Effect of dietary magnesium on Ascaris suum infections of mice

Low amounts of dietary magnesium affected the inflammatory tissue response in nonimmunized mice differently than in immunized mice. Eosinophil numbers and LPL activity in lung tissue following infection with A. suum larvae were altered by the level of magnesium in the diets of mice. Average or higher dietary levels of magnesium resulted in decreased numbers of lung larvae indicating an overall protective effect. Increases in eosinophil numbers or LPL activity were not directly related to the numbers of larvae/lungs. Larvae/livers, eosinophil numbers, and LPL activity were affected by the types of magnesium diets that mice received. Nonimmunized mice had differences in larvae/liver (at 2 days and 7 days pi) and LPL activity (at 2 days pi). Immunized mice had varying findings at 2 days pi but a direct relationship between dietary magnesium and numbers of larvae, numbers of eosinophils, and liver LPL activity at 7 days pi.     

Alterations in Ascaris suum larval burdens, eosinophil numbers, and lysophospholipase activity associated with low levels of dietary iron

The effect of various amounts of dietary iron on the immune response was investigated using BALB/cAnNCr/BR mice infected with Ascaris suum. Changes in numbers of larvae, numbers of eosinophils, and levels of lysophospholipase (LPL) activity in lung or liver tissues were analyzed from nonimmune and immunized mice at 2 and 7 days postinfection (PI). Various iron diets did not influence the numbers of tissue larvae, eosinophils, or the LPL activity in lungs or livers of nonimmunized mice at various times after infection. Lung and liver LPL activity was reduced in immunized mice without significant changes in larval numbers at 2 days PI. At 7 days PI, lung and liver LPL activity, eosinophil numbers, and numbers of larvae were increased in immunized mice receiving low iron diets. Results confirm that low iron diets affect the host response to A. suum.     

Kinetics of liver trapping of infective larvae in murine toxocariasis

Mice sensitized by prior infection with Toxocara canis eggs trap many larvae of a challenge infection within the liver. In this study the distribution of challenge larvae in sensitized mice was examined to determine the earliest onset of liver trapping and to establish if the previously described phenomenon truly represented larval trapping. In all experiments, C57BL/6J mice were infected with a sensitization dose of 125 infective T. canis eggs on day 0 postinfection (PI) and challenged with 500 infective eggs on day 28 PI. In the initial experiments, larval numbers were determined within the intestinal contents, intestinal wall, mesenteric tissues, liver, lungs, skeletal muscle, and brain of each mouse on days 0.5, 1, 2, 3, 5, and 6 postchallenge (PC). Migration patterns were similar among the test and control groups except the peak of larval numbers in the liver, seen at 1 day PC in control mice, was delayed until 3 days PC in the test group. Larval trapping occurred within the liver of test mice at least by day 5 PC. In subsequent experiments, larval numbers were determined within the liver, skeletal muscle, brain of each mouse, and within the eyes of each mouse group at 4, 8, 12, and 16 wk PC. Larval numbers within the liver of test mice were similar both at 5 days PC and 16 wk PC, implying that larvae were trapped in this organ rather than delayed in their migration to other body sites. Liver trapping did not protect the eyes or brain of sensitized mice from larval migration, nor did it result in larval killing.     

The organ tropism of mouse hepatitis virus A59 in mice is dependent on dose and route of inoculation

The organ tropism of MHV-A59, a murine coronavirus, was studied in 4-6 week-old C57BL/6 mice inoculated by different routes and with various amounts of virus. MHV-A59 caused hepatitis after intracerebral and intraperitoneal inoculation (two clearly artificial routes) and also after intranasal and intragastric inoculation (two routes more likely to mimic naturally acquired infection). For each route, the severity of hepatitis was dependent on the amount of virus inoculated. Significantly higher doses were needed to cause hepatitis by the intranasal or intragastric routes. We have shown previously that mice inoculated intracerebrally with MHV-A59 develop mild meningoencephalitis followed by chronic central nervous system (CNS) disease, characterized by primary demyelination (1). We extend these results here to show that acute CNS disease can be produced also by intranasal and intragastric inoculation, although much larger doses are needed as compared to intracerebral inoculation. Thus induction of demyelination, not only by the intracerebral route but also by the intranasal route, provides a useful model system to study virus-induced demyelination.     

