Synthesis and biological properties of S-adamantylated heterocyclic compounds

A series of new S-adamantylated compounds were prepared by adamanlyl cation attack on the thiol group. The biological activity of new compounds as the inducers of TNF-alpha in genetically modified mouse melanoma cells is presented.     

Determinants of occupational disability following a low back injury: a critical review of the literature

The aim of this research was to determine prognostic indicators of work disability in occupational back pain as reported in the literature, by systematically searching the research literature, assessing the methodological quality of the research, and synthesizing the findings into a concise summary. An article was considered eligible for review if research participants had an injury of the back, the article was based on original research, published in English, and involved a cohort with back pain less than 6 months post injury with at least one follow up assessment. Each article was independently reviewed by two blinded reviewers using 19 appraisal criteria for methodological quality of prognostic studies. Nineteen studies met the methodological standard to be included. Time since onset, demographic factors, functional disability, psychological distress, pain reports, previous episodes, and work environment were identified as important prognostic factors. Most studies compartmentalized the factors they considered. What is needed is a comprehensive multivariate biopsychosocial job-related model of work disability.     

Synthesis and pharmacological activity of new carbonyl derivatives of 1-aryl-2-iminoimidazolidine: part 2. Synthesis and pharmacological activity of 1,6-diaryl-5,7(1H)dioxo-2,3-dihydroimidazo[1,2-a][1,3,5]triazines

Synthesis and pharmacological activity of 1,6-diaryl-5,7(1H)dioxo-2,3-dihydroimidazo-[1,2-a][1,3,5]triazines (C) are presented. The title compounds were obtained from 1-arylimidazolinurea derivatives in cyclization reaction with difunctional carbonyl reagents--phosgene (method I) or carbonyldiimidazole (CDI) (method II). Their molecular structures were confirmed by the X-ray analysis of 1-phenyl-6-(4-chlorophenyl)-5,7(1H)-dioxo-2,3-dihydroimidazo[1,2-a][1,3,5]triazine (C2) crystals. Compounds C exhibited significant depressive action on the central nervous system (CNS) of the laboratory animals, correlated with very low acute toxicity (LD(50) > 2000 mg kg(-1) i.p.), and showed antinociceptive activity in behavioural models. Reversion of this effect by small dose of naloxone (5 mg kg(-1)) can suggest opioid-like mechanism of antinociception produced by these and other carbonyl derivatives of 1-aryl-2-iminoimidazolidine. Additionally, an effect on the serotonin neurotransmission pathway was also observed. The receptor mechanism of activity for investigated compounds was confirmed only for the opioid mu receptor in binding affinity assay test. Same tests performed for the serotonin 5-HT(2) and benzodiazepine BZD receptors showed no affinity for tested compounds. The opioid-like and serotonergic activities are similar to these described earlier for chain carbonyl 1-aryl-2-iminoimidazolidine derivatives containing urea moiety, mainly due to similar chemical structure, although compounds C are not able to adopt any of the higher energy conformations of urea derivatives. Rigid location of aromatic ring (Ar') at N6, acting as a spacer blocking any direct access to the carbonyl groups (e.g. through the hydrogen bonding), could be responsible for lack of affinity toward 5-HT(2) expressed in the binding assay test.     

Trimethyltin-evoked neuronal apoptosis and glia response in mixed cultures of rat hippocampal dentate gyrus: a new model for the study of the cell type-specific influence of neurotoxins

We investigated the effects of a potent neurotoxin, trimethyltin (TMT), on mixed neuronal/glial cultures derived from rat hippocampal dentate gyrus. We found that TMT induced neuronal cell death in a concentration dependent manner, which was estimated by microtubule degeneration, hematoxylin histological staining and the TUNEL method. This cell death is most probably of an apoptotic type as suggested by Hoechst staining. In parallel to studies the effects of TMT on neurons, its concentration dependent actions on astroglia and microglia were also examined using GFAP and GS-B4 isolectin as immunocytochemical markers, respectively. We found that neurotoxic concentrations of TMT evoked astrocytic swelling, whereas low, non-cytotoxic concentrations caused changes in microglia morphology characteristic of their active form. The combined results of our studies provide new data concerning the cell type-specific influence of TMT and indicate that the culture of dentate gyrus cells is a feasible in vitro modelforfurther studies of neuronal-glial interaction in response to toxic injury.     

Treatment of surfactant-damaged skin in humans with creams of different pH values

Skin surface has an acidic pH, whereas the body's internal environment maintains a near-neutral pH. The physiological role of the 'acidic mantle' and the function of the pH gradient throughout the stratum corneum remain unexplained. The pH gradient has been suggested to activate enzymes responsible for the maintenance of the skin barrier function and to facilitate the desquamation process in the stratum corneum. The aim of the study was to investigate the influence of pH of a moisturizing cream on barrier recovery in surfactant-damaged human skin. Volunteers had their skin damaged with sodium lauryl sulphate and treated those areas with the cream, adjusted to either pH 4.0 or 7.5. The study did not prove the superiority of a cream of pH 4.0 to a cream of pH 7.5 regarding promotion of skin barrier recovery, since no significant differences (p > 0.05) were found in transepidermal water loss, blood flow and skin capacitance between the treated areas.     

Value of exercise capacity and physical activity in the prevention of cardiovascular diseases—brief review of the current literature

A low level of physical activity and decreased exercise capacity are independent risk factors for cardiovascular and all-cause mortality. The assessment of the level of physical activity and its improvement following preventive procedures is methodologically difficult. In population studies, subjective methods, such as questionnaires, activity records and other somewhat imperfect measures (accelerometers, pedometers, and pulse monitors), are used. Direct and especially indirect assessment of physical capacity with exercise tests has become increasingly more accessible and cheap. Both methods have been proved to have high prognostic value. Assessment of physical capacity enables objectification of information on the level and effects of a subjects physical activity acquired via a questionnaire. Taking into account the above-mentioned issues, the role of the assessment of exercise capacity and its improvement is not adequately appreciated. Routine evaluation of exercise capacity has not been included in the current statements on epidemiology and prevention, even in those with an increased Framingham or SCORE risk index in whom low exercise tolerance has been proved to have an unfavorable influence on prognosis. The importance of an increase in the level of physical activity resulting in an improvement in exercise capacity in different population groups should be verified in the near future, but in our opinion there is indirect but strong evidence that actions to improve exercise capacity should become the main goals in the prevention of cardiovascular and all-cause mortality, such as cessation of cigarette smoking, body weight reduction, correction of lipid and carbohydrate metabolism disturbances, and a decrease in blood pressure.