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1.
PLoS One ; 16(7): e0255330, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34329355

RESUMEN

BACKGROUND: Male partner involvement (MPI) has been recognized as a priority area to be strengthened in Prevention of Mother to Child Transmission (PMTCT) of HIV. We explored the impact of Couple Oriented Counselling (COC) in MPI in sexual and reproductive health and associated factors. METHOD: From February 2009 to October 2011, pregnant women were enrolled at their first antenatal care visit (ANC-1) and followed up until 6 months after delivery in the Mother and Child Center of the Chantal Biya Foundation within the randomized prenahtest multicentric trial. The MPI index was defined using sexual and reproductive health behaviour variables by using multiple correspondence analysis followed by mixed classification. Men were considered as highly involved if they had shared their HIV test results with their partner, had discussed on HIV or condom used, had contributed financially to ANC, had accompanied their wife to ANC or had practiced safe sex. Factors associated to MPI were investigated by the logistic model with GEE estimation approach. RESULTS: A total of 484 pregnant women were enrolled. The median age of the women was 27 years (IQR: 23-31) and 55.23% had a gestational age greater than 16 weeks at ANC-1. Among them, HIV prevalence was 11.9% (95% CI: 9.0-15.4). The median duration of the women's relationship with their partner was 84 months (IQR: 48-120). MPI index at 6 months after delivery was significantly greater in the COC group than the classical counselling group (14.8% vs 8,82%; p = 0,043; Fig 1). The partners of the women who participated in the COC were more likely to be involved during follow up than others (aOR = 1.45; 95% CI = 1.00-2.10). Partners with no incoming activity (aOR = 2.90; 95% CI = 1.96-4.29), who did not used violence within the couple (aOR = 1.70; 95% CI = 1.07-2.68), and whose partner came early for ANC-1 (aOR = 1.37; 95% CI = 1.00-1.89) were more likely to be involved than others. CONCLUSION: MPI remains low in stable couples and COC improves partner involvement. Our findings also support the need of strengthening outreach towards "stable" couples and addressing barriers. This could go a long way to improve PMTCT outcomes in Cameroon. TRIAL REGISTRATION: PRENAHTEST, NCT01494961. Registered 15 December 2011-Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT01494961.


Asunto(s)
Consejo , Infecciones por VIH/prevención & control , VIH-1 , Transmisión Vertical de Enfermedad Infecciosa/prevención & control , Complicaciones Infecciosas del Embarazo/prevención & control , Salud Reproductiva , Parejas Sexuales , Adulto , Anciano , Femenino , Infecciones por VIH/epidemiología , Infecciones por VIH/transmisión , Humanos , Masculino , Persona de Mediana Edad , Embarazo , Complicaciones Infecciosas del Embarazo/epidemiología
2.
Nanoscale ; 12(47): 24020-24029, 2020 Dec 21.
Artículo en Inglés | MEDLINE | ID: mdl-33245306

RESUMEN

We report the elaboration of supercrystals made up of dodecanoic acid-coated 8.1 nm-Co nanocrystals with controlled supercrystallinity, morphology and magnetic properties. Supercrystal growth is controlled using a solvent-mediated ligand-ligand interaction strategy. Either face-centered cubic supercrystalline films or single colloidal crystals composed of cobalt nanocrystals are obtained. The change in supercrystal morphology is explained by Flory-type solvation theory using Hansen solubility colloidal parameters. The use of the same batch of Co nanocrystals for the fabrication of supercrystalline films and colloidal crystals enables accurate comparative structural and magnetic studies using (high-resolution) transmission electron microscopy, field emission gun scanning electron microscopy, grazing incidence small-angle X-ray scattering and vibrating sample magnetometry. The nearest neighbor distance between nanoparticles is interpreted using theoretical models proposed in the literature. We evidence the increase in both geometric anisotropy and magnetic dipolar interactions for colloidal crystals compared to supercrystalline films.

