Analysis of EGF+61A>G polymorphism and EGF serum levels in Brazilian glioma patients treated with perillyl alcohol-based therapy

Purpose

Malignant gliomas are associated with alteration in EGF/EGFR signaling. Functional EGF+61A>G polymorphism is implicated with risk, recurrence, and progression of glioma. This study aimed to establish a putative association of EGF+61A>G with risk of glioma development, production of angiogenic growth factor EGF, and the response to perillyl alcohol administered by intranasal route.

Methods

The study included 83 patients with recurrent glioma enrolled in Phase I/II trial for intranasal perillyl alcohol therapy and subjects without cancer (n?=?196) as control group. DNA was extracted from blood samples, EGF genotype performed with PCR–RFLP assay, and EGF circulating levels by enzyme immunoassay. Adequate statistical tests were performed to verify associations between polymorphism and glioma risk, and genotype correlation with EGF circulating levels. The log-rank test was also used to evaluate differences on patient survival.

Results

Patients with primary glioblastoma had high frequency of AA genotype (p?=?0.037) and A allele (p?=?0.037). Increased EGF circulating levels were observed in glioma patients with AA (p?=?0.042), AG (p?=?0.006), and AA?+?AG (p?=?0.008) genotypes compared with GG. Patients with GG genotype showed increased but not significant (p?>?0.05) survival rate, and EGF levels lower than 250?pg/mL was consistently (p?=?0.0374) associated with increased survival.

Conclusion

Presence of EGF+61A>G polymorphism in Brazilian subjects was associated with glioma risk and increased circulating EGF levels. Better response to perillyl alcohol-based therapy was observed in a group of adult Brazilian subjects with lower EGF levels.     

The pleiotropic effects of the hydroxy-methyl-glutaryl-CoA reductase inhibitors in rheumatologic disorders: a comprehensive review

The hydroxy-methyl-glutaryl-CoA reductase inhibitors (statins) are used extensively in the treatment for hyperlipidemia. They have also demonstrated a benefit in a variety of other disease processes, including a wide range of rheumatologic disorders. These secondary actions are known as pleiotropic effects. Our paper serves as a focused and updated discussion on the pleiotropic effects of statins in rheumatologic disorders and emphasizes the importance of randomized, placebo-controlled trials to further elucidate this interesting phenomenon.     

Laser Doppler anemometry measurements of steady flow through two bi-leaflet prosthetic heart valves

Introduction

In vitro hydrodynamic characterization of prosthetic heart valves provides important information regarding their operation, especially if performed by noninvasive techniques of anemometry. Once velocity profiles for each valve are provided, it is possible to compare them in terms of hydrodynamic performance. In this first experimental study using laser doppler anemometry with mechanical valves, the simulations were performed at a steady flow workbench.

Objective

To compare unidimensional velocity profiles at the central plane of two bi-leaflet aortic prosthesis from St. Jude (AGN 21 - 751 and 21 AJ - 501 models) exposed to a steady flow regime, on four distinct sections, three downstream and one upstream.

Methods

To provide similar conditions for the flow through each prosthesis by a steady flow workbench (water, flow rate of 17L/min. ) and, for the same sections and sweeps, to obtain the velocity profiles of each heart valve by unidimensional measurements.

Results

It was found that higher velocities correspond to the prosthesis with smaller inner diameter and instabilities of flow are larger as the section of interest is closer to the valve. Regions of recirculation, stagnation of flow, low pressure, and flow peak velocities were also found.

Conclusions

Considering the hydrodynamic aspect and for every section measured, it could be concluded that the prosthesis model AGN 21 - 751 (RegentTM) is superior to the 21 AJ - 501 model (Master Series). Based on the results, future studies can choose to focus on specific regions of the these valves.     

Inverse Correlation Between Vascular Calcification and Bone Mineral Density in Human Immunodeficiency Virus-Infected Patients

HIV-infected individuals suffer from accelerated aging, which manifests as premature cardiovascular and bone disease. However, little is known of the association of these two disorders in the HIV population. Our objective was to investigate the association between a marker of atherosclerosis (coronary artery calcium [CAC]) and low bone mineral density (BMD) in a cross-sectional cohort of HIV-infected patients. The study was conducted at the University of Modena and Reggio Emilia, Italy. A total of 636 consecutive middle-aged, HIV-infected subjects were recruited between January 2006 and December 2010. All patients underwent CAC and BMD assessment. Patients were categorized according to a CAC score <100 or >100 units based on previous literature that identified this cut-point as a marker of increased risk. Low femoral and lumbar spine BMD was defined as <25th percentile value for the study cohort. Logistic regression and bootstrap analysis were used to assess the independent association between CAC and BMD. The main outcome measure was a CAC score >100. Patients with CAC > 100 were older and more likely to be men, diabetic, and overweight. Patients with CAC < 100 had better renal function and a lower cardiovascular risk profile. After adjusting for age, sex, traditional and HIV-specific risk factors, vitamin D level, and PTH level, there was a significant association between CAC > 100 and low BMD for the femur (OR = 2.33, 95 % CI 1.09–4.99; p = 0.02) but not for the spine. Bootstrap analyses confirmed these findings. In summary, CAC was independently associated with low femoral BMD in HIV-infected patients. Future studies should test whether therapies that attenuate cardiovascular risk in HIV favorably impact bone health.     

The role of vitamin D in improving physical performance in the elderly

There is an ongoing debate over the role of serum 25(OH) vitamin D [25(OH)D] levels in maintaining or improving physical performance and muscle strength. Much of the controversy is because of the variability between studies in participants' characteristics, baseline serum 25(OH)D levels, and baseline physical functioning. The aim of this ancillary study conducted within a randomized controlled clinical trial was to investigate whether supplementation with 400 or 2000 IU vitamin D₃ daily for 6 months would improve measures of physical performance and muscle strength in a community‐dwelling elderly population aged 65 to 95 years. Those with the slowest gait speed improved their ability to do chair‐stand tests after vitamin D supplementation. This finding remained significant after controlling for potential confounding variables. There was also an inverse correlation between serum 25(OH)D levels and fat mass index (FMI) among women, suggesting that higher supplementation with vitamin D is needed as weight increases. The results of this study suggest that supplementation with vitamin D may be most beneficial in older populations who have low baseline physical functioning. © 2013 American Society for Bone and Mineral Research.     

Delayed wound healing in aged skin rat models after thermal injury is associated with an increased MMP-9, K6 and CD44 expression

Age-related differences in wound healing have been documented but little is known about the wound healing mechanism after burns. Our aim was to compare histological features and immunohistochemical expression of matrix metalloproteinase-9 (MMP-9), collagen IV, K6 and CD44 in the burn wound healing process in aged and young rats.