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Infectivity of the mouse mammary tumour virus (MMTV) is inhibited by mouse APOBEC3 (mA3) which is efficiently packaged into virions. As the inhibition is only partial, the virus can replicate in tissues expressing mA3 and complete its replication cycle. Here, we have examined the sensitivity of MMTV to inhibition by a human orthologue of mA3, A3G. We report that the virus containing A3G is only moderately susceptible to inhibition by the human factor. Whereas the vif-deficient HIV-1 vector produced in human epithelial cells expressing endogenous levels of A3G was efficiently inhibited, an MMTV vector remained fully infectious. Greater A3G expression levels were necessary to restrict infectivity of MMTV, but only when the factor retained its deaminase activity. Furthermore, the spreading kinetic of a replication competent MMTV was only moderately accelerated in cells with downmodulated A3G expression. These data suggest that MMTV has evolved a mechanism to neutralize antiviral activity of APOBEC3 proteins.

Background: Opisthorchis viverrini (OV) infection generates oxidative stress/free radicals and is considered as a primary cause ofcholangiocarcinoma since it primarily triggers sclerosing cholangitis., Objective: In this study, the impacts of andrographolide on acute opisthorchaisis in β-naphthoflavone (BNF)-exposed hamsters were investigated., Material and Method: Ethoxyresorufin O-deethylase (EROD) and methoxyresorufin O-demethylase (MROD) activities and Thiobarbituric acid reaction substances (TBARS) assay of andrographolide in acute opisthorchiasis in the BNF-exposed hamsters were assessed., Results: The results showed that andrographolide ameliorated the hepatic CYP1A1 and CYP1A2 activities by decreases of the specific enzymatic reactions of EROD and MROD, respectively, in the BNF-exposed hamsters. Moreover, andrographolide lowered the formation of malondialdehyde in the livers and brains of the hamsters., Conclusion: These observations revealed the promising chemo-protective and antioxidant activities of andrographolide via suppression of the specific EROD and MROD reactions and lipid peroxidation against acute opisthorchiasis in the BNF-exposed hamsters.

The naked mole-rat (NMR) Heterocephalus glaber is a unique and fascinating mammal exhibiting many unusual adaptations to a subterranean lifestyle. The recent discovery of their resistance to cancer and exceptional longevity has opened up new and important avenues of research. Part of this resistance to cancer has been attributed to the fact that NMRs produce a modified form of hyaluronan--a key constituent of the extracellular matrix--that is thought to confer increased elasticity of the skin as an adaptation for living in narrow tunnels. This so-called high molecular mass hyaluronan (HMM-HA) stems from two apparently unique substitutions in the hyaluronan synthase 2 enzyme (HAS2). To test whether other subterranean mammals with similar selection pressures also show molecular adaptation in their HAS2 gene, we sequenced the HAS2 gene for 11 subterranean mammals and closely related species, and combined these with data from 57 other mammals. Comparative screening revealed that one of the two putatively important HAS2 substitutions in the NMR predicted to have a significant effect on hyaluronan synthase function was uniquely shared by all African mole-rats. Interestingly, we also identified multiple other amino acid substitutions in key domains of the HAS2 molecule, although the biological consequences of these for hyaluronan synthesis remain to be determined. Despite these results, we found evidence of strong purifying selection acting on the HAS2 gene across all mammals, and the NMR remains unique in its particular HAS2 sequence. Our results indicate that more work is needed to determine whether the apparent cancer resistance seen in NMR is shared by other members of the African mole-rat clade., (© 2015 The Author(s) Published by the Royal Society. All rights reserved.)

