Factors associated with COVID-19 vaccine hesitancy among health personnel in Yaounde, Cameroon

Background. Health care personnel constitute a group at high risk of contracting COVID-19. However, the vaccination rate in this group in our context remains low. The objective of our study was to determine the factors associated with COVID-19 vaccine hesitancy among health care workers in Yaounde. Methods.We conducted a cross-sectional study of 360 health personnel in three hospitals in the city of Yaounde from January to March 2022, i.e., 3 months. All health personnel who gave their free consent were included. Ethical clearance was obtained from the Institutional Ethics and Research Committee of the Faculty of Medicine and Biomedical Sciences of the University of Yaounde I. A logistic regression was performed to search for factors associated with reluctance to vaccinate, with a significance level of 0.05. Results.The vaccination rate against COVID-19 was 34% (123). Factors associated with vaccine hesitancy were female gender (OR [95% CI] =3.5[2.2-5.5]; p<0.001), working outside a COVID-19 management unit (OR [95% CI]=6, [2.1-18.5]; p=0.001), fear of the harmfulness of COVID-19 vaccines (OR [CI 95%] =2.7[1.7-4.2]; p<0.001), and doubt of vaccine efficacy (OR [CI 95%] =4.0[2.5-6.4]; p<0.001). Conclusion:Health personnel are still reluctant to vaccinate in our context. Factors associated with hesitancy to vaccination against COVID-19 could help deconstruct apprehensions.

Introduction. La pandémie de la COVID-19 a ajouté un fardeau supplémentaire dans les pays aux systèmes de santé déjà fragiles. Objectif : déterminer la prévalence et la séroprévalence de la COVID-19 en cas de suspicion du paludisme au cours de la deuxième vagueà Yaoundé. Méthodologie. Une étude transversale descriptive a été menée au Centre Médical le Jourdain pendant 8 semaines du 19 Avril au 13 Juin 2021 soit durant la deuxième vague au Cameroun. Pour les 86 patients avec suspicion de paludisme, des prélèvements nasopharyngé et sanguins ont été réalisés pour la recherche d'antigène du SRAS- CoV 2 et des IgG et IgM anti-SARS-CoV-2 grâce aux kits STANDARDTM Q COVID-19 Ag de SD BIOSENSOR, Corée, 2020 et StandardTM Q COVID 19 Ac IgG/IgM de SD BIOSENSOR, Corée, 2020 respectivement. La confirmation du paludisme a été faite grâce à l'examen microscopique des étalements de sang colorés. Résultats. Le paludisme était confirmé dans 20,9% (18) des cas. Les prévalences de la COVID-19 et de la coïnfection COVID19/Paludisme étaient de 8,1% et de 0,9% respectivement. Sur les 25,6% (54) des patients avec des IgM anti-COVID-19, aucun cas de microscopie positive n'a été retrouvé. Par ailleurs un peu plus de la moitié des patients avaient des anticorps IgG anti-COVID-19 qu'ils aient une goutte épaisse positive ou pas soit 56,0% (42/75) et 52,2% (71/136) respectivement. Conclusion. En cas de suspicion du paludisme en zone impaludée, il parait non négligeable de considérer la COVID-19 comme un diagnostic différentiel.

Targeting macrophagic 17β-HSD7 by fenretinide for the treatment of nonalcoholic fatty liver disease

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide and macrophage polarization plays an important role in its pathogenesis. However, which molecule regulates macrophage polarization in NAFLD remains unclear. Herein, we showed NAFLD mice exhibited increased 17β-hydroxysteroid dehydrogenase type 7 (17β-HSD7) expression in hepatic macrophages concomitantly with elevated M1 polarization. Single-cell RNA sequencing on hepatic non-parenchymal cells isolated from wild-type littermates and macrophage-17β-HSD7 knockout mice fed with high fat diet (HFD) for 6 weeks revealed that lipid metabolism pathways were notably changed. Furthermore, 17β-HSD7 deficiency in macrophages attenuated HFD-induced hepatic steatosis, insulin resistance and liver injury. Mechanistically, 17β-HSD7 triggered NLRP3 inflammasome activation by increasing free cholesterol content, thereby promoting M1 polarization of macrophages and the secretion of pro-inflammatory cytokines. In addition, to help demonstrate that 17β-HSD7 is a potential drug target for NAFLD, fenretinide was screened out from an FDA-approved drug library based on its 17β-HSD7 dehydrogenase inhibitory activity. Fenretinide dose-dependently abrogated macrophage polarization and pro-inflammatory cytokines production, and subsequently inhibited fat deposition in hepatocytes co-cultured with macrophages. In conclusion, our findings suggest that blockade of 17β-HSD7 signaling by fenretinide would be a drug repurposing strategy for NAFLD treatment.

