Addressing the link between paraoxonase-1 gene variants and the incidence of early onset myocardial infarction

Introduction

The enzyme paraoxonase-1 (PON1) represents an endogenous defense mechanism against vascular oxidative stress, thereby contributing to the prevention of atherosclerosis. Several polymorphisms have been reported in the PON1 gene, including Q192R. PON1 phenotype is commonly expressed as the paraoxonase/arylesterase ratio (PON/ARE). The major aim of this study was to investigate the association between PON1 Q192R polymorphism, PON1 phenotypes and the incidence of early-onset acute myocardial infarction (AMI) in Egyptians.

Material and methods

The study subjects consisted of 102 AMI patients and 72 age-matched healthy controls. Genotyping and enzyme activities were determined using PCR-RFLP and kinetic spectrophotometric assays, respectively.

Results

The genotype distribution for the PON1 gene was significantly different between AMI patients (QQ = 38.24%, QR = 49.02%, RR = 12.75%) and controls (QQ = 66.67%, QR = 25%, RR = 8.33%). Allele frequencies were also significantly different between patients (Q = 62.75%, R = 37.25%) and controls (Q = 79.17%, R = 20.83%). The genotypes QR and RR showed higher risk for AMI compared to the homozygous QQ (odds ratio (OR) = 3.231, p < 0.001). The average PON/ARE ratio in MI patients (1.187 ±0.1) did not differ significantly from controls (1.118 ±0.26). However, it showed a significant difference among different genotypes in both AMI patients (QQ = 0.91 ±0.11, QR = 1.09 ±0.11 and RR = 2.65 ±0.4) (p = 0.0002) and controls (QQ = 0.68 ±0.1, QR = 1.07 ±0.11 and RR = 4.89 ±2.84) (p < 0.0001).

Conclusions

PON1 192R allele represents an independent risk factor for early-onset AMI in Egyptians, and PON1 Q192R polymorphism modulates the paraoxonase phenotype.     

The effects of varying poly(ethylene glycol) hydrogel crosslinking density and the crosslinking mechanism on protein accumulation in three-dimensional hydrogels

Matrix stiffness has been shown to play an important role in modulating various cell fate processes such as differentiation and cell cycle. Given that the stiffness can be easily tuned by varying the crosslinking density, poly(ethylene glycol) (PEG) hydrogels have been widely used as an artificial cell niche. However, little is known about how changes in the hydrogel crosslinking density may affect the accumulation of exogenous growth factors within 3-D hydrogel scaffolds formed by different crosslinking mechanisms. To address such shortcomings, we measured protein diffusivity and accumulation within PEG hydrogels with varying PEG molecular weight, concentration and crosslinking mechanism. We found that protein accumulation increased substantially above a critical mesh size, which was distinct from the protein diffusivity trend, highlighting the importance of using protein accumulation as a parameter to better predict the cell fates in addition to protein diffusivity, a parameter commonly reported by researchers studying protein diffusion in hydrogels. Furthermore, we found that chain-growth-polymerized gels allowed more protein accumulation than step-growth-polymerized gels, which may be the result of network heterogeneity. The strategy used here can help quantify the effects of varying the hydrogel crosslinking density and crosslinking mechanism on protein diffusion in different types of hydrogel. Such tools could be broadly useful for interpreting cellular responses in hydrogels of varying stiffness for various tissue engineering applications.     

