Nitroglycerine effects on portal vein mechanics and oxidative stress in portal hypertension

AIM:Тo examine the effects of nitroglycerine on portal vein haemodynamics and oxidative stress in patients with portal hypertension.METHODS:Thirty healthy controls and 39 patients with clinically verified portal hypertension and increasedvascular resistance participated in the study.Liver di-ameters,portal diameters and portal flow velocities were recorded using color flow imaging/pulsed Doppler detection.Cross-section area,portal flow and index of vascular resistance were calculated.In collected blood samples,superoxide anion radical (O 2-),hydrogen per-oxide (H 2 O 2),index of lipid peroxidation (measured as TBARS) and nitric oxide (NO) as a marker of endothelial response (measured as nitrite-NO 2-) were determined.Time-dependent analysis was performed at basal state and in 10th and 15th min after nitroglycerine (sublingual 0.5 mg) administration.RESULTS:Oxidative stress parameters changed sig-nificantly during the study.H 2 O 2 decreased at the end of study,probably via O 2-mediated disassembling in Haber Weiss and Fenton reaction;O 2-increased signifi-cantly probably due to increased diameter and tension and decreased shear rate level.Consequently O 2-and H 2 O 2 degradation products,like hydroxyl radical,initi-ated lipid peroxidation.Increased blood flow was to some extent lower in patients than in controls due to double paradoxes,flow velocity decreased,shear rate decreased significantly indicating non Newtonian char-acteristics of portal blood flow.CONCLUSION:This pilot study could be a starting point for further investigation and possible implemen-tation of some antioxidants in the treatment of portal hypertension.     

Association of serum sex steroid receptor bioactivity and sex steroid hormones with breast cancer risk in postmenopausal women

Postmenopausal women with elevated serum sex steroids have an increased risk of breast cancer. Most of this risk is believed to be exerted through binding of the sex steroids to their receptors. For the first time, we investigate the association of estrogen receptor (ER) and androgen receptor (AR) serum bioactivity (SB) in addition to hormone levels in samples from women with breast cancer collected before diagnosis. Two hundred postmenopausal women participating in the UK Collaborative Trial of Ovarian Cancer Screening who developed ER-positive breast cancer 0.6-5 years after sample donation were identified and matched to 400 controls. ER and AR bioassays were used to measure ERα, ERβ, and AR SB. Androgen and estrogen levels were measured with immunoassays. Subjects were classified according to quintiles of the respective marker among controls and the associations between SB and hormones with breast cancer risk were determined by logistic regression analysis. ERα and ERβ SB were significantly higher before diagnosis compared with controls, while estrogens showed no difference. Women had a twofold increased breast cancer risk if ERα SB (odds ratio (OR), 2.114; 95% confidence interval (CI), 1.050-4.425; P=0.040) was in the top quintile >2 years before diagnosis or estrone (OR, 2.205; 95% CI, 1.104-4.586; P=0.029) was in the top quintile <2 years before diagnosis. AR showed no significant association with breast cancer while androstenedione (OR, 3.187; 95% CI, 1.738-6.044; P=0.0003) and testosterone (OR, 2.145; 95% CI, 1.256-3.712; P=0.006) were significantly higher compared with controls and showed a strong association with an almost threefold increased breast cancer risk independent of time to diagnosis. This study provides further evidence on the association of androgens and estrogens with breast cancer. In addition, it reports that high ER but not AR SB is associated with increased breast risk >2 years before diagnosis.     

Rett syndrome: an eye‐tracking study of attention and recognition memory

Aim

The aim of this study was to examine attention and recognition memory for faces and patterns in Rett syndrome, a severely disabling neurodevelopmental disorder caused by mutations in the X‐linked MECP2 gene.

Method

Because Rett syndrome impairs speech and hand use, precluding most neuropsychological testing, the visual paired‐comparison paradigm (VPC) was used, together with eye tracking. In the VPC, two identical stimuli are presented for familiarization. On test, the familiar stimulus and a new one are paired, and recognition inferred from preferential looking to the novel target. Attention is measured by looking time, gaze dispersion, and number/length of fixations. Twenty‐seven female patients with Rett syndrome (mean age 10y 6mo; SD 6y 8mo, age range 2–22y) from the Rett clinic at a children's hospital were assessed in this study, along with 30 age‐ and sex‐matched typically developing participants (outpatients from the same hospital).