Ulcerative dermatitis (UD) is a common cause of morbidity and euthanasia in mice with a C57BL/6 (B6) background. The purposes of the current study were to determine whether UD lesions could be reliably produced in B6 mice lacking stearoyl-CoA desaturase 1 (SCD1(-/-) mice), to ascertain whether the UD lesions in SCD1(-/-) mice were similar to those found in other B6 mice, and to characterize the cell invasion phenotype of Staphlococcus xylosus cultured from the lesions. S. xylosus isolates from the environment and human skin were used as controls. SCD1(-/-) (n = 8 per group) and nontransgenic B6 control mice (n = 22 mice pooled from 3 groups that received different concentrations of conjugated linoleic acid) were fed standard rodent chow or a semipurified diet (NIH AIN76A) for 4 wk. Samples from other B6 mice with UD (field cases; n = 7) also were submitted for histology and culture. All of the SCD1(-/-) mice developed UD lesions by 4 wk on NIH AIN76A. None of SCD1(-/-) fed standard rodent chow and none of the wildtype B6 mice fed NIH AIN76A developed UD. Supplementation with conjugated linoleic acid did not affect ulcerogenesis. UD lesions in SCD1(-/-) mice and field cases were grossly and histologically similar. S. xylosus was isolated from SCD1(-/-) mice with UD (71%) and field cases of UD (43%). These isolates were the most cell-invasive, followed by the environmental isolate, and finally the human skin isolate. Our results provide a basis for further pathologic and clinical study of UD.

dsRNA-activated protein kinase (PKR) is activated by viral dsRNAs and phosphorylates eIF2a reducing translation of host and viral mRNA. Although infection with a chimeric West Nile virus (WNV) efficiently induced PKR and eIF2a phosphorylation, infections with natural lineage 1 or 2 strains did not. Investigation of the mechanism of suppression showed that among the cellular PKR inhibitor proteins tested, only Nck, known to interact with inactive PKR, colocalized and co-immunoprecipitated with PKR in WNV-infected cells and PKR phosphorylation did not increase in infected Nck1,2-/- cells. Several WNV stem-loop RNAs efficiently activated PKR in vitro but not in infected cells. WNV infection did not interfere with intracellular PKR activation by poly(I:C) and similar virus yields were produced by control and PKR-/- cells. The results indicate that PKR phosphorylation is not actively suppressed in WNV-infected cells but that PKR is not activated by the viral dsRNA in infected cells., (Copyright © 2011 Elsevier Inc. All rights reserved.)

The two related species, Rodentolepis straminea (Goeze, 1782) and Rodentolepis microstoma (Dujardin, 1845) (Cestoda, Hymenolepididae), both parasites of rodents, were compared morphologically and electrophoretically. Adult worms were isolated from three wild rodent species of the family Muridae (Apodemus flavicollis, Apodemus sylvaticus, and Mus musculus) from three different sites in Spain and France. Although these two species were strikingly similar in morphological appearance, some of the morphological and metrical features analysed (scolex, mature segments and eggs) can be used for differentiation. Fixed allelic differences were found. Of the ten enzymes detected by starch-gel electrophoresis, six (AAT, AK, GPI, MDH, NP, PGM) showed characteristic isoenzyme profiles in each species. Only in MPI, PEPC, PEPD, and ME enzyme loci were no differences found. The study revealed that the two taxa can be clearly differentiated.

We investigated the involvement of nitric oxide in Schistosoma-induced liver injury. We found that inducible nitric oxide synthase mRNA became detectable in the liver at the onset of parasite egg laying and levels then increased as the eggs accumulated in the organ. Enzyme concentration and activity paralleled mRNA levels. The event was a direct effect of egg deposition, as it occurred in the liver after natural infection, or in the lungs after i.v. injection of the eggs. However, nitric oxide seems to have no direct effect on the eggs since in vitro assays showed that the nitric oxide donor SIN-1 did not alter the ability of the eggs to hatch. L-Arginine and L-NAME, a nitric oxide synthase inhibitor, were administered to infected mice in an attempt to increase or reduce nitric oxide production, respectively. Arginine had no effect on the disease, whereas the inhibitor led to a marked decrease of hepatic injury with, in particular, reduced fibrosis and decreased lipid peroxidation. In conclusion, not only is inducible nitric oxide synthase activity unlikely to exert an anti-microbicidal effect against the egg stage of S. mansoni but it might lead to deleterious effects in the liver and therefore contribute to the pathology.

Mutation of a receptor tyrosine kinase gene, Mertk, in the Royal College of Surgeons (RCS) rat results in defective phagocytosis of photoreceptor outer segments by the retinal pigment epithelium (RPE) and retinal degeneration. We screened the human orthologue, MERTK, located at 2q14.1 (ref. 10), in 328 DNA samples from individuals with various retinal dystrophies and found three mutations in three individuals with retinitis pigmentosa (RP). Our findings are the first conclusive evidence implicating the RPE phagocytosis pathway in human retinal disease.

