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1.
Bioprocess Biosyst Eng ; 46(12): 1817-1824, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37878183

RESUMEN

The aim of this work was to synthesize 0.02 and 0.06 Mg-doped ZnO nanoparticles (NPs) using the aqueous extract of Plectranthus barbatus leaf. The structural integrity of the hexagonal phase was emphasized by X-ray diffraction analysis. The average crystallite size (D) of 0.02 and 0.06 Mg-doped ZnO NPs was found to be 23.83 and 26.95 nm, respectively. The scanning electron microscope images revealed a surface morphology of irregular nano-shapes of about 83 nm diameter with an elongated one-dimensional structure. The hemolysis activity demonstrated the safe nature of the synthesized materials at low doses. Antibacterial activity against S. aureus and E. coli, which assessed using the disc diffusion method, indicated that the prepared NPs could inhibit S. aureus but not E. coli. These findings suggest that the synthesized NPs could be explored for potential applications in biotechnology and medicine.


Asunto(s)
Nanopartículas del Metal , Óxido de Zinc , Humanos , Staphylococcus aureus , Óxido de Zinc/farmacología , Óxido de Zinc/química , Escherichia coli , Hemólisis , Extractos Vegetales/química , Pruebas de Sensibilidad Microbiana , Antibacterianos/farmacología , Antibacterianos/química , Difracción de Rayos X , Nanopartículas del Metal/química
2.
J Eur Acad Dermatol Venereol ; 35(2): 360-367, 2021 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-32639047

RESUMEN

Current clinical recommendations suggest that continuous treatment of moderate-to-severe psoriasis with biologic agents is more effective than intermittent treatment in terms of achieving remission and maintaining it. Intermittent treatment, however, may provide an alternative approach in patients unwilling or unable to maintain a continuous regimen, such as those who would prefer a 'treatment vacation' after achieving long-term remission, those who require treatment cessation owing to adverse events, and where insurance arrangements do not provide sufficient cover for continuous treatment. We conducted a literature search of PubMed to identify publications reporting data on the efficacy and safety of intermittent treatment with biologic agents in adults with psoriasis, specifically the use of inhibitors of tumour necrosis factor (adalimumab, certolizumab pegol, etanercept and infliximab), interleukin (IL)-12/IL-23 (ustekinumab), IL-23 (guselkumab) and IL-17 (brodalumab, ixekizumab and secukinumab). From our search, we identified 18 relevant publications reporting the intermittent use of the biologic therapies of interest: five described etanercept, three described adalimumab, two each described infliximab, ixekizumab or ustekinumab, and one each described certolizumab pegol, guselkumab, brodalumab and secukinumab. In general, there were large proportions of patients (≥60%) who were able to re-establish disease control (as defined by each study) following re-treatment, and the safety profiles of the various agents during re-treatment were as anticipated from their profiles observed during continuous dosing. The exception to these general findings was infliximab, which showed the lowest rate of efficacy-endpoint achievement (25% and 38% in two dosing groups evaluated) as well as a higher incidence of adverse infusion reactions compared with continuous dosing. In conclusion, the use of biologic agents in psoriasis is changing and current clinical data suggest that intermittent treatment may provide an effective and well-tolerated option for certain patients.


Asunto(s)
Factores Biológicos , Psoriasis , Adalimumab , Adulto , Anticuerpos Monoclonales/efectos adversos , Factores Biológicos/uso terapéutico , Humanos , Psoriasis/tratamiento farmacológico , Ustekinumab
3.
J Eur Acad Dermatol Venereol ; 33(6): 1006-1019, 2019 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-30968980

