Successful treatment of a case of idiopathic linear IgA bullous dermatosis with oral sulfasalazine

Linear IgA bullous dermatosis (LABD) is a rare acquired autoimmune chronic vesiculobullous dermatosis affecting primarily young children and older adults. We report a 17‐year‐old Chinese boy with a 2‐month history of intense itching erythema or tense vesicles on healthy skin or on an erythematous base, with parts of lesions arising a characteristic “cluster of jewels” pattern. With the characteristics of vesicles or blisters on the skin, subepidermal blisters with neutrophilic infiltrate on histology, and linear IgA deposits on the basement membrane zone and absence of other immunoglobulins on direct immunofluorescence, LABD was dignosized. Sulfapyridine has also been reported as one of the best options of systemic therapy for LABD. Our patient successfully treated with only oral sulfasalazine (alternative medicine of sulfasalazine), which is safe and effective.     

Maternal use of 5-aminosalicylates in early pregnancy and congenital malformation risk in the offspring

Abstract

Objective. Most previous studies have failed to demonstrate any effect of maternal use of 5-aminosalicylates (5-ASA) on malformation risk, but the number of infants studied have, in most cases, been low. The objective of the study was to get data from a large study with prospectively ascertained exposure information. Material and methods. The study was based on data in the Swedish Medical Birth Register (1996–2011) where identification of maternal drug use is made from midwife interviews in early pregnancy. The presence of congenital malformations was ascertained from three national registers. Adjusted odds ratios were calculated by the Mantel-Haenszel methodology. Results. Among 1,552,109 women, 3651 with 3721 infants had reported the use of 5-ASAs in early pregnancy. The risk of a major malformation was increased (1.37, 95% confidence interval = 1.17–1.62) and still more for a cardiovascular defect (1.74, 1.37–2.22). This effect seemed to be influenced by concomitant use of systemic glucocorticosteroids or immunosuppressants but some confounding by indication may also exist. There was no marked difference between the four 5-ASA drugs studied. Conclusions. Infants born of women who use 5-ASA drugs in early pregnancy have an increased risk of a congenital malformation, notably a cardiovascular defect. This could be a drug effect or an effect of an active inflammatory bowel disease.     

Amino acid derivatives of 5-ASA as novel prodrugs for intestinal drug delivery

In an attempt to obtain site-specific delivery of 5-ASA in the intestinal tract, we have determined the extent of absorption and metabolism of a number of novel 5-ASA derivatives, namely, (N-l-glutamyl)-amino-2-salicylic acid (1), (N-l-aspartyl)-amino-2-salicylic-acid (2), 5-aminosalicyl-l-proline-l-leucine (3), and 5-(N-l-glutamyl)-aminosalicyl-l-proline-l-leucine (4), which are selectively cleaved by intestinal brush border aminopeptidase A and carboxypeptidases. These novel prodrugs, 5-ASA, and sulfasalazine were administered to adult Fisher rats (N=30) and to animals that had undergone prior colostomy (N=30). Urine and feces were collected at timed intervals for 48 hr and the metabolites, 5-ASA, andN-acetyl-5-ASA were measured by high-performance liquid chromatography. The absorption and metabolism of all compounds were essentially identical in colostomized and normal animals. 5-ASA exhibited a rapid proximal intestinal absorption as evidenced by the high cumulative urinary excretion (>65%) and low fecal excretion. Sulfasalazine, as expected, exhibited a lower urinary recovery (<35%) and higher fecal excretion of 5-ASA and its metabolite. The novel glutamate and aspartate derivatives (1 and2) behaved similarly to sulfasalazine, while administration of the proline-leucine derivative (3) resulted in urinary and fecal recovery values intermediate with respect to those observed with 5-ASA and sulfasalazine. 5-(N-l-Glutamyl)-aminosalicyl-l-proline-l-leucine yielded the highest fecal recovery of 5-ASA and itsN-acetyl derivative, indicating a more efficient delivery to the distal bowel. Amino acid derivatives of 5-ASA appear to be potentially useful prodrugs for the site-specific delivery of 5-ASA to different regions of the intestinal tract.We acknowledge the Depha Team for financial support and Dr. Kenneth D.R. Setchell for discussions.     

