Arginase activity is associated with fibrosis in experimental infection with Taenia crassiceps, but does not play a major role in resistance to infection.

Murine infection with Taenia crassiceps cysticerci is used as an experimental model for human and animal cysticercosis. In this infection parasites can be found associated with an inflammatory infiltrate enriched with macrophages. Experimental evidence exists supporting a role for either NO-producing classically activated (CAMΦ) or arginase- and CD301-expressing alternatively activated macrophages (AAMΦ) in T. crassiceps resistance. In both cell types, arginine is utilized as an important mediator in macrophage effector functions. To investigate whether there is an association between arginine availability, susceptibility to T. crassiceps and other parameters such as fibrosis, BALB/c mice were infected intraperitoneally with cysticerci and treated daily with the arginase inhibitor nor-NOHA or supplemented with l-arginine and followed for eight weeks. The numbers and developmental stages of parasites were evaluated as well as the presence of CD301+ AAMΦ, arginase activity and collagen deposition in the peritoneal membrane. Treatment with the arginase inhibitor or supplementation with l-arginine did not change the parasitic load or profile of the infection. However, the arginase inhibitor significantly decreased the deposition of collagen. These results suggest that arginase activity does not interfere with parasite control during experimental infection with T. crassiceps, but it is important for fibrosis in cysticercosis.

Anti-oxidant activity of superoxide dismutase and glutathione peroxidase enzymes in skeletal muscles from slaughter cattle infected with Taenia saginata.

It is known that highly reactive oxygene species produced during normal cellular metabolism represent a powerful effector mechanism against parasites. Superoxide dismutase (SOD) and glutathione peroxidase (GPx) belong to the main defense anti-oxidants that prevent the formation of new free radical species. The aim of this study was to assess the activities of SOD and GPx in cattle tissues infected with Taenia saginata. We observed a statistically significant increase in the SOD and GPx activities (p=0.00003, 0.00008, respectively, Student's t-test) in skeletal muscles infected with T. saginata in spectrophotometric analysis. With the use of western blot technique, SOD synthesis stimulation has appeared in the host tissues containing cysticerci in contrast with the control samples. There was no statistically significant increase in the GPx band intensity observed in the studied samples in comparison to controls (Gene Tools Version 4.01 program). These results support the significance of anti-oxidant processes in host defense mechanism during parasitic infections.

Inhibition of p-450 aromatase prevents feminisation and induces protection during cysticercosis.

Cysticercotic male mice undergo an impressive feminisation process, characterised by 200 times increased serum 17beta-estradiol levels while testosterone and dihydrotestosterone are 90% reduced, which results in elevated parasite burden. Administration of Fadrozole (an aromatase inhibitor) in male and female mice suppressed the production of 17beta-estradiol, accompanied with a 70% reduction in parasite burden. This protective effect was associated in male mice with a recovery of the specific cellular immune response. Interleukin-6 (IL-6) serum levels, and its production by splenocytes, was augmented by 80%, together with a 10-fold increase in its expression in testes of infected male mice. Fadrozole treatment returned these levels to baseline values. Aromatase expression in the testes of infected male mice was not affected by Fadrozole. These results suggest that aromatase and IL-6 are key molecules in the production of the feminisation undergone by infected male mice and to Fadrozole treatment as a possible new therapeutic approach to cysticercosis.

Histochemistry of tissue reaction in skeletal muscles of cattle experimentally infected with Cysticercus bovis.

A close correlation between the intensity of tissue reaction in skeletal muscles and the localization of some enzymes in the bladder of C. bovis was demonstrated by histochemical methods. The most intensive tissue reaction was observed around the portion of bladder surrounding the opening of spiral canal, the tegument and subtegumental cells of which exhibit a high activity of alkaline phosphatase and acid phosphatase. Around this portion of bladder the tissue reaction is very strong, whereas around the remaining portion of the bladder, without any activity of these enzymes, the reaction is weak. The basic type of the reaction around the portion with alkaline and acid phosphatase activity is the formation of a pseudoepithelial rim, in which occur secondary changes leading to histochemical changes inside and around this rim. The cells of the unchanged pseudoepithelial rim contain proteins with tyrosine, tryptophan and cysteine. Among the cells is a large number of reticular fibres. Flat foci localized directly in this rim contain mostly fibrilar structures rich in acid mucosubstances with carboxyl and sulphate groups which are labile to testicular hyaluronidase and neuraminidase. They contain also a small amount of neutral mucosubstances and give negative reactions for tyrosine, tryptophan and cysteine. Fibrilar structure in these foci undergo dystrophic calcification. A conspicuous accumulation of mast cells is visible in the layers under the pseudoepithelial rim and clusters of cells containing lipopigment are present at the periphery of the connective tissue layer.

The activity of alkaline and acid phosphatase and non-specific esterase in experimental bovine cysticercosis at different stages of development.

