Transcriptional changes in response to ketamine ester-analogs SN 35210 and SN 35563 in the rat brain.

BACKGROUND: Ketamine ester analogs, SN 35210 and SN 35563, demonstrate different pharmacological profiles to ketamine in animal models. Both confer hypnosis with predictably rapid offset yet, paradoxically, SN35563 induces a prolonged anti-nociceptive state. To explore underlying mechanisms, broad transcriptome changes were measured and compared across four relevant target regions of the rat brain. RESULTS: SN 35563 produced large-scale alteration of gene expression in the Basolateral Amygdala (BLA) and Paraventricular Nucleus of the Thalamus (PVT), in excess of 10x that induced by ketamine and SN 35210. A smaller and quantitatively similar number of gene changes were observed in the Insula (INS) and Nucleus Accumbens (ACB) for all three agents. In the BLA and PVT, SN 35563 caused enrichment for gene pathways related to the function and structure of glutamatergic synapses in respect to: release of neurotransmitter, configuration of postsynaptic AMPA receptors, and the underlying cytoskeletal scaffolding and alignment. CONCLUSION: The analgesic ketamine ester analog SN 35563 induces profound large-scale changes in gene expression in key pain-related brain regions reflecting its unique prolonged pharmacodynamic profile.

Small Molecule Inhibitors of Lymphocyte Perforin as Focused Immunosuppressants for Infection and Autoimmunity.

New drugs that precisely target the immune mechanisms critical for cytotoxic T lymphocyte (CTL) and natural killer (NK) cell driven pathologies are desperately needed. In this perspective, we explore the cytolytic protein perforin as a target for therapeutic intervention. Perforin plays an indispensable role in CTL/NK killing and controls a range of immune pathologies, while being encoded by a single copy gene with no redundancy of function. An immunosuppressant targeting this protein would provide the first-ever therapy focused specifically on one of the principal cell death pathways contributing to allotransplant rejection and underpinning multiple autoimmune and postinfectious diseases. No drugs that selectively block perforin-dependent cell death are currently in clinical use, so this perspective will review published novel small molecule inhibitors, concluding with in vivo proof-of-concept experiments performed in mouse models of perforin-mediated immune pathologies that provide a potential pathway toward a clinically useful therapeutic agent.

Between-birth intervals in newly married Bulgarian families.

UNLABELLED: An essential component of the family planning of a newly married couple is determining not only the number of children but also the spacing of births. AIM: To study the preferences of newly married couples of Bulgarian ancestry from Plovdiv for between-birth intervals and factors that have effect on them. METHODS: The present transversal study was designed to investigate family planning in young families of Bulgarian origin from the town of Plovdiv at the time of submission of documents for state registration of marriage. The primary sociological information was gathered by a direct individual inquiry of 384 families. The data were compared with data from a similar study performed in 1995. RESULTS: Only one third of the women are willing to have a child immediately after marriage. Men prefer this to happen 1.61 +/- 0.07 year after the marriage while women favour longer protogenetic interval--1.84 +/- 0.06. The opinion of the spouses inquired about the age of women at last birth shows that there is statistically significant increase in this variable from 34.89 +/- 0.29 years in 1995 to 36.33 +/- 0.32 years in 2000. No statistically significant difference was found between the protogenetic intervals of 2000 and 1995. CONCLUSIONS: The increased age at marriage, the postponement of childbirth and increase in the anticipated age of last birth supports the thesis that the Bulgarian family type has undergone changes towards the family type characteristic for the countries in Western Europe.

Opinion of newly wed Greek couples about the nature and functions of modern family. Similarities and differences with the opinion of Bulgarian couples.

BACKGROUND: Among the European countries, Greece has exhibited a significant decline in its total fertility rate. Unlike Bulgaria, Greece conducts little in-depth research to study comprehensively the attitudes of newlywed couples toward family planning and reproductive behaviour. AIM: The present study aimed at exploring the opinion of newly married Greek couples about the nature and functions of modern family and comparing them with those of Bulgarian couples. MATERIAL AND METHODS: We conducted two parallel cross-sectional studies gathering the primary data by individual questionnaire survey using established methods. RESULTS: More than half of the respondents planned to have a child within two years after marriage. Most of the respondents think that the main purpose of having children in a family is to give meaning to a person's life. In both Greece and Bulgaria giving birth to a child in a family is believed to be the consequence of merely life-experience related and emotional prerequisites that arise from the deeply rooted traditional attitudes in these countries towards the value and role of family. The prevailing opinion is that children should be raised by the parents in their parents' home until they become three years of age. Greek women are more inclined than Bulgarian women to stay at home and raise their children even until they complete school and are ready to care for them after graduation and marriage.