Novel analogs of sulfasalazine as system xc− antiporter inhibitors: Insights from the molecular modeling studies

System x_c⁻ (Sx_c⁻), a cystine-glutamate antiporter, is established as an interesting target for the treatment of several pathologies including epileptic seizures, glioma, neurodegenerative diseases, and multiple sclerosis. Erastin, sorafenib, and sulfasalazine (SSZ) are a few of the established inhibitors of Sx_c⁻. However, its pharmacological inhibition with novel and potent agents is still very much required due to potential issues, for example, potency, bioavailability, and blood–brain barrier (BBB) permeability, with the current lead molecules such as SSZ. Therefore, in this study, we report the synthesis and structure–activity relationships (SAR) of SSZ derivatives along with molecular docking and dynamics simulations using the developed homology model of xCT chain of Sx_c⁻ antiporter. The generated homology model attempted to address the limitations of previously reported comparative protein models, thereby increasing the confidence in the computational modeling studies. The main objective of the present study was to derive a suitable lead structure from SSZ eliminating its potential issues for the treatment of glioblastoma multiforme (GBM), a deadly and malignant grade IV astrocytoma. The designed compounds with favorable Sx_c⁻ inhibitory activity following in vitro Sx_c⁻ inhibition studies, showed moderately potent cytotoxicity in patient-derived human glioblastoma cells, thereby generating potential interest in these compounds. The xCT-ligand model can be further optimized in search of potent lead molecules for novel drug discovery and development studies.     

复方谷氨酰胺联合柳氮磺吡啶治疗溃疡性结肠炎的疗效观察

目的 研究复方谷氨酰胺联合柳氮磺吡啶治疗溃疡性结肠炎的临床疗效。方法 选择2017年1月-2019年1月榆林市星元医院的120例溃疡性结肠炎患者作为研究对象,采用抽签法随机分为对照组和观察组,每组各60例。对照组患者口服柳氮磺吡啶肠溶片,6片/次,3次/d。观察组患者在对照组的基础上口服复方谷氨酰胺肠溶胶囊,3粒/次,3次/d。两组均治疗4周。观察两组患者的临床疗效,比较两组治疗前后的相关症状、评分情况,以及炎性因子水平。结果 治疗后,观察组的总有效率为91.67%,明显高于对照组的71.67%（P<0.05）。治疗后,观察组的黏液脓血便消失时间为（10.13±1.27）d,明显短于对照组的（19.73±2.45）d（P<0.05）。两组治疗后的疾病活动指数和腹痛程度评分均明显降低（P<0.05）,且观察组明显更低（P<0.05）。两组治疗后的血清白细胞介素（IL）-6、肿瘤坏死因子-α（TNF-α）、IL-8、超敏C反应蛋白（hs-CRP）水平均明显降低（P<0.05）,且观察组明显更低（P<0.05）。结论 复方谷氨酰胺联合柳氮磺吡啶对溃疡性结肠炎的疗效较佳,能明显减轻腹痛程度,改善炎症因子水平,降低疾病活动指数。     

高压氧治疗溃疡性结肠炎患者的疗效及对Th17/Treg细胞免疫调节的影响

目的 探讨高压氧治疗溃疡性结肠炎（UC）患者的疗效及其对外周血Thl7细胞（CD4＋ IL-17＋T细胞）与Treg细胞（CD4＋ CD25＋T细胞）数量的影响.方法 选择74例UC患者,随机分为柳氮磺胺吡啶组（对照组）38例和高压氧联合柳氮磺胺吡啶组（高压氧组）40例.治疗4周后,比较2组总有效率,同时采用流式细胞仪检测治疗前后CD4＋ IL-17＋T细胞与CD4＋CD25＋T细胞的表达百分比.结果 2组患者在治疗前外周血Thl7细胞所占比例、Treg细胞所占比例、Th17/Treg细胞的比值差异均无统计学意义（t=1.747,0 149,0 091,P＞0.05）.治疗后,2组患者外周血Thl7细胞所占比例均明显下降（t=14.679,17.486,P＜0.01）,Treg细胞所占比例均明显升高（t=9.85,13.042,P＜0.01）,而Th17/Treg细胞的比值则下降（t=12.5,9.09,P＜0.01）.高压氧组Thl7细胞所占比例下降程度、Treg细胞所占比例升高程度以及Th17/Treg细胞的比值下降程度较对照组更为明显（t=9.076,8.638,2.227,P＜0.05）.结论 Th17/Treg失衡可能参与UC的发生发展,而HBO联合柳氮磺胺吡啶正是通过调节Th17/Treg的失衡关系,改善免疫抑制功能,抑制炎症因子的释放来达到抗炎-促炎平衡的治疗作用,这可能是其治疗UC的免疫调节重要机制之一.     

