RESUMEN
BACKGROUND: Numerous studies have indicated that comorbid anxiety and depression are associated with a more severe course of illness. Yet generally, the study of the effect of psoriasis on patients' mental health has considered anxiety and depression to be separate states. OBJECTIVE: To measure the association between psoriasis and anxiety, depression and anxiety-depression co-occurrence among patients according to their socioeconomic statuses (SES). METHODS: A nationwide population-based study of psoriasis patients and age and gender frequency-matched controls (n = 255 862) was designed. Diagnostic data were obtained from Clalit Health Services, the largest managed care organization in Israel. This database was established using continuous real-time input from healthcare providers, pharmacies, medical care facilities and administrative computerized operating systems. RESULTS: After controlling for demographic and clinical variables, psoriasis was associated with anxiety (OR 1.11, 95% CI 1.01-1.23, P < 0.05), depression (OR 1.17, 95% CI 1.08-1.26, P < 0.001), and anxiety and depression co-occurrence (OR 1.32, 95% CI 1.21-1.45, P < 0.001) among patients with low SES, yet was associated only with anxiety (OR 1.15 95% CI 1.04-1.27, P < 0.001) but not depression or comorbid anxiety-depression among patients with high SES. Survival analyses indicated that between the ages of 40 and 60, the cumulative probability of psoriasis patients with low SES to suffer from anxiety, depression and their co-occurrence inclined more sharply with age as compared to psoriasis patients with high SES. CONCLUSIONS: As psoriasis patients with low SES are prone to suffer from more severe courses of anxiety and depression, the choice of treatment of psoriasis should address the SES as well as the underlying psychiatric disease.
Asunto(s)
Ansiedad/complicaciones , Depresión/complicaciones , Psoriasis/epidemiología , Clase Social , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Casos y Controles , Femenino , Humanos , Israel/epidemiología , Masculino , Persona de Mediana Edad , Psoriasis/complicaciones , Psoriasis/psicología , Adulto JovenRESUMEN
Tuberculosis (TB) infects one-third of the world population. Despite 50 years of available drug treatments, TB continues to increase at a significant rate. The failure to control TB stems in part from the expense of delivering treatment to infected individuals and from complex treatment regimens. Incomplete treatment has fueled the emergence of multi-drug resistant (MDR) strains of Mycobacterium tuberculosis (Mtb). Reducing non-compliance by reducing the duration of chemotherapy will have a great impact on TB control. The development of new drugs that either kill persisting organisms, inhibit bacilli from entering the persistent phase, or convert the persistent bacilli into actively growing cells susceptible to our current drugs will have a positive effect. We are taking a multidisciplinary approach that will identify and characterize new drug targets that are essential for persistent Mtb. Targets are exposed to a battery of analyses including microarray experiments, bioinformatics, and genetic techniques to prioritize potential drug targets from Mtb for structural analysis. Our core structural genomics pipeline works with the individual laboratories to produce diffraction quality crystals of targeted proteins, and structural analysis will be completed by the individual laboratories. We also have capabilities for functional analysis and the virtual ligand screening to identify novel inhibitors for target validation. Our overarching goals are to increase the knowledge of Mtb pathogenesis using the TB research community to drive structural genomics, particularly related to persistence, develop a central repository for TB research reagents, and discover chemical inhibitors of drug targets for future development of lead compounds.
