurysm was considered unfit for a direct clipping or ligation, and an EC-IC bypass was done in conjunction with staged clipping of the internal carotid artery or occlusion of the middle cerebral artery. All bypass grafts have remained patent postoperatively. None of the patients have developed ischemic complications in the 6-41 month period of follow-up.