4.
BJOG ; 123(8): 1311-8, 2016 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-26485578

RESUMEN

OBJECTIVE: To examine the associations between interpregnancy interval and later maternal cardiovascular disease (CVD) risk. DESIGN: Population-based record linkage study. SETTING: New South Wales, Australia, 1994-2011. POPULATION: 216 467 women having first and second liveborn singleton infants, excluding those with an existing or pregnancy-related CVD risk factor. METHODS: We linked birth records of mothers to the mothers' subsequent CVD (coronary heart disease, cerebrovascular events, and chronic heart failure) hospitalisation or death. Multivariable Cox proportional hazard regression was used to estimate adjusted hazard ratios (AHR) [95% confidence interval (CI)], accounting for maternal age, parity, socioeconomic status, and smoking during pregnancy. MAIN OUTCOME MEASURES: The first occurrence of a CVD hospitalisation or death after the second birth. RESULTS: In comparison with mothers with an interpregnancy interval of 18-23 months (reference category), the AHR among mothers with interpregnancy interval of <12 months was 1.56 (95% CI 1.18-2.07) and of 12-17 months was 1.13 (95% CI 0.84-1.51). The AHRs were 1.40 (95% CI 1.07-1.82), 1.87 (95% CI 1.21-2.89), and 3.41 (95% CI 1.07-10.91), corresponding to interpregnancy intervals of 24-59, 60-119, and ≥120 months, respectively. AHRs of specific CVD categories showed a similar pattern. CONCLUSIONS: Interpregnancy interval is associated with the risk of subsequent maternal CVD in a J-shaped fashion. The association is independent of the existing and pregnancy-related CVD risk factors analysed. Both short and long interpregnancy intervals can be used as risk markers to identify women with an elevated CVD risk later in life. TWEETABLE ABSTRACT: Interpregnancy interval is associated with the risk of subsequent maternal cardiovascular disease in a J-shaped fashion.


Asunto(s)
Intervalo entre Nacimientos/estadística & datos numéricos , Enfermedades Cardiovasculares/epidemiología , Hospitalización/estadística & datos numéricos , Adolescente , Adulto , Enfermedades Cardiovasculares/mortalidad , Femenino , Humanos , Almacenamiento y Recuperación de la Información , Edad Materna , Análisis Multivariante , Nueva Gales del Sur/epidemiología , Paridad , Embarazo , Modelos de Riesgos Proporcionales , Fumar/epidemiología , Clase Social , Adulto Joven
5.
Cardiovasc Intervent Radiol ; 38(6): 1573-88, 2015 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-26088719

RESUMEN

PURPOSE: To evaluate outcomes following treatment of transplant renal artery stenosis by percutaneous transluminal angioplasty and stent insertion. MATERIALS AND METHODS: A literature search was performed using Pubmed, MEDLINE, Embase, Wiley Interscience and the Cochrane Library databases. Outcome measures were glomerular filtration rate, creatinine, blood pressure and number of antihypertensive medications. Technical and clinical success, patency and complication rates were also analysed. RESULTS: Thirty-two studies met the inclusion criteria, involving a total of 884 interventions including PTA, stenting, or combinations of both. Clinical success rates were in the range 65.5-94%. The majority of studies reported technical success rates higher than 90%. Patency rates were in the range of 42-100%. However, the definition and diagnostic criteria for TRAS varied widely between studies. Also, marked heterogeneity was observed in the reporting of outcome measures with no consensus in outcome criteria or follow up schedule. CONCLUSION: Outcomes following PTA and stenting for the treatment of TRAS have been shown to be favourable. However, there is a distinct lack of well designed studies assessing outcomes following intervention. Outcome reporting may be improved by the introduction of standardised outcome measures with reporting of outcomes into a multi-centre registry.


Asunto(s)
Angioplastia , Trasplante de Riñón , Complicaciones Posoperatorias/terapia , Obstrucción de la Arteria Renal/terapia , Stents , Tasa de Filtración Glomerular , Humanos , Complicaciones Posoperatorias/cirugía , Obstrucción de la Arteria Renal/cirugía , Resultado del Tratamiento , Grado de Desobstrucción Vascular
6.
Case Rep Med ; 2013: 206971, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-24368916

RESUMEN

Although many Asians regard puffer fish as a delicacy since ancient times, puffer fish (Lageocephalus scitalleratus) is also a well-known source of possibly lethal food poisoning. The fish is gaining popularity in Singapore and can be found in quite a few restaurants now. Puffer fish contains tetrodotoxin (TTX), a potent poison affecting the neural pathway. Puffer fish poisoning may cause a constellation of symptoms, such as giddiness, numbness and tingling sensation of the mouth, paresthesia, and muscle weakness. Severe cases may present with respiratory depression, circulatory failure, and death. TTX poisonings have been reported in Japan, Taiwan, Hong Kong, Bangladesh, and the United States (Haque et al. 2008). We report a case of mild poisoning and suggest observation for such cases.

