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Systemic lupus erythematosus(SLE)is an autoimmune disease with unknown etiology and pathogenesis, and is characterized by multiple organ involvement and the production of autoantibodies.Late-onset SLE means that clinical symptoms first occur after 50 years of age, often without typical skin lesions and implicating fewer target organs.It exhibits low disease activity, a high degree of cumulative damage, high rates of comorbidity and mortality, and abnormal immunological profiles, which make its diagnosis difficult.Due to the physiological state and disease characteristics in the elderly, the treatment is slightly different from that for SLE.This article reviews the clinical features, diagnosis and treatment of late-onset SLE to provide a basis for accurate diagnosis and treatment.
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Objective To study the effects of exogenous double-stranded DNA antigen on the immunophenotypic changes of dendritic cells (DCs) derived from stem cells in mouse bone marrow. Methods LinCD117 (c-kit)+ hemopoietic stem cells were obtained from the bone marrow of C57 mice by magnetic affinity cell sorting. Some cytokines, including granulocyte-macrophage colony-stimulating factor, interleukin-4, tumor necrosis factor-α and so on, were used to enhance the proliferation or differentiation of stem cells to obtain mature, semimature and immature DCs. The double stranded DNA of kinetoplast (kDNA) was isolated from Trypanosoma equiperdum, and added to the culture media to pulse DCs. The immunophenotypic and morphologic features of DCs were analyzed by using flow cytometry and laser confocal microscopy respectively. Results The expression rates of CD117 and CD11c in DCs showed no significant changes after kDNA pulse compared with those before the pulse. In unpulsed immature, semi-mature and mature DCs, the expression rate was 11.42% ± 2.56%, 27.08% ± 5.29% and 44.63% ± 10.37% for MHC Ⅱ, 8.54% ± 2.01%, 31.35% ± 6.40% and52.96% ± 10.34% for CD80, 10.22% ± 3.47%, 32.15% ± 6.83% and 64.72% ± 9.68% for CD86, respectively.After pulse with the kDNA antigen, the expression rate increased by 15.63%, 9.66% and 4.12% (t = 6.21,4.35, 2.82, P < 0.05) for MHC Ⅱ, by 9.63%, 7.09% and 4.09% for CD80, by 13.16%, 9.75% and 3.10% for CD86, respectively in immature, semi-mature and mature DCs, respectively. The increase of expression rate of these membrane antigens in decreasing order was observed in immature DCs, semi-mature DCs and mature DCs. Conclusions The exogenous DNA antigen could enhance the maturation of bone marrow-derived DCs,likely by upregulating the expression of certain immunophenotypic membrane proteins, and the lower the maturity degree, the more liable the DCs to be affected by the antigen.
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Objective To investigate the effects of photodynamic reaction on cytokines production of HaCat keratinocytes treated with 5-aminolevulinic acid (ALA). Methods The HaCat cells were cocultured in vitro with different concentrations of ALA. Three hours later PpIX levels in HaCat cells were detected, and phtotodynamic reaction was induced by 632.8 nm laser radiation on cells. The cell death was analyzed using a flow cytometer to evaluate reactive intensity. The cytokines contents in supernatant were determined, including interleukin (IL)- lα, IL-6, basic fibroblast growth factor (bFGF), endothelin (ET)-1 and tumor necrosis factor (TNF)-α. Results Different cellular PpIX levels and cell death rates were seen according to ALA concentrations. The cell death rate did not exceed 10% and showed a positive linear relationship with ALA concentration (P＜0.05), when the later was at 0.0-1.6 mmol/L interval. The levels of IL-1α, bFGF and TNF-α increased as ALA concentration ascended at this interval (P＜0.05). No significant correlation was found between ALA concentration and IL-6 or ET-1 level (P＞0.05). Conclusion The photodynamic reactive intensity could be enhanced by increasing ALA concentration. And at certain scope, higher reactive grade might induce higher levels of keratinocyte-derived cytokines.
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Objective To investigate the effect of δ-aminolevulinic acid(ALA)-induced photodynamic reaction on biological characteristics of skin fibroblasts.Methods Human skin fihroblasts were isolated from the foreskin of children and cultured in the presence of 0.5 to 5.0 mmol/L ALA;three hours later,they were irradiated with 632.8 am laser followed by additional 12-hour culture.Then,MTI"assay and flow cytometry were used to measure the proliferation and apoptosis of cells.The levels of matrix metallopmteinase(MMP)1,-2 and-3 and hydroxyproline in the culture supematant of irradiated cells were determined by avidinbiotin complex-based ELISA and alkaline hydrolysis-based method,respectively.Results With the rise of ALA concentration from 0.5 to 5.0 mmol/L.the proliferation level of fibroblasts expressed as the absor-bance at 570 nm dropped from 0.45±0.05 to 0.32±0.04.and cell death rate increased from 6.4%±2.0% to 29.6%±2.2%.Meanwhile,the contents of MMP-1,-2 and -3 increased at the early stage,but decreased at the late stage,whereas the hydroxyproline level showed an inverse tendency during the increase of ALA concentration from 0.5 to 5.0 mmol/L.Conclusions Proper intensity of photodynamic reaction induced by ALA could enhance the secretion of MMP and inhibit the synthesis of collagen by skin fibroblasts,however,high concentration of ALA may exert an inverse effect.