Leptin does not influence surfactant synthesis in fetal sheep and mice lungs

In the fetus, leptin in the circulation increases at late gestation and likely influences fetal organ development. Increased surfactant by leptin was previously demonstrated in vitro using fetal lung explant. We hypothesized that leptin treatment given to fetal sheep and pregnant mice might increase surfactant synthesis in the fetal lung in vivo. At 122-124 days gestational age (term: 150 days), fetal sheep were injected with 5 mg of leptin or vehicle using ultrasound guidance. Three and a half days after injection, preterm lambs were delivered, and lung function was studied during 30-min ventilation, followed by pulmonary surfactant components analyses. Pregnant A/J mice were given 30 or 300 mg of leptin or vehicle by intraperitoneal injection according to five study protocols with different doses, number of treatments, and gestational ages to treat. Surfactant components were analyzed in fetal lung 24 h after the last maternal treatment. Leptin injection given to fetal sheep increased fetal body weight. Control and leptin-treated groups were similar in lung function (preterm newborn lamb), surfactant components pool sizes (lamb and fetal mice), and expression of genes related to surfactant synthesis in the lung (fetal mice). Likewise, saturated phosphatidylcholine and phospholipid were normal in mice lungs with absence of circulating leptin (ob/ob mice) at all ages. These studies coincided in findings that neither exogenously given leptin nor deficiency of leptin influenced fetal lung maturation or surfactant pool sizes in vivo. Furthermore, the key genes critically required for surfactant synthesis were not affected by leptin treatment.     

Distribution and disappearance of the radiolabeled carbon derived from L-arginine and taurine in the mouse

L-arginine and taurine are still in the center of physiological and pharmacological research. Although the fate of nitrogen of both compounds and of the ³⁵S-taurine is well-documented, the fate of the carbon skeleton has not been elucidated yet. We studied the organ distribution of ¹⁴C arginine and ¹⁴C taurine over time in the mouse using whole body autoradiography with densitometric image analysis. We describe different organ distribution patterns. Kidney, heart, lung, the Harderian gland, the central nervous system, intestine and testis showed a comparable pattern of arginine disappearance in contrast to rapid disappearance in the salivary gland and the accumulation pattern in bone and spleen. Data on ¹⁴C taurine of liver, kidneys, lung, testis and Harderian gland resembled the arginine pattern; Accumulation of taurine carbon was found in salivary gland, bone, intestine, heart and brain. Our studies challenge and demand further related studies to obtaining more information on the fate of the carbon skeleton of these amino acids.     

Eosinophilia, granuloma formation, migratory behaviour of second stage larvae in murine Toxocara canis infection. Effect of the inoculum size

Experimental infection of mice with Toxocara canis provides one of the best models for immunological and pathological studies of the visceral larva migrans syndrome. Blood eosinophilia, the migratory behaviour of second stage larvae and granuloma formation were studied in Swiss mice infected with Toxocara canis. Eosinophilia, spleen, liver and lung indexes were followed during a primary infection with different inoculum sizes (500 and 1500 eggs) while the migratory behaviour of larvae was studied in a primary infection with 1500 eggs over a period of 4 months. In mice infected with three challenges of 1500 eggs in order to elicit a strong inflammatory reaction in the tissues, a histopathological study was carried out. The results showed that eosinophilia, spleen and lung indexes (but not the liver index) were influenced by the parasite inoculum size. The migratory behaviour study showed that larval recovery was maximal three days post-infection, from the liver and lungs; the peak recovery from the skeletal muscles and brain being on days 15 and 30 post-infection, respectively. The histopathological study revealed the formation of granulomas in all the tissues examined (liver, lungs, kidneys, spleen, lymph nodes, myocardium etc.) but not in nervous tissue or in the retina of the eye. Granulomas in the lungs were larger than those found in the liver. The implications of these results are discussed considering host-parasite inter-relations.     

