Role of stearoyl-CoA desaturase and 1-acylglycerophosphorylcholine acyltransferase in the regulation of the acyl composition of phosphatidylcholine in rat liver

The role of stearoyl-CoA desaturase and 1-acylglycerophosphorylcholine (1-acylGPC) acyltransferase in regulating acyl composition of microsomal phosphatidylcholine was investigated in rat liver, using rats in five different kinds of physiological state: clofibric acid-fed rats, diabetic rats, insulin-treated diabetic rats, starved rats and starved-refed rats. There was a reverse linear correlation between 18:1 and 18:2 in the C-2 position, and a similar correlation was found between 18:1 and 18:2 in microsomal free fatty acids. The proportion of 18:1 or 18:2 in the C-2 position of phosphatidylcholine correlated with the proportion of the respective fatty acids in microsomal free unsaturated fatty acids which could be incorporated effectively, except for the group of clofibric acid-fed rats. In this group alone, 1-acylGPC acyltransferase was induced markedly. The proportion of 18:1 in microsomal free fatty acids correlated well with the activity of stearoyl-CoA desaturase. The physiological significance of stearoyl-CoA desaturase and 1-acylGPC acyltransferase was discussed in relation to the regulation of the acyl composition of phosphatidylcholine.     

有氧运动与饮食控制对2型糖尿病大鼠肝chemerin及其受体CMKLR1的影响

目的：研究4周有氧运动与饮食控制对2型糖尿病（DM）大鼠肝chemerin及其受体趋化因子样受体1（CMKLR1）的影响及其在改善糖脂代谢中的影响。方法：50只雄性SD大鼠随机分为正常对照组（Con,n=6）和糖尿病造模组（n=44）。采用高脂高糖饲料联合小剂量链脲佐菌素（STZ）（30 mg/kg）的方法制备2型糖尿病模型大鼠。造模成功的DM大鼠随机分为4组（n=6）：糖尿病对照组（DM）、糖尿病运动组（EDM）、改喂普通饲料的糖尿病饮食控制组（NDM）和糖尿病运动+饮食控制组（ENDM）。运动组大鼠进行为期4周中等强度跑台有氧运动,每周运动6 d。采用罗氏血糖仪检测大鼠空腹血糖（FBG）,全自动生化分析仪检测大鼠血清总胆固醇（TC）、甘油三酯（TG）和低密度脂蛋白（LDL）水平,real time PCR和Western blot分别检测大鼠肝chemerin、CMKLR1的mRNA和蛋白水平。结果：DM大鼠FBG和血清TC、TG、LDL水平显著升高的同时,肝chemerin和CMKLR1的mRNA和蛋白水平显著增加;4周有氧运动和/或饮食控制显著降低EDM、NDM和ENDM组FBG和血清TC、TG、LDL的同时,显著降低这3组大鼠的肝chemerin蛋白水平,其中ENDM组降低最显著（P<0.01）;NDM和ENDM组大鼠的肝CMKLR1蛋白水平升高（P<0.01）。结论：4周有氧运动和/或饮食控制降低2型糖尿病大鼠的肝chemerin蛋白水平、增加CMKLR1蛋白水平,这可能与其改善糖尿病大鼠的糖脂代谢有关。     

Effect of telmisartan on the expression of adiponectin receptors and nicotinamide adenine dinucleotide phosphate oxidase in the heart and aorta in type 2 diabetic rats

