Serum and lymph lipids in rabbits with carbon tetrachloride-induced cirrhosis of the liver

Lymph flow and the composition of lymph lipids from the hepatic and thoracic ducts of rabbits with cirrhosis of the liver (induced by 46-51 intramuscular injections of a mixture of carbon tetrachloride and olive oil at 4-day intervals) have been compared with those of control animals injected with olive oil only. In cirrhotic animals, the concentration of lymph lipids was not greatly altered, but lymph flow, and consequently the hourly transport of lipids by lymph were greatly increased; the increase in transport of cholesteryl esters, free cholesterol, and phospholipids by way of the thoracic and hepatic duct lymph was particularly striking. The concentration of these lipid fractions in serum from the cirrhotic rabbits was also increased. The differences normally observed between lipid fatty acid compositions of serum and lymph disappeared in cirrhotic animals; this is interpreted as due to increased hepatic permeability to lipoproteins.     

Amino acid composition of the lymph and blood in fever reactions of different durations

The amino acid composition of the thoracic duct lymph and blood following fever reactions (FR) of various duration has been studied in the experiments on rabbits. The experiments have shown that some changes in protein metabolism in FR are primarily manifested in amino acid lymph composition. Irrespective of FR duration the amino acid content in the lymph almost always increases, which confirms the opinion concerning catabolic process predominance in protein metabolism during FR. The lack of "cumulative" conditions in the blood, amino acid dilution in the large volume of the circulating blood, as well as the increase of vascular permeability during FR cause less marked increase in amino acid content in the blood than in the lymph.     

Effect of a modified terrilytin on ampicillin pharmacokinetics in experimental peritonitis

The effect of modified terrilytin, a new enzyme of the microbial origin on the pharmacokinetics of ampicillin in experimental peritonitis was studied on 16 pubertal rabbits. Peritonitis was caused by laparotomy and administration of a 15 per cent fecal suspension into the abdominal cavity. The drugs were injected intramuscularly: the enzyme in a dose of 5 PU/kg and the antibiotic in a dose of 10 mg/kg. The ampicillin levels in the blood and peritoneal exudate were determined with the agar-diffusion method. The specimens were collected 30 minutes, 1, 1.5 and 2 hours after administration of the drugs. The animals were divided into 2 groups: control (not treated with the enzyme) and experimental. An increase in the antibiotic levels in the blood and peritoneal exudate by 50--54 per cent was observed. The maximum increase was recorded 30 minutes after simultaneous administration of the drugs.     

Anesthetic and nephrotoxic effects of Telazol in New Zealand white rabbits.

Telazol was evaluated as an anesthetic for rabbits. Two groups of five rabbits each were injected intramuscularly with 32 or 64 mg/kg of Telazol, and the depth and duration of anesthesia period monitored. At both doses, the righting reflex was lost within 2 minutes postinjection. Animals in both groups responded to noxious stimuli for the duration of the anesthesia. Hematology and urinalyses were performed daily for 7 days postinjection. Hematologic parameters remained unchanged in both groups. In the high-dose group, blood urea nitrogen and serum creatinine levels increased 1 day postinjection and continued steadily throughout the week. Elevations in urine protein and the presence of casts correlated with this increase. In the low-dose group, blood urea nitrogen and creatinine levels increased and protein was present in the urine of four of five rabbits beginning approximately 5 days postinjection. Histologically, severe renal tubular necrosis was evident 7 days postinjection in all high-dose rabbits and in three rabbits in the low-dose group. Our results indicate that Telazol does not produce analgesia in rabbits and is nephrotoxic at both 32 and 64 mg/kg. We conclude that Telazol is contraindicated for use in rabbits.     

