Effects of a single postnatal methamphetamine administration on NMDA-induced seizures are sex- and prenatal exposure-specific

The aim of our study was to reveal whether acute methamphetamine (MA) administration changes the sensitivity to seizures induced by N-methyl-d-aspartate (NMDA) in prenatally MA-exposed adult rats. Adult rats with respect to sex and female estrous cycle (prenatally MA-exposed, prenatally saline-exposed, and controls) were divided into groups with acute MA (1 mg/kg) or without acute drug administration (saline injection). Intraperitoneal administration of 250 mg/kg of NMDA was used as a seizure model. The present study demonstrated that both prenatal MA and prenatal saline exposure decreased the latency to onset of stereotypy and clonic-tonic seizures. Acute MA administration decreased latency to onset of stereotypic behavior in all groups, while increased latency to onset of clonic-tonic seizures in prenatally saline-exposed rats. The duration of NMDA seizures was longer after acute MA administration relative to animals without acute MA pretreatment in both control groups. In addition, males displayed decreased susceptibility to NMDA-induced seizures relative to females regardless of their estrous cycle. Our study suggests that acute MA exposure changes susceptibility to NMDA-induced seizures in respect of prenatal exposure and sex. However, it seems that the effect of prenatal exposure is not induced by the drug per se but rather by the repeated injection exposure that causes prenatal stress.     

Ethanol-fixed material used for both classical and molecular identification purposes: Eudiplozoon nipponicum (Monogenea: Diplozoidae) as a case parasite species

This study is focused on the feasibility of two treatments of alcohol-fixed monogenean parasites which are intended to be use for the combined morphological and molecular characterizations. The monogenean parasite, Eudiplozoon nipponicum, was selected as a model parasite species; however it is expected that these techniques will be suitable for other monogeneans and other parasitic families. The haptor of diplozoid parasites is equipped with sclerotized attachment clamps and central hooks which are utilized for morphological identification. As parasite tissue become very tough and rigid when preserved in ethanol, using these structures for species identification without additional treatment is difficult. We investigated two different techniques to digest the surrounding tissues, the first was treatment with 10% sodium dodecyl sulphate (SDS) and the second treatment was proteinase K. Tissue was successfully digested in both treatments and all clamps, central hook and even individual sclerites of the clamps were clearly visible and well defined. After treatment, the digest was used to extract genomic DNA, and the second internal transcribed spacer of the ribosomal DNA genes (rDNA) was amplified. Nucleic acid sequence was obtained from 90% of parasite specimens processed by both treatments. Treatment of haptors with SDS was proven to be more successful with no visible changes or damage observed to sclerites even after a month. This method represents a useful tool for the combined morphological and molecular studies as the correct sequence can be assigned to the same individual worm from which haptoral parts have been obtained.     

Synthesis and Effect of the Structure of Bithienyl-Terminated Surfactants for Dielectric Layer Modification in Organic Transistor

A series of bithienyl-terminated surfactants with various alkyl chain lengths (from C8 to C13) and phosphono or chlorodimethylsilyl anchoring groups were synthesized by palladium-catalyzed hydrophosphonation, or platinum-catalyzed hydrosilylation as a key step. Surfactants were tested in pentacene or α-sexithiophene-based organic field-effect transistors (OFETs) for the modification of the dielectric surface. The studied surfactants increased the effective mobility of the α-sexithiophene-based device by up to one order of magnitude. The length of alkyl chain showed to be significant for the pentacene-based device, as the effective mobility only increased in the case of dielectric modification with bithienylundecylphosphonic acid. AFM allowed a better understanding of the morphology of semiconductors on bare SiO₂ and surfaces treated with bithienylundecylphosphonic acid.     

Association between health behaviour and self-reported health in Estonia, Finland, Latvia and Lithuania

BACKGROUND: The aim of the present study is to examine the associations of the selected health behaviours (daily smoking, frequent strong alcohol use, consumption of fresh vegetables less than 3 days a week and leisure time physical activity less than two/three times a week) to the self-assessed health after adjustment to the age and education in Estonia, Finland, Latvia and Lithuania. METHODS: Data from cross-sectional surveys carried out in all the above-mentioned countries were used. The methodology and questionnaires of the surveys were standardized between the participating countries within the Finbalt Health Monitor System. Logistic regression was used to assess the effect of self-perceived health status on prevalence of health behaviours. RESULTS: In Finland both women and men rated their health better than both genders in all the Baltic countries. In Finland self-assessment of health is significantly associated with most health behaviours, but in the Baltic counties the associations are weak or unstable. CONCLUSION: The results suggest that in Finland as in many other stable countries self-assessed health status was related to health behaviours and can be used as an indicator of health behaviours. In the Baltic countries, factors other than health behaviours may be more relevant to the self assessment of health status.     

Anxiety and sense of coherence in Roma and non-Roma coronary heart disease patients

Objective. Morbidity and mortality among Roma due to coronary heart disease (CHD) is high, but evidence on potential psychosocial pathways is lacking. This study aimed to assess the differences in the severity of anxiety symptoms and in the sense of coherence (SOC) between Roma and non-Roma CHD patients, crude and adjusted for age, sex, functional status and socio-economic status (SES).