Equisetin is an anti-obesity candidate through targeting 11β-HSD1

Obesity is increasingly prevalent globally, searching for therapeutic agents acting on adipose tissue is of great importance. Equisetin (EQST), a meroterpenoid isolated from a marine sponge-derived fungus, has been reported to display antibacterial and antiviral activities. Here, we revealed that EQST displayed anti-obesity effects acting on adipose tissue through inhibiting adipogenesis in vitro and attenuating HFD-induced obesity in mice, doing so without affecting food intake, blood pressure or heart rate. We demonstrated that EQST inhibited the enzyme activity of 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1), a therapeutic target of obesity in adipose tissue. Anti-obesity properties of EQST were all offset by applying excessive 11β-HSD1's substrates and 11β-HSD1 inhibition through knockdown in vitro or 11β-HSD1 knockout in vivo. In the 11β-HSD1 bypass model constructed by adding excess 11β-HSD1 products, EQST's anti-obesity effects disappeared. Furthermore, EQST directly bond to 11β-HSD1 protein and presented remarkable better intensity on 11β-HSD1 inhibition and better efficacy on anti-obesity than known 11β-HSD1 inhibitor. Therefore, EQST can be developed into anti-obesity candidate compound, and this study may provide more clues for developing higher effective 11β-HSD1 inhibitors.

Structural simplification: an efficient strategy in lead optimization

The trend toward designing large hydrophobic molecules for lead optimization is often associated with poor drug-likeness and high attrition rates in drug discovery and development. Structural simplification is a powerful strategy for improving the efficiency and success rate of drug design by avoiding "molecular obesity". The structural simplification of large or complex lead compounds by truncating unnecessary groups can not only improve their synthetic accessibility but also improve their pharmacokinetic profiles, reduce side effects and so on. This review will summarize the application of structural simplification in lead optimization. Numerous case studies, particularly those involving successful examples leading to marketed drugs or drug-like candidates, will be introduced and analyzed to illustrate the design strategies and guidelines for structural simplification.

Toxicological mechanisms of compatibility application of Sargassum pallidum-Glycyrrhiza uralensis on kidney in rats / 中草药

Objective To study the toxicological mechanisms of the compatibility application of Sargassum pallidum and Glycyrrhiza uralensis on kidney in rats. Methods Rats were divided into control, Sargassum pallidum (S), Glycyrrhiza uralensis (G), and Sargassum pallidum-Glycyrrhiza uralensis extract (S-G) groups, which were respectively exposed (gavages) for 4 weeks. Then, the levels of blood urea nitrogen (BUN), serum creatinine (Scr), aldosterone, cortisol, and electrolytes in rat serum and pathological sections of kidney were detected. Six active contents of Glycyrrhiza uralensis in kidney of rats were detected by UPLC-TQ/MS method. The expression of HSD11B2 in kidney was detected by Western blotting. Results Compared with the control group, all biochemical indicators of S group had no obvious change. It was found that the level of aldosterone from G group and S-G group was significantly lower than that from control group (P < 0.05, 0.01). In contrast to the control group, S. pallidum-G. uralensis extract led to significantly increased concentration of cortisol, BUN, and Scr in serum (P < 0.05, 0.01). The level of K+ and Cl- in S-G group was significantly lower than that in control group (P < 0.05, 0.01). Pathological examination showed that the G group had mild inflammation infiltration, and a serious inflammatory response accompanied by protein tube was absolved in S-G group. Compared with the G. uralensis extract group, the combination of S. pallidum and G. uralensis significantly raised the concentration of glycyrrhetinic acid (GA) in kidney (P < 0.05).When compared to that of control group, there was an inhibited expression of HSD11B2 in the kidney of L group and S-G group. Moreover, the expression of HSD11B2 in S-G group was markedly higher than that in G group (P < 0.05). Conclusion The toxicity of S-G group was mainly result that increased accumulation of GA, and inhibited the expression of HSD11B2, which resulted the aldosterone-cortisol system disorders.

Omic studies reveal the pathogenic lipid droplet proteins in non-alcoholic fatty liver disease

Non-alcoholic fatty liver disease (NAFLD) is an epidemic metabolic condition driven by an underlying lipid homeostasis disorder. The lipid droplet (LD), the main organelle involved in neutral lipid storage and hydrolysis, is a potential target for NAFLD therapeutic treatment. In this review, we summarize recent progress elucidating the connections between LD-associated proteins and NAFLD found by genome-wide association studies (GWAS), genomic and proteomic studies. Finally, we discuss a possible mechanism by which the protein 17β-hydroxysteroid dehydrogenase 13 (17β-HSD13) may promote the development of NAFLD.

