Effect and mechanism of fucoidan derivatives from Laminaria japonica in experimental adenine-induced chronic kidney disease

Ethnopharmacological relevance

Laminaria japonica is a popular seafood and medicinal plant in China, Chinese people use them as a traditional medicine for curing edema disease, a symptom of kidney diseases.

Materials and methods

The renal protective activity and mechanism of fucoidan derivatives was studied against adenine induced CKD in rats. The fucoidan derivatives were administered at dose of 50 and 150 mg/kg body weight. The serum urea nitrogen (SUN), serum creatinine (SCR) and some enzymic activity were detected.

Results

The SUN and SCR level decreased significantly with fucoidan derivatives administration. Histopathological changes of renal tubules and interstitium were markedly alleviated by fucoidan derivatives and the mesangial areas were also greatly reduced. Alterations were observed in the activities/levels of serum enzymic (CAT, GSH-PX) and non-enzymic (GSH) antioxidants, along with high level of malondialdehyde (MDA) in the CKD rats. However, normalized lipid peroxidation and antioxidant defenses occurred with fucoidan derivatives administration.

Conclusion

This study exhibited a new mechanism of fucoidan derivatives on CKD rats, that was the samples could alleviate renal tubules, interstitium and mesangial areas mediated by replacing the electronegative content of the glomerular cells and inhibition of mesangial cell proliferation. The study also proved the mechanism of fucoidan derivatives on the CKD rats had relationship with their antioxidant activities, the samples which could enhance the activity of antioxidant enzymes and reduce the LPO level could alleviate the symptom of CKD.     

Topical Application of Fucoidan Improves Atopic Dermatitis Symptoms in NC/Nga Mice

Fucoidan is a sulphated polysaccharide extracted from brown seaweed and possesses a wide range of pharmacological properties including antiallergic and immunologic activities. The present study attempted to examine the effectiveness of fucoidan from Undaria pinnatifida in the treatment of atopic dermatitis (AD) in the NC/Nga mice model. Three per cent fucoidan or 0.1% dexamethasone was topically applied to the dorsal skin of AD‐induced mice for 4 weeks. The dermatitis severity scores and scratch counts of fucoidan or dexamethasone‐treated animals were significantly lower than the control group. Histological analysis showed that the number of mast cells infiltrating into skin lesions and the epidermis thickness were significantly decreased after the treatments. Levels of serum histamine and IgE were also decreased. There was no significant difference on improvement of AD‐like symptoms between fucoidan and dexamethasone. To elucidate possible mechanism of action, effects of fucoidan on regulation of AD‐associated chemokines, such as thymus‐ and activation‐regulated chemokine (TARC), macrophage‐derived chemokine (MDC) and regulated upon activation, normal T‐cell expressed and secreted (RANTES) chemokine, were investigated in human epidermal keratinocytes. Fucoidan significantly inhibited mRNA expression of these chemokines in a dose‐dependent manner. This is the first animal study to demonstrate that fucoidan has significant effects on improving AD‐like conditions as effective as dexamethasone, a well‐recognized corticosteroid remedy for the disease. Copyright © 2012 John Wiley & Sons, Ltd.     

褐藻多糖硫酸酯对H2O2诱导皮层神经元氧化应激损伤保护作用

目的 研究褐藻多糖硫酸酯对H2O2诱导小鼠皮层神经元氧化损伤的保护作用,并探讨其作用机制.方法 以含有B-27的Neurobasal培养基无血清体外原代培养新生小鼠大脑皮层神经元,H2O2 (50μtmol/L)诱导氧化应激损伤模型,MTT法检测不同质量浓度(0.01、0.1、1g/L)褐藻多糖硫酸酯对细胞存活的影响,生化法测定乳酸脱氢酶(LDH)释放量和丙二醛(MDA)、超氧化物歧化酶(SOD)的活性.结果 与H2O2处理组比较,0.1、1g/L褐藻多糖硫酸酯能显著提高H2O2诱导损伤皮层神经元的存活率(P＜0.05),并且降低培养液中LDH的漏出量,抑制细胞内MDA的生成,提高细胞内SOD的活性.结论 褐藻多糖硫酸酯对H2O2损伤皮层神经元具有显著的保护作用,其机制与抗氧化作用有关.     

