Surgical outcome of anatomical endoscopic enucleation of the prostate: A systemic review and meta-analysis

An increasing number of evidences demonstrate the safety and efficacy of endoscopic enucleation of the prostate (EEP) using various energy devices. We performed a systemic literature search for all relevant randomised controlled trials (RCTs) comparing any EEP technique with TURP or open prostatectomy (OP). A total of 21 RCTs with 2,957 patients were included; the majority were studies of holmium laser or bipolar diathermy. Compared to TURP, EEP resulted in greater improvement in IPSS (MD: −0.56, 95% CI: −0.90 to −0.23), PVR (MD: −2.24, 95% CI: −4.45 to −0.03) and Qmax (MD: −1.07, 95% CI: −1.53 to −0.61). EEP was associated with more prostate tissue removed (MD: −9.73, 95% CI: −15.71 to −3.75), less haemoglobin loss (MD: −0.47, 95% CI: −0.70 to −0.23), shorter catheterisation time (MD: −22.82, 95% CI: −30.11 to −15.52) and shorter length of hospitalisation (MD: −1.05, 95% CI: −1.33 to −0.78). Compared to OP, EEP resulted in equivalent functional outcomes. However, EEP was associated with less haemoglobin loss (MD: −1.17, 95% CI: −1.98 to −0.37), shorter catheterisation time (MD: −89.74, 95% CI: −112.60 to −66.88) and shorter length of hospitalisation (MD: −3.91, 95% CI: −4.63 to −3.60). The current evidence supports that EEP can be considered as a new standard of the surgical management for BPH.     

PLXND1/SEMA3E Promotes Epithelial–Mesenchymal Transition Partly via the PI3K/AKT-Signaling Pathway and Induces Heterogenity in Colorectal Cancer

Annals of Surgical Oncology - Colorectal cancer (CRC) is a major cause of cancer-related deaths. Metastasis is enhanced through epithelial-mesenchymal transition (EMT), a process primarily induced...     

EGFL7 as a novel therapeutic candidate regulates cell invasion and anoikis in colorectal cancer through PI3K/AKT signaling pathway

International Journal of Clinical Oncology - Anoikis is a form of apoptosis, which inhibits metastatic cascade and deprives cancer cells with invasive capacity. Epidermal growth factor-like...     

Balloon‐occluded retrograde transvenous obliteration for recurrent fundal gastric variceal bleeding in an adolescent

Gastric variceal bleeding is associated with high morbidity and mortality. Balloon‐occluded retrograde transvenous obliteration is a relatively new treatment used to control bleeding gastric varices that involves transvenous sclerosis of gastric varices through a spontaneous gastrorenal shunt. Here, we report on a 14‐yr‐old patient that underwent balloon‐occluded retrograde transvenous obliteration for refractory bleeding fundal varices in the setting of esophageal varices and cirrhosis, which did not respond to medical management or endoscopic injection. This case report serves as a reminder that balloon‐occluded retrograde transvenous obliteration can successfully control fundal variceal bleeding in pediatric patients and may serve as a bridge to liver transplantation.     

Combinatorial biosynthesis of novel antibiotics related to daptomycin

Daptomycin, a cyclic lipopeptide produced by Streptomyces roseosporus, is the active ingredient of Cubicin (daptomycin-for-injection), a first-in-class antibiotic approved for treatment of skin and skin-structure infections caused by Gram-positive pathogens and bacteremia and endocarditis caused by Staphylococcus aureus, including methicillin-resistant strains. Genetic engineering of the nonribosomal peptide synthetase (NRPS) in the daptomycin biosynthetic pathway was exploited for the biosynthesis of novel active antibiotics. lambda-Red-mediated recombination was used to exchange single or multiple modules in the DptBC subunit of the NRPS to modify the daptomycin cyclic peptide core. We combined module exchanges, NRPS subunit exchanges, inactivation of the tailoring enzyme glutamic acid 3-methyltransferase, and natural variations of the lipid tail to generate a library of novel lipopeptides, some of which were as active as daptomycin against Gram-positive bacteria. One compound was more potent against an Escherichia coli imp mutant that has increased outer membrane permeability. This study established a robust combinatorial biosynthesis platform to produce novel peptide antibiotics in sufficient quantities for antimicrobial screening and drug development.     