Results

Although patients with Rett syndrome showed recognition of both faces and patterns, with novelty scores greater than chance (50%), their performance was significantly poorer than that of the typically developing comparison group. Their attention to both was less mature and marked by a more narrowly focused gaze, with fewer and longer fixations. When inspecting faces, attention to the eyes was similar in both groups; however, patients with Rett syndrome tended to ignore the nose and mouth.

Interpretation

This is one of the first studies to characterize attention and memory in individuals with Rett syndrome. Visually based techniques, such as the VPC, open a new avenue for quantifying the cognitive phenotype associated with this syndrome.     

Validation and cross-cultural adaptation of the Self-Assessment Disability Scale in patients with Parkinson’s disease in Serbia

The symptoms of Parkinson’s disease (PD) worsen over time affecting performance and causing disability. The purpose of this study was to translate the Self-Assessment Disability Scale in patients with Parkinson's disease (SADS-PD) into the Serbian language and assess its validity and reliability. From January to July 2012, 114 consecutive PD patients were recruited at the Neurology Clinic in Belgrade. The inclusion criteria were: ability to walk independently for at least 10 m, ability to stand for at least 90 s. The exclusion criteria were: cognitive impairment, the presence of other major neurologic, psychiatric, visual, audio-vestibular, and orthopedic disturbances. The 25-item SADS-PD was translated according to internationally-accepted methodology. The internal consistency of the scale was evaluated using Cronbach’s alpha coefficient. Test–retest reliability was evaluated using Kendall’s concordance coefficient for total scores. To evaluate construct validity, an exploratory factor analysis (principal component analysis, varimax rotation) was performed. Cronbach’s alpha coefficient was 0.984. Kendall’s concordance coefficient was 0.994. Duration of the disease, Hoehn & Yahr (H&Y) stage, Unified Parkinson’s Disease Rating Scale (UPDRS) motor score, history of falls, Hamilton’s Depression and Anxiety Rating Scales (HDRS and HARS) scores were significantly correlated with the total SADS-PD score. On factor analysis 25 items in the SADS-PD questionnaire were separated in two clusters with total matrix variance of 79.7 %. The psychometric properties of the cross-culturally adapted SADS-PD questionnaire (Serbian version) have outstanding validity and reliability as an instrument for evaluation of the extent of disability in patients with PD.     

Mechanisms of Pediatric Cerebral Arteriopathy: An Inflammatory Debate

Arteriopathy is the leading cause of childhood arterial ischemic stroke, but its mechanisms are poorly understood. This review explores the possible role of inflammatory mechanisms and evidence for inflammatory pathophysiology in specific pediatric cerebral arteriopathies. Pathologically proven small-vessel central nervous system vasculitis provides a definitive inflammatory model where available treatments are likely improving outcomes. In contrast, a common large-vessel arteriopathy presents many features suggestive of inflammation, but definitive proof remains elusive. Recent advances and future research directions, including biomarker, neuroimaging, and pathologic approaches and how they might address these important clinical questions, are discussed.     

Pharmacoepigenetics: an element of personalized therapy?

Introduction: Epigenetics is a rapidly growing field describing heritable alterations in gene expression that do not involve DNA sequence variations. Advances in epigenetics and epigenomics have influenced pharmacology, leading to the development of a new specialty, pharmacoepigenetics, the study of the epigenetic basis for the individual variation in drug response.

Areas covered: We present an overview of the major epigenetic mechanisms and their effects on the expression of drug metabolizing enzymes and drug transporters, as well as the epigenetic status of drug protein targets affecting therapy response. Recent advances in the development of pharmacoepigenetic biomarkers and epidrugs are also discussed.

Expert opinion: There is growing evidence that pharmacoepigenetics has the potential to become an important element of personalized medicine. Epigenetic modifications influence drug response, but they can also be modulated by drugs. Moreover, they can be monitored not only in the affected tissue, but also in body fluids. Nevertheless, there are very few examples of epigenetic biomarkers implemented in the clinical setting. Explanation of the interplay between genomic and epigenomic changes will contribute to the personalized medicine approach. Ultimately, both genetic biomarkers and epigenetic mechanisms should be taken into consideration in predicting drug response in the course of successful personalized therapy.