Cytological composition of lymph in fever reaction

This work deals with an investigation into the lymph cytologic composition of thoracic lymph duct of rabbits in fever reaction (FR) of various duration. FR was accompanied by quantitative and qualitative shifts in lymph cytologic composition. There was an alternative rise and fall of the leucocyte number in the first hours of fever. The number of little and medium leucocytes decreased while the number of eosinophiles, insufficiently differentiated cells-blasts, large lymphocytes, prolymphocytes increased. Our investigations revealed a significant role played by the lymphatic system in lymphoid cells mobilization in FR, which is evident by a considerable lymphocyte number gaining entrance to the blood through thoracic duct.     

THE TEMPO OF LYMPHOCYTE RECIRCULATION FROM BLOOD TO LYMPH IN THE RAT

Radioactively labelled thoracic duct lymphocytes were obtained either by incubation in vitro with ³H-uridine or ¹⁴C-uridine or by giving potential donors repeated injections of ³H-thymidine finishing 17 days before thoracic duct cannulation. These labelled TDL were injected i.v. into syngeneic recipients which had been subjected to splenectomy and thoracic duct cannulation on the previous day. The tempo of lymphocyte recirculation from blood to lymph was reflected by the time at which radioactivity was recovered in the thoracic duct lymphocyte output of the recipient. This was measured by scintillation counting of 2-hourly fractional collections for 36 hr after the injection. Two lines of evidence showed that the majority of small lymphocytes which label intensely with radioactive uridine in vitro were uniform in their 'migration potential'with a modal blood to lymph transit time of 14–18 hr. By contrast the cells which were labelled in vivo with ³H-thymidine included a slower population with a modal transit time of 24–28 hr. These conclusions can be more fully interpreted in the light of recent evidence on thymic-independent ('B') lymphocytes.     

Acute toxicity and radioprotective effectiveness of gammaphos on intramuscular administration to mice

In experiments on mice it was shown that acute toxicity of gammaphos (WR-2721) was 790 mg/kg and 862 mg-kg after intraperitoneal and intramuscular administration, respectively. Gammaphos in the dose of 100 mg/kg, injected intramuscularly, increased the radioresistance of mice in nearly the same way as cystamine, in the dose of 150 mg/kg, did. The increase in the dose of gammaphos up to 200 or 300 mg/kg, injected intramuscularly, enhanced the radioprotective effect. No change was observed in the radioprotective efficiency of gammaphos after intramuscular injection as compared to intraperitoneal administration of the protective agent in the same dose.     

Lysozyme activity in the leukocytes and blood serum of white rats administered massive doses of penicillin preparations]

Activity of lysozyme in the blood serum and leucocytes was determined. The experiments were carried out on albino unbred rats weighing 170 to 200 gm. Benzylpenicillin and oxacillin were administered intramuscularly in doses of 500000 Units/kg or 20000 gamma/kg once every 24 hours for 2, 4 and 6 days. The activity of lysozyme was determined by the turbidimetric and agar-diffusion methods. It was found that the activity of lysozyme in the leucocytes increased by the 5th day accompanied by a simultaneous decrease in its level in the serum followed by reaching the initial values. The data are indicative of the fact that the use of antibiotics in mega-doses is not contraindicated from the point of view of their effect on lysozyme activity.     

Arsenate-induced renal agenesis in rats

The developmental origin of arsenate-induced renal agenesis was investigated. Pregnant Wistar rats were each injected once ip with 45 mg/kg sodium arsenate at day 10 (sperm day = day 0). Pregnancy was terminated at various times following injection and the embryos recovered and serially sectioned. Renal agenesis resulted when the mesonephric duct failded to give rise to a ureteric bud with subsequent failure of induction of the metanephric blastema. The underlying defect was retardation in growth of the mesonephric duct, first observed 48 hours after arsenate injection. A shortened mesonephric duct also resulted in a failure of the mesonephros to attain normal size and in the male resulted in absence of the ductus deferens, seminal vesicle a variable portion of the epididymis. Due to the intimate association of the mesonephric and growing paramesonephric ducts, a shortened mesonephric duct resulted in a shortened paramesonephric duct with resultant lack of a uterine horn.     