8.
Rev Med Interne ; 31(12): 812-8, 2010 Dec.
Artículo en Francés | MEDLINE | ID: mdl-20926165

RESUMEN

PURPOSE: Haiphong is the second city of Vietnam most affected by HIV infection. Penicilliosis represents the third leading cause of opportunistic infection. However, this systemic fungal infection remains poorly knew by practitioners. This study aimed to clarify the clinical, diagnostic and therapeutic aspects of penicilliosis. METHODS: It is a descriptive study, prospective and retrospective, conducted over a 3-year period in Viet Tiep hospital, Haiphong. RESULTS: With 94 cases, penicilliosis represented 11% of opportunistic infections. The patients were young (mean: 33 years) and male (87%). The main symptoms were persistent fever (99%), weight loss (88%), skin lesions (86%), hepatomegaly (69%) and lymphadenopathy (68%). Anemia was noted in 77% of cases. The average CD4 count was 29/µL. The culture of skin biopsies and blood culture were positive for Penicillium marneffei in 94% and 90% of cases, respectively. Despite antiretroviral and antifungal therapy, the mortality rate was 18%. Itraconazole monotherapy, administered in 53 patients due to the unavailability of amphotericin B, did not significantly affect the survival compared to the recommended treatment received by the 41 other patients. CONCLUSION: In Haiphong, penicilliosis is one of the most frequent and severe opportunistic infections of AIDS. The diagnosis should be considered in all febrile and immunocompromised patients having spent time in Vietnam. The prognosis can be improved by early diagnosis through the blood culture and a good adherence to an appropriate antifungal therapy.


Asunto(s)
Infecciones Oportunistas Relacionadas con el SIDA/diagnóstico , Infecciones Oportunistas Relacionadas con el SIDA/tratamiento farmacológico , Antifúngicos/uso terapéutico , Huésped Inmunocomprometido , Micosis/diagnóstico , Micosis/tratamiento farmacológico , Penicillium , Infecciones Oportunistas Relacionadas con el SIDA/complicaciones , Infecciones Oportunistas Relacionadas con el SIDA/epidemiología , Adolescente , Adulto , Anfotericina B/uso terapéutico , Terapia Antirretroviral Altamente Activa/métodos , Diagnóstico Precoz , Femenino , Hospitalización/estadística & datos numéricos , Humanos , Itraconazol/uso terapéutico , Masculino , Persona de Mediana Edad , Micosis/epidemiología , Micosis/microbiología , Penicillium/aislamiento & purificación , Pronóstico , Estudios Prospectivos , Estudios Retrospectivos , Análisis de Supervivencia , Resultado del Tratamiento , Vietnam/epidemiología
9.
Nat Nanotechnol ; 4(11): 759-64, 2009 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-19893512

RESUMEN

The controlled creation, manipulation and detection of spin-polarized currents by purely electrical means remains a central challenge of spintronics. Efforts to meet this challenge by exploiting the coupling of the electron orbital motion to its spin, in particular Rashba spin-orbit coupling, have so far been unsuccessful. Recently, it has been shown theoretically that the confining potential of a small current-carrying wire with high intrinsic spin-orbit coupling leads to the accumulation of opposite spins at opposite edges of the wire, though not to a spin-polarized current. Here, we present experimental evidence that a quantum point contact -- a short wire -- made from a semiconductor with high intrinsic spin-orbit coupling can generate a completely spin-polarized current when its lateral confinement is made highly asymmetric. By avoiding the use of ferromagnetic contacts or external magnetic fields, such quantum point contacts may make feasible the development of a variety of semiconductor spintronic devices.

10.
ACS Nano ; 3(6): 1539-47, 2009 Jun 23.
Artículo en Inglés | MEDLINE | ID: mdl-19459692

RESUMEN

The origin of the magnetic anisotropy is explained in an assembly of aligned magnetic nanoparticles. For that, nanoparticles synthesized biologically by Magnetospirillum magneticum AMB-1 magnetotactic bacteria are used. For the first time, it is possible to differentiate between the two contributions arising from the alignment of the magnetosome easy axes and the strength of the magnetosome dipolar interactions. The magnetic anisotropy is shown to arise mainly from the dipolar interactions between the magnetosomes.