Curcumin has a palliative action on gentamicin-induced nephrotoxicity in rats

Generation of free radicals in kidney cortex plays an important role in the pathogenesis of gentamicin (GM) nephrotoxicity, and curcumin, the yellow curry pigment isolated from turmeric, has been confirmed to have a strong antioxidant action. Therefore, in the present work, we aimed at testing the possible protective or palliative effect of curcumin on GM nephrotoxicity. Curcumin was given to rats at an oral dose of 200 mg/kg/day for 10 days, and in some of these rats GM was also injected intramuscularly at a dose of 80 mg/kg/day during the last 6 days of the treatment. Nephrotoxicity was evaluated histopathologically by light microscopy, and biochemically by measuring the concentrations of creatinine and urea in serum, and reduced glutathione (GSH) concentration and superoxide dismutase (SOD) activity in renal cortex. The concentration of GM in renal cortex was measured microbiologically. GM significantly increased the concentrations of urea and creatinine (P < 0.05) by about 111 and 97%, respectively. GM treatment reduced cortical GSH concentration by about 31% (P < 0.05), and the activity of SOD by about 27% (P < 0.05). Curcumin significantly mitigated these effects. Sections from saline and curcumin-treated rats showed apparently normal proximal tubules. However, kidneys of GM-treated rats had a moderate degree of necrosis. The degree of necrosis appeared lessened when GM was given simultaneously with curcumin. The concentration of GM in the renal cortex of the rats given GM + curcumin was significantly (P < 0.05) lower than that found in rats treated with GM alone by about 39%. The results suggested that curcumin had ameliorated the histopathological and biochemical indices of nephrotoxicity in rats. Pending further studies, curcumin may potentially be useful as a nephroprotectant agent.     

EVEREST STUDY: Efficacy and Safety of Verteporfin Photodynamic Therapy in Combination with Ranibizumab or Alone Versus Ranibizumab Monotherapy in Patients with Symptomatic Macular Polypoidal Choroidal Vasculopathy

PURPOSE:: To assess the effects of verteporfin photodynamic therapy (PDT) combined with ranibizumab or alone versus ranibizumab monotherapy in patients with symptomatic macular polypoidal choroidal vasculopathy. METHODS:: In this multicenter, double-masked, primarily indocyanine green angiography-guided trial, 61 Asian patients were randomized to verteporfin PDT (standard fluence), ranibizumab 0.5 mg, or the combination. Patients were administered with verteporfin PDT/placebo and initiated with three consecutive monthly ranibizumab/sham injections starting Day 1, and re-treated (Months 3-5) as per predefined criteria. The primary endpoint was the proportion of patients with indocyanine green angiography-assessed complete regression of polyps at Month 6. Secondary endpoints included mean change in best-corrected visual acuity at Month 6 and safety. RESULTS:: At Month 6, verteporfin combined with ranibizumab or alone was superior to ranibizumab monotherapy in achieving complete polyp regression (77.8% and 71.4% vs. 28.6%; P < 0.01); mean change ± standard deviation in best-corrected visual acuity (letters) was 10.9 ± 10.9 (verteporfin PDT + ranibizumab), 7.5 ± 10.6 (verteporfin PDT), and 9.2 ± 12.4 (ranibizumab). There were no new safety findings with either drug used alone or in combination. CONCLUSION:: Verteporfin PDT combined with ranibizumab 0.5 mg or alone was superior to ranibizumab monotherapy in achieving complete regression of polyps in this 6-month study in patients with symptomatic macular polypoidal choroidal vasculopathy. All treatments were well tolerated over 6 months.     

Analysis of Predictive Factors for Lung Injury after Forward-Planned Intensity-Modulated Radiotherapy in Whole Breast Irradiation

Purpose

This study was performed to assess frequency, timings of occurrence, and predictors of radiologic lung damage (RLD) after forward-planned intensity-modulated radiotherapy (FIMRT) for whole breast irradiation.

Methods

We retrospectively reviewed medical records of 157 breast cancer patients and each of their serial chest computed tomography (CT) taken 4, 10, 16, and 22 months after completion of breast radiotherapy (RT). FIMRT was administered to whole breast only (n=152), or whole breast and supraclavicular regions (n=5). Dosimetric parameters, such as mean lung dose and lung volume receiving more than 10 to 50 Gy (V₁₀-V₅₀), and clinical parameters were analyzed in relation to radiologic lung damage.

