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1.
Int J Mol Sci ; 24(23)2023 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-38069100

RESUMO

The castration of stallions is traditionally performed after puberty, at around the age of 2 years old. No studies have focused on the effects of early castration on osteoarticular metabolism. Thus, we aimed to compare early castration (3 days after birth) with traditional castration (18 months of age) in horses. Testosterone and estradiol levels were monitored from birth to 33 months in both groups. We quantified the levels of biomarkers of cartilage and bone anabolism (CPII and N-MID) and catabolism (CTX-I and CTX-II), as well as of osteoarthritis (HA and COMP) and inflammation (IL-6 and PGE2). We observed a lack of parallelism between testosterone and estradiol synthesis after birth and during puberty in both groups. The extra-gonadal synthesis of steroids was observed around the 28-month mark, regardless of the castration age. We found the expression of estrogen receptor (ESR1) in cartilage and bone, whereas androgen receptor (AR) expression appeared to be restricted to bone. Nevertheless, with respect to osteoarticular metabolism, steroid hormone deprivation resulting from early castration had no discernable impact on the levels of biomarkers related to bone and cartilage metabolism, nor on those associated with OA and inflammation. Consequently, our research demonstrated that early castration does not disrupt bone and cartilage homeostasis.


Assuntos
Osteoartrite , Maturidade Sexual , Animais , Masculino , Cavalos , Orquiectomia , Castração , Testosterona/farmacologia , Estradiol/farmacologia , Inflamação , Biomarcadores
2.
Eur J Nutr ; 57(7): 2477-2488, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28770334

RESUMO

PURPOSE: Metabolic syndrome (MetS), a multicomponent condition, is a cardiovascular disease predictor. Although exposure to agricultural pesticides has been suggested as a potential contributor to the rising rates of obesity, type 2 diabetes, and other features of metabolic disorders, no studies have focused on the association between consumption of organic food (produced without synthetic pesticides) and MetS. We aimed to investigate the cross-sectional association between organic food consumption and MetS in French adults to determine whether it would be worth conducting further studies, particularly large prospective and randomised trials. METHODS: A total of 8174 participants from the NutriNet-Santé study who attended a clinical visit and completed an organic food frequency questionnaire were included in this cross-sectional analysis. We evaluated the association between the proportion of organic food in the diet (overall and by food group) and MetS using Poisson regression models while adjusting for potential confounders. RESULTS: Higher organic food consumption was negatively associated with the prevalence of MetS: adjusted prevalence ratio was 0.69 (95% CI 0.61, 0.78) when comparing the third tertile of proportion of organic food in the diet with the first one (p value <0.0001). Higher consumption of organic plant-based foods was also related to a lower probability of having MetS. In addition, when stratifying by lifestyle factors (nutritional quality of the diet, smoking status, and physical activity), a significant negative association was detected in each subgroup (p values <0.05), except among smokers. CONCLUSIONS: Our results showed that a higher organic food consumption was associated with a lower probability of having MetS. Additional prospective studies and randomised trials are required to ascertain the relationship between organic food consumption and metabolic disorders.


Assuntos
Dieta , Alimentos Orgânicos , Síndrome Metabólica/epidemiologia , Resíduos de Praguicidas/efeitos adversos , Adulto , Estudos Transversais , Diabetes Mellitus Tipo 2/epidemiologia , Dieta/normas , Feminino , Humanos , Masculino , Prevalência , Estudos Prospectivos , Fatores de Risco
3.
Gen Comp Endocrinol ; 233: 100-108, 2016 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-27222348

RESUMO

Estrogen receptors ESR1, ESR2 and GPER are present on mature ejaculated horse spermatozoa, suggesting these cells as putative targets for estrogens. Indeed, spermatozoa are exposed to high level of estrogens during the transit in the male and female genital tracts but their roles are not investigated. So, we evaluated in vitro the role of 17ß-estradiol during post-testicular maturations: regulation of motility, capacitation and acrosome reaction. Moreover according to the pseudo-seasonal breeder status of the stallion, we analyzed the putative seasonal variations in the presence of ESRs in spermatozoa. We showed that ESRs are more present on stallion sperm during the breeding season. We showed that capacitation and acrosome reaction are independent of estradiol action in horse. Estradiol can weakly modulate the motility and this effect is strictly associated with GPER and not with ESR1 and ESR2. The subcellular localization of GPER in the neck on stallion sperm is coherent with this effect. It seems that estrogens are not major regulators of sperm maturations associated to mare genital tract, so they could act during the epididymal maturations.


