PDE5 inhibition against acute renal ischemia reperfusion injury in rats: does vardenafil offer protection?

Purpose

To evaluate the effect of vardenafil on renal function after renal ischemia–reperfusion (IR) injury (IRI) in a rat model.

Materials and methods

Seventy-one Wistar rats were divided into 7 groups including (1) a vehicle-treated group, (2) a vehicle pretreated-IR group, (3–6) vardenafil pretreated-IR groups in doses of 0.02, 0.2, 2 and 20 μg/kg, respectively, (7) a group of IR followed by treatment with 2 μg/kg of vardenafil. Vardenafil or vehicle solution was administered one hour before unilateral nephrectomy and the induction of 45 min of ischemia on the contralateral kidney by clamping of renal pedicle. Four hours of reperfusion were allowed after renal ischemia. Studied parameters were serum creatinine, fractional excretion of sodium (FENa), and histological evaluation of renal specimens. In addition, renal tissue cGMP levels, ERK1/2 phosphorylation as well as renal function by renal scintigraphy were also evaluated.

Results

Administration of vardenafil before the induction of ischemia resulted in a significant reduction in creatinine and FENa levels as well as in less histological lesions observed in treated kidneys in comparison with the vehicle-treated group. The underlying mechanism of cytoprotection was cGMP depended and involved the phosphorylation of ERK proteins. Renal scintigraphy confirmed that PDE5 inhibition attenuates renal IRI.

Conclusions

Vardenafil attenuates renal IRI. Based on similar results from relevant studies on other PDE-5 inhibitors in renal and cardiac IRI, it can be assumed that all PDE-5 inhibitors share a common mechanism of cytoprotection.     

Blood Utilization After Primary Total Joint Arthroplasty in a Large Hospital Network

Background

Since a study in orthopedic hip fracture patients demonstrated that a liberal hemoglobin (Hb) threshold does not improve patient morbidity and mortality relative to a restrictive Hb threshold, the standard of care in total joint arthroplasty (TJA) should be examined to understand the variability of red blood cell (RBC) transfusion following TJA.

Questions/purposes

The study aimed to answer the following questions: (1) What is the blood utilization rate after primary TJA for individual surgeons within a large hospital network? (2) What is the comparison of hospital charges, length of stay (LOS), and discharge locations among TJA patients who were and were not transfused?

Methods

A retrospective study was conducted on 3,750 primary total knee arthroplasties (TKAs) and 2,070 primary total hip arthroplasties (THAs), and data was retrospectively collected over a 15-month period on the number of RBCs transfused per patient, along with demographic and cost details. The number of patients who received at least 1 RBC unit and the number of RBCs transfused per patient was calculated and stratified by surgeon.

Results

In the postoperative period, 19.3% TKA patients and 38.5% THA patients received a RBC transfusion. Transfusion rates following TJA varied widely between surgeons (TKA 4.8–63.8%, THA 4.3–86.8%). Transfused TKA patients received an average of 1.65 ± 0.03 RBCs, and THA patients received an average of 1.97 ± 0.14 RBCs. LOS and hospital charges for blood transfusion patients were higher than nontransfused patients.

Conclusion

Blood utilization after primary TJA varies greatly among surgeons, suggesting that resources may be misallocated. These findings highlight the need to standardize RBC transfusion practice following TJA.

Electronic supplementary material

The online version of this article (doi:10.1007/s11420-013-9327-y) contains supplementary material, which is available to authorized users.     

Head-to-head comparison between the EQ-5D-5L and the EQ-5D-3L in general population health surveys

Background

The EQ-5D has been frequently used in national health surveys. This study is a head-to-head comparison to assess how expanding the number of levels from three (EQ-5D-3L) to five in the new EQ-5D-5L version has improved its distribution, discriminatory power, and validity in the general population.

Methods

A representative sample (N?=?7554) from the Catalan Health Interview Survey 2011–2012, aged ≥18, answered both EQ-5D versions, and we evaluated the response redistribution and inconsistencies between them. To assess validity of this redistribution, we calculated the mean of the Visual Analogue Scale (VAS), which measures perceived health. The discriminatory power was examined with Shannon Indices, calculated for each dimension separately. Spanish preference value sets were applied to obtain utility indices, examining their distribution with statistics of central tendency and dispersion. We estimated the proportion of individuals reporting the best health state in EQ-5D-5L and EQ-5D-3L within groups of specific chronic conditions and their VAS mean.

Results

A very small reduction in the percentage of individuals with the best health state was observed, from 61.8% in EQ-5D-3L to 60.8% in EQ-5D-5L. In contrast, a large proportion of individuals reporting extreme problems in the 3 L version moved to severe problems (level 4) in the 5 L version, particularly for pain/discomfort (75.5%) and anxiety/depression (66.4%). The average proportion of inconsistencies was 0.9%. The pattern of the perceived health VAS mean confirmed the hypothesis established a priori, supporting the validity of the observed redistribution. Shannon index showed that absolute informativity was higher in the 5 L version for all dimensions. The means (SD) of the Spanish EQ-5D-3L and EQ-5D-5L indices were 0.87 (0.25) and 0.89 (0.22). The proportion of individuals with the best health state within each specific chronic condition was very similar, regardless of the EQ-5D version (≤?30% in half of the 28 chronic conditions).