RESUMEN

BACKGROUND: Anogenital warts (AGW) can cause economic burden on healthcare systems and are associated with emotional, psychological and physical issues. OBJECTIVE: To provide guidance to physicians on the diagnosis and management of AGW. METHODS: Fourteen global experts on AGW developed guidance on the diagnosis and management of AGW in an effort to unify international recommendations. Guidance was developed based on published international and national AGW guidelines and an evaluation of relevant literature published up to August 2016. Authors provided expert opinion based on their clinical experiences. RESULTS: A checklist for a patient's initial consultation is provided to help physicians when diagnosing AGW to get the relevant information from the patient in order to manage and treat the AGW effectively. A number of frequently asked questions are also provided to aid physicians when communicating with patients about AGW. Treatment of AGW should be individualized and selected based on the number, size, morphology, location, and keratinization of warts, and whether they are new or recurrent. Different techniques can be used to treat AGW including ablation, immunotherapy and other topical therapies. Combinations of these techniques are thought to be more effective at reducing AGW recurrence than monotherapy. A simplified algorithm was created suggesting patients with 1-5 warts should be treated with ablation followed by immunotherapy. Patients with >5 warts should use immunotherapy for 2 months followed by ablation and a second 2-month course of immunotherapy. Guidance for daily practice situations and the subsequent action that can be taken, as well as an algorithm for treatment of large warts, were also created. CONCLUSION: The guidance provided will help physicians with the diagnosis and management of AGW in order to improve the health and quality of life of patients with AGW.


Asunto(s)
Enfermedades del Ano , Condiloma Acuminado , Enfermedades de los Genitales Masculinos , Enfermedades del Ano/diagnóstico , Enfermedades del Ano/terapia , Condiloma Acuminado/diagnóstico , Condiloma Acuminado/terapia , Femenino , Enfermedades de los Genitales Femeninos/diagnóstico , Enfermedades de los Genitales Femeninos/terapia , Enfermedades de los Genitales Masculinos/diagnóstico , Enfermedades de los Genitales Masculinos/terapia , Humanos , Masculino , Infecciones por Papillomavirus/diagnóstico , Infecciones por Papillomavirus/terapia , Guías de Práctica Clínica como Asunto
4.
J Eur Acad Dermatol Venereol ; 31 Suppl 7: 4-35, 2017 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-28990222

RESUMEN

Acne has been estimated to affect the majority of people at some point in their life and is common in Middle Eastern countries. While acne is frequently perceived to be a self-limited disease of adolescence, there is an increasing population of adults with acne. Information about the management of acne in the Middle East is somewhat sparse; however, several studies have recently been conducted and will be discussed in this supplement.


Asunto(s)
Acné Vulgar/terapia , Acné Vulgar/diagnóstico , Acné Vulgar/epidemiología , Acné Vulgar/fisiopatología , Adolescente , Adulto , Diagnóstico Diferencial , Femenino , Humanos , Masculino , Medio Oriente/epidemiología , Educación del Paciente como Asunto , Factores de Riesgo , Adulto Joven
5.
Georgian Med News ; (214): 48-54, 2013 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-23388535

RESUMEN

Failure to thrive (FTT) is a common issue in practice. The definition of FTT differs among authors and among practices. FTT is usually categorized into organic vs. non-organic. This paper is a review of different articles that contains the terms "failure to thrive". A Review of articles was performed using Pub med and different journal websites. This article discusses the different definitions of FTT, the prevalence , the assessments , together with information on management. The initial step in managing an infant or child with FTT is to identify the cause whether it is "organic" or " non organic". An appropriate encounter would be by having a system-based approach. In addition to the pediatrician's skills in medical diagnosis and management, there is a need for evaluation of the child's temperament and development, oromotor functioning, nutritional needs and deficits, and family and social support systems.


