Low cortisol levels in active juvenile idiopathic arthritis

The aim of our study was to evaluate the neuroendocrine system in patients with juvenile idiopathic arthritis (JIA) regarding the activity of disease. Twenty-one JIA patients (mean age ± standard deviation 10.5 ± 4.1 years) were included. None of the patients was taking steroids or antitumor necrosis factor-α therapy during this study. Ten healthy volunteers and ten volunteers with upper respiratory tract infection composed the control groups. Furthermore, ten of the 21 JIA patients were also evaluated during the remission period. Erythrocyte sedimentation rate, C-reactive protein, adrenocorticotropic hormone (ACTH), cortisol, prolactin, insulin-like growth factor-1 (IGF-1), insulin-like growth factor-binding protein 3, free T3, free T4, thyroid-stimulating hormone, interleukin-6 (IL-6) levels, and 24-h urinary cortisol were evaluated both during the active period and remission. The median levels of ACTH and cortisol at 08:00 a.m. were significantly lower in patients with active JIA than patients in remission period and the control groups (p < 0.05). Furthermore, the median level of urine cortisol in active JIA patients was significantly lower than remission period and control groups (p < 0.05). The median level of IGF-1 was significantly lower in active patients than that of remission (p < 0.05). The median level of IL-6 in active JIA patients was significantly higher than those in remission and control groups (p < 0.05). Our preliminary study suggested that impaired secretion of adenohypophyseal hormones and distorted bilateral interactions between the immune and endocrine systems in JIA. Further studies are needed to clarify the consequences of the impaired hormone secretion in JIA.     

Exquisite sensitivity to subsecond, picomolar nitric oxide transients conferred on cells by guanylyl cyclase-coupled receptors

Nitric oxide (NO) functions as a diffusible transmitter in most tissues of the body and exerts its effects by binding to receptors harboring a guanylyl cyclase transduction domain, resulting in cGMP accumulation in target cells. Despite its widespread importance, very little is known about how this signaling pathway operates at physiological NO concentrations and in real time. To address these deficiencies, we have exploited the properties of a novel cGMP biosensor, named δ-FlincG, expressed in cells containing varying mixtures of NO-activated guanylyl cyclase and cGMP-hydrolyzing phosphodiesterase activity. Responsiveness to NO, signifying a physiologically relevant rise in cGMP to 30 nM or more, was seen at concentrations as low as 1 pM, making cells by far the most sensitive NO detectors yet encountered. Even cells coexpressing phosphodiesterase-5, a cGMP-activated isoform found in many NO target cells, responded to NO in concentrations as low as 10 pM. The dynamics of NO capture and signal transduction was revealed by administering timed puffs of NO from a local pipette. A puff lasting only 100 ms, giving a calculated peak intracellular NO concentration of 23 pM, was detectable. The results could be encapsulated in a quantitative model of cellular NO-cGMP signaling, which recapitulates the NO responsiveness reported previously from crude cGMP measurements on native cells, and which explains how NO is able to exert physiological effects at extremely low concentrations, when only a tiny proportion of its receptors would be occupied.     

Interrelations of serum leptin levels with adrenocorticotropic hormone,basal cortisol and dehydroepiandrosterone sulphate levels in patients with metabolic syndrome

ObjectivesThe aim of this study was to determine serum leptin levels, adrenocorticotropic hormone, basal cortisol and dehydroepiandrosterone sulphate levels in patients with metabolic syndrome.Material and methodsThe study was comprised of 35 female patients and who applied to Eskisehir Osmangazi University Medicine Faculty Endocrinology polyclinic due to the symptoms of obesity and diagnosed as having metabolic syndrome.ResultsPlasma adrenocorticotropic hormone and dehydroepiandrosterone sulphate levels of metabolic syndrome group were lower than controls (P < 0.001, P < 0.05, respectively). Serum basal cortisol, resistin and leptin levels of metabolic syndrome group were higher than control (P < 005, P < 0.01, P < 0.001, respectively).ConclusionsOur data suggest that hormonal changes in metabolic syndrome pathogenesis may be related with increased leptin levels and for that reason leptin may be an important marker in metabolic syndrome.     

