Hepatocytes from the periportal (afferent) and perivenous (efferent) zones of the liver parenchyma differ in their enzyme content and subcellular structures. Therefore, different functions are proposed for the two zones. (a) Oxidative energy metabolism, beta-oxidation, amino acid catabolism, ureagenesis from amino acids, gluconeogenesis, bile acid, and bilirubin excretion and oxidation protection are preferentially located in the periportal zone. (b) Glycolysis, liponeogenesis, ureagenesis from ammonia, and biotransformation are predominantly situated in the perivenous zone. Heterogeneity in the synthesis of plasma proteins also appears to exist. The heterogeneous expression of the genome in hepatocytes is apparently caused by the periportal to perivenous gradient in oxygen and hormone concentrations, and by a different autonomic innervation of the parenchymal zones.

Animals↗

PubMedDate not supplied

The human immune response to defined immunogens of Schistosoma mansoni: elevated antibody levels to paramyosin in stool-negative individuals from two endemic areas in Brazil.

Sera from individuals living in 2 areas endemic for Schistosoma mansoni in Minas Gerais, Brazil were assayed for the presence of antibodies against paramyosin and glutathione-S-transferase (GST), molecules previously implicated as vaccine immunogens from studies in laboratory hosts. A group was identified consisting of subjects who were stool-negative and had no record of previous infection but who were seropositive by enzyme-linked immunosorbent assay against crude adult worm antigen (SWAP). These individuals had anti-paramyosin antibody levels which were dramatically elevated with respect to those measured in infected (stool-positive) individuals living in the same endemic area. In contrast, the same 2 groups of stool-positive and stool-negative subjects could not be distinguished on the basis of their seroreactivity to either GST or SWAP. After chemotherapy, anti-paramyosin antibodies rose above pre-treatment levels and remained elevated in those individuals who became stool-negative. In contrast, anti-paramyosin antibodies decreased to pretreatment values in drug-treated individuals who failed to show complete parasitological cure. These results suggest that the immune response of humans to paramyosin may play a role in natural resistance to schistosome infection, and that an elevated antibody level against this antigen may be a useful correlate of drug-induced cure.

Adolescent↗

PubMedDate not supplied

Dissociation of antibody responses during human schistosomiasis and evidence for enhancement of granuloma size by anti-carbohydrate IgM.

Immunoglobulin (Ig) G and IgM antibody levels to soluble egg antigens (SEA), adult worm glycoproteins (AWGP), carbohydrate antigens (CHO) and cationic exchange fraction 6 (CEF6) were measured in serum specimens taken from Brazilian patients with acute, intestinal, hepato-intestinal and hepatosplenic schistosomiasis mansoni. The antibody levels varied among the groups, with the highest anti-egg antigen responses in the acute patients and the highest anti-adult worm responses in patients with chronic disease. The responses to the component parts of the egg antigens were dissociated, with anti-carbohydrate IgG and IgM responses being highest in the acute infection group and anti-CEF6 IgG responses being uniform among the clinical groups. The possibility of a direct role for anti-CHO antibody responses in egg-induced pathology was investigated using the mouse lung model. The anti-carbohydrate monoclonal antibody NIMP/M45 significantly enhanced granuloma formation. Mice given NIMP/M45 produced granulomas larger than those of naive mice or mice given an unrelated monoclonal antibody, and as large as those produced by mice which had been presensitized to egg antigens. The independent regulation of responses to egg antigens may indicate that such responses are minimized to reduce the pathological consequences of infection whilst allowing the development of protective anti-worm responses.

Acute Disease↗

PubMedDate not supplied

Levels of the schistosome circulating anodic and cathodic antigens in serum of schistosomiasis patients from Brazil.

Serum levels of 2 schistosome circulating antigens, the circulating anodic antigen (CAA) and the circulating cathodic antigen (CAA), were determined in persons infected with Schistosoma mansoni in Brazil. Sensitive monoclonal antibody-based enzyme-linked immunosorbent assays were used to measure levels of the 2 antigens. The study group consisted of 38 individuals with intestinal schistosomiasis, and 20 persons with the hepatosplenic form of the disease. Age and intensity of infection were comparable for the 2 groups. CAA was detected in 65.5% of all patients' sera and CCA was found in the serum of 82.8% of all patients. CAA levels correlated well with the egg output, as determined by duplicate Kato-Katz smears; CCA was significantly positively correlated with egg output in patients with intestinal schistosomiasis only. Whereas no significant difference was found between CAA titre in patients with intestinal schistosomiasis and those with the hepatosplenic form, a significantly higher CCA titre was found in patients with hepatosplenomegaly compared to patients with intestinal schistosomiasis.

