Resistin is elevated in cystic fibrosis sputum and correlates negatively with lung function

Background

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.

Attachment to Caregivers and Type 1 Diabetes in Children

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.     

Complications in Intermediate Uveitis: Prevalence,Time of Onset,and Effects on Vision in Short-Term and Long-Term Follow-Up

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.     

“Vinylogs” and “Acetylenylogs” of β-Adrenergic Agents

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 K_B's ranging from 73–93 nM while 3,4-dichloro substitution ( 5e ) markedly reduced antagonist potency (K_B = 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.     

Sodium MRI of the human kidney at 3 Tesla.

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.     

Tapered intraluminal versus imbricated extraluminal valve: comparison of two continence mechanisms for urinary diversion

One of the major limitations of continent intestinal reservoirs currently in use is failure of the efferent continence mechanisms. Unsatisfactory results have been reported in the literature in up to 40% of cases. While progress has been made toward better continence in urinary diversions, evolution of the actual continence mechanisms has been along two rather distinct paths: those with a valve mechanism placed inside the pouch (either by intussusception or surgical insertion), and those with the valve outside to the pouch (by imbrication of an externally located ileal segment). A canine experimental model was used to investigate a type of intraluminal continence mechanism and to compare it to an extraluminal imbricated ileocecal valve. In eight mongrel dogs a reservoir was made out of ascending and transverse colon with two different valve mechanisms--one intraluminal and one extraluminal--connected via separate stomas to the skin. Radiographic, sonographic, endoscopic and urodynamic studies of the pouch and its outlets were performed. Results showed that, in contrast to the extraluminal valve, continence in the intraluminal valve was volume dependent. The valve closing pressure of the intraluminal continence mechanism increased far beyond the values of the extraluminal valve (50.38 vs. 30.12 cm. H2O) at maximum pouch filling. Leakage of the intraluminal valve was observed at significantly higher pouch volumes than in the extraluminal valve (348 cc vs. 215 cc). In view of these results, the volume dependent intraluminal valve mechanism appears superior to an extraluminal type, especially at higher pouch volumes.     

Pre-clinical Cushing's syndrome: an unexpected frequent cause of poor glycaemic control in obese diabetic patients

OBJECTIVE Autonomous cortisol secretion without clinical stigmata of Cushing's syndrome (CS) has been recently recognized and termed pre-clinical or sub-clinical CS. The common assumption is that CS is an extremely rare cause of uncontrolled diabetes; however, the prevalence of this entity has not been studied. We assessed the prevalence of pre-clinical CS among obese patients with uncontrolled diabetes. PATIENTS AND DESIGN (1) In a retrospective analysis, the medical records of 63 patients with endogenous CS were reviewed. (2) In a cross-sectional study, 90 obese patients (BMI >25 kg/m²) followed in a University Hospital and the local Health Fund endocrine and diabetes clinics, with poorly controlled diabetes (glycosylated haemoglobin >9%), underwent an overnight 1 mg dexamethasone suppression. In patients with non-suppressible cortisol levels (>140 nmol/l), Liddle's 2 and 8 mg dexamethasone suppression tests and imaging studies were performed. MEASUREMENTS The prevalence of poorly controlled diabetes, the major presenting symptom of CS, was assessed in the retrospective analysis. The prevalence of ‘true’ CS and the false positive rate in the overnight dexamethasone suppression test were calculated. The endocrine evaluation of the patients with pre-clinical CS and the effects of surgical cure on glycaemic control are described. RESULTS In the retrospective analysis, 11 (17.5%) had diabetes and 2 (3.2%) lacked the classic physical characteristics of the syndrome. In the cross-sectional study, 4 patients failed to suppress plasma cortisol (<140 nmol/l). In one patient the diagnosis of CS was not confirmed by a standard Liddle’s test and was therefore considered false positive. In the other 3, the diagnosis of CS was confirmed (prevalence of 3.3%, 95% confidence interval 1–9%). In all other patients the overnight cortisol suppression test was normal (cortisol level 47.3 ± 2.5 nmol/l (mean ± SEM)). After surgical treatment of CS, glycaemic control was markedly improved in all 5 patients (2 from retrospective and 3 from cross-sectional studies). CONCLUSIONS The prevalence of pre-clinical Cushing's syndrome in obese patients with poorly controlled diabetes appears to be considerably higher than previously believed. The overnight dexamethasone suppression test proved to be a simple, sensitive and highly specific screening test for Cushing's syndrome despite the presence of obesity and hyperglycaemia.     

Reduction of scar formation in full-thickness wounds with topical celecoxib treatment

Adult wound repair occurs with an initial inflammatory response, reepithelialization, and the formation of a permanent scar. Although the inflammatory phase is often considered a necessity for successful adult wound healing, fetal healing studies have shown the ability to regenerate skin and to heal wounds in a scarless manner in the absence of inflammation. The cyclooxygenase-2 (COX-2) enzyme, a known mediator of inflammation, has been shown to contribute to a variety of inflammatory conditions and to the development of cancer in many organs. To examine the role of COX-2 in the wound healing process, incisional wounds were treated topically with the anti-inflammatory COX-2 inhibitor celecoxib. Acutely, celecoxib inhibited several parameters of inflammation in the wound site. This decrease in the early inflammatory phase of wound healing had a significant effect on later events in the wound healing process, namely a reduction in scar tissue formation, without disrupting reepithelialization or decreasing tensile strength. Our data suggest that in the absence of infection, adult wound healing is able to commence with decreased inflammation and that anti-inflammatory drugs may be used to improve the outcome of the repair process in the skin by limiting scar formation.