Double-Blind, Parallel Group Study to Compare the Clinical Effectiveness of Calcium Dobesilate 500 mg BID vs. Calcium Dobesilate LP 1 g OD, in Patients with Chronic Venous Insufficiency of the Lower Limbs

Background: Chronic venous insufficiency (CVI) describes a condition that affects the venous system of the lower extremities due to venous hypertension (VH. The prevalence is between 5% - 30%. CVI is associated with older age, smoking, lower extremity trauma, presence of an arteriovenous shunt, and elevated estrogen levels. All patients should be initially treated with conservative management. Venoactive drugs like calcium dobesilate are useful. Objectives: The primary objective compared the clinical improvement in patients with CVI, grades 0 - 3 of the CEAP classification of chronic venous disease, produced by two formulations of calcium dobesilate: calcium dobesilate LP 1 g OD vs calcium dobesilate 500 mg BID, immediate release. The secondary objective assessed the side effects of both formulations. Method: All patients took one tablet and one capsule at 7 am, and one capsule at 7 pm, for 8 weeks. One group received dobesilate 1 g OD and the other group received dobesilate 500 md BID. They were evaluated after 15, 30 and 60 days of treatment, using the symptom evaluation scale. Results: In both groups, there was a significant decrease in the symptom score after 15 days. Four patients in the Dobesilate OD group: had adverse effects, which did not require suspension of treatment. In the BID dobesilate group, there was one therapeutic failure, and one case of gastric discomfort. Conclusions: Prolonged-release Calcium dobesilate 1 g OD is as effective as calcium dobesilate 500 mg BID for the treatment of patients with chronic venous insufficiency.

Clinical effect of Calcium Dobesilate combinated with Alprostadil in the vascular endothelium of patients with diabetic nephropathy

Objective: To research the effect of calcium dobesilate combinated with alprostadil on the changes of vascular endothelium function in patients with t diabetic nephropathy (DN), and assess the clinical effect and record the untoward effect. Method: A totoal of 120 patients with DN, then they were randomly divided into control group (n=60) and observation group(n=60). Two groups were given hypoglycemic (melbinum)+improving circulatory (calcium dobesilate), and observation group were given alprostadil on the basic, they were treated 30 days. After treatment, we observed the changes of fasting plasma glucose (FBG), 2-hour postprandial blood glucose (2hPBG), the factot of vasomotion angiokinesis (nitrogen oxide (NO), endothelin-1 (ET-1), vascular endothelial growth factor (VEGF)), diastolic function of vascular endothelium (flow mediated dilation (FMD), nitroglycerin mediated dilation (NMD)), renal function index (glomerular filtration rate (GFR), creatinine (Cr), blood urea nitrogen (BUN), albumin excrete rate (AER), urinary albumin creatinine ratio (UACR), urinary albumin evacuate ratio (UAER)), and record the untoward effect. Results: After treatment, the FBG, 2hPBG were both lower than before treatment in both groups, the difference had statistical significance (P<0.05), and the FBG, 2hPBG in the observation group were lower than the control group, and the difference had statistical significance (P<0.05). After treatment, the ET-1, VEGF were both lower than before treatment in both groups, the difference had statistical significance (P<0.05), and the ET-1, VEGF in the observation group were lower than the control group, and the difference had statistical significance (P<0.05). After treatment, the NO, FDM, NDM were higher than before treatment in both groups, the difference had statistical significance (P<0.05), and the NO, FDM, NDM in the observation group were higher than the control group, and the difference had statistical significance (P<0.05). After treatment, the GFR, Cr, BUN, AER, UACR, and UAER were both lower than before treatment in both groups, the difference had statistical significance (P<0.05), and the GFR, Cr, BUN, UACR, and UAER in the observation group were lower than the control group, and the difference had statistical significance (P<0.05). Conclusions: Treatment of the patients with DN before improving the cardiovascular system and hypoglycemic, giving the alprostadil can improve the function of vascular endothelium, rasing the clinical effect and safety.

Effect of Calcium Dobesilate on Nephropathy in Type 2 Diabetic Rats

In order to investigate the effects and mechanisms of calcium dobesilate on renal lesions in experimental type 2 diabetic rats, dibetic rats were randomly divided into control group (group C) and experimental group (group D) treated with calcium dobesitate. The serum creatinine (Scr), protein kinase C (PKC), creatinine clearance (Ccr), transforming growth factor-beta 1 (TGF-β 1), type Ⅳ collagen were compared among the groups after 24 weeks. The renal tissues were observed under light microscopy and electron microscopy. The results showed that after 24 weeks, Scr, PKC, TGF-β 1 in group D were significantly lower than in group C, meanwhile, renal pathologic changes in group D were improved. Ccr had no difference between group C and group D. It was concluded that calcium dobesilate could ameliorate renal lesions in diabetic rats through inhibiting PKC and TGF-β 1.

