Decreased interleukin 35 and CD4+EBI3+ T cells in patients with active systemic lupus erythematosus.

BACKGROUND: Interleukin 35 (IL-35) is likely to contribute to the development of autoimmune diseases, as the Epstein-Barr virus-induced gene protein 3 (EBI3) is the specificity subunit of IL-35. Nevertheless, until recently, no studies have evaluated its role in systemic lupus erythematosus (SLE) in humans. The objective of this study was to investigate the serum IL-35 level and the percentage of CD4EBI3 T cells in the peripheral blood of patients with SLE and explore the roles of double-positive T cells and IL-35 in the pathogenesis of SLE and the effects of glucocorticoid on these roles. METHODS: Fifty-five hospitalized patients with SLE were recruited, and 20 volunteers were enrolled as healthy controls. Serum IL-35 levels were measured by enzyme-linked immunosorbent assay, and the percentage of CD4EBI3 T cells was analyzed by flow cytometry. RESULTS: The serum IL-35 level and the percentage of CD4EBI3 T cells were significantly decreased in patients with active SLE compared with healthy controls and patients with inactive SLE. The serum IL-35 level and the percentage of CD4EBI3 T cells were negatively correlated with the SLE disease activity index. The percentages of CD4EBI3 T cells and serum IL-35 levels in 10 untreated patients with active SLE were increased at days l, 3, and 7 after the treatment with methylprednisolone (0.8 mg·kg·d) compared with the percentages before the treatment. CONCLUSIONS: These results demonstrate that abnormalities in IL-35 and CD4EBI3 T cells may play important roles in the pathogenesis of SLE; the percentage of double-positive T cells and the level of IL-35 are parameters for the evaluation of SLE activity and severity.

Hydrogen sulfide inhibits the renal fibrosis of obstructive nephropathy.

Hydrogen sulfide has recently been found decreased in chronic kidney disease. Here we determined the effect and underlying mechanisms of hydrogen sulfide on a rat model of unilateral ureteral obstruction. Compared with normal rats, obstructive injury decreased the plasma hydrogen sulfide level. Cystathionine-ß-synthase, a hydrogen sulfide-producing enzyme, was dramatically reduced in the ureteral obstructed kidney, but another enzyme cystathionine-γ-lyase was increased. A hydrogen sulfide donor (sodium hydrogen sulfide) inhibited renal fibrosis by attenuating the production of collagen, extracellular matrix, and the expression of α-smooth muscle actin. Meanwhile, the infiltration of macrophages and the expression of inflammatory cytokines including interleukin-1ß, tumor necrosis factor-α, and monocyte chemoattractant protein-1 in the kidney were also decreased. In cultured kidney fibroblasts, a hydrogen sulfide donor inhibited the cell proliferation by reducing DNA synthesis and downregulating the expressions of proliferation-related proteins including proliferating cell nuclear antigen and c-Myc. Further, the hydrogen sulfide donor blocked the differentiation of quiescent renal fibroblasts to myofibroblasts by inhibiting the transforming growth factor-ß1-Smad and mitogen-activated protein kinase signaling pathways. Thus, low doses of hydrogen sulfide or its releasing compounds may have therapeutic potentials in treating chronic kidney disease.

[Abnormality and significance of interleukin-9 and CD4(+)interleukin-9(+) T-cells in peripheral blood of patients with systemic lupus erythematosus].

OBJECTIVE: To examine the protein and mRNA levels of interleukin-9(IL-9) and the frequencies of CD4(+)IL-9(+)T-cells in peripheral blood of patients with systemic lupus erythematosus (SLE) and explore the roles of double positive T cells and IL-9 in the pathogenesis of SLE and the effects of glucocorticoid. METHODS: Twenty-eight hospitalized SLE patients were recruited and 12 healthy volunteers selected as normal controls. The mRNA levels of IL-9 in peripheral blood were measured by real time-polymerase chain reaction (RT-PCR), plasma protein of IL-9 by enzyme-linked immunosorbent assay (ELISA) and frequencies of CD4(+)IL-9(+)T-cells by flow cytometry. And the differences between two groups and the effects of glucocorticoid were analyzed. RESULTS: (1) The mRNA levels of IL-9 were significantly elevated in SLE patients as compared with normal controls (P < 0.01). The serum levels of IL-9 were significantly higher in active and inactive SLE patients than those in healthy individuals (68 ± 11 vs 26 ± 6 ng/L, P < 0.01; 56 ± 14 vs 26 ± 6 ng/L, P < 0.05). The percentages of CD4(+)IL-9(+)T-cells increased in active SLE patients (1.96% ± 0.31%) versus inactive SLE patients (0.89% ± 0.13%, P < 0.01) and healthy controls (0.28% ± 0.05%, P < 0.001). And it was higher in inactive SLE patients than that in controls (P < 0.05). (2) The serum levels of IL-9 and the frequencies of CD4(+)IL-9(+)T-cells were positively correlated with SLE disease activity index (SLEDAI). (3) The frequencies of CD4(+)IL-9(+)T-cells and the serum levels of IL-9 in 8 untreated active SLE patients decreased at weeks 1, 2 and 3 after the therapy of methylprednisolone (0.8 mg×kg(-1)×d(-1)) versus those at pre-treatment. CONCLUSION: The abnormalities of IL-9 and CD4(+)IL-9(+)T-cells may play an important role in the pathogenesis of SLE. And the frequencies of CD4(+)IL-9(+)T-cells and the levels of IL-9 are evaluative parameters of SLE activity and severity.