ABSTRACT: BACKGROUND: Diabetic cardiovascular disease is associated with decreased adiponectin and increased oxidative stress. This study investigated the effect of telmisartan on the expression of adiponectin receptor 2 (adipoR2) and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunits in the heart and the expression of adiponectin receptor 1 (adipoR1) in aorta in type 2 diabetic rats. METHODS: Type 2 diabetes was induced by high-fat and high-sugar diet and intraperitoneal injection of a low dose of streptozotocin (STZ). Heart function, adipoR2, p22phox, NOX4, glucose transporter 4(GLUT4), monocyte chemoattractant protein-1(MCP-1) and connective tissue growth factor CTGFin the heart, and adipoR1, MCP-1 and nuclear factor kappa B (NF-kappaB) in aorta were analyzed in controls and diabetic rats treated with or without telmisartan (5mg/kg/d) by gavage for 12 weeks. RESULTS: Heart function, plasma and myocardial adiponectin levels, the expression of myocardial adipoR2 and GLUT4 were significantly decreased in diabetic rats (P<0.05). The expression of myocardial p22phox, NOX4, MCP-1, and CTGF was significantly increased in diabetic rats (P<0.05). The expression of adipoR1 was decreased and the expression of MCP-1 and NF-kappaB was increased in the abdominal aorta in diabetic rats (P<0.05). Telmisartan treatment significantly attenuated these changes in diabetic rats (P<0.05). CONCLUSIONS: Our results suggest that telmisartan upregulates the expression of myocardial adiponectin, its receptor 2 and GLUT4. Simultaneously, it downregulates the expression of myocardial p22phox, NOX4, MCP-1, and CTGF, contributing so to the improvement of heart function in diabetic rats. Telmisartan also induces a protective role on the vascular system by upregulating the expression of adipoR1 and downregulating the expression of MCP-1 and NF-kappaB in the abdominal aorta in diabetic rats. KEYWORDS: Telmisartan; Adiponectin receptor; NADPH oxidase; Type 2 diabetic; Cardiac; Aorta.     

川芎嗪促进大鼠部分肝切除后修复性再生机制的研究

目的:探讨大鼠部分肝切除后肝功能的变化及川芎嗪对肝修复性再生能力的影响。方法:在相同月龄的动物中按体重均衡的原则随机分组。实验动物共分为5组:设正常对照组(对照组)、青年假手术对照组(假术组)、青年肝切除组(青切组)、中年肝切除组(中切组)和中年肝切除治疗组(切治组),每组动物10只,常规饲养,自由饮水。参照Higgins and Aderson给大鼠施行肝脏70%切除手术,中切组大鼠术前以川芎嗪(200 mg/kg/d)腹腔注射7d,其余组注射生理盐水。假术组大鼠以同样的手术程序打开腹腔但不施行肝部分切除术。各组施行手术动物在切除术后24 h沿腹中线切开动物腹腔,于腹主动脉两髂分支处取血分离血清,切取所有肝脏,待测。采用试剂盒法分别测定各组血清中丙氨转氨酶(ALT)、谷草转氨酶(AST)含量;肝脏匀浆后,采用八木国夫法检测肝组织中丙二醛(MDA)含量,采用western blot法测定肝组织中核增殖抗原(PCNA)和铜锌超氧化物歧化酶(SOD1)、锰超氧化物歧化酶(SOD2)的蛋白表达。结果:与中切组相比手术动物相比,切治组组大鼠血清中ALT、AST水平显著降低(P<0.05),肝细胞中PCNA表达显著升高(P<0.05),肝组织中MDA含量显著降低(P<0.05);肝组织中SOD1、SOD2表达显著增加。结论:肝脏切除70%后,肝功受损,氧化应激增加,但核增殖能力增强。川芎嗪可以抑制肝切手术导致的氧化应激损伤,促进SOD的表达,抑制MDA的升高,降低ALT、AST水平,提高PCNA的表达。提示中年大鼠肝切除后肝功能受损与氧化应激相关,给予抗氧化药物能够促进肝再生修复能力,青年肝切除手术大鼠肝的修复能力强于中年动物。     

Mechanism of the stimulatory action of antisteroid RU486 on follicle-stimulating hormone secretion in the cyclic Rat