Asunto(s)
Antituberculosos/farmacología , Cristalografía , Diseño de Fármacos , Mycobacterium tuberculosis/efectos de los fármacos , Arginina/metabolismo , Proteínas Bacterianas/antagonistas & inhibidores , Proteínas Bacterianas/química , Evaluación Preclínica de Medicamentos , Hierro/metabolismo , Malato Sintasa/antagonistas & inhibidores , Malato Sintasa/química , Técnicas Analíticas Microfluídicas , Proteínas de Transporte de Monosacáridos/antagonistas & inhibidores , Proteínas de Transporte de Monosacáridos/química , Mycobacterium tuberculosis/genética , Mycobacterium tuberculosis/metabolismo , Ácidos Micólicos/antagonistas & inhibidores , Péptido Sintasas/antagonistas & inhibidores , Péptido Sintasas/química , Difracción de Rayos XRESUMEN
Tropomodulin (40 kDa) stabilizes the actin-tropomyosin filament by capping the P end (slow-growing end). The C-terminal half (C20, 20 kDa), an independently folded domain that is believed to be responsible for the P-end capping, has been crystallized. Crystals grew in the presence of Zn(2+) as the solution pH was increased from 3 towards the pI of the protein. The crystals belong to the trigonal space group R3. They have unit-cell parameters a = b = 69.6, c = 101.3 A (mean values, with a estimated standard deviation of 0.009 A) and diffract to 1.9 A resolution when the frozen crystals were measured at 120 K on a rotating-anode X-ray source at 120 K.
Asunto(s)
Proteínas Portadoras/química , Proteínas de Microfilamentos , Cristalización , Cristalografía por Rayos X , Fragmentos de Péptidos/química , Conformación Proteica , TropomodulinaRESUMEN
BACKGROUND: This study evaluated the effectiveness of group interpersonal psychotherapy (IPT-G) for patients suffering from moderate to severe major depressive disorder (MDD), and who responded to antidepressant drugs during the acute phase treatment. METHODS: Subjects were allocated into two groups: in the study group subjects entered IPT-G while in the comparison group subjects continued with standard treatment. All subjects were assessed five times during and 6 months after the termination of the IPT-G in a double-blind, matched-control design. RESULTS: Subjects who participated in the IPT-G demonstrated significant improvement of their depressive symptoms compared to those who received the standard treatment both during the group therapy and in a 6-month follow-up period. CONCLUSIONS: Our preliminary results suggest that IPT in a group setting might be effective for a subset of patients who respond to antidepressant medication. LIMITATIONS: Small group of patients, lack of different types of treatment as control groups.
Asunto(s)
Trastorno Depresivo Mayor/terapia , Relaciones Interpersonales , Psicoterapia de Grupo , Adulto , Anciano , Antidepresivos/administración & dosificación , Terapia Combinada , Trastorno Depresivo Mayor/diagnóstico , Trastorno Depresivo Mayor/psicología , Método Doble Ciego , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Proyectos Piloto , Resultado del TratamientoRESUMEN
The structure of tropomodulin, the unique capping protein for the pointed end (the slow-growing end) of an actin filament, was studied. An improved Escherichia coli expression system for chicken E-tropomodulin was established and tropomodulin was prepared, Tmod (N39), in which 15 amino acid residues from the original C-terminus are deleted at the DNA level. This expression and purification system accidentally co-produces an 11-kDa fragment with the original N-terminus (N11). By applying limited proteolysis to Tmod (N39), a 20-kDa C-terminal fragment (C20) was obtained. The limited proteolysis data, as well as the fluorescence spectrometry and CD analyses of Tmod (N39), C20 and N11, revealed that tropomodulin is an alpha-helical protein that consists of two distinct domains. The C-terminal half (20 kDa) is resistant to proteolysis, which suggests that this domain is tightly folded. In contrast, the N-terminal half is susceptible to proteolysis, indicating that in solution this half is likely to be extended or to form a highly flexible structure. Cross-linking experiments with glutaraldehyde indicated that Tmod (N39) and N11 can form complexes with tropomyosin, whereas C20 cannot. This confirms the previous report that the site(s) of interaction with tropomyosin resides in the N-terminal 11-kDa region of tropomodulin.
