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1.
Can Urol Assoc J ; 2024 Jul 15.
Article in English | MEDLINE | ID: mdl-39037512

ABSTRACT

INTRODUCTION: Breakages and repairs related to flexible digital reusable ureteroscopes (flURS) are expensive. Thus, we aimed to assess the cost-effectiveness of single-use flexible digital ureteroscopes (SUDFU). METHODS: We conducted a literature review on MEDLINE and EMBASE until September 19, 2018. Systematic reviews and guidelines were assessed for methodologic quality by using standardized grids (R-AMSTAR and AGREE-II). Original studies were analyzed according to local customized grids. The CAPS (Critical Appraisal Skills Program) tool enabled the assessment of the economic aspects in the literature. We also collected local data over a year in 2017-2018 and conducted an economic evaluation by cost minimization, comparing SUDFU and flURS in our center. By generating different flURS breakage reduction scenarios, we aimed to demonstrate the budgetary impact that would have SUFDU introduction in our center. RESULTS: Five economic studies were included. Data on flURS showed breakage rates between 6.4% and 13.2%, and mean numbers of interventions before breakage between 7.5 and 14.4. Four of the five economic analyses suggested a higher cost per intervention with SUDFU. Our local data demonstrated similar results (6.4% and 11.8 cases) and enabled us to estimate the annual number of ureteroscopies for which SUDFU would become profitable: 11-26 (depending on the chosen device). Furthermore, we illustrated how selective use of SUFDU can reduce annual costs by avoiding breakages in different scenarios. CONCLUSIONS: The mean cost per intervention with SUDFU is usually higher than with flURS in high-volume centers and exclusive use becomes unprofitable from a small number of cases.

2.
Int J Health Care Qual Assur ; 31(2): 150-161, 2018 Mar 12.
Article in English | MEDLINE | ID: mdl-29504875

ABSTRACT

Purpose The purpose of this paper is to increase efficiency in ORs without affecting quality of care by improving the workflow processes. Administrative processes independent of the surgical act can be challenging and may lead to clinical impacts such as increasing delays. The authors hypothesized that a Lean project could improve efficiency of surgical processes by reducing the length of stays in the recovery ward. Design/methodology/approach Two similar Lean projects were performed in the surgery departments of two hospitals of the Centre Hospitalier Universitaire de Québec: Hôtel Dieu de Quebec (HDQ) and Hôpital de l'Enfant Jesus (HEJ). The HDQ project designed around a Define, Measure, Analyse, Improve and Control process revision and a Kaizen workshop focused on patients who were hospitalized in a specific care unit after surgery and the HEJ project targeted patients in a post-operative ambulatory context. The recovery ward output delay was measured retrospectively before and after project. Findings For the HDQ Lean project, wasted time in the recovery ward was reduced by 62 minutes (68 percent reduction) between the two groups. The authors also observed an increase of about 25 percent of all admissions made in the daytime after the project compared to the time period before the project. For the HEJ Lean project, time passed in the recovery ward was reduced by 6 min (29 percent reduction). Originality/value These projects produced an improvement in the flow of the OR without targeting clinical practices in the OR itself. They demonstrated that change in administrative processes can have a great impact on the flow of clinical pathways and highlight the need for comprehensive and precise monitoring of every step of the elective surgery patient trajectory.


Subject(s)
Efficiency, Organizational , Operating Rooms/organization & administration , Quality Improvement/organization & administration , Recovery Room/organization & administration , Workflow , Aged , Anesthesiologists/organization & administration , Communication , Female , Humans , Male , Middle Aged , Nursing Staff, Hospital/organization & administration , Patient Admission , Quebec , Retrospective Studies , Time Factors
3.
BMC Geriatr ; 14: 83, 2014 Jul 02.
Article in English | MEDLINE | ID: mdl-24985335

