Endocrinology: Stimulation of ovarian adenylyl cyclase activity by gonadotrophins during the natural and gonadotrophin-induced cycles in the hamster

In this study we utilized the hamster ovary as a model to investigatethe effects of ovulation induction with gonadotrophin on theactivation of the signal transducer effector system, adenylylcyclase (AC). For this purpose, we prepared membrane particlesfrom the ovary and analysed both gonadotrophin-sensitive ACand non-receptor-mediated activation during a cycle in whichovulation and luteinization were achieved by pregnant mare’sserum gonadotrophin (PMSG)/human chorionic gonadotrophin (HCG)administration. Results were directly compared with AC activationin similarly prepared membranes obtained at different stagesof the natural unstimulated cycle. AC activity was quantifiedby the direct conversion of ATP substrate into cyclic adenosinemonophosphate (cAMP). Measurements of ovarian weights, serumoestradiol and progesterone concentrations provided a solidbase from which to evaluate the functional status of the ovaryat each time period during the natural and stimulated cycles.We found that ovarian membranes contain functional componentsof the AC system and demonstrated that AC is highly dependenton hormonal changes and the functional state of the ovary. Thus,during the natural cycle, ovarian AC showed relatively constantresponsiveness to follicle-stimulating hormone (FSH) throughoutthe cycle, whereas responsiveness to luteinizing hormone (LH)/HCGreached its peak during the luteal phase. On the other hand,during the stimulated cycle, sensitivity to FSH and LH/HCG variedconsiderably, being absent during the peri-ovulatory period.AC responsiveness to gonadotrophins was only regained 48 h afterovulation. Also during the peri-ovulatory period of the gonadotrophin-inducedcycle, stimulation of ovarian AC with non-hormonal activatorsdeclined. However, the rate of cAMP production in response tothese activators remained very high, indicating that despiterefractoriness to gonadotrophins, ovarian AC retained the capacityto generate cAMP at near maximal efficiency. Basal (non-stimulated)activity, guanine nucleotide activation, hormone responsivenessand stimulation by the non-hormonal activators NaF and forskolinwere all significantly increased in comparison with the naturalcycle. Basal activity alone was 7-fold higher than the activityobserved during the unstimulated cycle. These results suggestthat subsequent to exogenous gonadotrophin administration, thetransmembrane effector AC system must be primed for a higherlevel of activity in the ovarian tissue. This priming of theovarian AC system by exogenous gonadotrophin was also evidentwhen the enzyme was measured under conditions allowing maximalactivity, i.e. in the presence of a combination of NaF and forskolin.Maximal AC activity increased 4- to 5-fold compared with thenatural cycle. We conclude that gonadotrophin administrationinducing ovulation causes profound alterations in the expressionof AC in ovarian membranes. Gonadotrophin treatment increasedthe enzyme activity and induced a temporal desensitization toFSH and LH/HCG in the peri-ovulatory period of the stimulatedcycle. Because the gonadotrophin-sensitive AC system representsthe capacity of FSH and LH/HCG receptors to couple and elicita biological response, our results provide new insights intothe cellular mechanisms that regulate ovarian activity duringinduction of ovulation.     

An educational fair and poster approach to organization-wide mandatory education

BACKGROUND: An educational fair and poster approach was developed to meet organization-wide mandatory education requirements. METHOD: A multidisciplinary task force identified 25 mandatory topics. Task force members utilized posters to indicate key points (principles) and questions for each topic. Two interactive stations, body mechanics and fire safety, were developed to allow staff to actively participate and obtain immediate feedback on competency. This educational activity was presented in a fair-like atmosphere continuously over 3 days to reach a majority of staff. RESULTS: Ninety-three percent of the staff attended the educational activity. Department directors received immediate feedback on attendance, test scores, evaluation summaries and problem areas. Post-fair evaluation comments from department directors and staff were very positive. There was a major savings in both staff and staff development work hours. CONCLUSION: An educational fair and poster approach is an efficient method of providing organization-wide mandatory education. This approach can be adapted easily to any organization.     