Asunto(s)
Insuficiencia de Crecimiento/diagnóstico , Insuficiencia de Crecimiento/etiología , Desarrollo Infantil , Insuficiencia de Crecimiento/epidemiología , Insuficiencia de Crecimiento/terapia , Humanos , Lactante , Fenómenos Fisiológicos Nutricionales del Lactante
6.
Sci Rep ; 13(1): 12927, 2023 Aug 09.
Artículo en Inglés | MEDLINE | ID: mdl-37558688

RESUMEN

In this paper, tri-phase Fe2O3-MgO-CuO nanocomposites (NCs) and pure CuO, Fe2O3 and MgO nanoparticles (NPs) were prepared using sol-gel technique. The physical properties of the prepared products were examined using SEM, XRD, and UV-visible. The XRD data indicated the formation of pure CuO, Fe2O3 and MgO NPs, as well as nanocomposite formation with Fe2O3 (cubic), MgO (cubic), and CuO (monoclinic). The crystallite size of all the prepared samples was calculated via Scherrer's formula. The energy bandgap of CuO, Fe2O3 and MgO and Fe2O3-MgO-CuO NCs were computed from UV-visible spectroscopy as following 2.13, 2.29, 5.43 and 2.96 eV, respectively. The results showed that Fe2O3-MgO-CuO NCs is an alternative material for a wide range of applications as optoelectronics devices due to their outstanding properties.

7.
Bioinorg Chem Appl ; 2023: 4166128, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37780971

RESUMEN

Nanomaterials have unique physicochemical properties compared to their bulk counterparts. Besides, biologically synthesized nanoparticles (NPs) have proven superior to other methods. This work aimed to biosynthesize zinc oxide (ZnO) NPs using an aqueous extract of Lepidium sativum seed. The obtained ZnO NPs were characterized by X-ray diffraction, scanning electron microscopy, Fourier transform infrared, and ultraviolet-visible spectroscopy. The in vitro antibacterial activity of ZnO NPs against Gram-positive (S. aureus) and Gram-negative (E. coli) bacteria was assessed using the disk diffusion technique. The hemolytic impact was quantified spectrophotometrically. The results indicated a 24.2 nm crystallite size, a hexagonal structure phase, and a 3.48 eV optical bandgap. Antibacterial studies revealed a dose-dependent response with comparable activity to the standard drug (gentamicin) and higher activity against S. aureus than E. coli, e.g., the zone of inhibition at 120 mg/mL was 23 ± 1.25 and 16 ± 1.00 mm, respectively. The hemolysis assay showed no potential harm due to ZnO NPs toward red blood cells if utilized in low doses. As a result, it could be concluded that the reported biogenic method for synthesizing ZnO NPs is promising, resulting in hemocompatible NPs and comparable bactericidal agents.

8.
Andrologia ; 44 Suppl 1: 848-50, 2012 May.
Artículo en Inglés | MEDLINE | ID: mdl-22191729

RESUMEN

The aim was to determine the prevalence of compound genetic abnormalities in patients who are carriers of cystic fibrosis transmembrane regulator (CFTR) gene polymorphism and to compare our results with similar patients reported in the literature. One hundred and nine patients were identified to be carriers of CFTR gene polymorphism. Additional genetic testing for karyotype abnormalities or Y chromosome microdeletions (YMD) was performed. Three patients (2.75%) of 109 were identified to have compound genetic abnormalities. One patient had 5T/5T while the other had 6T/6T and the third had 9T/9T. The three patients had deletions of azoospermia factor regions (AZFa+b or AZFa+b+c). There were no karyotype abnormalities identified in our database. In the literature, four patients with compound CFTR mutations and YMD were identified, in three patients had karyotype abnormalities. In conclusion, compound genetic abnormalities in CFTR mutation patients can be a contributing factor when abnormal spermatogenesis is encountered.


Asunto(s)
Azoospermia/genética , Regulador de Conductancia de Transmembrana de Fibrosis Quística/genética , Infertilidad Masculina/genética , Polimorfismo Genético , Adulto , Deleción Cromosómica , Cromosomas Humanos Y , Humanos , Masculino
9.
Radiat Prot Dosimetry ; 194(2-3): 144-152, 2021 Jul 14.
Artículo en Inglés | MEDLINE | ID: mdl-34164691