Assuntos
Receptor alfa de Estrogênio/fisiologia , Receptor beta de Estrogênio/fisiologia , Cavalos/fisiologia , Receptores Acoplados a Proteínas G/fisiologia , Capacitação Espermática , Maturação do Esperma , Reação Acrossômica/efeitos dos fármacos , Animais , Epididimo/efeitos dos fármacos , Epididimo/metabolismo , Estradiol/farmacologia , Receptor alfa de Estrogênio/metabolismo , Receptor beta de Estrogênio/metabolismo , Feminino , Cavalos/genética , Masculino , Receptores de Estrogênio/metabolismo , Receptores de Estrogênio/fisiologia , Receptores Acoplados a Proteínas G/metabolismo , Capacitação Espermática/efeitos dos fármacos , Maturação do Esperma/efeitos dos fármacos , Maturação do Esperma/fisiologia , Motilidade dos Espermatozoides/efeitos dos fármacos , Transporte Espermático/efeitos dos fármacos , Espermatozoides/efeitos dos fármacos , Espermatozoides/metabolismo , Espermatozoides/fisiologia , Distribuição Tecidual
4.
Gen Comp Endocrinol ; 200: 35-43, 2014 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-24607572

RESUMO

Among mammals, the stallion produces the largest amount of testicular estrogens. These steroid hormones are produced mainly by Leydig and Sertoli cells in the testis and also in the epididymis. Their role in horse testicular physiology and their ability to act on spermatozoa are still unknown. In order to determine if spermatozoa are targets for estrogens, the presence of estrogen receptors in mature ejaculated spermatozoa has been investigated. The presence of a single isoform of ESR1 (66kDa) and ESR2 (61kDa) was found by Western-blot analysis in samples from seven stallions. Confocal analysis mainly showed a flagellar localization for both receptors. Immuno-TEM experiments revealed that they are mostly located near the membranes, which are classically associated with rapid, non-genomic, effects. Moreover, we evidenced the expression of the seven transmembrane estradiol binding receptor GPER in colt testis. The protein was also localized at the connecting piece in mature spermatozoa. In conclusion, our results suggest that horse spermatozoa are a target for estrogens, which could act on several receptors either during the epididymal transit and/or in the female genital tract.


Assuntos
Membrana Celular/metabolismo , Estrogênios/metabolismo , Cavalos/metabolismo , Receptores de Estrogênio/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Espermatozoides/metabolismo , Animais , Western Blotting , Ejaculação , Feminino , Citometria de Fluxo , Regulação da Expressão Gênica , Imuno-Histoquímica , Masculino , Transporte Proteico , Receptores Acoplados a Proteínas G/genética , Espermatozoides/citologia , Espermatozoides/ultraestrutura , Frações Subcelulares/metabolismo
5.
Trials ; 24(1): 438, 2023 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-37400867

RESUMO

BACKGROUND: Hypertension is the most frequent chronic pathology in France and in the world. It is one of the main modifiable cardiovascular risk factors. In France, 50% of treated hypertensives are uncontrolled and only 30% of treated patients are fully adherent to their antihypertensive treatment. Poor adherence to drug treatments is considered as one of the main causes of non-control of hypertension. Since 2018, a new profession has entered the French healthcare system: advanced practice nurses (APN). They have many broad-based skills, at the interface of nursing and medical exercises. The purpose of this study is to assess the impact of an APN intervention versus usual care on hypertension control. METHODS: The study will take place at the Hôtel-Dieu University Hospital, Paris, France, as prospective, open-label, controlled, randomized 1-to-1, monocentric, and superiority trial. The participants will be recruited during day hospitalization for cardiovascular assessment in the context of their hypertension management. Patients will be divided into two groups: a "usual care" group which will continue traditional follow-up (day hospitalization followed by consultation with a medical doctor (MD) within approximately 2-12 months) and an "intervention" group which will meet an APN between the day hospitalization and the MD consultation. Participants will be monitored until 12 months after the day hospitalization, depending on their last follow-up study appointment (MD consultation). The primary outcome is the rate of controlled BP (BP < 140/90 mmHg in office BP measurement) in each group. The hypothesis formulated is that an individual APN intervention, included in usual hypertension management, improves hypertension control. DISCUSSION: This innovative study will be the first in France where APNs are beginning to be established in the healthcare system. It will provide an objective look at this new profession and the impact it can have in the framework of global management of hypertension. TRIAL REGISTRATION: ClinicalTrials.gov NCT0448249. Registered on June 24, 2020.


