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1.
Knee Surg Sports Traumatol Arthrosc ; 29(10): 3254-3261, 2021 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-32607816

RESUMEN

PURPOSE: The purpose of the present study was to compare total (TKA) and unicondylar (UKA) knee arthroplasty for spontaneous osteonecrosis of the knee (SONK), and to investigate potential correlations to radiographic parameters. METHODS: All consecutive patients with a magnetic resonance imaging (MRI) proven SONK treated with either TKA or UKA between 2002 and 2018 were analysed. The primary outcomes were postoperative complications and failure rates. Functional assessment included Knee Society Score (KSS), WOMAC Score, and range of motion. A novel three-dimensional measurement method was established to determine the size of the osteonecrotic lesion. All outcome parameters were correlated to the size of the necrotic lesion using Spearman's rank correlation. RESULTS: The two treatment groups (34 TKAs, 37 UKAs) did not differ regarding age, body mass index, and ratio of the volume of the necrotic lesion to the volume of the femoral condyle (n.s.). At a mean follow-up of 6.6 years, patients with UKA had better functional outcomes compared to patients with a TKA (WOMAC Score 1.0 vs. 1.6, p = 0.04; KSS pain 86 vs. 83, n.s), with a similar complication rate. No correlation was found between necrotic lesion size and failure rate (n.s.). CONCLUSION: UKA is a valuable treatment option for SONK leading to good functional results and a low failure rate. In case of a surgeon's concern regarding implant anchorage, TKA represents an equivalent solution. The MR-tomographic size of the osteonecrotic lesions seems to have no influence on the results. LEVEL OF EVIDENCE: III.


Asunto(s)
Artroplastia de Reemplazo de Rodilla , Osteoartritis de la Rodilla , Osteonecrosis , Humanos , Articulación de la Rodilla/diagnóstico por imagen , Articulación de la Rodilla/cirugía , Osteoartritis de la Rodilla/cirugía , Osteonecrosis/cirugía , Resultado del Tratamiento
2.
Reprod Fertil Dev ; 32(2): 104-124, 2019 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-32188562

RESUMEN

Despite a long history of bovine superovulation research, significant commercial applications did not start until the early 1970s. For some 20 years thereafter, superovulation represented the primary tool for the production of cattle embryos. In the early 1990s, commercial invitro production (IVP) was initiated in cattle. Although ovum pick-up and IVP are now commercially practiced on a wide scale, superovulation and embryo recovery by flushing remain a widespread and very effective approach to the production of cattle embryos. This review covers both the history and the effects of multiple factors on superovulation in Bos taurus cattle. There are three general protocols for suitable pre-FSH programming of donors so that gonadotrophin-responsive follicles are available. Superovulation protocols vary widely based on the FSH source, the diluent used, the number and timing of FSH injections and the timing and utilisation of various prostaglandins, controlled internal progesterone releasing devices, gonadotrophin-releasing hormone, and other means of controlling follicular development and ovulation. The number of oocytes that can be stimulated to grow and ovulate within any given donor can be estimated by either ultrasound-guided sonography or by measuring concentrations of anti-Müllerian hormone in the blood. Animal-related factors that can influence the efficacy of superovulation include cattle breed, age, parity, genetics, lactational status and reproductive history. In addition, nutrition, stress, season, climate, weather and several semen factors are discussed.


Asunto(s)
Bovinos , Embrión de Mamíferos/citología , Inducción de la Ovulación/veterinaria , Superovulación/fisiología , Animales , Bovinos/embriología , Bovinos/fisiología , Desarrollo Embrionario/fisiología , Femenino , Fertilización In Vitro/veterinaria , Historia del Siglo XX , Historia del Siglo XXI , Técnicas de Maduración In Vitro de los Oocitos/métodos , Técnicas de Maduración In Vitro de los Oocitos/veterinaria , Oocitos/citología , Oocitos/fisiología , Oogénesis/fisiología , Ovulación/sangre , Ovulación/genética , Ovulación/fisiología , Inducción de la Ovulación/métodos , Embarazo , Superovulación/sangre , Superovulación/genética
3.
Spinal Cord ; 55(4): 383-389, 2017 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-27596027

