The trans/cis photoisomerization in hydrogen bonded complexes with stability controlled by substituent effects: 3-(6-aminopyridin-3-yl)acrylate case study

The association of aminopyridine-based acrylic acid and its salt was studied by NMR titration experiments. The AA (acceptor, acceptor) hydrogen-bonding pattern present in the salt forms a complex readily with a DD (donor, donor) hydrogen-bonding pattern of the substituted ureas even in polar and competitive environment. The double carbon–carbon bond in the acrylic acid derivative is subjected to photoisomerization. This is dependent on the association with substituted urea derivatives. The substituent in ureas influences the trans/cis isomerization kinetics and position of the photostationary state. Two mechanisms that influence the photoisomerization were proposed. To the best of our knowledge, the trans/cis photoisomerization influenced by the substituent in such a hydrogen-bonding pattern has not observed previously. It was shown that interaction with urea derivatives causes lowering of the trans-to-cis photoreaction rates.

The association of aminopyridine-based acrylic acid and its salt was studied by NMR titration experiments.     

Towards metabolically stable 5-HT7 receptor ligands: a study on 1-arylpiperazine derivatives and related isosters

Serotonin 7 (5-hydroxytryptamine7 or 5-HT₇) is the most recently identified serotonin receptor. It is involved in mood disorders and is studied as a target for antidepressants. Here, we report on the structural manipulation of the 5-HT₇ receptor ligand 4-[2-(3-methoxyphenyl)ethyl]-1-(2-methoxyphenyl)piperazine (1a) aimed at obtaining 5-HT₇ receptor ligands endowed with good in vitro metabolic stability. A set of N-[3-methoxyphenyl)ethyl-substituted] 1-arylpiperazine, 4-arylpiperidine and 1-aryl-4-aminopiperidine was synthesized and tested in radioligand binding assays at human cloned 5-HT₇ and 5-HT_1A receptors. In vitro metabolic stability of the target compounds was assessed after incubation with rat hepatic S9 microsomal fraction. Among the new compounds, 1-(2-biphenyl)-4-[2-(3-methoxyphenyl)ethyl]piperazine (1d) and 4-(2-biphenyl)-1-[2-(3-methoxyphenyl)ethyl]piperidine (2d) showed a good compromise between affinity at 5-HT₇ receptor (K _i = 7.5 nM and 13 nM, respectively) and in vitro metabolic stability (26 and 65 % recovery of parent compound, respectively) but were poorly selective over 5-HT_1A receptor.     

Longitudinal prediction of falls and near falls frequencies in Parkinson’s disease: a prospective cohort study

Journal of Neurology - Several prediction models for falls/near falls in Parkinson’s disease (PD) have been proposed. However, longitudinal predictors of frequency of falls/near falls are...     

Health-related quality of life in children with immunoglobulin A nephropathy – results of a multicentre national study

IntroductionImmunoglobulin A nephropathy (IgAN) may lead to end stage renal disease and severely affect patient functioning and wellbeing. The aim of the study was to evaluate health-related quality of life (HRQoL) in children and adolescents with IgAN, and compare HRQoL in relation to the disease course, social status and psychological factors, such as expressing anger and perceived personal competence.Material and methodsThe multicentre cross-sectional study included 51 patients ≥ 8 years from 7 paediatric nephrology centres in Poland. Psychometric analysis was performed using the Kidscreen-52 questionnaire to evaluate HRQoL, the Anger Expression Scale to evaluate the severity of anger and the Personal Competence Scale to measure general perception of personal competence.ResultsMean age of patients was 14.54 ±3.69 years; duration since the diagnosis of IgAN was 4.98 ±3.9 years. Patients with IgAN rated their psychological wellbeing as significantly worse compared to healthy peers (p < 0.05). The presence of proteinuria was associated with significantly worse physical wellbeing (58.72 ±18.45 vs. 74.44 ±22.97; p < 0.05). Current therapy (steroids/immunosuppressive drugs) had no effect on HRQoL in the study group. Perceived personal competence was rated high by 49% of children in the study group. Children with IgAN were characterized by lower intensity of expressed anger (p < 0.001) and significantly higher intensity of suppressed anger (p < 0.01) compared to reference ranges. Severity of expressed anger correlated positively with the parent relations and school environment dimensions of HRQoL.ConclusionsWe found lower HRQoL in regard to physical and psychological wellbeing in a group of Polish children with IgAN compared to healthy peers. HRQoL should be monitored in this patient group.     