Assuntos
Hipertensão , Humanos , Seguimentos , Estudos Prospectivos , Hipertensão/diagnóstico , Hipertensão/tratamento farmacológico , Anti-Hipertensivos/efeitos adversos , Encaminhamento e Consulta , Resultado do Tratamento , Ensaios Clínicos Controlados Aleatórios como Assunto
6.
Reprod Toxicol ; 118: 108363, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36931579

RESUMO

Although it is well established that testis produces estrogens, their precise effect is not fully documented, particularly during the prepubertal period. In a previous in vivo study, we demonstrated that an exposure of prepubertal rats (15-30 days post-partum (dpp)) to 17ß-estradiol (E2) delays the establishment of spermatogenesis. In order to characterize the mechanisms of action and the direct targets of E2 on the immature testis, we developed an organotypic culture model of testicular explants obtained from prepubertal rats (15, 20 and 25 dpp). To determine the involvement of nuclear estrogen receptors (ERs) in the effect of E2, particularly that of ESR1 which is the major ER expressed in the prepubertal testis, a pre-treatment with the full antagonist of this type of ERs (ICI 182.780) was performed. Histological analyses, gene expression studies and hormonal assays were conducted to investigate the effects of E2 on steroidogenesis- and spermatogenesis-related endpoints. Testicular explants from 15 dpp rats were unresponsive to E2 exposure while E2 effects were observed in those obtained from 20 and 25 dpp rats. An E2 exposure of testicular explants obtained from 20 dpp rats seemed to accelerate the establishment of spermatogenesis, whereas an E2 exposure of 25 dpp testicular explants induced a delay of this process. These effects could be related to the E2-induced modulation of steroidogenesis, and involved both ESR1-dependent and -independent mechanisms of action. Overall, this ex vivo study demonstrated differential age- and concentration-related effects of E2 on the testis during the prepubertal period.


Assuntos
Estradiol , Testículo , Masculino , Ratos , Animais , Estradiol/metabolismo , Estrogênios/farmacologia , Espermatogênese , Receptores de Estrogênio/metabolismo
7.
J Virol Methods ; 319: 114756, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37268046

RESUMO

Equine arteritis virus (EAV) is an Alphaarterivirus (family Arteriviridae, order Nidovirales) that frequently causes an influenza-like illness in adult horses, but can also cause the abortions in mares and death of newborn foals. Once primary infection has been established, EAV can persist in the reproductive tract of some stallions. However, the mechanisms enabling this persistence, which depends on testosterone, remain largely unknown. We aimed to establish an in vitro model of non-cytopathic EAV infection to study viral persistence. In this work, we infected several cell lines originating from the male reproductive tract of different species. EAV infection was fully cytopathic for 92BR (donkey cells) and DDT1 MF-2 (hamster cells) cells, and less cytopathic for PC-3 cells (human cells); ST cells (porcine cells) seemed to eliminate the virus; LNCaP (human cells) and GC-1 spg (murine cells) cells were not permissive to EAV infection; finally, TM3 cells (murine cells) were permissive to EAV infection without any overt cytopathic effects. Infected TM3 cells can be maintained at least 7 days in culture without any subculture. They can also be subcultured over 39 days (subculturing them at 1:2 the first time at 5 dpi and then every 2-3 days), but in this case, the percentage of infected cells remains low. Infected TM3 cells may therefore provide a new model to study the host-pathogen interactions and to help determine the mechanisms involved in EAV persistence in stallion reproductive tract.


Assuntos
Infecções por Arterivirus , Equartevirus , Doenças dos Cavalos , Cricetinae , Gravidez , Masculino , Cavalos , Animais , Humanos , Feminino , Camundongos , Suínos , Interações Hospedeiro-Patógeno , Genitália , Linhagem Celular , Infecções por Arterivirus/veterinária
8.
J Clin Hypertens (Greenwich) ; 24(10): 1266-1275, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-36177966