RESUMEN

STUDY DESIGN: A pilot randomised controlled trial. OBJECTIVES: The aims of this study were to evaluate the effectiveness and participant satisfaction of web-based physiotherapy in people with spinal cord injury (SCI). SETTING: Community patients of a national spinal injury unit in a university teaching hospital, Scotland, UK. METHODS: Twenty-four participants were recruited and randomised to receive 8 weeks of web-based physiotherapy (intervention), twice per week, or usual care (control). Individual exercise programmes were prescribed based on participants' abilities. The intervention was delivered via a website (www.webbasedphysio.com) and monitored and progressed remotely by the physiotherapist. RESULTS: Participants logged on to the website an average of 1.4±0.8 times per week. Between-group differences, although not significant, were more pronounced for the 6-min walk test. Participants were positive about using web-based physiotherapy and stated that they would be happy to use it again and would recommend it to others. Overall, it was rated as either good or excellent. CONCLUSIONS: Web-based physiotherapy was feasible and acceptable for people with SCI. Participants achieved good compliance with the intervention and rated the programme highly and beneficial for health and well-being at various states after injury. The results of this study warrant further work with a more homogeneous sample. SPONSORSHIP: This study was funded by the Queen Elizabeth National Spinal Injuries Unit, Glasgow, UK.


Asunto(s)
Terapia por Ejercicio/métodos , Internet , Traumatismos de la Médula Espinal/rehabilitación , Telerrehabilitación/métodos , Centros Médicos Académicos , Estudios de Factibilidad , Femenino , Humanos , Entrevistas como Asunto , Masculino , Persona de Mediana Edad , Satisfacción del Paciente , Fisioterapeutas , Proyectos Piloto , Investigación Cualitativa , Escocia , Traumatismos de la Médula Espinal/psicología , Encuestas y Cuestionarios , Resultado del Tratamiento , Prueba de Paso
4.
J Dairy Sci ; 100(12): 10314-10331, 2017 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-29153167

RESUMEN

Reproductive technology revolutionized dairy production during the past century. Artificial insemination was first successfully applied to cattle in the early 1900s. The next major developments involved semen extenders, invention of the electroejaculator, progeny testing, addition of antibiotics to semen during the 1930s and 1940s, and the major discovery of sperm cryopreservation with glycerol in 1949. The 1950s and 1960s were particularly productive with the development of protocols for the superovulation of cattle with both pregnant mare serum gonadotrophin/equine chorionic gonadotrophin and FSH, the first successful bovine embryo transfer, the discovery of sperm capacitation, the birth of rabbits after in vitro fertilization, and the development of insulated liquid nitrogen tanks. Improved semen extenders and the replacement of glass ampules with plastic semen straws followed. Some of the most noteworthy developments in the 1970s included the initial successes with in vitro culture of embryos, calves born after chromosomal sexing as embryos, embryo splitting resulting in the birth of twins, and development of computer-assisted semen analysis. The 1980s brought flow cytometric separation of X- and Y-bearing sperm, in vitro fertilization leading to the birth of live calves, clones produced by nuclear transfer from embryonic cells, and ovum pick-up via ultrasound-guided follicular aspiration. The 20th century ended with the birth of calves produced from AI with sexed semen, sheep and cattle clones produced by nuclear transfer from adult somatic cell nuclei, and the birth of transgenic cloned calves. The 21st century has seen the introduction of perhaps the most powerful biotechnology since the development of artificial insemination and cryopreservation. Quick, inexpensive genomic analysis via the use of single nucleotide polymorphism genotyping chips is revolutionizing the cattle breeding industry. Now, with the introduction of genome editing technology, the changes are becoming almost too rapid to fully digest.


Asunto(s)
Cruzamiento , Industria Lechera/métodos , Técnicas Reproductivas/veterinaria , Animales , Bovinos , Femenino , Inseminación Artificial/veterinaria , Masculino , Embarazo , Semen , Ovinos
5.
Spinal Cord ; 49(3): 445-50, 2011 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-20856261

