Effects of renin-angiotensin system blockers on renal outcomes and all-cause mortality in patients with diabetic nephropathy: an updated meta-analysis

BackgroundIn contrast to previous studies, recent data questioned the ability of renin-angiotensin-aldosterone system (RAAS) blockers to delay progression of diabetic nephropathy. This study evaluated the effect of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin-receptor blockers (ARBs) in patients with diabetic nephropathy.MethodsA systematic literature search of MEDLINE/PubMed and EMBASE databases was performed to identify randomized trials published up to June 2007 comparing the effects of ACEIs or ARBs with placebo and/or a regimen not including a RAAS blocker on the incidence of end-stage renal disease (ESRD), doubling of serum creatinine (DSC), or death from any cause in patients with diabetic nephropathy. Treatment effects were summarized as relative risks (RRs) using the Mantel-Haenszel fixed-effects model.ResultsOf the 1,028 originally identified studies, 24 fulfilled the inclusion criteria (20 using ACEIs and 4 using ARBs). Use of ACEIs was associated with a trend toward reduction of ESRD incidence (RR 0.70; 95% confidence interval (CI) 0.46-1.05) and use of ARBs with significant reduction of ESRD risk (RR 0.78; 95% CI 0.67-0.91). Both drug classes were associated with reduction in the risk of DSC (RR 0.71; 95% CI 0.56-0.91 for ACEIs and RR 0.79; 95% CI 0.68-0.91 for ARBs) but none affected all-cause mortality (RR 0.96; 95% CI 0.85-1.09 for ACEIs and RR 0.99; 95% CI 0.85-1.16 for ARBs).ConclusionTreatment of patients with diabetic nephropathy with a RAAS blocker reduces the risks of ESRD and DSC, but does not affect all-cause mortality. These findings are added to the evidence of a renoprotective role of RAAS blockers in such patients.American Journal of Hypertension (2008). doi:10.1038/ajh.2008.206American Journal of Hypertension (2008); 21, 8, 922-929. doi:10.1038/ajh.2008.206.     

The vicious circle between physical,psychological, and physiological characteristics of shift work in nurses: a multidimensional approach

Sleep and Breathing - To compare physical, psychological, and physiological adaptations between rotating and morning shift health workers using objective and subjective approaches. Forty nurses...     

Effects of Strength vs. Ballistic-Power Training on Throwing Performance

The purpose of the present study was to investigate the effects of 6 weeks strength vs. ballistic-power (Power) training on shot put throwing performance in novice throwers. Seventeen novice male shot-put throwers were divided into Strength (N = 9) and Power (n = 8) groups. The following measurements were performed before and after the training period: shot put throws, jumping performance (CMJ), Wingate anaerobic performance, 1RM strength, ballistic throws and evaluation of architectural and morphological characteristics of vastus lateralis. Throwing performance increased significantly but similarly after Strength and Power training (7.0-13.5% vs. 6.0-11.5%, respectively). Muscular strength in leg press increased more after Strength than after Power training (43% vs. 21%, respectively), while Power training induced an 8.5% increase in CMJ performance and 9.0 - 25.8% in ballistic throws. Peak power during the Wingate test increased similarly after Strength and Power training. Muscle thickness increased only after Strength training (10%, p < 0.05). Muscle fibre Cross Sectional Area (fCSA) increased in all fibre types after Strength training by 19-26% (p < 0.05), while only type IIx fibres hypertrophied significantly after Power training. Type IIx fibres (%) decreased after Strength but not after Power training. These results suggest that shot put throwing performance can be increased similarly after six weeks of either strength or ballistic power training in novice throwers, but with dissimilar muscular adaptations.

Key points

• Ballistic-power training with 30% of 1RM is equally effective in increasing shot put performance as strength training, in novice throwers, during a short training cycle of six weeks.
• In novice shot putters with relatively low initial muscle strength/mass, short-term strength training might be more important since it can increase both muscle strength and shot put performance.
• The ballistic type of power training resulted in a significant increase of the mass of type IIx muscle fibres and no change in their proportion. Thus, this type of training might be used effectively during the last weeks before competition, when the strength training load is usually reduced, in order to increase muscle power and shot put performance in novice shot putters.

Key words: Shot put, muscle fibres, ultrasound, ballistic training, muscle mass.     

Poly(N,N‐dimethylacrylamide)‐block‐Poly(L‐lysine) Hybrid Block Copolymers: Synthesis and Aqueous Solution Characterization

Four poly(N,N‐dimethylacrylamide)‐block‐poly(L ‐lysine) (PDMAM‐block‐PLL) hybrid diblock copolymers and two PLL homo‐polypeptides are prepared via ROP of ε‐trifluoroacetyl‐L ‐lysine N‐carboxyanhydride initiated by primary amino‐terminated PDMAM and n‐hexylamine respectively. The PLL blocks render the copolymers a multi‐responsive behavior in aqueous solution due to their conformational transitions from random coil to α‐helix with increasing pH, and from α‐helix to β‐sheet upon heating. The random coil‐to‐α‐helix transition is found to depend on the PLL length: the longer the peptide segment, the more readily the transition occurred. The same trend was observed for the α‐helix‐to‐β‐sheet transition, which was found to be inhibited for short polypeptides unless conjugated with the PDMAM block.

