Extragonadal LH/hCG action-Not yet time to rewrite textbooks

Gonadotropins are indispensable in both sexes in the regulation of gonadal sex steroid production and gametogenesis. In addition to their well-established classical actions, numerous recent publications have indicated the presence and function of luteinizing hormone/chorionic gonadotropin receptors (LH/hCG-R) in a variety of extragonadal tissues. However, the physiological significance of such effects has remained unclear. We have generated two genetically modified mouse models, one with excessive production of hCG and the other with targeted disruption of LH/hCG-R gene, and used them to address the functions of LH and hCG. Numerous gonadal and extragonadal phenotypes were found in the models with the two extremes of LH/hCG action. However, when the extragonadal effects were scrutinized in greater detail, they all appeared to arise through modification of gonadal function, either through enhanced or inhibited response to LH/hCG stimulation. Hence, further evidence is needed before the extragonadal LH/hCG-R expression can be considered functionally significant.Fil: Pakarainen, Tomi. University of Turku; FinlandiaFil: Ahtiainen, Petteri. University of Turku; FinlandiaFil: Zhang, Fu Ping. University of Helsinki; FinlandiaFil: Rulli, Susana Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Poutanen, Matti. University of Turku; FinlandiaFil: Huhtaniemi, Ilpo. University of Turku; Finlandia. IMperial College London; Reino Unid

Lähihoitajien lääkeinformaatiolähteet ja -tarpeet : kyselytutkimus lääkehoidon epätyypillisillä alueilla, kotihoidossa ja sosiaalihuollon yksiköissä työskenteleville lähi- ja perushoitajille

Healthcare professionals in patient care, including practical nurses, need medicines in-formation in their work. One strategic goal in national Medicines Information Strategy in Finland is to make sure, that healthcare professionals use reliable information sources and services. One part of the national medicines information network in Finland is work-ing group on medicines information for healthcare professionals. It's central aim is to advance availability of reliable medicines information in different environments in social- and healthcare. Objective of this study was to explore medicines information sources and needs among practical nurses. This study concentrated on practical nurses who work in atypical areas of medical care (for example at school and day care), homecare and social care and were members of The Finnish Union of Practical Nurses. Survey was made in co-operation by working group on medicines information for healthcare professionals and The Finnish Union of Practical Nurses. The survey was carried out in December 2013 - January 2014 by e-mail. The random sample consisted of 1 000 practical nurses. The material was analyzed using direct distributions, cross tabulation, Kruskal-Wallis -test and Mann-Whitney U-test. Open ended questions were analyzed by qualitative methods. The response rate was 67 (n = 666). The most commonly utilized medicines information among practical nurses were package leaflets (PL) and medical database Terveysportti. Those sources were also the most preferred ones. Practical nurses reported they would like to have additional medicines information about drug-drug interactions (86 %) and adverse effects (63 %). Information was also needed about generic drugs. The majority of practical nurses in this study were satisfied with current medicines information sources. Additional information about pharmacological treatment was needed by respondents, 14 % daily and 31 % weekly. 82 % of respondents would benefit from pharmacy's services in their work. 64 % of practical nurses had always or usually and 28 % had never mobile device for information seeking. 73 % of practical nurses took part in education concerning pharmacological care less than once in one to two years. Package leaflets and Terveysportti were the most commonly utilized and preferred medicines information sources. There is still need for detailed information about practical nurses' medicines information sources in various working environments.Kaikki potilaiden hoitoon osallistuvat terveydenhuollon ammattilaiset, myös lähihoi-tajat, tarvitsevat työssään lääkeinformaatiota. Lääkeinformaatiostrategian yksi tavoite on, että terveydenhuollon ammattilaiset käyttävät luotettavia tiedonlähteitä ja palve-luja. Kansallisen lääkeinformaatioverkoston Lääkeinformaatiota ammattilaisille -työryhmän keskeisenä tavoitteena on edistää luotettavan lääkeinformaation saatavuutta eri sosiaali- ja terveydenhuollon toimintaympäristöissä. Tämän tutkimuksen tavoitteena oli selvittää, millaisia potilas- ja lääkitysturvallisuuden kannalta oleellisia lääkeinformaatiotarpeita lähihoitajilla oli ja mitä lääkeinformaatiolähteitä he käyttivät. Tutkimus keskittyi erityisesti niin sanotuilla lääkehoidon epätyypillisillä alueilla kuten kouluissa ja päiväkodeissa sekä kotihoidossa ja sosiaalihuol-lossa työskenteleviin Suomen lähi- ja perushoitajaliittoon (SuPer) kuuluviin lähi- ja perushoitajiin. Lääkeinformaatiota ammattilaisille -työryhmän ja SuPerin yhteistyönä toteutettiin sähköinen kysely joulukuussa 2013 - tammikuussa 2014. SuPerin jäsenrekisteristä valit-tiin 1000 lähi- tai perushoitajaa satunnaisotannalla. Aineiston analyysimenetelmiä oli-vat suorat jakaumat, ristiintaulukointi, Kruskal-Wallis -testi sekä Mann-Whitney U-testi. Avoimet vastaukset analysoitiin teemoittelemalla ja ryhmittelemällä. Kyselyn vastausprosentti oli 67 (n = 666). Lähihoitajat käyttivät lääkeinformaatioläh-teistä pakkausselostetta, Terveysporttia tai kysyivät kollegalta. Mieluiten käytettäisiin Terveysporttia ja pakkausselostetta. Lähihoitajien lääkeinformaatiotarpeita olivat etenkin lääkkeiden yhteisvaikutukset (86 %) ja haittavaikutukset (63 %). Lisäksi tietoa kaivattiin rinnakkaislääkkeistä. Nykyisiin lääkeinformaatiokanaviin oltiin tyytyväisiä. Lisätietoa lääkehoidoista koki tarvitsevansa päivittäin 14 % ja viikoittain 31 % vastaajista. 82 % hyötyisi työssään apteekin palveluista. Lähihoitajista 64 %:lla oli aina tai useimmiten mobiililaite tiedonhakuun, 28 %:lla ei koskaan. Vastaajista 73 % osallistui lääkehoitoon liittyvään koulutukseen 1-2 vuoden välein tai harvemmin. Pakkausseloste ja Terveysportti olivat lähihoitajien käytetyimpiä ja mieluisimpia lääkeinformaatiolähteitä. Yksityiskohtaisemman tiedon saamiseksi lääkeinformaatiolähteiden käytöstä eri työympäristöissä olisi hyvä suorittaa jatkotutkimuksia