ABSTRACT

BACKGROUND: Within the context of an exploratory case study, the authors assessed the perceptions of family caregivers about the decision-making process regarding relocating their relative and about the applicability of an interprofessional approach to shared decision making (IP-SDM). They also assessed perceptions of health professionals and health managers about IP-SDM. METHODS: From November 2010 to October 2011, we worked with one IP home care team dedicated to older adults (the case) from a large primary health care organization in Quebec City, Canada. We identified six of their clients who had faced a decision about whether to stay at home or move to a long-term care facility in the past year and interviewed their family caregivers. We explored the decision-making process they had experienced regarding relocating their relative and their perceptions about the applicability of IP-SDM in this context. Attitudes towards IP-SDM and potential barriers to this approach were explored using a focus group with the participating IP home care team, individual interviews with 8 managers and a survey of 272 health professionals from the primary care organization. A hybrid process of inductive and deductive thematic analysis was used and data were triangulated across all sources. RESULTS: Family caregivers reported lack of agreement on the nature of the decision to be made, a disconnection between home care services and relatives' needs, and high cost of long-term care alternatives. Factors influencing their decision included their ability to provide care for their relative. While they felt somewhat supported by the IP home care team, they also felt pressured in the decision. Overall, they did not perceive they had been exposed to IP-SDM but agreed that it was applicable in this context. Results from the survey, focus group and interviews with health professionals and managers indicated they all had a favourable attitude towards IP-SDM but many barriers hampered its implementation in their practice. CONCLUSIONS: The family caregivers in this study did not experience IP-SDM when relocating their relative. Added to results obtained with health professionals and managers, this highlights the need for an effective intervention targeting identified barriers to implementing IP-SDM in this context.


Subject(s)
Caregivers , Decision Making , Home Care Services , Interprofessional Relations , Patient Care Team , Patient Participation/methods , Aged , Aged, 80 and over , Caregivers/standards , Female , Home Care Services/standards , Humans , Middle Aged , Patient Care Team/standards
4.
J Contin Educ Health Prof ; 33(4): 267-73, 2013.
Article in English | MEDLINE | ID: mdl-24347105

ABSTRACT

Shared decision making is now making inroads in health care professionals' continuing education curriculum, but there is no consensus on what core competencies are required by clinicians for effectively involving patients in health-related decisions. Ready-made programs for training clinicians in shared decision making are in high demand, but existing programs vary widely in their theoretical foundations, length, and content. An international, interdisciplinary group of 25 individuals met in 2012 to discuss theoretical approaches to making health-related decisions, compare notes on existing programs, take stock of stakeholders concerns, and deliberate on core competencies. This article summarizes the results of those discussions. Some participants believed that existing models already provide a sufficient conceptual basis for developing and implementing shared decision making competency-based training programs on a wide scale. Others argued that this would be premature as there is still no consensus on the definition of shared decision making or sufficient evidence to recommend specific competencies for implementing shared decision making. However, all participants agreed that there were 2 broad types of competencies that clinicians need for implementing shared decision making: relational competencies and risk communication competencies. Further multidisciplinary research could broaden and deepen our understanding of core competencies for shared decision making training.


Subject(s)
Clinical Competence , Decision Making , Education, Medical, Continuing/methods , Interdisciplinary Communication , International Cooperation , Program Development , Education, Medical, Continuing/standards , Health Knowledge, Attitudes, Practice , Humans , Needs Assessment , Physician-Patient Relations , Physicians, Family/education , Policy Making
5.
J Matern Fetal Neonatal Med ; 26(5): 513-9, 2013 Mar.
Article in English | MEDLINE | ID: mdl-23075231

ABSTRACT

OBJECTIVE: To examine maternal insulin resistance in relationship with maternal and fetal androgen levels as well as with term placenta mRNA and protein abundance of steroidogenic enzymes implicated in androgen dynamics. METHODS: The study included 20 women with gestational diabetes mellitus and 27 controls tested using a 120 min., 75 g oral glucose tolerance test. Maternal and fetal plasma concentrations of total testosterone, dihydrotestosterone (DHT) and dehydroepiandrosterone (DHEA) were measured by high-performance gas chromatography and chemical ionization mass spectrometry at 26.1 ± 3.7 weeks of pregnancy. RESULTS: Glycemic response to oral glucose over 120 min. as well as Matsuda insulin sensitivity and HOMA insulin resistance (HOMA-IR) indices were significantly associated with maternal testosterone levels (r = 0.31, r = -0.37 and r = 0.35 respectively, p ≤ 0.05 for all). Among male offspring, a positive association between maternal and fetal testosterone levels was observed (r = 0.43, p ≤ 0.05). Testosterone levels were higher in the cord blood of newborns from insulin-resistant mothers compared to newborns from insulin-sensitive mothers (0.48 ± 0.36 nmol/L vs. 0.29 ± 0.18 nmol/L p ≤ 0.05). No difference was observed in mRNA abundance or protein expression of placental steroidogenic enzymes according to the degree of maternal insulin resistance. CONCLUSION: Our results demonstrate a possible association between fetal and maternal androgen concentrations in relationship with insulin resistance.