Asunto(s)
Proteínas Portadoras/química , Proteínas Portadoras/metabolismo , Pollos , Proteínas de Microfilamentos , Secuencia de Aminoácidos , Animales , Proteínas Portadoras/genética , Proteínas Portadoras/aislamiento & purificación , Dicroismo Circular , Reactivos de Enlaces Cruzados/metabolismo , Endopeptidasas/metabolismo , Escherichia coli/genética , Fluorescencia , Expresión Génica , Glutaral/metabolismo , Espectrometría de Masas , Datos de Secuencia Molecular , Peso Molecular , Fragmentos de Péptidos/química , Fragmentos de Péptidos/aislamiento & purificación , Fragmentos de Péptidos/metabolismo , Unión Proteica , Estructura Terciaria de Proteína , Proteínas Recombinantes de Fusión/química , Proteínas Recombinantes de Fusión/aislamiento & purificación , Proteínas Recombinantes de Fusión/metabolismo , Tropomodulina , Tropomiosina/metabolismoRESUMEN
The strain B-1166 differs from the other strains of Bacillus thuringiensis ssp. finitimus because it has two crystal types with different localization in the sporulating cell, i.e., inside and outside of exosporium membrane. Two dissociants of the strain were obtained containing only one of the crystal types. The initial strain produces at least three various delta-endotoxins (Fin2, Fin3, and Fin5) differing from all other known entomocidal proteins; Fin2 and Fin3 are similar to each other but differ from Fin5. Both crystal types contain the same endotoxins (Fin2, Fin3, and Fin5). In the B-1166 strain the site of crystal deposition is not determined by their protein composition.
Asunto(s)
Bacillus thuringiensis/química , Proteínas Bacterianas/química , Toxinas Bacterianas/química , Endotoxinas/química , Secuencia de Aminoácidos , Bacillus thuringiensis/ultraestructura , Toxinas de Bacillus thuringiensis , Cromatografía por Intercambio Iónico , Electroforesis en Gel de Poliacrilamida , Proteínas Hemolisinas , Inmunodifusión , Microscopía ElectrónicaRESUMEN
Proteins of molecular weight 65 and 62 kD and having affinity for toxins Cry4B and Cry11A produced by Bacillus thuringiensis ssp. israelensis have been isolated from brush border membranes of Aedes aegypti larvae using affinity chromatography. Using a ligand blotting technique, we show that the binding of these proteins to the biotinylated toxins is reversible and that the two toxins compete for binding to the two proteins. These proteins are likely to be Cry4B and Cry11A toxin receptors in gut epithelial cells of Aedes aegypti larvae.
Asunto(s)
Aedes/crecimiento & desarrollo , Bacillus thuringiensis/metabolismo , Proteínas Bacterianas/metabolismo , Toxinas Bacterianas , Endotoxinas/metabolismo , Larva/metabolismo , Proteínas de la Membrana/metabolismo , Animales , Toxinas de Bacillus thuringiensis , Unión Competitiva , Cromatografía de Afinidad , Proteínas Hemolisinas , Proteínas de la Membrana/aislamiento & purificación , Unión ProteicaRESUMEN
In five experiments, rats were fed tryptophan (Tryp)-deficient diets with 6-12 micrograms/g zinc (Zn) and, in one experiment, a Zn-deficient diet to test the effect on clinical manifestations, plasma and bone Zn, and ability of picolinic acid (PA) or extra (12 micrograms/g) Zn to compensate. Tryp deficiency caused classical manifestations of pellagra although niacin intake was in excess of normal requirements. At marginal Zn intakes, oral PA caused a significant increase of plasma Zn and, compared with Tryp-adequate controls, Tryp deficiency resulted in lower plasma Zn and plasma:bone Zn ratios. Extra Zn (total 24 micrograms/g) was ineffective. Subcutaneous PA showed a tendency to lower plasma Zn. PA had no effect on clinical manifestations. We conclude that a Tryp metabolite other than nicotinic acid is necessary in the prevention of pellagra. Our hypothesis links this finding with the observed Tryp and PA effect on Zn metabolism.