EXPRESSION OF cAMP AND CREB IN THE HUMAN PENIS

The aim of this study is to investigate the expression of adenosine 3',5'-cyclic monophosphate (cAMP) and cAMP-response element-binding protein (CREB) in the human penis as it is known that luteinizing hormone (LH) regulates cellular function mostly through the cAMP signaling pathway and LH receptors are expressed by the penile endothelium. Penile tissue was obtained from three patients during partial or total penectomy due to a rectal cancer with secondary penile metastasis or squamous cell carcinoma of the penis. Immunohistochemistry was used for the detection of cAMP and CREB. Positive immunoreaction for cAMP was present in most cells of superficial, intermedial, and basal layer of urethral epithelium and in fibroblast-like cells (FLC) of interstitial tissue and endothelial cells (EC) of cavernous spaces in corpus spongiosum penis. Positive staining for cAMP was also visible in EC of cavernous spaces and in FLC of interstitial tissue in corpus cavernosum penis. Positive immunoreaction for CREB was present in the superficial and intermedial layer of urethral epithelium, and some positive immunoreaction was also noticed in EC of cavernous spaces and in FLC of interstitial tissue in corpus spongiosum penis. Positive staining was also visible in the EC of cavernous spaces and in fibroplast-like cells of the interstitial tissue in the corpus cavernosum penis. Our results show the presence of cAMP and CREB in the human penis. While LH exerts its actions through cAMP signaling system and our previous studies have shown the expression of luteinizing hormone/choriogonadotropin (LHCG) receptor in the mouse and human penis, this finding may support the hypothesis that LH could affect the spongious and cavernous tissue of the human penis and thereby influence the development of erectile dysfunction among aging men.Peer reviewe