The gene encoding the cytoplasmic copper/zinc superoxide dismutase (AVSOD1) from the filarial parasite Acanthocheilonema viteae was isolated from a genomic DNA library using a degenerate oligonucleotide probe. Additionally, cDNAs of the AVSOD1 and the secreted extracellular SOD (AVSOD2) were both cloned by RT-PCR, and the AVSOD2 was expressed at high levels in E. coli. The amino acid sequence of the AVSOD1 is 89.5 and 87.5% identical to that of the corresponding enzymes of Brugia pahangi and Onchocerca volvulus, respectively. In contrast, the AVSOD2 shows a lower degree of identity to the other filarial SODs and is extensively glycosylated. RT-PCR studies demonstrate the expression of both SOD subtypes in all developmental stages of A. viteae and indicate up-regulation of the AVSOD2 expression after transmission from the vector to the definitive host. This suggests an enhanced requirement for SOD activity in post-infective larval stages and adults of A. viteae. ELISAs performed with purified recombinant AVSOD2 show that the AVSOD2 is not a major target for the immune system in naturally infected jirds.

1. Total cellular proteins from the livers of 4-, 16- and 52-week-old hepatitis- and hepatoma-predisposed Long-Evans Cinnamon (LEC) rats were compared to those from the livers of the corresponding control rats [Long-Evans Agouti (LEA) rats] by two-dimensional gel electrophoresis. 2. A polypeptide, p50/7.2 (molecular weight x 10(-3)/isoelectric point) was only found in the LEC rats, and the p43/6.4 component was greater and the p51/6.8 component was less in the LEC rats than in the LEA rats during aging. 3. A polypeptide, p29/6.8, was dramatically greater in 4-week-old LEC rats than in 4-week-old LEA rats. 4. By sequencing and Western blotting analysis, the marked differences in the level of the p29/6.8 component were found to be due to carbonic anhydrase III.

The role of alkaline protease in the development of myocardial lesions in myopathic hamsters was studied. There was abnormal elevation of alkaline protease in the myopathic heart at 1 month of age, preceding the development of cardiac lesions. In vivo treatments of verapamil were carried out in 1-month-old myopathic animals for 30 days. Results indicated that the drug treatment was effective in preventing the occurrence of the severe myocardial lesions found in the untreated animals at 2 months of age. Reduced lesion development was associated concomitantly with lowered levels of alkaline protease activity. Withdrawal of drug treatment caused the return of severe lesions and high levels of alkaline protease. The study of the alkaline protease activity in the skeletal muscle of the myopathic hamster also showed a parallel relationship between the enzyme levels and severity of lesions. The results are discussed in light of possible involvement of a serine protease and a Ca2+-activated protease in producing the cardiac lesions.

The cystine aminopeptidase (CAP) activity was determined in plasma from guinea pigs at various stages of gestation and in pregnant guinea pigs infected with Campylobacter fetus subspecies intestinalis. The CAP activity decreased with length of gestation, which is in contrast to the changes in activity in persons. Infected guinea pigs near the time of abortion can be distinguished from normal guinea pigs on the basis of plasma CAP activity, if the plasma samples are taken 1 to 2 days before abortion. Among pregnant guinea pigs at the same stage of gestation, CAP activity was lower for infected than for normal pregnant animals. This test might be used to indicate probable disruption of placentation and the onset of abortion in the guinea pig.

Dried tansy ragwort, which contains pyrrolizidine alkaloids (PA), was fed to lactating dairy goats. Milk containing 7.5 ng of PA/g (dry weight basis) from these goats was fed to rats and calves. Rats fed a goats' milk diet for 180 days with a calculated total PA intake of 0.96 mg/rat had swollen hepatocytes of centrilobular distribution, and biliary hyperplasia, indicating PA involvement. Rats fed tansy ragwort at dietary levels of 1%, 0.1%, 0.01% and 0.001% (corresponding to PA intakes of 39.77, 5.04, 0.52, and 0.05 mg/rat) showed swollen hepatocytes, megalocytosis, biliary hyperplasia, and fibrosis. The histopathologic changes in the milk-fed rats and those given 0.001% tansy ragwort in the diet were similar. Definitive changes in 2 calves fed goats' milk were not detected. The results with rats indicate that PA are transferred in goats' milk and may produce hepatoxic effects.