     

Modified CLSI Extended-Spectrum β-Lactamase (ESBL) Confirmatory Test for Phenotypic Detection of ESBLs among Enterobacteriaceae Producing Various β-Lactamases

The worldwide dissemination of Enterobacteriaceae producing AmpC β-lactamases and carbapenemases makes difficult the phenotypic detection of extended-spectrum β-lactamases (ESBLs), as they may be masked by these additional enzymes. A modification of the CLSI ESBL confirmatory test was developed and evaluated in a comparative study for its ability to successfully detect ESBLs among Enterobacteriaceae producing various carbapenemases (Klebsiella pneumoniae carbapenemase [KPC], VIM, NDM, and OXA-48) and plasmidic or derepressed AmpCs. The modified CLSI ESBL confirmatory test was performed with cefotaxime and ceftazidime disks with and without clavulanate, on which both boronic acid (BA) and EDTA were dispensed. A total of 162 genotypically confirmed ESBL-positive Enterobacteriaceae isolates (83 carbapenemase/ESBL producers, 25 AmpC/ESBL producers, and 54 ESBL-only producers) were examined. For comparison, 139 genotypically confirmed ESBL-negative Enterobacteriaceae isolates (94 of them possessed carbapenemases and 20 possessed AmpCs) were also tested. The standard CLSI ESBL confirmatory test was positive for 106 of the 162 ESBL producers (sensitivity, 65.4%) and showed false-positive results for 4 of the 139 non-ESBL producers (specificity, 97.1%). The modified CLSI ESBL confirmatory test detected 158 of 162 ESBL producers (sensitivity, 97.5%) and showed no false-positive results for non-ESBL producers (specificity, 100%). The findings of the study demonstrate that the modified CLSI ESBL confirmatory test using antibiotic disks containing both BA and EDTA accurately detects ESBLs in Enterobacteriaceae regardless of the coexistence of additional β-lactam resistance mechanisms.     

Development of HLA-matched vascular grafts utilizing decellularized human umbilical artery

Worldwide, there is a great need of small diameter vascular grafts that can be used in human disorders such as cardiovascular and peripheral vascular disease. Until now, severe adverse reactions are caused from the use of synthetic or animal derived grafts, while the use of autologous vessels is restricted only in a small number of patients. The limited availability of the vessels might be resolved by the use of HLA-matched vascular grafts utilizing the decellularized human umbilical arteries. In this study, human umbilical arteries were decellularized and then repopulated with Mesenchymal Stem Cells. The HLA-genotype of the repopulated grafts, analyzed by Next Generation Sequencing technology, indicated their successful production. The HLA-matched vascular grafts could be generated efficiently and might be used in personalized medicine.     

Use of Boronic Acid Disk Tests To Detect Extended- Spectrum β-Lactamases in Clinical Isolates of KPC Carbapenemase-Possessing Enterobacteriaceae

