Glucocorticoid sensitivity in Behcet's disease

WOS: 000209773300007PubMed ID: 23781311Objective: Glucocorticoid (GC) sensitivity is highly variable among individuals and has been associated with susceptibility to develop (auto-) inflammatory disorders. The purpose of the study was to assess GC sensitivity in Behcet's disease (BD) by studying the distribution of four GC receptor (GR) gene polymorphisms and by measuring in vitro cellular GC sensitivity. Methods: Healthy controls and patients with BD in three independent cohorts were genotyped for four functional GR gene polymorphisms. To gain insight into functional differences in in vitro GC sensitivity, 19 patients with BD were studied using two bioassays and a whole-cell dexamethasone-binding assay. Finally, mRNA expression levels of GR splice variants (GR-alpha and GR-beta) were measured. Results: Healthy controls and BD patients in the three separate cohorts had similar distributions of the four GR polymorphisms. The Bcll and 9 beta minor alleles frequency differed significantly between Caucasians and Mideast and Turkish individuals. At the functional level, a decreased in vitro cellular GC sensitivity was observed. GR number in peripheral blood mononuclear cells was higher in BD compared with controls. The ratio of GR-alpha/GR-beta mRNA expression levels was significantly lower in BD. Conclusions: Polymorphisms in the GR gene are not associated with susceptibility to BD. However, in vitro cellular GC sensitivity is decreased in BD, possibly mediated by a relative higher expression of the dominant negative GR-b splice variant. This decreased in vitro GC sensitivity might play an as yet unidentified role in the pathophysiology of BD.The Dutch Arthritis AssociationThis work was supported by a grant from The Dutch Arthritis Association

Genome-wide association study identifies variants in the MHC class I, IL10, and IL23R-IL12RB2 regions associated with Behcet's disease

Behcet's disease is a genetically complex disease of unknown etiology characterized by recurrent inflammatory attacks affecting the orogenital mucosa, eyes and skin. We performed a genome-wide association study with 311,459 SNPs in 1,215 individuals with Behcet's disease (cases) and 1,278 healthy controls from Turkey. We confirmed the known association of Behcet's disease with HLA-B*51 and identified a second, independent association within the MHC Class I region. We also identified an association at IL10 (rs1518111, P = 1.88 x 10(-8)). Using a meta-analysis with an additional five cohorts from Turkey, the Middle East, Europe and Asia, comprising a total of 2,430 cases and 2,660 controls, we identified associations at IL10 (rs1518111, P = 3.54 x 10(-18), odds ratio = 1.45, 95% CI 1.34-1.58) and the IL23R-IL12RB2 locus (rs924080, P = 6.69 x 10(-9), OR = 1.28, 95% CI 1.18-1.39). The disease-associated IL10 variant (the rs1518111 A allele) was associated with diminished mRNA expression and low protein production

Mechanisms and therapeutic applications of electromagnetic therapy in Parkinson's disease

© 2015 Vadalà et al. Electromagnetic therapy is a non-invasive and safe approach for the management of several pathological conditions including neurodegenerative diseases. Parkinson's disease is a neurodegenerative pathology caused by abnormal degeneration of dopaminergic neurons in the ventral tegmental area and substantia nigra pars compacta in the midbrain resulting in damage to the basal ganglia. Electromagnetic therapy has been extensively used in the clinical setting in the form of transcranial magnetic stimulation, repetitive transcranial magnetic stimulation, high-frequency transcranial magnetic stimulation and pulsed electromagnetic field therapy which can also be used in the domestic setting. In this review, we discuss the mechanisms and therapeutic applications of electromagnetic therapy to alleviate motor and non-motor deficits that characterize Parkinson's disease

Cataractogenesis after Repeat Laser in situ Keratomileusis

There has been the unsubstantiated clinical impression that laser refractive surgery accelerates cataract development along with solid experimental data about the cataractogenic effects of excimer laser treatment. We present the first documented case of significant cataract formation in a young myope after repeat excimer laser ablation necessitating phacoemulsification with a posterior chamber implant. Proposed explanations include focusing of the ablation wave on the posterior capsule (acoustic wave lens epithelial damage), photooxidative stress of the lens (ultraviolet and inflammatory oxidative stress), and corticosteroid-induced cataract (lens toxicity)

