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Platynosomiasis is a common feline hepatic disease caused by Platynosomum fastosum (Trematoda - Dicrocoelidae), which is also known as 'lizard poisoning'. Most reports of feline platynosomiasis show that this disease is sporadic and manifests with uncommon lesions; its pathogenicity is still not well understood. This study aimed to describe liver injuries and enzymatic changes associated with natural P. fastosum infection in 47 stray cats in an endemic area. Overall, 38.3% (18/47) of cats were parasitized, and 2,358 flukes (P. fastosum) were collected (131 - mean intensity of parasitism; 50.2 - mean abundance). The alanine transaminase (ALT) measure was significantly higher in parasitized animals, while alkaline phosphatase (ALP) showed no statistical difference between parasitized and non-parasitized animals. In infected animals, gross pathological lesions and microscopic liver injuries ranged from mild to severe, and were similar to those in previous descriptions of feline platynosomiasis. Nonetheless, the intensity of parasitism was not related to the severity of macroscopic or microscopic hepatic injuries. However, feline platynosomiasis should be considered in the differential diagnosis of feline liver disorders, as well as, in any program of helminth control, even if no clinical abnormalities are present.

In C57BL/6 mice, Leishmania donovani infection in the liver provoked IFN-γ-induced expression of the immunity-related GTPases (IRG), Irgm1 and Irgm3. To gauge the antileishmanial effects of these macrophage factors in the liver, intracellular infection was analyzed in IRG-deficient mice. In early- (but not late-) stage infection, Irgm3(-/-) mice failed to properly control parasite replication, generated little tissue inflammation and were hyporesponsive to pentavalent antimony (Sb) chemotherapy. Observations limited to early-stage infection in Irgm1(-/-) mice demonstrated increased susceptibility and virtually no inflammatory cell recruitment to heavily-parasitized parenchymal foci but an intact response to chemotherapy. In L. donovani infection in the liver, the absence of either Irgm1 or Irgm3 impairs early inflammation and initial resistance; the absence of Irgm3, but not Irgm1, also appears to impair the intracellular efficacy of Sb chemotherapy., (Copyright © 2015 Elsevier Inc. All rights reserved.)

This study aimed to investigate the butyrylcholinesterase (BChE) activity in mice experimentally infected with Toxoplasma gondii during the acute phase. Twenty mice were divided in two groups with 10 animals each: group A was composed of uninfected mice while group B was formed by rodents infected with T. gondii. Five days after infection, blood was collected and serum separated, and fragments of liver and brain were obtained. In serum and liver homogenate was noted a significant reduction (P<0.05) in BChE activity in infected mice when compared with uninfected ones. In serum was observed an increase in the activity of alanine aminotransferase and urea, associated with reduction in alkaline phosphatase activity and in the levels of total protein and albumin. Histologically, there were foci of necrosis and parasites in the forms of tachyzoites and cysts, with bradyzoites in liver samples of infected animals. Based on these results, we conclude that toxoplasmosis reduces BChE activity in mice, and this alteration is probably related to the liver damage caused by the parasitism. Therefore, this enzymatic alteration can directly contribute to the pathogenesis of the disease., (Copyright © 2012 Elsevier GmbH. All rights reserved.)

Mixed parasite infections are common in many parts of the world, but little is known of the effects of concomitant parasite infections on the immune response or severity of clinical disease. We have used the nonlethal malaria infection model of Plasmodium chabaudi AS in combination with the gastrointestinal nematode Heligmosomoides bakeri polygyrus to investigate the impact of nematode infections on malarial morbidity and antimalarial immunity. The data demonstrate that wild-type C57BL/6 mice coinfected with both parasites simultaneously exhibit a striking increase in mortality, while mice deficient in IFN-gamma or IL-23 survive coinfection. The increase in mortality in wild-type mice was associated with severe liver pathology characterized by extensive coagulative necrosis and an increase in hepatic IFN-gamma, IL-17, and IL-22 mRNA expression. This is the first demonstration of increased malaria-associated pathology associated with a switch toward a proinflammatory environment, involving not only IFN-gamma but also the IL-17/IL-23 axis, as a result of coinfection with a gastrointestinal helminth.

