Effect of angiotensin blockade on the orthostatic response in patients with systemic arterial hypertension

INTRODUCTION AND OBJECTIVES: The effect of the treatment of arterial hypertension with angiotensin inhibitors on the autonomic response to orthostatism was studied. PATIENTS AND METHOD: In 20 hypertensive patients, enalapril (10 to 20 mg) was administered daily for four weeks. Then, irbesartan (150 to 300 mg) was given for four weeks. Finally, 10 mg of enalapril combined with 150 mg of irbesartan was prescribed for another four weeks. Heart rate variability at rest and during the head-up tilt test with controlled respiration was assessed at the beginning and end of each period. RESULTS: Mean arterial pressure showed a similar reduction in the three treatment periods. There were no changes in heart rate. Heart rate variability at rest showed differences in the spectral high-frequency component between the control and the treatment periods (p = 0.10). There was an increase in the high-frequency component between the control and the third (p = 0.047) and the fourth periods (p = 0.03). In the head-up tilt test there was a decrease in total spectral high-frequency power. CONCLUSIONS: There was no increase in orthostatic intolerance with these drugs in hypertensive patients. The absence of changes in heart rate in spite of a decrease in blood pressure suggests resetting of the baroreflex function. The long-term control of hypertension with these drugs may have a favorable effect on heart rate variability, with an increase in parasympathetic activity.     

Association of the Alu insertion polymorphism in the progesterone receptor gene with breast cancer in a Mexican population

Introduction

The progesterone receptor (PR) gene plays an important role in reproduction-related events. Data on polymorphisms in the PR gene have revealed associations with cancer, particularly for the Alu insertion polymorphism, which has been suggested to affect progesterone receptor function and contribute to tumor promotion in the mammary gland.

Material and methods

We examined the role of the Alu insertion polymorphism in the PR gene by comparing the genotypes of 209 healthy Mexican women with those of 481 Mexican women with breast cancer (BC).

Results

The genotype frequencies observed in the controls and BC patients were 0% and 4% for T2/T2 (Alu insertion), 16% and 21% for T1/T2, and 84% and 75% for T1/T1 (Alu deletion), respectively. The obtained odds ratio (OR) was 1.7, with a 95% confidence interval (95% CI) of 1.1–2.6, p = 0.009, for the T1/T2–T2/T2 genotypes. The association was also evident when the distributions of the T1/T2–T2/T2 genotypes in patients in the following categories were compared: obesity grade II (OR = 1.81, 95% CI: 1.03–3.18, p = 0.039) and the chemotherapy response (OR = 1.91, 95% CI: 1.27–3.067, p = 0.002).

Conclusions

The T1/T2–T2/T2 genotypes of the Alu insertion polymorphism in the PR gene are associated with BC susceptibility in the analyzed Mexican population.     

A New Generation of Electrospun Fibers Containing Bioactive Glass Particles for Wound Healing

Chitosan fibers blended with polyethylene oxide (CHIT_PEO) and crosslinked with genipin were fabricated by electrospinning technique. Subsequently, CHIT_PEO bioactive glass composite electrospun mats were fabricated with the aim to achieve flexible structures with adequate mechanical properties and improved biological performance respect to CHIT_PEO fibers, for potential applications in wound healing. Three different compositions of bioactive glasses (BG) were selected and investigated: 45S5 BG, a Sr and Mg containing bioactive glass (BGMS10) and a Zn-containing bioactive glass (BGMS_2Zn). Particulate BGs (particles size < 20 μm) were separately added to the starting CHIT_PEO solution before electrospinning. The two recently developed bioactive glasses (BGMS10 and BGMS_2Zn) showed very promising biological properties in terms of bioactivity and cellular viability; thus, such compositions were added for the first time to CHIT_PEO solution to fabricate composite electrospun mats. The incorporation of bioactive glass particles and their distribution into CHIT_PEO fibers were assessed by SEM and FTIR analyses. Furthermore, CHIT_PEO composite electrospun mats showed improved mechanical properties in terms of Young’s Modulus compared to neat CHIT_PEO fibers; on the contrary, the values of tensile strain at break (%) were comparable. Biological performance in terms of cellular viability was investigated by means of WST-8 assay and CHIT_PEO composite electrospun mats showed cytocompatibility and the desired cellular viability.     

Exploring isoxazoles and pyrrolidinones decorated with the 4,6‐dimethoxy‐1,3,5‐triazine unit as human farnesyltransferase inhibitors

Unprecedented triazinyl‐isoxazoles were afforded via an effective cycloaddition reaction between nitrile oxides and the scarcely described 2‐ethynyl‐4,6‐dimethoxy‐1,3,5‐triazine as dipolarophile. The biological evaluation of the newly synthesized compounds showed that the inhibition of human farnesyltransferase by zinc complexation could be improved with triazine‐isoxazole moieties. The replacement of the isoxazole unit by a pyrrolidin‐2‐one was detrimental to the inhibitory activity while the pyrrolidin‐2‐thione derivatives conserved the biological potential. The potential of selected compounds to disrupt protein farnesylation in Chinese hamster ovary (CHO) cells transfected with pEGFP‐CAAX was also evaluated.