Mechanisms of retinal neuroprotection of calcium dobesilate：therapeutic implications

Current treatments for diabetic retinopathy （DR） are based on laser photocoagulation and intravitreal injections of corti- costeroids or anti-vascular endothelial growth factor （VEGF） agents. These treatments are applicable only at advanced stages of the disease. In addition, they are expensive, require a vitreo- retinal specialist and are associated with significant adverse ef- fects. Therefore, new pharmacological treatments for the early stages of the disease are needed.

Effects of Calcium Dobesilate on Glomerulus TIMP1 and Collagen Ⅳ of Diabetic Rats

Summary ： To observe the effects of calcium dobesilate on the expression of glomerular tissue inhibitor of metalloproteinase 1 （TIMP1）, collagen Ⅳ , and ultrastrueture of glomerular basement mem- brane in diabetic rats, rats model of diabetes was established by unilateral nephreetomy and intraperitoneal injection of 1% STZ （55 mg/kg）, and rats were administered calcium dobesilate 100 mg/ kg （DD group） or distilled water （DM group） respectively. 12 weeks later, the changes in the renal uhrastrueture and ereatinine clearance rate （Cer） were examined in each group. The expression of glomerular TIMP1 and collagen Ⅳ were studied by immunohistoehemieal staining. Our results showed that after 12 weeks, the Cer in DD group increased and was significantly higher than that in DM group. Electron microscopy showed that thickness of glomerular capillary basement membrane （GBM） in Group DD was less than that of DM group. No hyperplasia of collagen fibers was found, and the distance betweeh the holes of endothelial cells in DD group was not as even as that in the normal group, but more even than that of DM group, and podocyte processes was still in order. Immunohistochemical staining of glomeruli showed that expression of TIMP1 and collagen Ⅳ in DD group were significantly less than those of DM group DM. It is concluded that calcium dobesilate can improve diabetic nephropathy by inhibiting the overaccumulation of collagen Ⅳ and calcium dobesilate may also contribute to diabetes by inhibiting the expression of TIMP1.

Protective effect of calcium dobesilate combined with benazepril therapy on renal injury in patients with early diabetic nephropathy and the possible molecular mechanisms

Objective:To explore the protective effect of calcium dobesilate combined with benazepril therapy on renal injury in patients with early diabetic nephropathy and the possible molecular mechanisms.Methods:A total of 50 patients with early diabetic nephropathy treated in our hospital between May 2012 and January 2016 were collected, and according to the random number table, the patients were divided into observation group (n=25) and control group (n=25). On the basis of conventional treatment, control group of patients received benazepril therapy, observation group of patients received calcium dobesilate combined with benazepril therapy, and the treatment lasted for 3 months. Before and after treatment, automatic biochemical analyzer was used to detect the levels of renal injury indexes in peripheral blood, RIA method was used to detect the levels of renal injury indexes in urine, ELISA method was used to detect the levels of renal fibrosis indexes and Western-blot method was used to detect the protein expression of TGF-β1/BMP-7 and Smad signaling pathway molecules in renal tissue. Results: Before treatment, differences in renal injury index levels, renal fibrosis index levels and signaling pathway molecule protein expression were not statistically significant between two groups of patients. After treatment, BUN, SCr andβ-TP levels in the peripheral blood as well as KIM-1 level in urine of observation group were lower than those of control group;renal fibrosis indexes TGF-β1, CTGF, TIMP-1, LN and HA levels in serum of observation group were lower than those of control group;TGF-β1 and Smad2/3 protein expression in renal tissue of observation group were lower than those of control group while Smad7 and BMP-7 protein expression were higher than those of control group.Conclusion: Calcium dobesilate combined with benazepril therapy can reduce the renal injury and inhibit the fibrosis process in patients with early diabetic nephropathy, and it achieves the above effect by regulating the TGF-β1/BMP-7 and Smad signaling pathway function.

