Asunto(s)
Tumor de Buschke-Lowenstein/tratamiento farmacológico , Condiloma Acuminado/tratamiento farmacológico , Ciclopropanos/administración & dosificación , Inmunoterapia/métodos , Vulva/efectos de los fármacos , Anciano de 80 o más Años , Tumor de Buschke-Lowenstein/diagnóstico , Condiloma Acuminado/diagnóstico , Femenino , Humanos , Resultado del Tratamiento , Vulva/patologíaAsunto(s)
Alopecia/tratamiento farmacológico , Visita a Consultorio Médico/estadística & datos numéricos , Cooperación del Paciente/estadística & datos numéricos , Fotograbar , Inhibidores de 5-alfa-Reductasa/uso terapéutico , Corticoesteroides/uso terapéutico , Alopecia Areata/tratamiento farmacológico , Ciclopropanos/uso terapéutico , Fármacos Dermatológicos/uso terapéutico , Dermoscopía , Femenino , Humanos , Masculino , Minoxidil/uso terapéutico , Probabilidad , Estudios RetrospectivosRESUMEN
The current study investigates the dissolution rate performance of amorphous solid solutions of a poorly water-soluble drug, efavirenz (EFV), in amorphous Soluplus® (SOL) and Kollidon® VA 64 (KVA64) polymeric systems. For the purpose of the study, various formulations with varying drug loadings of 30, 50, and 70% w/w were developed via hot-melt extrusion processing and adopting a Box-Behnken design of experiment (DoE) approach. The polymers were selected based on the Hansen solubility parameter calculation and the prediction of the possible drug-polymer miscibility. In DoE experiments, a Box-Behnken factorial design was conducted to evaluate the effect of independent variables such as Soluplus® ratio (A1), HME screw speed (A2), and processing temperature (A3), and Kollidon®VA64 ratio (B1), screw speed (B2), and processing temperature (B3) on responses such as solubility (X1 and Y1) and dissolution rate (X2 and Y2) for both ASS [EFV:SOL] and BSS [EFV:KVA64] systems. DSC and XRD data confirmed that bulk crystalline EFV transformed to amorphous form during the HME processing. Advanced chemical analyses conducted via 2D COSY NMR, FTIR chemical imaging, AFM analysis, and FTIR showed that EFV was homogenously dispersed in the respective polymer matrices. The maximum solubility and dissolution rate was observed in formulations containing 30% EFV with both SOL and KVA64 alone. This could be attributed to the maximum drug-polymer miscibility in the optimized formulations. The actual and predicted values of both responses were found precise and close to each other.
Asunto(s)
Benzoxazinas/química , Composición de Medicamentos/métodos , Alquinos , Rastreo Diferencial de Calorimetría , Ciclopropanos , Calor , Tamaño de la Partícula , Polímeros/química , Povidona/química , Solubilidad , Espectroscopía Infrarroja por Transformada de Fourier , Difracción de Rayos XAsunto(s)
Acetatos/administración & dosificación , Cetirizina/administración & dosificación , Antagonistas de los Receptores Histamínicos H1 no Sedantes/administración & dosificación , Antagonistas de Leucotrieno/administración & dosificación , Quinolinas/administración & dosificación , Ensayos Clínicos Controlados Aleatorios como Asunto/métodos , Urticaria/tratamiento farmacológico , Enfermedad Crónica , Ciclopropanos , Método Doble Ciego , Resistencia a Medicamentos/efectos de los fármacos , Resistencia a Medicamentos/fisiología , Humanos , Ensayos Clínicos Controlados Aleatorios como Asunto/normas , Sulfuros , Resultado del Tratamiento , Urticaria/diagnósticoAsunto(s)
Acetatos/administración & dosificación , Cetirizina/administración & dosificación , Antagonistas de los Receptores Histamínicos H1 no Sedantes/administración & dosificación , Antagonistas de Leucotrieno/administración & dosificación , Quinolinas/administración & dosificación , Ensayos Clínicos Controlados Aleatorios como Asunto/métodos , Urticaria/tratamiento farmacológico , Enfermedad Crónica , Ciclopropanos , Método Doble Ciego , Resistencia a Medicamentos/efectos de los fármacos , Resistencia a Medicamentos/fisiología , Humanos , Ensayos Clínicos Controlados Aleatorios como Asunto/normas , Sulfuros , Resultado del Tratamiento , Urticaria/diagnósticoRESUMEN