11.
AIDS Care ; 19(7): 878-87, 2007 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-17712691

RESUMEN

This qualitative study was conducted to explore health-seeking behaviour for sexually transmitted infections (STIs) and HIV testing among female sex workers (FSWs) in the cities of Hanoi and Da Nang, Vietnam. Data were gathered from in-depth interviews, focus groups and participant observation. Results suggest that women's decision to seek STI treatment and HIV testing is influenced by the complex interplay of personal risk perceptions, social relationships and community discourse. The women exhibited adequate knowledge of HIV while their knowledge of STIs was limited. They demonstrated high-risk perceptions of HIV, but they showed little concern for STIs. Most women sought treatment at pharmacies when they noticed symptoms of the genital tract. Their decision to seek care in health facilities and HIV testing was hampered by the high costs of treatment, judgmental attitudes of service providers, and a lack of information on testing services. Future interventions need to focus on strengthening knowledge of STIs and the STI-HIV association, and increasing awareness of HIV counselling and testing services. Training for STI service providers including pharmacies and private practitioners on sex-worker friendly and non-judgmental services and counselling skills should be emphasized to provide timely diagnosis and treatment of STIs, and to refer women to HIV testing.


Asunto(s)
Infecciones por VIH/prevención & control , Conocimientos, Actitudes y Práctica en Salud , Aceptación de la Atención de Salud/psicología , Trabajo Sexual , Enfermedades de Transmisión Sexual/terapia , Adulto , Femenino , Grupos Focales , Humanos , Masculino , Investigación Cualitativa , Conducta Sexual , Enfermedades de Transmisión Sexual/prevención & control , Encuestas y Cuestionarios , Vietnam
12.
Rev Pneumol Clin ; 63(3): 139-46, 2007 Jun.
Artículo en Francés | MEDLINE | ID: mdl-17675937

RESUMEN

OBJECTIVE OF THE STUDY: To know the mechanisms and causes of death in Vietnamese VIH-infected patients hospitalized for tuberculosis. METHODS: Retrospective analysis of a monocentric cohort of 143 consecutive co infected patients admitted to Pham Ngoc Thach Hospital, in Ho Chi Minh City, between January 2004 and November 2004. MAIN RESULTS: All the patients were HIV-infected and AFB smear positive. The CD4 T lymphocyte count was 55/mm3 and the body mass index was 15.8 +/- 2 kg/m2. During the first three months after hospital admission and tuberculosis diagnosis, the percentage of deaths was 28.7% (41/143). The mechanisms of deaths were: progressive cachexia, acute respiratory failure, cardiogenic or bacteremic shock, coma and unexpected cardio respiratory arrest. The causes of death were tuberculosis (particularly mechanical complications such as compressive pneumothorax, pericarditis or pleuritis), metabolic disorders (mainly hyponatrémie and dyskaliema) and associated infection. In multivariate analysis, two parameters (available at admission) were predictive of short-term death: anemia (p=0.024) and hyponatrémie (p=0.026). CONCLUSION: The short term mortality of co infected patients with AIDS and tuberculosis remains high in developing countries. However, some causes of death such as compressive pneumothorax-pleuritis-pericarditis, metabolic disorder or even associated opportunistic infection i. e. pneumocystosis may be prevented or cured. Consequently, such patients must be carefully monitored and more particularly those with severe anemia and/or hyponatrémie at admission. Similarly appropriate diagnostic algorithms must be used in case of unfavorable evolution particularly to diagnose curable complication.