RESUMO

Lifestyle recommendations are first-line elements in the management of arterial hypertension. This cross-sectional study aimed to analyze the level to which lifestyle recommendations are used in hypertension management in France, using data from the Esteban study, which was implemented by Santé Publique France, France's public health agency, from 2014 to 2016 on a representative sample of the French population. The study sample comprised 440 adult Esteban participants who were aware they had hypertension and were aged 18-74 years old. The main outcomes were the proportion of participants who received lifestyle recommendations in their hypertension management plan, and the proportion of recommendations according to the three following dimensions: physical activity, weight loss, and changes in diet. Over half (57.0%) of the 440 participants declared they did not receive lifestyle recommendations as part of their hypertension management plan in the year preceding the study. Of these, 39.0% did not receive pharmacological treatment either. Physical activity was recommended to 31.8% of sedentary participants and weight loss to 26.8% of participants with overweight or obesity. One-fifth of the study sample (20.1%) received dietary recommendations. Of these, 69% and 10.7% were advised to limit their salt and alcohol intake, respectively. Lifestyle interventions are too rarely recommended in hypertension management plans in France. Adherence to lifestyle recommendations needs in-depth discussion not only at the time of diagnosis but also throughout follow-up.


Assuntos
Hipertensão , Adulto , Humanos , Adolescente , Adulto Jovem , Pessoa de Meia-Idade , Idoso , Hipertensão/terapia , Hipertensão/tratamento farmacológico , Estudos Transversais , Estilo de Vida , Redução de Peso , Cloreto de Sódio na Dieta , França/epidemiologia
9.
Reprod Toxicol ; 111: 211-224, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35700937

RESUMO

Over the past few decades, male fertility has been decreasing worldwide. Many studies attribute this outcome to endocrine disruptors exposure such as bisphenol A (BPA), which is a chemical compound used in plastics synthesis and exhibiting estrogenic activity. In order to assess how the window of exposure modulates the effects of BPA on the testis, prepubertal (15 dpp to 30 dpp) and pubertal (60 dpp to 75 dpp) male Sprague-Dawley rats were exposed to BPA (50 µg/kg bw/day), 17-ß-estradiol (E2) (20 µg/kg bw/day) as a positive control, or to a combination of these compounds. For both periods of exposure, the rats were sacrificed and their testes were collected at 75 dpp. The histological analysis and the quantification of the gene expression of testis cell markers by RT-qPCR confirmed the complete spermatogenesis in all groups for both periods of exposure. However, our results suggest a deleterious effect of BPA on the blood-testis barrier in adults after pubertal exposure as BPA and BPA+E2 treatments induced a decrease in caveolin-1 and connexin-43 gene expression; which are proteins of the junctional complexes. As none of these effects were found after a prepubertal exposure, these results suggested the reversibility of BPA's effects. Caution must be taken when transposing this finding to humans and further studies are needed in this regard. However, from a regulatory perspective, this study emphasizes the importance of taking into account different periods of exposure, as they present different sensitivities to BPA exposure.


Assuntos
Disruptores Endócrinos , Estradiol , Animais , Compostos Benzidrílicos/toxicidade , Disruptores Endócrinos/metabolismo , Estradiol/metabolismo , Masculino , Fenóis , Ratos , Ratos Sprague-Dawley , Testículo
10.
PLoS One ; 17(10): e0275337, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36251660

RESUMO

Type 2 diabetes (T2D) induces hyperglycemia, alters hemoglobin (Hb), red blood cell (RBC) deformability and impairs hemorheology. The question remains whether RBC breakdown and intravascular hemolysis (IVH) occur in T2D patients. We characterized RBC-degradation products and vesiculation in a case-control study of 109 T2D patients and 65 control subjects. We quantified heme-related absorbance by spectrophotometry and circulating extracellular vesicles (EV) by flow cytometry and electron microscopy. Heme-related absorbance was increased in T2D vs. control plasma (+57%) and further elevated in obese T2D plasma (+27%). However, large CD235a+ EV were not increased in T2D plasma. EV from T2D plasma, or shed by isolated T2D RBC, were notably smaller in diameter (-27%) and carried heme-related absorbance. In T2D plasma, higher heme-related absorbance (+30%) was associated to peripheral sensory neuropathy, and no other vascular complication. In vitro, T2D RBC-derived EV triggered endothelial stress and thrombin activation in a phosphatidylserine- and heme-dependent fashion. We concluded that T2D was associated with low-grade IVH. Plasma absorbance may constitute a novel biomarker of peripheral neuropathy in T2D, while flow cytometry focusing on large EV may be maladapted to characterize RBC EV in T2D. Moreover, therapeutics limiting IVH or neutralizing RBC breakdown products might bolster vasculoprotection in T2D.