RESUMEN

STUDY DESIGN: Keeping physically active is important for people who mobilize using a wheelchair. However, current tools to measure physical activity in the wheelchair are either not validated or limited in their application. The purpose of this study was to develop and validate a monitoring system to measure wheelchair movement. METHODS: The system developed consisted of a tri-axial accelerometer placed on the wheel of a wheelchair and an analysis algorithm to interpret the acceleration signals. The two accelerometer outputs in the plane of the wheel were used to calculate the angle of the wheel. From this, outcome measures of wheel revolutions, absolute angle and duration of movement were derived and the direction of movement (forwards or backwards) could be distinguished. Concurrent validity was assessed in comparison with video analysis in 14 people with spinal cord injury using their wheelchair on an indoor track and outdoor wheelchair skills course. Validity was assessed using intraclass correlation coefficients (ICC(2,1)) and Bland-Altman plots. RESULTS: The monitoring system demonstrated excellent validity for wheel revolutions, absolute angle and duration of movement (ICC(2,1)>0.999, 0.999, 0.981, respectively) in both manual and powered wheelchairs, when the wheelchair was propelled forwards and backwards, and for movements of various durations. CONCLUSION: This study has found this monitoring system to be an accurate and objective tool for measuring detailed information on wheelchair movement and maneuvering regardless of the propulsion technique, direction and speed.


Asunto(s)
Diseño de Equipo/instrumentación , Monitoreo Fisiológico/instrumentación , Paraplejía/rehabilitación , Esfuerzo Físico/fisiología , Aptitud Física/fisiología , Silla de Ruedas/estadística & datos numéricos , Adulto , Diseño de Equipo/métodos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Monitoreo Fisiológico/métodos , Adulto Joven
6.
Reprod Fertil Dev ; 22(1): 119-25, 2010.
Artículo en Inglés | MEDLINE | ID: mdl-20003853

RESUMEN

Media designed for the recovery, holding and cryopreservation of bovine and equine embryos are available from several commercial sources. In years past, some of these media contained bovine serum, although inclusion of serum in embryo transfer media is now largely discontinued due to issues relating to storage and biosecurity. Currently, bovine serum albumin (BSA) is included in most commercially manufactured media intended for use in embryo transfer (ET). Although BSA poses less risk than serum for the transmission of infectious disease, its inclusion still entails risk of viral contamination. The present review briefly describes the various components of ET media and the development of efficacious ET media containing no products of animal origin. An evaluation of the efficacy of recovery, holding, slow controlled freezing and vitrification media in both research and commercial ET embryo transfer settings is also presented.


Asunto(s)
Bovinos/embriología , Criopreservación/veterinaria , Medios de Cultivo , Animales , Criopreservación/métodos , Medios de Cultivo/farmacología , Transferencia de Embrión/métodos , Transferencia de Embrión/veterinaria , Embrión de Mamíferos/efectos de los fármacos , Albúmina Sérica Bovina/farmacología
7.
Theriogenology ; 71(4): 690-7, 2009 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-18995895

RESUMEN

To investigate why the preferred means to produce bovine embryos in Brazil has changed from in vivo to in vitro, we compared these two approaches in the same Nelore cows (n=30) and assessed total embryo production and pregnancy rates. Without a specific schedule, all cows were subjected to ultrasound-guided ovum pick up (OPU)/in vitro production (IVP) and MOET, with intervals ranging from 15 to 45 d between procedures, respectively. To produce in vivo embryos, cows were superovulated and embryos were recovered nonsurgically from 1 to 3 times (1.4+/-0.6), whereas OPU/IVP was repeated from 1 to 5 times (3.2+/-1.2) in each donor cow during a 12-mo interval. Embryos obtained from both methods were transferred to crossbred heifers. On average, 25.6+/-15.3 immature oocytes were collected per OPU attempt. The average number of embryos produced by OPU/IVP (9.4+/-5.3) was higher (P<0.05) than the MOET method (6.7+/-3.7). However, pregnancy rates were lower (P<0.05) following transfer of IVP (33.5%) versus in vivo-derived embryos (41.5%) embryos. Embryonic losses between Days 30 and 60 and fetal sex ratio were similar (P>0.05) between in vivo and in vitro-derived embryos. We concluded that in Nelore cows, with an interval of 15 d between OPU procedures, it was possible to produce more embryos and pregnancies compared to conventional MOET.


Asunto(s)
Transferencia de Embrión/veterinaria , Fertilización In Vitro/veterinaria , Índice de Embarazo , Animales , Bovinos , Femenino , Embarazo , Superovulación
8.
Med Trop (Mars) ; 68(2): 182-8, 2008 Apr.
Artículo en Francés | MEDLINE | ID: mdl-18630054

RESUMEN

This article presents the results of an expert consultation meeting aimed at evaluating the safety and public health implications of administering supplemental iron to infants and young children in malaria-endemic areas. Participants at this meeting that took place in Lyon, France on June 12-14, 2006 reached consensus on several important issues related to iron supplementation for infants and young children in malaria-endemic areas. The conclusions in this report apply specifically to regions where malaria is endemic.


