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1.
Anaesthesia ; 77(9): 1010-1017, 2022 09.
Artículo en Inglés | MEDLINE | ID: mdl-35727620

RESUMEN

Numerous studies support the idea that neuromuscular blockade facilitates facemask ventilation after induction of anaesthesia. Although improved airway patency or pulmonary compliance and a resolution of laryngospasm have been suggested as possible causes, the exact mechanism remains unclear. We aimed to assess whether neuromuscular blockade improves facemask ventilation and to clarify whether this phenomenon is associated with the vocal cord angle. This prospective observational study included patients aged between 20 and 65 years scheduled for elective surgery under general anaesthesia. After induction of anaesthesia, patients' lungs were ventilated with pressure-controlled ventilation using a facemask. During facemask ventilation, a flexible bronchoscope was inserted through a self-sealing diaphragm at the elbow connector attached to the facemask and breathing circuit and positioned to allow a continuous view of the vocal cords. The mean tidal volume and vocal cord angle were measured before and after administration of neuromuscular blocking drugs. Of 108 patients, 100 completed the study. Mean (SD) tidal volume ((11.0 (3.9) ml.kg-1 vs. 13.6 (2.6) ml.kg-1 ; p < 0.001) and mean (SD) vocal cord angle (17° (10°) vs. 26° (5°); p < 0.001) increased significantly after neuromuscular blockade. The proportional increase in mean tidal volume after neuromuscular blockade was positively correlated with vocal cord angle (Spearman's ρ = 0.803; p < 0.001). In conclusion, neuromuscular blockade facilitated facemask ventilation, and the improvement was correlated with further opening of the vocal cords.


Asunto(s)
Bloqueo Neuromuscular , Adulto , Anciano , Anestesia General , Humanos , Pulmón , Máscaras , Persona de Mediana Edad , Pliegues Vocales , Adulto Joven
2.
Eur J Neurol ; 27(2): 343-351, 2020 02.
Artículo en Inglés | MEDLINE | ID: mdl-31535427

RESUMEN

BACKGROUND AND PURPOSE: The rate at which the chance of a good outcome of endovascular stroke therapy (EVT) decays with time when eligible patients are selected by baseline diffusion-weighted magnetic resonance imaging (DWI-MRI) and whether ischaemic core size affects this rate remain to be investigated. METHODS: This study analyses a prospective multicentre registry of stroke patients treated with EVT based on pretreatment DWI-MRI that was categorized into three groups: small [Diffusion-Weighted Imaging Alberta Stroke Program Early Computed Tomography Score (DWI-ASPECTS)] (8-10), moderate (5-7) and large (<5) cores. The main outcome was a good outcome at 90 days (modified Rankin Scale 0-2). The interaction between onset-to-groin puncture time (OTP) and DWI-ASPECTS categories regarding functional outcomes was investigated. RESULTS: Ultimately, 985 patients (age 69 ± 11 years; male 55%) were analysed. Potential interaction effects between the DWI-ASPECTS categories and OTP on a good outcome at 90 days were observed (Pinteraction  = 0.06). Every 60-min delay in OTP was associated with a 16% reduced likelihood of a good outcome at 90 days amongst patients with large cores, although no associations were observed amongst patients with small to moderate cores. Interestingly, the adjusted rates of a good outcome at 90 days steeply declined between 65 and 213 min of OTP and then remained smooth throughout 24 h of OTP (Pnonlinearity  = 0.15). CONCLUSIONS: Our study showed that the probability of a good outcome after EVT nonlinearly decreased, with a steeper decline at earlier OTP than at later OTP. Discrepant effects of OTP on functional outcomes by baseline DWI-ASPECTS categories were observed. Thus, different strategies for EVT based on time and ischaemic core size are warranted.


Asunto(s)
Accidente Cerebrovascular , Anciano , Anciano de 80 o más Años , Alberta , Isquemia Encefálica/diagnóstico por imagen , Isquemia Encefálica/terapia , Imagen de Difusión por Resonancia Magnética , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Accidente Cerebrovascular/diagnóstico por imagen , Accidente Cerebrovascular/terapia , Tiempo de Tratamiento , Resultado del Tratamiento
3.
Clin Exp Immunol ; 192(2): 151-164, 2018 05.
Artículo en Inglés | MEDLINE | ID: mdl-29363753

