Strongyloides stercoralis larvae excretion patterns before and after treatment.

The variability of larval excretion impedes the parasitological diagnosis of Strongyloides stercoralis in infected individuals. We assessed the number of larvae excreted per gram (LPG) stool in 219 samples from 38 infected individuals over 7 consecutive days before and in 470 samples from 44 persons for 21 consecutive days after ivermectin treatment (200 µg kg-1 BW). The diagnostic sensitivity of a single stool sample was about 75% for individuals with low-intensity infections (⩽1 LPG) and increased to 95% for those with high-intensity infections (⩾10 LPG). Doubling the number of samples examined per person increased sensitivity to more than 95%, even for low-intensity infections. There was no indication of a cyclic excretion of larvae. After treatment, all individuals stopped excreting larvae within 3 days. Larvae were not detected during any of the following 18 days (total 388 Baermann and 388 Koga Agar tests). Two stool samples, collected on consecutive days, are recommended in settings where low or heterogeneous infection intensities are likely. In this way, taking into account the possible biological variability in excretion, the efficacy of ivermectin treatment can be assessed as soon as 4 days after treatment.

Single application of low-dose mycophenolate mofetil-OX7-immunoliposomes ameliorates experimental mesangial proliferative glomerulonephritis.

IgA nephropathy, one of the most frequent forms of glomerulonephritis, characterized by mesangial hypercellularity and glomerular extracellular matrix (ECM) expansion, often leads to end-stage renal disease over a prolonged period. We investigated whether antiproliferative treatment in a single low dose specifically targeted to the glomerular mesangium by immunoliposomes (ILs) results in an amelioration of mesangial proliferative glomerulonephritis in rats (anti-Thy1.1 nephritis). Mycophenolate mofetil (MMF) containing ILs was generated that targets the Thy1.1 antigen (OX-7) in rat mesangial cells. Treatment benefit of a single intravenous dose of these ILs given 2 days after disease induction was investigated by stereology, immunohistochemistry, and functional analyses (creatinine, albuminuria) until day +9 and was compared among untreated and free MMF-treated rats using six male Wistar rats per group. MMF-loaded OX7-IL prevented creatinine increase and albuminuria. Stereological analyses of MMF OX7-IL-treated animals yielded 30% reduction of mesangial cells on day +9 and a 40% reduction of glomerular ECM volume on day +5, compared with all of the other nephritic animals. Furthermore, at days +5 and +9 we observed decreased ECM content and decreased glomerular volume (day +5) in the MMF-OX7-IL-treated group compared with the nephritic group treated with free MMF. In conclusion, MMF-OX7-IL-based directed drug delivery represents a novel approach for treating mesangial cell-mediated forms of glomerulonephritis.

Meta-analyses qualify metzincins and related genes as acute rejection markers in renal transplant patients.

Definition of acute renal allograft rejection (AR) markers remains clinically relevant. Features of T-cell-mediated AR are tubulointerstitial and vascular inflammation associated with excessive extracellular matrix (ECM) remodeling, regulated by metzincins, including matrix metalloproteases (MMP). Our study focused on expression of metzincins (METS), and metzincins and related genes (MARGS) in renal allograft biopsies using four independent microarray data sets. Our own cases included normal histology (N, n = 20), borderline changes (BL, n = 4), AR (n = 10) and AR + IF/TA (n = 7). MARGS enriched in all data sets were further examined on mRNA and/or protein level in additional patients. METS and MARGS differentiated AR from BL, AR + IF/TA and N in a principal component analysis. Their expression changes correlated to Banff t- and i-scores. Two AR classifiers, based on METS (including MMP7, TIMP1), or on MARGS were established in our own and validated in the three additional data sets. Thirteen MARGS were significantly enriched in AR patients of all data sets comprising MMP7, -9, TIMP1, -2, thrombospondin2 (THBS2) and fibrillin1. RT-PCR using microdissected glomeruli/tubuli confirmed MMP7, -9 and THBS2 microarray results; immunohistochemistry showed augmentation of MMP2, -9 and TIMP1 in AR. TIMP1 and THBS2 were enriched in AR patient serum. Therefore, differentially expressed METS and MARGS especially TIMP1, MMP7/-9 represent potential molecular AR markers.