Asunto(s)
Anemia Ferropénica/prevención & control , Suplementos Dietéticos , Enfermedades Endémicas , Hierro/uso terapéutico , Malaria/prevención & control , Anemia Ferropénica/epidemiología , Niño , Humanos , Lactante , Malaria/epidemiología , Organización Mundial de la Salud
9.
Theriogenology ; 67(7): 1233-8, 2007 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-17331571

RESUMEN

Many environmental conditions for in vitro embryo production (IVP) systems for cattle have been relatively standardised, e.g. media composition, temperature, pH, water quality, and atmospheric composition. However, little attention has been paid to the quality of ambient laboratory air and the gas environment in incubators. Although a few studies have examined the effects of chemical air contamination on IVP of human embryos, there are no published accounts for domestic animal embryos. Therefore, this study investigated the effects of an intra-incubator carbon-activated air filtration system (CODA) during in vitro culture (IVC) on embryonic development and subsequent pregnancy rate of bovine embryos. Immature cumulus-oocyte-complexes (COCs) were obtained twice-weekly by ultrasonic-guided transvaginal oocyte aspiration. The COCs were matured in TCM199/FCS/LH/FSH, fertilized with frozen-thawed Percoll-separated semen, and subsequently cultured for 7 day in SOFaaBSA. Day 7 embryos were transferred either fresh or frozen/thawed. The experimental design was a 2 x 2 factorial; presumptive zygotes were placed either in a conventional CO(2)-O(2)-N(2) incubator (Control group) or in an identical CO(2)-O(2)-N(2) incubator with a CODA intra-incubator air purification unit (CODA group) for IVC. The embryo production rate at Day 7 was not affected by the CODA air purification unit (23.4 and 24.7% morulae and blastocysts per oocyte for control and CODA, respectively) nor was there any significant effect on embryo stage or quality. However, the pregnancy rate was improved (P=0.043) for both fresh (46.3% versus 41.0%) and frozen/thawed embryos (40.8% versus 35.6%). In conclusion, atmospheric purification by the CODA intra-incubator air purification unit significantly increased pregnancy rate following transfer of in vitro-produced bovine embryos.


Asunto(s)
Bovinos/fisiología , Transferencia de Embrión/veterinaria , Fertilización In Vitro/veterinaria , Incubadoras , Contaminación del Aire Interior , Animales , Carbono/química , Estudios Cruzados , Femenino , Fertilización In Vitro/métodos , Filtración/métodos , Masculino , Embarazo , Distribución Aleatoria
10.
Theriogenology ; 65(1): 4-16, 2006 Jan 07.
Artículo en Inglés | MEDLINE | ID: mdl-16289326

RESUMEN

Embryo transfer practice and results were examined over a 20-year period in Holstein cows and heifers within four commercial embryo transfer programs located in different areas of North America. Mean embryo production per collection decreased (P < 0.05) in one program over time, but not in the other three. Changes in the type of cows entering embryo transfer programs, the number of times they were superstimulated and changes in the brands of gonadotropins used for superstimulation all complicated the analysis of embryo production over time. Data reveal higher pregnancy rates (P < 0.001) following transfer of embryos into Holstein heifers than into lactating dairy cows. It is not clear whether pregnancy rates have decreased over time as a result of the change from surgical to non-surgical embryo transfer. In the two programs in which pregnancy rates were analyzed, there was a decrease (P < 0.001) when non-surgical transfers were adopted in one program, while no change occurred in the other. One of the biggest changes in all programs was that more than 50% of embryos recovered from donors are now frozen after collection, whereas the majority were transferred fresh 20 years ago.


