Protein feeding and the activity of adenosine deaminase and purine nucleoside phosphorylase in rat thymus

It is known that the thymus is severely affected by nutritional deficiency. Adenosine deaminase (ADA) and Purine Nucleoside Phosphorilase (PNP) are thought to be important for normal lymphocyte development. The present paper studies the effect provoked on the activity of these thymic enzymes in growing rats by marginal(PF15), moderate(PF20) and severe(PF25) protein deprivation and the subsequent oral administration of a 20% dietary protein during 9 days (R). Results were expressed as μmol uric acid x 10⁻¹/W, per five minutes, where W = Tw (mg)/Bw(g)^0.75. (Mean ± S.D.). Statistical differences between PF15 and Control (C) in: ADA (17.5±4.1 vs. 10.5±2.8), PNP (7.1±0.8 vs. 3.7±0.9); PF20 and C in:, ADA (15.7±4.5 vs. 9.1±3.0), PNP (10.3±4.1 vs. 3.9±1.0); PF25 and C in: ADA (17.0±2.6 vs. 9.1±3.0) and PNP (11.5±4.2 vs. 3.9±1.0) were observed (p< 0.01). When PF25 was refed with a 20% casein diet(R), activity of ADA and PNP decreased significantly when compared to PF25. No statistical differences in ADA and PNP were observed between R and its Control (7.4±2.5 vs. 9.3±1.8; 3.6±0.5 vs. 3.9±0.6, respectively). The results show that protein deprivation at weaning provokes increase in ADA and PNP activities. The refeeding with a 20% protein diet during 9 days is enough to reverse the effect produced by severe protein malnutrition on ADA and PNP activities.     

Effect of purine nucleosides and nucleotides on the in vivo radiation response of normal tissue in the rat

WAG/Rij rats were exposed to single doses of radiation following intraperitoneal injection of inosine, pyruvate and inorganic phosphate (IPP). When skin reactions and structural damage were scored in the hind legs of irradiated rats, IPP was observed to decrease radiation sensitivity. Radioprotection was also observed in rats that were pretreated, with inosine alone and with the purine nucleosides adenosine and guanossine. The purine nucleotides 5′-inosine monophosphate (IMP), 5′-adenosine monophosphate (AMP), 5′-guanosine monophosphate (GMP) and cyclic adenosine 3′,5′-monophosphate (cyclic AMP) were also protective. The purine bases hypoxanthine, adenine and guanine were not protective. A decline in blood pressure was observed following administration of either IPP or inosine alone but not following AMP or cyclic AMP. The mechanism(s) whereby the purine nucleosides and nucleotides result in radioprotection are currently being investigated.     

黄芩清热除痹胶囊联合西药治疗急性痛风性关节炎的临床效果

目的：探讨黄芩清热除痹胶囊治疗急性痛风性关节炎的临床效果。方法：选取2018年1月至2021年6月安徽中医药大学第一附属医院收治的急性痛风性关节炎患者80例作为研究对象,按照随机数字表法分为对照组和观察组,每组40例。对照组使用西药治疗。观察组在对照组用药基础上给予黄芩清热除痹胶囊。比较2组的治疗效果、自感关节疼痛治疗起效时间、超敏C反应蛋白（hs-CRP）、尿酸(UA)、红细胞沉降率（ESR）、Toll样受体4(TLR4)阳性比例、中医症状评分、视觉模拟评分（VAS）及不良反应发生率。结果：观察组的治疗效果（97.50%）优于对照组（75.00%）;观察组的自感关节疼痛治疗起效时间短于对照组;2组在治疗后的hs-CRP、UA、ESR、TLR4、VAS、中医症状评分均降低,观察组均低于对照组;观察组的不良反应发生率（7.50%）低于对照组（25.00%）（均P<0.05）。结论：针对急性痛风性关节炎的就诊患者,在常规使用西药治疗的基础上给予黄芩清热除痹胶囊,有助于减轻疼痛程度,改善各项血液相关指标及疾病的相关中医症状评分,提升疗效,不良反应发生率较低。     