羟苯磺酸钙对基于Trinder反应原理的血清ADA、 Crea、UA、TG、TC、GSP水平的影响

目的研究羟苯磺酸钙对血清生化检测结果的影响。方法10份血清分别加入10mg/L羟苯磺酸钙的血清为实验样品,测定各生化项目数值,计算偏倚,筛选出平均偏倚大于1/2总允许误差(TE)的项目。配置50、40、30、20、10、5mg/L羟苯磺酸钙干扰的血清,检测平均偏倚大于1/2 TE的项目结果,计算偏倚。结果羟苯磺酸钙浓度为10mg/L时,ADA、Crea、UA、TG、TC、GSP 6个项目的偏倚大于1/2 TE。随着羟苯磺酸钙浓度的增高,Crea、UA、TG、TC、GSP、ADA与真实水平的平均偏倚呈负向增高状态。此6项测试在羟苯磺酸钙浓度为5mg/L时,平均偏倚最低,分别为-10.47%、-6.44%、-7.16%、-5.53%、-10.95%、-18.87%;在羟苯磺酸钙浓度为50mg/L时,平均偏倚最高,分别为-42.99%、-22.23%、-27.84%、-9.83%、-36.08%、-57.32%。结论羟苯磺酸钙对基于Trinder反应原理的血清生化检测有影响,随着样本中羟苯磺酸钙浓度的增大,相对偏倚负向增大。

EFFECT OF ADDED DIETARY CALCIUM ON ESOPHAGEAL EPITHELIAL-CELL PROLIFERATION IN SUBJECTS AT HIGH RISK FOR ESOPHAGEAL CANCER: A DOUBLE-BLIND INTER-VENTION STUDY

A randomized double-blind intervention trial was carried determine whether oral calcium supplementation could lower the proliferation of epithelial cells of the esophagus. 41 subjects identified with precancerous lesions by histopathology were randomized to receive oral supplementation of their conventional diets with 0.6 g of calcium as calcium carbonate or placebo. Both at the entry to the study and at the end of the treatment, seven months later, the subjects were examined, with an emphasis on the frequency and distribution of proliferating epithelial cells of the esophagus. Patterns of cell proliferation was defined by dividing the esophageal epithelium into cell columns oriented perpendicularly to the basal cell layer and by comparing the numbers and fractions of tritiated thymidine-labeled epithelial cells in the various cell columns and cell compartments.Before dietary supplementation with calcium, the profile of proliferating epithelial cells in the esophageal compartments in calcium group is similar to that in the placebo group, which is comparable to that previously observed in subjects with high risk for esophageal cancer. Seven months after supplementation having been started, in calcium group, proliferation was significantly reduced and the profile of the esophageal columns approached to that previously observed in subjects at low risk for esophageal cancer, however, in the placebo group, the proliferation and profile maintain at the same level as that before supplementation. Our findings indicate that oral calcium supplementation induces a more quiescent equilibrium in epithelial-cell proliferation in the esophageal mucosa of the subjects at high-risk for esophageal cancer, similar to that observed in subjects at low risk.

碳酸钙联合维生素AD治疗小儿佝偻病的效果分析

目的:分析碳酸钙联合维生素AD治疗小儿佝偻病的效果。方法:选取2021年1月—2022年12月察布查尔锡伯自治县人民医院收治的120例佝偻病患儿作为研究对象,随机分为对照组与观察组,各60例。对照组给予碳酸钙治疗,观察组在对照组基础上给予维生素AD治疗。比较两组治疗效果。结果:观察组治疗总有效率高于对照组,差异有统计学意义(P=0.002)。治疗后,两组血磷、血钙、25-羟基维生素D_(3)水平高于治疗前,且观察组高于对照组,骨碱性磷酸酶水平低于治疗前,且观察组低于对照组,差异有统计学意义(P<0.05)。治疗后,两组桡骨、尺骨骨密度高于治疗前,且观察组高于对照组,差异有统计学意义(P<0.05)。两组不良反应总发生率比较,差异无统计学意义(P=0.714)。结论:碳酸钙联合维生素AD治疗小儿佝偻病的效果显著,能够改善血生化指标,增加骨密度,且安全性较高。