Assuntos
Diabetes Mellitus Tipo 2 , Traumatismos dos Nervos Periféricos , Biomarcadores/metabolismo , Estudos de Casos e Controles , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/metabolismo , Eritrócitos/metabolismo , Heme/metabolismo , Hemoglobinas/metabolismo , Hemólise , Humanos , Traumatismos dos Nervos Periféricos/metabolismo , Fosfatidilserinas/metabolismo , Trombina/metabolismo
11.
Domest Anim Endocrinol ; 79: 106691, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-34844012

RESUMO

Although vitamin D acts in various biological processes, it plays a critical role in the maintenance of bone health, and regulates calcium homeostasis. In humans and rodents, the main tissues involved in vitamin D metabolism are the liver and the kidneys, however it has been shown that the testis has strongly participated in its bioactivation. Indeed, in these different species, enzymes metabolizing vitamin D (CYP27A1, CYP27B1 and CYP2R1) have been demonstrated in this tissue. Moreover, men with hypogonadism have shown a decrease in circulating levels of vitamin D. In equine species, the castration of males is a regular practice to reduce the behavior of stallions deemed too aggressive. Castration is carried out at various ages: in foals during their growth or in adulthood once they have reached their optimum size. Although horses exhibit atypical vitamin D metabolism with low circulating levels of vitamin D, it was suggested that testis may contribute to its activation as has been described in rodents and humans; castration could therefore be likely to affect its metabolism. In this study, blood levels of bioactive form of vitamin D (1 α,25[OH] 2 vitamin D 3 ) were measured before and after castration at different ages: 1 wk, after puberty (2 yr) and at adulthood (6 yr). The gene expression of enzymes involved in vitamin D metabolism has been sought in the testis of different experimental groups. No change in bioactive vitamin D3 levels was observed after castration regardless of the age at the time of surgery. The exceptional status of equine species is confirmed with a low or a lack of testis contribution to vitamin D metabolism, regardless of testicular development. This is demonstrated by a low or a lack of signal from enzymes involved in vitamin D bioactivation. Therefore, horses constitute a unique model in comparative endocrinology.


Assuntos
Testículo , Vitamina D , Animais , Colecalciferol/metabolismo , Sistema Enzimático do Citocromo P-450/genética , Cavalos/genética , Humanos , Masculino , RNA Mensageiro/metabolismo
12.
Biochemistry ; 50(47): 10284-92, 2011 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-22035182

RESUMO

1α,25-Dihydroxyvitamin D(3) (1,25D(3)) is the active metabolite of vitamin D(3) and the major calcium regulatory hormone in tissues. The aim of this work was to investigate the mechanism of action of 1,25D(3) on (45)Ca(2+) uptake in Sertoli cells from 30-day-old rats. Results showed that 10(-9) and 10(-12) M 1,25D(3) increased the rate of (45)Ca(2+) uptake 5 and 15 min after hormone exposure and that 1α,25(OH)(2) lumisterol(3) (JN) produced a similar effect suggesting that 1,25D(3) action occurs via a putative membrane receptor. The involvement of voltage-dependent calcium channels (VDCC) in 1,25D(3) action was evidenced by using nifedipine, while the use of Bapta-AM demonstrated that intracellular calcium was not implicated. Moreover, the incubation with ouabain and digoxin increased the rate of (45)Ca(2+) uptake, indicating that the effect of 1,25D(3) may also result from Na(+)/K(+)-ATPase inhibition. In addition, we demonstrated that the mechanism underlying the hormone action involved extracellular signal-regulated kinase (ERK) and protein kinase C (PKC) activation in a phospholipase C-independent way. Furthermore, a local elevation of the level of cAMP, as demonstrated by incubating cells with dibutyryl cAMP or a phosphodiesterase inhibitor, produced an effect similar to that of 1,25D(3), and the inhibition of protein kinase A (PKA) nullified the hormone action. In conclusion, the stimulatory effect of 1,25D(3) on (45)Ca(2+) uptake in Sertoli cells occurs via VDCC, as well as PKA, PKC, and ERK activation. These protein kinases seem to act by inhibiting Na(+)/K(+)-ATPase or directly phosphorylating calcium channels. The Na(+)/K(+)-ATPase inhibition may result in Na(+)/Ca(2+) exchanger activation in reverse mode and consequently induce the uptake of calcium into the cells.