The effects of schistosomiasis on microsomal enzymes were studied on post-infection day 90 when accumulated damage and fibrosis are most intense but granulomatous reaction around the eggs harbored in the liver is smaller than during the earlier phases. Swiss Webster (SW) and DBA/2 mice of either sex (N = 12 per sex per group) were infected with 100 Schistosoma mansoni cercariae on postnatal day 10 and killed on post-infection day 90. Cytochrome P-450 (CYP) concentration and alkoxyresorufin-O-dealkylases (EROD, MROD, BROD, and PROD), p-nitrophenol-hydroxylase (PNPH), coumarin-7-hydroxylase (COH), and UDP-glucuronosyltransferase (UGT) activities were measured in hepatic microsomes. Age-matched mice of the same sex and strain were used as controls. In S. mansoni-infected mice, CYP1A- and 2B-mediated activities (control = 100%) were reduced in SW (EROD: male (M) 36%, female (F) 38%; MROD: M 38%, F 39%; BROD: M 46%, F 19%; PROD: M 50%, F 28%) and DBA/2 mice (EROD: M 64%, F 58%; MROD: M 60%; BROD: F 49%; PROD: M 73%) while PNPH (CYP2E1) was decreased in SW (M 31%, F 38%) but not in DBA/2 mice. COH did not differ between infected and control DBA/2 and UGT, a phase-2 enzyme, was not altered by infection. In conclusion, chronic S. mansoni infection reduced total CYP content and all CYP-mediated activities evaluated in SW mice, including those catalyzed by CYP2E1 (PNPH), CYP1A (EROD, MROD) and 2B (BROD, PROD). In DBA/2 mice, however, CYP2A5- and 2E1-mediated activities remained unchanged while total CYP content and activities mediated by other CYP isoforms were depressed during chronic schistosomiasis.

Arylsulfatase B (ASB) hydrolyzes the desulfation of N-acetylgalactosamine-4-sulfate at the non-reducing terminal of glycosaminoglycans. This enzyme activity was found to be elevated in mice schistosomiasis. In the present study, the catalytic and immunological properties of purified ASB from the liver of Schistosoma-infected mouse was investigated in the presence and absence of the schistosomicidal drugs praziquantel and Commiphora extract. The in vitro effect of praziquantel was found to be inhibitory with a Ki value of 5.5 x 10(-4) M while that of commiphora extract was as an activator. Furthermore, these drugs did not have an observed effect on the immunological properties of ASB with regard to its binding to its polyclonal rabbit antibody. These results indicate that some schistosomicidal drugs may reverse the alteration of the catalytic properties of the enzyme in schistosomiasis.

Progressive weight gain, faecal egg counts, packed cell volume, percent eosinophils in blood, serum antibody and serum levels of glutamate dehydrogenase and gamma-glutamyl transpeptidase were recorded in seven swamp buffalo (Bubalis bubalis), 7 Ongole (Bos indicus) and four Bali calves (Bos sundiacus) which were infected orally with 15 metacercariae of Fasciola gigantica twice weekly for 32 weeks. Similar observations were made on four buffalo, 4 Ongole calves and 3 Bali calves maintained fluke-free as controls. Flukes were counted at slaughter 36 weeks after initial infection. Mean daily weight gains of infected Bali (228 +/- 100 (SD) g/day) and infected Ongole calves (328 +/- 57 (SD) g/day) were lower (p = 0.026 and 0.067, respectively) than those of control calves (405 +/- 107 (SD) g/day), but infected buffalo calves (379 +/- 78 (SD) g/day) had similar weight gains to those of the controls (p = 0.57). Throughout the trial, faecal Fasciola egg counts in buffaloes were about one-fifth of counts of Ongole calves, and counts in Bali calves were intermediate. Ongole calves had three times the number of flukes at slaughter in their liver compared to buffalo and Bali calves, which had similar numbers. However, there was evidence that Bali calves had acquired a degree of resistance about 24 weeks after infection commenced and may have lost adult flukes as a consequence.

The levels of arylsulfatases A and B, alpha-amylase, aspartate transcarbamylase, and gamma-glutamyl transpeptidase were investigated during the infection of mice with schistosoma mansoni. This infection caused a significant (p < 0.001) increase in the activity of hepatic arylsulfatase B (ASB), aspartate transcarbamylases and gamma-glutamyl transpeptidase. A non-significant difference occurred for alpha-amylase (p < 0.3) and arylsulfatase A (p > 0.5) when compared to the control. The specific activity of hepatic ASB was progressively increased with the progression of the Schistosoma-infection. Moreover, the kinetic studies of hepatic ASB in Schistosoma-infection showed that a slight decrease in the value of K(m) and about a 40% increase in V(max) when compared to the control. In addition, the pH optimum of hepatic ASB was altered from 6 to 7 as a result of schistosomiasis. These observations suggest that there are schistosomiasis-associated changes of the catalytic and kinetic properties of hepatic ASB.