Subject(s)
Androgens/blood , Diabetes, Gestational/blood , Fetal Blood/chemistry , Insulin Resistance/physiology , 17-Hydroxysteroid Dehydrogenases/genetics , Adult , Aromatase/genetics , Dehydroepiandrosterone/blood , Dihydrotestosterone/blood , Female , Gestational Age , Glucose Tolerance Test , Humans , Infant, Newborn , Male , Placenta/enzymology , Pregnancy , RNA, Messenger/analysis , Steroids/biosynthesis , Testosterone/blood
6.
Patient Educ Couns ; 88(2): 159-69, 2012 Aug.
Article in English | MEDLINE | ID: mdl-22305195

ABSTRACT

OBJECTIVE: To identify and analyze training programs in shared decision-making (SDM) for health professionals. METHODS: We conducted an environmental scan looking for programs that train health professionals in SDM. Pairs of reviewers independently analyzed the programs identified using a standardized data extraction sheet. The developers of the programs validated the data extracted. RESULTS: We identified 54 programs conducted between 1996 and 2011 in 14 countries and 10 languages. Thirty-four programs targeted licensed health professionals, 10 targeted pre-licensure health professionals, and 10 targeted both. Most targeted only the medical profession (n=32); six targeted more than one health profession. The five most frequently mentioned teaching methods were case-based discussion, small group educational session, role play, printed educational material, and audit and feedback. Thirty-six programs reported having evaluated their impacts but evaluation data was available only for 17. CONCLUSIONS: Health professional training programs in SDM vary widely in how and what they deliver, and evidence of their effectiveness is sparse. PRACTICE IMPLICATIONS: This study suggests there is a need for international consensus on ways to address the variability in SDM training programs. We need agreed criteria for certifying the programs and for determining the most effective types of training.


Subject(s)
Decision Making , Health Knowledge, Attitudes, Practice , Health Personnel/education , Patient Participation , Environment , Humans , Patient-Centered Care , Program Evaluation , Surveys and Questionnaires
7.
Metabolism ; 61(5): 689-98, 2012 May.
Article in English | MEDLINE | ID: mdl-22154325

ABSTRACT

We tested the hypothesis that visceral obesity is the best correlate of abdominal adipose tissue macrophage infiltration in women. Omental and subcutaneous fat samples were surgically obtained from 40 women (age, 47.0 ± 4.0 years; body mass index, 28.4 ± 5.8 kg/m(2)). CD68+ cells were identified using fluorescence immunohistochemistry. Expression of macrophage markers was measured by real-time reverse transcriptase polymerase chain reaction. Body composition and fat distribution were measured by dual-energy x-ray absorptiometry and computed tomography, respectively. Mean CD68+ cell percentage tended to be higher in subcutaneous (18.3%) compared with omental adipose tissue (15.5%, P = .07). Positive correlations were observed between CD68+ cell percentage as well as CD68 messenger RNA expression in a given depot vs the other (P ≤ .01). Visceral adipose tissue area and omental adipocyte diameter were positively related to CD68+ cell percentage in omental fat (r = 0.52 and r = 0.35, P ≤ .05). Total and visceral adipose tissue areas as well as subcutaneous adipocyte diameter were significantly correlated with CD68+ cell percentage in subcutaneous adipose tissue (0.32 ≤ r ≤ 0.40, P ≤ .05). Adipose tissue areas and subcutaneous adipocyte diameter were also significantly associated with expression of commonly used macrophage markers including CD68 in the subcutaneous fat compartment (0.32 ≤ r ≤ 0.57, P ≤ .05). Visceral adipose tissue area was the best correlate of CD68+ cell percentage in both omental and subcutaneous fat tissues, explaining, respectively, 20% and 12% of the variance in models also including subcutaneous adipose tissue area, adipocyte sizes, and total body fat mass. Visceral adipose tissue accumulation is the best correlate of macrophage infiltration in both the subcutaneous and omental fat compartments of lean to obese women.


