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1.
Nature ; 622(7981): 80-86, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37674074

RESUMO

The functionalization of C-H bonds in organic molecules is one of the most direct approaches for chemical synthesis. Recent advances in catalysis have allowed native chemical groups such as carboxylic acids, ketones and amines to control and direct C(sp3)-H activation1-4. However, alcohols, among the most common functionalities in organic chemistry5, have remained intractable because of their low affinity for late transition-metal catalysts6,7. Here we describe ligands that enable alcohol-directed arylation of δ-C(sp3)-H bonds. We use charge balance and a secondary-coordination-sphere hydrogen-bonding interaction-evidenced by structure-activity relationship studies, computational modelling and crystallographic data-to stabilize L-type hydroxyl coordination to palladium, thereby facilitating the assembly of the key C-H cleavage transition state. In contrast to previous studies in C-H activation, in which secondary interactions were used to control selectivity in the context of established reactivity8-13, this report demonstrates the feasibility of using secondary interactions to enable challenging, previously unknown reactivity by enhancing substrate-catalyst affinity.

2.
Phys Rev Lett ; 128(10): 107701, 2022 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-35333085

RESUMO

Superconductor-semiconductor hybrid devices are at the heart of several proposed approaches to quantum information processing, but their basic properties remain to be understood. We embed a two-dimensional Al-InAs hybrid system in a resonant microwave circuit, probing the breakdown of superconductivity due to an applied magnetic field. We find a fingerprint from the two-component nature of the hybrid system, and quantitatively compare with a theory that includes the contribution of intraband p±ip pairing in the InAs, as well as the emergence of Bogoliubov-Fermi surfaces due to magnetic field. Separately resolving the Al and InAs contributions allows us to determine the carrier density and mobility in the InAs.

3.
Phys Rev Lett ; 125(13): 131802, 2020 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-33034464

RESUMO

We report the final measurement of the neutrino oscillation parameters Δm_{32}^{2} and sin^{2}θ_{23} using all data from the MINOS and MINOS+ experiments. These data were collected using a total exposure of 23.76×10^{20} protons on target producing ν_{µ} and ν[over ¯]_{µ} beams and 60.75 kt yr exposure to atmospheric neutrinos. The measurement of the disappearance of ν_{µ} and the appearance of ν_{e} events between the Near and Far detectors yields |Δm_{32}^{2}|=2.40_{-0.09}^{+0.08}(2.45_{-0.08}^{+0.07})×10^{-3} eV^{2} and sin^{2}θ_{23}=0.43_{-0.04}^{+0.20}(0.42_{-0.03}^{+0.07}) at 68% C.L. for normal (inverted) hierarchy.

4.
Artigo em Inglês | MEDLINE | ID: mdl-23125867

RESUMO

Aims. To investigate the antidiabetic effect of the traditional Vietnamese herb Gynostemma pentaphyllum (GP) together with sulfonylurea (SU) in 25 drug-naïve type 2 diabetic patients. Methods. After 4-week treatment with gliclazide (SU), 30 mg daily, all patients were randomly assigned into 2 groups to add on GP extract or placebo extract, 6 g daily, during eight weeks. Results. After 4-week SU treatment, fasting plasma glucose (FPG) and HbA(1C) decreased significantly (P < 0.001). FPG was further reduced after add-on therapy with 2.9 ± 1.7 and 0.9 ± 0.6 mmol/L in the GP and placebo groups, respectively (P < 0.001). Therapy with GP extract also reduced 30- and 120-minute oral glucose tolerance test postload values. HbA(1C) levels decreased approximately 2% units in the GP group compared to 0.7% unit in the placebo group (P < 0.001). Conclusion. GP extract in addition to SU offers an alternative to addition of other oral medication to treat type 2 diabetic patients.