High prevalence of anti-HEV antibodies among patients with immunosuppression and hepatic disorders in eastern Poland

IntroductionThe incidence of hepatitis E virus (HEV) infections in Poland is largely unknown. This study aimed to describe seroprevalence of markers of HEV infection among patients with immunodeficiency of diverse etiology and patients with advanced chronic liver diseases.Material and methodsFour hundred fifty patients were enrolled; among them, 180 persons were solid organ transplant recipients, 90 patients were HIV-infected and 180 persons had confirmed liver cirrhosis of different etiology. Serum anti-HEV-IgG, IgM antibodies and HEV-antigen were detected by ELISA (Wantai, China).ResultsIn the group of transplant recipients, serum anti-HEV-IgG antibodies were detected in 40.6%, IgM in 1.1% and HEV-Ag in 2.8% of subjects. In the HIV-infected population 37.7% had anti-HEV-IgG, 1.1% had anti-HEV-IgM and none had HEV-Ag. Among patients with advanced chronic liver diseases the highest prevalence of anti-HEV-IgG was recorded in alcohol-related liver cirrhosis (52.1%) (p = 0.049). In the population of all liver cirrhotics anti-HEV-IgG seroprevalence was 48.3%, anti-HEV-IgM seroprevalence was 5.0% and HEV-Ag seroprevalence was 1.7%. Older age and male gender were significant risk factors associated with increased anti-HEV-IgG prevalence, p = 0.0004 and p = 0.02, respectively.ConclusionsIn this large cohort a high seroprevalence of anti-HEV-IgG was detected in comparison to other European countries, with the highest rates in patients with alcoholic liver disease and in transplant recipients.     

Predictors of Coronary and Carotid Atherosclerosis in Patients with Severe Degenerative Aortic Stenosis

Background. Patients with degenerative aortic stenosis (AS) exhibit elevated prevalence of coronary artery disease (CAD) and internal carotid artery stenosis (ICAS). Our aim was to investigate prevalence of significant CAD and ICAS in relation to demographic and cardiovascular risk profile among patients with severe degenerative AS.Methods. We studied 145 consecutive patients (77 men and 68 women) aged 49-91 years (median, 76) with severe degenerative AS who underwent coronary angiography and carotid ultrasonography in our tertiary care center. The patients were divided into two groups according to the presence of either significant CAD (n=86) or ICAS (n=22).Results. The prevalence of significant CAD or ICAS was higher with increasing number of traditional risk factors (hypertension, hypercholesterolemia, diabetes, smoking habit) and decreasing renal function. We found interactions between age and gender in terms of CAD (p=0.01) and ICAS (p=0.06), which was confirmed by multivariate approach. With the reference to men with a below-median age, the prevalence of CAD or ICAS increased in men aged >76 years (89% vs. 55% and 28% vs. 14%, respectively), whereas the respective percentages were lower in older vs. younger women (48% vs. 54% and 7% vs. 17%).Conclusions. In severe degenerative AS gender modulates the association of age with coronary and carotid atherosclerosis with its lower prevalence in women aged >76 years compared to their younger counterparts. This may result from a hypothetical “survival bias”, i.e., an excessive risk of death in very elderly women with severe AS and coexisting relevant coronary or carotid atherosclerosis.     