RESUMEN

The outdoor gamma radiation dose rates due to natural radioactivity and due to the artificial radionuclides released from the Chernobyl and Fukushima accidents and Algeciras incident were assessed in the Algiers province (capital of Algeria). Furthermore, the dose rates induced by the cosmic rays were analytically calculated in the province concerned. The recorded dose rates due to terrestrial outdoor gamma radiation were found to range from 14.3 ± 0.7 to 114.3 ± 5.7 nGy h -1, those due to cosmic rays ranged from 32.021 ± 0.013 to 34.029 ± 0.367 nGy h -1, while the contribution of the dose rate due to external exposure induced by 137Cs deposits, from major accidents, was estimated to be less than 0.3 nGy h-1. The spatial distributions of terrestrial and cosmic rays dose rates were mapped using QGIS software. The obtained radiological baseline maps can be used as reference information to assess any changes in the radiation exposure levels having an impact on the population health.


Asunto(s)
Monitoreo de Radiación , Contaminantes Radiactivos del Suelo , Argelia , Radiación de Fondo , Radioisótopos de Cesio , Rayos gamma , Dosis de Radiación , Contaminantes Radiactivos del Suelo/análisis
10.
J Dermatolog Treat ; 30(6): 578-581, 2019 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-30426810

RESUMEN

Aim: Acne vulgaris is a common inflammatory skin disease in the Middle East, similar to other regions of the world. In the Middle East, there are a relatively large proportion of patients with darker pigmentation (Fitzgerald skin types III-VI) who are prone to developing post-inflammatory hyperpigmentation (PIH) as a sequela of acne. Data are sparse on the frequency and characteristics of PIH throughout the world. What information is available indicates that pigmentation problems can be very bothersome for patients and are often quite long-lasting. Thus, it is important for clinicians to be aware of the scope of the problem of acne-associated PIH as well as potential treatment options. Methods: Prospective non-interventional study of acne patients consulting dermatologists (n = 262) in the Middle East. Results: PIH was present in 87.2% of subjects. The majority of subjects (52.6%) reported that PIH had been present for one year or longer. Of note, 69.0% of subjects reported excoriating their acne lesions, suggesting that this may be a key modifiable risk factor for clinicians to stress during patient education efforts. Conclusions: PIH was bothersome for patients, with half of subjects indicating that PIH was more bothersome than acne. In addition to our study results, we present here a brief overview of PIH and its treatment.


Asunto(s)
Acné Vulgar/patología , Hiperpigmentación/diagnóstico , Acné Vulgar/complicaciones , Adolescente , Adulto , Femenino , Humanos , Hiperpigmentación/etiología , Masculino , Medio Oriente , Estudios Prospectivos , Factores de Riesgo , Piel/patología , Encuestas y Cuestionarios , Adulto Joven
11.
Gulf J Oncolog ; 1(13): 83-6, 2013 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-23339984

RESUMEN

UNLABELLED: Adenoid cystic carcinoma of the breast is a very rare neoplasm. We report a case of adenoid cystic carcinoma of the right breast presented with painless lump in the upper outer quadrant managed with lumpectomy, axillary lymph node staging and adjuvant local external radiotherapy to the whole breast with simultaneous integrated boost to the site of primary disease using respiratory gated intensity modulated radiotherapy. The available literature is reviewed. KEYWORDS: Adenoid cystic cancer breast, mastectomy, adjuvant radiotherapy.


Asunto(s)
Mama , Carcinoma Adenoide Quístico , Neoplasias de la Mama , Humanos , Mastectomía , Mastectomía Segmentaria
12.
Int J Tuberc Lung Dis ; 17(4): 456-61, 2013 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-23485378