No statistically significant difference in alkaline phosphatase levels was demonstrated in animals injected with the FBJ virus. However, there was a significant increase associated with the development of osteosarcomas in response to the iv injection of 1.0 uCi 90 Sr/g body weight into 11-18-mo-old Anl:CFl females. It was proposed that alkaline phosphatase determinations can be used as well as roentenographic analysis to detect 90Sr-induced tumors in mice.

Spontaneously occurring calcified lesions were found in the tongues of DBA/2NCrj and CBA/BrA mice. In the DBA/2NCrj strain, the frequency of the lesion was 80% (males) and 88% (females). The youngest age of a mouse with this lesion was 18 days after birth, and 3-4 lesions were found in the tongue of 6- to 8-week-old mice. In CBA/BrA mice, 20% of females and 48% of males had the lesions. No significant differences were found in the serum calcium concentrations in high and low lesion-developing strains, but the alkaline phosphatase activities in the high-developing DBA/2NCrj, DBA/LiA, and CBA/BrA strains were higher than in strains with no calcified lesions.

The purpose of this paper was to show whether the activity of the zinc-dependent enzyme alkaline ribonuclease in zinc-sensitive tissues allows conclusions to be drawn on the Zn supply status. For this 27 weaned male Sprague-Dawley rats were divided into three groups of 9 animals each. A Zn deficiency group, which was given a diet with a Zn content of 3 ppm ad libitum, was compared to a pair-fed and an ad libitum control group with a Zn content in the diet of 60 ppm each. After 22 trial days the animals were killed, and the zinc and protein contents as well as the activity of the alkaline ribonuclease in the serum, testicles, femur, urine, liver, and kidneys were determined. Although the Zn concentration in the serum, testicles, femur, and kidneys of the deficiency animals were significantly reduced, the alkaline ribonuclease showed an increased activity only in the kidneys, in the testicles the activity was reduced, and in the serum, femur, urine and liver it remained unchanged. The protein concentration in serum and femur was reduced because of Zn deficiency, whereas the decrease in testicles, liver and kidneys must be attributed to the reduced feed intake. The influence of the dietary Zn deficiency on the activity of the alkaline ribonuclease was therefore more the result of an altered feed intake and growth rate than a direct effect of zinc on the enzymatic system. Therefore the determination of the activity of the alkaline ribonuclease can be excluded as a parameter for the diagnosis of Zn supply and Zn deficiency.

The prairie dog is a useful experimental animal model for studies of cholesterol gallstone pathogenesis. The unique susceptibility to rapid induction of gallstones solely by feeding of a 1.2% cholesterol diet in this species could result from low levels of hepatic cholesterol 7 alpha-hydroxylase. With optimal assay conditions in hepatic microsomes, a basal specific activity of about 25 pmol/min per g protein was found. Administration of diets containing 1.2% cholesterol or 5% cholestyramine caused hydroxylase levels to increase 60 and 250%, respectively. This response pattern is similar to that observed in other species under the same conditions, indicating that abnormally low basal or inappropriately unresponsive hydroxylase levels are not susceptibility factors unique to this model. With optimal assay conditions for hydroxymethylglutaryl-CoA reductase, a Km of 32.5 microM (S-HMG-CoA) and basal specific activities of between 60 and 175 pmol/min per mg protein were found. Following feeding of either sodium chenodeoxycholate or sodium cholate, in reasonable pharmacologic doses, no suppression of hydroxylase and reductase levels was found. These findings undermine the widely held view that the therapeutic effect of oral chenodeoxycholate in man for cholesterol gallstone dissolution is directly mediated by suppression of the activities of these enzymes.

The clonal origin of spontaneous multiple mammary tumors in mice was examined. For this purpose, hybrid female mice (Pgk-1b/Pgk-1a), F1[SHN(Pgk-1b) X C3H/He (Pgk-1a)], with X-chromosome inactivation mosaicism with regard to the phosphoglycerate kinase (PGK)-1 isozyme together with a high incidence of spontaneous mammary tumors were constructed. Thirty-seven of 45 mammary tumors (82%) in mosaic mice had a single phenotype of PGK, indicating monoclonal origin. The multiple mammary tumors formed in these mice varied in PGK type, indicating independent cellular origins.