Background: Liver disorders are the major manifestations of schistosomiasis mansoni. Factors that account for increased concentrations of cholestasis-indicating enzymes in the hepatosplenic form of the disease are unknown., Objective: To assess the correlation between increased gamma-glutamyltransferase serum levels and both the parasitic load and ultrasound alterations in patients with schistosomiasis., Patients and Methods: Twenty-five patients with the chronic form of schistosomiasis were assessed for the presence or absence of increased enzymatic levels, for the parasitic load (low x medium/high) and for ultrasound parameters. Furthermore, analysis of prothrombin time and a platelet count were performed., Results: Of the 25 patients, 13 showed increased gamma-glutamyltransferase plasma levels. No significant correlation was found between increased gamma-glutamyltransferase levels and the parasitic load, or between increased enzyme levels and ultrasound alterations. Nor did the prothrombin index or the platelet count differ between the two groups (normal gamma-glutamyltransferase levels and increased gamma-glutamyltransferase levels)., Conclusion: The parasitic load explains no rise in gamma-glutamyltransferase plasma levels in patients with the chronic form of schistosomiasis, and conventional ultrasound is not a sensitive method to detect the alteration suggested by the increased enzyme level in those patients.

The purpose of this study was to examine in vivo the activity of cytochrome P450 (CYP) 2A6, an enzyme capable of activating carcinogens, including N-nitrosodimethylamine, in humans with the carcinogenic liver fluke infection, opisthorchiasis viverrini, before and after treatment with the antiparasitic agent, praziquantel. Coumarin hydroxylase activity of CYP 2A6 was assessed by administering a probe drug, coumarin, and measuring its metabolite, 7-hydroxycoumarin, in urines collected between 0-2 h and 2-4 h of 106 people with varying intensities of Opisthorchis viverrini infection. Five individuals who did not excrete any detectable 7-hydroxy coumarin (and have a genetic defect probably leading to an absence of catalytic activity of the CYP 2A6 protein) were excluded from analysis. Infected people excreted an average of 22.7 mumol of 7-hydroxycoumarin in the first 2 h after taking the drug, whereas the mean of the uninfected group was 19.4 mumol; this difference did not reach statistical significance (P = 0.10). However, a highly significant increase in CYP 2A6-related activity was observed in infected individuals who also had radiological evidence of biliary fibrosis (28.1 mumol) compared to those without (19.4 mumol; P = 0.01). Reassessments of coumarin hydroxylase activity of CYP 2A6 made 2 months after praziquantel treatment showed highly significant reductions in the amount of 7-hydroxycoumarin excreted among the infected groups but no difference in the uninfected group. These results suggest that expression of CYP 2A6 is induced among chronically infected people who also have fibrosis of the intrahepatic bile duct. As already demonstrated in an animal model and now observed in humans for the first time, this increase in CYP 2A6-related enzyme activity may represent an important mechanistic link between inflammatory products of chronic liver fluke infection (e.g., DNA alkylation damage from endogenously formed N-nitrosamines) and the high risk of cholangiocarcinoma faced by infected individuals.

In contrast to alcoholic liver disease, schistosomiasis leads to presinusoidal hepatic fibrosis, which determines the prognosis of the disease. Since conventional liver function tests and liver biopsy provide little information about the dynamics of the fibrotic process, we measured the activities of two circulating enzymes of collagen turnover, namely serum galactosylhydroxylysyl-glucosyl-transferase and plasma prolidase activity, together with undulin, a novel extracellular matrix glycoprotein. The study encompassed 15 healthy control subjects. 69 patients with various stages of Schistosoma mansoni/hematobium infection [28 with early active infection and no organ involvement, 27 with hepatosplenic involvement, and 14 with complications of portal hypertension] and 16 patients with alcoholic liver cirrhosis. Liver biopsies were obtained from 30 schistosomal patients for histopathological grading. Serum galactosylhydroxylysyl-glucosyl-transferase was significantly increased in all clinical stages of schistosomiasis (p < 0.05), but normal in alcoholic cirrhosis. In contrast, plasma prolidase activity showed a significant increase only in early schistosomiasis (p < 0.01), but dropped to subnormal levels in advanced stages (p < 0.001). Undulin was highly elevated both in alcoholic patients and in all schistosomal groups (p < 0.001), and was capable of distinguishing between early and advanced schistosomal stages. We conclude that serum undulin may be a valuable non-invasive parameter for monitoring the course of schistosomal and alcoholic liver disease.