Design. We examined 607 CHD patients (mean age 58.0 ± 7.4, 28.7% female) scheduled for coronary angiography, 98 (16.1%) of whom were Roma. Anxiety symptoms were measured using the Hospital Anxiety and Depression Scale and SOC using the 13-item Orientation to Life Questionnaire. Data were analysed using hierarchical regression.

Results. Roma ethnicity was associated with more severe anxiety (B = 1.89; [95% confidence interval (CI) = 0.79; 2.98]) adjusted for age, sex, functional status and SES. Roma ethnicity was also associated with lower SOC (B = ?4.77; [95% CI = ?7.85; ?1.68]) adjusted for age, sex and functional status. The latter association lost statistical significance after adjustment for SES.

Conclusion. Roma ethnicity is associated with more anxiety symptoms and lower SOC among CHD patients. Our findings indicate that Roma CHD patients have a worse position regarding psychosocial factors that increase mortality and thus require additional attention.     

4-arylazo-3,5-diamino-1H-pyrazole CDK inhibitors: SAR study, crystal structure in complex with CDK2, selectivity, and cellular effects

In a routine screening of our small-molecule compound collection we recently identified 4-arylazo-3,5-diamino-1H-pyrazoles as a novel group of ATP antagonists with moderate potency against CDK2-cyclin E. A preliminary SAR study based on 35 analogues suggests ways in which the pharmacophore could be further optimized, for example, via substitutions in the 4-aryl ring. Enzyme kinetics studies with the lead compound and X-ray crystallography of an inhibitor-CDK2 complex demonstrated that its mode of inhibition is competitive. Functional kinase assays confirmed the selectivity toward CDKs, with a preference for CDK9-cyclin T1. The most potent inhibitor, 4-[(3,5-diamino-1H-pyrazol-4-yl)diazenyl]phenol 31b (CAN508), reduced the frequency of S-phase cells of the cancer cell line HT-29 in antiproliferation assays. Further observed cellular effects included decreased phosphorylation of the retinoblastoma protein and the C-terminal domain of RNA polymerase II, inhibition of mRNA synthesis, and induction of the tumor suppressor protein p53, all of which are consistent with inhibition of CDK9.     

The Utility of 2-Deoxy-2-[F-18]fluoro-<Emphasis Type="SmallCaps">d</Emphasis>-glucose Positron Emission Tomography in the Investigation of Patients with Disseminated Carcinoma of Unknown Primary Origin

Purpose A retrospective analysis of the use of 2-deoxy-2-[F-18]fluoro-d-glucose (FDG) positron emission tomography (PET) was performed in patients with histologically proven disseminated carcinoma of unknown primary tumor (CUP).Procedures The records of 31 patients with CUP, excluding patients with isolated neck metastases, were reviewed to identify the ability of PET to detect the putative primary site (PPS) and/or to change therapeutic management.Results In eight out of 31 cases (26%), a PPS was confirmed, either definitively (one pathologically, one radiologically) (true positive) or clinically (six cases). For three cases (10%), histological evidence of a primary tumor distant from the PPS was found (false positive). In a further seven cases (23%), the PPS remained unconfirmed, whereas for 13 cases (42%) no PPS was identified. In five out of seven patients in whom the PET suggested a high probability of having identified the primary site, the PPS was confirmed definitively or clinically. PET altered clinical management in at least 12 cases (38%).Conclusions PET contributed to the management of previously extensively investigated patients with CUP. Identification of a PPS and/or change in management was documented in 38% of cases, the majority of which were lung or pancreatic cancer. These findings are worthy of evaluation in a prospective study.     

Cardiovascular tissue engineering I. Perfusion bioreactors: a review

Tissue engineering is a fast-evolving field of biomedical science and technology with future promise to manufacture living tissues and organs for replacement, repair, and regeneration of diseased organs. Owing to the specific role of hemodynamics in the development, maintenance, and functioning of the cardiovascular system, bioreactors are a fundamental of cardiovascular tissue engineering. The development of perfusion bioreactor technology for cardiovascular tissue engineering is a direct sequence of previous historic successes in extracorporeal circulation techniques. Bioreactors provide a fluidic environment for tissue engineered tissue and organs, and guarantee their viability, maturation, biomonitoring, testing, storage, and transportation. There are different types of bioreactors and they vary greatly in their size, complexity, and functional capabilities. Although progress in design and functional properties of perfusion bioreactors for tissue engineered blood vessels, heart valves, and myocardial patches is obvious, there are some challenges and insufficiently addressed issues, and room for bioreactor design improvement and performance optimization. These challenges include creating a triple perfusion bioreactor for vascularized tubular tissue engineered cardiac construct; designing and manufacturing fluidics-based perfused minibioreactors; incorporation of systematic mathematical modeling and computer simulation based on computational fluid dynamics into the bioreactor designing process; and development of automatic systems of hydrodynamic regime control. Designing and engineering of built-in noninvasive biomonitoring systems is another important challenge. The optimal and most efficient perfusion and conditioning regime, which accelerates tissue maturation of tissue-engineered constructs also remains to be determined. This is a first article in a series of reviews on critical elements of cardiovascular tissue engineering technology describing the current status, unsolved problems, and challenges of bioreactor technology in cardiovascular tissue engineering and outlining future trends and developments.