RESUMEN

Food allergy is a major public health problem. Studies have shown that long-term interactions between activated leucocyte cell adhesion molecule (ALCAM/CD166) on the surface of antigen-presenting cells, and CD6, a co-stimulatory molecule, influence immune responses. However, there are currently no studies on the functions of ALCAM in food allergy. Therefore, we aimed to identify the functions of ALCAM in ovalbumin (OVA)-induced food allergy using ALCAM-deficient mice. Wild-type (WT) and ALCAM-deficient (ALCAM-/- ) mice were sensitized intraperitoneally and with orally fed OVA. The mice were killed, and parameters related to food allergy and T helper type 2 (Th2) immune responses were analysed. ALCAM serum levels increased and mRNA expression decreased in OVA-challenged WT mice. Serum immunoglobulin (Ig)E levels, Th2 cytokine mRNA and histological injuries were higher in OVA-challenged WT mice than in control mice, and these were attenuated in ALCAM-/- mice. T cell proliferation of total cells, CD3+ CD4+ T cells and activated T cells in immune tissues were diminished in OVA-challenged ALCAM-/- mice. Proliferation of co-cultured T cells and dendritic cells (DCs) was decreased by the anti-CD6 antibody. In addition, WT mice sensitized by adoptive transfer of OVA-pulsed ALCAM-/- BM-derived DCs showed reduced immune responses. Lastly, serum ALCAM levels were higher in children with food allergy than in control subjects. In this study, serum levels of ALCAM were elevated in food allergy-induced WT mice and children with food allergy. Moreover, immune responses and T cell activation were attenuated in OVA-challenged ALCAM-/- mice. These results indicate that ALCAM regulates food allergy by affecting T cell activation.


Asunto(s)
Molécula de Adhesión Celular del Leucocito Activado/genética , Hipersensibilidad a los Alimentos/inmunología , Regulación de la Expresión Génica/inmunología , Células Th2/inmunología , Molécula de Adhesión Celular del Leucocito Activado/sangre , Traslado Adoptivo , Animales , Antígenos CD/genética , Antígenos CD/inmunología , Antígenos de Diferenciación de Linfocitos T/genética , Antígenos de Diferenciación de Linfocitos T/inmunología , Proliferación Celular , Niño , Preescolar , Técnicas de Cocultivo , Citocinas/genética , Citocinas/inmunología , Células Dendríticas/inmunología , Modelos Animales de Enfermedad , Femenino , Humanos , Inmunoglobulina E/sangre , Activación de Linfocitos , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Noqueados , Ovalbúmina
4.
Clin Exp Allergy ; 46(5): 688-95, 2016 05.
Artículo en Inglés | MEDLINE | ID: mdl-26661728

RESUMEN

BACKGROUND: Clusterin is a sensitive cellular biosensor of oxidative stress and has been studied as a biomarker for inflammation-associated diseases. Clusterin levels in childhood asthma have not been evaluated. OBJECTIVES: (1) To evaluate sputum clusterin levels in children with asthma compared to a control group. (2) To assess the relationships between sputum clusterin levels and airway inflammation, pulmonary function, and bronchial hyperresponsiveness. METHODS: This study included 170 children aged 5-18 years with stable asthma (n = 91), asthma exacerbation (n = 29), or no asthma (healthy controls; n = 50). Induced sputum, pulmonary function, and methacholine challenge tests were performed. Stable asthma was classified into two groups according to the severity. Clusterin levels in sputum were measured using an enzyme-linked immunosorbent assay. RESULTS: Children with stable asthma had a higher clusterin level than healthy controls [4540 (3872-5651) pg/mL vs. 3857 (1054-4369) pg/mL, P < 0.001]. The clusterin level was also more elevated in eosinophil-dominant sputum than in non-eosinophilic sputum in stable asthma [5094 (4243-6257) pg/mL vs. 4110 (1871-4839) pg/mL, P = 0.0017]. Clusterin levels were associated with asthma severity. Paradoxically, clusterin levels were lower during asthma exacerbation than in stable asthma [1838 (350-4790] pg/mL vs. 4540 (3872-5651) pg/mL, P < 0.001]. Clusterin levels were strongly correlated with the methacholine concentration that caused a 20% decrease in the forced expiratory volume in 1 s (r = -0.617, P < 0.001); there was no significant correlation between clusterin levels and other pulmonary function parameters. CONCLUSIONS AND CLINICAL RELEVANCE: Clusterin levels were altered in children with stable asthma and asthma exacerbation because of its antioxidant and anti-inflammatory effects. Clusterin may be a marker that reflects airway inflammation and severity of symptoms, and it can be used in the assessment and management of childhood asthma.


Asunto(s)
Asma/inmunología , Asma/metabolismo , Clusterina/metabolismo , Esputo/metabolismo , Adolescente , Asma/diagnóstico , Biomarcadores , Pruebas de Provocación Bronquial , Estudios de Casos y Controles , Niño , Preescolar , Progresión de la Enfermedad , Eosinófilos , Femenino , Volumen Espiratorio Forzado , Humanos , Recuento de Leucocitos , Masculino , Espirometría
5.
Int J Cosmet Sci ; 38(3): 286-93, 2016 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-26564311