Renal allografts with IF/TA display distinct expression profiles of metzincins and related genes.

Chronic renal allograft injury is often reflected by interstitial fibrosis (IF) and tubular atrophy (TA) without evidence of specific etiology. In most instances, IF/TA remains an irreversible disorder, representing a major cause of long-term allograft loss. As members of the protease family metzincins and functionally related genes are involved in fibrotic and sclerotic processes of the extracellular matrix (ECM), we hypothesized their deregulation in IF/TA. Gene expression and protein level analyses using allograft biopsies with and without Banff'05 classified IF/TA illustrated their deregulation. Expression profiles of these genes differentiated IF/TA from Banff'05 classified Normal biopsies in three independent microarray studies and demonstrated histological progression of IF/TA I to III. Significant upregulation of matrix metalloprotease-7 (MMP-7) and thrombospondin-2 (THBS-2) in IF/TA biopsies and sera was revealed in two independent patient sets. Furthermore, elevated THBS-2, osteopontin (SPP1) and beta-catenin may play regulatory roles on MMP. Our findings further suggest that deregulated ECM remodeling and possibly epithelial to mesenchymal transition (EMT) are implicated in IF/TA of kidney transplants, and that metzincins and related genes play an important role in these processes. Profiling of these genes may be used to complement IF/TA diagnosis and to disclose IF/TA progression in kidney transplant recipients.

Advanced glycation end products regulate extracellular matrix protein and protease expression by human glomerular mesangial cells.

Advanced glycation end products (AGEs) may play a role in the pathogenesis of diabetic nephropathy, by modulating extracellular matrix turnover. AGEs are known to activate specific membrane receptors, including the receptor for AGE (RAGE). In the present study, we analyzed the various receptors for AGEs expressed by human mesangial cells and we studied the effects of glycated albumin and of carboxymethyl lysine on matrix protein and remodelling enzyme synthesis. Membrane RAGE expression was confirmed by FACS analysis. Microarray methods, RT-PCR, and Northern blot analysis were used to detect and confirm specific gene induction. Zymographic analysis and ELISA were used to measure the induction of tPA and PAI-1. We show herein that cultured human mesangial cells express AGE receptor type 1, type 2 and type 3 and RAGE. AGEs (200 microg/ml) induced at least a 2-fold increase in mRNA for 10 genes involved in ECM remodelling, including tPA, PAI-1 and TIMP-3. The increase in tPA synthesis was confirmed by fibrin zymography. The stimulation of PAI-1 synthesis was confirmed by ELISA. AGEs increased PAI-1 mRNA through a signalling pathway involving reactive oxygen species, the MAP kinases ERK-1/ERK-2 and the nuclear transcription factor NF-kappaB, but not AP-1. Carboxymethyl lysine (CML, 5 microM), which is a RAGE ligand, also stimulated PAI-1 synthesis by mesangial cells. In addition, a blocking anti-RAGE antibody partially inhibited the AGE-stimulated gene expression and decreased the PAI-1 accumulation induced by AGEs and by CML. Inhibition of AGE receptors or neutralization of the protease inhibitors TIMP-3 and PAI-1 could represent an important new therapeutic strategy for diabetic nephropathy.

Experimental heart transplantation: effect of cyclosporine on expression and activity of metzincins.