Subject(s)
Adipose Tissue/pathology , Intra-Abdominal Fat/pathology , Macrophages/pathology , Adipocytes/physiology , Adipocytes/ultrastructure , Adult , Antigens, CD/metabolism , Antigens, Differentiation, Myelomonocytic/metabolism , Biomarkers , Blood Glucose/physiology , Body Fat Distribution , Body Mass Index , CD11 Antigens , Female , Homeostasis/physiology , Humans , Immunohistochemistry , Inflammation/blood , Lipids/blood , Lipoproteins/blood , Middle Aged , Obesity/pathology , RNA, Messenger/biosynthesis , RNA, Messenger/genetics , Real-Time Polymerase Chain Reaction , Waist Circumference
8.
Endocrine ; 40(2): 203-11, 2011 Oct.
Article in English | MEDLINE | ID: mdl-21877158

ABSTRACT

The human placenta produces high amounts of estradiol. 17ß-hydroxysteroid dehydrogenase type 2 (17ßHSD2) is expressed by placental endothelial cells and was proposed to regulate sex hormone levels. Previous results obtained in term placenta suggested that 17ßHSD2 expression and activity differ among umbilical cord vessels. In this study, 17ßHSD2 expression level and enzymatic activity, and estrogen receptor α and ß expression levels, were measured in endothelial cell cultures from umbilical arteries (HUAEC) and vein (HUVEC) using real-time quantitative PCR, western blot, and radiolabeled steroids. 17ßHSD2-specific activities were also measured in proximal and distal segments of freshly isolated umbilical cord arteries and vein. 17ßHSD2 mRNA level and activity were higher in HUAEC than in HUVEC. Activity was higher in umbilical arteries than in the umbilical vein. In arteries, enzymatic activity was higher near the placenta, suggesting a gradient of expression. No difference was found in ERα expression, whereas ERß was expressed at a higher level in HUAEC than in HUVEC. Expression profiles of estrogen receptors and 17ßHSD2 suggest a vessel type-specific response to estrogens. Our data support a differential modulation of biologically active sex steroid levels according to the vessel type in the foeto-placental unit, with apparent higher inactivation in the arterial system.


Subject(s)
Endothelium, Vascular/metabolism , Estradiol Dehydrogenases/metabolism , Gene Expression Regulation, Developmental , Gonadal Steroid Hormones/metabolism , Human Umbilical Vein Endothelial Cells/metabolism , Pregnancy Proteins/metabolism , Umbilical Arteries/cytology , Cells, Cultured , Endothelium, Vascular/cytology , Estradiol/metabolism , Estradiol Dehydrogenases/genetics , Estrogen Receptor alpha/genetics , Estrogen Receptor alpha/metabolism , Estrogen Receptor beta/genetics , Estrogen Receptor beta/metabolism , Female , Humans , Organ Specificity , Placenta/metabolism , Pregnancy , RNA, Messenger/metabolism , Real-Time Polymerase Chain Reaction , Reverse Transcriptase Polymerase Chain Reaction , Testosterone/metabolism
9.
Implement Sci ; 6: 68, 2011 Jul 05.
Article in English | MEDLINE | ID: mdl-21729310

ABSTRACT

BACKGROUND: Shared decision-making is not widely implemented in healthcare. We aimed to set a research agenda about promoting shared decision-making through continuing professional development. METHODS: Thirty-six participants met for two days. RESULTS: Participants suggested ways to improve an environmental scan that had inventoried 53 shared decision-making training programs from 14 countries. Their proposed research agenda included reaching an international consensus on shared decision-making competencies and creating a framework for accrediting continuing professional development initiatives in shared decision-making. CONCLUSIONS: Variability in shared decision-making training programs showcases the need for quality assurance frameworks.