The pharmacokinetics of two commonly used anticancer drugs, methotrexate (MTX) and 5-fluorouracil (5-FU), were investigated in normal and bilharzial-infested mice. Liver glucose-6-phosphatase activity and antipyrine clearance were used as parameters of liver function. Liver glucose-6-phosphatase activity was significantly reduced in bilharzial-infested mice compared with the normal controls. Bilharzial infestation caused a significant reduction in the elimination (beta) and clearance rate (Cl) of antipyrine, whereas its elimination half-life (t1/2 beta) was increased in comparison with the normal controls. A similar pattern was also obtained after MTX and 5-FU administration in bilharzial mice, compared to controls. These results indicate that hepatic bilharziasis causes a significant reduction in the hepatic clearance and elimination of MTX and 5-FU, whereas their areas under the concentration-time curve were significantly increased. These findings may have to be considered in the treatment of bilharzial cancer patients.

Aims: To evaluate serum gamma glutamyltransferase (GGT) activity in a group of non-alcoholic patients with the hepatointestinal form of schistosomiasis; and the response of both GGT and alkaline phosphatase to an ethanol challenge in two subgroups of patients with different baseline serum concentrations of GGT., Methods: Seventy six non-alcoholic, non-smoking hepatitis B virus (HBV) negative men with normal body mass index, who denied blood product transfusion or use of medication, were studied (30 healthy volunteers (control group) and 46 patients with the hepatointestinal form of schistosomiasis). GGT activities were determined in all subjects and the ethanol test (measurement of GGT and alkaline phosphatase (ALP) before and 24 hours after the ingestion of 1 g/kg of ethanol) was performed in 14 patients (7 with GGT below 25 IU/l and seven with GGT above 25 IU/l). The ethanol serum concentrations were determined in the samples collected one hour after ingestion of the solution in four patients with schistosomiasis., Results: The mean serum ethanol concentration one hour after the ingestion was 0.7 g/l and all patients were clinically intoxicated. GGT was below 25 IU/l in all 30 volunteers and in 33 of the patients with schistosomiasis. In 13 patients the GGT varied from 28 to 140 IU/l. The two enzymes GGT and ALP determined in the 14 patients submitted to the test were positively correlated in the baseline samples (r = 0.8130) as well as in the samples obtained 24 hours after stimulation (r = 0.7921). Neither the plasma activity of GGT nor the GGT:ALP ratio was affected by the ethanol challenge., Conclusions: These results suggest that the mechanisms for the increase of GGT serum activity in schistosomiasis and in alcoholism differ. In the latter, microsomal induction increases GGT serum activity, while alterations in the biliary tree may be responsible for the increase observed in patients with schistosomiasis.

Extracts prepared from tissue with granulomatous inflammation experimentally produced in liver of CBA-strain mice showed increased hydrolysis of leukotriene D4 (LTD4), Leu-Leu and Ala-Gly as compared with normal hepatic cells. Two dipeptidases, Leu-Leu dipeptidase and Ala-Gly dipeptidase, were purified from hepatic granulomas, and quantitative conversion of LTD4 into leukotriene E4 (LTE4) by both enzymes was demonstrated. M(r) values of the purified enzymes were 178,000 for Leu-Leu dipeptidase and 183,000 for Ala-Gly dipeptidase. The enzymes showed homogeneity, appearing as a single band on SDS/PAGE, and the M(r) values of the subunits were 56,000 and 57,000 for Leu-Leu and Ala-Gly dipeptidase respectively. The amino acid compositions of the two enzymes differed considerably from each other. The activity of Leu-Leu dipeptidase was inhibited by bestatin and captopril and stabilized with MnCl2. The Km for LTD4 was 25 microM with a V(max.) of 49.0 mumols/min per mg. In contrast, the activity of Ala-Gly dipeptidase was inhibited by cilastatin, cytinylglycine, EDTA and dithiothreitol, and also by captopril. The Km for LTD4 was 5.3 microM with a V(max.) of 50.4 mumols/min per mg. The findings indicate that the conversion of LTD4 into LTE4 by microsomal dipeptidases is elevated during granulomatous tissue reaction. This enzyme activity may become useful for biochemical quantification of the pathological tissue reaction that occurs in organized granulomas.

Murine schistosomiasis is usually associated with hepatic granulomatous lesions together with high serum and granuloma angiotensin converting enzyme (ACE) activity. Praziquantel (PRZ) which is known to reduce granuloma size was studied to show whether this effect is related to changes in ACE activity. Furthermore, captopril was studied to show whether by inhibiting ACE activity, the drug could also affect granuloma size. PRZ, captopril, and their combination led to significant reduction in liver granuloma. However, in normal mice, captopril was shown to increase rather than decrease serum ACE. The decrease in ACE activity by PRZ was correlated with its curative effect in infected mice. However, in experimentally induced pulmonary granulomata, the drug reduced granuloma size without affecting ACE activity of either serum or granuloma. It may be concluded that reduction in ACE activity may be beneficial as far as diminution of granuloma size is concerned and irrespective of whether there is an active infection or not. The possible use of Captopril as an antihypertensive in bilharzial infections associated with hypertension would probably not adversely affect the granulomatous lesions.