RESUMEN

OBJECTIVE: The Korean Cosmetic Act regulates the use of functional cosmetics) by the law. Four functional cosmetic groups, whitening, anti-wrinkle, UV protection and combination of whitening and anti-wrinkle, were categorized according to the Korean Cosmetic Act and Functional Cosmetics Codex. In this study, high-performance liquid chromatography (HPLC) coupled with photodiode array detection (DAD) was employed for the simultaneous detection of arbutin (and its decomposition product, hydroquinone), niacinamide, ascorbyl glucoside, ethyl ascorbyl ether and adenosine in functional cosmetic products such as creams, emulsions and lotions. METHODS: Separation by HPLC-DAD was conducted using a C18 column with a gradient elution of 5 mm KH2PO4 buffer (containing 0.1% phosphoric acid) and methanol (containing 0.1% phosphoric acid). The wavelengths for the detection of arbutin, hydroquinone, niacinamide, adenosine, ascorbyl glucoside and ethyl ascorbyl ether were 283, 289, 261, 257, 238 and 245 nm, respectively. RESULTS: This method exhibited good linearity (R(2) ≥ 0.999), precision (expressed as relative standard deviation (RSD) < 2%) and mean recoveries (89.42-104.89%). The results obtained by monitoring 100 market samples showed that the detected levels of the tested materials are within the acceptable authorized concentration. CONCLUSION: The method developed herein is simple and can be used for market survey and quality control of functional cosmetics.


Asunto(s)
Adenosina/administración & dosificación , Cromatografía Líquida de Alta Presión/métodos , Cosméticos , Preparaciones para Aclaramiento de la Piel , Límite de Detección , Solubilidad , Espectrofotometría Ultravioleta/métodos , Agua
6.
Haemophilia ; 21(2): 196-203, 2015 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-25495591

RESUMEN

A newly developed recombinant factor IX (BAX326(1) ) was investigated for prophylactic use in paediatric patients aged <12 years with severe (FIX level <1%) or moderately severe (FIX level 1-2%) haemophilia B. The aim of this prospective clinical trial was to assess the safety, haemostatic efficacy and pharmacokinetic profile of BAX326 in previously treated paediatric patients. BAX326 was administered as prophylaxis twice a week for a period of 6 months, and on demand for treatment of bleeds. Safety was assessed by the occurrence of related AEs, thrombotic events and immunologic assessments. Efficacy was evaluated by annualized bleeding rate (ABR), and by treatment response rating (excellent, good, fair, none). PK was assessed over 72 h. None of the 23 treated paediatric subjects had treatment-related SAEs or AEs. There were no thrombotic events, inhibitory or specific binding antibodies against FIX, rFurin or CHO protein. Twenty-six bleeds (19 non-joint vs. 7 joint bleeds) occurred (mean ABR 2.7 ± 3.14, median 2.0), of which 23 were injury-related. Twenty subjects (87%) did not experience any bleeds of spontaneous aetiology. Haemostatic efficacy of BAX326 was excellent or good for >96% of bleeds (100% of minor, 88.9% of moderate and 100% of major bleeds); the majority (88.5%) resolved after 1-2 infusions. Longer T1/2 and lower IR were observed in younger children (<6 years) compared to those aged 6 to 12 years. BAX326 administered as prophylactic treatment as well as for controlling bleeds is efficacious and safe in paediatric patients aged <12 years with haemophilia B.


Asunto(s)
Factor IX/farmacología , Factor IX/uso terapéutico , Hemofilia B/tratamiento farmacológico , Proteínas Recombinantes/farmacología , Proteínas Recombinantes/uso terapéutico , Adolescente , Factores de Edad , Niño , Preescolar , Femenino , Hemofilia B/sangre , Hemofilia B/complicaciones , Hemorragia/tratamiento farmacológico , Hemorragia/etiología , Hemorragia/prevención & control , Humanos , Lactante , Masculino , Premedicación , Retratamiento , Factores de Tiempo , Resultado del Tratamiento
7.
Clin Exp Dermatol ; 40(6): 665-71, 2015 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-25684357

RESUMEN

BACKGROUND: Atopic dermatitis (AD) and contact dermatitis (CD) are both T cell-mediated eczematous disorders. Interleukin (IL)-17, expressed by T helper (Th)17 cells, is involved in recruitment of inflammatory cells into AD and CD skin. AIM: In this study, we investigated whether IL-17 regulates immune dysregulation and affects skin barrier in oxazolone (OXA)-induced AD-like and CD-like disease models in mice, by comparing IL-17 null mutant (IL-17(-/-) ) vs. wild-type (WT) mouse strains in the models. METHODS: IL-17(-/-) and WT Balb/c mice were used for OXA induction of AD-like and CD-like skin diseases. Ear swelling was measured by a micrometer. Skin biopsies were obtained for RNA isolation and histology. Real-time quantitative PCR analysis was performed to quantify mRNA expression of Th2 cytokines. Skin permeability was measured by a vapometer, and structural changes in the skin were evaluated by electron and confocal microscopy. RESULTS: Both OXA-induced AD and CD responses were alleviated in IL-17(-/-) mice relative to WT, as demonstrated by reductions in ear swelling, inflammatory cell infiltration and levels of Th2 cytokines. These endpoints were used to characterize inflammatory dysregulation in both AD and CD models. Skin-barrier dysfunction, measured by increases in transepidermal water loss and dysfunction of lamellar bodies, and reductions in lipid distribution, were seen in both AD and CD in WT mice. In IL-17(-/-) mice, however, these responses were significantly diminished. CONCLUSIONS: The results indicate that the IL-17 gene may play a role in modulating immune dysregulation and affecting skin barrier in OXA-induced AD-like and CD-like skin disease models in the Balb/c mouse.