Metzincins, such as matrix metalloproteases (MMP), and extracellular matrix (ECM) proteins are differentially regulated in inflammation. We hypothesised that metzincins are also dysregulated in experimental acute cardiac allograft rejection. We investigated the Dark Agouti-to-Lewis (DA-to-Lew) rat model of acute cardiac allograft rejection. Cyclosporine (CsA) (7.5 mg/kg/d) was given from transplantation to sacrifice (day +5). At that time, mRNA levels were analysed by Affymetrix genechip and quantitative reverse transcription polymerase chain reaction (qRTPCR). MMP protein and activities were analysed by immunohistology, fluorometry, zymography and Western blots. In untreated rejected DA allografts, mRNA levels of MMP-2/-7/-9/-/12-/14, a disintegrin and metalloprotease (ADAM)-17, tissue inhibitor of metalloprotease (TIMP)-1/-3 were increased, whereas MMP-11/-16/-24 and TIMP-2/-4 were lowered compared to native DA hearts. With respect to these untreated allografts, CsA lowered mRNA levels of MMP-7, TIMP-1/-3 (TIMP-2/-4 remained relatively low) and ADAM17, but augmented mRNA levels of MMP-11/-16/-23 and of many ECM genes. Immunohistology showed increased staining of MMP-2 in acute rejection (AR). Overall MMP activity was augmented in both transplanted groups, but CsA reduced MMP-9 activity and MMP-14 production. Taken together, MMP and TIMP were upregulated during acute AR. CsA ameliorated histology of rejection but showed potential pro-fibrotic effects. Thus, MMP and TIMP may play a role in acute cardiac allograft rejection, and beneficial modification of the MMP-ECM balance requires interventions beyond CsA.

Six-year follow-up of azathioprine and mycophenolate mofetil use during the first 6 months of renal transplantation.

Long-term follow-up examination to test whether therapy with mycophenolate mofetil (MMF) or azathioprine (AZA) during the first year translates into different graft or patient survival and graft function is important. Therefore, 6-year follow-up data of a group of 80 consecutive renal transplant recipients were analyzed. The first group of 40 patients was treated with AZA, cyclosporine and prednisone and the second group with MMF, cyclosporine and prednisone for the first 6 months. Graft failure rates were compared during follow-up. Creatinine, inverse slope of creatinine (delta/creatinine) and 24-hour proteinuria at 6 years post transplantation were compared. The Kaplan-Meier analyses for death-censored and non-censored graft failure showed no difference between the groups. Creatinine values at 6 years for the AZA Group were 139 +/- 36 micromol/l (95% CI 125.9-151.2 micromol/l) and for the MMF Group 149 +/- 52 micromol/l (95% CI 133.9-164.9 micromol/l). Delta/creatinine and 24-hour proteinuria at 6 years did not differ between the two groups. We conclude that an initial 6-month treatment with MMF as opposed to AZA reduced the early rejection rate, but did not result in superior long-term graft function or survival after 6 years of follow-up observation.

Pre-eclampsia with acute heart failure postpartum as primary manifestation of systemic lupus erythematosus.

Pre-eclampsia occurs in 2-5% of pregnancies of healthy women. Here, we present a rare case of pre-eclampsia with overt acute heart failure, which was the primary manifestation of systemic lupus erythematosus with cardiac and renal involvement.

[Pancreas transplantation--indications and results updated]. / Pankreastransplantation-- Indikation, Vorgehen, Chancen und Probleme.

Pancreas transplantation has evolved within two decades from a poorly accepted therapeutic option to a highly successful procedure in the treatment of type 1 diabetes mellitus. Combined Pancreas-kidney transplantation is usually performed, but the value of pancreas after kidney transplant recently increased dramatically. Novel surgical techniques together with very effective immunosuppression (e.g. Prograf) and CellCept) and better postoperative management offer excellent long-term graft and patient survival with full insulin independence. Pancreas transplantation (alone or simultaneous with kidney) is highly cost-effective compared to any conservative alternatives.

Prophylactic hemodialysis after radiocontrast media in patients with renal insufficiency is potentially harmful.