Serum trypsin was measured by radioimmunoassay in 30 patients with hepatosplenic schistosomiasis and 30 healthy controls. Patients with hepatosplenic schistosomiasis had a significantly lower serum trypsin 164.3 +/- 43.3 ng/ml than controls 241.3 +/- 74.0 ng/ml (P less than 0.001). It is concluded that the exocrine pancreatic function is impaired with regard to serum trypsin in hepatosplenic schistosomiasis.

The hepatosplenic form of Schistosoma mansoni infection contributes considerably to morbidity and mortality in endemic areas. The present study investigated serum protein concentrations and serum enzyme activities of 58 Sudanese patients with hepatosplenic schistosomiasis. All of them had a history of infection with S. mansoni and one or several episodes of oesophageal bleeding due to portal hypertension. Diagnosis was based on clinical (n = 24), ultrasonographical (n = 18) and histological (n = 16) grounds. The control group consisted of 40 Sudanese healthy blood donors. Serum albumin was found to be significantly lower in patients with hepatosplenic schistosomiasis (median = 37 g/l) than in controls (median = 47 g/l). Serum enzyme analysis revealed only minimal alterations of cellular enzyme activities, but a marked decrease of cholinesterase activity. Serum albumin concentration correlated significantly with cholinesterase activity. We conclude that liver function in patients with schistosomiasis and portal hypertension is partially disturbed. Low serum albumin and low cholinesterase activity reflected an impaired protein synthesis of the liver. Destruction of parenchymal liver cells was mild or absent.

The inflammatory processes that develop during the advanced stages of hepatic schistosomiasis mansoni have been related in this study to: (a) accumulation of siderosomes; (b) capacity of the ferrous/ferric ions to unleash the formation of free radicals; (c) peroxidation of membrane lipids and; (d) reduction of stability of the membranes of several components of the hepatic lysosomal compartment. The lysosomes isolated from the livers of infected mice by 100 cercariae, with 80 and 100 days of infection, were respectively 2.5 and almost 4 times weaker than the control ones isolated from livers of non-infected mice. The presence of a great quantity of siderosomes has been demonstrated by transmission electronic microscopy and X-ray spectrometry microanalysis.

1. Angiotensin I hydrolases, Mr 140,000 and Mr 70,000 were separated by gel filtration from Tris-HCl buffer extract of hepatic granulomas developed in mice with schistosomiasis. Two enzymes had different substrate specificity. 2. Mr 140,000 hydrolase activity was inhibited by captopril as reported for angiotensin converting enzyme (ACE), while that of Mr 70,000 hydrolase activity was inhibited by potato carboxypeptidase inhibitor. 3. An intermediary, des-Leu10-angiotensin I and then angiotensin II were formed from angiotensin I by Mr 70,000 hydrolase. 4. The findings suggest that Mr 70,000 enzyme is tissue carboxypeptidase A, and it generates angiotensin II in granulomatous inflammation as does ACE.

A study was made of 20 rats infested by Giardia muris in which a histologic study was made of the liver, as well as of 25 patients with giardiasis and elevated alanine-aminotransferase levels. Patients with positive A or B hepatitis markers, cholelithiasis or history of drug or alcohol use were excluded. Tests of liver function and liver biopsy were performed and antiparasite therapy was given during three months of follow-up, after which the liver biopsy was repeated. Humoral alterations were compared to those of 30 patients with acute viral hepatitis (15 type A and 15 type B) over the same periods of time. In 20% of the rats, nonspecific liver lesions were found. In the patients liver enzymes and the thymol test normalized a month after treatment and serum bile acids became normal in the third month. The liver biopsy demonstrated hepatic damage in 94% of the patients (in 20 cases cell lesions and in 12 cases inflammatory lesions) which regressed in the third month, the follow-up biopsy being normal after eradication of the parasite was confirmed. The comparative study with viral hepatitis showed highly significant differences in all the variables studied during the follow-up stage. Emphasis is placed on the importance of this lesion and its differential diagnosis to prevent its progression to chronic liver disease.