Assessment of the level of vaccine-induced anti-HBs antibodies in children with inflammatory systemic connective tissue diseases treated with immunosuppression

Objectives

Protective vaccinations are the most effective method of prevention of type B virus hepatitis. The aim of the study was to determine whether in children receiving immunosuppressive therapy due to inflammatory systemic connective tissue diseases the protective concentration of the anti-HBs antibodies produced after vaccination against type B virus hepatitis in infancy is maintained.

Material and methods

The concentration of anti-HBs antibodies was assessed in the sera of 50 children with inflammatory connective tissue diseases – 37 girls (74%) and 13 boys (26%), aged 1.5–17.5 years – during the immunosuppressive treatment, which lasted at least 6 months. The control group consisted of 50 healthy children – 28 girls (56%) and 22 boys (44%) aged 2–17 years. All children were vaccinated in infancy with Engerix B vaccine according to the 0–1–6 months schedule. The antibody concentration of ≥ 10 mIU/ml in patients is regarded as protective.

Results

No protective antibody concentrations were found in 25 cases (50%) in the group of diseased children and only in 2 children in the control group (4%).

Conclusions

The concentration of vaccine-induced antibodies should be assessed in children with inflammatory systemic connective tissue diseases and, in case of the absence of a protective concentration, revaccination should be started. The use of glucocorticosteroids, synthetic and biological disease-modifying antirheumatic drugs is no contraindication to vaccination against hepatitis B.     

Plasma concentration of atrial natriuretic peptide is related to the duration of atrial fibrillation in patients with advanced heart failure

BACKGROUND: Plasma concentration of atrial natriuretic peptide (ANP) is elevated in patients with atrial fibrillation (AF) and in patients with chronic heart failure (CHF).Aim. To assess ANP level in patients with permanent AF and advanced CHF. METHODS: The study group consisted of 41 patients (27 males, mean age 62+/-8 years) with AF of a mean duration of 8.8 months. Twenty six (63%) patients were in NYHA class II, and 15 (37%) - in NYHA class III or IV. All patients underwent clinical and echocardiographic evaluation as well as ANP plasma concentration assessment. Multiple regression analysis was used to identify factors which determine ANP plasma concentration. RESULTS: Mean ANP plasma concentration was 52.4+/-22.7 pg/ml in the whole study group; 38.6+/-10.8 pg/ml in NYHA class II patients and 74.9+/-18.7 pg/ml in NYHA class III-IV subjects (p<0.0001). Among echocardiographic parameters, patients with NYHA class III or IV had significantly lower left ventricular ejection fraction and greater left atrial volume than patients with NYHA class II (32% versus 56%, p<0.0001 and 101.0+/-23.8 cm(3) versus 83.4+/-16.1 cm(3), p<0.006, respectively). Multiple regression analysis revealed a significant negative correlation between AF duration and ANP level (p=0.0013) in a group of patients with NYHA class III or IV and identified AF duration as an independent predictor of ANP plasma concentration in this group of patients. CONCLUSIONS: ANP plasma concentration in patients with persistent AF and advanced CHF is determined by AF duration - the longer the AF duration the lower the ANP level.     

Use of argon plasma coagulation in advanced cancers of the upper digestive tract

Endoscopy being a diagnostic tool, allows also a nonsurgical treatment of upper gastrointestinal tract neoplasms, even at their advanced stage. Argon plasma coagulation (APC) is a contact-free method of monopolar coagulation, based primarily on the effects of high frequency electrical current flow in the ionized argon. The study used in 14 patients, aged 56-85 years, with advanced carcinoma of oesophagus and/or cardia. Carcinoma was diagnosed upon the results of endoscopic and microscopic examinations. The following parameters were included in the analysis: electrical current power, number of treatment sessions, stage of dysphagia, oesophagus passage, localization and type of a tumor. The analysis revealed that APC is a highly effective as well as safe method of palliative treatment of advanced oesophageal and/or cardiac cancers. Moreover, it was noted that APC is more effective in adenocarcinomas than in squamous cell carcinomas.