The adaptive responses to sucrose and fat diets were investigated in two species of spiny mice, Acomys russatus and Acomys cahirinus, in relation to their propensity to develop diabetic-like symptoms. A russatus gained weight pronouncedly, both on regular and fat-rich seed diet, did not exhibit hyperglycemia or hyperlipidemia but had highly increased hepatic triglyceride content in association with high levels of circulating free fatty acids and incidence of ketonuria in 10 of 41 animals. On the other hand, A. cahirinus exhibited a moderate weight gain on the fat diet which was accompanied by hyperglycemia but no hyperlipidemia or ketonuria. Neither weight gain nor ketonuria were evident in A. russatus and A. cahirinus on the sucrose-rich diet, but there was hyperlipidemia in the latter species. A. cahirinus, in particular, showed many-fold induction of liver enzymes, of regulatory importance in the pathways of glycolysis and lipogenesis, which could be linked to the hyperlipidemia in this species. On the fat diet there was a smaller increase in activity in enzymes related to gluconeogenesis in A. russatus compared with A. cahirinus, as well as a smaller suppression of glycolytic and lipogenic enzymes. Adipose tissue lipoprotein lipase activity rose in response to the fat-rich diet, more markedly in A. russatus than A. cahirinus in correlation to the more marked weight gain and hyperinsulinemia in this species. The affluent diets, especially sucrose, elicited an increase in circulating triiodothyronine levels which was more pronounced in A. cahirinus than in A. russatus.(ABSTRACT TRUNCATED AT 250 WORDS)

Trypanosoma brucei EATRO 110 infection in deer mice (Peromyscus maniculatus) produced anemia in 15 of 42 mice between postinoculation days 14 and 70. The infected anemic (IA) mice had significantly higher reticulocyte counts (P less than 0.025), spleen (P less than 0.001) and liver (P less than 0.005) weights, and higher parasitemia than did infected nonanemic (INA) mice. gamma-Globulin concentrations of infected mice were markedly increased, and values for INA mice were 10% higher than values for IA mice. Erythrocyte hexokinase, glucose-6-phosphate dehydrogenase, glutathione peroxidase, glutathione reductase, and pyruvate kinase activities were increased in infected mice, whereas phosphofructokinase was only slightly decreased in infected mice. Seemingly, development of anemia was not related to defects in erythrocyte metabolism. Serum iron values of infected mice were similar to those of controls. Storage iron (hemosiderin and ferritin) concentrations were increased in the spleen and to a lesser extent in the liver. The activity of superoxide dismutase, an enzyme that favors conversion of easily mobilized soluble ferritin to poorly mobilized insoluble hemosiderin, was decreased per unit weight of the enlarged spleen, although total activity was increased. The superoxide dismutase activity per unit weight of liver was not altered in infected mice although total liver activities were increased. These findings, as well as the marked reticulocytosis, indicate that lack of iron supply does not have a part in precipitating the anemia of T brucei infection. Leukocytosis was present in infected animals and was associated with lymphocytosis, eosinopenia, basophilia, and monocytosis; these changes were more marked in IA than in INA mice.

The skin of a new hairless mutation in the rat termed "bald" was examined histologically and enzyme histochemically with animals from three weeks to 18 months of age. The loss of hair in homozygous (bald) rats proved to occur as follows: a club hair rising within the hair follicle in the first catagen phase was not anchored and fell out due to dilatation of the follicular lumen. In the skin of bald rats from two to three months of age on, two types of cyst developed, one from the infundibulum of the hair follicle and the other from a lower follicular portion left in the dermis. Each had histologic patterns different from each other. The wall of the former cyst contained various-sized keratohyaline granules in a large number, while the latter was keratinized without granules. In addition to cyst formation, foreign-body granulomas frequently appeared from three months of age on, originating from degenerated follicular portions in the dermis. In advanced cases after 12 months of age, the granulomatous lesions were sharply demarcated from the other tissue. Histochemically, acid phosphatase activity was observed in the skin of bald rats, in the wall of the dilated hair follicles and the cystic wall where progressive keratinization with age occurred. This enzymatic activity tended to heighten as keratinization proceeded.