A case of non-cirrhotic portal hypertension associated with anti-retroviral therapy in a Japanese patient with human immunodeficiency virus infection

The diagnosis of non-cirrhotic portal hypertension (NCPH), a rare but potentially life-threatening complication in human immunodeficiency virus (HIV)-positive individuals, often occurs only after the emergence of fatal manifestations such as bleeding of esophageal varices. We herein report a female Japanese HIV patient who developed NCPH approximately 4 years after discontinuation of 65 months of didanosine (ddI) administration. The patient presented with severe ascites, bloody bowel discharge, extreme abdominal swelling, and symptoms of portal hypertension but no sign of liver cirrhosis. Examination revealed esophageal varices, oozing-like bleeding from a wide part of the colon, significant atrophy of the right lobe of the liver, and arterio-portal shunting and recanalization from the left medial segment branch of the portal vein to a paraumbilical vein, but no visible obstruction of the main trunk of the portal vein. Treatment for esophageal varices consisted of coagulation therapy with argon plasma after enforcement by endoscopic sclerotherapy and oral administration of β-blockers for elevated portal blood pressure. The patient has not experienced gastrointestinal bleeding in the approximately 5 years since the diagnosis of NCPH. Reviewing this case suggests the importance of suspecting NCPH in HIV patients with liver dysfunction of unknown etiology with a history of ddI and other purine analogs use, as well as the importance of controlling portal hypertension and esophageal varices in the treatment of NCPH.     

嘌呤类似物单用或联合环磷酰胺治疗慢性淋巴细胞白血病安全性的Meta分析

目的系统评价嘌呤类似物联合环磷酰胺与单用嘌呤类似物治疗慢性淋巴细胞白血病（CLL）的安全性。方法检索PubMed数据库、ISI数据库、Embase数据库、Cochrane图书馆临床对照试验数据库、OVID数据库嘌呤类似物联合环磷酰胺、单用嘌呤类似物治疗CLL的随机对照试验,按Cochrance协作网推荐的方法进行质量评价、资料提取,采用Revman4．3．2软件进行Meta分析。结果共纳入4个随机对照试验,包括1358例患者。Meta分析结果显示,嘌呤类似物联合环磷酰胺与单用嘌呤类似物比较,严重白细胞减少（Ⅲ-Ⅳ级）发生率增加,差异有统计学意义[RR=1．47,95％置信区间（CI）1．10—1．98,P=0．011;严重贫血（Ⅲ—Ⅳ级）（RR=1．03,95％C10．74—1．43,P=0．87）、血小板减少（Ⅲ～Ⅳ级）（RR=1．28,95％CIO．99～1．65,P=0．06）发生率差异无统计学意义。结论与单用嘌呤类似物治疗CLL比较,嘌呤类似物联合环磷酰胺严重贫血、血小板减少发生率无明显增加,但严重白细胞减少发生率增加,临床使用时应引起重视。     

Synthesis and anticancer activity of (RS)-9-(2,3-dihydro-1,4-benzoxaheteroin-2-ylmethyl)-9H-purines

Herein are reported the synthesis and anticancer activity against the human breast cancer cell line MCF-7 of a series of substituted (RS)-9-(2,3-dihydro-1,4-benzoxathiin-2-ylmethyl)-9H-purine derivatives and (RS)-9-(2,3-dihydro-1,4-benzodioxin-2-ylmethyl)-9H-purine derivatives. When the Mitsunobu reaction was carried out between (RS)-2,3-dihydro-1,4-benzoxathiin-3-methanol and the heterocyclic bases 6-chloro-, 2,6-dichloro, and 6-bromo-purines under microwave-assisted conditions, a formal 1,4-sulfur migration takes place through two consecutive oxyranium and episulfonium rings, giving rise to the corresponding (RS)-9-(2,3-dihydro-1,4-benzodioxin-3-ylmethyl)-9H-purine derivatives, previously reported by us. The most active compound (RS)-2,6-dichloro-9-(2,3-dihydro-1,4-benzoxathiin-2-ylmethyl)-9H-purine shows an IC₅₀ = 2.75 ± 0.02 μM. When the cancerous cells were treated with this compound, a significant increase of apoptotic cells (70.08 ± 0.33%) was obtained in relation to the control ones. The induction of the G₂/M cell cycle arrest and apoptosis by the three most active compounds is associated with increased phosphorylation of eIF2α in human breast cancer cells.     