5.
Rev Epidemiol Sante Publique ; 60(6): 437-46, 2012 Dec.
Artigo em Francês | MEDLINE | ID: mdl-23137871

RESUMO

BACKGROUND: Cervical cancer (CC) is almost always induced by some oncogenic types of human papillomavirus (HPV). In Vietnam, it is the first leading cause of cancer in women, with highest prevalence in Ho Chi Minh City (HCMC). Since 2006, prevention of the CC has been improved by licensure of recombinant vaccines directed against HPV 16 and 18, effective when administered before the age of first sexual intercourse. A national program for routine immunization of pre-adolescent girls in addition to cytological screening of adult women would greatly reduce the impact of CC in Vietnam but vaccines remain expensive and it is unclear how this strategy would be accepted by the target population. The aim of this study was to assess the acceptability of HPV vaccination by pediatricians, mothers with a daughter aged 9-15 years and young women aged 16-26 years in HCMC. METHODS: Between March and June 2010, a cross-sectional survey of knowledge and attitudes was administered to 115 pediatricians in the pediatric hospital, 210 mothers and 400 young women attending the gynecology department of the University Hospital. RESULTS: Pediatricians generally had a good perception of the risk but they still lacked knowledge about HPV vaccination, given by 66% of them. Among mothers, 18% knew the relationship between HPV infection and CC, 43% had heard of HPV vaccination and 40% agreed to vaccinate their daughter. Among young women, 35% knew the risk, 49% knew the vaccine and 38% wanted to be vaccinated. Level of education, amount of income and celibacy were positively related to intention to be vaccinated. The lack of information on HPV vaccination and the high cost of vaccines were the main causes of refusal or indecision. CONCLUSION: Routine HPV vaccination of girls in HCMC will be well accepted by the population if a large campaign of health education is implemented by the government and if the affordability of vaccines is facilitated.


Assuntos
Papillomaviridae/imunologia , Infecções por Papillomavirus/prevenção & controle , Vacinas contra Papillomavirus/administração & dosagem , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Neoplasias do Colo do Útero/prevenção & controle , Adolescente , Adulto , Criança , Estudos Transversais , Feminino , Humanos , Mães , Neoplasias do Colo do Útero/virologia , Vietnã , Adulto Jovem
6.
Rev Med Brux ; 32(6 Suppl): S58-65, 2011.
Artigo em Francês | MEDLINE | ID: mdl-22458059

RESUMO

Treatment of complex fractures of the proximal humerus is still controversial. This prospective study was designed to evaluate the results of open reduction and proximal nailing in complex fractures of the proximal humerus. Fifteen patients aged 39 to 83 years (average: 59 years) presenting severely displaced fractures of the proximal humerus were observed after open reduction and fixation by proximal nailing (Telegraph) combined with screwing and/or osteosuture of the tuberosities. The patients were evaluated at one year clinically and radiologically. The Constant score, DASH score and Simple Shoulder Test were calculated. Complementarily, patients were submitted to an isokinetic test. At one year follow-up, the average range of motion was 85 degrees (40 degrees-170 degrees) for elevation, 82 degrees (40 degrees-170 degrees) for abduction, L3 for internal rotation and 34 degrees (10-60 degrees) for external rotation. The average visual analog score was 3 points (0-8 points). The Constant score varied from 17 to 92 points (average: 48 points). Isokinetic evaluation showed mostly a strength deficit in abduction even for patients presenting an excellent result. Functional results were related to the quality of the surgical reduction but also to patients' collaboration. Various treatment methods for complex fracture of the proximal humerus are reported in the literature. When a nearly anatomical reduction is achieved, the here-described method of open reduction and proximal nailing permits to obtain good functional results in most patients. This option should be considered for young patients and even in the elderly where results are comparable to that obtained with hemiarthroplasty in the same condition.


Assuntos
Pinos Ortopédicos , Fixação Interna de Fraturas/instrumentação , Fixação Interna de Fraturas/métodos , Fraturas do Ombro/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Escala de Gravidade do Ferimento , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
7.
Chemosphere ; 283: 131101, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34182628

RESUMO

In this study, the effect of salinity on the removal of organic matter and nitrogen concentrations in bioreactor was investigated using a hybrid bench scale down-flow hanging sponge (DHS) system for 145 days of operation. The reactor had three identical sections that were filled to 30% volume with Bio-Bact to serve as attached media. The DHS reactor was fed with domestic wastewater that was mixed with increasing concentration of sodium chloride from 0.5 to 3.0% stepwise. The influent and effluent concentrations of BOD5, CODCr, NH4+-N, and TN were analyzed to evaluate the performance of the DHS reactor during the operational period. Results indicate that when salinity was increased from 0.5 to 3.0%, the removal efficiency gradually decreased from 80.3% to 61.5% for CODCr, 76.4%-65.0% for BOD5, 64.1%-48.4% for NH4+-N, and 50%-36% for TN. Besides, the changes in biofilm characteristics with increasing salinity were observed during the operational period. The results indicate that salinity has a significant influence on the removal of organic matters and nitrogen transformation in the biofilm of the bioreactor. Even so, the DHS reactor revealed a good potential for treating saline wastewater.