Binding and uptake of cationic lipid:pDNA complexes by polarized airway epithelial cells

To better understand the barriers associated with cationic lipid-mediated gene transfer to polarized epithelial cells, Fischer rat thyroid (FRT) cells and polarized normal human bronchial epithelial (NHBE) cells grown on filter supports at an air-liquid interface were used to study the binding and uptake of cationic lipid:plasmid DNA (pDNA) complexes. The efficiencies of binding and uptake of cationic lipid:pDNA complexes by these cell systems were monitored using fluorescence microscopy of fluorescently tagged lipid or pDNA probes. Fluorescent probe bound to the cell surface was differentiated from internalized probe by adding trypan blue, which quenched the fluorescence of bound but not internalized probes. For proliferating cells, binding and internalization of the cationic lipid:pDNA complexes were determined to be efficient. In contrast, little binding or internalization of the complexes was observed using polarized epithelial cells. However, after aspirating a small area of cells from the filter support, virtually all of the cells adjoining this newly formed edge bound and internalized the cationic lipid:pDNA complexes. To determine if their uptake in edge cells was related to the ability of the complexes to access the basolateral membranes of these cells, the binding and uptake of complexes was monitored in polarized NHBE cells that had been pretreated with EGTA or Ca2+-free media, strategies known to disrupt tight junctions. Cells treated in this manner bound and internalized cationic lipid:pDNA complexes efficiently and also expressed significant levels of transgene product. Control cells with intact tight junctions neither bound complexes nor expressed significant transgene product. These data confirm and extend earlier observations that the polarized apical membranes of airway epithelial cells are resistant to transfection by lipid:pDNA complexes. Further, in contrast to previous studies that have shown the entry step of complexes is not an important barrier for COS and HeLa cells, binding and entry of complexes in polarized NHBE cells appear to be rate limiting. These findings suggest that strategies designed to open the tight junctions of polarized epithelial cells may improve gene delivery to these cells for diseases such as cystic fibrosis (CF).     

Plasma Protein Growth Arrest�CSpecific 6 Levels Are Associated With Altered Glucose Tolerance, Inflammation, and Endothelial Dysfunction

OBJECTIVE

Plasma protein growth arrest–specific 6 (Gas6) is important to the inflammatory process and is involved in the development of diabetic renal and vascular complications. We set out to determine whether plasma Gas6 levels are associated with altered glucose tolerance, insulin sensitivity, inflammation, and endothelial dysfunction.

RESEARCH DESIGN AND METHODS

A total of 278 adults, including 96 with normal glucose tolerance (NGT), 82 with impaired glucose tolerance (IGT), and 100 with type 2 diabetes were recruited. Plasma Gas6 concentration and biochemical, proinflammatory, and endothelial variables were determined. Insulin sensitivity was examined by homeostasis model assessment.

RESULTS

Plasma Gas6 concentration was significantly lower among patients with type 2 diabetes compared with subjects with NGT (P < 0.001). The plasma Gas6 value was inversely correlated with fasting glucose, tumor necrosis factor (TNF)-α, interleukin (IL)-6, and vascular cell adhesion molecule (VCAM)-1. In multivariate logistic regression analysis, after adjustment for established diabetes risk factors, higher plasma Gas6 concentrations were significantly associated with a decreased risk of type 2 diabetes. Moreover, the association became slightly stronger after further adjustment for TNF-α, IL-6, high-sensitive C-reactive protein, E-selectin, intercellular adhesion molecule-1, and VCAM-1.