Asunto(s)
Dermatitis Atópica/inmunología , Dermatitis por Contacto/inmunología , Interleucina-17/inmunología , Animales , Citocinas/metabolismo , Dermatitis Atópica/metabolismo , Dermatitis Atópica/patología , Dermatitis por Contacto/metabolismo , Dermatitis por Contacto/patología , Modelos Animales de Enfermedad , Oído , Ratones , Ratones Endogámicos BALB C , Microscopía Electrónica , Reacción en Cadena en Tiempo Real de la Polimerasa , Células Th2/metabolismo , Pérdida Insensible de Agua/fisiología
8.
Haemophilia ; 20(1): 15-24, 2014 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-23834666

RESUMEN

BAX326 is a recombinant factor IX (rFIX; nonacog gamma) manufactured without the addition of any materials of human or animal origin, and with two viral inactivation steps (solvent/detergent treatment and 15 nm nanofiltration). The aim of this prospective trial was to investigate the pharmacokinetics, haemostatic efficacy and safety of BAX326 in previously treated patients aged 12-65 years with severe or moderately severe haemophilia B. BAX326 was safe and well tolerated in all 73 treated subjects; adverse events considered related to treatment (2.7% incidence, all non-serious) were transient and mild, and no hypersensitivity reactions, inhibitor formation or thrombotic events were observed. Pharmacokinetic (PK) equivalence (n = 28) between BAX326 and a licensed rFIX was confirmed in terms of the ratio of geometric mean AUC(0-72) h per dose. Twice-weekly prophylaxis [mean duration 6.2 (±0.7) months; 1.8 (±0.1) infusions per week, 49.5 (±4.8) IU kg(-1) per infusion] was effective in preventing bleeding episodes, with a significantly lower (79%, P < 0.001) annualized bleed rate (4.2) compared to an on-demand treatment in a historical control group (20.0); 24 of 56 subjects on prophylaxis (43%) did not bleed throughout the study observation period. Of 249 total acute bleeds, 211 (84.7%) were controlled with one to two infusions of BAX326. Haemostatic efficacy at resolution of bleed was rated excellent or good in 96.0% of all treated bleeding episodes. The results of this study indicate that BAX326 is safe and efficacious in treating bleeds and routine prophylaxis in patients aged 12 years and older with haemophilia B.


Asunto(s)
Factor IX/uso terapéutico , Hemofilia B/tratamiento farmacológico , Proteínas Recombinantes , Adolescente , Adulto , Anciano , Coagulación Sanguínea/efectos de los fármacos , Niño , Factor IX/farmacocinética , Femenino , Hemofilia B/sangre , Humanos , Masculino , Persona de Mediana Edad , Premedicación , Calidad de Vida , Índice de Severidad de la Enfermedad , Resultado del Tratamiento , Adulto Joven
9.
Skin Pharmacol Physiol ; 27(3): 132-40, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-24434642

RESUMEN

PURPOSE: Ultraviolet (UV) light from sunlight is an important environmental factor causing hazardous health effects, including various skin disorders. UV irradiation downregulates reactive oxygen species (ROS) elimination pathways, thereby promoting the production of ROS, which are implicated in mitochondria-mediated apoptosis. Walnuts, the seeds of Juglandis sinensis L., are a highly nutritious food and have been shown to have a number of pharmacological activities. To our knowledge, no study on the protective effects of walnuts on human epidermal keratinocytes has been reported previously. Here, we investigated the protective effects of walnuts against UVB (50 mJ/cm(2)) -induced mitochondria-mediated apoptosis. PROCEDURES AND RESULTS: Walnuts significantly and dose-dependently reduced UVB-induced apoptotic toxicity by lactate dehydrogenase assay kit. Walnuts decreased mitochondrial dysfunction, B-cell lymphoma 2 (Bcl-2)-associated X (Bax) protein levels, and cytochrome c release from mitochondria, while increasing Bcl-2 protein levels using immunofluorescence, Western blot, or kit analysis. Moreover, walnuts inhibited caspase-3 activity, indicating an inhibition of the apoptotic cascade, and induced the expression of heme oxygenase and NAD(P)H dehydrogenase via NF-E2-related factor-2 activation using immunofluorescence or Western blot analysis. CONCLUSION: Together, these results demonstrate that walnuts can protect human epidermal keratinocytes against UVB-induced mitochondria-mediated apoptosis by regulating ROS elimination pathways.


