IntroductionIn this study, we analysed the number of IL-17+ cells in facet joints, in the peripheral blood (PB) and synovial fluid (SF) of spondyloarthritis (SpA) patients and compared these results with those of patients with other rheumatic diseases and controls.MethodsImmunohistochemical analysis of IL-17+ cells was performed in facet joints of 33 ankylosing spondylitis (AS) patients and compared with data from 20 osteoarthritis (OA) patients. The frequency of IL-17+CD4+ T cells in PB and SF of SpA patients (PB n = 30, SF n = 11), rheumatoid arthritis (RA) patients (PB n = 14, SF n = 7), OA patients (PB n = 10) and healthy controls (PB n = 12) was analysed after stimulation with Staphylococcus aureus Enterotoxin B and phorbol 12-myristate 13-acetate/ionomycin and quantified by flow cytometry.ResultsIn AS facet joints, the frequency of IL-17-secreting cells was significantly higher than in samples obtained from OA patients (P < 0.001), with a slight predominance of IL-17+ cells among the mononuclear cells (61.5% ± 14.9%) compared to cells with polysegmental nuclei. Immunofluorescence microscopy revealed that the majority of IL-17+ cells were myeloperoxidase-positive (35.84 ± 13.06/high-power field (HPF) and CD15+ neutrophils (24.25 ± 10.36/HPF), while CD3+ T cells (0.51 ± 0.49/HPF) and AA-1+ mast cells (2.28 ± 1.96/HPF) were less often IL-17-positive. The frequency of IL-17+CD4+ T cells in the PB and SF of SpA patients did not differ significantly compared to RA patients, OA patients or healthy controls.ConclusionsOur data suggest an important role for IL-17 in the inflammatory processes in AS. However, the innate immune pathway might be of greater relevance than the Th17-mediated adaptive immune response.
The significant proportion of depressed patients that are resistant to monoaminergic drug therapy and the slow onset of therapeutic effects of the selective serotonin reuptake inhibitors (SSRIs)/serotonin/noradrenaline reuptake inhibitors (SNRIs) are two major reasons for the sustained search for new antidepressants. In an attempt to identify common underlying mechanisms for fast-and slow-acting antidepressant modalities, we have examined the transcriptional changes in seven different brain regions of the rat brain induced by three clinically effective antidepressant treatments: electro convulsive therapy (ECT), sleep deprivation (SD), and fluoxetine (FLX), the most commonly used slow-onset antidepressant. Each of these antidepressant treatments was applied with the same regimen known to have clinical efficacy: 2 days of ECT (four sessions per day), 24 h of SD, and 14 days of daily treatment of FLX, respectively. Transcriptional changes were evaluated on RNA extracted from seven different brain regions using the Affymetrix rat genome microarray 230 2.0. The gene chip data were validated using in situ hybridization or autoradiography for selected genes. The major findings of the study are:1. The transcriptional changes induced by SD, ECT and SSRI display a regionally specific distribution distinct to each treatment. 2. The fast-onset, short-lived antidepressant treatments ECT and SD evoked transcriptional changes primarily in the catecholaminergic system, whereas the slow-onset antidepressant FLX treatment evoked transcriptional changes in the serotonergic system. 3. ECT and SD affect in a similar manner the same brain regions, primarily the locus coeruleus, whereas the effects of FLX were primarily in the dorsal raphe and hypothalamus, suggesting that both different regions and pathways account for fast onset but short lasting effects as compared to slow-onset but long-lasting effects. However, the similarity between effects of ECT and SD is somewhat confounded by the fact that the two treatments appear to regulate a number of transcripts in an opposite manner. 4. Multiple transcripts (e.g. brain-derived neurotrophic factor (BDNF), serum/glucocorticoidregulated kinase (Sgk1)), whose level was reported to be affected by antidepressants or behavioral manipulations, were also found to be regulated by the treatments used in the present study. Several novel findings of transcriptional regulation upon one, two or all three treatments were made, for the latter we highlight homer, erg2, HSP27, the proto oncogene ret, sulfotransferase family 1A (Sult1a1), glycerol 3-phosphate dehydrogenase (GPD3), the orphan receptor G protein-coupled receptor 88 (GPR88) and a large number of expressed sequence tags (ESTs). 5. Transcripts encoding proteins involved in synaptic plasticity in the hippocampus were strongly affected by ECT and SD, but not by FLX.The novel transcripts, concomitantly regulated by several antidepressant treatments, may represent novel targets for fast onset, long-duration antidepressants.