These experiments explored the mechanism underlying FSH hypersecretion on estrous afternoon in rats injected with RU486 (RU) on proestrus. Four-day cyclic rats were injected with RU at 12:00 h on proestrus (1 or 4 mg/0.2 ml oil; s.c.), and its effects on LH and FSH secretion at 18:30 h on estrus were compared with those of antiprogestagens ZK299 (ZK) (1 or 4 mg/0.2 ml oil; s.c.) and Org31806 (OR) (2 or 8 mg/0.2 ml oil; s.c.). Additionally, rats treated with RU or nembutal (PB) (60 mg/kg; i.p. at 13:00 h on proestrus) were injected with an LHRH antagonist (LHRHa) at 10:00 h on estrus (1 mg/0.2 ml saline; s.c.) or progesterone (P) (7.7, 15.5 or 30.9 mg/0.2 ml oil; s.c.) on proestrus at 10:00 h in RU-injected rats and at 14:00 h in PB-injected rats. Animals were killed by decapitation at 18:30 h on estrus and serum LH and FSH concentrations were determined. Rats treated with 1 or 4 mg of RU or Org or 4 mg of ZK recorded increased serum FSH on estrous afternoon, while 1 mg ZK had no effect. PB increased mainly serum LH levels and, to a lesser extent, FSH levels. P decreased serum FSH concentrations in both RU- and PB-injected rats. LHRHa reversed the effects of PB on FSH secretions, but reduced FSH hypersecretion induced by RU only. These results are interpreted to mean that, in the absence of proestrous afternoon P-inhibitory action of the neural stimulus controlling LHRH release, FSH secretion on estrous afternoon involves two components: one is LHRH dependent while, in contrast to LH secretion, the other is LHRH independent, and only expressed in a low estrogen background.     

Experimental adhesion model: effect of viscosities of fluids put in the peritoneal cavity on preventing peritoneal adhesions.

In this study we assessed the effectiveness of fluid viscosities placed in the peritoneal cavity to prevent postoperative peritoneal adhesions. Thirty-six Wistar albino female rats (average weight: 160 +/- 30 g, average age: 6.5 months) were divided into three groups of equal number. A standard adhesion pattern was formed in each group. Then, 3 ml isotonic sodium chloride solution (relative viscosity value: 1) was added into the peritoneal cavity of group 1; 3 ml standard 6% hydroxy ethyl starch solution (HES) (relative viscosity value: 2.9) was added into the peritoneal cavity of group 2; and a standard HES solution that was concentrated by dehydration (relative viscosity value: 249.7) was added into the peritoneal cavity of group 3. All rats were sacrificed on postoperative day 10 and the adhesions that formed were graded. In group 1, grade-3 adhesions developed in 9 (75%) rats, and grade-2 developed in 3 (25%) rats. In group 2, grade-3 adhesions developed in 1 (8.3%) rat, grade-2 developed in 6 (50%) rats, and grade-1 developed in 5 (41.6%) rats; in group 3, grade-3 adhesions developed in 9 (75%) rats, and grade-2 developed in 3 (25%) rats. The adhesion scores of group 3 and group 1 were equal to each other (P=1), while the adhesion score of group 2 was significantly less (chi(2): 18.23, P<0.001). Increasing the viscosity of fluids that are inserted in the peritoneal cavity may reduce the formation of postoperative peritoneal adhesions till a critical value of unknown viscosity is achieved. The mechanism behind this process remains unclear.     

钙调神经磷酸酶在肾血管性高血压大鼠心肌肥厚发展中的作用

本文观察了钙调神经磷酸酶(calcineurin,CaN)在肾血管性高血压大鼠肥厚心肌中的表达和活性以及CaN抑制剂——环孢菌素A(cyclosporine A,CsA)对逆转心肌肥厚的影响。利用两肾一夹肾血管性高血压大鼠心肌肥厚模型,观察大鼠心肌肥厚程度、CaN mRNA和蛋白质表达及CaN活性的改变。结果显示:大鼠左室重与胫骨长度的比值和光镜下心肌细胞横截面积在两肾一夹2月和3月组都较相应假手术组增高(P<0.05),CsA组大鼠左室重与胫骨长度比值、心肌细胞横截面积较两肾一夹2月和3月组均显著下降(P<0.05),与假手术组无显著性差异。大鼠心肌CaN mRNA和蛋白质表达及CaN活性在两肾一夹2月和3月组均高于相应假手术组(P<0.05),在CsA组低于两肾一夹2月和3月组(P<0.05)。这些结果提示,CaN参与肾血管性高血压大鼠心肌肥厚发展,抑制CaN活性可逆转心肌肥厚。     

