Resistin is an immunometabolic mediator that is elevated in several inflammatory disorders. A ligand for Toll-like receptor 4, resistin modulates the recruitment and activation of myeloid cells, notably neutrophils. Neutrophils are major drivers of cystic fibrosis (CF) lung disease, in part due to the release of human neutrophil elastase- and myeloperoxidase-rich primary granules, leading to tissue damage. Here we assessed the relationship of resistin to CF lung disease.
Methods
Resistin levels were measured in plasma and sputum from three retrospective CF cohorts spanning a wide range of disease. We also assessed the ability of neutrophils to secrete resistin upon activation in vitro. Finally, we constructed a multivariate model assessing the relationship between resistin levels and lung function.
Results
Plasma resistin levels were only marginally higher in CF than in healthy control subjects. By contrast, sputum resistin levels were very high in CF, reaching 50–100 fold higher levels than in plasma. Among CF patients, higher plasma resistin levels were associated with allergic bronchopulmonary aspergillosis, and higher sputum resistin levels were associated with CF-related diabetes. Mechanistically, in vitro release of neutrophil primary granules was concomitant with resistin secretion. Overall, sputum resistin levels were negatively correlated with CF lung function, independently of other variables (age, sex, and genotype).
Conclusions
Our data establish relationships between resistin levels in the plasma and sputum of CF patients that correlate with disease status, and identify resistin as a novel mechanistic link between neutrophilic inflammation and lung disease in CF. 相似文献
Attachment is a behavioral and physiological system, which enables individual’s dynamic adaptation to its environment. Attachment develops in close interaction between an infant and his/her mother, plays an important role in the development of the infant’s brain, and influences the quality of interpersonal relationships throughout life.Security of attachment is believed to influence individual response to stress, exposing insecurely organized individuals to deregulated autonomic nervous system and exaggerated hypothalamic-pituitary-adrenal activity, which, in turn, produces increased and prolonged exposure to stress-hormones. Such stress responses may have considerable implications for the development of diverse health-risk conditions, such as insulin resistance and hyperlipidemia, shown by numerous studies.Although the mechanisms are not yet fully understood, there is compelling evidence highlighting the role of psychological stress in the development of type 1 diabetes (T1D). One of the possible contributing factors for the development of T1D may be the influence of attachment security on individual stress reactivity. Thus, the suggestion is that insecurely attached individuals are more prone to experience increased and prolonged influence of stress hormones and other mechanisms causing pancreatic beta-cell destruction.The present paper opens with a short overview of the field of attachment in children, the principal attachment classifications and their historic development, describes the influence of attachment security on individual stress-reactivity and the role of the latter in the development of T1D. Following is a review of recent literature on the attachment in patients with T1D with a conclusion of a proposed role of attachment organization in the etiology of T1D. 相似文献
Purpose: To study the prevalence and time of onset of ocular complications in intermediate uveitis (IU) and to assess their effects on visual outcome in short-term and long-term follow-up.
Methods: A retrospective cohort study of patients with IU who had a minimal follow-up of one year.
Results: 96 patients (174 eyes, 70% females) were included with a mean age at presentation of 30 years. Children constituted 38% of all patients. Mean follow- up was 64.9 months. Pars planitis was the most common form followed by sarcoidosis and multiple sclerosis. Cystoid macular edema (CME), cataract, epiretinal membrane and posterior synechiae were the most prevalent complications. Posterior synechiae, band keratopathy, cataract and papillitis at presentation were associated with worse presenting visual acuity (VA). Of the late-onset complications, glaucoma/ocular hypertension (OHT) was the most significantly associated with worse long-term VA. Most sight-threatening complications (namely CME and glaucoma) were diagnosed at presentation while late complications predominantly affected the posterior segment and included among others peripheral retinal elevations, vasoproliferative tumors, and vitreous hemorrhage. Median LogMAR VA improved at short-term and long-term follow-up, from 0.2 to 0.1 (p<0.001). Subgroup analysis revealed significant VA improvement for eyes with all the different complications except for eyes with glaucoma/OHT.