Efeito de poliformismos genéticos do gene HSD11b1 sobre o risco para desenvolver depressão na população brasileira / Effect of HSD11b1 gene polymorphisms on the risk of developing depression in the Brazilian populationPalavras-chave em inglêsDepression

A depressão tem sido considerada uma das principais causas de incapacidade e caracteriza-se pela a presença de humor triste e perda de interesse ou prazer, acompanhada de alterações somáticas e cognitivas que afetam significativamente a capacidade de funcionamento do indivíduo. Evidências sugerem que o hormônio relacionado ao estresse, o cortisol, está envolvido na fisiopatologia da depressão em adultos. Isso pode estar relacionado com estresse precoce durante o desenvolvimento inicial, o que poderia levar a uma maior vulnerabilidade para desenvolver depressão e risco de tentativa de suicídio na fase adulta. O cortisol tem sua liberação mediada pelo eixo hipotálamo-hipófise-adrenal (HPA) e a alteração deste eixo pode afetar significativamente a biodisponibilidade do cortisol circulante. É comprovado também que fatores ambientais e genéticos permeiam a causa da depressão e o eixo HPA tem sido implicado na fisiopatologia de transtornos depressivos. O gene HSD11B1 que codifica a enzima 11?-hidroxiesteróide desidrogenase tipo1 que é a responsável por converter cortisona em cortisol permeia a função do eixo HPA. Com isso, polimorfismos genéticos no gene HSD11B1 podem afetar o risco para desenvolver depressão e o risco de suicídio. O objeto foi avaliar se genótipos e haplótipos do gene HSD11B1 estão associados com risco de depressão, com a gravidade dos sintomas e com o comportamento suicida, considerando o estresse precoce como um fator ambiental. Foram incluídos 107 pacientes depressivos e 67 pacientes saudáveis incluídos como controles. Todos os sujeitos foram submetidos a uma avaliação psicométrica com a Escala MINI, escala GRID-HAMD21, Questionário de Traumas Infantis CTQ e Escala Beck de Ideação Suicida. Foi encontrada associação significativa com o polimorfismo rs11119328 nos genótipos para risco aumentado de pelo menos uma tentativa de suicídio (OR: 12,53, p = 0,045) E uma associação de genótipos variantes do polimorfismo rs11811440 com humor eutímico para tratamento farmacológico otimizado (OR: 0,05, P = 0,027). Concluímos que os polimorfismos do gene HSD11B1 podem ser biomarcadores relevantes para detectar indivíduos geneticamente vulneráveis a desenvolver depressão e a cometer suicídio

Depression has been considered one of the main cause of disability and is characterized by the presence of sad mood and loss of interest or pleasure, accompanied by somatic and cognitive changes that significantly affect the ability of the individual to function. Evidence suggests that the stress-related hormone, cortisol, is involved in the pathophysiology of depression in adults. This may be related to adverse experiences in childhood during early development, which could lead to increased vulnerability to developing depression and suicide attempt risk in adulthood. Cortisol has its release mediated by the hypothalamic-pituitary-adrenal axis (HPA) and the alteration of this axis can significantly affect the bioavailability of the circulating cortisol. It is also proven that environmental and genetic factors permeate the cause of depression and the HPA axis has been implicated in the pathophysiology of depressive disorders. The HSD11B1 gene encoding the 11?-hydroxysteroid dehydrogenase type 1 enzyme that is responsible for converting cortisone to cortisol permeates HPA axis function. Thus, genetic polymorphisms in the HSD11B1 gene may affect the risk of developing depression and the risk of suicide. The objective was to evaluate if genotypes and haplotypes of the HSD11B1 gene are associated with risk of depression, with severity of symptoms and with suicidal behavior, considering early stress as an environmental factor. We included 107 depressive patients and 67 healthy patients included as controls. All subjects underwent a psychometric evaluation with the MINI Scale, GRID-HAMD21 Scale, Child Trauma Questionnaire CTQ and Beck Scale of Suicidal Ideation. It was found a significant association with rs11119328 polymorphism in genotypes at increased risk of at least one suicide attempt (OR: 12.53, p = 0.045) and an association of rs11811440 polymorphism genotypes with euthymic humor for optimized pharmacological treatment (OR: 0.05, P = 0.027). We conclude that HSD11B1 gene polymorphisms may be relevant biomarkers for detecting genetically vulnerable individuals to develop depression and commit suicide

Efeito de poliformismos genéticos do gene HSD11b1 sobre o risco para desenvolver depressão na população brasileira / Effect of HSD11b1 gene polymorphisms on the risk of developing depression in the Brazilian population