腹腔镜胆囊切除术前使用单次低分子肝素钙对预防下肢深静脉血栓形成疗效临床研究

目的:对比研究术前单次使用低分子肝素钙在腹腔镜胆囊切除术(LC)预防下肢深静脉血栓形成(DVT)疗效。方法:对LC患者按进院先后随机分组,研究组(A组)术前15 min皮下注射5 000μg低分子肝素钙,再行LC。对照组(B组)行常规LC手术。术后3 d常规行下肢血管彩超检查。结果:A组的血栓率为0.54%,B组的血栓率为6%,比较差异有统计学意义(P<0.05)。结论:腹腔镜胆囊切除术前使用单次低分子肝素钙对预防下肢深静脉血栓形成疗效明显,对术中术后出血无明显影响。     

Safety assessment of new antithrombotic agents: lessons from the EXTEND study on ximelagatran

BACKGROUND: Ximelagatran, the first oral direct thrombin inhibitor, was shown to be an effective antithrombotic agent but was associated with potential liver toxicity after prolonged administration. OBJECTIVES AND METHODS: The aim of the EXTEND study was to assess safety and efficacy of extended administration (35 days) of ximelagatran or enoxaparin for the prevention of venous thromboembolism after elective hip replacement and hip fracture surgery. A follow-up period, including assessment of liver enzymes (in particular alanine aminotransferase; ALAT), until post-operative day 180 was planned, with visits at days 56 and 180. RESULTS: Randomization and administration of study drugs were stopped following a report of serious liver injury occurring 3 weeks after completion of ximelagatran treatment. At the time of study termination, 1158 patients had been randomized and 641 had completed the 35-day treatment; with 303 ximelagatran and 265 enoxaparin patients remaining in the study through to the day 56 follow-up visit. Overall, 58 patients showed an ALAT increase to >2x upper limit of normal: 31 treated with enoxaparin, 27 with ximelagatran. Three ximelagatran patients also showed symptoms potentially related to liver toxicity. Eleven ximelagatran patients showed an ALAT increase after study treatment ended. The clinical development of ximelagatran was terminated and the drug withdrawn from the market. Evaluation of the relative efficacy of the two treatments as specified in the protocol was impossible due to the premature termination of the study. CONCLUSIONS: Prolonged administration of ximelagatran was associated with an increased risk of liver toxicity. In a substantial proportion of patients, ALAT increase occurred after treatment withdrawal. The findings seen with ximelagatran should be considered when designing studies with new antithrombotic agents.     

低分子肝素钙改善急性胰腺炎患者胰腺血流灌注功能的观察

目的探讨低分子肝素钙对改善急性胰腺炎（AP）患者胰腺血流灌注的作用。方法将82例AP患者,其中重症急性胰腺炎（SAP）19例,轻症急性胰腺炎（MAP）63例,按就诊顺序分为常规治疗组40例和联合治疗组42例,以健康志愿者22例作对照组。常规治疗组采用常规治疗,联合治疗组采用常规治疗＋低分子肝素钙,以64层螺旋CT检测血流灌注参数血流量、血容量、平均通过时间（MTT）和表面通透性（PS）为观察指标。结果对照组血流量、血容量分别为（342．21±145．24）ml／（100g·min）、（27．20±8．32）ml／100g显著高于MAP组和SAP组（P〈0．05）,同时MAP组血流量显著高于SAP组（P〈0．05）。常规治疗组AP患者经常规治疗后血流量、血容量较治疗前轻度升高,差异无统计学意义（P〉0．05）;联合治疗组AP患者治疗后血流量、血容量较治疗前明显升高,差异有统计学意义（P〈0．05）。联合治疗组患者平均治疗日程、住院日程和常规治疗组相比明显缩短（P〈0．05）。结论AP的CT灌注参数可以作为判断胰腺炎微循环严重程度的一个量化指标,早期使用低分子肝素钙治疗AP对改善胰腺血流灌注具有较好的作用。     