Morbosità da parto cesareo multiplo

Obiettivo: quantificare il rischio materno associato a parti cesarei (PC) multipli e determinare se il terzo cesareo definisce una soglia per l’aumento della morbosità. Metodi: dal gennaio 1997 al gennaio 2002, le cartelle cliniche relative a 3.191 donne che avevano partorito con taglio cesareo al nostro centro di riferimento ostetrico, sono state esaminate per alcuni indicatori scelti di morbosità materna. Le donne sono state assegnate a diversi gruppi in base al numero di PC, e la frequenza di ciascun indicatore è stata determinata. Per confrontare il rischio nei vari gruppi e rispetto al terzo cesareo, è stato poi ricavato, tra le donne raggruppate in base al numero di PC consecutivi, un punteggio composito per ogni indicatore. Risultati: sulla base di tutti gli indicatori studiati, la morbosità aumentava con i successivi PC fino a tutto il terzo. Rispetto a quest’ultimo, tuttavia, il rischio di morbosità importante risultava significativamente più elevato con il quinto, e molto peggio con il sesto per quanto riguarda placenta previa [odds ratio (OR) = 3,8; intervallo di confidenza al 95% (IC 95%) = 1,9-7,4], placente accreta (OR = 6,1; IC 95% = 2,0-18,4) e isterectomia (OR = 5,9; IC 95% = 1,5-24,4). Ma il terzo e il quarto PC comportavano lo stesso rischio di importante morbosità per placenta previa (OR = 1,4; IC 95% = 0,8-2,2), placenta accreta (OR = 1,0; IC 95% = 0,3- 2,9) e isterectomia (OR = 0,3; IC 95% = 0,0-2,7). Conclusioni: il terzo cesareo non definisce una soglia per l’aumento del rischio materno. La morbosità complessiva aumenta invece continuamente a ogni successivo PC. Tuttavia, in particolare per la morbosità importante dovuta alla triade placenta previa, placenta accreta e isterectomia durante il PC, il quarto PC comporta lo stesso rischio del terzo

Hot-knife conization of the cervix: clinical and pathologic findings from a study introducing a new technique.

OBJECTIVE: To introduce an alternative method for conization of the cervix using a Teflon-coated hot knife and to evaluate thermal distortion, adequacy of excision, operating time, blood loss, and short- and long-term effects of this method. METHODS: Between 1987-1993, 88 patients underwent cervical conization using a Teflon-coated hot knife at temperatures ranging from 110-130C. Histopathologic slides were reviewed simultaneously by two pathologists, who assessed thermal distortion, adequacy of excision, and interpretability of the surgical margins. Clinical information was obtained prospectively, including operating time, blood loss, and depth and volume of the excised cone. In addition, data were accumulated retrospectively from 40 randomly selected patients who underwent cold-knife conization between 1985-1990. Short- and long-term data were assessed for healing and scarring and the adequacy of postoperative Papanicolaou smears in the hot-knife patients. RESULTS: Thermal injury was minimal, with 300 mu or less in 83 patients (92%) and 350-600 mu in four patients. One patient had thermal distortion of 1500 mu. All slides were interpreted adequately. Blood loss was mild to moderate in 84 of 88 patients (95%) in the hot-knife group and in 34 of 40 patients (85%) in the cold-knife group. No patient in the hot-knife group needed blood transfusion or hospitalization. Operating time was reduced by as much as 67% when the hot knife was used. Thirteen percent of the hot-knife patients developed stenosis of the external os. No patient in the hot-knife group developed recurrence within 2 years of surgery. CONCLUSION: Using a Teflon-coated hot knife for conization of the cervix produces adequate surgical margins and reduces blood loss and operating time over that with cold-knife conization. Long-term follow-up reveals no increase in cervical stenosis and demonstrates adequate cytologic smears in the hot-knife patients

Efficacy on sleep parameters and tolerability of melatonin in individuals with sleep or mental disorders: A systematic review and meta-analysis

We conducted the first systematic review and series of meta-analyses to assess the efficacy and tolerability of melatonin in children/adolescents or adults with sleep or mental health disorders, using the same set of criteria across disorders and ages. Based on a pre-registered protocol (PROPSPERO: CRD42021289827), we searched a broad range of electronic databases up to 02.02.2021 for randomized control trials (RCTs) of melatonin. We assessed study quality using the Risk of Bias tool, v2. We included a total of 34 RCTs (21 in children/adolescents: N = 984; 13 in adults: N = 1014). We found evidence that melatonin significantly improved sleep onset latency and total sleep time, but not sleep awaking, in children and adolescents with a variety of neurodevelopmental disorders, and sleep onset latency (measured by diary) as well as total sleep time (measured with polysomnography) in adults with delayed sleep phase disorder. No evidence of significant differences between melatonin and placebo was found in terms of tolerability. We discuss clinical and research implications of our findings.</p