小儿四维葡钙颗粒联合维生素AD滴剂治疗小儿维生素D缺乏性佝偻病的临床效果

目的观察小儿四维葡钙颗粒联合维生素AD滴剂治疗小儿维生素D缺乏性佝偻病的临床效果。方法选取广东医科大学顺德妇女儿童医院2020年10月至2022年11月收治的110例维生素D缺乏性佝偻病患儿,采用随机数字表法分为两组,每组各55例。常规组使用维生素AD滴剂治疗,联合组在常规组基础上采用小儿四维葡钙颗粒治疗,比较两组的临床疗效、生化指标以及不良反应总发生率。结果联合组治疗总有效率高于常规组(P<0.05)。治疗前,两组碱性磷酸酶(ALP)、25-羟基维生素D_(3)[25-(OH)D_(3)]、血磷及血钙水平比较,差异无统计学意义(P>0.05);治疗后,两组ALP水平均降低,25-(OH)D_(3)、血磷及血钙水平均升高,且联合组ALP水平低于常规组,25-(OH)D_(3)、血磷及血钙水平高于常规组,差异有统计学意义(P<0.05)。两组不良反应总发生率比较,差异无统计学意义(P>0.05)。结论小儿四维葡钙颗粒联合维生素AD滴剂治疗小儿维生素D缺乏性佝偻病的临床效果显著,能够改善生化指标,且不会增加不良反应,值得推广。

紫外分光光度法直接测定AD钙盐中维生素A的含量

AD钙盐中的维生素A是以其乙酸酯的形态加入,而后者不溶于水。根据此性质,将AD钙盐试样用水浸取即可使维生素A与基体组分离,将不溶物分出,溶于乙醇中并定容为10 mL,随即可在此试样乙醇溶液中用UV-分光光度法测定维生素A。在维生素A的吸收峰325 nm波长处,用1 cm石英吸收皿以乙醇作参比液测得其吸光度。用高纯度的维生素A乙醇酯(纯度99.9%)作标准制作标准曲线,得其线性回归方程为cVC=16.899A+0.059,r=0.999 6,方法的回收率在97.7%至100.1%之间。此方法远较国家标准方法和药典方法简单、可行。

溶剂萃取紫外光谱法直接测定AD钙盐中维生素D的含量

应用溶剂萃取 ,利用紫外分光光度法直接测定了AD钙营养盐中维生素D的含量。实验结果表明 :维生素D不溶于水 ,易溶于乙醇中 ,在无水乙醇中较为稳定 ,在乙醇溶液中的特征吸收峰为λmax2 6 5nm。标准曲线的线性关系好 ,r =0 .9996 ,实验添加回收率为 98.0 4 %。

调心方对氧化损伤型类AD模型大鼠“有害网络”作用的研究

研究调心方 (主药 :党参、桂枝、茯苓、菖蒲、远志 )防治阿尔茨海默病 (AD)的作用机理。SD雄性大鼠采用二羟延胡索酸 (DHF) +FeCl3+ADP左侧脑室注射法建立氧化损伤型类AD模型。造模前 1周开始以调心方灌胃 ,连续 4周 ,并与西药Donepezil比较。治疗期间及之后 ,观察大鼠空间学习记忆能力、大脑皮质细胞色素氧化酶Ⅱ型亚基 (COⅡ )mRNA表达、大脑皮质和海马APPmRNA表达、大脑皮质Aβ沉积及脑组织Ca2 + 含量等指标的变化。结果 :与正常组比较 ,氧化损伤型类AD模型大鼠上述各项指标呈现不同程度的异常变化 ,调心方具有明显的纠正作用 ,且效果优于西药。结论 :调心方可以阻断AD鼠的“有害网络”的形成 。

嗅三针对AD大鼠的治疗效应与海马细胞钙稳态的相关性研究

目的:探讨嗅三针疗法对阿尔茨海默病(AD)大鼠的疗效与海马细胞钙稳态的相关性。方法:成年SD雄性大鼠50只,随机分为正常对照组、AD模型组、AD嗅神经切断模型组、嗅三针组和嗅三针对照组,每组10只。制作AD大鼠模型和AD嗅神经切断大鼠模型,通过嗅三针治疗,测试大鼠水迷宫学习记忆能力并采用荧光分光光度法测定海马细胞内Ca2+浓度。结果:水迷宫定位航行试验结果显示:平均逃避潜伏期和平均游泳路程比较,正常对照组和嗅三针组均明显短于AD模型组(P<0.01);嗅三针对照组短于AD模型组(P<0.05);嗅三针组短于嗅三针对照组(P<0.05);AD模型组与AD嗅神经切断模型组相比较,其差异无显著性意义(P>0.05)。海马细胞内Ca2+浓度比较:正常对照组、嗅三针组和嗅三针对照组均明显低于AD模型组(P<0.01);嗅三针组低于嗅三针对照组(P<0.05);AD模型组与AD嗅神经切断模型组相比较,其差异无显著性意义(P>0.05)。结论:嗅三针能够显著增强AD大鼠学习记忆功能,并且能够降低海马细胞内Ca2+浓度,其治疗效应的发挥依赖于嗅觉传导通路的完整性。