Infants with very low birth weights have less need of transfusions if given epoetin beta during the first six weeks of life (250 IU per kilogram three times a week). We recommend early epoetin treatment for all such infants, but further studies of nutrition and iron supplementation during treatment are needed.
Objective. The interleukin-12 (IL-12) family of cytokines has been suggested to play a critical role in inflammatory autoimmune diseases, and recent studies analyzing peripheral blood and synovial fluid from patients with spondyloarthritides suggest that IL-23 might be a proinflammatory factor in these disorders. This study was undertaken to investigate the presence and source of IL-23 in the spines of patients with ankylosing spondylitis (AS).Methods
ObjectiveThe aim of the study was to assess the risk of adverse pregnancy outcomes after antenatal antiretroviral therapy in a well-defined prospective cohort of nontransmitting HIV-infected women. MethodsProspective monitoring of 183 mother-child pairs from 13 centres in Germany and Austria, delivering between 1995 and 2001, was carried out. Following German-Austrian guidelines recommending an elective Caesarean section (CS) at 36 weeks, prematurity was defined as o36 weeks' gestation for these analyses. ResultsOf 183 mother-child pairs, 42% were exposed to antenatal monotherapy and 17% to dual therapy. Of the 75 women exposed to highly active antiretroviral therapy (HAART), 21 (28%) received protease inhibitor (PI)-based HAART and the remaining 54 received nonnucleoside reverse transcriptase inhibitor-based HAART. In multivariable analysis (176 pregnancies), PI-based HAART exposure during pregnancy was associated with an increased risk of premature delivery [adjusted odds ratio 3.40; 95% confidence interval (CI) 1.13-10.2; P 5 0.029, compared with monotherapy]. Congenital abnormalities affected 3.3% infants. Perinatally, 18.9% of children (34 of 179) had respiratory problems requiring interventions, which were associated with prematurity but not with type of treatment exposure. From adjusted regression analysis, the mean birth weight z-score for children exposed to HAART with PI ( 1 0.46; 95% CI 0.01-0.92; P 5 0.047) or dual therapy ( 1 0.43; 95% CI 0.03-0.82; P 5 0.034) was slightly but significantly higher than that for those exposed to monotherapy; head circumference was appropriate for gestational age and there were no significant differences between treatment groups. ConclusionsUse of antenatal PI-based HAART initiated before or during pregnancy was associated with a significantly increased risk of premature delivery at o36 weeks' gestation. The overall crude prematurity rate was 34% (63 of 183; 95% CI 28-42).Keywords: congenital abnormalities, HAART, HIV, pregnancy, prematurity There is a consistent body of evidence from European studies showing an increased risk of premature delivery with antenatal combination antiretroviral therapy (ART) and highly active antiretroviral therapy (HAART), especially with regimens containing a protease inhibitor (PI) [5,[7][8][9][10]. Although most studies based in the USA have not found such an association [11][12][13], a more recent, singlecentre study from Florida reported results consistent with those from Europe [14]. Concerns have also been raised over the possible teratogenic effects related to ART exposure in early pregnancy when organogenesis is occurring, although recent reports indicating a low prevalence of congenital malformations in infants with ART exposure have been reassuring [15,16].We assessed the risk of adverse pregnancy outcomes, namely neonatal and perinatal morbidity, prematurity and birth defects, associated with the use of antenatal ART in a well-defined bi-national cohort of nontransmitting HIVinfected pregnant women and their children. MethodsP...
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