The entry of T and B lymphocytes into rat popliteal lymph nodes undergoing a graft-versus-host reaction

The entry of radiolabeled blood-borne T and B lymphocytes into resting popliteal lymph nodes and popliteal lymph nodes stimulated with semiallogeneic lymphocytes was investigated in rats. Thoracic duct lymphocytes separated into T- and B-lymphocyte populations on nylon-wool columns were radiolabeled with 51chromium and equal numbers of T or B lymphocytes were injected intravenously. While the ratio of T and B lymphocytes in the blood is approximately 3:1 it was found that the ratio of T to B lymphocytes migrating into lymph nodes was approximately 9 T to 1 B lymphocyte in both resting and antigenically stimulated lymph nodes. Since the ratio of T to B lymphocytes in thoracic duct lymph is similar to that of blood, there is a disparity between the number of T cells entering and leaving lymph nodes. These results suggest that some T lymphocytes may return to the blood directly and/or there is increased T lymphocyte death in lymph nodes.     

大鼠胰腺炎相关性急性肺损伤模型的探讨

目的研究5%牛磺胆酸钠(TAC)逆行胆胰管注射诱发急性胰腺炎相关肺损伤的大鼠模型。方法采用改进的胆胰管逆行注射TAC造成大鼠急性出血坏死型胰腺炎(AHNP)模型,将大鼠随机分为3组:AHNP组、假手术组、地塞米松(DXM)治疗组。造模成功后,立即静脉注射大剂量DXM(5 mg/kg)。术后于3、6、12 h处死,留取外周血测定血清淀粉酶、脂肪酶,取右肺中叶测定肺湿干比值及作病理切片,计算等级评分评价肺损伤;行支气管肺泡灌洗,以灌洗液白蛋白与血清白蛋白含量比值计算肺指数。结果AHNP组36、、12 h肺通透性指数、湿干比值及病理学评分逐渐增加,经单因素方差分析,61、2 h组高于3 h组(P<0.05),前两者于6、12 h组组内比较差异不显著(P>0.05)。DXM组于术后61、2 h,各项肺损伤指标均低于AHNP组(P<0.05)。结论TAC胆胰管逆行注射造成AHNP模型大鼠于术后6 h即出现明显的肺损伤表现,符合PALI病理改变,与临床AHNP合并急性肺损伤(ALI)的病理过程相似,可于此时相点作为研究AHNP合并肺损伤的模型。     

Freezing of rat lymphocytes. 2. Distribution and circulation of frozen-thawed 51Cr-labelled cells

Radioactive labelled synegenic fresh and frozen-thawed rat lymphoid cells were injected into groups of animals and their distribution in liver, spleen, lung, lymph nodes, and thoracic duct recorded. Principally the same pattern of distribution was demonstrated after injection of both fresh and frozen-thawed cells. However, more radioactivity was recovered from the liver and less from lymph nodes and thoracic ducts in recipients of frozen-thawed than of fresh cell preparations. This is caused by some damage to the cells in the freeze-thaw process.     

Involvement of prostaglandins in paraquat intoxication

Paraquat is known to cause severe lung damage through pulmonary edema as its initial feature of toxicity. The purpose of this study was to investigate the toxicity of paraquat in rabbits intraperitoneally injected with 2 or 4 mg/kg/day of the herbicide for a period of 7 days. In the lung, prostaglandin levels of the intoxicated rabbits showed a significant increase in PGF2 alpha. This increase was dose dependent. However, a nonsignificant change in the 6-keto-PGF1 alpha was also observed. Plasma and serum levels of thromboxane-B2 were also significantly elevated but the levels of 6-keto-PGF1 alpha were affected nonsignificantly. The pathology of elevated levels of PGF2 alpha and TXB2 in the lung and blood, in response to paraquat toxicity, is discussed.     