Adolescent↗

PubMedDate not supplied

Analysis of anti-keyhole limpet haemocyanin antibody in Brazilians supports its use for the diagnosis of acute schistosomiasis mansoni.

Antibody (immunoglobulin (Ig) G) to the haemocyanin of the keyhole limpet (KLH) (Megathura crenulata), which shares a well defined carbohydrate epitope with the surface of schistosomula of Schistosoma mansoni, was determined by enzyme-linked immunosorbent assay (ELISA) in the sera of Brazilians with acute schistosomiasis. Of 53 such individuals tested, 51 had a level of KLH reactivity in excess of the mean +2 standard deviations of that exhibited by chronically infected individuals. This difference in reactivity allowed the acute cases to be readily identified by visual inspection of ELISA plates. The levels of IgG in patients with hepatointestinal and hepatosplenic schistosomiasis, as well as in non-infected, seropositive residents of endemic areas and infected children from endemic areas, were not statistically different from those of intestinal patients. Significant levels of anti-KLH IgG were not detected in patients with leishmaniasis, Chagas disease, ancylostomiasis or ascariasis. The results support the use of KLH as a means of rapidly and easily identifying individuals with acute schistosomiasis.

Adolescent↗

PubMedDate not supplied

Dot-dye-immunoassay and dot-ELISA for the serological differentiation of acute and chronic schistosomiasis mansoni using keyhole limpet haemocyanin as antigen.

Two immunoassays, dot enzyme-linked immunosorbent assay (dot-ELISA) and dot-dye immunoassay (dot-DIA), using soluble egg antigen and keyhole limpet haemocyanin as antigens, were evaluated for the serological differentiation of 25 acute and 37 chronic patients infected with Schistosoma mansoni and 20 non-infected individuals, in comparison with ELISA. Efficiency was 92.7%, 90.0% for ELISA, dot-ELISA and dot-DIA, respectively. Dipstick dot-ELISA and dot-DIA are described and shown to be reliable cheap and simple methods for the serological differentiation of acute and chronic schistosomiasis.

Acute Disease↗

PubMedDate not supplied

Evaluation of proteinuria in an area of Brazil endemic for schistosomiasis using a single urine sample.

A two-step protocol was designed to evaluate the frequency of proteinuria related to Schistosoma mansoni infection in an endemic area, as measured by the protein/creatinine ratio (P/C R). A pre-test on 32 in-patients with renal disease and 20 healthy individuals showed a high correlation (r = 0.948) between the classical measurement of protein excretion per square metre of body surface during 24 h and the P/C R. The P/C R was then used to evaluate the frequency of proteinuria in 189 individuals in an endemic area in the northeast of Minas Gerais state, Brazil, with a schistosomiasis prevalence of 49.3% and 3.4% with the hepatosplenic form. The low prevalence of proteinuria (1.06%) in the studied population can be attributed to the accuracy of the method used and to the low prevalence of the hepato-splenic form of schistosomiasis. The P/C R is a reliable and appropriate method for the measurement of proteinuria in field studies.

Adolescent↗

PubMedDate not supplied

The serological differentiation of acute and chronic Schistosoma japonicum infection by ELISA using keyhole limpet haemocyanin as antigen.

Antibodies (immunoglobulin (Ig) G and IgM) that recognize keyhole limpet haemocyanin (KLH), which shares a well defined carbohydrate epitope with the surface of larval schistosomes, were determined by enzyme-linked immunosorbent assay in patients with acute or chronic schistosomiasis japonica. Marked differences in IgG and IgM responses were evident between acute and chronically infected patients at a serum dilution of up to 1:2000. The acute sera had mean (+/- standard deviation) optical density values at 405 nm for IgG and IgM of 0.64 +/- 0.18 and 0.30 +/- 0.19 respectively; the chronic sera had mean readings for IgG and IgM of 0.14 +/- 0.08 and 0.04 +/- 0.03 respectively. Setting the lowest positive limit at 2 standard deviations above the mean value for chronic sera, 41 (98%) of the 42 patients previously diagnosed as having acute schistosomiasis were correctly identified by anti-KLH IgG and 35 (83%) of the 42 patients were correctly identified by anti-KLH IgM detection. Of 17 patients studied longitudinally, IgG optical density values dropped 45% and those of 5 patients fell below the established cut-off level 6 months after treatment. This study supports the use of KLH for rapidly and easily identifying individuals with acute Schistosoma japonicum infection.