Effect of egg dosage and host genotype on liver trapping in murine larval toxocariasis

In this study we examined the effect of various initial sensitizing doses of infective Toxocara canis eggs and the effect of murine host genotype on the level of trapping of larvae in the liver after larval challenge. In the initial experiments, C57BL/6J mice were infected with a sensitization dose of 5, 25, 75, 125, or 250 infective T. canis eggs on day 0 postinfection (PI). On day 28 PI all mice were challenged with 500 infective eggs. On days 7, 14, and 21 postchallenge (PC) larval numbers within individual livers were determined. Trapping of larvae was observed in mice receiving a sensitization dose of 25 or more eggs. At 7 and 14 days PC the level of trapping increased with sensitization egg dose up to a dose of 125 eggs. At 21 days PC the level of trapping reached a plateau at a sensitization dose of 75 eggs. The peak level of larval trapping was observed on day 7 and day 14 PC following sensitization doses of 125 and 250 eggs, respectively. In the subsequent experiments, mice of various strains and H-2 haplotypes were inoculated with an initial sensitization dose of 125 eggs and a challenge dose of 500 eggs on day 0 and day 28 PI, respectively. Larval trapping within the liver was determined on day 14 PC. C57BL/6J mice trapped significantly more larvae than DBA/2J mice (P less than 0.01); all other strains trapped larvae at a lower, but statistically similar, level to the C57BL6/J mice.(ABSTRACT TRUNCATED AT 250 WORDS)     

Immune therapy of a persistent and disseminated viral infection.

The mechanism of viral clearance was studied by using the mouse model of chronic infection with lymphocytic choriomeningitis virus. Distinct patterns of viral clearance and histopathology were observed in different organs after adoptive immune therapy of persistently infected (carrier) mice. Clearance from the liver occurred within 30 days and was accompanied by extensive mononuclear cell infiltrates and necrosis of hepatocytes. Infectious virus and viral antigen were eliminated concurrently. This pattern of viral clearance was also seen in most other tissues (i.e., lung, spleen, lymph nodes, pancreas, etc.). In contrast, a different pattern of clearance was observed in the brain. Infectious virus was eliminated within 30 days, but viral antigen persisted in the central nervous systems of treated carrier mice for up to 90 days. The urinary system was the most resistant to immune therapy. Elimination of infectious virus and viral antigen from the kidney took greater than 200 days and even then was not complete; trace levels of infectious virus were still present in the kidneys of some treated carrier mice. After immune therapy, viral antigen in the kidney was located within renal tubules that costained for intracellular mouse immunoglobulin G. This unusual staining pattern, coupled with the observation of large numbers of plasma cells within the kidney, suggests that virus-immunoglobulin G complexes found in the tubules may represent in situ immune complex formation as opposed to deposition of circulating immune complexes. In conclusion, these results suggest that the site (organ) of viral persistence is an important consideration in developing treatment strategies for controlling chronic viral infections.     

简易高效的小鼠肝再生模型的建立

目的建立一种简易、高效的小鼠2/3肝切除方法。方法取3月龄健康昆明小鼠,进行肝顺次结扎切除手术,观察术后小鼠生存和肝组织再生状况。结果通过顺次结扎切除左小叶和中央小叶,可在15min内完成小鼠2/3肝脏切除手术,术后成活率为90%,术后42h时可见肝组织再生,术后7d肝脏可恢复75%以上的肝组织原质量。结论通过分叶顺次肝切除术,可准确量化肝脏切除的程度,简便易行、成功率高,为肝再生的机理研究提供了理想的动物模型。     

Susceptibility of rats to infection with Toxocara pteropodis

Infective eggs of Toxocara pteropodis were administered to Wistar rats via oral and parenteral routes. Third-stage larvae were recovered from the livers of suckling young 8 days after oral infection, and from livers and lungs after intraperitoneal or subcutaneous inoculation of eggs. These larvae were short-lived as none were found in suckling mice killed 2 weeks post-infection. Larvae were not recovered from tissues of rats aged 22 days or more when inoculated orally, indicating that refractoriness to infection develops rapidly with growth. Small numbers of larvae were recovered from the lungs of older rats 4 days after subcutaneous but not after oral inoculation. Adult male Buffalo and Fisher rats were also totally resistant to oral infection. Hence, rats differ from mice in their susceptibility to T. pteropodis.     