Assuntos
Esgotos , Águas Residuárias , Reatores Biológicos , Nitrogênio/análise , Eliminação de Resíduos Líquidos
8.
Horm Metab Res ; 42(5): 353-7, 2010 May.
Artigo em Inglês | MEDLINE | ID: mdl-20213586

RESUMO

The aim of the study was to investigate the antidiabetic effect of the traditional Vietnamese herb Gynostemma pentaphyllum in 24 drug-naïve type 2 diabetic patients. All patients were randomized to authenticated Gynostemma pentaphyllum tea or placebo tea, 6 g daily, during twelve weeks and received information regarding diet and exercise. Fasting plasma glucose, insulin levels, and glycosylated hemoglobin (HbA(1C)) were measured before, during, and after the treatment. Oral glucose tolerance tests were performed every four weeks. After 12-week treatment, fasting plasma glucose levels totally decreased to an extent of 3.0+/-1.8 mmol/l in the Gynostemma pentaphyllum tea group as compared to a decrease of 0.6+/-2.2 mmol/l in the control group (p<0.01). HbA(1C) levels after 12 weeks decreased approximately 2% units in the Gynostemma pentaphyllum group compared to 0.2% unit in the controls (p<0.001). Change in Homeostasis Model Assessment-Insulin Resistance between baseline and twelfth week indicated that insulin resistance decreased significantly in the Gynostemma pentaphyllum group (-2.1+/-3.0) compared with that (+1.1+/-3.3) in the control group (p<0.05). There were no hypoglycemias, or adverse effects regarding kidney and liver parameters or gastrointestinal function. In addition, lipid profiles, glucagon, cortisol levels, body measurements, and blood pressure were not different between the groups. This study shows a prompt improvement of glycemia and insulin sensitivity, and thereby provides a basis for a novel, effective, and safe approach, using Gynostemma pentaphyllum tea, to treat type 2 diabetic patients.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Gynostemma/química , Hipoglicemiantes/farmacologia , Idoso , Antropometria , Glicemia/metabolismo , Peso Corporal/efeitos dos fármacos , Relação Dose-Resposta a Droga , Método Duplo-Cego , Feminino , Teste de Tolerância a Glucose , Hemoglobinas Glicadas/metabolismo , Humanos , Insulina/sangue , Resistência à Insulina , Rim/efeitos dos fármacos , Rim/metabolismo , Metabolismo dos Lipídeos/efeitos dos fármacos , Lipídeos/sangue , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Pessoa de Meia-Idade , Extratos Vegetais/farmacologia
9.
Methods Find Exp Clin Pharmacol ; 31(3): 165-9, 2009 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-19536359

RESUMO

The prevalence of type 2 diabetes in developing countries is increasing. In Vietnam, several plants are thought to be useful for the treatment of type 2 diabetes. This study has been performed to screen the hypoglycemic effects of eight Vietnamese herbs used in traditional medicine for the treatment of diabetes. Blood glucose levels were measured before and several times after oral or i.p. administration of the ethanol-based plant extracts in normal mice. The extracts that reduced blood glucose both orally and i.p. were also studied in glucose tolerance tests in mice. Gynostemma pentaphyllum Makino (Cucurbitaceae) at doses of 200 and 300 mg/kg i.p. or 1500 mg/kg orally reduced blood glucose in mice (P < 0.001 for all compared to control group using NaCl 0.9%). Similarly, Anemarrhena asphodeloides Bunge (Liliaceae) at 200 and 300 mg/kg i.p. (P < 0.001 vs. control group) and 1500 mg/kg orally reduced blood glucose 4 h after administration (P < 0.001). Angiopteris evecta Forst. Hoffn. (Marattiaceae) 300 mg/kg i.p. and 1500 mg/kg orally strongly reduced blood glucose levels (P < 0.001 vs. control groups). All three extracts when dosed at 1000 mg/kg orally suppressed the rise in blood glucose in normal mice during a glucose tolerance test. We have found three herbs that reduced blood glucose and inhibited increases in blood glucose after a glucose challenge in normal mice.