PURPOSE: Acute renal failure induced by contrast media is an important cause of hospital-acquired renal insufficiency. Preexisting renal failure and the dose of contrast media are known risk factors for the development of radiocontrast nephropathy. We performed a randomized trial to test whether radiocontrast nephropathy can be avoided by prophylactic hemodialysis immediately after the administration of contrast media in patients with impaired renal function. SUBJECTS AND METHODS: Renal function and other parameters, hemodialysis requirement, and relevant clinical events were recorded before and during the 6 days after administration of contrast media in 113 patients with a baseline serum creatinine level >200 microm/L (>2.3 mg/dL). Patients were randomly assigned to either hemodialysis (n = 55) or nonhemodialysis (n = 58) treatment after parenteral low-osmolality contrast media. RESULTS: The characteristics of the patients in the two groups were similar. Compared with baseline levels, the mean [+/- SD] serum creatinine level decreased at day 1 (277 +/- 95 microm/L), peaked at day 4 (353 +/- 126 microm/L), and returned to baseline at day 6 (327 +/- 119 microm/L, P <0.05 by analysis of variance) after administration of contrast media in the hemodialysis group, whereas in the nonhemodialysis group, no significant changes in mean serum creatinine level were observed. Eleven patients required 1 or more hemodialyses (8 in the hemodialysis group and 3 in the nonhemodialysis group, P = 0.12), 6 of whom (4 vs. 2, P = 0.44) required 3 or more hemodialyses. Clinically relevant events included pulmonary edema (1 vs. 4 patients, P = 0.36), myocardial infarction (2 vs. 2), stroke (2 vs. 0, P = 0.24), and death (1 vs. 1). CONCLUSIONS: The strategy of performing hemodialysis immediately after the administration of low-osmolality contrast media in all patients with a reduced renal function did not diminish the rate of complications, including radiocontrast nephropathy.

Judgment analysis in clinical nephrology.

To ameliorate the clinical performance of nephrologists, improving their clinical judgment is crucial. No methodology for judgment analysis in nephrology is currently available. Therefore, we designed a trial to assess the intraphysician consistency of the judgment of typical non-end-stage renal disease (ESRD) patients by 24 board-certified nephrologists. The participants were asked to analyze cases to determine the interobserver variability with respect to diagnosis, therapy, prognosis, and strategy of follow-up. They were unaware that every patient was presented on 2 occasions separated by a period of 6 months. Of the 1,288 questionnaires that were completed, 28 cases belonged to 1 of the following 3 groups: (A) patients once with, once without renal histology, (B) patients twice without histology, and (C) patients twice with histology. Only cases of group (A) differed at the 2 occasions of assessment with respect to knowledge of histology. The results from the first and second assessment were compared and analyzed. The median (95% confidence interval) percentages of changed diagnoses were 64% (59% to 68%), 50% (44% to 62%), and 33% (26% to 47%) in groups A, B, and C, respectively, indicating large intraobserver variability. The frequency of changes in diagnoses declined with the degree of confidence in the first diagnosis in all 3 groups. The subjective desire to know the histology was without impact on the frequency of changes in diagnoses. However, a knowledge of the histology enhanced the degree of confidence in the diagnoses. Interestingly, the enormous variability in changing diagnoses from one analysis to the other was not reflected by corresponding changes in the judgment of prognosis, therapy to be prescribed, or strategy of follow-up. The individual judgment with respect to diagnosis of clinical cases is inconsistent and highly dependent on the subjective degree of confidence in the diagnosis. The practical relevant consequences traditionally derived from a diagnosis (therapy, prognosis, and strategy of follow-up) are only marginally, if at all, affected by changing the diagnosis. Thus, the utility of "diagnosis" for judgment analysis in clinical nephrology should be reconsidered.

Intestinal amoebiasis, giardiasis and geohelminthiases: their association with other intestinal parasites and reported intestinal symptoms.

