The aim of the study is to investigate the radioprotective effect of polysaccharide extract from Sipunculus nudus (SNP). Beagle dogs were randomly divided into the following six groups. Group-1: Un-treated and un-irradiated controls. Group-2: Exposed to a single acute dose of 2 Gy γ-radiation alone. Groups-3, 4 and 5: Oral administration of SNP at 50, 100 or 200 mg/kg body weight once a day for 7 days followed by a single acute whole body exposure to 2 Gy γ-radiation. The same doses of SNP were administered for further 27 days. Group-6: Positive controls treated with 1.6 mg/kg Nilestriol by gavage after radiation. Blood parameters including white/red cells and platelet counts, as well as hemoglobin level, were assessed every other day for 34 days (7 days before and 27 days of experiment). Serum separated from aliquots of the same blood sample was used to estimate enzyme activity of antioxidant superoxide-dismutase, and to determine levels of free radical, nitric oxide, hydroxyl and superoxide anion. At the end of the experiment, all dogs were euthanized to weigh the organs for organ co-efficient calculation. Pathological changes were assessed in the bone marrow. The results showed that the dogs exposed to γ-radiation alone exhibited a typical hematopoietic syndrome. In contrast, at the end of 27 days experiment, dogs received oral administration of SNP+γ-radiation showed: (i) a much improved blood picture as indicated by shorter duration of leucopenia, neutropenia, thrombocytopenia (platelet counts), as well as hemoglobin levels, (ii) significantly improved hematopoietic activity in the bone marrow, (iii) substantial decrease in nitric oxide levels, and notable increase in activity of antioxidant superoxide dismutase. The results suggested that oral administration of SNP in Beagle dogs was effective in facilitating the recovery of hematopoietic bone marrow damage induced by γ-radiation.

Objective To study the DNA damage of bone marrow cells of mice after exposure to Radon.Methods Twenty-four mice were randomly divided into four groups, one control group and three experimental groups with the cumulative doses of radon at 27 WLM (low dose group), 52 WLM (middle dose group) and 105 WLM ( high dose group). DNA damage induced by radon in bone marrow of mice was detected by methods of single cell gel electrophoresis (SCGE), micronucleus(MN) and laser scanning confocal microscope (LSCM) observation. Results The DNA strand breakage, rate of MN and apoptosis increased significantly in the high dose group, but not in the middle and low dose groups. Conclusions Exposure to radon could induce DNA damage in bone marrow cells of mice at high levels.

This study examined the tissues distribution and pharmacokinetics of rhTNT-IL2, a fusion protein, in rats and macaques after iv. injection. The rhTNT-IL2 was labeled with 125I. The 125I-rhTNT-IL2 was administered into rats and macaques at a dose of 250 μg·kg−1 and 125 μg·kg−1, respectively. Upon administration, rhTNT-IL2 declined in tri-exponentially with the half-lives of 1.78 h (T 1/2α), 25.06 h (T 1/2β), 114.19 h (T 1/2γ) for rats and 1.87 h (T 1/2α), 9.82 h (T 1/2β), 43.17 h (T 1/2γ) for macaques. The fraction of 125I-rhTNT-IL2 excreted in feces was low (about 1%), while the majority of 125I-rhTN-IL2 was excreted in urine. The tissue distributions showed that the liver, spleen and heart were major organs for deposition of the fusion protein in rats and macaques in 48-hour post-injection, and the fusion protein could not penetrate through blood brain barrier.

Aim: To investigate the pharmacokinetics and biodistribution of 125I labeled rhTNT-IL2 in rats, a novel fusion protein of recombinant human monoclonal antibody of tumour karyon and Interleukin 2 by genetically engineer. Methods: Rats were divided into three groups and administrated with 0.125, 0.25 and 2.5 mg · kg-1 respectively, and blood, tissues, urine and ordure were taken at exset times. Radioactivity was measured in all samples before and after trichloroacetic acid (TCA) precipitation. Data of blood were analyzed using DSA1.0 software. Results: Blood radioactivity in rats decreased tri-exponentially with half-lives of 1.77-3.03 h(T 1/2 α), 24.58-28.88 h(T 1/2 β), 82.17-114.09 h (T 1/2 γ). Liver, spleen, lung, kidney and ovary were the major organs for deposition of I-rhTNT-IL2 in rats. Urinary excretion represented the major pathway of elimination, with 67.1% of the administrated dose excreted in urine over 24 h. Conclusion: These findings indicate that rhTNT-IL2 has a potential therapeutic use in tumour necrosis therapy.