Assuntos
Hiperglicemia/tratamento farmacológico , Hipoglicemiantes/farmacologia , Extratos Vegetais/farmacologia , Animais , Avaliação Pré-Clínica de Medicamentos , Teste de Tolerância a Glucose , Hipoglicemiantes/isolamento & purificação , Camundongos , Vietnã
10.
Int J Drug Policy ; 72: 84-90, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31351752

RESUMO

BACKGROUND: In Australia, Hepatitis C Virus (HCV) treatment is declining, despite broad access to direct-acting antiviral medication. People who inject drugs are proportionally over-represented in emergency department presentations. Emergency department assessment of people who have injected drugs for HCV presents an opportunity to engage this marginalised population with treatment. We describe the outcomes of risk-based screening and point-of-care anti-HCV testing for emergency department patients, and linkage to outpatient antiviral treatment. METHODS: During the three-month study period, consecutive adult patients who presented to the emergency department during the study times were screened for risk factors and offered the OraQuick oral HCV antibody test. Those with reactive results were offered venepuncture in the emergency department for confirmatory testing and direct-acting antiviral treatment in clinic. The main outcome measures were the number and proportion of viremic participants that were linked to the hepatitis clinic, commenced treatment and achieved a sustained viral response. Secondary outcome measures were the proportion (%) of presentations screened that were oral antibody reactive, and the prevalence and type of HCV risk factors. RESULTS: During the study period, 2408 of the 3931 (61%) presentations to the emergency department were eligible for screening. Of these 2408 patients, 1122 (47%) participated, 307 (13%) declined participation and 977 (41%) could not be approached during their time in the emergency department. Among the 1122 participants, 378 (34%) reported at least one risk factor. Subsequently, 368 (97%) of the 378 participants underwent OraQuick anti-HCV test, and 50 (14%) had a reactive result. A risk factor of ever having injected drugs was present in 44 (88%) of participants who were sero-positive. Of the 45 that had blood tested, 30 (67%) were HCV ribonucleic acid (RNA) positive. Three participants died. Of the 27 remaining participants, 10 (37%) commenced treatment and 7 of these 10 (70%) obtained a cure. There was a high rate of homelessness (24%) among anti-HCV positive participants. CONCLUSION: Among emergency department participants with a risk factor for HCV, positive serology was common using a rapid point-of-care test. A history of injecting drug use was identified as the risk factor with highest yield for positive HCV serology, and is suitable as a single screening question. However, linkage to care post ED presentation was low in this marginalised population. There is a need for new pathways to improve the care cascade for marginalised individuals living with HCV infection.


Assuntos
Serviço Hospitalar de Emergência , Hepatite C/diagnóstico , Sistemas Automatizados de Assistência Junto ao Leito , Abuso de Substâncias por Via Intravenosa/complicações , Adulto , Antivirais/administração & dosagem , Austrália , Feminino , Seguimentos , Hepacivirus/isolamento & purificação , Hepatite C/tratamento farmacológico , Hepatite C/epidemiologia , Pessoas Mal Alojadas/estatística & dados numéricos , Humanos , Masculino , Programas de Rastreamento/métodos , Programas de Rastreamento/estatística & dados numéricos , Pessoa de Meia-Idade , Estudos Prospectivos , RNA Viral/análise , Fatores de Risco , Abuso de Substâncias por Via Intravenosa/epidemiologia
11.
Sci Rep ; 8(1): 2245, 2018 02 02.
Artigo em Inglês | MEDLINE | ID: mdl-29396452

RESUMO

Excessive scar formation can form disabling contractures that result in a debilitating psychological outcome. Sustainable hydrophobic corticosteroid release in vivo is essential to regulate the wound healing process. Functional hydrogel particles are widely applied for sustainable release. However, due to the limited aqueous solubility of hydrophobic compounds, most of the corticosteroid is released from the hydrogels within seconds, causing undesirable scar formation and recurrence. In this study, a novel polymerization-induced phase separation is investigated to form well-defined polyethylene glycol diacrylate (PEGDA) core/alginate shell structured hydrogel particles using microfluidics without toxic organic solvents. Based on their wettability preference, hydrophobic corticosteroid-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles are compartmentalized in the PEGDA core during polymerization to control the corticosteroid release. The distribution of the PLGA nanoparticles is precisely regulated by the phase separation boundary and characterized using a fluorescent dye. The thickness of the shell and partition coefficients are determined using the UV intensity and irradiation period. Upon encapsulation of the PLGA nanoparticles within the poly(PEGDA) core, a long-term corticosteroid treatment is developed and effective scar therapeutic outcomes are evaluated using both in vitro and in vivo models.