The activity of sulphaquinoxaline, robenidine, methyl benzoquate, clopidol and a mixture of methyl benzoquate and clopidol (Lerbek; Dow), was studied in rabbits infected with hepatic coccidiosis due to Eimeria stiedai. Growth inhibition, oocyst production and the activity in the serum of glutamate dehydrogenase and gamma glutamyltransferase were studied as indicators of parasite development. Only sulphaquinoxaline and Lerbek gave satisfactory control of this parasite. The latter formulation was more effective than either of its constituents used alone.

Mice infected with Schistosoma mansoni represent a model for study of hepatic fibrosis in humans. Production of trypsin-activatable inactive collagenase and EDTA-sensitive neutral protease was measured in the culture medium in which granuloma explants or primary cultures were maintained. Collagenase production was maximal in granulomas obtained from liver of mice 8 weeks postinfection and was inhibited by Actinomycin D or cycloheximide, and enhanced by lymphocyte factor(s) or heparin. Isolated schistosome eggs did not release these enzymatic activities but did release EDTA-insensitive protease activity. Both enzymes were separated by ion-exchange chromatography and purified to homogeneity. Isolated collagenase had an isoelectric point of 6.2 and molecular weight of 60,000 and had the functional characteristics of a tissue collagenase. The specific activity of collagenase was 33 units per mg protein at an optimum pH 7.5 and lacked proteolytic activity against noncollagenous protein substrates. Isolated EDTA-sensitive neutral protease had specific caseinolytic activity of 150 units per mg protein and gelatinolytic activity of 300 units per mg protein at an optimum pH 7.5; the enzyme lacked activity against undenatured collagen. Isoelectric point was pH 6.0. Protease activity was inhibited by known inhibitors of collagenases. Production and activation of EDTA-sensitive neutral protease and collagenase accompany increased collagen synthesis and content in the liver of mice 8 weeks postinfection with S. mansoni cercariae. Continued accumulation of liver collagen under these conditions suggests an insufficiency in collagenase activity relative to the increase in collagen synthesis.

A study has been made of changes in alcohol dehydrogenase (ADH) isozymes in livers of rats infected with the following trypanosomes: Trypanosoma cruzi, T. rhodesiense, T. congolense, and six geographical isolates of T. lewisi. A control group of the same age was injected with saline, and another left uninjected. Liver homogenates were electrophoresed in noble agar gels followed by formazan staining according to the method of Ursprung and Leone (1965). Of a total of 25 replicates, 15 showed that the level of rat liver ADH isozymes was similar in the uninjected and saline injected animals; 6 replicates showed a slightly higher level of ADH isozymes in uninjected than saline injected control rat livers, and 4 replicates had a higher level in saline injected than in the uninjected. With either 1-octanol or ethanol as substrate, a marked elevation of ADH activity was observed beginning with day 7 post inoculation in rat livers infected with T. cruzi, T. lewisi, and T. congolense, or as early as day 4 post inoculation with T. rhodesiense. The elevation persisted 59 days or more in rat livers infected with T. lewisi, but rats infected with the pathogenic species usually died 5 to 14 days after infection. The elevation of ADH isozymes has also been demonstrated spectrophotometrically for the first 5 minutes of reaction time, using acetaldehyde as substrate. Also observed in livers infected with pathogenic species and certain strains of T. lewisi were: (1) ADH isozyme pattern changes involving an elevated level of certain isozymes only, and (2) abnormal isozyme mobilities.

Angiotensin I converting enzyme activity is detectable in serum and isolated liver granulomas of mice infected with Schistosoma mansoni. At the chronic phase of the infection (20 wk) the intensity of the granulomatous response spontaneously diminishes. Concomitantly, an increase in angiotensin I converting enzyme activity is observed. The objective of this investigation was to determine the source of this elevated angiotensin I converting enzyme activity. In chronically infected mice, measurements showed that angiotensin I converting enzyme activity in hepatic venous blood was higher than that of peripheral venous blood. In contrast, normal mice demonstrated no difference in regional venous angiotensin I converting enzyme activity. Isolated liver granulomas cultured in vitro released angiotensin I converting enzyme into the culture medium. When granulomas were dispersed into single cell suspension, angiotensin I converting enzyme activity was traced to the adherent cell fraction. Both granulomas and adherent cells from granulomas of the chronically (20 wk) infected mice secreted far more angiotensin I converting enzyme than those from animals with acute (8 wk) infection. Cycloheximide partially inhibited enzyme release. We conclude that in murine schistosomiasis, angiotensin I converting enzyme is produced by the granuloma macrophage. The enzyme is released from the granuloma into the circulation probably resulting in increased serum angiotensin I converting enzyme activity. The role of elevated angiotensin I converting enzyme activity within the lesion as well as the circulation remains to be elucidated.