RESUMEN

BACKGROUND: The lack of applicable population-based methods to measure tuberculosis (TB) incidence rates directly at country level emphasises the global need to generate robust TB surveillance data to ascertain trends in disease burden and to assess the performance of TB control programmes in the context of the United Nations Millenium Development Goals and World Health Organization targets for TB control. OBJECTIVE: To estimate the incidence of TB cases (all forms) and sputum smear-positive disease, and the level of under-reporting of TB in Yemen in 2010. METHODS: Record-linkage and three-source capture-recapture analysis of data collected through active prospective longitudinal surveillance within the public and private non-National Tuberculosis Programme sector in twelve Yemeni governorates, selected by stratified cluster random sampling. RESULTS: For all TB cases, the estimated ratio of notified to incident cases and completeness of case ascertainment after record linkage, i.e., the ratio of detected to incident cases, was respectively 71% (95%CI 64-80) and 75% (95%CI 68-85). For sputum smear-positive TB cases, these ratios were respectively 67% (95%CI 58-75) and 76% (95%CI 66-84). CONCLUSION: We estimate that there were 13 082 (95%CI 11 610-14 513) TB cases in Yemen in 2010. Under-reporting of TB in Yemen is estimated at 29% (95%CI 20-36).


Asunto(s)
Países en Desarrollo , Recursos en Salud , Tuberculosis/epidemiología , Análisis por Conglomerados , Países en Desarrollo/economía , Notificación de Enfermedades , Recursos en Salud/economía , Humanos , Incidencia , Estudios Longitudinales , Registro Médico Coordinado , Mycobacterium tuberculosis/aislamiento & purificación , Estudios Prospectivos , Esputo/microbiología , Factores de Tiempo , Tuberculosis/diagnóstico , Tuberculosis/economía , Tuberculosis/microbiología , Tuberculosis Pulmonar/diagnóstico , Tuberculosis Pulmonar/epidemiología , Tuberculosis Pulmonar/microbiología , Yemen/epidemiología
14.
J Fr Ophtalmol ; 31(6 Pt 1): 597-604, 2008 Jun.
Artículo en Francés | MEDLINE | ID: mdl-18772811

RESUMEN

BACKGROUND: Alport syndrome is an inherited disease resulting in kidney failure, hearing loss, and ocular abnormalities. The purpose of this study was to describe the incidence and type of ocular abnormalities and to determine inheritance of this syndrome in our population. PATIENTS AND METHODS: A total of 32 patients, from ten different families in South Tunisia, underwent a complete ocular examination. Inheritance was determined using pedigrees and genotyping. RESULTS: The best corrected visual acuity was 7.6/10. Biomicroscopy showed polymorphous dystrophy in 3%, anterior lenticonus in 28%, lens opacities in 3%, cataract in 19%, and retinal flecks in 37%. The genetic survey found five families with X-linked Alport syndrome, four families with recessive autosomal disease, and one family with dominant autosomal disease. DISCUSSION: Ocular abnormalities have been reported in 9%-82% of Alport syndrome patients. They are rare in childhood and increase in frequency and severity with age. The types of ocular defects described mostly involve the lens, the retina and more rarely the cornea. The most common changes are anterior lenticonus and perimacular retinal flecks. In approximately 85%, Alport syndrome is X-linked. In the remaining 15%, the transmission is autosomal recessive and exceptionally autosomal dominant. CONCLUSION: Ocular examination is a precious help for Alport syndrome diagnosis. It can also determine the prognosis of nephropathy.


Asunto(s)
Oftalmopatías/etiología , Cristalino/anomalías , Nefritis Hereditaria/patología , Adolescente , Adulto , Anciano , Catarata/epidemiología , Catarata/etiología , Catarata/genética , Enfermedades de la Córnea/epidemiología , Enfermedades de la Córnea/etiología , Enfermedades de la Córnea/genética , Oftalmopatías/epidemiología , Oftalmopatías/genética , Femenino , Genes Dominantes , Genes Recesivos , Genes Ligados a X , Humanos , Enfermedades del Cristalino/epidemiología , Enfermedades del Cristalino/etiología , Enfermedades del Cristalino/genética , Masculino , Persona de Mediana Edad , Nefritis Hereditaria/epidemiología , Nefritis Hereditaria/genética , Enfermedades de la Retina/epidemiología , Enfermedades de la Retina/etiología , Enfermedades de la Retina/genética , Retinitis Pigmentosa/epidemiología , Retinitis Pigmentosa/etiología , Retinitis Pigmentosa/genética , Túnez/epidemiología , Trastornos de la Visión/epidemiología , Trastornos de la Visión/etiología , Trastornos de la Visión/genética , Agudeza Visual , Adulto Joven
15.
Mol Cell Biochem ; 300(1-2): 39-46, 2007 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-17541508