In order to determine reported signs and symptoms that may predict an intestinal parasitic infection, 241 schoolchildren in western Côte d'Ivoire were interviewed with a simple questionnaire and their stool specimens were examined over several consecutive days. Special emphasis was placed on (i) assessing infections by Entamoeba histolytica/E. dispar, Giardia duodenalis and by intestinal worms, (ii) looking for associations between these parasites, and (iii) looking for associations between these parasites and commonly perceived intestinal signs and symptoms. Complete questionnaire results, intestinal helminth infections derived from 4 Kato-Katz thick smears, and intestinal protozoa infections assessed on a single day by a formalin-ether concentration procedure were obtained from 209 children (87%). A logistic regression modelling approach showed that an infection with E. histolytica/E. dispar was significantly associated with an Entamoeba coli infection. However, for G. duodenalis, hookworm and Ascaris lumbricoides, no association was found between any of these parasites and other intestinal parasites. In a multivariate analysis reported diarrhoea was the only symptom positively associated with an E. histolytica/E. dispar infection (P = 0.028). Its diagnostic performance showed a low sensitivity (28%), a high specificity (85%) and moderate positive and negative predictive values (52% and 67%, respectively). Surprisingly, reported 'turning stomach' was less often reported by children infected with G. duodenalis (borderline significance, P = 0.057). It is concluded that reported diarrhoea could be a symptom worth exploring further for the rapid identification of schoolchildren infected with E. histolytica/E. dispar.

Species-specific field testing of Entamoeba spp. in an area of high endemicity.

Entamoeba histolytica has been separated in recent years into 2 morphologically identical species: the apathogenic E. dispar and the pathogenic E. histolytica, only the latter being pathogenic. Although various laboratory techniques allow discrimination between the 2 species there is a lack of field data about the suitability of available diagnostic tests for use in epidemiological studies and few epidemiological studies using species-specific diagnosis have been performed at community level in endemic areas, especially in sub-Saharan Africa. We conducted a repeated cross-sectional study of 967 schoolchildren in central Côte d'Ivoire to compare and evaluate light microscopy, 2 different antigen detection assays, and one polymerase chain reaction (PCR) assay. Microscopy and a non-specific antigen capture Entamoeba enzyme-linked immunosorbent assay (ELISA) were used for the primary screening of all children (time t0). The prevalence of the E. histolytica/E. dispar species complex at t0 was 18.8% by single microscopical examination and 31.4% using the non-specific ELISA. Approximately 2 months after the initial screening, fresh stool specimens were collected on 2 consecutive days (t1 and t2) from (i) all the children who were positive by microscopy at t0 (n = 182) and (ii) 155 randomly selected children who were negative at the primary screening. These samples were tested with a second antigen detection ELISA specific for E. histolytica (n = 238) and with a species-specific PCR assay (n = 193). The second and third examinations (t1 and t2) revealed an additional 43 infections with the species complex E. histolytica/E. dispar, so that the cumulative microscopical prevalence for t1 and t2 was 27.7%. The overall prevalence of E. histolytica by species-specific ELISA antigen detection was low (0.83%), while the prevalence of E. dispar was 15%. When analysing only microscopically positive samples by PCR (n = 129), the ratio E. histolytica: E. dispar was very low (1:46), suggesting that the vast majority of Entamoeba infections in this area were apathogenic. Both species-specific tests performed well but the ELISA was easier to use for large-scale field screening.

Studies on the ecology of Bulinus globosus, the intermediate host of Schistosoma haematobium in the Ifakara area, Tanzania.

