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1.
P T ; 44(7): 412-415, 2019 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-31258312

RESUMEN

Chronic obstructive pulmonary disease can be attributed to genetic conditions and predispositions, among other factors. Alpha-1 antitrypsin deficiency (AATD) is a significant risk factor for COPD development and progression, and aggressive screening for all patients with COPD or adult-onset asthma is encouraged.

2.
PLoS One ; 11(8): e0158735, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-27479208

RESUMEN

Agriculture workers have increased rates of airway and skeletal disease. Inhalant exposure to agricultural organic dust extract (ODE) induces bone deterioration in mice; yet, mechanisms underlying lung-bone crosstalk remain unclear. Because Toll-like receptor 2 (TLR2) and TLR4 are important in mediating the airway consequences of ODE, this study investigated their role in regulating bone responses. First, swine facility ODE stimulated wild-type (WT) bone marrow macrophages to form osteoclasts, and this finding was inhibited in TLR4 knock-out (KO), but not TLR2 KO cells. Next, using an established intranasal inhalation exposure model, WT, TLR2 KO and TLR4 KO mice were treated daily with ODE or saline for 3 weeks. ODE-induced airway neutrophil influx and cytokine/chemokine release were similarly reduced in TLR2 and TLR4 KO animals as compared to WT mice. Utilizing micro-computed tomography (CT), analysis of tibia showed loss of bone mineral density, volume and deterioration of bone micro-architecture and mechanical strength induced by ODE in WT mice were significantly reduced in TLR4 but not TLR2 KO animals. Bone marrow osteoclast precursor cell populations were analyzed by flow cytometry from exposed animals. In WT animals, exposure to inhalant ODE increased osteoclast precursor cell populations as compared to saline, an effect that was reduced in TLR4 but not TLR2 KO mice. These results show that TLR2 and TLR4 pathways mediate ODE-induced airway inflammation, but bone deterioration consequences following inhalant ODE treatment is strongly dependent upon TLR4. Thus, the TLR4 signaling pathway appears critical in regulating the lung-bone inflammatory axis to microbial component-enriched organic dust exposures.


Asunto(s)
Contaminantes Atmosféricos/toxicidad , Enfermedades Óseas Metabólicas/etiología , Polvo/análisis , Transducción de Señal/efectos de los fármacos , Receptor Toll-Like 4/metabolismo , Contaminantes Atmosféricos/química , Animales , Enfermedades Óseas Metabólicas/diagnóstico por imagen , Enfermedades Óseas Metabólicas/metabolismo , Células de la Médula Ósea/citología , Líquido del Lavado Bronquioalveolar/química , Líquido del Lavado Bronquioalveolar/citología , Quimiocinas/análisis , Citocinas/análisis , Modelos Animales de Enfermedad , Exposición por Inhalación , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Neutrófilos/citología , Neutrófilos/inmunología , Osteoclastos/citología , Osteoclastos/metabolismo , Osteogénesis/efectos de los fármacos , Neumonía/etiología , Neumonía/metabolismo , Fosfatasa Ácida Tartratorresistente/sangre , Tibia/diagnóstico por imagen , Receptor Toll-Like 2/deficiencia , Receptor Toll-Like 2/genética , Receptor Toll-Like 2/metabolismo , Receptor Toll-Like 4/deficiencia , Receptor Toll-Like 4/genética
3.
Int Immunopharmacol ; 23(1): 356-63, 2014 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-25086344

RESUMEN

Based upon age and type of farming exposures, a wide range of studies demonstrate either protective or deleterious effects of the farming environment on asthma. In this review, we highlight key studies supporting the concept that farming exposure protects children from asthma and atopy based on studies performed largely in European pediatric cohorts. Various types of farming in certain regions appear to have a greater effect on asthma protection, as does the consumption of unpasteurized milk. In the United State, where concentrated animal feeding operations (CAFOs) are more common, asthma is increased in children exposed especially to swine CAFOs; whereas, rates of atopy and allergy are lower in these children. We also review studies evaluating the role of farming exposures both as a child and/or as an adult on asthma seen in adults. The importance of microbes in farming environments and the contribution of various components of the innate immune system including toll-like receptors to the underlying mechanisms of asthma related to farming exposures are also reviewed.


Asunto(s)
Asma/inmunología , Exposición a Riesgos Ambientales , Inmunidad Innata , Receptores Toll-Like/inmunología , Adulto , Alimentación Animal/efectos adversos , Animales , Asma/prevención & control , Bovinos , Niño , Europa (Continente) , Humanos , Leche/inmunología , Porcinos , Estados Unidos
4.
J Grad Med Educ ; 6(4): 733-7, 2014 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-26140127

RESUMEN

BACKGROUND: Internal medicine residents receive limited training on how to be good stewards of health care dollars while preserving high-quality care. INTERVENTION: We implemented a clinical process change and an educational intervention focused on the appropriate use of preoperative diagnostic testing by residents at a Veterans Administration (VA) medical center. METHODS: The clinical process change consisted of reducing routine ordering of preoperative tests in the absence of specific indications. Residents received a short didactic session, which included algorithms for determining the appropriate use of perioperative diagnostic testing. One outcome was the average cost savings on preoperative testing for a continuous cohort of patients referred for elective knee or hip surgery. Resident knowledge and confidence prior to and after the intervention was measured by pre- and posttest. RESULTS: The mean cost of preoperative testing decreased from $74 to $28 per patient after the dual intervention (P < .001). The bulk of cost savings came from elimination of unnecessary blood and urine tests, as well as reduced numbers of electrocardiograms and chest radiographs. Among residents who completed the pretest and posttest, the mean score on the pretest was 54%, compared with 80% on the posttest (P  =  .027). Following the educational intervention, 70% of residents stated they felt "very comfortable" ordering appropriate preoperative testing (P  =  .006). CONCLUSIONS: This initiative required few resources, and it simultaneously improved the educational experience for residents and reduced costs. Other institutions may be able to adopt or adapt this intervention to reduce unnecessary diagnostic expenditures.

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