A depressão tem sido considerada uma das principais causas de incapacidade e caracteriza-se pela a presença de humor triste e perda de interesse ou prazer, acompanhada de alterações somáticas e cognitivas que afetam significativamente a capacidade de funcionamento do indivíduo. Evidências sugerem que o hormônio relacionado ao estresse, o cortisol, está envolvido na fisiopatologia da depressão em adultos. Isso pode estar relacionado com estresse precoce durante o desenvolvimento inicial, o que poderia levar a uma maior vulnerabilidade para desenvolver depressão e risco de tentativa de suicídio na fase adulta. O cortisol tem sua liberação mediada pelo eixo hipotálamo-hipófise-adrenal (HPA) e a alteração deste eixo pode afetar significativamente a biodisponibilidade do cortisol circulante. É comprovado também que fatores ambientais e genéticos permeiam a causa da depressão e o eixo HPA tem sido implicado na fisiopatologia de transtornos depressivos. O gene HSD11B1 que codifica a enzima 11?-hidroxiesteróide desidrogenase tipo1 que é a responsável por converter cortisona em cortisol permeia a função do eixo HPA. Com isso, polimorfismos genéticos no gene HSD11B1 podem afetar o risco para desenvolver depressão e o risco de suicídio. O objeto foi avaliar se genótipos e haplótipos do gene HSD11B1 estão associados com risco de depressão, com a gravidade dos sintomas e com o comportamento suicida, considerando o estresse precoce como um fator ambiental. Foram incluídos 107 pacientes depressivos e 67 pacientes saudáveis incluídos como controles. Todos os sujeitos foram submetidos a uma avaliação psicométrica com a Escala MINI, escala GRID-HAMD21, Questionário de Traumas Infantis CTQ e Escala Beck de Ideação Suicida. Foi encontrada associação significativa com o polimorfismo rs11119328 nos genótipos para risco aumentado de pelo menos uma tentativa de suicídio (OR: 12,53, p = 0,045) E uma associação de genótipos variantes do polimorfismo rs11811440 com humor eutímico para tratamento farmacológico otimizado (OR: 0,05, P = 0,027). Concluímos que os polimorfismos do gene HSD11B1 podem ser biomarcadores relevantes para detectar indivíduos geneticamente vulneráveis a desenvolver depressão e a cometer suicídio

Depression has been considered one of the main cause of disability and is characterized by the presence of sad mood and loss of interest or pleasure, accompanied by somatic and cognitive changes that significantly affect the ability of the individual to function. Evidence suggests that the stress-related hormone, cortisol, is involved in the pathophysiology of depression in adults. This may be related to adverse experiences in childhood during early development, which could lead to increased vulnerability to developing depression and suicide attempt risk in adulthood. Cortisol has its release mediated by the hypothalamic-pituitary-adrenal axis (HPA) and the alteration of this axis can significantly affect the bioavailability of the circulating cortisol. It is also proven that environmental and genetic factors permeate the cause of depression and the HPA axis has been implicated in the pathophysiology of depressive disorders. The HSD11B1 gene encoding the 11?-hydroxysteroid dehydrogenase type 1 enzyme that is responsible for converting cortisone to cortisol permeates HPA axis function. Thus, genetic polymorphisms in the HSD11B1 gene may affect the risk of developing depression and the risk of suicide. The objective was to evaluate if genotypes and haplotypes of the HSD11B1 gene are associated with risk of depression, with severity of symptoms and with suicidal behavior, considering early stress as an environmental factor. We included 107 depressive patients and 67 healthy patients included as controls. All subjects underwent a psychometric evaluation with the MINI Scale, GRID-HAMD21 Scale, Child Trauma Questionnaire CTQ and Beck Scale of Suicidal Ideation. It was found a significant association with rs11119328 polymorphism in genotypes at increased risk of at least one suicide attempt (OR: 12.53, p = 0.045) and an association of rs11811440 polymorphism genotypes with euthymic humor for optimized pharmacological treatment (OR: 0.05, P = 0.027). We conclude that HSD11B1 gene polymorphisms may be relevant biomarkers for detecting genetically vulnerable individuals to develop depression and commit suicide

Research progress on natural products with selective inhibition against 11β-HSD1 / 中草药

11β-Hydroxysteroid dehydrogenase (11β-HSD) is a metabolic enzyme of glucocorticoid. Growing evidence suggests that inhibiting over-expression of 11β-HSD1 and reducing partial effects of glucocorticoid could be the strategy to treat type 2 diabetes, as well as metabolic syndrome. Researching and developmenting selective 11β-HSD1 inhibitors may become a new direction. As natural products (NPs) have represented a cornerstone of pharmaceutical research, literatures on the development of natural products with selective inhibition against 11β-HSD1 published during the last 10 years were selected, and the inhibitors were classified according to the way how to find them. This paper will provide reference for the further research on the selective 11β-HSD1 inhibitors.