Assuntos
Corticosteroides/uso terapêutico , Cicatriz/terapia , Portadores de Fármacos/química , Hidrogéis/uso terapêutico , Microfluídica/métodos , Animais , Portadores de Fármacos/uso terapêutico , Feminino , Hidrogel de Polietilenoglicol-Dimetacrilato/química , Interações Hidrofóbicas e Hidrofílicas , Nanopartículas/química , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Coelhos , Cicatrização/fisiologia
12.
Mol Immunol ; 32(8): 555-64, 1995 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-7541890

RESUMO

Major histocompatibility complex (MHC) class II molecules are cell surface glycoproteins and are known to display processed antigens on the surface of antigen presenting cells (APC). Within the APC, the loading of processed antigenic peptides to MHC class II molecules is known to take place in the endosomal compartment at acidic pH environment. The present study describes the in vitro effect of pH on binding of four biotinylated myelin basic protein (MBP) peptides to affinity purified HLA-DR2 containing a mixture of DRB1*1501 and DRB5*0101 beta chain. The binding affinity of the selected peptides are in the order of MBP(83-102)Y83 > MBP(124-143) > MBP(143-168) > MBP(1-14). Most of these peptides in association with HLA-DR2 are considered as immunodominant epitopes for human multiple sclerosis autoimmune disorder. One epitope, MBP(1-14), had almost no affinity to purified HLA-DR2 and was used as a control peptide in all binding assays. The quantitation of the bound peptide at various pH was carried out by antibody capture of complexes followed by avidin-alkaline phosphatase detection system. Among four peptides tested, only the highest affinity MBP(83-102)Y83 peptide showed maximum binding to purified HLA-DR2 at acidic pH. Two other epitopes, MBP(124-143) and MBP(143-168), showed maximum binding at basic and neutral pH values, respectively. The binding of only high affinity peptides, MBP(83-102)Y83 and MBP(124-143), was significantly affected by changing the pH of the binding buffer. Such alteration in pH of the binding buffer resulted in 100% occupancy of DR2 with both high affinity MBP peptides. In contrast, no significant increase in binding of the low affinity MBP(143-168) peptide was observed at altered pH values. The specificity of the increased binding of high affinity peptides to HLA-DR2 at optimum pH was demonstrated by competitive binding assays using non-biotinylated peptides. Finally, the stability of various MBP peptide bound complexes was tested at 4 degrees, 25 degrees and 37 degrees C which correlates well with their affinity to HLA-DR2. These results suggest that pH plays an important role in in vitro binding of antigenic peptides and such manipulation of binding conditions can be utilized in generating 100% loaded MHC class II with high affinity antigenic peptides. Since high affinity peptides are generally considered as major immunodominant epitopes, the in vitro pH dependent binding can be utilized in screening immunodominant epitopes of various autoantigens and generating complexes of defined composition.


Assuntos
Antígeno HLA-DR2/metabolismo , Proteína Básica da Mielina/química , Proteína Básica da Mielina/metabolismo , Peptídeos/química , Peptídeos/metabolismo , Sequência de Aminoácidos , Linhagem Celular , Ensaio de Imunoadsorção Enzimática , Humanos , Concentração de Íons de Hidrogênio , Dados de Sequência Molecular , Ligação Proteica/fisiologia
13.
Mol Immunol ; 31(15): 1161-8, 1994 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-7523870