Asunto(s)
Apoptosis/efectos de los fármacos , Juglans/química , Queratinocitos/efectos de los fármacos , Extractos Vegetales/farmacología , Apoptosis/efectos de la radiación , Western Blotting , Caspasa 3/metabolismo , Línea Celular , Citocromos c/metabolismo , Relación Dosis-Respuesta a Droga , Epidermis/efectos de los fármacos , Epidermis/efectos de la radiación , Técnica del Anticuerpo Fluorescente , Humanos , Queratinocitos/patología , Queratinocitos/efectos de la radiación , L-Lactato Deshidrogenasa/metabolismo , Mitocondrias/efectos de los fármacos , Mitocondrias/patología , Mitocondrias/efectos de la radiación , Extractos Vegetales/administración & dosificación , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Semillas , Rayos Ultravioleta/efectos adversos , Regulación hacia Arriba/efectos de los fármacos , Proteína X Asociada a bcl-2/metabolismo
10.
Skin Pharmacol Physiol ; 25(2): 93-9, 2012.
Artículo en Inglés | MEDLINE | ID: mdl-22301773

RESUMEN

BACKGROUND: Oxidative radicals are major environmental causes of human skin damage. Oxidative defense factors, including nuclear factor erythroid-derived 2-related factor 2 (Nrf2), are centrally involved in repairing skin cells or protecting them from oxidative damage. Coriandrum sativum L. (coriander; CS) is a commonly consumed food and a traditional phytomedicine in Asia and Europe. In this study, we examined the protective effects of a standardized CS leaf extract against oxidative stress in human HaCaT keratinocytes. METHODS AND RESULTS: CS significantly and dose-dependently protected cells against reduced cell viability caused by H2O2-induced damage, as assessed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Other assays demonstrated that CS protected HaCaT cells by increasing the levels of glutathione and activities of oxidative defense enzymes, such as superoxide dismutase and catalase. Moreover, it increased the expression of activated Nrf2, which plays a crucial role in protecting skin cells against oxidative stress. CONCLUSION: These results suggest that CS protects human keratinocytes from H2O2-induced oxidative stress through antioxidant effects.


Asunto(s)
Coriandrum/química , Queratinocitos/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Extractos Vegetales/farmacología , Antioxidantes/metabolismo , Catalasa/metabolismo , Línea Celular , Supervivencia Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Glutatión/metabolismo , Humanos , Peróxido de Hidrógeno/toxicidad , Queratinocitos/metabolismo , Medicina Tradicional , Factor 2 Relacionado con NF-E2/metabolismo , Extractos Vegetales/administración & dosificación , Superóxido Dismutasa/efectos de los fármacos , Superóxido Dismutasa/metabolismo
11.
Acta Neurol Scand ; 123(5): 325-31, 2011 May.
Artículo en Inglés | MEDLINE | ID: mdl-21426306

RESUMEN

BACKGROUND: It has not been clarified whether the disparity in ischemic stroke outcome between populations is caused by ethnic and geographic differences or by variations in case mix. Propensity score matching (PSM) analysis can overcome some analytical problems but is rarely used in stroke outcome research. This study was to compare the ischemic stroke case-fatality between two PSM cohorts of Sweden and Korea. METHODS: Prognostic variables related to baseline characteristics and stroke care were included in our PSM model. Then, we selected 7675 Swedish and 1220 Korean patients with ischemic stroke from each stroke registers and performed one-to-one matching based on propensity scores of each patient. RESULTS: After PSM, all measured variables were well balanced in 1163 matched subjects, and the 90-day case-fatality was identical 6.2% (HR 0.997, 95%CI 0.905-1.099) in Sweden and Korea. CONCLUSIONS: No difference is found in the 90-day case-fatality in propensity score-matched Swedish and Korean patients with ischemic stroke.


Asunto(s)
Isquemia Encefálica/mortalidad , Accidente Cerebrovascular/mortalidad , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Evaluación de Resultado en la Atención de Salud , Pronóstico , Puntaje de Propensión , Sistema de Registros , República de Corea/epidemiología , Factores de Riesgo , Suecia/epidemiología , Resultado del Tratamiento
12.
Gene Ther ; 16(3): 437-40, 2009 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-18800154