Subject(s)
Decision Making , Education, Medical, Continuing , Cooperative Behavior , Education , Education, Medical, Continuing/methods , Health Knowledge, Attitudes, Practice , Humans , International Cooperation , Patient Participation
10.
Gynecol Endocrinol ; 27(11): 905-9, 2011 Nov.
Article in English | MEDLINE | ID: mdl-21500993

ABSTRACT

Our objective was to determine whether sex hormone-binding globulin (SHBG) concentrations are associated with gestational diabetes mellitus (GDM) and whether this association is independent of prepregnancy body mass index (BMI). The relationship between maternal SHBG concentrations and birthweight in the offspring was also examined. The study included 47 women (20 with GDM, 27 controls). GDM screening and fasting serum SHBG measurements were performed at 26.1 ± 3.7 weeks of pregnancy. A trend was observed for significantly lower SHBG concentrations in GDM patients (179 ± 36 vs. 195 ± 36 nmol/l, p ≤ 0.08). Prepregnancy BMI and BMI at the time of GDM screening were both correlated with SHBG concentrations (r = -0.49 and r =  -0.53, respectively; p ≤ 0.001). In multivariate regression analyses, only prepregnancy BMI or BMI at the time of GDM screening remained significant predictors of GDM risk [odds ratio (OR):1.23, 95% confidence interval (CI):1.06-1.47, p ≤ 0.01 and OR:1.18, 95% CI:1.02-1.39, p ≤ 0.02] while SHBG level did not. On the other hand, 10.7% of the variance in birthweight was explained by SHBG concentrations (p ≤ 0.01) independent of the presence of GDM, parity, maternal age, maternal prepregnancy BMI, maternal height, and offspring sex. In conclusion, although SHBG concentration is not an independent predictor of GDM risk when obesity is considered, it is a significant predictor of infant birthweight independent of GDM and prepregnancy BMI.


Subject(s)
Diabetes, Gestational/blood , Obesity , Sex Hormone-Binding Globulin/metabolism , Adult , Birth Weight , Body Mass Index , Diabetes, Gestational/diagnosis , Female , Glucose Tolerance Test , Humans , Infant, Newborn , Pregnancy , Pregnancy Trimesters , Prenatal Diagnosis , Regression Analysis
11.
Clin Endocrinol (Oxf) ; 72(2): 176-88, 2010 Feb.
Article in English | MEDLINE | ID: mdl-19500113

ABSTRACT

OBJECTIVE: To examine the effects of aromatizable or nonaromatizable androgens on abdominal subcutaneous (SC) and omental (OM) adipose tissue lipid metabolism and adipogenesis in men and women. DESIGN AND SUBJECTS: Primary organ and preadipocyte cultures were established from surgical samples obtained in men (n = 22) and women undergoing biliopancreatic diversions (n = 12) or gynaecological surgeries (n = 8). Cultures were treated with testosterone, dihydrotestosterone (DHT) and methyltrienolone (R1881). MEASUREMENTS: Heparin-releasable lipoprotein lipase (HR-LPL) activity, glycerol release, adiponectin secretion, glycerol-3-phosphate dehydrogenase activity and lipid accumulation were measured. RESULTS: In organ cultures from men, DHT had a statistically significant inhibitory effect on HR-LPL activity in the OM compartment. Testosterone significantly inhibited HR-LPL activity in SC and OM cultures. In women, high DHT concentrations tended to inhibit HR-LPL activity in OM cultures. Minor androgenic effects were observed for basal and isoproterenol-stimulated lipolysis as well as adiponectin release in men. On the other hand, adipocyte differentiation was significantly and dose-dependently inhibited by DHT, testosterone and R1881 in SC and OM cultures from both sexes. These effects did not differ according to adipose tissue depot but appeared to be more pronounced in women than in men. CONCLUSIONS: Androgens slightly decreased HR-LPL activity in adipose tissue organ cultures, but markedly inhibited adipogenesis in SC and OM primary preadipocyte cultures in both sexes. Androgenic effects on adipose tissue in men vs. women may not differ in terms of direction but in the magnitude of their negative impact on adipogenesis and lipid synthesis.


Subject(s)
Adipocytes/cytology , Adipose Tissue/drug effects , Adipose Tissue/metabolism , Androgens/pharmacology , Cell Differentiation/drug effects , Adipocytes/drug effects , Adult , Aged , Apoptosis/drug effects , Blotting, Western , Cells, Cultured , Dihydrotestosterone/pharmacology , Female , Glycerolphosphate Dehydrogenase/genetics , Glycerolphosphate Dehydrogenase/metabolism , Humans , Lipid Metabolism/drug effects , Male , Metribolone/pharmacology , Middle Aged , Organ Culture Techniques , Polymerase Chain Reaction , Testosterone/pharmacology
12.
Obesity (Silver Spring) ; 17(3): 424-30, 2009 Mar.
Article in English | MEDLINE | ID: mdl-19219061