RESUMO

Affinity-purified major histocompatibility complex (MHC) class II molecules are known to bind antigenic peptides in vitro. The percentage of MHC class II molecules occupied with such peptides is usually very low and varies significantly depending upon the sequence and size of a given antigenic peptide. The present study describes a method by which complete saturation of affinity-purified MHC class II with antigenic peptide can be achieved by simply incubating purified MHC class II molecules at neutral pH in the presence of several 100-fold molar excess of antigenic peptide. Complexes of human HLA-DR2 and a peptide analog from human myelin basic protein MBP (83-102)Y83 were selected for this study. The on-rate kinetic results showed saturation of MHC class II occupancy at 300-500-fold molar excess peptide concentrations. The specificity of the MBP (83-102)Y83 peptide binding to HLA-DR2 at higher peptide concentration was demonstrated by incubating an equivalent amount of another epitope from myelin basic protein [MBP (1-14) peptide] as well as by competitive binding assays. The quantitation of bound peptide was carried out using biotinylated-MBP (83-102)Y83 peptide which showed 100-125% occupancy of HLA-DR2 with a recovery of 100%. The presence of a single peptide entity in purified complexes was confirmed by reverse-phase narrowbore HPLC analysis of the acid extracted supernatant and by mass spectrometry analysis. Two-dimensional gel electrophoresis (IEF/SDS) of purified HLA-DR2 and DR2.MBP (83-102)Y83 complexes showed the absence of various endogenous polypeptides in 100% loaded complexes. These results demonstrate that higher peptide concentrations can be useful in generating MHC class II-peptide complexes of defined composition. Such complexes of MHC class II occupied with a single peptide may have significant clinical relevance for antigen-specific therapy of various autoimmune diseases and may provide better understanding of MHC-peptide-TCR interactions.


Assuntos
Antígeno HLA-DR2/imunologia , Proteína Básica da Mielina/imunologia , Sequência de Aminoácidos , Anticorpos Monoclonais/imunologia , Ligação Competitiva/imunologia , Linhagem Celular Transformada , Cromatografia Líquida de Alta Pressão/métodos , Eletroforese em Gel Bidimensional , Humanos , Hibridomas , Dados de Sequência Molecular , Ligação Proteica/imunologia
14.
Bone Joint J ; 97-B(8): 1017-23, 2015 08.
Artigo em Inglês | MEDLINE | ID: mdl-26224815

RESUMO

The interaction between the lumbosacral spine and the pelvis is dynamically related to positional change, and may be complicated by co-existing pathology. This review summarises the current literature examining the effect of sagittal spinal deformity on pelvic and acetabular orientation during total hip arthroplasty (THA) and provides recommendations to aid in placement of the acetabular component for patients with co-existing spinal pathology or long spinal fusions. Pre-operatively, patients can be divided into four categories based on the flexibility and sagittal balance of the spine. Using this information as a guide, placement of the acetabular component can be optimal based on the type and significance of co-existing spinal deformity.


Assuntos
Acetábulo/cirurgia , Artroplastia de Quadril/métodos , Doenças da Coluna Vertebral/fisiopatologia , Prótese de Quadril , Humanos , Região Lombossacral/fisiopatologia , Ossos Pélvicos/fisiopatologia , Postura/fisiologia
15.
Mol Cell Endocrinol ; 184(1-2): 115-23, 2001 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-11694347

RESUMO

Previous studies have established that the cell-cell adhesion molecule-1 (CEACAM1, previously known as C-CAM1) functions as a tumor suppressor in prostate cancer and is involved in the regulation of prostate growth and differentiation. However, the molecular mechanism that modulates CEACAM1 expression in the prostate is not well defined. Since the growth of prostate epithelial cells is androgen-regulated, we investigated the effects of androgen and the androgen receptor (AR) on CEACAM1 expression. Transient transfection experiments showed that the AR can enhance the Ceacam1 promoter activity in a ligand-dependent manner and that the regulatory element resides within a relatively short (-249 to -194 bp) segment of the 5'-flanking region of the Ceacam1 gene. This androgen regulation is likely through direct AR-promoter binding because a mutant AR defective in DNA binding failed to upregulate reporter gene expression. Furthermore, electrophoretic mobility shift assays demonstrated that the AR specifically binds to this sequence, and mutation analysis of the potential ARE sequences revealed a region within the sequence that was required for the AR to activate the Ceacam1 gene. Therefore, the regulation of Ceacam1 gene expression by androgen may be one of the mechanisms by which androgen regulates prostatic function.