RESUMEN

Billions of neurons are interconnected in the central nervous system (CNS). Identification of specific neuronal circuit is indispensable for understanding the relationship between structure and function in the CNS. The midbrain dopamine (DA) neuron system consists of the retrorubral area (A8), the substantia nigra (SN; A9) and the ventral tegmental area (VTA; A10). We hypothesized that genetic methods using cell-type-specific promoters may offer the possibility to express tracer molecules in DA neurons to facilitate neuronal tracing. To address this, we used the 2.5 kb rat tyrosine hydroxylase (TH) promoter in adenovirus or adeno-associated virus (AAV) to express tracers specifically in DA neurons. We found that stereotaxic injection of TH promoter containing adenoviral construct resulted in cell-type-specific transgene expression in the noradrenaline (NA) neurons of the locus coeruleus (LC). However, it caused a significant toxicity to DA neurons in the SN. In contrast, stereotaxic injection of TH promoter containing AAV to the SN resulted in cell-type-specific transgene expression in DA neurons with no detectable toxicity. Taken together, our results demonstrate that it is possible to selectively trace DA neuronal circuits in rodent brains using the TH promoter in the context of AAV.


Asunto(s)
Dopamina/biosíntesis , Regulación Enzimológica de la Expresión Génica/fisiología , Mesencéfalo/metabolismo , Neuronas/metabolismo , Tirosina 3-Monooxigenasa/genética , Animales , Dependovirus/genética , Técnicas de Transferencia de Gen , Vectores Genéticos , Vías Nerviosas/fisiología , Regiones Promotoras Genéticas , Ratas , Transgenes/fisiología , Tirosina 3-Monooxigenasa/metabolismo
13.
Biochim Biophys Acta ; 1254(1): 45-50, 1995 Jan 03.
Artículo en Inglés | MEDLINE | ID: mdl-7811745

RESUMEN

The relationship between glycosylation, dimerization, and heparin affinity of lipoprotein lipase (LPL) was studied in 3T3-L1 adipocytes. Three forms of LPL subunits were found in normal cells; totally endo H-resistant (57 kDa), partially sensitive (54 kDa), and totally sensitive (51 kDa) forms. LPL in normal cells was active, dimeric, and showed high affinity for heparin. LPL in cells treated with tunicamycin, preventing the transfer of N-linked oligosaccharide chain, was unglycosylated (51 kDa) and inactive. LPL proteins were found as an aggregate, and had low affinity for heparin. After treatment with castanospermine, an inhibitor of ER glucosidase I, 80% of LPL activity was inhibited. Most of LPL proteins were totally endo H-sensitive, present as an aggregate, and had low affinity for heparin. LPL in cells treated with deoxymannojirimycin, an inhibitor of Golgi mannosidase I, was active, dimeric, and had high affinity for heparin as in normal cells. But LPL subunits were all endo H-sensitive. These results suggest that core glycosylation and subsequent removal of glucose residue is required, but processing after Golgi mannosidase I is not necessary for dimerization and acquisition of high heparin affinity of LPL.


Asunto(s)
Adipocitos/enzimología , Heparina/metabolismo , Lipoproteína Lipasa/metabolismo , Células 3T3 , Adipocitos/ultraestructura , Animales , Membrana Celular/enzimología , Cromatografía de Afinidad , Glicósido Hidrolasas/farmacología , Glicosilación , Heparina/química , Lipoproteína Lipasa/química , Lipoproteína Lipasa/aislamiento & purificación , Ratones , Conformación Molecular
14.
Diabetes ; 30(4): 310-3, 1981 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-6781960

RESUMEN

To determine the mechanism of hyperchloremic acidosis during recovery from diabetic ketoacidosis (DKA), serial measurements were made in eight patients of serum and urinary electrolytes and organic acids, and of urinary net acid. On admission, the average decrease in serum total CO2 was 17.5 mmol/L, corresponding to the excess anion gap, 18.5 meq/L, and the serum organic acids, 17.1 meq/L. With the treatment, the anion gap and organic acids decreased by 16.1 and 14.7 meq/L, respectively, but the serum CO2 increased only by 8.4 mmol/L; serum electrolyte balance was maintained by increase in chloride concentration. Fluid retention was insufficient to explain the disparity between the increase in CO2 and the decrease in organic acids. Renal loss of bicarbonate precursors during treatment was modest and was exceeded by renal bicarbonate production. The disparity between the increase in serum CO2 and the decrease in organic acids during treatment of DKA may be explained to a large extent by a difference in volume of distribution between bicarbonate and organic anions. The renal loss of ketone anions before admission, however, is ultimately responsible for the persistence of substantial metabolic acidosis.