Induction of Rat Liver Alkaline Phosphatase by Bile Duct Ligation

Bile duct ligation causes a five- to sevenfold increase in the activity of rat liver alkaline phosphatase within 12 hours after ligation and a similar rise in the activity of alkaline phosphatase in serum. The increased serum activity is due entirely to the appearance of a new isoenzyme that has the properties of rat liver alkaline phosphatase. The increase in both serum and liver alkaline phosphatase is prevented by the prior administration of cycloheximide in a dose that inhibits protein synthesis by 70%. Rat liver alkaline phosphatase was then purified to homogeneity. Antibody was raised to purified rat liver alkaline phosphatase in rabbits. The antibody was coupled to sepharose 4B and affinity columns made. ³-H-leucine was then injected into the portal veins of sham operated rats and rats with bile duct ligation four hours after ligation. One hour after injection and five hours after ligation, animals were sacrificed. Liver alkaline phosphatase was purified by means of affinity chromatography and double immunoprecipitation with rabbit antibody to rat liver alkaline phosphatase and goat anti-rabbit gamma globulin. Bile duct ligation increased the incorporation of ³-H-leucine into liver alkaline phosphatase more than threefold compared with sham operated rats, 164 CPM/mg protein vs. 49 CPM/mg protein (p < .001). The data indicate that the increased activity of rat liver alkaline phosphatase after bile duct ligation is due to enzyme induction rather than to activation of a pre-existing, relatively inactive enzyme.     

异甘草酸镁对胆道梗阻致肝损伤肝功能保护作用的动物实验研究

目的:探讨异甘草酸镁注射液对大鼠梗阻性黄疸肝损伤的保护作用。方法:选用健康雄性SD大鼠32只,随机分成4组,每组各8只,分别为胆总管结扎+异甘草酸镁注射液常规剂量组(BMc组);胆总管结扎+异甘草酸镁注射液高剂量组(BMh组);胆总管结扎+0.9%生理盐水注射液组(BN组)和假手术组(Sham组)。BN和Sham组以生理盐水30 mg/kg/日腹腔注射,BMc组以异甘草酸镁30 mg/kg/日腹腔注射,BMh组以异甘草酸镁60 mg/kg/日腹腔注射。术后不同时间对各组大鼠眼眶取血并获得血清。在全自动生化分析仪器检测肝功能指标:丙氨酸氨基转移酶(Alanine aminotransferase,ALT)、天冬氨酸氨基转移酶(Aspartate aminotransferase,AST)、直接胆红素(Direct bilirubin,DBil)。结果:BN、BMc和BMh组大鼠在胆管结扎后血清中ALT和AST指标明显升高。随着梗阻时间的增加,BM和BMh组大鼠血清中ALT和AST的水平均明显低于BN组(P0.01),但两组之间并无明显区别。手术后BN、BMc和BMh组大鼠在胆管结扎后血清中D-Bil水平明显高于Sham组(P0.01),但随着梗阻时间的延长,各组间D-Bil的水平变化不明显。结论:异甘草酸镁注射液可以有效降低梗阻性黄疸大鼠血清转氨酶水平,对肝功能有明显的保护作用。     

The migration of lymphocytes across specialized vascular endothelium. VI. The migratory behaviour of thoracic duct lymphocytes retransferred from the lymph nodes, spleen, blood, or lymph of a primary recipient

Thoracic duct lymphocytes labelled with 51Cr were injected into a primary recipient and then were transferred for a second time from the lymph nodes (cervical and/or mesenteric), spleen, lymph, or blood into a series of final recipients. Measurement of the organ distribution of labelled lymphocytes in the final recipients enabled three main conclusions to be drawn. (1) Lymphocytes that had localized in the spleen, mesenteric lymph nodes (LN), or cervical LN of the first recipient showed no tendency to return in increased numbers to the same organ in the final recipient. (2) Lymphocytes that had recently entered the spleen or LN were temporarily impaired in their ability to reenter LN. This capacity was recharged when the cells returned to the lymph and the blood. (3) Lymphocytes that had been passaged from blood to lymph and collected for up to 4 hr at room temperature entered the LN of a recipient much faster than did nonpassaged thoracic duct lymphocytes collected overnight at 0 degree C. Supplementary experiments indicated that the different migratory behavior of thoracic duct lymphocytes under these two circumstances was mainly a consequence of their handling in vitro during the collecting and the labelling procedures. This functional impairment was not associated with a diminished ability to enter the spleen and bone marrow or to survive in recipients for up to 24 hr.     