Assuntos
Androgênios/fisiologia , Antígenos CD/genética , Antígenos de Diferenciação/genética , Regulação da Expressão Gênica/efeitos dos fármacos , Animais , Antígenos CD/efeitos dos fármacos , Antígenos de Diferenciação/efeitos dos fármacos , Sítios de Ligação/genética , Moléculas de Adesão Celular , Proteínas de Ligação a DNA/fisiologia , Células HeLa , Humanos , Mutagênese Sítio-Dirigida , Regiões Promotoras Genéticas/efeitos dos fármacos , Ratos , Receptores Androgênicos/genética , Receptores Androgênicos/metabolismo , Receptores Androgênicos/fisiologia , Transfecção
16.
J Chem Neuroanat ; 17(3): 169-77, 1999 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-10609866

RESUMO

Cholecystokinin-8-like-immunoreactive (CCK-8-LI) fibers in laminae VII and X of the rat lumbosacral spinal cord demarcate the position of preganglionic autonomic neurons. This investigation reveals that adult male Sprague-Dawley, or King-Holtzman/Sprague-Dawley rats contain more CCK-8-LI fibers in lumbosacral laminae VII and X than adult females. Furthermore, testicular feminization mutation male rats (which lack 85-90% of their functional androgen receptors) contain fewer CCK-8-LI fibers than normal male or female rats, with the amount of CCK-8-LI being reduced to a greater extent in the sympathetic vs. the parasympathetic regions of the lumbosacral spinal cord. Thus, CCK-8-LI in testicular feminization mutation male rats has a distinctly female-like pattern. These results suggest that testosterone is a regulatory factor for CCK-8-LI fibers found in laminae VII and X of the lumbosacral spinal cord. Sexual dimorphism in lumbosacral CCK-8-LI fibers may contribute to modulating the final common pathway which differentially regulates the reproductive organs and stereotypic reproductive behavior, and may be involved with the sex differences described for pain.


Assuntos
Vias Autônomas/metabolismo , Receptores Androgênicos/metabolismo , Sincalida/metabolismo , Medula Espinal/metabolismo , Síndrome de Resistência a Andrógenos/metabolismo , Animais , Feminino , Região Lombossacral , Masculino , Ratos , Ratos Sprague-Dawley , Fatores Sexuais
17.
Neurosci Lett ; 276(3): 165-8, 1999 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-10612631

RESUMO

The gray matter surrounding the central canal of rat lumbar spinal cord contains a population of spinothalamic neurons which has been shown to co-contain cholecystokinin-8 (CCK-8) and galanin (GAL) (Ju, G., Melander, T., Hökfelt, T. and Frey, P., Immunohistochemical evidence for a spinothalamic pathway co-containing cholecystokinin- and galanin-like immunoreactivities in the rat. Neuroscience, 20 (1987) 439-456). A previous study from our laboratory has shown that female rats have only 62% the number of GAL-containing midline neurons present in males. Counts of CCK-8-containing midline neurons reveal that females have 59% the number observed in males. These results indicate that the degree of sexual dimorphism seen for CCK-8 is the same for GAL in these midline lumbar neurons, and suggests that androgens modulate the production of the co-contained GAL and CCK-8 in a similar fashion within male rat spinal cords.


Assuntos
Neurônios/metabolismo , Caracteres Sexuais , Sincalida/metabolismo , Medula Espinal/metabolismo , Animais , Contagem de Células , Feminino , Galanina/metabolismo , Região Lombossacral , Masculino , Neurônios/citologia , Ratos , Ratos Sprague-Dawley , Medula Espinal/citologia
18.
Exp Clin Endocrinol Diabetes ; 112(9): 520-5, 2004 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-15505760

RESUMO

BACKGROUND: The hypoglycemic effect of extract of Anemarrhena asphodeloides has been accounted for by the substance mangiferin which increases insulin sensitivity. The present study aimed to investigate whether an ethanol extract of Anemarrhena asphodeloides would stimulate insulin secretion and if so, further elucidate the mechanism behind this effect. METHODS: Isolated pancreatic islets of normal Wistar rats and spontaneously diabetic Goto-Kakizaki (GK) rats were batch incubated or perifused to study effect of Anemarrhena asphodeloides extract (TH2) on insulin release. RESULTS: At 3.3 mM glucose, 2, 4, and 8 mg/ml TH2 increased the insulin release of Wistar rat islets 2.5-, 4.1-, and 5.7-fold, respectively (p < 0.05) and of GK rat islets 1.7-, 3.0-, and 6.3-fold, respectively (p < 0.01). Similarly at 16.7 mM glucose, 2, 4 and 8 mg/ml TH2 increased insulin release of Wistar rat islets 1.5-, 2.2-, and 3.8-fold, respectively (p < 0.05) and of GK rat 2.5-, 4.2-, and 11.9-fold, respectively (p < 0.01). In perifusions of islets, TH2 also increased insulin secretion that returned to basal levels when TH2 was omitted from the perifusate. Mangiferin had no effect on insulin secretion of islets. In islets depolarized by 30 mM KCl and B-cell K-ATP channels kept open by 0.25 mM diazoxide, TH2 (8 mg/ml) further enhanced insulin secretion at 3.3 but not at 16.7 mM glucose. Pertussis toxin suppressed the insulin stimulating effect of 2 and 8 mg/ml TH2 by 35 % and 47 % (p < 0.05 and p < 0.001, respectively). CONCLUSIONS: Ethanol extract of the roots of Anemarrhena asphodeloides contains a substance, TH2, that stimulates insulin secretion both at 3.3 and 16.7 mM glucose in islets of normal Wistar and diabetic GK rats. The mechanism behind TH2-stimulated insulin secretion involves an effect on the exocytotic machinery of the B-cell, mediated via pertussis toxin-sensitive Gi- (or Ge-) proteins.