乳酸杆菌脂磷壁酸抑制脂多糖诱导的大鼠肝脏Kupffer 细胞TLR4 通路 的激活

目的：探讨保加利亚乳酸杆菌脂磷壁酸（Lipoteichoic Acid of ,LBG-LTA）对大鼠肝脏Kupffer细胞 Toll样受体4（Toll-like receptor 4,TLR4）信号通路的作用。方法：雄性健康Wistar大鼠10 只（2 月龄,体重250～300 g）处死后,分 离培养肝脏Kupffer 细胞;培养LBG,并提取制备LBG-LTA;Kupffer 细胞,在有或无LBG-LTA（0.1、1、10 ug/mL）预处理的情况 下,给予脂多糖（lipopolysaccharide,LPS,1 EU/mL）刺激后,Western blot 检测各孔Kupffer细胞的TLR4、TANK 结合激酶1（TANK binding kinase-1,TBK1）及核中的核因子B（nuclear factor-kB,NF-kB）水平,酶联免疫吸附法检测各孔培养上清中的肿瘤坏死因子 alpha（tumor necrosis factor-alpha,TNF-alpha）和白介素1beta（interleukin-1beta,IL-1beta）。结果：分离的Kupffer 细胞经不同浓度LBG-LTA 预处理 后,其在LPS刺激下所表达的TLR4、TBK1、核中NF- kB的水平及生成的TNF-alpha和IL-1茁明显低于无LBG-LTA预处理情况下的 LPS 孔（P<0.05）,且LBG-LTA 的作用呈浓度依赖性。结论：LBG-LTA以浓度依赖的方式抑制了LPS 诱导下大鼠Kupffer细胞 TLR4 通路的激活。     

Serodiagnosis of cilia-associated respiratory bacillus infection by the indirect immunofluorescence assay technique

Antibody to cilia-associated respiratory (CAR) bacillus was detected by the indirect immunofluorescence assay (IFA) technique using tracheal sections of infected mice as antigen in serum samples collected from rats infected naturally and experimentally. Nine of 23 cases of natural infection were positive in IFA antibody, with titres ranging from 1:10 to 1:80, and all these antibody-positive cases were also histologically positive. The remaining 14 cases were negative in both IFA antibody and histological diagnosis, even though some of them were infected with Sendai virus and Mycoplasma pulmonis. In the experimental infection, serum samples collected from 18 rats on days 4, 7, 14, 21, 28 and 56 post-inoculation (PI) (three rats for each point) and examined for IFA antibody revealed that seroconversion occurred in one rat on day 14 PI and in three rats on day 21 PI. Antibody titres of 1:80 to 1:160 remained to the termination of the experiment. The IFA technique was useful for the diagnosis of CAR bacillus infection except in the early stage of the infection.     

α-亚麻酸对糖尿病大鼠炎症介质和氧化应激的影响

目的:观察α-亚麻酸(ALA)对糖尿病大鼠体内炎症介质和氧化应激的影响,探讨ALA在糖尿病防治中的作用。方法:雄性SD大鼠高脂饮食喂养4周后,腹腔注射链脲佐菌素(STZ)30 mg/kg建立2型糖尿病(T2DM)模型。将大鼠随机分为3组(n=10):正常对照组、糖尿病模型组和ALA治疗组(500μg/kg.d)。4周后测定大鼠血清中肿瘤坏死因子(TNF-α)、可溶性P-选择素(sP-selectin)、可溶性细胞间黏附分子(sICAM-1)、一氧化氮(NO)、丙二醛(MDA)的含量以及超氧化物岐化酶(SOD)和过氧化氢酶(CAT)的活性。结果:与正常对照组相比,糖尿病大鼠血清中炎症介质TNF-α、sP-selectin和sICAM-1的含量增加,血清NO含量下降而MDA升高,同时抗氧化酶SOD和CAT的活性降低;ALA治疗可显著降低糖尿病大鼠血清中TNF-α、sP-selectin和sICAM-1的含量(与STZ+vehicle组相比,P<0.01),增加血清NO水平并减少MDA含量,升高抗氧化酶SOD和CAT的活性(与STZ+vehicle组相比,均P<0.05)。结论:ALA可显著降低糖尿病大鼠血清炎症介质的生成,减轻氧化应激水平,具有抗炎和抗氧化作用。提示ALA对糖尿病及糖尿病并发症的发生发展可能具有一定的防治作用。     