Study on the Potential Targets of Guizhi Decoction Regulating Ying and Wei Based on Reverse Molecular Docking Technology / 中国药房

OBJECTIVE:To study the potential targets of Guizhi decoction regulating Ying and Wei based oncorrespondence between formulation and syndromerelationship and reverse molecular docking technology. METHODS:Active ingredients related to Guizhi decoction were obtained by literature retrievals,and PharmMapper Server was used for reverse molecular docking for ac-tive ingredients. The potential receptors of Guizhi decoction were found on the basis of docking scores,then AutoDock Vina was conducted for positive molecular docking test to observe the affinity between the ligand and the receptor molecule. 75 rats were ran-domly divided into normal group,model group,Guizhi decoction high-dose,medium-dose,low-dose groups(12,8,4 g/kg),15 in each group. Except for normal group,rats in other groups were induced for models with disharmony between Ying and Wei. Af-ter modeling,rats were intragastrically administrated once a day,for 5 d. After administration,11β-HSD1 expression levels in adi-pose tissue and muscle tissue of rats were detected. RESULTS:Reverse molecular docking for active ingredients of Guizhi decoc-tion found that 11β-HSD1 was the frequent receptor,and positive docking test confirmed that uralsaponin b,glycyrrhetnic acid and carbenoxolone and so on had higher affinity with 11β-HSD1. Results of animal test showed,compared with normal group,11β-HSD1 expression levels in adipose tissue and muscle tissue in model group were increased (P<0.05);and compared with model group,11β-HSD1 expression levels in adipose tissue and muscle tissue in Guizhi decoction high-dose group were decreased (P<0.05). CONCLUSIONS:Guizhi decoction regulating Ying and Wei has certain correlation with 11β-HSD1,while the reverse molec-ular docking technology can provide a feasible technical way to studycorrespondence between formulation and syndromerelation-ship.

Hiperaldosteronismo primario y otras formas de hipertensión arterial endocrina / Primary hyperaldosteronism and other forms of endocrine arterial hypertension

La hipertensión arterial (HTA) dependiente de mineralocorticoides representa actualmente una de las formas secundarias de hipertensión de mayor prevalencia. Entre las causas más prevalentes está el hiperaldosteronismo primario (HAP) cuya prevalencia es cercana al 10 por ciento de la población de hipertensos. El HAP se detecta principalmente por una elevación de la razón aldosterona a actividad renina plasmática (ARR), ya que la hipokalemia es infrecuente de encontrar. La fisiopatología del HAP se presenta como un desequilibrio en el control electrolítico a nivel renal, por mayor actividad del receptor mineralocorticoides (MR), lo cual aumenta el volumen intravascular y la presión arterial. Recientemente se ha demostrado también que el exceso de aldosterona afecta también el endotelio vascular, el tejido cardiaco entre otros. Este exceso puede ser por una alteración a nivel de la glándula suprarrenal (generalmente hiperplasia o adenoma) o formas genéticas (familiares). Por otra parte, alteraciones parciales o totales de la enzima 11ß-Hidroxiesteroide deshidrogenasa tipo 2 (11ß-HSD2) resulta en una metabolización total o parcial de cortisol, imitando los efectos de aldosterona sobre MR. La actividad de esta enzima se evalúa midiendo la razón cortisol a cortisona en suero por HPLC-MS/MS. La prevalencia de alteraciones parciales de la actividad de la enzima 11ß-HSD2 en estudios de cohorte alcanza en alrededor del 15 por ciento en población hipertensa. El diagnóstico del HAP o deficiencias de 11BHSD2, permitiría un tratamiento específico del cuadro hipertensivo mediantes el uso de bloqueadores del receptor mineralocorticoideo y/o uso de corticoides de acción prolongada sin actividad mineralocorticoidea como dexametasona o betametasona.(AU)

Mineralocorticoid arterial Hypertension represents currently one of the secondary forms of hypertension most prevalent. Among the most prevalent causes is the primary aldosteronism (PA) whose prevalence is close to 10 percect of the hypertensive population. PA is detected by elevated aldosterone to plasma renin activity ratio (ARR) and the hypokalemia is rare to find. The pathophysiology of PA is presented as a renal electrolyte imbalance, increasing mineralocorticoid receptor (MR) activity, intravascular volume and blood pressure. Recently it has also shown that excessive aldosterone also affects vascular endothelium, heart tissue among others. This excess can be associated to an adrenal gland (usually hyperplasia or adenoma) or genetic (familiar) alteration. Similarly, partial or total impairment in 11ß-hydroxysteroid dehydrogenase type 2 (11ß-HSD2) enzyme affects the cortisol metabolism, mimicking the effects of aldosterone on MR. The activity of this enzyme is evaluated by measuring the serum cortisol to cortisone ratio by HPLC-MS/MS. The prevalence of partial alterations of the activity of 11ß-HSD2 enzyme in cohort studies reached at around 15 percent in hypertensive population. The diagnosis of PA or an impairment in 11ß-HSD2 activity allows specific treatments of hypertensive patients using mineralocorticoid receptor blockers and/or use of long-acting corticosteroids without mineralocorticoid activity as dexamethasone or betamethasone.(AU)

Annexin A5 regulates Leydig cell testosterone production via ERK1/2 pathway / 亚洲男科学杂志(英文版)