BACKGROUND: Chronic urticaria is a vexing problem for patients and treating physicians alike. The EAACI/GA[2]LEN/EDF/WAO guidelines advocate an increased antihistamine dosage up to four times the standard, before adding leukotriene receptor antagonists. Patients are frequently intolerant of these higher dosages. We conducted this study to determine whether the addition of leukotriene receptor antagonists to the standard antihistamine dose was comparable to higher dosages of antihistamines alone, in terms of efficacy, safety and quality of life changes. We compared levocetirizine 10 mg (double dose of standard) versus a combination of levocetirizine 5 mg and montelukast 10 mg in cases of chronic urticaria not responding to single daily dose of 5 mg levocetirizine. METHODS: A single-center, double-blind, randomized, active-controlled, parallel group phase IV trial (CTRI/2014/12/005261) was conducted on 120 patients of chronic urticaria of either sex not responding to 5 mg levocetirizine. Patients were randomized into receiving either levocetirizine 10 mg or levocetirizine 5 mg + montelukast 10 mg for 4 weeks. Primary outcome measures were Urticaria Activity Score (UAS) and Urticaria Total Severity Score (TSS). Routine hematological and biochemical tests and treatment-emergent adverse events were monitored for safety. RESULTS: Fifty-two patients on levocetirizine 10 mg group and 51 patients on levocetirizine 5 mg + montelukast 10 mg group were analyzed. UAS and TSS reduced significantly in both treatment groups and reduction of score were comparable in between the groups (P = 0.628, P = 0.824, respectively). Among adverse effects, sedation was noted significantly more (P = 0.013) in levocetirizine 10 mg group. Quality of life was significantly improved in levocetirizine 5 mg + montelukast 10 mg group (P = 0.031). LIMITATIONS: The limitation of the study was that the follow-up period was 4 weeks. CONCLUSION: EAACI/GA[2]LEN/EDF/WAO guidelines need to be more flexible in allowing usage of montelukast before escalation of anti-histamine dosage.
Asunto(s)
Acetatos/administración & dosificación , Cetirizina/administración & dosificación , Quinolinas/administración & dosificación , Urticaria/diagnóstico , Urticaria/tratamiento farmacológico , Acetatos/efectos adversos , Adolescente , Adulto , Anciano , Cetirizina/efectos adversos , Enfermedad Crónica , Ciclopropanos , Método Doble Ciego , Resistencia a Medicamentos/efectos de los fármacos , Resistencia a Medicamentos/inmunología , Quimioterapia Combinada , Femenino , Estudios de Seguimiento , Antagonistas de los Receptores Histamínicos H1 no Sedantes/administración & dosificación , Antagonistas de los Receptores Histamínicos H1 no Sedantes/efectos adversos , Humanos , Hipnóticos y Sedantes/administración & dosificación , Hipnóticos y Sedantes/efectos adversos , Antagonistas de Leucotrieno/administración & dosificación , Antagonistas de Leucotrieno/efectos adversos , Masculino , Persona de Mediana Edad , Quinolinas/efectos adversos , Sulfuros , Resultado del Tratamiento , Urticaria/inmunología , Adulto JovenRESUMEN
BACKGROUND: Despite recent significant therapeutic advances, vitiligo remains a clinical conundrum. Topical immunotherapy has been extensively tested in the treatment of various dermatologic disorders, especially those believed to have an immunologic basis. AIM: To evaluate the role of topical diphenylcyclopropenone (DPCP) in the treatment of vitiligo. METHODS: Nineteen patients with limited vitiligo lesions were enrolled in this study. After sensitization with 2% lotion of DPCP in acetone, progressively higher concentrations beginning at 0.001% up to 2% were applied weekly for 6 months to the depigmented skin lesions. RESULTS: Thirteen of the 19 patients were evaluated at the end of 6 months. Four patients with focal vitiligo, one patient with vitiligo vulgaris, and three patients with segmental vitiligo showed marked (grade 3) repigmentation. CONCLUSION: Marginal and central repigmentation with hyperpigmented borders was seen in the majority of lesions. Further controlled trials should be undertaken to evaluate the use of topical DPCP in vitiligo.