Assuntos
Anemarrhena/química , Diabetes Mellitus/genética , Diabetes Mellitus/metabolismo , Insulina/metabolismo , Ilhotas Pancreáticas/efeitos dos fármacos , Ilhotas Pancreáticas/metabolismo , Extratos Vegetais/farmacologia , Animais , Diabetes Mellitus/fisiopatologia , Eletrofisiologia , Etanol , Técnicas In Vitro , Secreção de Insulina , Ilhotas Pancreáticas/fisiopatologia , Cinética , Toxina Pertussis/farmacologia , Raízes de Plantas/química , Cloreto de Potássio/farmacologia , Ratos , Ratos Endogâmicos , Ratos Wistar , Solventes , Xantonas/farmacologia
19.
J Perinatol ; 8(3): 193-8, 1988.
Artigo em Inglês | MEDLINE | ID: mdl-3225660

RESUMO

Thirty pairs of healthy, growing preterm infants were included in this randomized prospective study comparing thermal weaning at 1700 g with that at 1800 g. Based on an intention-to-treat analysis, infants weaned at 1700 g were discharged 1.1 days sooner than those weaned at 1800 g. However, this result was not statistically significant (p = 0.13). On the other hand, differences are apparent between treatments in some strata based on birth weight (p = 0.0056). Evidence also existed that time from entry (at 1500 g) to discharge depended on birth weight stratum (p = 0.010). No infant in either group lost weight after successful weaning, and mean 24-hour weight gains were similar for both groups. Two infants were weaned at 1800 g requiring return to the incubator due to hypothermia, and four infants weaned at 1700 g likewise requiring return to the incubator. The number weaned at 1700 g who had birth weight of 1000 g or less and who developed hypothermia appeared substantial (three of six such infants). Thus, it appears that thermal weaning at 1700 g may be safe and effective only for prematures with birth weight above 1000 g. Additional study appears needed.


Assuntos
Incubadoras para Lactentes , Recém-Nascido Prematuro/fisiologia , Peso Corporal , Temperatura Alta , Humanos , Recém-Nascido , Estudos Prospectivos , Distribuição Aleatória
20.
J Nutr Metab ; 2013: 765383, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23431428

RESUMO

Aims. To evaluate the effect of the traditional Vietnamese herb Gynostemma pentaphyllum tea on insulin sensitivity in drug-naïve type 2 diabetic patients. Methods. Patients received GP or placebo tea 6 g daily for four weeks and vice versa with a 2-week wash-out period. At the end of each period, a somatostatin-insulin-glucose infusion test (SIGIT) was performed to evaluate the insulin sensitivity. Fasting plasma glucose (FPG), HbA(1C), and oral glucose tolerance tests and insulin levels were measured before, during, and after the treatment. Results. FPG and steady-state plasma glucose (SIGIT mean) were lower after GP treatment compared to placebo treatment (P < 0.001). The levels of FPG in the control group were slightly reduced to 0.2 ± 1.5 versus 1.9 ± 1.0 mmol/L in GP group (P < 0.001), and the effect on FPG was reversed after exchanging treatments. The glycometabolic improvements were achieved without any major change of circulating insulin levels. There were no changes in lipids, body measurements, blood pressure, and no reported hypoglycemias or acute adverse effects regarding kidney and liver parameters. Conclusion. The results of this study suggested that the GP tea exerted antidiabetic effect by improving insulin sensitivity.

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