This study was to investigate the effect of annexin A5 on testosterone secretion from primary rat Leydig cells and the underlying mechanisms. Isolated rat Leydig cells were treated with annexin A5. Testosterone production was detected by chemiluminescence assay. The protein and mRNA of Steroidogenic acute regulatory (StAR), P450scc, 3β-hydroxysteroid dehydrogenase (3β-HSD), 17β-hydroxysteroid dehydrogenase (17β-HSD), and 17α-hydroxylase were examined by Western blotting and semi-quantitative RT-PCR, respectively. Annexin A5 significantly stimulated testosterone secretion from rat Leydig cells in dose- and time-dependent manners and increased mRNA and protein expression of StAR, P450scc, 3β-HSD, and 17β-HSD but not 17α-hydroxylase. Annexin A5 knockdown by siRNA significantly decreased the level of testosterone and protein expression of P450scc, 3β-HSD, and 17β-HSD. The significant activation of ERK1/2 signaling was observed at 5, 10, and 30 min after annexin A5 treatment. After the pretreatment of Leydig cells with ERK inhibitor PD98059 (50 μmol l-1 ) for 20 min, the effects of annexin A5 on promoting testosterone secretion and increasing the expression of P450scc, 3β-HSD, and 17β-HSD were completely abrogated (P < 0.05). Thus, ERK1/2 signaling is involved in the roles of annexin A5 in mediating testosterone production and the expression of P450scc, 3β-HSD, and 17β-HSD in Leydig cells.

Clinical characteristics and genetic analysis in two patients with 3β-hydroxysteroid dehydrogenase deficiency / 中华内分泌代谢杂志

Objective To analyze the clinical characteristics of two patients with 3β-hydroxysteroid dehydrogenase deficiency and to explore their molecular genetic defects.Methods The clinical features and laboratory data of two patients were collected.The exons of HSD3B2 gene were amplified by PCR and sequenced by Sanger sequencing.Results Patient 1, aged 5 yrs old, was raised as a girl with 46, XY karyotype, presented with hyperpigmentation, female infant vulva, clitoral hypertrophy, and bilateral cryptorchidism;Patient 2, aged 11 yrs old, was raised as a girl at birth but as a boy after 1 yr old for known 46, XY karyotype, presented with hyperpigmentation, micropenis and severe hypospadias.Both patients had markedly elevated adrenocorticotropin and decreased cortisol.Two homozygous missense mutations in HSD3B2 gene were identified:conversions of codon Pro155 toLeu(p.P155L)inpatient1,andcodonAla82toThr(p.A82T)inpatient2,bothofwhichwerereportedforthe first time in China.Conclusion The patients with 3β-hydroxysteroid dehydrogenase deficiency in 46,XY karyotype mainly present with male pseudohermaphroditism and adrenocortical deficiency, and the diagnosis should rely on the steroids detection and HSD3B2 gene screening.

The role of 11β-HSD1 in metabolic syndrome / 中国糖尿病杂志

[Summary] MS ,which is highly related tothe occurrence of cardiovascular disease and T2DM ,is characterized by glucose and fat metabolic dysregulation ,central obesity ,hypertension and hyperuricemia.11β‐hydroxysteroid dehydrogenase type 1 (11β‐HSD1) is regarded as a new therapeutic target for MS.11β‐HSD1 converts inactive glucocorticoid to active glucocorticoid. 11β‐HSD1 knockout improves obesity , hyperlipidemia andhyperglycemia. The inhibition of 11β‐HSD1 alleviates IR in human and rodents ,but the application of 11β‐HSD1 inhibitors is limited by the side effects.

The effects of gossypol acetate on the morphological features and the gene expression in the bone tissues of the femoral head of Sprague-Dawley rat in vivo after treated with dexamethasone / 重庆医学

Objective To explore the effects of gossypol acetate on the morphological features and the gene expression in the femoral head of Sprague-Dawley rat in vivo after treated with dexamethasone .Methods Dexamethasone(Dex) was injected into the abdominal cavity of SD rats at an dose of 10 mg/kg ,twice a week ,and feed gossypol acetate 5 mg · kg -1 · d-1 .The controls re-ceived saline 2 mL injection .The treatment lasted for 12 and 20 weeks .The slices of the femoral head were made for HE and immu-nohistochemical study .The total mRNA was extracted for RT-PCR assessment .Results The cancellous bone trabecular became sparse ,trabecular bone area ratio decreased ,bone marrow fat tissue increased .These changes were fitted for pathological character of bone necrosis .The gossypol acetate could not affect the pathological changes .The proportion of the positive stained osteoblasts increased ,adipocytes decreased .PPARγ,C/EBPα,11β-HSD1 expression enhanced ,Runx2 down regulated in the treatment groups and GAA group .Conclusion Dex can induce evident pathological changes conform to the characters of femoral head necrosis .They may have closed correlation between 11β-HSD1 and the gene expression .But GAA could not affected the pathological changes and abnormality of the gene expression .