CONCLUSIONS

Plasma Gas6 is associated with altered glucose tolerance, inflammation, and endothelial dysfunction. It also may represent a novel independent risk factor of type 2 diabetes and a potential surrogate marker of inflammation and endothelial dysfunction.The epidemic of type 2 diabetes and impaired glucose tolerance (IGT) is one of the main causes of morbidity and mortality worldwide (1). In both disorders, tissues such as muscle, fat, liver, and endothelial cells become less responsive or, in some cases, resistant to insulin (2). Although it is well established that insulin resistance and impaired insulin secretion are central to the pathogenesis of type 2 diabetes, it has been unclear how these abnormalities arise and how they are related to many different clinical and biochemical features common in type 2 diabetes, including central obesity, hypertension, accelerated atherosclerosis, chronic inflammation, dyslipidemia, and disordered hemostasis.Protein growth arrest–specific 6 (Gas6) was the last addition to the family of plasma vitamin K–dependent proteins. Gas6 was cloned and characterized in 1993 and found to be similar to plasma anticoagulant protein S (3). Soon after, it was recognized as a growth factor–like molecule, as it interacted with receptor tyrosine kinases of the TAM (Tyro-3, Axl, Mer) family (4). The Gas6/TAM system regulates an intriguing mix of processes, including cell survival and proliferation, cell adhesion and migration, blood clot stabilization, and inflammatory cytokine release (5–8). Therefore, the role of the Gas6/TAM system has been found to be important in inflammation; hemostasis; autoimmune disease; nervous, reproductive, and vascular systems; and cancer (9).Recently, several reports (10–12) revealed that the Gas6/TAM system was involved in the pathogenesis of diabetic renal and vascular disease. Expression of Gas6/TAM was increased in the glomerulus of diabetic rats, which led to mesangial and glomerular hypertrophy (10). In vascular smooth muscle cells (VSMCs), Gas6/TAM signaling increased cell survival in the presence of low glucose and increased cell migration in the presence of high glucose (11). VSMC migration was increased in patients with diabetes, and diabetes accelerated the accumulation of VSMCs in atherosclerotic lesions (12). These preclinical studies indicate that Gas6/TAM likely represents an important pathogenic mechanism for renal and cardiovascular complications associated with diabetes. However, little is known about the clinical significance of the Gas6/TAM system in patients with diabetes and its association with various biochemical variables that are common in diabetic patients. We have addressed this issue by conducting a cross-sectional study to determine whether plasma Gas6 levels are associated with altered glucose tolerance, insulin sensitivity, inflammatory, and endothelial dysfunction markers in humans.     

A-61827 (A-60969), a new fluoronaphthyridine with activity against both aerobic and anaerobic bacteria.

A-61827 (A-60969 is the hydrochloric salt of A-61827) is a new aryl-fluoronaphthyridine which is active against aerobic and anaerobic bacteria. The MICs of A-61827 for 90% of strains (MIC90) of staphylococci and streptococci were less than or equal to 1 microgram/ml and were generally 1 to 4 twofold dilutions less than those of ciprofloxacin for these bacteria. The MIC90S of A-61827 for members of the family Enterobacteriaceae and Pseudomonas aeruginosa were also less than or equal to 1 microgram/ml. Ciprofloxacin was 1 to 3 twofold dilutions more active than A-61827 against these gram-negative bacteria. Neisseria gonorrhoeae, Campylobacter jejuni, and Haemophilus influenzae were susceptible to less than 0.06 microgram of A-61827 per ml. The MIC90 of A-61827 for Legionella pneumophila was 0.25 microgram/ml. A-61827 was as potent or 1 to 2 twofold dilutions more potent than ciprofloxacin against these organisms. The MIC90 of A-61827 for all anaerobic bacteria was less than or equal to 4 micrograms/ml compared with less than or equal to 32 micrograms/ml for ciprofloxacin. In mouse protection tests, A-61827 was as active as ciprofloxacin against Escherichia coli, P. aeruginosa, and Salmonella typhimurium and 5 to 10 times more active than ciprofloxacin against Staphylococcus aureus and Streptococcus pyogenes. A-61827 was as active as ciprofloxacin against P. aeruginosa in a mouse pyelonephritis model and more active than ciprofloxacin and metronidazole in a mouse Bacteroides fragilis abscess model. After oral administration of 100 mg/kg to mice, the peak concentrations of A-61827 and ciprofloxacin in serum were 2.3 and 2.4 micrograms/ml and the half-lives in serum were 3.9 and 1.2 h, respectively.