<span id="ChDivSummary" name="ChDivSummary" class="abstract-text">目的研究125I标记的重组人肿瘤坏死单抗白细胞介素2融合蛋白（rhTNTIL2）单次静脉注射后在大鼠体内的药代动力学过程。方法用125I标记rhTNTIL2,γ放射免疫计数器检测三氯醋酸（TCA）沉淀前后血浆、组织、尿和粪的放射性计数,用DSA1.0软件拟合药物动力学模型,并计算相应参数。结果125IrhTNTIL2单次静脉注射后在大鼠体内的动力学过程符合三室模型,T12α为1.77～3.03h,T12β为24.58～28.88h,T1/2γ为82.17～114.09h。125IrhTNTIL2在大鼠肝、脾、肺、肾、卵巢等组织器官中有较高的积聚,而脑中放射性活度较小。125IrhTNTIL2主要经肾由尿排泄,给药后24h,67.1%的药物由尿排出。125IrhTNTIL2从粪中排泄的量甚微。结论125IrhTNTIL2在大鼠体内药代动力学过程的研究为其进一步的开发具有指导价值。</span>

Objective To study the subchronic toxicity of the oxidized hair dyes in mice.[Methods] Commercial oxidized hair dyes were applied onto the skin of mice once everyday for a month.During the testing period,biological effects were observed,including body weight,biochemical examination of blood,histopathology of skin,liver,spleen,lung and kidney,and bone marrow genotoxicity.[Results] As the dose increased,the blood biochemical indicators(ALT,ALP,BUN and CR) changed significantly,the weight of body and organs(liver,lung)decreased but increased for kidney.Alteration of histopathology showed that in high dose group many nuclei pyknosed in germinal cells and sebaceous gland cells, germinal cells of peri-hair follicles decreased,inflammatory cells infiltrated in coriun tissue.Compared to control and low dose group,the hair follicles decreased significantly.The DNA strand breaks were observed in the mouse bone marrow cells and epidermic cells. [Conclusion] The results suggested that potential genotoxic risks of the oxidized hair dyes could not be ruled out.

Objective To examine roles of catechins in protecting liver and decreasing enzyme activity.Methods Chronic CCl 4 induced hepatic injury model was prepared in rat.Effects of catechins on levels of ALT,AST,MDA in rat serum and hydroxyproline levels in liver tissue as well as hepatic morphologic changes were observed.Results After treated with catechins for two months,ALT activities,MDA levels in serum and hydroxyproline levels in liver tissue were significantly decreased in the two catechin groups(100, 200 mg/kg respectively,P0 01,or P0 05).Catechin was similar to biphenyl dimethylesterate in decreasing hydroxy proline levels and improving pathological changes in liver tissues,however,better than biphenyl dimethylesterate in anti peroxidization of membrane lipid.Conclusions Catechins had the protective effect against chronic chemical hepatic injury by decreasing transaminase activities and alleviating hepatic pathologic injury.

The present study examines the effect of lipopolysaccharides and proinflammatory cytokines on the expression of the second isoform of the angiotensin II receptor (AT2), which may have a role in lowering collagen deposition in cardiac tissue. Cardiac fibroblasts express high levels of both angiotensin II type 1 (AT1) and type 2 receptors. Incubation with lipopolysaccharides for 24 h dose- and time-dependently decreased angiotensin II AT2 receptor expression with no apparent difference in the affinity. Actinomycin D, cycloheximide, Nω-nitro-l-arginine methyl ester and the protein tyrosine kinase inhibitor herbimycin A, but not the protein kinase C inhibitors bisindolylmaleimide and calphostin C, abolished the inhibitory action of lipopolysaccharides. The cytokines interleukin-1β and tissue necrosis factor-α mimicked the effect of lipopolysaccharides. All three compounds induced inducible nitric oxide synthase (iNOS). The nitric oxide donor sodium nitroprusside and the cGMP analog 8-bromoguanosine cyclic monophosphate downregulated angiotensin II AT 2 receptor expression. The findings are consistent with the pathway in which lipopolysaccharides or cytokines induce iNOS. The data suggest that lipopolysaccharide- or cytokine-dependent induction of iNOS and resultant production of nitric oxide leads to the production of cGMP, which in turn downregulates expression of the angiotensin II AT 2 receptor in cardiac fibroblasts.