Asunto(s)
Bovinos/fisiología , Industria Lechera/tendencias , Transferencia de Embrión/veterinaria , Lactancia/fisiología , Superovulación , Animales , Cruzamiento/métodos , Bovinos/embriología , Transferencia de Embrión/tendencias , Femenino , Gonadotropinas/farmacología , Embarazo , Índice de Embarazo , Estudios Retrospectivos , Recolección de Tejidos y Órganos/veterinaria
11.
Theriogenology ; 65(1): 65-76, 2006 Jan 07.
Artículo en Inglés | MEDLINE | ID: mdl-16289325

RESUMEN

Bovine embryo transfer is a well-established commercial industry that is often associated with veterinary practices. Practitioners offering embryo transfer services may possess a very high standard of technical expertise; however, success in the production of embryos and the impregnation of recipients cannot be achieved unless the cattle are healthy and maintained in a well-managed cattle operation. In addition to appropriate gonadotropin treatments of donor cattle, the use of highly fertile semen, known to have been properly stored and handled is required for success. Recipient cattle must be managed with the same attention to detail as donors. Traditionally, PGF has been used for the synchronization of recipients. However, PGF is limited in its effectiveness early and late in the bovine estrus cycle. Recipient estrus synchronization with progesterone releasing intravaginal inserts has been successful and high pregnancy rates have resulted following embryo transfer.


Asunto(s)
Bovinos/fisiología , Industria Lechera , Transferencia de Embrión/veterinaria , Superovulación/fisiología , Animales , Industria Lechera/normas , Estro/fisiología , Sincronización del Estro/efectos de los fármacos , Femenino , Inseminación Artificial/veterinaria , Masculino , Embarazo , Índice de Embarazo , Progesterona/farmacología , Prostaglandinas F/farmacología , Resultado del Tratamiento
12.
Cancer Res ; 52(2): 267-74, 1992 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-1728400

RESUMEN

The development of molecular dosimetry methods will simplify the identification of people at high risk for cancer. A combined monoclonal antibody immunoaffinity chromatography/high performance liquid chromatography method has been devised to isolate and quantify aflatoxin-DNA adducts and other metabolites in rat urine samples. We report the production of 11 different monoclonal antibodies recognizing aflatoxin B1, aflatoxin Q1, aflatoxin G1, aflatoxicol, and aflatoxin M1 and the application of these antibodies to a multiple monoclonal antibody affinity chromatography technique. Using the multiple monoclonal antibody affinity column with rat urines obtained from dosed animals, between 90 and 95% of total aflatoxin metabolites can be bound to the column and isolated. Analytical immunoaffinity chromatography/high performance liquid chromatography analysis of these isolated aflatoxins reveals that more than 55% of the aflatoxins in rat urine are aflatoxin-dihydrodiol, aflatoxin-N7-guanine, aflatoxin Q1, aflatoxin M1, aflatoxin P1, and aflatoxin B1, accounting for 1.5, 9.6, 1.8, 34.5, 8.0, and 1.0% of the total aflatoxins, respectively. Further, a perchloric acid digestion of the aflatoxin-N7-guanine peak was used to confirm its identity by its conversion to guanine. The measurement of aflatoxin-N7-guanine excretion in rat urine was examined to assess its utility as a marker of DNA adduct formation in the liver, and a dose-dependent excretion in urine was found with a correlation coefficient of 0.99. A comparison of the dose-dependent residual levels of aflatoxin binding to liver DNA with the amount of aflatoxin-N7-guanine excreted in urine showed a correlation coefficient of 0.98. Besides the nucleic acid adduct excretion data, aflatoxin M1 and aflatoxin P1 were evaluated as molecular dosimeters in the urine. Aflatoxin M1 was found to be an excellent marker, whereas no linear relationship between dose and aflatoxin P1 excretion in urine was found.


Asunto(s)
Aflatoxina B1/análogos & derivados , Aflatoxinas/inmunología , Guanina/análogos & derivados , Aflatoxina B1/inmunología , Aflatoxina B1/orina , Aflatoxinas/análisis , Aflatoxinas/metabolismo , Animales , Anticuerpos Monoclonales , Afinidad de Anticuerpos , Cromatografía de Afinidad , Cromatografía Líquida de Alta Presión , Guanina/inmunología , Guanina/orina , Ratas , Análisis de Regresión
13.
Rev Sci Tech ; 24(1): 393-403, 2005 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-16110904

RESUMEN

Over a period of approximately thirty years, commercial bovine embryo transfer has become a large international business. The technology is well established, and more than 500,000 embryos are produced annually from superovulated cows world wide. Since bovine embryos with intact zonae pellucidae can be specified pathogen-free through washing procedures, thousands of frozen embryos are routinely sold and transferred between countries. Throughout the world, approximately 15% of bovine embryos are produced by in vitro technology. Polymerase chain reaction technology is currently being used for sexing embryos on a small scale, and it is likely that this technology will be used for 'embryo diagnostics' in the future. Semen sexing is an established technology and is likely to be used on a small scale in the near future, especially in in vitro embryo production systems. The cloning of adult cattle through nuclear transfer and the production of cloned, transgenic cattle has been technically achieved. However, this is an expensive and inefficient technology, which is being used primarily by the pharmaceutical industry. Benefits in agriculture are likely to be minimal in the near future.