Assuntos
Cálcio/metabolismo , Ratos/metabolismo , Células de Sertoli/metabolismo , Transdução de Sinais , Vitamina D/análogos & derivados , Animais , Transporte Biológico , Canais de Cálcio/metabolismo , Células Cultivadas , Masculino , Ratos/crescimento & desenvolvimento , Ratos Wistar , Testículo/citologia , Testículo/crescimento & desenvolvimento , Testículo/metabolismo , Fatores de Tempo , Vitamina D/metabolismo
13.
Arch Biochem Biophys ; 515(1-2): 46-53, 2011 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-21933661

RESUMO

1α,25-Dihydroxyvitamin D(3) (1,25D(3)) is critical for the maintenance of normal reproduction since reduced fertility is observed in vitamin D-deficient male rats. The aim of this study was to investigate the effect of 1,25D(3) in 30-day-old rat testicular plasma membrane targets (calcium uptake and gamma-glutamyl transpeptidase (GGTP) activity), as well as to highlight the role of protein kinases in the mechanism of action of 1,25D(3). The results demonstrated that 1,25D(3) induced a fast increase in calcium uptake in rat testis through a nongenomic mechanism of action. This effect was dependent on PKA, PKC and MEK. Moreover, ionic channels, such as ATP- and Ca(2+)-dependent K(+) channels and Ca(2+)-dependent Cl(-) channels, are involved in the mechanism of action. The use of BAPTA-AM showed that [Ca(2+)](i) was also implicated, and the incubation with digoxin produced an increase in (45)Ca(2+) uptake indicating that the effect of 1,25D(3) may also result from Na(+)/K(+)-ATPase inhibition. In addition, 1,25D(3) was able to increase the GGTP activity. Considered together, our results indicate a PKA/PKC/MEK-dependent 1,25D(3) pathway as well as ionic involvement leading to (45)Ca(2+) uptake in immature rat testis. These findings demonstrate that 1,25D(3) stimulates calcium uptake and increases GGTP activity which may be involved in male reproductive functions.


Assuntos
Calcitriol/metabolismo , Canais Iônicos/metabolismo , Testículo/metabolismo , gama-Glutamiltransferase/metabolismo , Animais , Membrana Celular/metabolismo , Masculino , Ratos , Ratos Wistar , Testículo/enzimologia
14.
Reprod Fertil Dev ; 23(5): 725-35, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21635821

RESUMO

It is well known that the vitamin D endocrine system is involved in physiological and biochemical events in numerous tissues, especially gut, bone and kidney but also testis. Therefore, in this study the effect and mechanisms of action of 1α,25(OH)(2) vitamin D(3) (1,25D) on aromatase gene expression in immature rat Sertoli cells were evaluated. Vitamin D receptor transcripts were present in immature Sertoli cells as well as in adult testicular germ cells and somatic cells. The treatment of immature Sertoli cells with 100 nM 1,25D increased the amount of aromatase transcript, mainly in 30-day-old rats. The protein kinase A (PKA) blocker, H89, partially inhibited the 1,25D effect. The stimulation of aromatase gene expression in 30-day-old Sertoli cells by the agonist 1α,25(OH)(2) lumisterol(3), and the suppression of the 1,25D effect by the antagonists 1ß,25(OH)(2) vitamin D(3) and (23S)-25-dehydro-1α (OH)-vitamin D(3)-26,23-lactone suggested, besides a genomic effect of 1,25D, the existence of non-genomic activation of the membrane-bound vitamin D receptor involving the PKA pathway.


Assuntos
Aromatase/metabolismo , Calcitriol/metabolismo , Células de Sertoli/enzimologia , Fatores Etários , Animais , Aromatase/genética , Calcitriol/análogos & derivados , Calcitriol/farmacologia , Proteínas Quinases Dependentes de AMP Cíclico/antagonistas & inibidores , Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , Ergosterol/farmacologia , Regulação Enzimológica da Expressão Gênica , Isoquinolinas/farmacologia , Masculino , Inibidores de Proteínas Quinases/farmacologia , RNA Mensageiro/metabolismo , Ratos , Ratos Sprague-Dawley , Receptores de Calcitriol/antagonistas & inibidores , Receptores de Calcitriol/genética , Receptores de Calcitriol/metabolismo , Células de Sertoli/efeitos dos fármacos , Sulfonamidas/farmacologia
15.
Eur J Hosp Pharm ; 28(Suppl 2): e197-e202, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34183458