Results

In total, 104 patients (66.2%) developed RLD after whole breast FIMRT. Among the cases of RLD, 84.7% were detected at 4 months, and 15.3% at 10 months after completion of RT. More patients of 47 or younger were found to have RLD at 10 months after RT than patients older than the age (11.7% vs. 2.9%, p=0.01). In univariate and multivariate analyses, age >47 and V₄₀ >7.2% were significant predictors for higher risk of RLD.

Conclusion

RLD were not infrequently detected in follow-up CT after whole breast FIMRT. More detected cases of RLD among younger patients are believed to have developed at later points after RT than those of older patients. Age and V₄₀ were significant predictors for RLD after whole breast intensity-modulated radiotherapy.     

Assessment of the link between endothelin K198n Snp,endothelin concentration and acute myocardial infarction in Egyptians

The aim of the current study was to assess the link between EDN K198N SNP, ET‐1 serum concentration and acute myocardial infarction (AMI) in Egyptians. The study cohort consisted of 84 patients at AMI onset and 84 age‐matched healthy controls. Endothelin genotypes and concentrations were determined by sequencing and ELISA, respectively. Genotype distribution was not significantly different between AMI patients and controls (P=.8341). The mean serum ET‐1 concentration of patients (13.83±0.7 pg/mL) was significantly higher than controls (7.26±0.2 pg/mL) (P<.0001). ET‐1 serum concentrations did not vary significantly among various EDN genotypes in patients (P=.378) and controls (P=.6164). Hence, we conclude that EDN K198N genotypes were not related to either ET‐1 concentration or incidence of early‐onset AMI in Egyptians. But, AMI patients had higher ET‐1 concentrations than controls.     

The place of ultrasound in urogynaecology clinic

Urinary incontinence is a silent epidemic severely affecting the quality of life of women. Clinical assessment alone has been shown to be an ineffective way of assessing women with lower urinary tract dysfunction; hence, there is a need for urodynamic studies. Nevertheless, urodynamics cannot explain all the symptoms and is not always available. Ultrasound scan is becoming more useful in the field of urogynaecology. It is safe, non-invasive and acceptable technique for the patients. In this review, we explore the place of modern ultrasound in managing women attending urogynaecology clinic.     

Correlation Between Waist:Height Ratio and Serum Nitric Oxide Level in Children with Atopic Dermatitis

Atopic dermatitis (AD) is the most common chronic inflammatory disease of early childhood. This study shows that nitric oxide levels positively correlate with the clinical severity of AD, waist:height ratio, and weight.     

Study of the role of tumor necrosis factor-α (–308 G/A) and interleukin-10 (–1082 G/A) polymorphisms as potential risk factors to acute kidney injury in patients with severe sepsis using high-resolution melting curve analysis

Rational: Septic acute kidney injury (AKI) is a prevalent complication in intensive care units with an increased incidence of complications.

Objective: The aim of the present study was to assess the use of high-resolution melting curve (HRM) analysis in investigating whether the genetic polymorphisms; –308?G/A of tumor necrosis factor-α (TNF-α), and –1082?G?/A of Interleukin-10 (IL-10) genes may predispose patients diagnosed with severe sepsis to the development of AKI.

Methods: One hundred and fifty patients with severe sepsis participated in the present study; only sixty-six developed AKI. Both polymorphisms were studied using HRM analysis.

Main findings: The low producer genotype of both studied polymorphism of TNF-α and IL-10 genes was associated with AKI. Using logistic regression analysis, the low producer genotypes remained an independent risk factor for AKI. A statistically significant difference was detected between both studied groups as regards the low producer genotype in both TNF-α?(–308?G/A) and interleukin-10 (IL-10) (–1082?G/A) polymorphisms being prevalent in patients developing AKI.

Principle conclusions: The low producer genotypes of both TNF-α (–308?G/A) and IL-10 (–1082?G/A) polymorphisms could be considered a risk factor for the development of AKI in critically ill patients with severe sepsis, thus management technique implemented for this category should be modulated rescuing this sector of patients from the grave deterioration to acute kidney injury. Using HRM for genotyping proved to be a highly efficient, simple, cost-effective genotyping technique that is most appropriate for the routine study of large-scale samples.