Asunto(s)
Infecciones Oportunistas Relacionadas con el SIDA/mortalidad , Infecciones por VIH/mortalidad , Tuberculosis Pulmonar/mortalidad , Adulto , Índice de Masa Corporal , Recuento de Linfocito CD4 , Caquexia/mortalidad , Estudios de Cohortes , Coma/mortalidad , Muerte Súbita Cardíaca/epidemiología , Femenino , Mortalidad Hospitalaria , Humanos , Hiponatremia/mortalidad , Masculino , Persona de Mediana Edad , Pericarditis/mortalidad , Pleuresia/mortalidad , Neumotórax/mortalidad , Insuficiencia Respiratoria/mortalidad , Estudios Retrospectivos , Factores de Riesgo , Choque Cardiogénico/mortalidad , Choque Séptico/mortalidad , Vietnam/epidemiología
13.
Langmuir ; 21(22): 10234-9, 2005 Oct 25.
Artículo en Inglés | MEDLINE | ID: mdl-16229550

RESUMEN

Solid structures made of collapsed cylinders organized in hexagonal, stripes and wavy line-like structures are fabricated by slow evaporation of maghemite nanocrystals dispersed in hexane and subjected to an applied field perpendicular to the substrate. The sizes of the experimental structures are well described by a theory based on the minimization of the total free energy. Comparison between experiment and theory shows that the structures are explained by a labyrinthine instability enabled by a colloidal liquid-gas phase transition during the evaporation process. From the theoretical model and experimental data, it is concluded that the height determines the radius of the cylinders, whereas the phase ratio of the magnetic to the total volume and the field strength have little influence under the conditions studied here.

14.
Singapore Med J ; 46(4): 172-8, 2005 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-15800723

RESUMEN

INTRODUCTION: Accidents with foreign bodies are common in the paediatric population. It is impossible to mandate that all foreign bodies (FB) in the ear, nose and throat (ENT) of children should be removed by the specialty-trained physicians. This study evaluates the management of ENT FB removal in children achieved by emergency physicians not trained in otolaryngology in an urban tertiary care paediatric emergency department. METHODS: A retrospective study was conducted on consecutive paediatric patients presenting with suspected foreign body in the ear, nose or throat to the children's emergency department (ED) of KK Women's and Children's Hospital over a 10-month period. Removal methods, foreign body types, rates of successful removal and associated complications were evaluated. RESULTS: There were 353 patients, most of whom presented after office hours. An attempt at removal of FB by the emergency physician was made in 76.8 percent of the cases. ENT specialist referral in the ED was made in 1.7 percent of the cases. 50.1 percent of cases were discharged after successful removal of FB in the ED. 4.2 percent of cases were admitted for removal of FB and 44.8 percent of cases were referred to the ENT specialist clinic for further assessment. CONCLUSION: The emergency physician managed most cases in the ED and urgent referral to ENT specialists was not required. Complications and morbidity often occur from repeated attempts at removal of the FB. ENT opinion should be sought whenever there is doubt. The ED physician should be skilled in techniques of FB removal, especially throat FB, which had the lowest rate of success in our study.


Asunto(s)
Oído , Cuerpos Extraños/epidemiología , Nariz , Faringe , Distribución por Edad , Niño , Preescolar , Servicio de Urgencia en Hospital/estadística & datos numéricos , Femenino , Cuerpos Extraños/terapia , Humanos , Orofaringe , Otolaringología , Derivación y Consulta/estadística & datos numéricos , Estudios Retrospectivos , Singapur/epidemiología
15.
Singapore Med J ; 46(1): 38-40; quiz 41, 2005 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-15633008

RESUMEN

A 24-year-old man presented with generalised malaise and myalgia for three days. He presented to the Emergency Department after a fall at his workplace due to weakness. 12-lead electrocardiogram (ECG) showed normal sinus rhythm with ST depression in the leads V4 to V6, with a U wave. The tallest U wave appeared in V3. These ECG features are characteristic of hypokalaemia. ECG changes in hypokalaemia and differential diagnosis are discussed. A second case of thyrotoxic periodic paralysis with similar ECG changes of hypokalaemia is also presented.


Asunto(s)
Electrocardiografía , Hipopotasemia/complicaciones , Hipopotasemia/diagnóstico , Enfermedades Musculares/etiología , Dolor/etiología , Adulto , Diagnóstico Diferencial , Fatiga/etiología , Humanos , Masculino
16.
Am J Gastroenterol ; 95(1): 195-8, 2000 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-10638582