RESUMEN

In vivo biotelemetry studies have demonstrated that heart rate (HR) is progressively and rapidly reduced after administration of streptozotocin (STZ) and that the reduction in HR can be partially normalized with insulin replacement. Reductions in HR have also been reported in isolated perfused heart and superfused right atrial preparations suggesting that intrinsic defects in the heart are at least partly responsible for the bradycardia. The regional effects of STZ-induced diabetes mellitus (DM) on action potentials (APs) in the sinoatrial node (SAN), right and left atria and ventricles have been compared in the spontaneously beating Langendorff perfused rat heart 10-12 weeks after treatment. HR was significantly reduced in STZ-induced diabetic rat heart (174 +/- 9 BPM) compared to controls (241 +/- 12 BPM). The duration of AP repolarization at 50% and 70% from peak AP was significantly prolonged in SAN, right atrium and right ventricle from STZ-induced diabetic rat compared to age-matched controls. In the SAN AP duration (APD) at 50% and 70% were 51.7 +/- 2.2 and 59.5 +/- 2.3 ms in diabetic rat heart compared to 45.2 +/- 1.7 and 50.0 +/- 1.6 ms in controls, respectively. In contrast APD at 50% and 70% were not significantly altered in the left atrium and left ventricle. Regional defects in the expression and/or electrophysiology of SAN ion channels, and in particular those involved in AP repolarization, might underlie heart rhythm disturbances in the STZ-induced DM rat.


Asunto(s)
Potenciales de Acción/fisiología , Diabetes Mellitus Experimental/fisiopatología , Nodo Sinoatrial/fisiopatología , Potenciales de Acción/efectos de los fármacos , Animales , Diabetes Mellitus Experimental/inducido químicamente , Atrios Cardíacos/efectos de los fármacos , Atrios Cardíacos/fisiopatología , Frecuencia Cardíaca/efectos de los fármacos , Frecuencia Cardíaca/fisiología , Ventrículos Cardíacos/efectos de los fármacos , Ventrículos Cardíacos/fisiopatología , Ratas , Nodo Sinoatrial/efectos de los fármacos , Estreptozocina/farmacología
16.
Theor Appl Genet ; 113(4): 673-83, 2006 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-16807733

RESUMEN

Developmental mutants serve as a useful material to unravel the mechanisms necessary for organ development. The polycotyledon (poc) mutant of tomato, with multiple cotyledons in the seedling and varied phenotypic effects in the adult plant is one such mutant. Studies using physiological and anatomical methods in our lab suggest that POC is involved in the negative regulation of polar auxin transport, which is likely the reason for the pleiotropic phenotype in the mutant. Because of the physiological significance of the polycotyledon mutant described in this paper and also being first of its kind in tomato and also other plant species, we are using a map-based cloning approach to map the polycotyledon gene. Molecular mapping of this locus using segregating interspecific F2 mapping population localized polycotyledon gene close to TG424 marker on the long arm of chromosome 9. The closest marker mapped was a PCR marker identified in this study, E8A2 at a distance of 7.4 cM from the poc locus. The absence of tightly linked RAPD markers and the non-availability of more mapped markers in this region led us to initiate chromosome walk to polycotyledon gene. Both the flanking markers TG248 and E8A2 were used to screen the BAC library and a contig was developed for TG248 marker. The BAC-end sequences were analyzed for their use as RFLP markers to enrich this region for markers. Analysis of the BAC-end sequences revealed that poc is localized in the region surrounded by copia-like retrotransposon elements explaining the absence of markers in the euchromatin region on long arm of chromosome 9. Further studies identified two BAC-end sequences which mapped around the poc locus and also indicated very low physical versus genetic distance ratio in this region. The double mutant analyses of poc with the other two known polycotyledon mutants of tomato, pct and dem revealed allelism with pct; therefore, the poc mutant was named as pct1-2, and also the original pct mutant was renamed as pct1-1.