Asunto(s)
Cruzamiento/métodos , Bovinos/genética , Técnicas Reproductivas Asistidas/veterinaria , Análisis para Determinación del Sexo/veterinaria , Animales , Bovinos/embriología , Clonación de Organismos/veterinaria , Comercio , Transferencia de Embrión/veterinaria , Femenino , Masculino , Técnicas Reproductivas Asistidas/tendencias
14.
Pharmacogenetics ; 3(6): 275-80, 1993 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-7908586

RESUMEN

The objective of this study was to determine the CYP2D6 genotype of a black Zimbabwean population. Genotyping was carried out using Eco RI and Xba I RFLP, and allele-specific PCR amplification. Of 114 Zimbabwean samples analysed, no individual homozygous for any of the defect allelic forms CYP2D6A, CYP2D6B or CYP2D6D or combinations thereof was found. The allele frequencies of the three defect genes were 0, 1.8 and 3.9%, respectively. No subject carrying the Xba I 44 kb haplotype, indicative for poor metabolizers among Caucasians, was identified, whereas five individuals being heterozygous with a 29/42 kb haplotype were seen. Three out of the four CYP2D6B alleles found were associated with the 29/42 kb haplotype. Our findings are in agreement with the 0-2% prevalence of poor metabolizers (PMs) in the black populations previously phenotyped. The very low frequency of the CYP2D6B allele in the Zimbabwean population is different from very recent data from black Americans (allele frequency = 8.5%) and might indicate the Caucasian ancestry of this allele. Taken together, our data indicate important interethnic differences in the CYP2D locus between Caucasian, Asian and different black populations.


Asunto(s)
Población Negra/genética , Sistema Enzimático del Citocromo P-450/genética , Oxigenasas de Función Mixta/genética , Polimorfismo Genético , Secuencia de Bases , Citocromo P-450 CYP2D6 , Cartilla de ADN , Genotipo , Humanos , Datos de Secuencia Molecular , Reacción en Cadena de la Polimerasa , Polimorfismo de Longitud del Fragmento de Restricción , Zimbabwe
15.
Clin Pharmacol Ther ; 57(1): 25-31, 1995 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-7828378

RESUMEN

Caffeine is increasingly used as a biochemical probe for liver function, in cancer epidemiology, and in pharmacogenetics, with its recognized ability to assess the activities of CYP1A2, xanthine oxidase, and N-acetyltransferase-2. The activity of these hepatic enzymes was tested in 45 Shona children from a rural area of Zimbabwe with use of caffeine as a probe. Many of these rural black children had lower indexes of CYP1A2 activity than otherwise on our extensive records; the average value (3.78 +/- 2.9) was significantly (p < 0.001) lower than that of healthy white urban children from Zimbabwe (8.86 +/- 3.36) or from Canada (7.92 +/- 1.88), or that of healthy Canadian adults (5.96 +/- 2.4). A higher CYP1A2 activity in children than in adults is usual. The low CYP1A2 activity of the children from rural Zimbabwe calls for medical studies and suggests a widespread and perhaps serious impairment of certain liver functions. Causes could be parasitic infections with Schistosoma mansoni, causing schistosomiasis, which are endemic, in addition to generally poor nutrition and frequent iodine deficiency. By contrast, the xanthine oxidase activity in rural Shona children was slightly higher than that reported for a healthy Canadian adult population. The N-acetyltransferase activities were comparable in both the rural and urban children and were also similar to those reported in a population study of healthy adult Canadians.


