Brasofensine treatment for Parkinson's disease in combination with levodopa/carbidopa

OBJECTIVE: To investigate the safety, tolerability, pharmacokinetic, and pharmacodynamic properties of the dopamine transporter antagonist brasofensine (BMS-204756) in patients with Parkinson's disease receiving levodopa/carbidopa treatment. METHODS: A 4-period crossover study was performed in 8 men (mean age 66 y) with moderate Parkinson's disease (Hoehn-Yahr stage II-IV). A dose escalation study was used in which each patient was given a single oral dose of brasofensine 0.5, 1, 2, or 4 mg, which was coadministered with the patient's usual dose of levodopa/carbidopa. RESULTS: The maximum concentration (Cmax) values of brasofensine observed in plasma after oral administration were 0.35, 0.82, 2.14, and 3.27 ng/mL for the 0.5-, 1-, 2-, and 4-mg doses, respectively; these concentrations occurred 4 hours (time to Cmax) after administration in all cases. Exposure to brasofensine (based on AUC0-infinity) increased at a rate greater than proportional to dose. Based on the motor performance subscale of the Unified Parkinson's Disease Rating Scale, no change in patient disability was observed at any dose level. CONCLUSIONS: Brasofensine was safe and well tolerated in the patient cohort studied at daily doses of up to 4 mg. Adverse events were generally mild in intensity, and included headache, insomnia, phlebitis, dizziness, ecchymosis, and vomiting.     

Mannan-binding lectin-2 (MBL2) gene polymorphisms in prenatal and perinatal cytomegalovirus infections

Cytomegalovirus (CMV) is the leading cause of congenital infections among neonates. About 10% of newborns with such an infection have clinical symptoms at birth and about 1% of infected fetuses die due to developmental malformations. Mannan-binding lectin (MBL) is considered to be an important factor in innate immunity. Its deficiency is believed to predispose to various (including viral) infections. The aim of this study was to investigate the possible role of MBL2 gene polymorphisms in prenatal and perinatal CMV infections. The frequencies of MBL2 gene exon 1 mutations as well as MBL deficiency-associated variants (LXPA/O+O/O) among newborns with confirmed cytomegalovirus infection were not significantly lower than among non-infected individuals. The distribution of MBL2 haplotypes was similar between the groups studied. These data suggest MBL does not have a major influence on susceptibility to prenatal or perinatal CMV infections.     

Quality of life in patients undergoing cardiac resynchronisation therapy

BACKGROUND: Cardiac resynchronisation therapy (CRT) is often recommended for the treatment of patients with severe heart failure and cardiac dyssynchrony. The procedure efficacy should be evaluated not only by objective criteria and clinical end points, but also by patients' subjective opinion of their everyday functioning. AIM: To assess the quality of life (QoL) in patients treated with CRT. METHODS: The study comprised 26 CRT patients: 18 males and 8 females, aged 63.3+/-9.5 (34-75) years. The QoL was evaluated by NHP questionnaires twice: before CRT implantation and 15+/-4 months (mean) after the procedure. RESULTS: There was a significant improvement in the mean values of energy (2.9 vs. 2; p <0.01), physical mobility (4.3 vs. 3; p <0.05) and emotional reactions (5.2 vs. 3.7; p <0.05) following CRT. However, some aspects of everyday functioning did not improve after CRT. They included looking after the home (66.7 vs. 66.7%) and sex life (54.2 vs. 70.8%). An improvement was observed in home life (33.3 vs. 20.8%) and social life (61.5 vs. 50%). CONCLUSIONS: Cardiac resynchronisation therapy improves patients' QoL. The psycho-social condition of CRT patients needs further, larger studies and should be taken into account by attending health professionals.     