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Objective To investigate the pathological characteristics of lupus-like renal damages induced by double stranded DNA (dsDNA) derived from Trypanosoma Equiperdum (TE). Methods The TEs were propagated in normal rats and isolated from fresh rat blood by DEAE cellulose-chromatography. Their kinetoplast dsDNA (kDNA) was purified with Gibson's method. The emulsive mixture of kDNA and incomplete Freund's adjuvant (IFA) was injected into normal BALB/c mice subcutaneously. Eight weeks Later some parameters were examined, including sera titers of ANA and anti-dsDNA antibodies, 24h urine protein concentration, ESR, BUN, Scr and renal histological active index (AI). The pathological characteristics of renal tissues were observed under optical and electron microscopes, and then compared with that of BXSB mice and lupfis nephritis (LN) patients with positive anti-dsDNA antibodies in the sera. Results The results of all immunological parameters of TE kDNA-immunized mice corresponded with that of LN. Their renal damages mainly represented nephropathy syndrome. The pathological characteristics of these mice were similar to that of BXSB mice and LN patients, but Ⅱ (mesangial proliferative) and Ⅳ (diffuse proliferative) subtypes were more common in the former. Conclusion The pathological characteristics of renal damages in the mice immunized with TE dsDNA are similar to that of human LN induced by anti-dsDNA antibodies. This mice model could be used as a tool for invostigating the pathogenesis of LN.
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The iron chelators can be utilized in target cells to improve 5-aminolaevulinic acid (ALA)-based photodynamic therapy (PDT). The purpose of this study is to compare the effect of two kinds of iron chelators, desferrioxamine (DFO) and ethylenediaminetetraacetic acid (EDTA) on the enhancement of ALA-PDT. HaCat cells were cultured in medium containing 2.0 mmol/L of ALA and 0.5 mmol/L of DFO or EDTA. After 3-h incubation in the dark, the concentration of cellular protoporphyrin IX (PpIX) was detected by high performance liquid chromatography (HPLC), and the fluorescence of PpIX was observed at 630 nm emission under confocal laser scanning microscope. For PDT, HaCat cells were irradiated using 632.8 nm laser, and the fractions of apoptotic and necrotic cells were flow cytometrically assayed. Related differences in morphology and ultrastructure of Ha-Cat cells were observed using optical microscope or transmission electron microscope. Compared to incubation with ALA alone, the addition of DFO or EDTA increased the concentration of cellular PpIX and the fluorescent density of PpIX, and also increased cell death ratio after PDT. PDT using ALA plus DFO produced the highest cellular PpIX level, greatest cell death ratio and most severe structural damage to the cells. It was concluded that both DFO and EDTA could enhance ALA-based PpIX production and PDT. Compared to the non-specific iron chelator of EDTA, the specific chelator, DFO, showed more potential for the enhancement.
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< 0.05; 8.9% vs 0.1%, x2 = 8.23, P< 0.05). Conclusion Low concentration (0.1%) of DMSO could enhance the effect of ALA-PDT on HaCaT cells.
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Objective To evaluate the effects of δ-aminolaevulinic acid-photodynamic therapy (ALA-PDT) in the treatment of primary carcinomas on the facial skin. Methods In the accordance of these tumors' sites and morphology, 14 patients with squamous cell carcinoma (SCC), 38 patients with basal cell carcinoma (BCC) and 5 patients with Bowen disease were given four to eight times of topical ALA followed by PDT. Results Ten (71.4%) SCC cases, 34 (89.5%) BCC cases and all (100%) Bowen disease cases completely recovered after ALA-PDT. The others all obtained signifi-cant improvement after final treatment. Their unaffected tissues around these tumors kept well and no scaring appeared after ALA-PDT. The recurrence rates among the completely-recovered cases were 10.0% (SCC), 11.8% (BCC) and 0% (Bowen disease), respectively, by the end of six-month's follow-up. Conclusions Topical ALA-PDT is an effective new therapeutical method with lower recur-rence rates, fewer side effects, no scar formation and excellent cosmetic results for primary carcinomas localizing on the facial skin.
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<p><b>OBJECTIVE</b>To use partial differential -aminolevulinic acid induced photodynamic therapy (ALA-PDT) increasingly in treating skin cancers and other diseases in many countries and to explore the efficacy of ALA-PDT for skin cancers in China.</p><p><b>METHODS</b>Eighty-eight patients, including 34 cases of basal cell carcinoma (BCC), 32 cases of squamous cell carcinoma (SCC), two cases of basal-squamous cell carcinoma (BSCC), one case of verrucuous carcinoma, nine cases of Bowen disease, two cases Paget disease of the nipple and eight cases of extramammary Paget disease, were treated by the partial differential alpha-aminolevulinic acid induced photodynamic therapy first in China from 1997 to 2000.</p><p><b>RESULTS</b>All BCC, including 11 cases of superficial lesions and 29 solid lesions, achieved complete reaction (CR) by 1-4 times of the ALA-PDT. Except one patient with adenoid SCC (grade III), all SCC (grade I and grade II) patients achieved complete remission by 3-6 times of ALA-PDT. All Bowen diseases achieved complete reaction by 1-4 times. Although for Paget diseases it could not cure the disease simply by ALA-PDT, it could control the symptoms. The recurrence rates were 11% (4/34) for BCC, and 22% (7/32) for SCC by following up 1-3 years after the therapy. The continuous therapy is still effective.</p><p><b>CONCLUSIONS</b>ALA-PDT is an effective, non-traumatic treatment for patients with BCC, SCC, Bowen and Paget diseases. It is especially suitable for older and weaker patients or those who are not tolerable to other therapies. It also has a unique advantage for tumors in specific anatomical areas. It is a new alternative modality for skin cancer therapies.</p>