Serum and urinary RNase activity was determined in 15 normal children and in 52 children in various clinical stages of schistosomal hepatic fibrosis. The activity of serum RNase was compared with that of serum GOT, GPT and AP. The activity of serum and urinary RNase in the different schistosomal groups was significantly higher than in healthy children. The elevated levels of serum and urinary RNase activity were possibly due to malnutrition with tissue catabolism, zinc-deficiency and liver cell injury. Treatment with Astiban and protein-rich diet resulted in a significant decrease in serum and urinary RNase activity and an in significant drop in serum GOT, GPT and AP. Serum and urinary RNase appear to be more sensitive indices for evaluating the early metabolic disturbances in schistosomal patients than GOT, GPT or AP. Our findings also showed that the severity of cases could be graded according to the level of urinary RNase.

Schistosomiasis mansoni is characterized by granulomatous inflammations, deposition of collagen, and irreversible liver fibrosis. In chronic infections fibrosis is cumulative, while collagen synthesis and degradation are diminished. In the present study, we compared collagenase, elastase, and nonspecific neutral protease (NP) activities in isolated vigorous (8-week infection) and immunomodulated (18-20-week infection) liver granulomas. Enzyme activity was localized in the adherent macrophage (greater than 90% purity) and nonadherent eosinophil-rich (greater than 70% purity) cell fractions of the disaggregated granulomas. Collagenase levels were approximately two times higher in granuloma extracts and explant culture supernates of the vigorous as compared with the immunoregulated lesions. However, macrophages and eosinophil-rich cells derived from either type of granuloma secreted similar enzyme levels. Elastase and NP levels in granuloma extracts and secretions of adherent macrophage and eosinophil-rich cell populations were the same in vigorous or immunomodulated lesions but were significantly greater in vigorous granuloma culture supernates. In addition to active collagenase, trypsin activatable latent collagenase was also present in both types of granuloma extracts, explants and eosinophil-rich cell culture supernates. Latent elastase was also detected in granuloma extracts or explant supernates but was absent from secretions of granuloma cells. These results suggest that the presence of active neutral proteases within granulomas may play an important role in the regulation of tissue repair and remodeling during the fibrotic process.

Determination of serum enzymatic activities in hepatosplenic bilharziasis (H.S.B.) were conducted in 100 bilharzial patients, in different stages and 30 controls SGot, SGPT, ALK pH, ALD and SLDH with its both fractions heat stable and labile.). Early elevation of serum enzymatic activities of SGOT, SGPT and SALK. pH, may be considered as a sensitive parameter for functional changes in H.S.B. rather than other conventional liver function tests. The elevated enzymic activity of total LDH in this study was associated with elevation in its both fractions. In particular, the changes in the total activity was in parallel with that of its heat labile fraction. The latter may be considered as a confirmatory test for marked deterioration of liver functions in H.S.B. The changes in the heat stable fraction was inconstant and may be attributed to extrahepatic bilharzial dissimilation. Significantly high serum enzymatic activity of SALD was found in cases of H.S.B. particularly those showing striking muscle wasting.

In schistosomiasis mansoni the parasite egg-induced granulomatous tissue inflammations resolve by fibrosis. Intralesional collagen synthesis and deposition are influenced by collagenase, elastase activity that is diminished at the chronic stage of the disease. To determine the cause of diminished neutral protease activity, the authors determined levels of the antiprotease/alpha 2-macroglobulin (alpha 2M) and alpha 1-protease inhibitor (alpha 1Pi) in extracts or secretions of liver granulomas of infected mice. By ELISA, both antiproteases were detected in granuloma-derived substances, as well as supernatants of cultured, adherent granuloma macrophages. In all samples, alpha 2M was the predominant inhibitor. Antiprotease levels were similar in granuloma-derived samples obtained from acutely and chronically infected mice. However, supernatants of cultured adherent macrophages isolated from granulomas of mice with acute infection contained levels of protease inhibitors several times higher than those of similar preparations obtained from chronically infected animals. Gel filtration of samples on Sephacryl S-200 columns did not separate collagenase and elastase from protease inhibitors. By chromatofocusing, a few inhibitor-free collagenase as well as enzyme-free alpha 2M and alpha 1Pi-active peaks were eluted. The bulk of the material that eluted at the acidic region contained protease-antiprotease activity indicating the presence of enzyme-inhibitor complexes. The intragranulomatous presence of antiproteases complexed with protease enzymes emphasizes their importance in the possible enhancement of fibrosis.