ROC trials update on prehospital hypertonic saline resuscitation in the aftermath of the US-Canadian trials

The objectives of this review are to assess the current state of hypertonic saline as a prehospital resuscitation fluid in hypotensive trauma patients, particularly after the 3 major Resuscitation Outcomes Consortium trauma trials in the US and Canada were halted due to futility. Hemorrhage and traumatic brain injury are the leading causes of death in both military and civilian populations. Prehospital fluid resuscitation remains controversial in civilian trauma, but small-volume resuscitation with hypertonic fluids is of utility in military scenarios with prolonged or delayed evacuation times. A large body of pre-clinical and clinical literature has accumulated over the past 30 years on the hemodynamic and, most recently, the anti-inflammatory properties of hypertonic saline, alone or with dextran-70. This review assesses the current state of hypertonic fluid resuscitation in the aftermath of the failed Resuscitation Outcomes Consortium trials.

Modulatory effect of BclI GR gene polymorphisms on the obesity phenotype in Brazilian patients with Cushing's disease

OBJECTIVES: Patients with Cushing's disease exhibit wide phenotypic variability in the severity of obesity, diabetes and hypertension. In the general population, several glucocorticoid receptor genes (NR3C1) and HSD11B1 polymorphisms are associated with altered glucocorticoid sensitivity and/or metabolism, resulting in an increased or reduced risk of an adverse metabolic profile. Our aim was to analyze the association of NR3C1 and HSD11B1 gene variants with the severity of some clinical and hormonal features of Cushing's disease. METHODS: Sixty-four patients presenting with Cushing's disease were diagnosed based on adrenocorticotrophic hormone levels, high-dose dexamethasone suppression tests and/or inferior petrosal sinus sampling and magnetic resonance imaging. The A3669G, ER22/23EK, N363S BclI-NR3C1 and HSD11B1-rs12086634 variants were screened. RESULTS: The BclI, HSD11B1-rs12086634 and A3669G variants were found in 36%, 19.5% and 14% of alleles, respectively. The N363S and ER22/23EK polymorphisms were identified in heterozygosis once in only two patients (1.5% of alleles). There were no differences in the weight gain or prevalence of diabetes and hypertension in the patients carrying the abovementioned alleles compared to the wild-type carriers. Interestingly, the mean body mass index (BMI) of the BclI carriers was significantly higher than the non-carriers (34.4±7 kg/m2 vs. 29.6±4.7 kg/m2, respectively). None of the polymorphisms were associated with the basal adrenocorticotrophic hormone, FU levels or F level after dexamethasone suppression testing. CONCLUSION: Although Cushing's disease results from increased glucocorticoid secretion, we observed that interindividual variability in the peripheral glucocorticoid sensitivity, mediated by the glucocorticoid receptor, could modulate the obesity phenotype. .

Effect of green tea (Camellia sinensis L.) extract on morphological and functional changes in adult male gonads of albino rats.

Green tea, prepared from the steamed and dried leaves of the shrub Camellia sinensis, is known for its antioxidant and anti-carcinogenic effects. However, its effects on male gonadal functions have not been explored adequately and the present investigation has been undertaken to evaluate the effect of green tea extract on gonads of adult male albino rats. Results of in vivo studies showed that green tea extract (GTE) at mild (1.25 g%, ≡ 5 cups of tea/day), moderate (2.5 g%, ≡ 10 cups of tea/day) and high (5.0 g%, ≡ 20 cups of tea/day) doses, for a period of 26 days, altered morphology and histology of testis and accessory sex organs. A significant dose-dependent decrease in the sperm counts, inhibited activities of testicular ∆53- and 17-hydroxysteroid dehydrogenase (∆5-3-HSD and 17-HSD respectively) and decreased serum testosterone level were noticed. Significant increase in serum LH level was observed after moderate and high doses; serum FSH level also increased but not significantly. Histopathological examination showed inhibition of spermatogenesis evidenced by preferential loss of matured and elongated spermatids. Results of this study showed that GTE at relatively high dose may cause impairment of both the morphological and normal functional status of testis in rodents and thus its consumption at relatively high doses raises concern on male reproductive function in spite of its other beneficial effects.