丁酸钠器官毒性研究

目的:研究组蛋白去乙酰化酶抑制剂(histone deacetylase inhibition HDACi):丁酸钠(Sodium Butyrate Na B)腹腔连续给药对BALB/C小鼠体重增长及器官发育的影响。方法:20只健康,3周BALB/C小鼠随机分成2组(丁酸钠组和对照组);丁酸钠组腹腔注射丁酸钠(Na B)1.2 g/Kg·d,连续21天;对照组同时间腹腔注射等量生理盐水。21天后,测量体重;行4%多聚甲醛灌注、固定,取心脏,肝脏,脾脏,肺脏,肾脏,脑组织以及小肠组织器官,做石蜡切片,HE染色两组比较有无器官损害。结果:1.丁酸钠组与对照组比较,两组动物体重增长良好,平均增长11 g,两组间无统计学差异(P0.05)。2.HE染色见丁酸钠组:心肌细胞无变性,坏死,无炎性细胞浸润,无肉芽组织形成;脾脏红、白髓结构清晰,脾窦无扩张,未见炎性细胞浸润;肺间质无扩张,充血,未见纤维化,肺泡无水肿;肾小管上皮细胞无变性坏死,肾间质未见水肿;脑细胞周围间隙和小血管间隙无增宽;肠道纤毛上皮排列整齐,肠壁无出血,坏死,无渗出;肝细胞围绕中央静脉呈放射状排列,细胞无水肿,无胆汁淤积。未发现上述器官的病理变化。结论:丁酸钠长期腹腔给药安全,无明显毒副作用。     

Genotoxicity and repair capability of Mus musculus DNA following the oral exposure to Tramadol

Tramadol is an analgesic and psychoactive drug that acts primarily upon the central nervous system where it alters brain function, resulting in temporary changes in perception, mood, consciousness and behavior. The aim of present study was to analyze the genotoxicity and repair capability of DNA after Tramadol exposure in albino mice (Mus musculus). For this purpose, forty mice were divided equally into four groups as; a control group (without drug) and three treatment groups that were treated with three doses of Tramadol as minimum dose group, Intermediate dose group and maximum dose group, corresponding to 25 mg/kg, 50 mg/kg and 75 mg/kg of body weight respectively. The dose was given orally for 15 days. After 15 days peripheral blood was drawn from half mice of each group and subjected to comet assay. While the remaining half mice were given a recovery period of 15 days and same procedure was used for blood collection and comet assay. Significant difference in various comet parameters was observed among control and exposed groups. Maximum damage was observed at highest concentration 75 mg/kg of Tramadol and minimum damage was observed at dose 25 mg/kg of Tramadol, while results of repaired mice group showed that repair capability of Tramadol was minor and recovery of Tramadol required a lot of time. It can be concluded that Tramadol cause genotoxicity that is dose dependent and has low repair capability.     

Effects of irradiation on the biology of the infective larvae of Toxocara canis in the mouse

Mice were infected with either 2,000 normal or irradiated embryonated eggs of Toxocara canis and the number of larvae in their livers, lungs, brains, and carcasses investigated at 5, 20, and 33 days of infection. Mortality of mice infected with normal eggs was 33% between day 4 and 8 postinfection but there was no mortality among mice infected with irradiated eggs. Irradiation with 60, 90, or 150 kr of X-rays inhibited the migration of larvae from the livers and lungs and their accumulation in brain and carcass in proportion to the irradiation dose. By day 33 of infection, the ratio of larvae in liver and lungs to larvae in brain and carcass was 0.16 in normal mice, 0.42 in 60-kr mice, 0.98 in 90-kr mice, and 23.3 in 150-kr mice. Irradiated larvae, particularly those migrating through the peritoneal cavity, died faster than normal larvae until day 20. Irradiation favored survival after day 20. By days 20 and 33 postinfection the total parasite load was 29% and 8%, respectively, of the administered dose in control mice, 18% and 12% in 60-kr mice, 8% and 4% in 90-kr mice, and 0.9% and 0.3% in 150-kr mice. Irradiation of infective T. canis larvae, then, reduces their pathogenicity, inhibits their migration from liver and lungs, kills some of the parasites during the first 3 weeks of infection, but favors their late survival in the host.     