We evaluated boronic acid (BA)-based methods for their ability to detect extended-spectrum β-lactamases (ESBLs) among clinical isolates of KPC-producing members of the Enterobacteriaceae family. A total of 155 isolates of Klebsiella pneumoniae (n = 141), Escherichia coli (n = 6), Enterobacter aerogenes (n = 6), and Klebsiella oxytoca (n = 2) genotypically confirmed to be KPC producers were analyzed. As many as 118 isolates harbored ESBLs (103 harbored SHV-type ESBLs, 13 harbored CTX-M-type ESBLs, and 2 harbored both SHV- and CTX-M-type ESBLs); the remaining 37 isolates were genotypically negative for ESBL production. The CLSI ESBL confirmatory test was positive for 79 of the 118 ESBL producers (sensitivity, 66.9%), while all 37 non-ESBL producers were negative (specificity, 100%). When a ≥5-mm increase in the zone diameter of either the cefotaxime (CTX)-clavulanate (CA) or the ceftazidime (CAZ)-CA disks containing BA compared with the zone diameter of the CTX or CAZ disks containing BA was considered to be a positive result for ESBL production, the method detected all 118 ESBL producers (sensitivity, 100%) and showed no false-positive results for non-ESBL producers (specificity, 100%). Double-disk synergy tests, in which disks of CTX, CAZ, aztreonam, or cefepime in combination with BA were placed at distances of 20, 25, and 30 mm (center to center) from a disk containing amoxicillin (amoxicilline)-clavulanate-BA, were able to detect 116 (98.3%), 101 (85.6%), and 28 (23.7%) of the ESBL-positive isolates, respectively; no false-positive results for non-ESBL-producing isolates were detected. Our results demonstrate that the modified CLSI ESBL confirmatory test with antibiotic disks containing BA is the most accurate phenotypic method for the detection of ESBLs in Enterobacteriaceae producing KPC carbapenemases.During the last decade, carbapenem resistance has emerged among clinical isolates of the Enterobacteriaceae family, and this is increasingly attributed to the production of β-lactamases capable of hydrolyzing carbapenems (23). Among these enzymes, a new type of Ambler class A β-lactamase, the Klebsiella pneumoniae carbapenemase (KPC), has been rapidly spreading among K. pneumoniae isolates and other Enterobacteriaceae in the northeastern regions of the United States and has now spread to several regions of North and South America, as well as in Israel, China, and Greece (2, 13, 16, 21).The current spread of KPC enzymes makes them a potential threat to currently available antibiotic-based treatments. These enzymes confer various levels of resistance to all β-lactams, including carbapenems, even though cefamycins and ceftazidime are only weakly hydrolyzed (15, 18). KPC-possessing strains frequently carry extended-spectrum β-lactamase (ESBL) genes (1, 3, 8, 13, 24), which could possibly contribute to the expression and dissemination of the β-lactam resistance trait (8, 18, 21). It should be also noted that KPCs and ESBLs are mostly plasmid-encoded determinants that can easily disseminate to other enterobacterial strains (3, 7, 15, 18, 26). Therefore, the phenotypic detection of ESBLs in KPC-producing isolates of the Enterobacteriaceae is of potential interest for epidemiological purposes as well as for limiting the spread of the underlying resistance mechanisms.The CLSI recommends a phenotypic confirmatory test for ESBL production that consists of measuring the growth-inhibitory zones around both cefotaxime (CTX) and ceftazidime (CAZ) disks with or without clavulanate (CA) for K. pneumoniae, Klebsiella oxytoca, Escherichia coli, and Proteus mirabilis (4). Different double-disk synergy tests (DDSTs) based on the synergy of amoxicillin (amoxicilline)-clavulanate (AMC) with extended-spectrum cephalosporins and aztreonam have also been extensively used for the detection of ESBLs (7). However, strategies for the laboratory identification of ESBLs need to be reviewed and adjusted as additional mechanisms of resistance to β-lactams coexist in enterobacterial strains (7). KPCs hydrolyze several β-lactam antibiotics, and hence, the presence of an ESBL can be masked by the expression of a KPC. Moreover, the weak inhibition of KPCs by the β-lactam inhibitors (15, 18, 30) may interfere with the interpretation of ESBL detection methods and KPC enzymes may be mistaken for ESBLs. Thus, there is a need to accurately detect ESBLs in the presence of coexisting KPC expression.Boronic acid (BA) compounds were recently reported to be reversible inhibitors of KPCs (6, 16, 27). In particular, we have shown that BA disk assays are considered positive for the detection of the KPC enzyme when the growth-inhibitory zone diameter around a meropenem, imipenem, or cefepime disk with phenylboronic acid is 5 mm or greater of the growth-inhibitory zone diameter around the disk containing meropenem or cefepime alone (27). The results of this study also showed that BA affected the activity of CAZ in ESBL-negative KPC-producing isolates but not in SHV ESBL-positive KPC-producing isolates, most likely due to the presence of the SHV ESBL, which is not restrained by BA (27). BA-based tests with disks of CAZ and CTX have also been successfully employed for the identification of ESBLs in AmpC producers (11, 25). These observations led us to design a modified CLSI ESBL confirmatory test using antibiotic disks containing BA as well as different DDSTs employing BA for the accurate detection of ESBLs in KPC-producing enterobacterial isolates.     

IGF-I and NGFβ enhance in vitro progressive motility and vitality of human spermatozoa

Purpose

Progressive motility (PM) and vitality are positively associated with fertilization ability of spermatozoa. Here, the effects of IGF-I and NGFβ on PM and vitality of human spermatozoa were investigated.

Methods

Forty-three volunteers gave semen samples after 2-3 days of sexual abstinence. Each sample was processed with density gradient centrifugation and sperm washing. The pellet was divided into 3 aliquots. An aliquot containing one million of progressively motile spermatozoa was incubated for an hour (37°C) in standard culture medium (control group), and two aliquots with the same number of progressively motile spermatozoa were incubated in medium supplemented with IGF-I or NGFβ. Two concentrations of IGF-I (100 ng/ml and 1000 ng/ml) and NGFβ (0,5 ng/ml and 5 ng/ml) were tested.

Results

Both growth factors significantly increased PM and vitality in comparison with control either at the low or the high concentration. IGF-I seemed to be more effective than NGFβ. The effects did not seem to be dose dependent with the exception of the effect of IGF-I on vitality.

Conclusions

The enhancement of PM and vitality of human spermatozoa by IGF-I and NGFβ opens new ways for the improvement of sperm processing. Further research is needed to determine the most effective concentrations.