调心方对氧化损伤型类AD大鼠空间记忆能力和神经元钙稳态的影响

目的 :探讨调心方对氧化损伤型类AD大鼠空间学习记忆能力、脑神经元钙稳态的影响。方法 :采用二羟延胡索酸(DHF)加FeCl3 ADP左侧脑室注射 ,造成大鼠氧化损伤型类AD大鼠模型 ;Morris水迷宫法观察大鼠空间学习记忆能力 ;荧光分光光度法测皮质和海马胞浆钙离子浓度。结果 :与对照组比较 ,模型鼠空间学习记忆能力显著下降 ,皮层、海马胞浆钙稳态失衡 ,调心方对此有明显改善作用。结论 :调心方具有改善氧化损伤型类AD大鼠空间学习记忆障碍。

AD钙盐中维生素A的测定方法研究

目的 目前关于AD钙盐中维生素A的含量分析的较好方法未见报道 ,国标及药典中维生素A的含量的测定方法较为烦琐 ,一般实验条件难以进行 ,本实验目的是选择简便易行的分析方法。方法 研究了应用溶剂萃取 ,用紫外分光光度法直接测定维生素A的含量的方法。结果 该方法的灵敏度高、线性关系好 (r =0 .996 8) ,平均回收率为 98.86 %。结论 该方法准确、可靠简便易行。适合于企业及一般实验条件 。

AD钙奶对ICR小鼠生长发育的影响

[目的] 探讨AD钙奶对ICR小鼠生长发育的作用。[方法] 将清洁级ICR种鼠体重为26～28克,饲喂全价颗粒饲料,饲养于SPF级动物实验室内。将ICR种鼠随机分为4组,设立3个剂量组和对照组,给样途经灌胃。[结果] 与对照组相比,AD钙奶组体重增长情况、牙齿萌出时间、开眼时间、睾丸下降时间、尾长和胫骨长、空中翻正试验、游泳发育试验等均存在显著性差异。

调心方对Aβ所致AD大鼠“有害网络”作用的实验研究

目的 :观察调心方对Aβ所致“AD”模型大鼠氧化损伤、能量代谢受抑和钙稳态失衡等多因素构成的“有害网络”作用的影响。方法 :采用Aβ1 40片段左侧脑室注射法建立Aβ沉积型“AD“大鼠模型 ;Morris水迷宫法观察大鼠空间学习记忆能力 ;Clark氧电极法观察线粒体呼吸链琥珀酸脱氢酶、NADH脱氢酶和细胞色素氧化酶活性 ;Fura2 /AM 荧光法测定脑神经元胞浆内Ca2 + 含量 ;分光光度法检测脑组织超氧化物歧化酶 (SOD)活性、过氧化脂质产物—丙二醛 (MDA)和活性氧类 (ROS)含量 ;电子显微镜观察脑皮层和海马线粒体超微结构 ;以及调心方对AD大鼠上述指标变化的影响。结果 :与正常组比较 ,AD模型大鼠上述各项指标呈现不同程度的异常变化 ,调心方具有明显的纠正作用。结论 :调心方可以通过纠正上述各项指标的异常变化 ,防治AD的发生与发展。

碳酸钙加维生素AD治疗小儿佝偻病的临床效果评价

目的 评价碳酸钙加维生素AD治疗小儿佝偻病的临床效果。方法 60例小儿佝偻病患儿,随机分为研究组与常规组,各30例。常规组应用碳酸钙治疗,研究组应用碳酸钙加维生素AD治疗。比较两组治疗前后骨密度、生化指标,治疗效果,不良反应发生情况。结果 治疗后,研究组桡骨、尺骨骨密度均高于常规组,差异有统计学意义(P<0.05)。治疗后,研究组骨碱性磷酸酶、血钙水平显著优于常规组,差异有统计学意义(P<0.05)。研究组治疗总有效率96.67%高于常规组的66.67%,差异有统计学意义(χ^(2)=9.0167, P=0.0027<0.05)。两组不良反应发生率比较,差异无统计学意义(χ^(2)=1.0169,P=0.3132>0.05)。结论 采取碳酸钙加维生素AD治疗小儿佝偻病的效果明显优于单一碳酸钙治疗,可有效改善患儿骨密度以及相关生化指标。

Role of presynaptic calcium stores for neural network dysfunction in Alzheimer＇s disease

Alzheimer’s disease（AD）is the most common form of dementia representing a major problem for public health.In 2017 there were an estimated 50 million patients worldwide and this number is expected to almost double every 20years,reaching 75 million in 2030 and 131.5 million in 2050（https：//www.alz.co.uk/research/statistics）.