溃结汤对大鼠溃疡性结肠炎治疗及肠黏膜NF-κB的影响

目的探讨溃疡性结肠炎（UC）大鼠肠黏膜NF-κB的活化以及本科自拟中药溃结汤（KJT）对其影响和对UC的治疗作用。方法取50只健康成年Wistar大鼠,应用复合法（2,4-二硝基氯苯＋乙酸）制备细胞免疫反应性UC大鼠模型。取已造模成功Wistar大鼠40只,随机均分为模型组、KJT低剂量组、KJT高剂量组、柳氮磺胺吡啶（SASP）组,并设正常对照组Wistar大鼠10只。观察指标包括结肠重量,大体形态黏膜损伤程度评分,HE染色病理观察,扫描电镜肠黏膜损伤观察,NF-κB p65免疫组化染色（应用图像分析系统处理）。结果模型组结肠重量,大体形态黏膜损伤程度评分较对照组显著增加,NF-κB p65的表达水平显著升高,KJT低剂量组、KJT高剂量组、SASP组上述指标较模型组显著下降。结论 NF-κB表达的增加可能与UC的发生、发展有关;KJT和SASP的抗炎作用可能是通过抑制NF-κB的表达实现。     

The effects of an orally administered probiotic on sulfasalazine metabolism in individuals with rheumatoid arthritis: a preliminary study

Aim: To carry out a pilot study to investigate the effect of short‐term oral probiotic administration on the metabolism of sulfasalazine (SSZ) in patients with rheumatoid arthritis (RA) stabilized on SSZ. Methods: Twelve subjects with RA taking stable doses of SSZ for a minimum of 3 months prior to the study, received a probiotic preparation contained three strains of bacteria (1.8 × 10⁹ CFU/day) twice daily for 1 week. Single point blood and 12‐h urine samples were taken before and after probiotic treatment and 3 weeks following discontinuation of probiotics, for determination of SSZ and its metabolites. The presence of the probiotic bacteria in the feces of patients was investigated by denaturing gradient gel electrophoresis (DGGE). Results: Adverse events recorded were three instances of gastrointestinal disturbance and one flare of RA. Plasma and urinary levels of SSZ and its metabolites showed no statistically significant changes after probiotic administration and the incidence of gastrointestinal disturbance did not appear to be ascribed to higher sulfapyridine plasma levels. Probiotic‐specific DGGE bands were detected in the feces of some patients after the treatment period. Conclusions: Short‐term treatment of RA patients with a multi‐strain probiotic did not significantly influence SSZ metabolism as has been demonstrated in animal models.     

复方血竭制剂与5-氨基水杨酸在溃疡性结肠炎临床维持缓解治疗中的疗效比较

目的比较复方血竭灌肠液及口服5-氨基水杨酸（SASP）在溃疡性结肠炎（UC）临床维持缓解治疗中的疗效。方法以血竭、白芨为原料制备复方血竭灌肠液,对51例UC患者（血竭组）进行灌肠治疗6个月;SASP组给予SASP1.5g1次/d口服维持6个月,比较两组患者的复发率及治疗中的副作用。结果血竭组和SASP组疗效间差别无显著性意义（P〉0.05）;血竭组消化道反应、血液系统毒性、肝肾功能损害明显小于对照组（P〈0.01）。结论复方血竭灌肠可用于高危患者及SASP治疗无效者的维持治疗方案。