ABSTRACT

Our objective was to examine omental and subcutaneous adipocyte adiponectin release in women. We tested the hypothesis that adiponectin release would be reduced to a greater extent in omental than in subcutaneous adipocytes of women with visceral obesity. Omental and subcutaneous adipose tissue samples were obtained from 52 women undergoing abdominal hysterectomies (age: 47.1 +/- 4.8 years; BMI: 26.7 +/- 4.7 kg/m(2)). Adipocytes were isolated and their adiponectin release in the medium was measured over 2 h. Measures of body fat accumulation and distribution were obtained using dual-energy X-ray absorptiometry and computed tomography, respectively. Adiponectin release by omental and subcutaneous adipocytes was similar in lean individuals; however, in subsamples of obese or visceral obese women, adiponectin release by omental adipocytes was significantly reduced while that of subcutaneous adipocytes was not affected. Omental adipocyte adiponectin release was significantly and negatively correlated with total body fat mass (r = -0.47, P < 0.01), visceral adipose tissue area (r = -0.50, P < 0.01), omental adipocyte diameter (r = -0.43, P < 0.01), triglyceride levels (r = -0.32, P < or = 0.05), cholesterol/high-density lipoprotein (HDL)-cholesterol (r = -0.31, P < or = 0.05), fasting glucose (r = -0.39, P < or = 0.01), fasting insulin (r = -0.36, P < or = 0.05), homeostasis model assessment index (r = -0.39, P < or = 0.01), and positively associated with HDL-cholesterol concentrations (r = 0.33, P < or = 0.05). Adiponectin release from subcutaneous cells was not associated with any measure of adiposity, lipid profile, or glucose homeostasis. In conclusion, compared to subcutaneous adipocyte adiponectin release, omental adipocyte adiponectin release is reduced to a greater extent in visceral obese women and better predicts obesity-associated metabolic abnormalities.


Subject(s)
Adipocytes/metabolism , Adiponectin/metabolism , Body Fat Distribution , Intra-Abdominal Fat/metabolism , Obesity/metabolism , Absorptiometry, Photon , Adipocytes/cytology , Adipocytes/pathology , Adult , Blood Glucose/metabolism , Cytokines/blood , Female , Humans , Insulin/blood , Lipids/blood , Middle Aged , Obesity/pathology , Omentum/cytology , Omentum/metabolism , Omentum/pathology , Subcutaneous Fat/cytology , Subcutaneous Fat/metabolism , Subcutaneous Fat/pathology , Tomography, X-Ray Computed
13.
Reprod Biol Endocrinol ; 5: 30, 2007 Jul 10.
Article in English | MEDLINE | ID: mdl-17623101

ABSTRACT

BACKGROUND: During human pregnancy, the placental villi produces high amounts of estradiol. This steroid is secreted by the syncytium, which is directly in contact with maternal blood. Estradiol has to cross placental foetal vessels to reach foetal circulation. The enzyme 17beta-hydroxysteroid dehydrogenase type 2 (17beta-HSD2) was detected in placental endothelial cells of foetal vessels inside the villi. This enzyme catalyzes the conversion of estradiol to estrone, and of testosterone to androstenedione. It was proposed that estradiol level into foetal circulation could be regulated by 17beta-HSD2. METHODS: We obtained placentas from 10 to 26 6/7 weeks of pregnancy from women undergoing voluntary termination of pregnancy, term placentas were collected after normal spontaneous vaginal deliveries. We quantified 17beta-HSD2 mRNA levels in mid-gestation and term human placenta by RT-QPCR. We produced a new anti-17beta-HSD2 antibody to study its spatio-temporal expression by immunohistochemistry. We also compared steroid levels (testosterone, estrone and estradiol) and 17beta-HSD2 mRNA and protein levels between term placenta and endometrium. RESULTS: High 17beta-HSD2 mRNA and protein levels were found in both mid-gestation and term placentas. However, we showed that 17beta-HSD2 mRNA levels increase by 2.27 fold between mid-gestation and term. This period coincides with a transitional phase in the development of the villous vasculature. In mid-gestation placenta, high levels of 17beta-HSD2 were found in mesenchymal villi and immature intermediate villi, more precisely in endothelial cells of the stromal channel. At term, high levels of 17beta-HSD2 were found in the numerous sinusoidal capillaries of terminal villi. 17beta-HSD2 mRNA and protein levels in term placentas were respectively 25.4 fold and 30 to 60 fold higher than in the endometrium. Steroid levels were also significantly higher in term placenta than in the endometrium. CONCLUSION: The spatial and temporal expression of 17beta-HSD2 in the placenta during pregnancy and the comparison of 17beta-HSD2 expression and steroid levels between placental villi and endometrium are compatible with a role in the modulation of active and inactive forms of estrogens. Our observations strongly support the hypothesis that 17beta-HSD2 acts as a barrier decreasing estradiol secretion rates in the foetal circulation.