低分子肝素治疗心绞痛的疗效研究

目的观察低分子肝素治疗心绞痛的疗效。方法选择符合心绞痛患者80例,随机分为治疗组A42例（低分子肝素组＋常规药物治疗）,和对照组B38例（未使用低分子肝素组）,比较两组治疗心绞痛的疗效。结果治疗组有效率95．2％,对照组有效率65．79％,两组存在显著差异。结论低分子肝素联合常规治疗药物对心绞痛患者是安全有效的治疗方法。     

低分子肝素治疗新生儿硬肿症的疗效观察

目的比较低分子肝素与标准肝素治疗新生儿硬肿症的有效性。方法将42例新生儿硬肿症患儿分为两组,低分子肝素组（22例）：常规基础治疗加用低分子肝素钙40U/（kg.次）,皮下注射,2次/d;标准肝素组（20例）：常规基础治疗加用标准肝素0.5mg/（kg.次）,皮下注射,2次/d。结果两组患儿经治疗后硬肿消退时间基本相似。但两组肝素使用时间比较,低分子肝素组明显短于标准肝素组（P〈0.05）。结论低分子肝素较标准肝素治疗新生儿硬肿疗效肯定且安全可靠。     

Anti-HIV activity of extracts and compounds from algae and cyanobacteria

The human immunodeficiency virus (HIV) is the retrovirus that causes the acquired immune deficiency disease syndrome (AIDS). This review discusses the anti-HIV activity of extracts and compounds isolated from freshwater and marine algae, and cyanobacteria (formerly called "blue-green algae"). Compounds and extracts with anti-HIV activity are also active against other retroviruses such as herpes simplex virus (HSV), but the amount of antiviral activity varies with the compound and the virus. Most of the research has focused on sulfated homopolysaccharides and heteropolysaccharides. Sulfoglycolipids, carrageenans, fucoidan, sesquiterpene hydroquinones, and other classes of compounds with anti-HIV activity that have been isolated from algae have received less attention. Most studies have used in vitro test systems, but a few in vivo studies have been carried out using compounds isolated from algae or analogs produced synthetically or isolated from other natural sources. Sulfated homopolysaccharides are more potent than sulfated heteropolysaccharides. The presence of the sulfate group is necessary for anti-HIV activity, and potency increases with the degree of sulfation. Studies using nonsulfated and sulfated homo- and heteropolysaccharides isolated from algae or other natural sources, or synthesized, have revealed the mechanisms of binding of drugs to the virion, and the mechanisms of viral binding to host cells. However, given the few classes of compounds investigated, most of the pharmacopeia of compounds in algae and cyanobacteria with antiretroviral activity is probably not known.     

Examination of megalin in renal tubular epithelium from patients with Dent disease

Dent disease is characteristic for the urinary loss of low-molecular-weight proteins and calcium, leading to renal calcification and, in some patients, chronic renal failure. This disorder is caused by loss-of-function mutations in the renal chloride channel gene, CLCN5. The animal model of this disease has demonstrated the possible role of disturbed megalin expression, which is a member of the low-density lipoprotein receptor family and is associated with renal reabsorption of a variety of proteins, in Dent disease. We examined the expression of megalin in the renal tubular epithelium of two unrelated patients with Dent disease. One patient, whose CLCN5 gene was completely deleted, showed significantly decreased staining of megalin compared with controls, while there was no change in another patient with partial deletion of the gene. These results demonstrated that mutation of CLCN5 in some patients with Dent disease may impair the expression of megalin, resulting in abnormal calcium metabolism, manifested as hypercalciuria and nephrocalcinosis.