Asunto(s)
Cotiledón/crecimiento & desarrollo , Genes de Plantas , Solanum lycopersicum/genética , Alelos , Transporte Biológico/fisiología , Paseo de Cromosoma , Cromosomas de las Plantas , Clonación Molecular , Cotiledón/anatomía & histología , Cotiledón/genética , Prueba de Complementación Genética , Ligamiento Genético , Marcadores Genéticos , Ácidos Indolacéticos/metabolismo , Solanum lycopersicum/anatomía & histología , Solanum lycopersicum/crecimiento & desarrollo , Fenotipo , Polimorfismo de Longitud del Fragmento de Restricción , Plantones/anatomía & histología , Plantones/genética , Plantones/crecimiento & desarrollo
17.
J Biol Chem ; 270(40): 23540-5, 1995 Oct 06.
Artículo en Inglés | MEDLINE | ID: mdl-7559518

RESUMEN

L-Tryptophan 2',3'-oxidase, an amino acid alpha,beta-dehydrogenase isolated from Chromobacterium violaceum, catalyzes the formation of a double bond between the C alpha and C beta carbons of various tryptophan derivatives provided that they possess: (i) a L-enantiomeric configuration, (ii) an alpha-carbonyl group, and (iii) an unsubstituted and unmodified indole nucleus. Kinetic parameters were evaluated for a series of tryptophan analogues, providing information on the contribution of each chemical group to substrate binding. The stereochemistry of the dehydro product was determined to be a Z-configuration from proton nuclear magnetic resonance assignments. No reaction can be observed in the presence of other aromatic beta-substituted alanyl residues which behave neither as substrates nor as inhibitors and therefore do not compete against this reaction. The enzymatic synthesis of alpha,beta-dehydrotryptophanyl peptides from 5 to 24 residues was successfully achieved without side product formation, irrespective of the position of the tryptophan residue in the amino acid sequence. A reactional mechanism involving a direct alpha,beta-dehydrogenation of the tryptophan side chain is proposed.


Asunto(s)
Chromobacterium/enzimología , Oxidorreductasas/metabolismo , Secuencia de Aminoácidos , Sitios de Unión , Indoles/química , Indoles/metabolismo , Cinética , Datos de Secuencia Molecular , Péptidos/química , Péptidos/metabolismo , Estereoisomerismo , Especificidad por Sustrato , Triptófano/análogos & derivados , Triptófano/química , Triptófano/metabolismo
18.
J Clin Pharm Ther ; 28(6): 479-83, 2003 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-14651671

RESUMEN

OBJECTIVE: To assess the effectiveness of monitoring of serum concentration of aminoglycosides in neonates. METHOD: A retrospective evaluation of serum concentration monitoring of aminoglycosides (gentamicin and amikacin) and vancomycin in neonates treated for sepsis in a maternity and children hospital in Jeddah, Saudi Arabia, over the period 1998-2000. RESULTS: The total number of requests for monitoring increased sixfold in 1999 and 12-fold in 2000 relative to 1998. For aminoglycosides, the incidence of both subtherapeutic peak and toxic trough serum levels decreased significantly (P < 0.05) in 1999 and 2000 compared with 1998. Furthermore, the rate of neonatal mortality caused by sepsis showed reduction in both 1999 (34%) and 2000 (35%) in comparison with 1998 (45%). Vancomycin trough (effective) concentration monitoring revealed no change in the incidence (30%) of levels at subtherapeutic values (<5.0 microg/mL) between the compared years. Furthermore, the rate of toxic levels (>10 microg/mL) increased in both 1999 (31%) and 2000 (39%) relative to 1998 (25%). CONCLUSION: Therapeutic drug monitoring of vancomycin needs re-evaluation in the hospital to explain why existing methods are ineffective.