RESUMO

OBJECTIVES: In recent years, hospital pharmacists have gained more importance in the clinical support of patients. However, most of the studies evaluating the impact of clinical pharmacy have only studied patients' adherence or satisfaction. The aim of this study was to evaluate the direct clinical outcomes of a pharmacist-led educational intervention in patients with chronic disease. METHODS: We conducted a randomised, controlled, parallel, physician-blinded study in a day hospital and a consultation unit of a French teaching hospital over a 1-year period. Patients with hypertension, type 2 diabetes or hypercholesterolaemia who did not reach their therapeutic goals despite drug therapy were eligible. Patients in the intervention group received an intervention from a hospital pharmacist who provided patient education on pathology and drug management. The primary outcome was the proportion of patients reaching their therapeutic goals for blood pressure, glycated haemoglobin level or low-density lipoprotein cholesterol level at the 3-month follow-up consultation. RESULTS: From January to December 2015, 89 patients were included and 73 completed the study. In the intervention group, 61.7% (21/34) of the patients reached their therapeutic goals compared with 33.3% (13/39) in the control group (p=0.015). The intervention was significantly more effective in polypharmacy patients (60.0% (12/20) vs 16.7% (4/24); p=0.005), in those aged >60 years (57.9% (11/19) vs 26.1% (6/23); p=0.037) and in patients with a high education level (68.8% (11/16) vs 29.4% (5/17); p=0.024). CONCLUSION: A single pharmacist-led educational intervention has a clinical impact, doubling the proportion of patients reaching their therapeutic goals at 3 months, especially in polypharmacy patients and those aged >60 years. This study confirms the value of clinical involvement of hospital pharmacists in patient care in a consultation unit and day hospital.


Assuntos
Diabetes Mellitus Tipo 2 , Hipercolesterolemia , Hipertensão , Serviço de Farmácia Hospitalar , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/epidemiologia , Humanos , Hipercolesterolemia/tratamento farmacológico , Hipercolesterolemia/epidemiologia , Hipertensão/diagnóstico , Hipertensão/tratamento farmacológico , Hipertensão/epidemiologia , Pessoa de Meia-Idade , Farmacêuticos
16.
Environ Pollut ; 269: 116140, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-33316489

RESUMO

On 15th April 2019, Parisians watched in shock as Notre-Dame de Paris, the iconic cathedral that has towered over their city for almost 900 years, was engulfed in flames. Although flames destroyed the spire and considerably weakened the structure, no human lives were lost. However, as some amounts of lead volatilized and deposited in the surrounding areas, fears of potential intoxication began to rise. We investigated the impact of this fire on the blood lead levels of adults in Paris according to the distance between the cathedral and where they live or work. The geometric mean of blood lead levels of the study population was 1.49µg/dl (95% CI [1.38-1.62]) with a prevalence of blood lead levels≥5.0µg/dL of 5.0%. Despite the early legitimate fears of intoxication, the fire that destroyed a significant part of the Notre-Dame cathedral did not increase the blood lead levels of adults living and working in the vicinity.


Assuntos
Incêndios , Chumbo , Adulto , Humanos
17.
Theriogenology ; 172: 36-46, 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34091204

RESUMO

The aim of this study was to investigate the rapid response pathway and gene and protein expression profiles of the rat testis in response to estradiol (E2) and 1α,25(OH)2 vitamin D3 (1,25-D3), to understand how they mediate their effects on the first spermatogenic wave. To do this, we compared the effects of 1,25-D3 and E2 on 45calcium(Ca2+) uptake and the involvement of estrogen receptors (ESR) in their rapid responses. Additionally, we studied the downstream signal transduction effects of 1,25-D3 and E2 on cyclin A1/B1 and cellular cycle protein expression. As previously observed for 1,25-D3, E2 also increased 45Ca2+ uptake in immature rat testes via voltage-dependent Ca2+ channels, Ca2+-dependent chloride channels and via the activation of protein kinase C, protein kinase A and mitogen-activated protein kinase kinase (MEK). Elevated aromatase expression by testes was observed in the presence of 1,25-D3 and both hormones decreased ESR mRNA expression. Furthermore, 1,25-D3 and E2 diminished cyclin A1 mRNA expression, but E2 did not affect cyclin B1 mRNA levels. Consistent with these findings, the immunocontent of cyclin A1 and B1 in the testes was also increased by 1,25-D3 and E2. 1,25-D3 increased expressions of the p16 and p53 proteins, supporting the anti-proliferative and pro-apoptotic properties of 1,25-D3, while E2 also augmented p16. Data indicate that both hormones trigger rapid responses at the plasma membrane that may control the expression of gene and proteins related to cell cycle regulation, and thereby modulate spermatogenesis.


