Characterization of human H1N1 influenza virus variants selected in vitro with zanamivir in the presence of sialic acid-containing molecules

Understanding the molecular mechanisms of influenza virus resistance to neuraminidase inhibitors is a main concern for their clinical use. In an attempt to reproduce in vivo selective conditions where influenza virus resistance to neuraminidase inhibitors can occur the zanamivir selection of an A/H1N1 influenza virus strain was carried out in Madin-Darby canine kidney cells performed in the presence or absence of sialic acid-containing inhibitor analogues that act as virus decoy receptors. The zanamivir-selected variants passaged in the presence of sialic acid-containing molecules resembling the human-like virus receptor lost the ability to bind red blood cells. Furthermore, whereas all zanamivir-selected variants exhibited a robust reduction in susceptibility to zanamivir in plaque assays only those obtained after extensive passages acquired a powerful neuraminidase enzyme resistance to zanamivir and oseltamivir. Evidence that balanced neuraminidase and hemagglutinin activities mediated by mutations induced during selection could play a role in the decrease of virus replication susceptibility to zanamivir is reported.     

Polyphenolic extract attenuates fatty acid-induced steatosis and oxidative stress in hepatic and endothelial cells

Purpose

Phenolic compounds (PC) of virgin olive oil exert several biochemical and pharmacological beneficial effects. Some dietary PC seem to prevent/improve obesity and metabolic-related disorders such as non-alcoholic fatty liver disease (NAFLD). We investigated the possible effects of PC extracted from olive pomace (PEOP) and of the main single molecules present in the extract (tyrosol, apigenin, oleuropein, p-coumaric and caffeic acid) in protecting hepatocytes and endothelial cells against triglyceride accumulation and oxidative stress.

Methods

Rat hepatoma and human endothelial cells were exposed to a mixture of oleate/palmitate to mimic the condition of NAFLD and atherosclerosis, respectively. Then, cells were incubated for 24 h in the absence or in the presence of PC or PEOP. Different parameters were evaluated, such as lipid accumulation and oxidative stress-related markers.

Results

In hepatic cells, expression of peroxisome proliferator-activated receptors (PPARs) and of stearoyl-CoA desaturase 1 (SCD-1) were assessed as index of lipid metabolism. In endothelial cells, expression of intercellular adhesion molecule-1 (ICAM-1), activation of nuclear factor kappa-B (NF-kB), release of nitric oxide (NO), and wound-healing rate were assessed as index of inflammation.

Conclusion

PEOP extract ameliorated hepatic lipid accumulation and lipid-dependent oxidative imbalance thus showing potential applications as therapeutic agent tuning down hepatosteatosis and atherosclerosis.

     

Incipient chronic traumatic encephalopathy in active American football players: neuropsychological assessment and brain perfusion measures

Neurological Sciences - Chronic traumatic encephalopathy (CTE) is a degenerative disease caused by repetitive traumatic brain injury (TBI). Because CTE can be definitely diagnosed only post-mortem,...     

The Role of Robot-assisted Radical Prostatectomy and Pelvic Lymph Node Dissection in the Management of High-risk Prostate Cancer: A Systematic Review

Context

The role of robot-assisted radical prostatectomy (RARP) for men with high-risk (HR) prostate cancer (PCa) has not been well studied.

Objective

To evaluate the indications for surgical treatment, technical aspects such as nerve sparing (NS) and lymph node dissection (LND), and perioperative outcomes of men with HR PCa treated with RARP.

Evidence acquisition

A systematic expert review of the literature was performed in October 2012, searching the Medline, Web of Science, and Scopus databases. Studies with a precise HR definition, robotic focus, and reporting of perioperative and pathologic outcomes were included.

Evidence synthesis

A total of 12 papers (1360 patients) evaluating RARP in HR PCa were retrieved. Most studies (67%) used the D’Amico classification for defining HR. Biopsy Gleason grade 8–10 was the most frequent HR identifier (61%). Length of follow-up ranged from 9.7 to 37.7 mo. Incidence of NS varied, although when performed did not appear to compromise oncologic outcomes. Extended LND (ELND) revealed positive nodes in up to a third of patients. The rate of symptomatic lymphocele after ELND was 3%. Overall mean operative time was 168 min, estimated blood loss was 189 ml, length of hospital stay was 3.2 d, and catheterization time was 7.8 d. The 12-mo continence rates using a no-pad definition ranged from 51% to 95% with potency recovery ranging from 52% to 60%. The rate of organ-confined disease was 35%, and the positive margin rate was 35%. Three-year biochemical recurrence–free survival ranged from 45% to 86%.

Conclusions

Although the use of RARP for HR PCa has been relatively limited, it appears safe and effective for select patients. Short-term results are similar to the literature on open radical prostatectomy. Variability exists for NS and the template of LND, although ELND improves staging and removes a higher number of metastatic nodes. Further study is required to assess long-term outcomes.     

Using Protamine Can Significantly Reduce the Incidence of Bleeding Complications after Carotid Endarterectomy without Increasing the Risk of Ischemic Cerebral Events

Background

Controversy persists regarding the use of protamine sulfate (PS) during carotid endarterectomy (CEA), chiefly because of conflicting experiences reporting both less bleeding and a higher stroke risk. The goal of the present study was to test the hypothesis that reversing heparin with PS after CEA significantly reduces the incidence of bleeding complications without increasing the risk of postoperative stroke.

Methods

From January 2010 to December 2012 all consecutive patients undergoing CEA under general anesthesia at our institution received 5,000 U of heparin prior to carotid clamping, which was partially (half-dose) reversed with PS 25 mg immediately after declamping (group I). Heparinization had never been reversed with PS in earlier CEAs performed from 1998 to 2009 at the same institution (group II). All patients were assessed preoperatively and postoperatively by a neurologist, and cerebral magnetic resonance imaging was performed in all group I patients to exclude any silent cerebral infarction. End points of the study were bleeding complications, perioperative (30-day) stroke, and death.

Results

Overall, 219 CEAs (201 patients) were performed in group I, and 1,458 CEAs (1,294 patients) in group II. Demographics, risk factors, and preoperative antiplatelet medication were comparable in the two groups. The incidence of adverse events (group I vs group II) was as follows: stroke (0 vs 0.5 % [8/1,458], p = 0.27); death (0 vs 0 %); neck bleeding (0 vs 8.2 % [120/1,458], p < 0.001).

Conclusions

The results of the present study demonstrate that (1) partially neutralizing heparin with PS after CEA can significantly reduce the risk of bleeding complications, and (2) there is no association between the administration of PS and the incidence of postoperative stroke.