Adipose tissue in various stages of fish oil-induced yellow fat disease in the rat had the same acid phosphatase and 5-nucleotidase activity pattern as similar stages of the disorder in mink and pig. A weak acid phosphatase and 5-nucleotidase activity was seen in interstitial lipofuscin-laden macrophages in "stage M" yellow fat disease without fat cell degeneration. Activity of these macrophagic enzymes increased when there was fat cell degeneration ("stage S" and "stage E" yellow fat disease). This different phosphatase activity in the same cell type may result from phagocytosis of substrates with variable digestibility. Macrophages directly surrounding affected fat cells in steatitis areas ("stage S" and "stage E") had strong acid phosphatase and 5-nucleotidase activity. As in the pig, increased 5-nucleotidase activity was found in affected fat cells, which probably indicates plasma membrane damage. Increased nonspecific esterase activity occurred around affected fat cells. Only a small part of this esterase activity originated from inflammatory cells. This indicates that an increase of esterase activity in degenerating adipose tissue may be an endogeneous process in this tissue.

The kinetics of the release of a liver enzyme, glutamate dehydrogenase, into the serum of Fasciola hepatica infected rats was studied. The results support previous work that has shown that barriers to reinfection with this parasite are met before any pronounced liver damage takes place. The presence of this enzyme in serum can be used as an indicator of resistance to reinfection.

Serum biochemical analyses were done on F344 rats in the early and late stages of mononuclear cell leukemia. There were marked increases in serum bilirubin, alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase and alkaline phosphatase. Increases in these parameters generally were more severe in the late stages of leukemia. Both direct and indirect-reacting bilirubin were increased with the unconjugated form predominating early and the conjugated form predominating late in the course of the disease. Lactate dehydrogenase isoenzyme determination correlated with histological examination indicated that liver damage was responsible for the observed changes. Urinalysis revealed marked hemoglobinuria, bilirubinuria and increased urine urobilinogen. Serum protein electrophoresis revealed marked reductions in the alpha globulin fractions.

Values of serum and plasma LDH in rats were comparatively studied, and the following results were obtained: 1) The activity of LDH increased in serum with time during clotting, but no changes of LDH activity were found in plasma. 2) When platelet rich plasma (PRP) was recalcified and allowed to clot, LDH-release from platelets with a corresponding increase of serum LDH was observed, but addition of ADP or thrombin to PRP did not have an effect on LDH-release. 3) LDH-release from platelets by calcium was not inhibited by aspirin, and it was influenced by the quality of the test tube. 4) Values of serum and plasma LDH on experimentally induced liver-damaged or kidney-damaged rats and tumor-bearing rats were examined in relation to their tissue damages, revealing that plasma LDH activity represents the condition of a disease better than serum LDH activity.

Acute hemorrhagic pancreatitis (AHP) was induced in 43 anesthetized rats by retrograde injection of sodium taurodeoxycholic acid into the common pancreatic biliary duct. At postinjection hours 1, 3, 6, 12, and 18, samples of plasma and hemorrhagic ascitic fluid (HAF) were obtained from rats in which AHP was induced and from rats that were sham operated. Early phase components of the kallikrein kinin system, including kallikrein-like (KK) activity and prekallikrein (PKK) and kallikrein inhibitor (KKI) concentrations, were measured in plasma and HAF samples. In the rats with induced AHP, PKK concentrations were decreased significantly in 18-hour plasma samples (P less than 0.05) and in all HAF samples (P less than 0.001) from 1 to 18 hours after induction of AHP. The KK activity was significantly increased (P less than 0.001) in the 6- and 12-hour plasma samples. In the 1-hour HAF samples, KK activity was increased greater than 10 times over that in the plasma pool of rats and remained increased for 18 hours. The KKI concentrations were markedly decreased in all HAF samples. In the sham-operated group, no significant change was observed. Histopathologic changes included edema, extensive hemorrhage, focal necrosis of many acinar cells around the head of the pancreas, slight inflammatory cell infiltration, vascular thrombosis, and partial lysis of pancreatic ducts. The extent of the changes of PKK, KK, and KKI values in HAF was greater than the extent of those in plasma. Increasing KK activity in plasma and HAF is indicative of bradykinin generation and the participation of this system in local and systemic pathologic change.(ABSTRACT TRUNCATED AT 250 WORDS)