Asunto(s)
Acetiltransferasas/metabolismo , Sistema Enzimático del Citocromo P-450/metabolismo , Hígado/enzimología , Oxidorreductasas/metabolismo , Xantina Oxidasa/metabolismo , Adolescente , Adulto , Cafeína/metabolismo , Cafeína/orina , Canadá/etnología , Niño , Cromatografía Líquida de Alta Presión , Citocromo P-450 CYP1A2 , Femenino , Humanos , Masculino , Población Rural , Población Urbana , Zimbabwe/etnología
16.
Clin Pharmacol Ther ; 57(6): 656-61, 1995 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-7781265

RESUMEN

The S-mephenytoin hydroxylase has recently been identified as cytochrome P450 2C19 (CYP2C19). This enzyme metabolizes mephenytoin, diazepam, omeprazole, and citalopram and has been shown to be polymorphically distributed. One clinical implication of CYP2C19-dependent drug metabolism for persons who reside in tropical regions is in the use of the antimalarial drug chloroguanide hydrochloride, which is apparently biotransformed to its active metabolite by this isozyme. In this investigation we studied mephenytoin metabolism in 103 black Zimbabwean Shona subjects. Four were identified as poor metabolizers (4%). This prevalence is comparable to that in white subjects (2% to 5%) but lower than the 15% to 20% incidence of poor metabolizers among Oriental subjects. Of the subjects phenotyped, 84 were genotyped for the G-->A mutation in exon 5 of CYP2C19, which creates a cryptic splice site, causing the production of a nonfunctional protein. Three of the four poor metabolizers were homozygous for this mutation, whereas the fourth one was heterozygous. The G-->A mutation has been shown to predict the incidence more than 60% of poor metabolizers among white subjects and Japanese subjects, and in the current investigation we also obtained a similar relationship in the black population.


Asunto(s)
Hidrocarburo de Aril Hidroxilasas , Sistema Enzimático del Citocromo P-450/genética , Oxigenasas de Función Mixta/genética , Adulto , Secuencia de Bases , Citocromo P-450 CYP2C19 , Etnicidad/genética , Genotipo , Humanos , Datos de Secuencia Molecular , Fenotipo , Reacción en Cadena de la Polimerasa , Zimbabwe
17.
Free Radic Biol Med ; 22(1-2): 321-7, 1997.
Artículo en Inglés | MEDLINE | ID: mdl-8958157

RESUMEN

The effect of chloroquine (CHQ) administration on antioxidant enzymes in rat liver and kidney was studied. Male Sprague-Dawley rats were administered 20 mg/kg CHQ once a week for 4 weeks (chronic treatment) or a single dose at 10 or 20 mg/kg (acute treatment). Antioxidant enzyme activities were determined in cytosolic fractions of liver and kidney, whereas reduced glutathione (GSH) and malondialdehyde (MDA) were determined in tissue samples. Results indicate minimal effects of acute CHQ treatment, whereas chronic treatment with CHQ differentially affected antioxidant enzymes in the two organs. Superoxide dismutase activity was increased nearly twofold, while activities of selenium glutathione peroxidase (GPX), catalase, and NAD (P) H: quinone oxidoreductase were decreased in livers of CHQ-treated rats compared to controls. No significant effects of CHQ on glutathione reductase, GSH, and MDA levels were seen in the liver. Fewer effects of CHQ were observed in the kidney where a decrease in GPX activity and an increase in MDA levels was seen. Lowering of antioxidant enzymes activities in the liver by CHQ could render the organ more susceptible to subsequent oxidative stress; while increased MDA production after CHQ treatment in the kidney indicate that the organ is being subjected to oxidative stress. This could have implications for prolonged chloroquine intake.


Asunto(s)
Antimaláricos/farmacología , Antioxidantes/metabolismo , Cloroquina/farmacología , Riñón/efectos de los fármacos , Hígado/efectos de los fármacos , Animales , Catalasa/metabolismo , Evaluación Preclínica de Medicamentos , Glutatión/metabolismo , Glutatión Peroxidasa/metabolismo , Riñón/enzimología , Hígado/enzimología , Masculino , Malondialdehído/metabolismo , NAD(P)H Deshidrogenasa (Quinona)/metabolismo , Ratas , Ratas Sprague-Dawley , Superóxido Dismutasa/metabolismo
18.
AIDS Res Hum Retroviruses ; 5(5): 507-16, 1989 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-2590554