The response of the blood proteins to ablation of the capsaicin-sensitive nerves

Effects of neurotoxic doses of capsaicin (150 mg/kg) on the protein content in electrophoretic fractions (PAAG) in the Wistar rat plasma were studied. In early period (7 days) after administration of capsaicin, an increase of the alpha1-, alpha2-globulins and a decrease of the albumin, gamma-globulins, were observed. After 14-30 days, increase of the albumin and decrease of the alpha1-, gammay-globulins were detected. The ablation of the capsaicin-sensitive nerves abrogated the changes of positive and negative acute phase reactants induced by zymosan and diminished the content of gamma-globulins.     

Insulin transport by thoracic duct of male rabbits with CCI4-induced liver cirrhosis.

Insulin concentration in the peripheral blood and the thoracic duct lymph from male rabbits with CCl4-induced liver cirrhosis was measured using a radioimmunoassay technique. Although insulin concentration in the lymph was lower in the cirrhotic animals than in the control ones, the hourly transport of the hormone by the lymphatic vessel of the cirrhotic animals markedly increased in company with the higher flow rate of the lymph.     

Nephrotoxicity of tiletamine in New Zealand white rabbits.

Tiletamine and zolazepam, the two constituents of Telazol, were evaluated independently to determine which agent was responsible for the nephrotoxicity caused by Telazol in New Zealand White rabbits. Five rabbits were injected i.m. with 32 mg/kg of tiletamine, four animals received 7.5 mg/kg of tiletamine, and five rabbits received 32 mg/kg of zolazepam. Urinalysis was performed and blood urea nitrogen and serum creatinine were monitored for 7 days postinjection. In all five rabbits injected with the high dose of tiletamine, blood urea nitrogen and creatinine rose by 3 days postinjection and increased steadily throughout the week. By 4 days postinjection, urine protein and glucose were elevated and cellular and protein casts were present. No serum chemistry or urine abnormalities were detected in rabbits receiving low doses of tiletamine, zolazepam, or in the four control rabbits. All animals were euthanized and necropsied at 7 days postinjection. Histopathology showed severe renal tubular necrosis in all five rabbits injected with 32 mg/kg tiletamine. Mild nephrosis was present in three of four rabbits injected with 7.5 mg/kg of tiletamine. No lesions were present in the zolazepam-injected or control rabbits. The results of this study show that tiletamine is the constituent responsible for the nephrotoxicity of Telazol in rabbits. They further demonstrate that doses commonly used for anesthetic induction or restraint can produce renal lesions in rabbits.     

Absorption and lymphatic transport of cholesterol in the rat

Rats with thoracic duct fistulae were fed triolein and triolein containing various amounts of labeled cholesterol. The analysis of the lymph lipids gave the following results. In the fasting state the cholesterol transported via the thoracic duct was 0.87 micromole/hr. Feeding 800 micromoles of triolein gave a maximum rate of transport of cholesterol of 1.65 micromoles/hr. Addition of cholesterol to the triolein further increased the cholesterol transport to a maximal rate of almost 5 micromoles/hr when 50 micromoles of cholesterol were fed per 800 micromoles of triolein. The exogenous fraction of the cholesterol transported increased linearly with increasing cholesterol load, constituting at the highest dose almost 90% of the total cholesterol transported. An almost constant fraction (about 0.4) of the dietary cholesterol was recovered in the thoracic duct lymph in 24 hr irrespective of the dose fed, from a trace up to 100 micromoles in 800 micromoles of triolein. Cholesterol absorption has the characteristics of a passive diffusion process.