Adipose tissue lipoprotein lipase activity (LPL) falls dramatically during experimental infection of mice by Plasmodium chabaudi. The decrease in this activity accounts for the seric accumulation of triacyl-glyceride-rich lipoproteins (chylomicrons mainly and Very Low Density Lipoproteins (VLDL) partly). This loss of tissue LPL enzyme activity is moreover enhanced, in capillary vessels, by a simultaneous decrease in the activatory power of serum towards the enzyme. This phenomenon is mainly related to the presence of Very Low Density Lipoproteins. In the mouse VLDL apoprotein composition is supposed to be modified. On the contrary, in fatal infection of mice by P. vinckei the adipose tissue lipoprotein lipase (LPL) activity is normal or even increased.

1. Seizure prone (SP)-gerbils (Meriones unguiculatus) tested repeatedly in an open field exhibited habituation of seizures after one or two trials and subsequently showed more ambulatory activity than non-seizure prone (NSP) individuals. 2. A subset of 5 SP and 5 NSP animals were killed and portions of each cerebral hemisphere, the cerebellum and the brainstem medulla were analysed for glutamine synthetase (GS). 3. GFAP immunohistochemistry was used on forebrain sections to assay astrocyte density. 4. It was found by MANOVA, PCA and regression analyses that seizures and ambulatory activity were related to a deficiency in cerebral GS. 5. Rearing behaviour was related to medullary brainstem and cerebellar GS concentrations. 6. The decreased GS of the seizure-prone gerbils was not apparently associated with a deficiency of astrocytes, perhaps the reverse. 7. The results are discussed in relation to glial-neuronal interactions modulating arousal and the propensity for seizures.

Sesbania drummondii, a toxic leguminous shrub found throughout the southeastern United States, induces different responses in chicken vs rat hepatic microsomal monooxygenase systems. Groups of 4- to 8-week-old Sprague-Dawley rats and White Leghorn chickens were given extracts of S drummondii by gavage for 3 days. Doses, which were 0.4 and 0.8% of daily body weights, respectively, for the rats and chickens, were adjusted to induce similar clinical lesions in the 2 species. The hepatic microsomal monooxygenase systems of control and treated animals were compared, using cytochrome P-450 content, cytochrome b5 content, NADH- and NADPH-cytochrome c-reductase activity, and 6 cytochrome P-450 mediated enzyme activities. Increases of twofold in the cytochrome P-450 content, NADPH-cytochrome c-reductase, aminopyrine-N-demethylase, aniline hydroxylase, ethoxycoumarin-O-deethylase, and aryl hydrocarbon hydroxylase activities; fourfold in the aldrin epoxidase activity; and 15-fold in the ethoxyresorufin-O-deethylase activity were observed in the S drummondii-treated chickens. In contrast, the treated rats had nearly twofold decreases in these values, suggesting a species-specific effect of S drummondii on microsomal monooxygenase systems, ie, induced with S drummondii.

Portions of duodenum, jejunum, and ileum from 21 hamsters clinically affected with enteritis were examined for enzymes. Utilizing a variety of techniques, the activities of alkaline phosphatase, nonspecific esterases, leucine aminopeptidase, beta-glucuronidase, and methyl green pyroninophilia were determined. The activities of enzymes normally associated with tissue proliferation and active protein synthesis were decreased, whereas those enzymes associated by cytolysis were increased.

Premature activation of proteolytic zymogens (trypsinogen, chymotrypsinogen) as an early step in the pathogenesis of exocrine pancreatic insufficency (EPI) syndrome in CBA/J mice was investigated in electrophoresed pancreatic homogenates. Polyacrylamide gels containing extracts from control pancreas required prior activation of trypsinogen and chymotrypsinogen (with exogenously added enterokinase and trypsin, respectively) to produce activity staining with specific synthetic substrates. On the contrary, bands of activity staining in gels containing homogenates from mice with EPI syndrome could be readily detected without trypsin or enterokinase preincubation. Subcellular fractionation of control and diseased pancreas revealed that the premature intracellular proteolysis was confined to the zymogren granule fraction, which, even in very moderately affected pancreases (10 to 30% acinar cell autolysis), was very labile in vitro. These proteolytic events reflect the biochemical consequences of zymogen granule destabilization that were observed at the ultrastructural level.