下丘脑室旁核注射GLP-1 对糖尿病大鼠中枢GLP-1 受体表达

目的:探讨下丘脑室旁核(hypothalamic paraventricular nucleus,PVN)注射GLP-1(胰高血糖素样肽-1)对糖尿病大鼠胃排空的影响及机制。方法:30只Wistar大鼠随机分为正常对照组(NC组)、糖尿病组(DM组)和GLP-1干预组(GLP-1组),每组各10只。DM组和GLP-1组腹腔注射链脲佐菌素,三组大鼠均PVN区埋置套管,恢复7d,GLP-1组微量注射0.5μg/0.5μl的GLP-1,NC组和DM组大鼠PVN区微量注射等体积生理盐水。甲基纤维素-酚红灌胃法检测胃排空;半定量RT-PCR检测大鼠下丘脑GLP-1RmRNA的表达。结果:DM组胃排空率较NC组明显升高(P<0.05),GLP-1组胃排空明显低于DM组(P<0.05),GLP-1组和NC组差异无统计学意义(P>0.05)。GLP-1组下丘脑GLP-1RmRNA的表达明显高于DM组和NC组(P<0.05),并与胃排空率成负相关(P<0.05)。DM组和NC组差异无统计学意义(P>0.05)。结论:PVN区注射GLP-1可以抑制糖尿病大鼠早期胃排空加速,作用机制可能和促进下丘脑GLP-1受体表达有关。     

Sequence specificity of Hprt lymphocyte mutation in rats fed the hepatocarcinogen 2-acetylaminofluorene

Rats fed the hepatocarcinogen 2-acetylaminofluorene (2-AAF) have a low, but significantly increased, frequency of lymphocyte Hprt mutants. In this study, mutants from 2-AAF-fed and control F344 rats were examined for mutations in the Hprt gene in order to determine if the 2-AAF treatment resulted in an agent-specific mutation profile. The most common mutation from 2-AAF-treated rats was G:C-->T:A transversion (32% of all mutations) followed by 1-basepair (bp) deletion (19%); there were very few (5%) G:C-->A:T transitions. Among mutations from control rats, G:C-->A:T transition was the most common (43%), and there were very few G:C-->T:A transversions (5%) and no 1-bp deletions. The profile of mutations from 2-AAF-fed rats was significantly different from control rats (P = 0.003) and was consistent with the types of mutations produced by 2-AAF in vitro. The results of this study indicate that even weak mutational responses in the lymphocyte Hprt assay are capable of producing mutation profiles that reflect the DNA damage inducing them.     

Effect of cyclosporin-A on the blood--retinal barrier permeability in streptozotocin-induced diabetes

BACKGROUND: Our previous results showed that in retinas from streptozotocin (STZ)-induced diabetic rats there is an increased level of interleukin-1beta (IL-1beta). This cytokine may be involved in the expression of the inducible isoform of the nitric oxide synthase (iNOS), with consequent synthesis of large amounts of NO and blood-retinal barrier (BRB) breakdown. AIMS: The aim of this work was to examine whether the administration of cyclosporin-A (Cs-A) to STZ-induced diabetic rats inhibits the synthesis of IL-1beta and the expression of the inducible proteins, iNOS and cyclo-oxygenase-2 (COX-2) in retinal cells, and whether the activity of these proteins contribute to BRB breakdown. METHODS: The level of IL-1beta was evaluated by ELISA and the NO production by L-[3H]-citrulline formation. Expression of iNOS and COX-2 proteins was determined by two methods, western blot and immunohistochemistry. The permeability of the BRB was assessed by quantification of the vitreous protein. RESULTS AND DISCUSSION: Our results indicated that the levels of IL-1beta and NO in retinas from Cs-A-treated diabetic rats are significantly reduced, as compared to that in non-treated diabetic rats. The treatment of diabetic rats with Cs-A also significantly inhibited the expression of the inducible proteins, iNOS and COX-2. The evaluation of the vitreous protein content revealed that Cs-A also reduces the BRB permeability. Taken together, these results suggest that the increased production of the inflammatory mediators, IL-1beta and NO, in diabetes may affect the BRB permeability and therefore contribute to the development of diabetic retinopathy.     