Conclusion: IU is a chronic low-grade uveitis that may be associated with protean early and late complications of the anterior or posterior segments or both. Optimal treatment regimens are imperative for the strict control of inflammation and proper management of complications thus allowing a favorable long-term prognosis. 相似文献
Vinylogous (Groups III and V ) and acetylenologous (Group IV ) analogs of the classical β-adrenergic agents — stimulants and blockers — were prepared in order to evaluate the effect of degree of saturation, position of unsaturation and rigidity of the chain linking the aromatic ring and the amino containing functional group on biological activity. Derivatives from Group III , which represent 4-aryl-3-butenyl-2-ol-amine analogs of Group II , retained β1-adrenoceptor antagonist activity albeit substantially less potent (50–200-fold) than that possessed by their aryloxy counterparts. Consistent with the SAR for Group II compounds, substitution at position 2 of the aromatic ring yielded the most potent antagonists ( 5a, 5d, 5g ), with KB's ranging from 73–93 nM while 3,4-dichloro substitution ( 5e ) markedly reduced antagonist potency (KB = 2,400 nM). Agonist activity was also noted for 5b and 5d , suggesting that these compounds may be best classified as partial agonists. Representatives from Groups IV and V were inactive as antagonists at the β1-adrenoceptor confirming the importance of the spatial relationship between the hydroxyl and the amino nitrogen. 相似文献
The sodium concentration gradient in the kidney (from the cortex to the medulla) serves to regulate fluid homeostasis and is tightly coupled to renal function. It was previously shown that renal function and pathophysiology can be characterized in rat kidneys by measuring the sodium gradient with (23)Na MRI. This study demonstrates for the first time the ability of (23)Na MRI to map the distribution of sodium in the human kidney and to quantify the corticomedullary sodium gradient. The study was performed on a 3T Signa LX scanner (GE) using an in-house-built quadrature surface coil. (23)Na images of volunteers were acquired using a 3D coronal gradient-echo sequence at a spatial resolution of 0.3 x 0.3 x 1.5 cm(3) in a 25-min scan time. The signal intensity (relative to the noise) increased linearly from the cortex to each of the medullae with a mean slope of 1.6 +/- 0.2 in relative arbitrary units per mm (Rel.u./mm, N = 6) and then decreased, as expected, toward the renal pelvis. Water deprivation (12 hr) induced a significant increase of 25% (P < 0.05) in this gradient. Based on these results, we suggest that sodium MRI can serve as a valuable noninvasive method for functional imaging of the human kidney. 相似文献
Spinal axons in the larval sea lamprey regenerate following a complete spinal transection. It is not known whether regenerating growth cones require contact with cellular elements or whether the basement membrane and collagenous meninx primitiva which surround the spinal cord are sufficient for neurite out-growth. To determine this, a freeze lesion was made which severed axons, destroyed neuronal perikarya, and greatly reduced the number of glial cells. After at least 10 weeks of recovery, 50 neurites from 31 Müller and Mauthner axons were labeled by intracellular injection of HRP. Eighty-six percent of these neurites did not regenerate into the lesion site. No neurites grew through the lesion. No animals recovered coordinated swimming. These results suggest that glial and/or neuronal surfaces are required for axonal regeneration. Moreover, a monolayer of glial cells appears to be suboptimal and a three-dimensional matrix of cells may be necessary to promote regeneration in the lamprey spinal cord. 相似文献
BACKGROUND CONTEXT: Retrolisthesis is relatively rare but when present has been associated with increased back pain and impaired back function. Neither the prevalence of this condition in individuals with lumbar disc herniations nor its possible relation to preoperative back pain and dysfunction has been well studied. PURPOSE: The purposes of this study were as follows: (1) to determine the prevalence of retrolisthesis (alone or in combination with other degenerative conditions) in individuals with confirmed L5-S1 disc herniation who later underwent lumbar discectomy; (2) to determine if there is any association between retrolisthesis and degenerative changes within the same vertebral motion segment; and (3) to