Asunto(s)
Amicacina/sangre , Antibacterianos/sangre , Gentamicinas/sangre , Sepsis/tratamiento farmacológico , Vancomicina/sangre , Amicacina/uso terapéutico , Antibacterianos/uso terapéutico , Gentamicinas/uso terapéutico , Humanos , Incidencia , Recién Nacido , Estudios Retrospectivos , Arabia Saudita , Sepsis/mortalidad , Vancomicina/uso terapéutico
19.
J Autoimmun ; 23(1): 75-80, 2004 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-15236755

RESUMEN

Autoimmune thyroid diseases (AITDs), which include Hashimoto thyroiditis (HT), Graves' disease (GD) and primary idiopathic myxoedema (PIM), are recognized as multifactorial diseases. In this study, we have examined single and haplotypic genetic variation across the major histocompatibility complex (MHC) in a Tunisian isolate with a high prevalence of AITDs (62 patients: 32 with GD, 9 with HT and 21 with PIM). Genotyping was performed for HLA class I and II alleles as well as polymorphisms within tumor necrosis factor (TNF), lymphotoxin alpha (TLalpha) and heat shock protein (HSP70-02 and HSP70-hom) genes. Our results showed association of HLA-A2-B50-TNF 2 haplotype with AITDs (p = 0.045). Linkage analysis using Simwalk2 program has shown significant result with TNF -308 gene polymorphism (p = 0.03). The FBAT has given evidence for genetic association with TNF -308 and HLA-DR gene polymorphisms. TNF 2 allele was associated with GD (p = 0.0011), whereas TNF 1, HLA-DR11 and DR12 (p = 0.0039, p = 0.00089 and p = 0.0056, respectively) were rather implicated in HT pathogenesis. Results found by TDT-STDT have confirmed the involvement of the TNF -308 gene polymorphism in AITD pathogenesis (p < 10(-9)).


Asunto(s)
Complejo Mayor de Histocompatibilidad , Polimorfismo Genético , Tiroiditis Autoinmune/inmunología , Factor de Necrosis Tumoral alfa/inmunología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Mapeo Cromosómico , Femenino , Enfermedad de Graves/genética , Enfermedad de Graves/inmunología , Humanos , Masculino , Persona de Mediana Edad , Análisis de Secuencia de ADN , Tiroiditis Autoinmune/genética , Factor de Necrosis Tumoral alfa/genética , Túnez
20.
Bioconjug Chem ; 8(4): 472-80, 1997.
Artículo en Inglés | MEDLINE | ID: mdl-9258443

RESUMEN

Upon agonist activation, the nicotinic acetylcholine receptor undergoes allosteric transitions leading to channel opening and sodium ion influx. The molecular structure of the agonist binding site has been mapped previously by photoaffinity labeling, but most photosensitive probes used for this purpose interact only with closed receptor states (resting or desensitized). We have synthesized two novel photoactivatable 4-diazocyclohexa-2,5-dienone derivatives as cholinergic agonist candidates, with the objective of identifying structural changes at the acetylcholine binding site associated with receptor activation. One of these ligands, 9b, is a functional agonist at muscle acetylcholine receptors in human TE 671 cells. In photolabeling experiments with 9b, up to 35% inactivation of agonist binding sites was observed at Torpedo acetylcholine receptors. Tritiated 9b was synthesized, and photolabeling was found to occur mainly on the alpha-subunit in a partially protectable manner. This novel radiolabeled photoprobe appears to be suitable for future investigation of the molecular dynamics of allosteric transitions occurring at the active acetylcholine receptor binding site.


Asunto(s)
Receptores Nicotínicos/química , Animales , Línea Celular , Humanos , Espectroscopía de Resonancia Magnética , Espectrometría de Masas , Sondas Moleculares , Agonistas Nicotínicos/farmacología , Técnicas de Placa-Clamp , Fotoquímica , Receptores Nicotínicos/efectos de los fármacos , Receptores Nicotínicos/metabolismo , Torpedo , Tritio
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