Assuntos
Cálcio , Estradiol , Animais , Membrana Celular , Colecalciferol , Estradiol/farmacologia , Genômica , Masculino , Ratos , Transdução de Sinais , Testículo
18.
Reprod Fertil Dev ; 22(3): 508-15, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-20188023

RESUMO

Aromatase, the enzyme responsible for the transformation of androgens into oestrogens, is encoded by the cyp19 gene expressed in the testis. The aim of the present study was to analyse the evolution of aromatase gene expression under FSH control in rat Sertoli cells between 10 and 30 days post partum, corresponding to the end of the proliferative period of Sertoli cells, establishment of the blood-testis barrier and acquisition of the mature phenotype. The maximum stimulatory effect of FSH on aromatase gene expression was obtained in 20-day-old rat Sertoli cells, compared with cells from 10- and 30-day-old rats, in parallel with the differentiation of Sertoli cells. Using two effectors of the protein kinase A pathway (i.e. forskolin and dibutyryl-cAMP) revealed differential effects between cells from rats aged 20 and 30 days, implying the involvement of another signalling pathway. Experiments using the specific phosphatidylinositol 3-kinase (PI3-K) inhibitor LY294002 revealed that PI3-K is strongly involved in FSH-induced aromatase expression in Sertoli cells from both 20- and 30-day-old rats. In vivo, this decrease could be explained by a negative effect exerted by germ cells because, in coculture, aromatase gene expression in 20-day-old Sertoli cells is greatly diminished.


Assuntos
Envelhecimento/genética , Aromatase/genética , Hormônio Foliculoestimulante/metabolismo , Células de Sertoli/metabolismo , Fatores Etários , Análise de Variância , Animais , Aromatase/metabolismo , Barreira Hematotesticular/efeitos dos fármacos , Barreira Hematotesticular/metabolismo , Células Cultivadas , Cromonas/farmacologia , Inibidores Enzimáticos/farmacologia , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Regulação Enzimológica da Expressão Gênica/fisiologia , Isoquinolinas/farmacologia , Masculino , Morfolinas/farmacologia , Fosfatidilinositol 3-Quinases/genética , Fosfatidilinositol 3-Quinases/metabolismo , Ratos , Ratos Sprague-Dawley , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Células de Sertoli/citologia , Células de Sertoli/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/fisiologia , Sulfonamidas/farmacologia
19.
J Clin Hypertens (Greenwich) ; 22(12): 2204-2213, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32966691

RESUMO

Home blood pressure monitoring (HBPM) is increasingly being promoted in hypertension guidelines to improve hypertension management. Possessing a HBPM device could improve blood pressure (BP) control and prognostic impact. The aims of this study were to estimate the possession rate of HBPM devices in the French population and in hypertensive adults, and to investigate the determinants of possessing such devices at home. Cross-sectional analyses were performed using data from the Esteban survey, which comprised a representative sample of the French population. Among the 2,054 study participants, 673 had hypertension. Of these, 385 were aware they had it. Weighted logistic regressions were performed to investigate the factors (socioeconomic, clinical, drug treatment, and healthcare visits) associated with possessing a HBPM device. 20.9% of the study sample, 42.1% of those with hypertension, and 54% of those aware of their hypertension, possessed a HBPM device. Female gender (OR = 2.03, 95%CI [1.46; 2.60]), smoking (OR = 2.33, 95%CI [1.51; 3.15]), antihypertensive drugs (OR = 1.75, 95%CI [1.06; 2.44]), general practitioner (GP) visits (OR = 3.28, 95%CI [1.84; 4.68]), and diabetes (OR = 0.41 95% CI [0.14; 0.68]) were associated with possessing a HBPM device among those aware of their hypertension. Over 20% of the study population possessed a HBPM device at home. This proportion rose to one in two in those aware or their hypertension. Among the latter, possessing a device was positively associated with female gender, GP visits, and antihypertensive drug use. Increasing possession of HBPM devices in the hypertensive population could foster better management of the condition.


Assuntos
Monitorização Ambulatorial da Pressão Arterial , Hipertensão , Adulto , Anti-Hipertensivos/uso terapêutico , Pressão Sanguínea , Estudos Transversais , Feminino , França/epidemiologia , Humanos , Hipertensão/diagnóstico , Hipertensão/tratamento farmacológico , Hipertensão/epidemiologia
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