Asunto(s)
Pelagra/etiología , Ácidos Picolínicos/farmacología , Triptófano/deficiencia , Zinc/metabolismo , Animales , Peso Corporal , Huesos/metabolismo , Dieta , Masculino , Pelagra/prevención & control , Ratas , Ratas Endogámicas , Distribución Tisular , Zinc/fisiologíaRESUMEN
The physical properties of deoxyhemoglobin S gels formed from solutions at concentrations and temperatures approaching those in vivo have been characterized by stress relaxation using a rotational rheometer. Gels were annealed in the rheometer and then subjected to a constant shear strain; thereafter the stress sustained was followed with time. Gels with solid-like behavior held stress indefinitely, and were characterized by yield temperature (the temperature at which stress decreased). Gels with less solid behavior were unable to hold target stress, and were characterized by yield stress (maximum stress attained) and equilibrium stress (final stress held). The samples were ultracentrifuged to calculate pellet and polymer masses. The solidity of the gels, as measured by yield temperature or yield stress, was related to the initial hemoglobin concentration, pellet and polymer masses, shear history, temperature, and the temperature and time of annealing. Solidity increased significantly with time when gels were annealed at 37 degrees C, whereas, when annealed at 25 degrees C, no or minimal increases in solidity were noted. Studies suggest that polymerization occurs rapidly and is completed early in or before the gel annealing period and that the increase in solidity with time of annealing is mainly due to factors other than polymer mass, i.e. alignment, increasing bond strength, water loss. The chemical activity of deoxyhemoglobin S did not affect the solidity of the formed gels. When the resultant polymer masses were comparable, gels formed from samples with albumin present (higher initial total protein concentration, but lower initial deoxyhemoglobin S concentration), had the same behavior as gels formed from solutions with higher initial hemoglobin S concentration. These findings demonstrate that gel annealing conditions must be standardized when comparing the rheologic behaviors of deoxyhemoglobin S gels and indicate that the gel's physical properties (influenced by polymer mass, shear history, annealing time) must be considered in understanding pathophysiology of sickling disorders.
Asunto(s)
Hemoglobina Falciforme , Reología , Secuencia de Aminoácidos , Fenómenos Químicos , Química Física , Geles , Humanos , Sustancias Macromoleculares , Estrés Mecánico , Temperatura , ViscosidadRESUMEN
To facilitate nighttime management of patients with glycogen storage disease, intragastric drip infusions of concentrated solutions of either glucose or dextrins has been recommended. This paper reports a removable maxillary acrylic appliance used successfully as a feeding device.
Asunto(s)
Nutrición Enteral/instrumentación , Enfermedad del Almacenamiento de Glucógeno/terapia , Preescolar , Diseño de Equipo , Humanos , Masculino , Aparatos Ortodóncicos RemoviblesRESUMEN
We report an infant who developed clinical manifestations of zinc deficiency during the first month of life although the diet was adequate for zinc and no other causes could be ascertained. The diagnosis was confirmed by low plasma-zinc concentrations and a positive response to zinc treatment. The fatty acid profile of plasma phospholipids was typical of zinc deficiency (ie, arachidonic acid was markedly decreased). The transient nature of this disorder was evident when no relapse occurred after cessation of zinc therapy and plasma-zinc and arachidonic acid concentrations remained normal. Several explanations for the development of transient neonatal zinc deficiency are offered. The observation demonstrates that occasional infants may have requirements for zinc that are beyond the intakes of the conventional RDA.
Asunto(s)
Zinc/deficiencia , Blefaritis/etiología , Candidiasis Bucal/etiología , Dermatitis del Pañal/etiología , Ácidos Grasos/análisis , Femenino , Humanos , Recién Nacido , Terapia Ortomolecular/efectos adversos , Fosfolípidos/sangre , Factores de Tiempo , Zinc/sangre , Zinc/uso terapéuticoRESUMEN
Examination of two sisters ages 2 years 10 months and 6 years four months with gyrate atrophy of the choroid and retina provided an opportunity for detailed clinical investigation. Although the chorioretinal lesions were confined to the peripheral retina in the older case and were quite minimal in the younger case, there was electroretinographic evidence of marked involvement of the cone and rod systems. These cases offer an opportunity to assess an arginine restricted diet in preventing the progress of the disease.