Subject(s)
17-Hydroxysteroid Dehydrogenases/metabolism , Chorionic Villi/enzymology , Pregnancy Trimester, Second/genetics , Pregnancy Trimester, Third/genetics , RNA, Messenger/biosynthesis , 17-Hydroxysteroid Dehydrogenases/biosynthesis , 17-Hydroxysteroid Dehydrogenases/genetics , 17-Hydroxysteroid Dehydrogenases/physiology , Chorionic Villi/physiology , Estradiol Dehydrogenases , Female , Gene Expression Regulation, Enzymologic , Humans , Pregnancy , RNA, Messenger/analysis , RNA, Messenger/genetics
14.
J Clin Endocrinol Metab ; 87(8): 3883-92, 2002 Aug.
Article in English | MEDLINE | ID: mdl-12161528

ABSTRACT

Androgens delay lung maturation through their action on lung fibroblasts. Knowing that testosterone is secreted by the lung epithelial-like cell line A-549, we have studied the metabolism of androgens by several human lung diploid fibroblasts cell lines. No 17-ketosteroid reductase activity was detected. In contrast, testosterone was transformed mainly into androstenedione and androstanedione with no 5 alpha-dihydrotestosterone formed, indicating the presence of 17 beta- hydroxysteroid dehydrogenase (HSD) type 2 and 5 alpha-reductase activities. The eight cell lines analyzed had either a low or high 17 beta-HSD type 2 activity level. No correlation between these levels and the sex or age stage of cells was established, but Northern blot analysis of human lung RNA samples of five adult subjects revealed very similar variations between subjects in the level of 17 beta-HSD type 2 mRNA. The 5 alpha-reductase activity had a marked substrate preference for androstenedione, the product of 17 beta-HSD type 2. When tritiated testosterone was used as substrate, only barely detectable levels of 5 alpha-dihydrotestosterone were observed by HPLC in the presence of the 17 beta-HSD type 2 inhibitor EM-919. The use of unlabeled testosterone or of the antiandrogen hydroxyflutamide demonstrated that the tritiated testosterone substrate itself had no effect on levels of 5 alpha-reduction. In fact, in these cells, 5 alpha-reductase has no significant activity on testosterone, but it further converts the product of 17 beta-HSD type 2, thus playing a role with 17 beta-HSD type 2 in androgen inactivation. Because androgens delay lung maturation and surfactant synthesis by their action on lung fibroblasts, it is of particular interest to find that the steroid metabolism of these lung fibroblast cells is oriented toward androgen inactivation. Because lung fibroblasts of subjects with low 17 beta-HSD type 2 expression levels are likely to be exposed to higher levels of androgens, an allelic variation of the 17 beta-HSD-2 gene is suspected, which would result in familial incidence of respiratory distress. This is in line with reported cases of familial incidence of respiratory distress.


Subject(s)
17-Hydroxysteroid Dehydrogenases/metabolism , 3-Oxo-5-alpha-Steroid 4-Dehydrogenase/metabolism , Androgens/metabolism , Fibroblasts/enzymology , Lung/cytology , 17-Hydroxysteroid Dehydrogenases/genetics , 3-Hydroxysteroid Dehydrogenases/genetics , 3-Hydroxysteroid Dehydrogenases/metabolism , 3-Oxo-5-alpha-Steroid 4-Dehydrogenase/genetics , Androstenedione/metabolism , Cells, Cultured , Cytosol/enzymology , Dihydrotestosterone/metabolism , Enzyme Activation/physiology , Estradiol Dehydrogenases , Fibroblasts/cytology , Gene Expression Regulation, Enzymologic/physiology , Humans , Microsomes/enzymology , RNA, Messenger/analysis , Testosterone/metabolism
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