"促育生精方" 对环磷酰胺致大鼠不育模型CatSper1 基因和CatSper2基 因的影响

目的：研究" 促育生精方" 对精子特异性钙通道蛋白CatSper1、CatSper2 表达的影响。方法：采用Real-time PCR 法检测 CatSper1 mRNA、CatSper2 mRNA 在各组大鼠（模型组、低剂量组、中剂量组、高剂量组、空白对照组）精子中的表达;用Western blot 检测各组CatSper1 蛋白,CatSper2 蛋白的表达。结果：成功建立大鼠不育模型。CatSper1 mRNA、CatSper2 mRNA表达量为： 中、高剂量组显著高于模型组（P＜0.05）。CatSper1、CatSper2蛋白表达量：中、高剂量组显著高于模型组（P＜0.05）。结论：促育生精 方能有效提高少弱精症模型大鼠精子特异性钙通道CatSper1、CatSper2 基因及其蛋白的表达。     

Formation of mercapturic acids in rats after the administration of aralkyl esters

1. Benzylmercapturic acid and hippuric acid were isolated from the urine of rats that had been injected subcutaneously with benzyl acetate. 2. 1-Menaphthylmercapturic acid and 1-naphthoic acid were isolated from the urine of rats after the subcutaneous injection of each of the following compounds: 1-menaphthyl alcohol and its acetate, propionate, butyrate and benzoate esters. 3. A quantitative method for determining 1-menaphthylmercapturic acid in urine was developed and used to measure the excretion of this compound in the urine of rats in the 4-day period after the subcutaneous injection of 1-menaphthyl alcohol and its acetate, propionate, butyrate and benzoate esters. 4. Chromatographic evidence was obtained for the presence of S-(1-menaphthyl)glutathione and S-(1-menaphthyl)-l-cysteine in bile collected from rats with cannulated bile ducts after the animals had been injected subcutaneously with each of the following compounds: S-(1-menaphthyl)glutathione, 1-menaphthyl acetate, propionate and butyrate. 5. Benzylmercapturic acid and 1-menaphthylmercapturic acid were isolated from the urine of rats that had been injected with sodium benzyl sulphate and sodium 1-menaphthyl sulphate respectively.     

常压氧与高压氧对成年大鼠脑缺血再灌注损伤后 微血管新生影响的比较

目的:研究常压氧与高压氧对成年大鼠脑缺血再灌注损伤后微血管新生影响的差异。方法:将成年SD雄性大鼠随机分为三组:假手术组(SS组)、常压氧治疗组(NBO组)、高压氧治疗组(HBO组),每组又随机分为3、7、10天三个亚组。采用线栓法对NBO组和HBO组大鼠进行大脑中动脉栓塞(MCAO),缺血1.5小时后拔出栓子再灌注,NBO组进行常压氧治疗,HBO组进行高压氧治疗。大鼠分别在3、7、10天麻醉处死,取脑组织切片,血管内皮生长因子(VEGF)、VEGF受体-1(FLT-1)和CD34免疫组化染色,光镜观察取图和统计分析。结果:NBO各组与SS各组相比,VEGF、FLT-1和CD34阳性细胞数目均明显增多(P<0.05);HBO各组与NBO各组比较,7天、10天组VEGF、FLT-1和CD34阳性细胞数目均显著增多(P<0.05)。结论:HBO治疗较NBO治疗对成年大鼠微血管的新生更有促进作用。     

Nervonic acid is transferred from the maternal diet to milk and tissues of suckling rat pups

Three experiments were designed to investigate the metabolism of dietary nervonic acid (24:1n-9, NA) during reproduction in the rat. The first experiment determined the effect of early development on the sphingomyelin (SM) composition of rat heart and liver tissues. Rats were fed a standard chow diet and the SM fatty acid composition of the hearts and livers were analyzed of 18-20 day old fetuses, 14 day old sucklings and adult rats. The 18:0 content of SM decreases with age, while 23:0 and iso 24:0 increase with age. In the second experiment pregnant rats were fed diets supplemented with either canola, corn or peanut oil to determine the effect of diets high in 24:1n-9 and 24:0 on liver and heart SM at birth and after 14 days of suckling. Pups from the dams fed the corn oil diet had elevated 24:2n-6 in SM from heart and liver at birth, but the content of NA was not altered by dietary fat type. In the third experiment oil mixtures were designed to provide elevated levels of 22:1 and 24:1 (canola-N25), 22:0 and 24:0 (peanut-flax) or <0.01% of these fatty acids (olive-flax) and were supplemented to the diets of lactating rats. Canola-N25 oil supplemented to lactating rats resulted in increased 24:1n-9 and 24:1/24:0 with decreased 22:0 and 24:0 in milk SM relative to the other groups. The SM composition of livers of the suckling rats showed significant changes reflecting the changes in milk SM composition after 6 days of milk consumption. These experiments suggest that dietary NA and is not readily transferred across the placental barrier but does readily cross the mammary epithelium and is incorporated into milk SM. In addition, NA in milk appears to cross the intestinal epithelium where it is incorporated into the SM of heart and liver of suckling rats.     