Asunto(s)
Coroides/patología , Ornitina-Oxo-Ácido Transaminasa/deficiencia , Ornitina/sangre , Retina/patología , Transaminasas/deficiencia , Atrofia , Niño , Preescolar , Electrooculografía , Electrorretinografía , Femenino , Angiografía con Fluoresceína , Estudios de Seguimiento , HumanosRESUMEN
Three children with acrodermatitis enteropathica (AE) were treated with oral zinc dipicolinate (zinc-PA). The daily dose of zinc required to prevent exacerbations, when administered as the dipicolinate complex, was one-third the minimum amount of zinc required as the sulfate salt. The concentration of picolinic acid in the plasma of asymptomatic children with AE was significantly less than that of normal children. However, oral treatment with PA alone was ineffective. The plasma of the three AE children contained a measurable quantity of kynurenine which was undetectable in plasma from normal children. Absorption of an oral zinc load was normal. The results support the hypothesis that the genetic defect in AE is in the tryptophan pathway, although the role of PA in zinc metabolism remains to be defined.
Asunto(s)
Acrodermatitis/metabolismo , Enfermedades Intestinales/metabolismo , Ácidos Picolínicos/metabolismo , Triptófano/metabolismo , Acrodermatitis/tratamiento farmacológico , Adolescente , Niño , Femenino , Humanos , Enfermedades Intestinales/tratamiento farmacológico , Quinurenina/sangre , Masculino , Ácidos Picolínicos/uso terapéutico , Zinc/sangreRESUMEN
A patient with classical symptoms of non-ketotic hyperglycinaemia (NKH) is presented. Threonine dehydratase was undetectable in a liver autopsy specimen, which was obtained within 1 h of death and immediately frozen at -70 degrees C. Activities of four marker enzymes were normal. This represents the first documentation of an inborn error of threonine metabolism and a new explanation of NKH.
Asunto(s)
Glicina/sangre , Treonina Deshidratasa/deficiencia , Glutamato Deshidrogenasa/metabolismo , Humanos , Lactante , L-Lactato Deshidrogenasa/metabolismo , Hígado/enzimología , Masculino , Ornitina Carbamoiltransferasa/metabolismoAsunto(s)
Errores Innatos del Metabolismo de los Aminoácidos/metabolismo , Glicina/líquido cefalorraquídeo , Treonina/metabolismo , Errores Innatos del Metabolismo de los Aminoácidos/diagnóstico , Errores Innatos del Metabolismo de los Aminoácidos/tratamiento farmacológico , Benzoatos/uso terapéutico , Ácido Benzoico , Glicina/sangre , Humanos , Lactante , Recién NacidoRESUMEN
Picolinic acid (PA) is a metabolite of tryptophan that chelates trace metals, including zinc. Several recent observations have suggested a role for PA in zinc metabolism. The enzyme responsible for its formation is picolinic carboxylase (PC). We have measured PC in rats under a variety of conditions, using tissues that play a role in zinc metabolism. PC activity was demonstrated in liver and kidney and was not detectable in pancreas and brain. Activity was most pronounced in kidney. In male suckling rats, PC increased gradually, reaching maximum levels on the 21st day of life. Only liver PC showed marked variations under different physiological conditions. Liver PC was higher on the 21st day of life than in adulthood. It was higher in female than in male adult rats. In pregnant rats, liver PC decreased gradually toward the end of gestation, reaching the lowest point near delivery; however, a 12-fold increase occurred during lactation. Liver PC activity of rats with symptoms of pellagra showed a fivefold increase over controls with similar body weight, whereas liver PC of chronically starved rats showed only a twofold increase over controls with twice their body weight.