GNB3 C825T and ACE I/D polymorphisms on the sodium-proton exchanger and the prevalence of essential hypertension in males

BACKGROUND: The aim of the study was to verify the hypothesis if the interaction between the G protein beta3 subunit (GNB3) C825T polymorphism and ACE I/D polymorphism could lead to the disclosure of increased activity of sodium-proton exchanger and hypertension. METHODS: The study included 44 male patients, median age: 40 years. Patients were divided into two groups: 26 patients with essential hypertension (EH), and 18 subjects in the normotensive group (C). RESULTS: CT + TT genotypes of GNB3 predominated in patients with hypertension (65%) compared to normotensive patients (12%) (p <0.01). No significant differences were observed in the frequency of ACE gene polymorphisms between the examined groups. Significantly higher activity of erythrocyte NHE in patients with EH was observed: median 8.83 (interquartile range 4.27) mmol/l RBC/h, compared to C: median 6.18 (2.80) mmol/l RBC/h, p <0.001. Multiple logistic regression analysis showed that the presence of the T allele increased the risk of hypertension 16-fold (p <0.01) and higher erythrocyte NHE activity 2-fold per each unit of activity (p <0.01). DD genotype of ACE polymorphism did not increase the risk of hypertension. No significant interaction of the influence of GNB3 T allele and ACE DD genotype on the risk of hypertension was observed. In multiple linear regression analysis, none of the examined genotypes and their interactions influenced NHE activity. CONCLUSIONS: The presence of the T allele of GNB3 polymorphism and increased activity of erythrocyte NHE independently of ACE genotype increase the risk of hypertension.     

Sorption of pharmaceuticals and personal care products (PPCPs) onto a sustainable cotton based adsorbent

The significant rise in contamination of wastewater, water and ground water or sediments with PPCPs is a clear evidence that nowadays applied treatment methods are inefficient in removal of these contaminants. In this study a novel cotton based adsorbent is used for efficient sorption of naproxen (NAP), caffeine (CAF) and triclosan (TCS). The adsorption of tested contaminants differed significantly: the highest amount of PPCPs sorbed was noted for TCS sorption onto CMT9 137 mg g^?1, whereas the lowest adsorbed amount, 19.73 mg g^?1, was observed for NAP sorption onto CMT13. The presence of co-solute affected both the mechanism of sorption and the amount of PPCPs sorbed: in the presence of TCS the sorption of NAP was changed from chemical to physical. Similarly, in the presence of TCS the mechanism of NAP sorption onto CMT13 changed from chemisorption to diffusion inside the pores. The presence of CAF definitely increased NAP sorption and partitioning. The presence of TCS increased CAF sorption, whereas the presence of NAP in the solution increased CAF sorption only onto CMT11. The NAP sorption in the presence of CAF was significantly enhanced and data confirmed that diffusion through the pores is the most often observed mechanism of selected PPCPs sorption onto CMTs. It is believed that the synthesized cotton-based adsorbents offer a unique opportunity for the sustainable PPCP removal from wastewater.     

Serum copeptin levels in adolescents with primary hypertension

Background

The prevalence of hypertension continues to rise in the pediatric population. In recent years, there has been an increasing amount of reports on serum arginine vasopressin and its derivative, copeptin, in blood pressure control, but its role is still unclear. The objective of this study was to assess serum copeptin in adolescents with essential hypertension.

Methods

The study cohort consisted of 84 subjects (30 girls and 54 boys) aged 11–18 years, divided into two groups: hypertension (HT) – 53 subjects with confirmed primary hypertension and R - reference group – 31 subjects in whom hypertension was excluded on the basis of ambulatory blood pressure monitoring (ABPM) (white-coat hypertension). Serum copeptin concentration was measured using a commercially available enzyme-linked immunosorbent assay kit (USCN).

Results

Hypertensive patients had higher serum copeptin levels (median, 267 [Q1–Q3: 151.1–499.7 pg/ml]) than controls (median, 107.3 [Q1–Q3: 36.7–203.4 pg/ml]), (p?<?0.01). Statistically significant difference was found both in males and females. In both groups, positive correlations between serum copeptin and uric acid levels (r?=?0.31, p?<?0.01), albuminuria (r?=?0.45, p?<?0.01), serum triglycerides (r?=?0.3, p?<?0.05), body mass index (BMI) standard deviation score (SDS) (r?=?0.24, p?<?0.05) and 24-h systolic blood pressure (SBP) (r?=?0.37, p?<?0.01) and diastolic blood pressure (DBP) (r?=?0.23, p?<?0.05) were found.

Conclusions

In summary, higher serum copeptin levels, a surrogate for arginine vasopressin (AVP) release, are associated not only with systolic and diastolic blood pressure but also with several components of metabolic syndrome including obesity, elevated concentration of triglycerides, albuminuria, and serum uric acid level. However, for the time being, more research is needed in order to confirm the role of serum copeptin as a novel marker of elevated blood pressure and predictor of metabolic syndrome.