The activity of alkaline and acid phosphatase and non-specific esterase was detected both in the parasite and in the tissue reaction on days 21, 23, 42, 168 and 261 after experimental infection. A very high activity of all enzymes was found in 21- and 23-day-old C. bovis in the tegument of whole bladder. In 42, 168 and 261 days old cysticerci the activity of alkaline acid phosphatase was limited only to a part of bladder surrounding the opening of the spinal canal, whereas the activity of non-specific esterase was present in the whole bladder. The activity of non-specific esterase was localized in subtegumental cells of the bladder wall and in small bodies in the bladder and scolex. These bodies increased in number with the age of the cysticercus. In the tissue reaction, a high activity of alkaline phosphatase was detected only in the period of about 20 days after infection in the layer of activated fibroblasts. The activity of acid phosphatase was demonstrated in the tissue reaction in all time periods and was localized in the histiocytes, macrophages, necrotic exudate, necrotic foci and pigment cells at the periphery of tissue reaction. These cells exhibited also the activity of non-specific esterase.

Contribution to the symptomatology of experimental bovine cysticercosis.

Results of clinical and laboratory examination of animals experimentally infected with Taenia saginata eggs are described. At the early stage of infection, increased temperature, cough, muscle shaking and unstable pace were observed. The locomotive disorders disappeared only on day 50 p.i. Leukocytosis and peripheric eosinophilia were found at the early stage of infection. On days 14-28 p.i. the activity of serum creatine-kinase (CK) significantly increased. The activity of other enzymes (AST, ALT, LD, ALP and ALD) examined was increased only slightly and irregularly. The lipid content in blood serum markedly increased on days 9-16 p.i.

[Effect of an experimental infestation with Cysticercus ovis on serum enzyme activity in lambs]. / Vliianie na eksperimentalnata invaziia s Cysticercus ovis vurkhu aktivnostta na niakoi serumni enzimi na agneta.

The changes were followed up that take place in the activity of the more important serum enzymes, such as glutamate oxalacetate transaminase, glutamate pyruvate transaminase, serum dehydrogenase, malate dehydrogenase, lactate dehydrogenase, creatine phosphokinase, and alkaline phosphatase, as well as aldolase in the development of the experimental infection with various doses of Taenia ovis eggs in lambs. Used were 14 two-month-old lambs divided into test groups of 4 animals each and a control group of two lambs. In the lambs of three of the test groups infected with 4000, 7000, and 30 000 T. ovis eggs, respectively, no signs were observed of enhanced serum enzyme activity up to the 35th day following infection. Later on there was a drop of the activity of these enzymes however, with the exception of alkaline phosphatase the values of all studied serum enzymes remained higher than the normal ones up to the end of the experiment.

[Total LDH activity and isoenzyme spectrum in experimental Cysticercus ovis infestation of lambs and kids]. / Obshta aktivnost i izoenzimen spektur na LDKh pri eksperimentalno invazirani s Cysticercus ovis agneta i kozleta.

Investigations were carried out with 10 lambs and 4 kids at the age of two months, divided into three groups. The test animals of the first group (5 lambs) were infected with 7,000 T. ovis eggs each, and those of the second group (5 lambs) and those of the third group (4 kids)--with 20,000 T. ovis eggs each. It was found that following infection the total activity of lactate dehydrogenase (LDH) rose, reaching its peak values on the 12th and 15th day. On the 12th day the strongly enhanced enzyme activity was due to the rise of LDH1, while on the 15th day the enhancement was associated with the rise of LDH5 that was characteristic of the skeletal muscles. In the period of forming the connective tissue capsule around the cysticerci the changes in the total activity and the isoenzyme spectrum were more slightly manifested. After the 30th day both the activity and the spectrum of LDH steadily came back to normal. With a C. ovis infection there was also a strongly expressed response on the part of hemopoietic organs, with a pronounced LDH3 activity.

Modified expression of steroid 5 alpha-reductase as well as aromatase, but not cholesterol side-chain cleavage enzyme, in the reproductive system of male mice during (Taenia crassiceps) cysticercosis.

Infection with Taenia crassiceps cysticerci in male mice produces an increase in serum estradiol levels, whereas serum testosterone is abolished. Concomitantly, complete atrophy of the reproductive tract of infected male mice is observed. The present study was under-taken to determine the expression pattern of three key steroidogenic enzymes in the reproductive tissues of normal and infected male mice. In infected mice, serum estradiol levels were increased 97 times as compared with control mice of the same age. Testosterone and dihydrotestosterone levels were completely inhibited. The expression of 5 alpha-reductase in the reproductive tract was markedly reduced, whereas aromatase mRNA levels were highly elevated in the testes of parasitized mice. No change in the mRNA content for cholesterol side-chain cleavage enzyme was evident. The overall results suggest that the change in the normal production of sex steroids in infected male mice is produced concomitantly by the inhibition of expression of the 5 alpha-reductase enzyme and the activation of aromatase gene expression. This induces a preferential metabolism from testosterone toestradiol instead of the normal metabolism from testosterone to dihydrotestosterone.