Acute Disease↗

PubMedDate not supplied

Oral fluids for the immunodiagnosis of Schistosoma mansoni infection.

Saliva and oral transudate were evaluated for their potential as human specimens in the detection of IgG antibodies against soluble Schistosoma mansoni egg antigen (SEA). Preliminary laboratory testing of 49 subjects, 37 with parasitological proven infection and 12 negative controls, displayed 100% sensitivity in ELISA using serum and oral transudate and 94.6% using saliva. The specificity of the ELISA with serum was 100% versus 91.7% with both oral fluids. Significant Spearman rank correlations of anti-SEA IgG levels with egg counts were observed for serum, oral transudate and saliva (P < 0.05). The sensitivity of dot-ELISA was 100% for serum, 89% for transudate and 81% for saliva, and specificity was 100% for all 3 samples. The immunodiagnostic value of ELISA for the detection of anti-SEA IgG antibodies in oral transudate was further evaluated in 197 individuals from an endemic area of Brazil. The ELISA using serum and oral transudate showed sensitivities of 98.8% and 100% respectively and specificities of 67.8% and 64.3% respectively. Use of oral fluids for the diagnosis of S. mansoni infection was equivalent to sera with respect to test efficacy, offering an alternative to blood collection.

Adolescent↗

PubMedDate not supplied

Antibody subclass profile and avidity during acute and chronic human Schistosoma mansoni infection.

The avidity of IgA, IgM, IgG and IgG subclass antibodies against Schistosoma mansoni soluble egg antigen (SEA) was determined by ELISA in serum samples collected in 1995 from individuals in Brazil with acute (n = 36) and chronic (n = 40) schistosomiasis. Fifteen individuals at the acute phase were also evaluated 6 months after clinical diagnosis. Predominance of low-avidity IgG, IgG1, IgG2, IgG3 and IgA characterized the acute phase. IgG4 was detected in only 2 individuals with acute disease (5.6%). Levels of anti-SEA IgM were similar between the study groups. IgG1 avidity showed the strongest association with the chronological evolution of the infection, presenting 100% of low avidity during the acute infection and reaching 100% of high avidity 6 months after. It is suggested that distinct anti-Schistosoma egg antigens subclass profile and antibody avidity characterize the clinical phases of S. mansoni infection. In particular, determination of anti-SEA IgG1 offers a new tool for the laboratory analysis of the disease.

Acute Disease↗

PubMedDate not supplied

The role of nutritional status and insulin-like growth factor in reduced physical growth in hepatosplenic Schistosoma mansoni infection.

The influence of nutritional status and hormonal growth activity on the impaired somatic development of adolescents with the hepatosplenic clinical form of Schistosoma mansoni infection (HS), the intestinal form with high (IH) or low (IL) egg output and non-infected (NI) individuals was evaluated (in Comercinho, Minas Gerais State, Brazil, in 1996-97) by measuring body mass index (BMI), insulin-like growth promoting factor (IGF-I) and its carrier protein (IGFBP-3). BMI, IGF-I and IGFBP-3 concentrations were significantly lower in the HS group compared with the IH and the NI groups, irrespective of age. BMI did not remain associated with the clinical form in the bi-variate model that included IGF-I and BMI or IGFBP-3 and BMI, suggesting that in these groups IGF-I and IGFBP-3 levels were related to the clinical form but independent of nutritional status. It is suggested that physical growth impairment in hepatosplenic S. mansoni infection results from the synergistic action of both hepatic damage and nutritional restriction.

Adolescent↗

PubMedDate not supplied

Daily fluctuation of levels of circulating cathodic antigen in urine of children infected with Schistosoma mansoni in Brazil.

The fluctuation of circulating cathodic antigen (CCA) levels in urine was studied in 69 Brazilian school-children infected with Schistosoma mansoni and compared to egg counts. Faeces and urine samples were simultaneously collected at 7 times during a period of 2 weeks. CCA was determined by enzyme-linked immunosorbent assay and could be detected in 96% of the urine samples; the individual mean CCA level ranged from 609 to 350,700 pg/mL. 90% of the faecal samples contained S. mansoni eggs and the individual mean egg output ranged from 9 to 5510 eggs/g. The Spearman rank correlation coefficient between these individual means was 0.69. Kendall's coefficient of concordance (W) was 0.88 for CCA levels and 0.80 for egg counts.

Adolescent↗

PubMedDate not supplied

Assessment of oltipraz in schistosomiasis mansoni. Clinical trial.

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Adolescent↗