Asunto(s)
Acidosis/metabolismo , Cloruros/sangre , Cetoacidosis Diabética/metabolismo , Dióxido de Carbono/sangre , Diabetes Mellitus/metabolismo , Humanos , Equilibrio Hidroelectrolítico
15.
J Bone Miner Res ; 8(7): 789-94, 1993 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-8352061

RESUMEN

The role of net gastrointestinal (GI) alkali absorption in the development of hypocitraturia was investigated. The net GI absorption of alkali was estimated from the difference between simple urinary cations (Ca, Mg, Na, and K) and anions (Cl and P). In 131 normal subjects, the 24 h urinary citrate was positively correlated with the net GI absorption of alkali (r = 0.49, p < 0.001). In 11 patients with distal renal tubular acidosis (RTA), urinary citrate excretion was subnormal relative to net GI alkali absorption, with data from most patients residing outside the 95% confidence ellipse described for normal subjects. However, the normal relationship between urinary citrate and net absorbed alkali was maintained in 11 patients with chronic diarrheal syndrome (CDS) and in 124 stone-forming patients devoid of RTA or CDS, half of whom had "idiopathic" hypocitraturia. The 18 stone-forming patients without RTA or CDS received potassium citrate (30-60 mEq/day). Both urinary citrate and net GI alkali absorption increased, yielding a significantly positive correlation (r = 0.62, p < 0.0001), with the slope indistinguishable from that of normal subjects. Thus, urinary citrate was normally dependent on the net GI absorption of alkali. This dependence was less marked in RTA, confirming the renal origin of hypocitraturia. However, the normal dependence was maintained in CDS and in idiopathic hypocitraturia, suggesting that reduced citrate excretion was largely dietary in origin as a result of low net alkali absorption (from a probable relative deficiency of vegetables and fruits or a relative excess of animal proteins).


Asunto(s)
Álcalis/metabolismo , Citratos/orina , Absorción Intestinal , Cálculos Renales/metabolismo , Acidosis Tubular Renal/metabolismo , Acidosis Tubular Renal/orina , Adulto , Anciano , Calcio , Citratos/uso terapéutico , Ácido Cítrico , Femenino , Humanos , Cálculos Renales/orina , Masculino , Persona de Mediana Edad
16.
Medicine (Baltimore) ; 77(2): 73-82, 1998 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-9556700

RESUMEN

This report describes a case of d-lactic acidosis observed by the authors and then reviews all case reports of d-lactic acidosis in the literature in order to define its clinical and biochemical features and pathogenetic mechanisms. The report also reviews the literature on metabolism of d-lactic acid in humans. The clinical presentation of d-lactic acidosis is characterized by episodes of encephalopathy and metabolic acidosis. The diagnosis should be considered in a patient who presents with metabolic acidosis and high serum anion gap, normal lactate level, negative Acetest, short bowel syndrome or other forms of malabsorption, and characteristic neurologic findings. Development of the syndrome requires the following conditions 1) carbohydrate malabsorption with increased delivery of nutrients to the colon, 2) colonic bacterial flora of a type that produces d-lactic acid, 3) ingestion of large amounts of carbohydrate, 4) diminished colonic motility, allowing time for nutrients in the colon to undergo bacterial fermentation, and 5) impaired d-lactate metabolism. In contrast to the initial assumption that d-lactic acid is not metabolized by humans, analysis of published data shows a substantial rate of metabolism of d-lactate by normal humans. Estimates based on these data suggest that impaired metabolism of d-lactate is almost a prerequisite for the development of the syndrome.


Asunto(s)
Acidosis Láctica/diagnóstico , Acidosis Láctica/epidemiología , Acidosis Láctica/etiología , Acidosis Láctica/metabolismo , Acidosis Láctica/terapia , Adolescente , Adulto , Distribución por Edad , Niño , Preescolar , Heces/microbiología , Femenino , Humanos , Incidencia , Ácido Láctico/metabolismo , Masculino , Persona de Mediana Edad , Síndrome del Intestino Corto/complicaciones
17.
J Clin Epidemiol ; 42(4): 367-75, 1989.
Artículo en Inglés | MEDLINE | ID: mdl-2723697

RESUMEN

Agreement between surrogate and subject reports of current food frequencies and other eating habits, smoking behavior and weight was assessed in 1982-1983 for 180 husbands and wives, aged 45 through 64 years. Agreement was measured by per cent exact agreement and weighted kappa for frequencies of 30 itemized foods or food groups, and for surrogate- and subject-based quintiles of frequencies of eight broad food groups and of vitamin A and C consumption indexes. Surrogate and subject mean frequencies were generally similar, but at the individual level of analysis, agreement varied widely. Agreement was greatest, among the food items and groups, for alcoholic beverages, and among the other items, for smoking status. Extreme misclassification by quintile was very small, but only 40% of persons self-classified in either extreme quintile were similarly classified by their spouses. This level of misclassification may result in the dilution of real relationships between diet and health.