Increased myogenic potential and fusion of matrilysin-expressing myoblasts transplanted in mice

The success of myoblast transplantation in clinical trials has been limited in part by the low dispersion of grafted cells outside the injection site. Our research group previously reported that the culture of myoblasts with concanavalin A, a stimulator of metalloproteinase production, increased their migration. Several lines of evidence also suggested that muscle cell fusion involves metalloproteinase-sensitive mechanisms. To determine whether the increased expression of metalloproteinases had an influence on myoblast fusion and dispersion through the muscle following transplantation, we generated a myoblast cell line expressing human matrilysin (MMP-7). The MMP-7-expressing myoblasts were obtained by the stable transfection of a matrilysin expression vector in a TnILacZ immortomouse myoblast clone. Matrilysin-expressing myoblasts showed a highly increased in vitro fusion index, forming seven times (p < 0.001) more myotubes than the control cell line and three times (p < 0.001) more myotubes than the Immortomyoblast parental clone. Single-site transplantation of matrilysin-expressing myoblasts generated more fibers (p < 0.001), over a greater surface (p < 0.001) than the control cell line. The cotransplantation of matrilysin-expressing myoblasts and of normal human myoblasts in SCID mice increased the number of human dystrophin-positive fibers and myotubes by sixfold. Although no significant increased migration of myoblasts outside the injection sites was observed, our results show that the metalloproteinase activity can improve the myogenic potential of myoblasts in vitro and the fusion of myoblasts with host fibers in vivo. MMP-7 expression may be useful in increasing myoblast transplantation success.     

Neuroleptics related to butaclamol. An investigation of the effects of chlorine substituents on the aromatic rings.

The synthesis of analogues of the antipsychotic drug butaclamol bearing chloro substituents on the benzene rings is described. On the basis of a perceived topographical similarity of a putative chlorophenylethylamine pharmacophore present in these analogues and in VUFB-10032 and doclothepin, agents related to octoclothepin which do not induce catalepsy, they have been tested for "noncataleptic" neuroleptic activity. None of the butaclamol analogues exhibit this type of activity. Depending on the position of the chlorine, the analogues either retained butaclamol-like activity or were inactive.     

How clerks understand the requests of people living with aphasia in service encounters

ABSTRACT

Aphasia often restricts participation. People living with aphasia (PLWA) engage in fewer activities, which leads to fewer interactions than before aphasia. Analyses of interactions with non-familiar people in activities of daily life could provide knowledge about how to integrate these situations in rehabilitation and facilitate ongoing PLWA participation post-rehabilitation. This qualitative study is the first to examine how PLWA make their requests understood in service encounters despite aphasia. Six people living with moderate or severe aphasia were video-recorded in situations of service encounters, e.g., pharmacies, specialised shops, restaurants, and others. We identified fifty-nine occurrences with one or several difficulties in the formulation of the request. They were examined, including the clerks’ responses and ensuing interaction using multimodal conversation analysis. Results showed that PLWA used nonverbal communication within the physical environment and the context of the interaction to support verbal production. In the majority of situations, the clerks understood the request promptly. In other situations, they both collaborated to achieve a clear understanding of the request. Moreover, the findings attest to the competence of people living with moderate or severe aphasia in engaging in service encounters and add to the knowledge base about interaction and social participation in aphasia.     

Female Genital Cosmetic Surgery

ObjectiveTo provide Canadian gynaecologists with evidence-based direction for female genital cosmetic surgery in response to increasing requests for, and availability of, vaginal and vulvar surgeries that fall well outside the traditional realm of medically-indicated reconstructions.EvidencePublished literature was retrieved through searches of PubMed or MEDLINE, CINAHL, and The Cochrane Library in 2011 and 2012 using appropriate controlled vocabulary and key words (female genital cosmetic surgery). Results were restricted to systematic reviews, randomized control trials/controlled clinical trials, and observational studies. There were no date or language restrictions. Searches were updated on a regular basis and incorporated in the guideline to May 2012. Grey (unpublished) literature was identified through searching the websites of health technology assessment and health technology-related agencies, clinical practice guideline collections, clinical trial registries, and national and international medical specialty societies.ValuesThe quality of evidence in this document was rated using the criteria described in the Report of the Canadian Task Force on Preventive Health Care (Table).