Conclusion

Although the proportion of individuals with the best possible health state is still very high, our findings support that the increase of levels provided by the EQ-5D-5L contributed to the validity and discriminatory power of this new version to measure health in general population, as in the national health surveys.

     

A comparative study on subacute toxicity of arsenic trioxide and dimethylarsinic acid on antioxidant status in Crandell Rees feline kidney (CRFK), human hepatocellular carcinoma (PLC/PRF/5), and epithelioma papulosum cyprini (EPC) cell lines

Arsenic (As) is a global contaminant of terrestrial and aquatic environments posing concern for environmental and human health. The effects of subacute concentrations of arsenic trioxide (As^III) and dimethylarsinic acid (DMA^V) were examined using Crandell Rees feline kidney (CRFK), human hepatocellular carcinoma (PLC/PRF/5), and epithelioma papulosum cyprini (EPC). Whole monolayer with suffering cells (confluence 100%, pyknosis and refractive cells; value scale = 2) led to identification of subacute As concentrations for the three cell lines. The selected As^III concentrations were 1.33 µM for CRFK and 33.37 µM for PLC/PRF/5 and EPC, at 48 hr time point. The selected DMA^V concentrations were 0.67 mM for PLC/PRF/5, 1.33 mM for CRFK, and 2.67 mM for EPC for 48 hr. Unlike the As^III test, the three cell lines did not exhibit marked susceptibility to DMA^V-mediated toxicity. Several oxidative stress biomarker levels, directly or indirectly associated with reactive oxygen species (ROS) elimination including superoxide dismutase, catalase, glutathione peroxidases, glutathione reductase, glutathione S-transferase, glyoxalase I, glyoxalase II, and total glutathione, were determined in the three cell lines at 24 and 48 hr. Antioxidant responses in metal-treated cells were significantly altered compared to controls, suggesting a perturbation of redox state. The weakening of antioxidant pathway in either healthy or tumoral cells was greater using As^III than DMA^V. Differences in level of several oxidative stress biomarkers suggest that the oxidative stress mechanism induced by As^III is distinctly different from DMA^V. Multifaceted mechanisms of action underlying ROS generation in tumor and nontumor cells versus As^III and DMA^V exposure are thus involved. Since As-mediated toxicity is quite complex, more data regarding both oxidant-enhancement and oxidant-lowering strategies may be useful to improve knowledge regarding the influence of As on human and animal cells.     

Serum Retinol,Folic Acid,and Copper Are Associated With Sperm Abnormalities in Men With Obesity

Background and objectives: Micronutrients may influence the development and differentiation of sperm cells. The aim of this study was to assess the possible association of deficiencies in several vitamins and trace elements with sperm abnormalities in men with obesity.

Participants and methods: Thirty male patients with moderate to severe obesity and ten lean controls who gave written informed consent were included. Anthropometric parameters were recorded. Hormonal and lipid profiles were analyzed, as well as serum concentrations of zinc, copper, retinol, α-tocopherol, 25-hydroxyvitamin D, cobalamin, and folic acid. For sperm analysis, we used the reference values proposed by the World Health Organization.

Results: Fourteen of the thirty men (47%) presented abnormal sperm results. The most common abnormality was low motility in 33% of them, followed by low sperm concentration in 27% of the patients. Patients with abnormal sperm results showed lower serum folic acid (p = 0.005) and higher serum estradiol (p = 0.015) and copper (p = 0.033) than lean controls. The ejaculate volume inversely correlated with body mass index (BMI; r = ?0.378, p = 0.016) and serum estradiol (r = ?0.328, p = 0.041). Total number of sperm correlated inversely with BMI (r = ?0.428, p = 0.006) and serum estradiol (r = ?0.507, p = 0.001) and positively with serum folic acid (r = 0.356, p = 0.026) and retinol (r = 0.421, p = 0.009). Total motility of sperm inversely correlated with BMI (r = ?0.433, p = 0.005), serum estradiol (r = ?0.475, p = 0.002), and copper (r = ?0.416, p = 0.012) and positively correlated with serum folic acid (r = 0.522, p = 0.001) and retinol (r = 0.350, p = 0.034).

Conclusions: Sperm abnormalities in men with obesity are associated with excess body weight and micronutrient concentrations.     

The effect of photobiomodulation using low-level laser therapy on tooth sensitivity after dental bleaching: a systematic review

Lasers in Medical Science - The authors aimed to conduct a systematic review to assess data from the current literature on the effectiveness of low-level laser therapy (LLLT) in preventing tooth...