Combined administration of secretin and oxytocin inhibits chronic colitis and associated activation of forebrain neurons

Background The pathogenesis of inflammatory bowel disease is unknown; however, the disorder is aggravated by psychological stress and is itself psychologically stressful. Chronic intestinal inflammation, moreover, has been reported to activate forebrain neurons. We tested the hypotheses that the chronically inflamed bowel signals to the brain through the vagi and that administration of a combination of secretin (S) and oxytocin (OT) inhibits this signaling. Methods Three daily enemas containing 2,4,6‐trinitrobenzene sulfonic acid (TNBS), which were given to rats produced chronic colitis and ongoing activation of Fos in brain neurons. Key Results Fos was induced in neurons in the paraventricular nucleus of the hypothalamus, basolateral amygdala, central amygdala, and piriform cortex. Subdiaphragmatic vagotomy failed to inhibit this activation of Fos, suggesting that colitis activates forebrain neurons independently of the vagi. When administered intravenously, but not when given intracerebroventricularly, in doses that were individually ineffective, combined S/OT prevented colitis‐associated activation of central neurons. Strikingly, S/OT decreased inflammatory infiltrates into the colon and colonic expression of tumor necrosis factor‐α and interferon‐γ. Conclusions & Inferences These observations suggest that chronic colonic inflammation is ameliorated by the systemic administration of S/OT, which probably explains the parallel ability of systemic S/OT to inhibit the colitis‐associated activation of forebrain neurons. It is possible that S and OT, which are endogenous to the colon, might normally combine to restrict the severity of colonic inflammatory responses and that advantage might be taken of this system to develop novel means of treating inflammation‐associated intestinal disorders.     

Does obesity impact lymph node retrieval in colon cancer surgery?

Background

Evaluation of lymph nodes is important for the optimal treatment of colon adenocarcinoma. Few studies have assessed whether lymph node harvest is compromised by obesity. We hypothesized that lymph node retrieval in colon cancer resection would be reduced in obese patients.

Methods

Patients undergoing resection for colon adenocarcinoma diagnosed from 2000 to 2007 were reviewed retrospectively and stratified by body mass index (BMI). Lymph node harvest was evaluated.

Results

A total of 401 patients were included. Their mean age was 72.8 years, and 44% were men. Their mean BMI was 28.2 kg/m². Mean lymph node recovery among BMI groups was as follows: BMI less than 18.5 was 20.6; BMI of 18.5 to 24.9 was 25.1; BMI of 25 to 29.9 was 23.1; BMI of 30 to 34.9 was 22.4; BMI of 35 to 39.9 was 19.0; and BMI of 40 or greater was 21.1 nodes (P = .321). Surgical time increased with increasing BMI (P = .005). Adequacy of node harvest differed by stage (P = .007), left-sided versus right-sided resections (P = .001), and pathology technician (P = .001).

Conclusions

Lymph node retrieval was not affected by BMI.     

Designing siRNA-conjugated plant oil-based nanoparticles for gene silencing and cancer therapy

Abstract

In this study, the anticancer activities of two siRNA carriers were compared using a human lung adenocarcinoma epithelial cell line (A549). Firstly, poly(styrene)-graft-poly(linoleic acid) (PS-g-PLina) and poly(styrene)-graft-poly(linoleic acid)-graft-poly(ethylene glycol) (PS-g-PLina-g-PEG) graft copolymers were synthesized by free-radical polymerization. PS-PLina and PS-PLina-PEG nanoparticles (NPs) were prepared by solvent evaporation method and were then characterized. The size was found as 150?±?10?nm for PS-PLina and 184?±?6?nm for PS-PLina-PEG NPs. The NPs were functionalized with poly(l-lysine) (PLL) for c-myc siRNA conjugation. siRNA entrapment efficiencies were found in the range of 4–63% for PS-PLina-PLL and 6–42% for PS-PLina-PEG-PLL NPs. The short-term stability test was realised for 1?month. siRNA release profiles were also investigated. In vitro anticancer activity of siRNA-NPs was determined by MTT, flow cytometry, and fluorescence microscopy analyses. Obtained findings showed that both NPs systems were promising as siRNA delivery tool for lung cancer therapy.     

Preterm Infant Swallowing of Thin and Nectar-Thick Liquids: Changes in Lingual–Palatal Coordination and Relation to Bolus Transit

Tongue–soft palate coordination and bolus head pharyngeal transit were studied by means of postacquisition kinematic analysis of videofluoroscopic swallowing images of ten preterm infants referred from hospital NICUs due to poor oral feeding and suspicion of aspiration. Sequences of coordinated tongue–soft palate movements and bolus transits during swallows of thin-consistency and nectar-thick-consistency barium were digitized, and time series data were used to calculate continuous relative phase, a measure of coordination. During swallows of nectar-thick compared to thin barium, tongue–soft palate coordination was more likely to be antiphase, bolus head pharyngeal transit time was longer, and coordination was significantly correlated with bolus head pharyngeal transit. Analysis of successive swallows indicated that tongue–soft palate coordination variability decreased with nectar-thick but not with thin-consistency barium. Together, the results suggest that slower-moving bolus transits may promote greater opportunity for available sensory information to be used to modulate timing of tongue–soft palate movements so that they are more effective for pumping liquids.