Anticancer activity and cDNA microarray studies of a (RS)-1,2,3,5-tetrahydro-4,1-benzoxazepine-3-yl]-6-chloro-9H-purine, and an acyclic (RS)-O,N-acetalic 6-chloro-7H-purine

Completing a SAR study, a series of (RS)-6-substituted-7- or 9-(1,2,3,5-tetrahydro-4,1-benzoxazepine-3-yl)-7H or 9H-purines was previously prepared. The most potent antiproliferative agent against the MCF-7 adenocarcinoma cell line that belongs to the benzoxazepine O,N-acetalic family is (RS)-9-[1-(9H-fluorenyl-9-methoxycarbonyl)-1,2,3,5-tetrahydro-4,1-benzoxazepine-3-yl]-6-chloro-9H-purine (16, IC₅₀ = 0.67 ± 0.18 μM), whilst (RS)-7-{2-(N-hydroxymethylphenyl)-2-nitrobenzenesulfonamido]-1-methoxyethyl}-6-chloro-7H-purine (37) shows the lowest IC₅₀ value between the family of acyclic O,N-acetals (IC₅₀ = 3.25 ± 0.23 μM). Moreover, 16 showed the better in vitro Therapeutic Index in breast cell lines (3.19), whilst 37 was found to be 3.69-fold more active against HT-29 human colon cancer cell line than versus IEC-6 normal rat intestinal epithelial cell line. The global apoptotic cells caused by 16 and 37 against MCF-7 were 80.08% and 54.85% of cell population after 48 h, respectively. cDNA microarray technology reveals potential drug targets, which are mainly centred on positive apoptosis regulatory pathway genes, and the repression of genes involved in carcinogenesis, proliferation and tumour invasion.     

Targeting gene therapy for hepatocarcinoma cells with the E. coli purine nucleoside phosphorylase suicide gene system directed by a chimeric alpha-fetoprotein promoter

For hepatocarcinoma (HCC) gene therapy, the tumoricidal efficacy and selective expression of therapeutic gene remain two major challenges. The Escherichia coli (E. coli) purine nucleoside phosphorylase (PNP)/9-(2-deoxy-beta-dribofuranosyl)-6-methylpurine (MeP-dR) suicide gene system exhibits excellent anti-tumor effects, indicating this system directed by a HCC-specific promoter would offer a possibility of targeting gene therapy for HCC. To test this hypothesis, here, we prepared a plasmid (p[HRE]AF/PNP) containing the E. coli PNP/MeP-dR system and a chimeric human alpha-fetoprotein (AFP) promoter, [HRE]AF. We introduced this plasmid into AFP-positive and low-AFP-generating human HCC cells, and evaluated its therapeutic effects on both human HCC cell lines. In the presence of hypoxia, the E. coli PNP gene directed by the [HRE]AF promoter were HCC-specifically expressed in two human HCC cell lines and, moreover, the [HRE]AF-PNP/MeP-dR therapy would yield significant and selective cytotoxicity in both AFP-positive and low-AFP-generating HCC cells. Our findings suggest the [HRE]AF-PNP/MeP-dR therapy has worthy potentialities as an effective strategy for targeting therapy of AFP-positive, and especially AFP-negative or low-AFP-generating HCC.     

低嘌呤饮食联合碳酸氢钠、非布司他治疗肥胖合并高尿酸血症的临床研究

目的 探究低嘌呤饮食联合碳酸氢钠、非布司他治疗肥胖合并高尿酸血症的临床疗效.方法 前瞻性选取2018年1月至2019年3月保定市第一中心医院收治的肥胖合并高尿酸血症患者124例,采用随机数字表法分为观察组与对照组,对照组采用低嘌呤饮食治疗,观察组在对照组基础上联合碳酸氢钠、非布司他治疗.对比2组患者治疗前和治疗后3个月...