Correlation between function-morphology of effect of the stress and flunitrazepam administered during gestation in adult mouse ovary / Correlación entre la función y la morfología de los efectos de estrés y flunitrazepam administrado durante la gestación en ovario de ratón adulto

Previously we report long lasting effects on ovary of mice prenatally exposed to flunitrazepam (FNZ), a benzodiazepine with tranquilized action. In this work we find that the FNZ don't prevent the effects on ovary prenatally exposure to stress in mice. We studied adult females born from mothers that had been stressed by immobilization on day 6 ofgestation (GD-6) or group S, and from mothers stressed also by immobilization at GD-6, but which received a single oral dose of FNZ immediately after the stress group FNZS. The control groups were the SS that received the GD-6 saline solution and the group NT non-treated. Their ovaries were extracted for histology studies and to observe the activity of 3b hydroxysteroid dehydrogenase/isomerase (3 b-HSD). The histological analysis revealed high staining affinity ovarian cell of S and FNZS. Double oocytes and apoptotic bodies were found in the secondary atretic follicles, as well as abnormal primordial, primary and secondary follicle populations, as compared to SS and NT groups. The primordial, primary, and secondary follicles were significantly reduced in the experimental groups. But the primary and secondary atretic follicles were higher in both groups, and the number of corpora lutea was lower in both groups. The activity of 3 b-HSD was abnormally increased in both FNZS- and S-groups. These findings suggest that FNZ did not counteract the impairing effects of prenatal stress on adult offspring ovarian follicles, and could rather be responsible for long lasting changes occurring during embryonic programming.

Previamente comprobamos efectos de larga duración sobre el ovario de ratones expuestos prenatalmente a flunitrazepam (FNZ), una benzodiazepina con acción tranquilizante. En este trabajo encontramos que el FNZ, no revierte los efectos producidos por la exposición prenatal a estrés. Estudiamos hembras adultas nacidas de madres que se estresaron por inmovilización el día 6 de la gestación (DG-6) o grupo S, y de madres estresadas también por inmovilización el DG-6, las que recibieron una sola dosis de FNZ inmediatamente después del estrés (grupo FNZS). Los grupos de control fueron el SS al que se le administró solución salina y el NT no tratado. Se extrajeron sus ovarios para su estudio histológico y para observar la actividad de delta 3b-deshidroxiesteroide dehidrogenasa/isomerasa (3 b-HSD). El análisis histológico reveló una gran afinidad tintoreal en los ovarios de los grupos S y FNZS. En los ovarios de los ratones del grupo FNZS se encontraron en los folículos secundarios atrésicos ovocitos dobles y cuerpos apoptóticos así como una población mayor de folículos anormales primordiales, primarios y secundarios en comparación con los grupos SS y NT. Los folículos primarios y secundarios tuvieron una reducción significativa en los grupos experimentales pero los folículos atrésicos primarios y secundarios fueron más en ambos grupos y el número de cuerpos lúteos fue menor en ambos grupos. La actividad de 3 b-HSD aumentó de manera anormal tanto en los grupos FNZ y S. Estos hallazgos sugieren que el FNZ no contrarresta los efectos negativos del estrés prenatal sobre los folículos ováricos de las crías adultas, y podría ser responsable de los cambios largo plazo que ocurren a durante la programación embrionaria.

Role of 11â-hydroxysteroid dehydrogenase 2 renal activity in potassium homeostasis in rats with chronic renal failure

Aldosterone concentrations vary in advanced chronic renal failure (CRF). The isozyme 11â-hydroxysteroid dehydrogenase 2 (11â-HSD2), which confers aldosterone specificity for mineralocorticoid receptors in distal tubules and collecting ducts, has been reported to be decreased or normal in patients with renal diseases. Our objective was to determine the role of aldosterone and 11â-HSD2 renal microsome activity, normalized for glomerular filtration rate (GFR), in maintaining K+ homeostasis in 5/6 nephrectomized rats. Male Wistar rats weighing 180-220 g at the beginning of the study were used. Rats with experimental CRF obtained by 5/6 nephrectomy (N = 9) and sham rats (N = 10) were maintained for 4 months. Systolic blood pressure and plasma creatinine (Pcr) concentration were measured at the end of the experiment. Sodium and potassium excretion and GFR were evaluated before and after spironolactone administration (10 mg·kg-1·day-1 for 7 days) and 11â-HSD2 activity on renal microsomes was determined. Systolic blood pressure (means ± SEM; Sham = 105 ± 8 and CRF = 149 ± 10 mmHg) and Pcr (Sham = 0.42 ± 0.03 and CRF = 2.53 ± 0.26 mg/dL) were higher (P < 0.05) while GFR (Sham = 1.46 ± 0.26 and CRF = 0.61 ± 0.06 mL/min) was lower (P < 0.05) in CRF, and plasma aldosterone (Pald) was the same in the two groups. Urinary sodium and potassium excretion was similar in the two groups under basal conditions but, after spironolactone treatment, only potassium excretion was decreased in CRF rats (sham = 0.95 ± 0.090 (before) vs 0.89 ± 0.09 µEq/min (after) and CRF = 1.05 ± 0.05 (before) vs 0.37 ± 0.07 µEq/min (after); P < 0.05). 11â-HSD2 activity on renal microsomes was lower in CRF rats (sham = 0.807 ± 0.09 and CRF = 0.217 ± 0.07 nmol·min-1·mg protein-1; P < 0.05), although when normalized for mL GFR it was similar in both groups. We conclude that K+ homeostasis is ...