Oral chromium(VI) does not affect the frequency of micronuclei in hematopoietic cells of adult mice and of transplacentally exposed fetuses

Chromium(VI) compounds are genotoxic in a variety of cellular systems. Their potential carcinogenicity is affected by toxicokinetic patterns restricting bioavailability to certain targets, and by metabolic pathways affecting interaction of chromate-derived reactive species with DNA. Epidemiological data indicate that chromium(VI) can be carcinogenic to the human respiratory tract following inhalation at doses that are only achieved in certain occupational settings. However, concern has been raised that adverse effects may also result from oral intake. In order to further explore this issue, we performed studies in BDF1 and Swiss mice of both genders and various age. Sodium dichromate dihydrate and potassium dichromate were administered either with the drinking water, up to a concentration of 500 mg chromium(VI)/l for up to 210 consecutive days, or in a single intragastric dose of 17.7 mg/kg body weight. Under these conditions, no increase of the micronucleus frequency was observed in either bone marrow or peripheral blood erythrocytes. Conversely, the same compounds induced a clastogenic damage following intraperitoneal injection, which by-passes detoxification mechanisms. In addition, due to the hypothesis that susceptibility may be increased during the period of embryogenesis, we treated pregnant mice, up to a concentration of 10 mg chromium(VI)/l drinking water. There was no effect on the numbers of fetuses/dam and on body weight of fetuses. Again, no toxic or genotoxic effect was observed either in bone marrow of pregnant mice or in liver and peripheral blood of their fetuses. Thus, even at doses that largely exceed drinking water standards (up to 10,000 times) or by massive intragastric administration, chromium(VI) is not genotoxic to hematopoietic cells of either adult mice or transplacentally exposed fetuses. These conclusions are consistent with the poor toxicity and lack of carcinogenicity of oral chromium(VI), and are mechanistically explained by the high efficiency of chromium(VI) detoxification processes in the gastrointestinal tract.     

Oral chromium(VI) does not affect the frequency of micronuclei in hematopoietic cells of adult mice and of transplacentally exposed fetuses

Chromium(VI) compounds are genotoxic in a variety of cellular systems. Their potential carcinogenicity is affected by toxicokinetic patterns restricting bioavailability to certain targets, and by metabolic pathways affecting interaction of chromate-derived reactive species with DNA. Epidemiological data indicate that chromium(VI) can be carcinogenic to the human respiratory tract following inhalation at doses that are only achieved in certain occupational settings. However, concern has been raised that adverse effects may also result from oral intake. In order to further explore this issue, we performed studies in BDF1 and Swiss mice of both genders and various age. Sodium dichromate dihydrate and potassium dichromate were administered either with the drinking water, up to a concentration of 500 mg chromium(VI)/l for up to 210 consecutive days, or in a single intragastric dose of 17.7 mg/kg body weight. Under these conditions, no increase of the micronucleus frequency was observed in either bone marrow or peripheral blood erythrocytes. Conversely, the same compounds induced a clastogenic damage following intraperitoneal injection, which by-passes detoxification mechanisms. In addition, due to the hypothesis that susceptibility may be increased during the period of embryogenesis, we treated pregnant mice, up to a concentration of 10mg chromium(VI)/l drinking water. There was no effect on the numbers of fetuses/dam and on body weight of fetuses. Again, no toxic or genotoxic effect was observed either in bone marrow of pregnant mice or in liver and peripheral blood of their fetuses. Thus, even at doses that largely exceed drinking water standards (up to 10,000 times) or by massive intragastric administration, chromium(VI) is not genotoxic to hematopoietic cells of either adult mice or transplacentally exposed fetuses. These conclusions are consistent with the poor toxicity and lack of carcinogenicity of oral chromium(VI), and are mechanistically explained by the high efficiency of chromium(VI) detoxification processes in the gastrointestinal tract.     

