ABSTRACT
OBJECTIVE@#To test the hypothesis that the inhibition of endoplasmic reticulum (ER) stress-induced apoptosis in oxidized low-density lipoproteins (ox-LDL)-induced human aortic-vascular smooth muscle cells (HA-VSMCs) was associated with suppression of the protein kinase RNA-like ER kinase (PERK)-eukaryotic translation initiation factor 2α (eIF2α)-activating transcription factor 4 (ATF4)-CCAAT/enhancer binding protein homologous protein (CHOP) signaling pathway by Pollen Typhae total flavone (PTF).@*METHODS@#Primary HA-VSMCs were cultured and identified. The cultured HA-VSMCs were randomized into 5 groups, including a normal control group, an ox-LDL group (70 μg/mL high ox-LDL), an HPTF group (70 μg/mL high ox-LDL+500 μg/mL PTF), an MPTF group (70 μg/mL high ox-LDL+250 μg/mL PTF), and a LPTF group (70 μg/mL high ox-LDL+100 μg/mL PTF) in the first part; and a normal control group, an ox-LDL group (70 μg/mL high ox-LDL), an MPTF group (70 μg/mL high ox-LDL+250 μg/mL PTF), a shRNA group (transducted with PERK shRNA lentiviral particles), a scramble shRNA group (transducted with control shRNA lentiviral particles), an MPTF+ox-LDL+shRNA group (250 μg/mL PTF+70 μg/mL high ox-LDL+PERK shRNA lentiviral particles) and an ox-LDL+shRNA group (70 μg/mL high ox-LDL+PERK shRNA lentiviral particles) in the second part. The protein expression levels of ER-associated apoptosis proteins were detected by Western blot, and their mRNA expression levels were detected by quantitative real-time reverse transcription-polymerase chain reaction. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was applied to test cell viability, and the level of apoptosis was monitored by flow cytometry.@*RESULTS@#The MTT assay and flow cytometry showed that the ox-LDL group had a significant increase in apoptosis, which was attenuated in PTF treatment groups and shRNA groups. Moreover, the ox-LDL group had increased protein and mRNA levels of binding immunoglobulin protein and ER-associated apoptosis proteins, such as PERK, eIF2α, ATF4 and CHOP, which were attenuated in PTF treatment groups and shRNA groups.@*CONCLUSIONS@#The apoptosis induced by ox-LDL had a strong relation to ER stress. The protective effect of PTF on ER stressinduced apoptosis was associated with inhibition of the PERK-eIF2α-ATF4-CHOP pathway, which might be a potential therapeutic strategy for enhancing the stability of atherosclerotic plaques.
ABSTRACT
<p><b>OBJECTIVE</b>Propylthiouracil (PTU) as a drug used during the treatment of hyperthyroidism could induce antineutrophil cytoplasmic autoantibody-positive vasculitis. Here the author reported a childhood case of antineutrophil cytoplasmic autoantibody-positive vasculitis induced by PTU, which is rarely described.</p><p><b>METHODS</b>The diagnosis was made according to the symptoms, signs, serum markers and renal biopsy, and the relevant literature was reviewed.</p><p><b>RESULTS</b>The 12-year-old girl presented with gross hematuria, proteinuria, renal function damage [Ccr 52.46 ml/(min. 1.73 m(2))], positive antineutrophil cytoplasmic autoantibody (ANCA-MPO) (MPO ELISA 140%) and a vasculitis lesion in the renal biopsy sample. She had been treated with PTU for 5 years because of Graves disease. After the diagnosis, the PTU was withdrawn, and prednisone (40 mg/d) and cyclophosphamide (25 mg, Bid) were applied. Three weeks after the therapy with prednisone and cyclophosphamide the gross hematuria disappeared. Three months after the treatment the renal function returned to normal [Ccr 124 mg/(min.1.73 m(2))], and the titer of ANCA-MPO decreased from 140% to 57%.</p><p><b>CONCLUSION</b>PTU may induce antineutrophil cytoplasmic autoantibody positive vasculitis. A right diagnosis and treatment can improve its prognosis of the disease.</p>
Subject(s)
Child , Female , Humans , Antibodies, Antineutrophil Cytoplasmic , Blood , Antithyroid Agents , Therapeutic Uses , Diagnosis, Differential , Hyperthyroidism , Drug Therapy , Prognosis , Propylthiouracil , Therapeutic Uses , Treatment Outcome , Vasculitis , Diagnosis , TherapeuticsABSTRACT
<p><b>OBJECTIVE</b>To investigate the clinical and pathological characteristics of focal segmental glomerulosclerosis (FSGS) in children.</p><p><b>METHODS</b>The data of 38 children,aged from one and half to 15 years, 25 boys and 13 girls, with primary FSGS were studied retrospectively.</p><p><b>RESULTS</b>Majority of the cases in this study were school-aged children. The average age of initial onset was 8.9 +/- 3.68 years. The ratio of boys to girls was 1.92. The clinical manifestation included isolated proteinuria in 3 cases, proteinuria and hematuria in 1 and nephrotic syndrome in 34 (simple type in 16 and nephritic type in 18). Of 38 cases, 24 (63%) presented with hematuria, 11 (29%) with hypertension and 7 (18%) with decreased creatinine clearance. The pathologic classification included perihilar variant in 17 cases, peripheral variant in 14 and tip variant in 7. The predominant clinical feature of children with tip variant was simple type of nephrotic syndrome (86%). Microscopic hematuria was not common (29%). Blood pressure and renal function were normal. The children with diffuse mesangial hypercellularity superimposed on changes of FSGS (in 21 of 38 cases) were more likely to have hematuria (76%) and less simple nephrotic syndrome (30%). The initial treatment response to prednisone in 34 cases with nephrotic syndrome showed sensitive in 12 cases, resistant in 21 and unknown in 1. Transition from sensitive to resistant occurred in six of 12 children. Three of 4 cases with non-nephrotic syndrome showed no response and the remaining one had unknown response. It was found that 44% of children who received cyclophosphamide and 83% of children who received pulse methylprednisolone and pulse cyclophosphamide or cyclosporin A in addition to oral steroids had complete or partial remission. Correlation analysis showed that the level of proteinuria after treatment was correlated directly with renal tubulointerstitial lesion and renal function (Pr = 0.48, P < 0.05; Pr = 0.45, P < 0.05).</p><p><b>CONCLUSION</b>FSGS was common in school-aged children. The predominant presenting feature was nephrotic syndrome. Hematuria was common. Hypertension and renal insufficiency were less frequently seen. The renal biopsy showed multiple variants. Pulse methylprednisolone and pulse cyclophosphamide or cyclosporin A treatments showed relatively good response.</p>