Four systems involved with congenital abnormalities: a new type of syndromic hearing loss - ADOC Wang's syndrome?

Syndromic hearing impairment encompasses hundreds of phenotypes. We identified a young female patient affected by the unique combination of dysplasia of the auricular system, patent ductus arteriosus (PDA), choroideremia, and enamel hypoplasia. The patient was treated with PDA ligature and left exploratory tympanotomy. Impairment in all four systems suggests a correlation with the neural crest. It is presumed that all of the features result from the same origin, probably through autosomal recessive inheritance or a novel mutation during the embryonic period. When audio-dento-oculo-cardio systems are involved, we suggest that this new syndrome can be named 'ADOC Wang's syndrome', summarizing the disorders of the four systems and indicative of the founding person (Dr Wang, the first and corresponding author of the paper).

SSRI use by tinnitus patients: interactions between depression and tinnitus severity.

Depression is often coincident with chronic tinnitus, and several studies have suggested that antidepressant medications may play a role in relieving tinnitus as well as depression. We conducted a retrospective study of the use of selective serotonin reuptake inhibitors (SSRIs) by patients at a large tinnitus clinic to assess the effects of these antidepressants on tinnitus severity. We focused on a subgroup of 30 patients with depression who had begun taking SSRI medication after the onset of their tinnitus; these patients had also been treated with psychotherapy by a mental health clinician. At a mean follow-up of 20.6 months, only 10 of the 30 patients reported that they were still experiencing major depression. Moreover, this group as a whole demonstrated a statistically significant improvement in tinnitus symptoms as reflected by a reduction in their Tinnitus Severity Index scores. We conclude that SSRIs represent one category of tools that can be used to help patients with severe tinnitus and depression. Like all antidepressant medications, SSRIs should be used in conjunction with psychotherapy to facilitate patient improvement.

Electrical stimulation for intraoperative evaluation of thoracic pedicle screw placement.

STUDY DESIGN: Thoracic pedicle screws were stimulated electrically while recording electromyography (EMG) activity in associated muscle groups intraoperatively. Screw position was then evaluated after surgery using computed tomography (CT). The CT results were compared with evoked EMG threshold values. OBJECTIVE: To report our experience with pedicle screw stimulation in thoracic vertebrae in 22 patients who underwent thoracic level spinal instrumentation from May 1999 to March 2001. SUMMARY OF BACKGROUND DATA: Pedicle screw stimulation for intraoperative assessment of screw placement has been reported in lumbosacral spinal procedures. Evoked EMG thresholds >10 or 11 mA are associated with increased probability of vertebral cortex violation and postoperative complications. Thresholds >15 mA provide a 98% confidence of accurate screw positioning on postoperative CT scans. METHODS: Evoked EMG activity was recorded from ulnar carpal flexors, intercostals, or abdominal muscle groups, depending on the level of screw placement. Postoperative CT scans were read by a staff orthopedic spine surgeon, a senior resident in orthopedics, and a musculoskeletal radiologist. RESULTS: Results of 87 screws are reported. Five screws (5.7%) showed penetration on postoperative CT scans. Six screws (6.9%) had stimulation thresholds < or =11 mA, of which three showed cortical breakthrough. Of the 81 screws with thresholds >11 mA, 79 (97.5%) were within the vertebra. No postoperative neurologic complications were noted in any of the 22 patients. CONCLUSION: These results are consistent with previous studies of lumbosacral pedicle screws. In this series, stimulation thresholds >11 mA have a 97.5% negative predictive value, suggesting that cortical violation is highly unlikely. Although judgment of screw placement should not depend solely on stimulation thresholds, pedicle screw stimulation may provide rapid and useful intraoperative information on screw placement during procedures involving the use of thoracic pedicle screws.