RESUMEN

We constructed a human immunodeficiency virus (HIV) trans-activator cDNA (tat) encoding the N-terminal 76 amino acids of the viral trans-activator followed by two additional amino acids (val and pro). This cDNA encoded a functional trans-activator (TAT) as shown by cotransfection into murine cells with a HIV promoter-chloramphenicol acetyltransferase DNA construct. The tat cDNA was cloned into an avian retroviral expression vector, a modified spleen necrosis virus (SNV), and high-titer infectious stocks of recombinant virus (SNV-tat) were recovered from dog cells. Hybridization analyses indicated that SNV-tat was stably propagated in these cells for months. We also prepared recombinant cells that stably carry reporter genes, either a human gene encoding a soluble CD4 receptor (sCD4) or the human preprorenin gene, under the transcriptional control of the HIV promoter. Medium obtained from these cell cultures after infection with control viruses or an SNV carrying an antisense tat contained only low background levels of sCD4 or prorenin (HRN) as determined by specific immunoassays (1-10 ng protein per 10(6) cells per ml medium). In contrast, cells infected with SNV carrying tat in the transcriptional sense orientation secreted 75 +/- 7 ng sCD4 and 73 +/- 4 ng HRN per 10(6) cells per ml medium. Moreover, these proteins were constitutively secreted at these levels during months of subculturing. The data indicate that sCD4 and HRN are secreted from these cells because of a TAT-mediated trans-activation of the HIV reporter gene DNA and/or RNA. This combination of recombinant cells, SNV-tat, and specific immunoassays provide a rapid, quantitative, and safe bioassay to seek inhibitors of TAT.


Asunto(s)
VIH/genética , Transactivadores/biosíntesis , Transfección , Animales , Antígenos CD4/genética , Células Cultivadas , Clonación Molecular , ADN Viral/biosíntesis , ADN Viral/genética , Perros , Inmunoensayo , Regiones Promotoras Genéticas
19.
Biochem Pharmacol ; 48(9): 1779-83, 1994 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-7980647

RESUMEN

The metabolism of praziquantel (PZQ) was studied in microsomes isolated from livers of differently pretreated rats and in the presence of various inhibitors of cytochrome P450 (P450) isoforms. Microsomes from phenobarbitone (PB)-pretreated rats metabolised PZQ to its major metabolite 4OH-praziquantel (4OH-PZQ) at a greater rate than those from 20-methylcholanthrene (MC) and saline (SA) pretreated rats. The Vmax for the PB microsomes was 600 nmol 4OH-PZQ formed/mg/min x 10(-3) compared to 91.4 nmol/mg/min x 10(-3) for MC and 238 nmol/mg/min x 10(-3) for SA microsomes. These results indicate that PZQ is metabolised by PB-inducible isoforms of P450. Inhibitor studies were conducted with microsomes from SA-pretreated animals. In these studies, caffeine, disulfuram, and tolbutamide were poor inhibitors of the metabolism of PZQ to 4OH-PZQ, with I50 values not determinable. Quinidine and quinine inhibited the hydroxylation of PZQ but with high Ki values. 17 alpha-Ethynylestradiol, cimetidine and diphenylhydramine were effective inhibitors of the formation of 4OH-PZQ, with 17 alpha-ethynylestradiol being the most potent with a Ki of 0.5 +/- 0.05 microM. From the known specificities of these P450 inhibitors, it is therefore concluded that cytochromes P450 1A2, 2E1, 2C9-10, and 2D6 probably do not contribute significantly to the metabolism of PZQ to its major metabolite in rats. It is likely that cytochromes P450 2B1 and 3A, both inducible by PB, are predominantly responsible for the formation of 4OH-PZQ.


Asunto(s)
Inhibidores Enzimáticos del Citocromo P-450 , Microsomas Hepáticos/metabolismo , Praziquantel/metabolismo , Animales , Difenhidramina/farmacología , Hidroxilación/efectos de los fármacos , Cinética , Masculino , Quinidina/farmacología , Quinina/farmacología , Ratas , Ratas Sprague-Dawley
20.
Biochem Pharmacol ; 40(2): 379-82, 1990 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-1695846

RESUMEN

The covalent binding of [14C]acetylaminofluorene (AAF) to macromolecules in vivo and in vitro was measured in Schistosoma mansoni-infected and in non-infected mice. Liver microsomes from infected mice demonstrated a 42% decreased capacity to mediate covalent binding of AAF to DNA. In addition, the extent of binding of AAF to liver macromolecules in vivo was generally less in infected than non-infected mice.


Asunto(s)
2-Acetilaminofluoreno/metabolismo , Hígado/metabolismo , Esquistosomiasis/metabolismo , Animales , ADN/metabolismo , Técnicas In Vitro , Ratones , Ratones Endogámicos BALB C , Unión Proteica , ARN/metabolismo
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