Asunto(s)
Peso Corporal , Recolección de Datos/métodos , Dieta/estadística & datos numéricos , Matrimonio , Fumar/epidemiología , Anciano , Femenino , Encuestas Epidemiológicas , Humanos , Entrevistas como Asunto , Masculino , Persona de Mediana Edad , Distribución Aleatoria , Factores Socioeconómicos
18.
Metabolism ; 34(7): 621-5, 1985 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-4010522

RESUMEN

This study was carried out to investigate the renal handling of d- and l-lactate and the extent of their metabolism in men. Ten healthy male subjects were given an intravenous (IV) infusion of a racemic mixture of d- and l-lactate. At an infusion rate of 1.0 to 1.3 meq/kg body weight of each isomer, d-lactate achieved a concentration in plasma of 1.7 to 3.0 meq/L, and l-lactate 2.8 to 4.2 meq/L. At these levels, fractional excretion of d-lactate ranged from 40% to 65%, while fractional excretion of l-lactate was always less than 5%. At a higher infusion rate, 1.8 to 2.0 meq/kg/h, plasma concentrations of d- and l-lactate reached 4.5 to 6.0 meq/L, and 4.0 to 6.7 meq/L, respectively. Fractional excretion of d-lactate then ranged from 61% to 100%, while that of l-lactate ranged from 9% to 30%. At plasma concentrations of d-lactate less than 3.0 meq/L, reabsorption of l-lactate was nearly complete, but when plasma d-lactate exceeded 3.0 meq/L, reabsorption of l-lactate was considerably impaired. Similarly, for a given concentration of plasma d-lactate, its reabsorption was more efficient when the plasma l-lactate concentration and fractional excretion of l-lactate were low than when they were high. At an infusion rate of d-lactate of 1.0 to 1.3 meq/L, about 90% of the infused lactate was metabolized, and at a higher infusion rate, still more than 75% of the infused lactate was metabolized.(ABSTRACT TRUNCATED AT 250 WORDS)


Asunto(s)
Riñón/metabolismo , Lactatos/metabolismo , Creatinina/sangre , Creatinina/orina , Tasa de Filtración Glomerular , Humanos , Isomerismo , Túbulos Renales/metabolismo , Lactatos/sangre , Lactatos/orina , Masculino , Tasa de Depuración Metabólica
19.
Mol Cells ; 10(1): 108-12, 2000 Feb 29.
Artículo en Inglés | MEDLINE | ID: mdl-10774756

RESUMEN

cDNA clones encoding sweet potato AGPase large subunit (iAGPLI) from the cDNA library constructed from the tuberous root were isolated. Two clones were characterized and named iAGPLI-a and iAGPLI-b. They were 1,661 bp and 1,277 bp in length and contained partial open reading frames of 450 and 306 amino acids, respectively. Both nucleic acid and amino acid sequence identities between iAGPLI-a and iAGPLI-b were 83.8% and 97.3%, respectively. Based on the amino acid sequence analysis, iAGPLI-a and iAGPLI-b share the highest sequence identity (81%) with potato AGPase large subunit. The iAGPLI-a and iAGPLI-b genes were expressed predominantly in the stem and weakly in the tuberous root, and no transcript was expressed in other tissues. The sweet potato genome contains several copies of the iAGPLI gene.


Asunto(s)
ADN Complementario/aislamiento & purificación , Nucleotidiltransferasas/genética , Solanaceae/genética , Secuencia de Aminoácidos , Secuencia de Bases , Northern Blotting , Southern Blotting , ADN Complementario/química , ADN Complementario/genética , ADN de Plantas/genética , Dosificación de Gen , Regulación Enzimológica de la Expresión Génica , Regulación de la Expresión Génica de las Plantas , Glucosa-1-Fosfato Adenililtransferasa , Isoenzimas/genética , Datos de Secuencia Molecular , Filogenia , Polimorfismo Genético , ARN de Planta/genética , ARN de Planta/metabolismo , Alineación de Secuencia , Análisis de Secuencia de ADN , Homología de Secuencia de Aminoácido , Solanaceae/enzimología , Distribución Tisular
20.
Am J Prev Med ; 13(3): 153-8, 1997.
Artículo en Inglés | MEDLINE | ID: mdl-9181201

RESUMEN

OBJECTIVE: Our objective was to evaluate the effectiveness of using simulated patient instructors and the Ockene method to instruct third-year medical students in smoking-cessation counseling techniques. DESIGN: We used a clinical exercise with self-study preparation and simulated patient instructors. METHODS: One hundred fifty-nine students participated in a smoking-cessation counseling session in which cognitive and behavioral endpoints were assessed by simulated patient instructors and the students themselves. RESULTS: Student performance in the cognitive and behavioral components of model smoking-cessation counseling was acceptable. Specific areas of weakness, such as the tendency of students to underemphasize the personal and social benefits of smoking cessation, and to overestimate their competence on a number of skill items, were identified. Student evaluation of the exercise was positive. CONCLUSIONS: Smoking-cessation counseling can be taught effectively to third-year medical students by simulated patient instructors during a clinical clerkship.


Asunto(s)
Prácticas Clínicas , Consejo/educación , Simulación de Paciente , Cese del Hábito de Fumar , Estudios de Evaluación como Asunto , Femenino , Humanos , Masculino , Estudiantes de Medicina/psicología , Enseñanza/métodos
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