Asunto(s)
Ciclopropanos/administración & dosificación , Inmunoterapia/métodos , Vitíligo/tratamiento farmacológico , Vitíligo/inmunología , Administración Tópica , Adolescente , Adulto , Niño , Relación Dosis-Respuesta Inmunológica , Femenino , Humanos , Masculino , Persona de Mediana Edad , Proyectos Piloto , Vitíligo/patología , Adulto JovenAsunto(s)
Alopecia Areata/terapia , Ciclopropanos/uso terapéutico , Inmunoterapia , Administración Tópica , Adolescente , Adulto , Niño , Preescolar , Femenino , HumanosAsunto(s)
Acetatos/administración & dosificación , Cetirizina/administración & dosificación , Quinolinas/administración & dosificación , Urticaria , Administración Oral , Adulto , Enfermedad Crónica , Ciclopropanos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Sulfuros , Urticaria/tratamiento farmacológico , Urticaria/patologíaAsunto(s)
Quimioterapia/enfermería , Alquinos , Fármacos Anti-VIH/uso terapéutico , Antibióticos Antituberculosos/uso terapéutico , Anticuerpos Monoclonales/uso terapéutico , Anticuerpos Monoclonales Humanizados , Antineoplásicos/uso terapéutico , Antivirales/uso terapéutico , Benzoxazinas , Ciclopropanos , Didesoxinucleósidos/uso terapéutico , Monitoreo de Drogas/métodos , Monitoreo de Drogas/enfermería , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Ácido Etidrónico/análogos & derivados , Ácido Etidrónico/uso terapéutico , Humanos , Infliximab , Leprostáticos/uso terapéutico , Osteítis Deformante/tratamiento farmacológico , Oxazinas/uso terapéutico , Rifampin/análogos & derivados , Rifampin/uso terapéutico , Ácido Risedrónico , Talidomida/uso terapéutico , Tionucleótidos/uso terapéutico , TrastuzumabRESUMEN
The major mycolic acid produced by Mycobacterium tuberculosis contains two cis-cyclopropanes in the meromycolate chain. The gene whose product cyclopropanates the proximal double bond was cloned by homology to a putative cyclopropane synthase identified from the Mycobacterium leprae genome sequencing project. This gene, named cma2, was sequenced and found to be 52% identical to cma1 (which cyclopropanates the distal double bond) and 73% identical to the gene from M. leprae. Both cma genes were found to be restricted in distribution to pathogenic species of mycobacteria. Expression of cma2 in Mycobacterium smegmatis resulted in the cyclopropanation of the proximal double bond in the alpha 1 series of mycolic acids. Coexpression of both cyclopropane synthases resulted in cyclopropanation of both centers, producing a molecule structurally similar to the M. tuberculosis alpha-dicyclopropyl mycolates. Differential scanning calorimetry of purified cell walls and mycolic acids demonstrated that cyclopropanation of the proximal position raised the observed transition temperature by 3 degrees C. These results suggest that cyclopropanation contributes to the structural integrity of the cell wall complex.
Asunto(s)
Mycobacterium tuberculosis/metabolismo , Ácidos Micólicos/metabolismo , Secuencia de Aminoácidos , Secuencia de Bases , Pared Celular/química , Clonación Molecular , Ciclopropanos/química , Cartilla de ADN/genética , ADN Bacteriano/genética , Expresión Génica , Genes Bacterianos , Espectroscopía de Resonancia Magnética , Fluidez de la Membrana , Metiltransferasas/genética , Metiltransferasas/metabolismo , Datos de Secuencia Molecular , Estructura Molecular , Mycobacterium leprae/enzimología , Mycobacterium leprae/genética , Mycobacterium tuberculosis/enzimología , Mycobacterium tuberculosis/genética , Ácidos Micólicos/química , Homología de Secuencia de AminoácidoRESUMEN
Mycolic acids represent a major constituent of the mycobacterial cell wall complex, which provides the first line of defense against potentially lethal environmental conditions. Slow-growing pathogenic mycobacteria such as Mycobacterium tuberculosis modify their mycolic acids by cyclopropanation, whereas fast-growing saprophytic species such as Mycobacterium smegmatis do not, suggesting that this modification may be associated with an increase in oxidative stress experienced by the slow-growing species. We have demonstrated the transformation of the distal cis double bond in the major mycolic acid of M. smegmatis to a cis-cyclopropane ring upon introduction of cosmid DNA from M. tuberculosis. This activity was localized to a single gene (cma1) encoding a protein that was 34% identical to the cyclopropane fatty acid synthase from Escherichia coli. Adjacent regions of the DNA sequence encode open reading frames that display homology to other fatty acid biosynthetic enzymes, indicating that some of the genes required for mycolic acid biosynthesis may be clustered in this region. M. smegmatis overexpressing the cma1 gene product significantly resist killing by hydrogen peroxide, suggesting that this modification may be an important adaptation of slow-growing mycobacteria to oxidative stress.