Elastic properties of the rat respiratory system related to age

The experiments were performed on male rats of the Wistar strain under urethane anaesthesia (1.3 g/kg i.p.). Changes of oesophageal and tracheal pressures were registered in a group of 30 spontaneously breathing, supine rats, of 295 +/- 13 g average body weight during lung inflations with 1-5 ml of air. In another group of 25 rats of 70 +/- 6 g average body weight (young rats) we made the measurements during inflation with volumes 0.5-2 ml. The measurements were also performed in a group of 10 paralyzed, ventilated rats with 347 +/- 24 g average body weight and inflations 1-5 ml. Compliance of the lungs (CL), chest wall (CW) and of the respiratory system (Crs) was calculated from the linear part of the pressure-volume curve during inflation. The results indicate: 1. Cw is significantly (p less than 0.001) higher in young (134.7 ml.kPa-1.kg-1) than in adult rats (44.1 ml.kPa-1.kg-1). CL (related to body weight) is not significantly different in young and adult rats. 2. Cw is significantly (p less than 0.001) higher than CL. 3. No difference was observed in CLs Cw and Crs between paralyzed and spontaneously breathing animals.     

Novel stereoselectivity of rat liver cytochrome(s) P450 toward enantiomers of the trans-1,2-dihydrodiol of triphenylene

Metabolism of 3H-labeled (+)-(S,S)- and (-)-(R,R)-1,2-dihydrodiols of triphenylene by rat liver microsomes and 11 purified isozymes of cytochrome P450 in a reconstituted monooxygenase system has been examined. Although both enantiomers were metabolized at comparable rates, the distribution of metabolites between phenolic dihydrodiols and bay-region, 1,2-diol 3,4-epoxide diastereomers varied substantially with the different systems. Treatment of rats with phenobarbital (PB) or 3-methylcholanthrene (MC) caused a slight reduction or less than a twofold increase, respectively, in the rate of total metabolism (per nanomole of cytochrome P450) of the enantiomeric dihydrodiols compared to microsomes from control rats. Among the 11 isozymes of cytochrome P450 tested, only cytochromes P450c (P450IA1) and P450d (P450IA2) had significant catalytic activity. With either enantiomer of triphenylene 1,2-dihydrodiol, both purified cytochrome P450c (P450IA1) and liver microsomes from MC-treated rats formed diol epoxides and phenolic dihydrodiols in approximately equal amounts. Purifed cytochrome P450d (P450IA2), however, formed bay-region diol epoxides and phenolic dihydrodiols in an 80:20 ratio. Interestingly, liver microsomes from control or PB-treated rats produced only diol epoxides and little or no phenolic dihydrodiols. The diol epoxide diastereomers differ in that the epoxide oxygen is either cis (diol epoxide-1) or trans (diol epoxide-2) to the benzylic 1-hydroxyl group. With either purified cytochromes P450 (isozymes c or d) or liver microsomes from MC-treated rats, diol epoxide-2 is favored over diol epoxide-1 by at least 4:1 when the (-)-enantiomer is the substrate, while diol epoxide-1 is favored by at least 5:1 when the (+)- enantiomer is the substrate. In contrast, with liver microsomes from control or PB-treated rats, formation of diol epoxide-1 relative to diol epoxide-2 was favored by at least 2:1 regardless of the substrate enantiomer metabolized. This is the first instance where the ratio of diol epoxide-1/diol epoxide-2 metabolites is independent of the dihydrodiol enantiomer metabolized. Experiments with antibodies indicate that a large percentage of the metabolism by microsomes from control and PB-treated rats is catalyzed by cytochrome P450p (P450IIIA1), resulting in the altered stereoselectivity of these microsomes compared to that of the liver microsomes from MC-treated rats.