It has been previously demonstrated that collagenase activity and collagen synthesis in hepatic granulomas of mice infected with S. mansoni cercariae are maximal 8 weeks after infection; however, total liver collagen content continues to increase. Now the anatomic relationships among collagenase and collagen, granulomas, and hepatic parenchyma in normal mice and in mice infected with S. mansoni are studied. Trypsin-activated collagenase was purified from the media of cultured granuloma explants and anti-collagenase immunoglobulin G was purified from immunized rabbits. The IgG cross-reacted with liver granulomas and active and inactive forms of collagenase, but did not react by immunodiffusion in agar with other neutral proteases or homogenates of schistosome eggs or normal liver. Cryostat sections of liver from normal and infected mice were studied by indirect immunohistochemical methods using fluorescein, rhodamine, and peroxidase labels. Collagenase localization was restricted to areas of collagen deposits in granulomas and hepatic parenchyma. Ultrastructural studies revealed collagenase on the surface of collagen fibers. Hepatocytes of normal mice showed delicate staining at the sinusoidal surface. At all times, immunoreactive collagenase was intimately associated with its substrate, where it presumably initiated collagen degradation. This localization provides a rationale for possible therapeutic approaches to control fibrogenesis through collagenase induction or activation.

The activity of a mixture of sulphadimethoxine and pyrimethamine (10:3) as prophylactic medication and prophylactic and therapeutic medication was studied in rabbits experimentally infected with Eimeria stiedai. The haematocrit index (packed cell volume) and haemoglobin levels were studied for assessment of drug toxicity. The activity in serum of aspartate aminotransferase (AST) and alanine aminotransferase, alkaline phosphatase and gamma-glutamyltranspeptidase were studied as indicators of hepatic lesions. Parasite development was followed on the basis of the presence of oocysts; other parameters were analysed in order to monitor the performance of infected animals. All the parameters studied showed that the chemoprophylactic medication provided efficient control of the infection and of the hepatic lesions. Serum AST activity was seen to be a good indicator of the effect of the drugs on the liver.

The serum activities of monoamine oxidase (MAO), gamma-glutamyl transferase (GGT) and glutamic dehydrogenase (GDH) enzymes were measured in 25 patients with Schistosoma mansoni infection (Group I), 26 patients with schistosomal hepatosplenomegaly and ascites (Group II) and 21 normal controls. The activities of these enzymes were compared with those of serum aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP). The mean levels of MAO, GGT and GDH of Group I were not significantly different from controls. The mean levels of MAO and GGT in Group II, however, were significantly different from corresponding mean levels of Group I and the controls at P less than .001. Changes in the mean level of GDH and ALT were not significant. By contrast, the levels of AST and ALP in both groups showed significant elevation over control levels at P less than .001. These results indicate that estimation of the two enzymes MAO and GGT may aid in the biochemical differentiation of the stages of schistosomiasis and their associated hepatic complications.

Cholylglycine levels were measured by radioimmunoassay in sera from 10 control CFI female mice and 22 CFI female mice experimentally infected with Schistosoma mansoni. Cholylglycine was significantly elevated in sera of all but one of the chronically infected animals. Serum aspartate transaminase was within normal limits in all the infected animals; while five infected mice had elevated serum alkaline phosphatase and all these five also had high levels of serum cholylglycine. Marked hepatic histopathological changes were demonstrated in all the infected animals. The data suggest that serum cholylglycine is a highly sensitive index for hepatic dysfunction in chronic hepatic schistosomiasis mansoni.

Serum glutamyl transferase (gamma-GT), serum total protein, albumin, aspartate aminotransferase (GOT), alanine aminotransferase (GPT), alkaline phosphatase and bilirubin were measured in 55 males and 45 females suffering from O. viverrini infection and in apparently healthy non-infected individuals. A decrease in total protein, albumin and bilirubin, as well as an increase in GOT, GPT and gamma-GT was observed in males with O. viverrini infection, whereas alkaline phosphatase remained unaffected. In female patients with O. viverrini, serum total protein and albumin also decreased, GOT and GPT increased, whereas gamma-GT remained unchanged. The difference in gamma-GT alteration between females and males is discussed with regard to the possible significance of alcohol consumption and in relation to the parasitic infection and its possible implications for malignancy, associated with liver fluke infection.

A study on serum monoamine oxidase (MAO) levels in fibrotic disease processes led us to investigate patients with moderate to severe burns. Strikingly low serum MAO activity was found in patients with relatively recent, severe injuries. So far, we have no explanation to offer for the phenomena observed.