Effects of monosodium-L-glutamate administration on serum levels of reproductive hormones and cholesterol, epididymal sperm reserves and testicular histomorphology of male albino rats

This study investigated the effects of administration of monosodium L-glutamate (MSG) on serum gonadotrophin-releasing hormone (GnRH), luteinising hormone (LH), testosterone and total cholesterol (TC), cauda epididymal sperm reserves (CESR) and testicular histomorphology of adult male albino rats. Eighty-four rats, randomly assigned to 7 groups of 12 rats each, were used for the study. Varying low doses (0.25, 0.50 or 1.00 g/kg body weight) of MSG were administered orally or subcutaneously at 48-h intervals for six weeks. Serum GnRH, LH, testosterone and TC, and CESR were evaluated on days 14, 28 and 42 of MSG administration. Testicular histomorphology was evaluated on day 42. The results showed that the mean serum GnRH, LH and testosterone levels, and the CESR of all the treated groups were significantly (P < 0.05) lower than those of the untreated control on days 14, 28 and 42 of MSG administration. The mean serum TC levels of all the treated groups were also significantly (P < 0.05) lower than those of the control group on days 14 and 28. No lesions were observed on sections of the testes. It was concluded that MSG administration for 14, 28 and 42 days led to significantly lower serum levels of GnRH, LH, testosterone and TC, and significantly lower CESR

”Nyt on kovat piipussa” – miesten kokemuksia penissyöpään sairastumisesta

Penissyöpä on harvinainen ja varsin tuntematon sairaus, jonka pääsääntöinen hoitomuoto on kirurginen hoito. Tutkimuksen tarkoituksena oli kuvata miesten kokemuksia penissyöpään sairastumisesta, mitä Suomessa ei ole aikaisemmin tutkittu. Aineisto kerättiin vuonna 2019 yksilöhaastatteluilla ja kirjallisilla vastauksilla penissyöpään sairastuneilta, kirurgisesti hoidetuilta miehiltä (n=14). Aineisto analysoitiin aineistolähtöisellä sisällönanalyysillä. Miesten voimavaroja sairaudesta selviytymisessä heikensivät ajatuksia kuormittavat tunteet, vakavan sairauden aiheuttama pelko, miehuuden menettämisen tunne, yksinjäämisen kokemus, huoli läheisten jaksamisesta sekä taloudelliset huolet. Miesten voimavaroja puolestaan tuki omien selviytymiskeinojen rakentuminen, puhumisen taito, läheisten tuki, usko tulevaisuuteen sekä sairauden hyväksyminen osana elämää. Hoidetuksi tulemisen tunnetta heikensi epäluottamusterveydenhuollon ammattilaisiin, tiedonpuute hoidon vaikutuksista sekä organisaatiokeskeinen toiminta. Hoidetuksi tulemisen tunnetta vahvisti turvallisuudentunne hoitoprosessista, rehellinen informaatio, osallisuus päätöksenteossa sekä merkityksellinen kohtaaminen

Randomised double-blind phase 3 clinical study testing impact of atorvastatin on prostate cancer progression after initiation of androgen deprivation therapy : study protocol

Introduction Blood cholesterol is likely a risk factor for prostate cancer prognosis and use of statins is associated with lowered risk of prostate cancer recurrence and progression. Furthermore, use of statins has been associated with prolonged time before development of castration resistance (CR) during androgen deprivation therapy (ADT) for prostate cancer. However, the efficacy of statins on delaying castration-resistance has not been tested in a randomised placebo-controlled setting. This study aims to test statins' efficacy compared to placebo in delaying development of CR during ADT treatment for primary metastatic or recurrent prostate cancer. Secondary aim is to explore effect of statin intervention on prostate cancer mortality and lipid metabolism during ADT. Methods and analysis In this randomised placebo-controlled trial, a total of 400 men with de novo metastatic prostate cancer or recurrent disease after primary treatment and starting ADT will be recruited and randomised 1:1 to use daily 80 mg of atorvastatin or placebo. All researchers, study nurses and patients will be blinded throughout the trial. Patients are followed until disease recurrence or death. Primary outcome is time to formation of CR after initiation of ADT. Serum lipid levels (total cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL) and trigyserides) are analysed to test whether changes in serum cholesterol parameters during ADT predict length of treatment response. Furthermore, the trial will compare quality of life, cardiovascular morbidity, changes in blood glucose and circulating cell-free DNA, and urine lipidome during trial. Ethics and dissemination This study is approved by the Regional ethics committees of the Pirkanrnaa Hospital District, Science centre, Tampere, Finland (R18065M) and Tarto University Hospital, Tarto, Estonia (319/T-6). All participants read and sign informed consent form before study entry. After publication of results for the primary endpoints, anonymised summary metadata and statistical code will be made openly available. The data will not include any information that could make it possible to identify a given participant.Peer reviewe