RESUMEN

OBJECTIVE: The aim of this study was to identify factors associated with severe outcome in patients with ischemic colitis. METHODS: The files of 60 consecutive inpatients (34 women, 26 men, mean age 67 yr) with ischemic colitis were reviewed. The following data were analyzed: age, sex, smoking, medications, history of cardiovascular disease, metabolic disease, chronic renal failure and hemodialysis, the time elapsed between the first symptoms and the diagnosis, and the site and extension of their colonic involvement. Patients were divided into two groups according to outcome: those with severe disease, including those who died from ischemic colitis (n = 3) or who required surgical resection (n = 21); and those with mild forms of colitis who were treated successfully without surgery (n = 36). The two groups were compared by means of univariate and multivariate analysis to identify factors associated with unfavorable outcomes. Only patients who had a complete examination of the colon (n = 51) were entered into the statistical analysis. RESULTS: By univariate analysis, chronic renal failure (p = 0.03), hemodialysis (p = 0.01), short delay between symptoms and diagnosis (p = 0.01), and right colonic involvement (p = 0.002) were significantly more common in the patients with severe colitis. By logistic regression, right colonic involvement was the only factor independently associated with severity (p = 0.01). Right-sided lesions were present in 82% of patients on dialysis but in only 26% of patients not on dialysis (p = 0.0005). CONCLUSIONS: Right colonic involvement is associated with severe forms of ischemic colitis and occurs frequently in patients with chronic renal failure requiring hemodialysis.


Asunto(s)
Colitis Isquémica/patología , Colon/patología , Fallo Renal Crónico/terapia , Diálisis Renal/efectos adversos , Adulto , Anciano , Anciano de 80 o más Años , Colitis Isquémica/etiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pronóstico
17.
J Bioenerg Biomembr ; 29(1): 71-80, 1997 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-9067804

RESUMEN

As part of the ongoing studies aimed at elucidating the mechanism of the energy conserving function of mitochondrial complex I, NADH: ubiquinone (Q) reductase, we have investigated how short-chain Q analogs activate the proton pumping function of this complex. Using a pH-sensitive fluorescent dye we have monitored both the extent and initial velocity of proton pumping of complex I in submitochondrial particles. The results are consistent with two sites of interaction of Q analogs with complex I, each having different proton pumping capacity. One is the physiological site which leads to a rapid proton pumping and a stoichiometric consumption of NADH associated with the reduction of the most hydrophobic Q analogs. Of these, heptyl-Q appears to be the most efficient substrate in the assay of proton pumping. Q analogs with a short-chain of less than six carbons interact with a second site which drives a slow proton pumping activity associated with NADH oxidation that is overstoichiometric to the reduced quinone acceptor. This activity is also nonphysiological, since hydrophilic Q analogs show little or no respiratory control ratio of their NADH:Q reductase activity, contrary to hydrophobic Q analogs.


Asunto(s)
Mitocondrias/enzimología , NAD(P)H Deshidrogenasa (Quinona)/metabolismo , Bombas de Protones/efectos de los fármacos , Ubiquinona/análogos & derivados , Aminoacridinas/química , Activación Enzimática , Colorantes Fluorescentes/química , Mitocondrias/efectos de los fármacos , NAD(P)H Deshidrogenasa (Quinona)/efectos de los fármacos , Ubiquinona/farmacología
18.
Diabetes ; 45(11): 1531-4, 1996 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-8866557

RESUMEN

Human intoxication with the rodenticide Vacor [N-3-pyridylmethyl-N'-p-nitrophenyl urea or 1-(4-nitrophenyl)-3-(3-pyridylmethyl) urea] induces acute IDDM. We report here that Vacor specifically inhibits the NADH:ubiquinone reductase activity of complex I in mammalian mitochondria. The activity of other respiratory enzymes of mitochondria is unaffected by Vacor at concentrations that completely inhibit the redox and energetic function of complex I. Vacor inhibition of complex I activity quantitatively correlates with the inhibition of insulin release in insulinoma cells and pancreatic islets and is also consistent with the doses reported in cases of human poisoning. These results indicate that the toxic and diabetogenic action of Vacor primarily derives from the inhibition of mitochondrial respiration of NAD-linked substrates in the high-energy demanding cells of the pancreatic islets. This newly identified mechanism of the pathological effects resulting from Vacor intoxication could constitute a paradigm in which to understand environmental or metabolic causes of IDDM.