Larval recovery of Toxocara canis in organs and tissues of experimentally infected Rattus norvegicus

The aim of this note was to record for the first time the recovery of Toxocara canis larvae from tissues and organs of Rattus norvegicus (Berkenhout, 1769), Wistar strain, until the 60th day after experimental infection. Rats were orally infected with embryonated T. canis eggs, killed on days 3, 5, 8, 10, 15, 30, and 60 after inoculation and larvae were recovered from liver, lungs, kidneys, brain, and carcass after acid digestion, showing a pattern of migration similar of that previously observed in mice.     

Observations on Toxocara pteropodis infections in mice

Infection in mice with Toxocara pteropodis was investigated. In mice fed infective eggs, third-stage larvae hatched out and penetrated the mucosa, predominantly that of the lower intestine. They travelled via the portal vein to the liver, where they remained at least 14 months. They grew in length from 430 +/- 15 micron, at three days post infection (p.i.), to 600 +/- 50 micron, at six to nine weeks p.i., after which time growth ceased. Blood eosinophilia appeared at 28 days p.i., and eosinophil levels continued to rise gradually beyond this time. In female mice the larvae did not migrate from the liver in response to pregnancy or lactation. When infective eggs were inoculated subcutaneously or intra-peritoneally, larvae hatched out and ultimately appeared in the liver in larger numbers than seen with oral infections.     

Mechanism of hypocalcemia induced by intraperitoneal, intragastric, and intravenous administration of ethanol to the rat

Acute hypocalcemic effects of intraperitoneal administration of 3 and 5 g ethanol/kg body weight; intragastric administration of 3, 5, and 7 g ethanol/kg body weight; and intravenous administration of 2.5 a ethanol/kg body weight were investigated in 20 h fasted female Wistar rats. Dose-dependent hypocalcemia was similarly induced by intraperitoneal and intragastric routes of administration. Net calcium efflux from plasma, as indicated by the plasma 45Ca activity, was unaffected by 3 g ethanol/kg body weight but was delayed at higher doses of ethanol. Intragastric, but not intraperitoneal, administration of ethanol increased the gastrointestinal luminal calcium content partly by enhancing calcium secretion. Significantly increased tissue 45Ca content 30 min after ethanol administration was evident in the duodenum (31%), jejunum (27%), and colon (33%) in the intragastric ethanol-treated group and in the duodenum (40%), jejunum (38%), ileum (45%), colon (39%), and liver (25%) in the intraperitoneal ethanol-treated group. Thus, the hypocalcemia induced by both intraperitoneal and intragastric administration of ethanol could be partly accounted for by the suppression of calcium efflux from some soft tissues. In contrast, intravenous administration of ethanol was found to enhance the calcium efflux from plasma without affecting the net 45Ca content in the soft tissues. The mechanism(s) by which ethanol affects calcium transport has yet to be elucidated.     

Kinetics and organ distribution of [14C]-sialic acid-GM3 and [3H]-sphingosine-GM1 after intravenous injection in rats.

Serum kinetics and organ distribution of [14C]-sialic acid-GM3 and [3H]-sphingosine-GM1, administered as an intravenous bolus, were analysed in Wistar rats. [3H]-GM1 and [14C]-GM3 had serum half-lives of 1.4 hours and 1.8 hours, respectively. Three hours after injection 75% of the GM1- and 38% of the GM3-associated label were present in the liver. Smaller yet significant amounts of label were present in the central nervous system, kidneys and lung. In vitro studies showed that [14C]-GM3 and [3H]-GM1 incubated with serum were predominantly bound to the High Density Lipoprotein and the Low Density Lipoprotein fractions. These results suggest a rapid serum clearance of exogenous gangliosides by the liver in rats.