Animal models for aberrations of gonadotropin action

During the last two decades a large number of genetically modified mouse lines with altered gonadotropin action have been generated. These mouse lines fall into three categories: the lack-of-function mice, gain-of-function mice, and the mice generated by breeding the abovementioned lines with other disease model lines. The mouse strains lacking gonadotropin action have elucidated the necessity of the pituitary hormones in pubertal development and function of gonads, and revealed the processes from the original genetic defect to the pathological phenotype such as hypo- or hypergonadotropic hypogonadism. Conversely, the strains of the second group depict consequences of chronic gonadotropin action. The lines vary from those expressing constitutively active receptors and those secreting follicle-stimulating hormone (FSH) with slowly increasing amounts to those producing human choriogonadotropin (hCG), amount of which corresponds to 2000-fold luteinizing hormone (LH)/hCG biological activity. Accordingly, the phenotypes diverge from mild anomalies and enhanced fertility to disrupted gametogenesis, but eventually chronic, enhanced and non-pulsatile action of both FSH and LH leads to female and male infertility and/or hyper- and neoplasias in most of the gonadotropin gain-of-function mice. Elevated gonadotropin levels also alter the function of several extra-gonadal tissues either directly or indirectly via increased sex steroid production. These effects include promotion of tumorigenesis in tissues such as the pituitary, mammary and adrenal glands. Finally, the crossbreedings of the current mouse strains with other disease models are likely to uncover the contribution of gonadotropins in novel biological systems, as exemplified by the recent crossbreed of LHCG receptor deficient mice with Alzheimer disease mice

Randomised double-blind phase 3 clinical study testing impact of atorvastatin on prostate cancer progression after initiation of androgen deprivation therapy: study protocol

Introduction Blood cholesterol is likely a risk factor for prostate cancer prognosis and use of statins is associated with lowered risk of prostate cancer recurrence and progression. Furthermore, use of statins has been associated with prolonged time before development of castration resistance (CR) during androgen deprivation therapy (ADT) for prostate cancer. However, the efficacy of statins on delaying castration-resistance has not been tested in a randomised placebo-controlled setting.This study aims to test statins’ efficacy compared to placebo in delaying development of CR during ADT treatment for primary metastatic or recurrent prostate cancer. Secondary aim is to explore effect of statin intervention on prostate cancer mortality and lipid metabolism during ADT.Methods and analysis In this randomised placebo-controlled trial, a total of 400 men with de novo metastatic prostate cancer or recurrent disease after primary treatment and starting ADT will be recruited and randomised 1:1 to use daily 80 mg of atorvastatin or placebo. All researchers, study nurses and patients will be blinded throughout the trial. Patients are followed until disease recurrence or death. Primary outcome is time to formation of CR after initiation of ADT. Serum lipid levels (total cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL) and trigyserides) are analysed to test whether changes in serum cholesterol parameters during ADT predict length of treatment response. Furthermore, the trial will compare quality of life, cardiovascular morbidity, changes in blood glucose and circulating cell-free DNA, and urine lipidome during trial.Ethics and dissemination This study is approved by the Regional ethics committees of the Pirkanmaa Hospital District, Science centre, Tampere, Finland (R18065M) and Tarto University Hospital, Tarto, Estonia (319/T-6). All participants read and sign informed consent form before study entry. After publication of results for the primary endpoints, anonymised summary metadata and statistical code will be made openly available. The data will not include any information that could make it possible to identify a given participant.</p