Asunto(s)
Diabetes Mellitus Tipo 1/inducido químicamente , Mitocondrias Cardíacas/enzimología , Mitocondrias Hepáticas/enzimología , NAD(P)H Deshidrogenasa (Quinona)/antagonistas & inhibidores , Compuestos de Fenilurea/envenenamiento , Rodenticidas/envenenamiento , Partículas Submitocóndricas/enzimología , Animales , Bovinos , Línea Celular , Cricetinae , Humanos , Insulina/metabolismo , Antagonistas de Insulina/farmacología , Secreción de Insulina , Insulinoma , Islotes Pancreáticos/efectos de los fármacos , Islotes Pancreáticos/metabolismo , Consumo de Oxígeno/efectos de los fármacos , Neoplasias Pancreáticas , Compuestos de Fenilurea/farmacología , Ratas , Rodenticidas/farmacología , Células Tumorales Cultivadas
19.
Arch Biochem Biophys ; 330(2): 395-400, 1996 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-8660670

RESUMEN

We have studied the interaction of idebenone (2,3-dimethoxy-5-methy-6-(10-hydroxy)decyl-1,4-benzoquinone) with the energy-conserving complexes of the respiratory chain in beef heart mitochondria and compared its energetic efficiency with that of other analogs of coenzyme Q. Idebenone is a very effective substrate for succinate:Q reductase and ubiquinol:cytochrome c reductase, but it is clearly a poor substrate for NADH:Q reductase (complex I). Indeed, idebenone is a strong inhibitor of both the redox and proton pumping activity of complex I, showing effects in part similar to those of coenzyme Q-2. However, the mechanism of idebenone interaction with complex I may be different from that of Q-2 because of its different sensitivity to inhibitors. The possible relevance of the present findings to the therapeutic use of idebenone is discussed.


Asunto(s)
Benzoquinonas/metabolismo , Mitocondrias Cardíacas/metabolismo , Ubiquinona/análogos & derivados , Animales , Benzoquinonas/farmacología , Bovinos , Transporte de Electrón/efectos de los fármacos , Metabolismo Energético , Inhibidores Enzimáticos/farmacología , Técnicas In Vitro , Mitocondrias Cardíacas/efectos de los fármacos , NAD(P)H Deshidrogenasa (Quinona)/antagonistas & inhibidores , NAD(P)H Deshidrogenasa (Quinona)/metabolismo , Oxidación-Reducción , Especificidad por Sustrato , Ubiquinona/metabolismo , Ubiquinona/farmacología
20.
Biochem J ; 313 ( Pt 1): 327-34, 1996 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-8546703

RESUMEN

We report the first detailed study on the ubiquinone (coenzyme Q; abbreviated to Q) analogue specificity of mitochondrial complex I, NADH:Q reductase, in intact submitochondrial particles. The enzymic function of complex I has been investigated using a series of analogues of Q as electron acceptor substrates for both electron transport activity and the associated generation of membrane potential. Q analogues with a saturated substituent of one to three carbons at position 6 of the 2,3-dimethoxy-5-methyl-1,4-benzoquinone ring have the fastest rates of electron transport activity, and analogues with a substituent of seven to nine carbon atoms have the highest values of association constant derived from NADH:Q reductase activity. The rate of NADH:Q reductase activity is potently but incompletely inhibited by rotenone, and the residual rotenone-insensitive rate is stimulated by Q analogues in different ways depending on the hydrophobicity of their substituent. Membrane potential measurements have been undertaken to evaluate the energetic efficiency of complex I with various Q analogues. Only hydrophobic analogues such as nonyl-Q or undecyl-Q show an efficiency of membrane potential generation equivalent to that of endogenous Q. The less hydrophobic analogues as well as the isoprenoid analogue Q-2 are more efficient as substrates for the redox activity of complex I than for membrane potential generation. Thus the hydrophilic Q analogues act also as electron sinks and interact incompletely with the physiological Q site in complex I that pumps protons and generates membrane potential.


Asunto(s)
Mitocondrias/enzimología , NAD(P)H Deshidrogenasa (Quinona)/metabolismo , Ubiquinona/metabolismo , Animales , Benzoquinonas/metabolismo , Sitios de Unión , Bovinos , Potenciales de la Membrana/fisiología , NAD/metabolismo , Oxidación-Reducción , Rotenona/farmacología , Sensibilidad y Especificidad , Especificidad por Sustrato , Ubiquinona/análogos & derivados
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