determine the relation between retrolisthesis (alone or in combination with other degenerative conditions) and preoperative low back pain, physical function, and quality of life. STUDY DESIGN/SETTING: Cross-sectional study. PATIENT SAMPLE: A total of 125 individuals were identified for incorporation into this study. All patients had confirmed L5-S1 disc herniation on magnetic resonance imaging (MRI) and later underwent L5-S1 discectomy. All patients were enrolled in the Spine Patient Outcomes Research Trial (SPORT) study; data were obtained from the multi-institutional database comprised of SPORT patients from across the United States. OUTCOME MEASURES: Retrolisthesis, degenerative change on MRI, and Modic changes. METHODS: MRI scans of the lumbar spine were assessed at spinal level L5-S1 for all 125 patients. Retrolisthesis was defined as posterior subluxation of 8% or more. Disc degeneration was defined as any loss of disc signal on T2 imaging. Modic changes were graded 1 to 3 and collectively classified as vertebral endplate degenerative changes. The presence of facet arthropathy and ligamentum flavum hypertrophy was classified jointly as posterior degenerative changes. RESULTS: The overall incidence of retrolisthesis at L5-S1 in our study was 23.2%. Retrolisthesis combined with posterior degenerative changes, degenerative disc disease, or vertebral endplate changes had incidences of 4.8%, 16%, and 4.8% respectively. The prevalence of retrolisthesis did not vary by sex, age, race, smoking status, or education level when compared with individuals with normal sagittal alignment. However, individuals with retrolisthesis were more likely to be receiving workers' compensation than those without retrolisthesis. Increased age was found to be associated with individuals having vertebral endplate degenerative changes (both alone and in conjunction with retrolisthesis) and degenerative disc disease. Individuals who had retrolisthesis with concomitant vertebral endplate degenerative changes were more often smokers and had no insurance. The presence of retrolisthesis was not associated with an increased incidence of having degenerative disc disease, posterior degenerative changes, or vertebral endplate changes. No statistical significance was found between the presence of retrolisthesis on the degree of patient preoperative low back pain and physical function. Patients with degenerative disc disease were found to have increased leg pain compared with those patients without degenerative disc changes. CONCLUSIONS: We found no significant relationship between retrolisthesis in patients with L5-S1 disc herniation and worse baseline pain or function. It is possible that the contribution of pain or dysfunction related to retrolisthesis was far overshadowed by the presence of symptoms caused by the concomitant disc herniation. It remains to be seen whether retrolisthesis will affect outcome after discectomy in these patients. 相似文献
OBJECTIVE: To evaluate the user experience and acceptability of an electronic patient monitoring system. SETTING AND PARTICIPANTS: 822 Military and civilian personnel at a health clinic at a major US military headquarters used an Internet and telephone-based electronic monitoring system to report vaccination-site responses and symptoms after receiving the smallpox vaccination. Focus groups of vaccinees were conducted to help develop a survey about the experience that was distributed to 379 vaccinees (96% completion rate). RESULTS: Users of the electronic monitoring system reported that it was fast and easy to use and reported they would use a system like this again and recommend an electronic monitoring system to a friend or relative. Most users (84%) were comfortable with a physician tracking their vaccine reaction using their electronic reports, but only half (51%) were comfortable with eliminating the post-vaccination follow-up visit with their health-care provider based on their electronic reports. CONCLUSIONS: This electronic monitoring system was well received by vaccinees and allowed health-care providers to track the status of vaccinees. However, vaccinees were not comfortable replacing a physician visit with electronic monitoring, at least for the smallpox vaccination. A monitoring system like this may be useful in public health settings, such as mass vaccination or prophylaxis during a bioterrorism event, a pandemic influenza outbreak, or another public health emergency. 相似文献