During a period of 2 years, the ecology of Bulinus globosus was studied in 8 habitats in two streams near Ifakara, SE-Tanzania. The relative Bulinus densities were followed monthly. Two different methods for estimating snail densities (man/time vs. palmleaf traps) gave comparable results. Bulinus densities were constantly low throughout the year in the stream, but they showed distinct seasonal fluctuations in adjacent pools, with a density-peak at the end of the small rainy season. B. globosus, identified by starch gel electrophoresis, was found to be the only intermediate host for urinary schistosomiasis in the investigated streams. A correlation of the Bulinus densities with several abiotic and biotic factors revealed that pH, temperature and conductivity had little effect on the Bulinus population, as they oscillated within the tolerated limits. No correlation of the distribution of B. globosus and other snail species was found. Rainfall patterns have a distinct influence on snail densities. They determine the duration of desiccation and affect the snails by fluctuations of the water level and by the fast increase of water velocity after heavy rains. B. globosus shows a clear predilection for the sedge Cyperus exaltatus as support for oviposition. It is also preferred as food and/or food-support. During the dry season, oviposition of B. globosus is concentrated in clearly defined sites ("breeding pockets"), which, due to the lowering of the water level, become isolated from the stream or retain only a small connection to it. These sites form important reservoirs of B. globosus, from where the snails are spread when the sites are flooded during the subsequent rainy season. The significance of these observations for control measures is discussed.

Frequency of haematuria and proteinuria among Schistosoma haematobium infected children of two communities from Liberia and Tanzania.

The frequencies of haematuria and proteinuria among children of two rural communities with different Schistosoma haematobium endemicity from Liberia and Tanzania were compared. Although the prevalence and intensity of S. haematobium infections were lower in the Tanzanian community, the frequencies of haematuria and proteinuria were significantly higher when compared to the Liberian community. The semi-quantitative dip stick tests for haematuria and proteinuria showed a comparable, good specificity (haematuria 85%, proteinuria 80%), but a community-specific sensitivity. The dip stick test for haematuria detected 85% (proteinuria 82%) of all S. haematobium infected subjects in Tanzania compared to 68% (proteinuria 57%) in Liberia. The significance of these observations in relation to S. haematobium related morbidity is discussed.

Longitudinal study on the health status of children in a rural Tanzanian community: parasitoses and nutrition following control measures against intestinal parasites.

Three repeated cross-sectional surveys were undertaken among children (1 month to 15 years) of a rural community in southeastern Tanzania. The study was part of a longitudinal project on the interactions among nutrition, parasitic infections and immunity within a primary health care programme emphasizing village health workers. All children underwent interviews and parasitological, anthropometric, anamnestic and clinical examinations. Out of 550-590 children examined each year, a cohort of 170 children could be followed for three consecutive years. Malaria was holo- to hyperendemic in the community, P. falciparum accounting for greater than 90% of the infections. The parasite and spleen rates were 88% and 67%, respectively, and the average enlarged spleen index was 2.0 among children from 2-9 years in 1982. Transmission of malaria was high and stable as indicated by a parasite rate of 80% among infants between 1 month and 1 year during the whole period of study. G. lamblia, hookworm (N. americanus), Strongyloides spp. and Schistosoma haematobium were highly prevalent and annual incidence rates were high, while Entamoeba histolytica, Ascaris and Trichuris were of minor importance. Prevalence and incidence of parasitic infections did not differ by sex. Multiparasitism was very frequent and less than 11% of all children were parasite-free in each year. Not a single child remained parasite-free for three consecutive years. An anthropometric assessment showed a high degree of stunting (35-71%) and a substantial proportion of wasting (3-20%). The growth potential was normal in girls and boys during the whole period of study. There were indications that malaria was the main contributory factor to growth retardation among young children. Hookworm infection did not significantly affect the packed-cell volume of the children, probably owing to the low intensity of infection. Due to the multiparasitism and the lack of parasite-free individuals, single-parasite and single-nutrient effects were difficult to unravel. A latrine campaign followed by a single mass treatment against hookworm (single oral dose of albendazole, 400 mg) and/or G. lamblia (single oral dose of ornidazole, 40 mg/kg) only temporarily affected the prevalence and incidence of G. lamblia, and only resulted in a decrease in the intensity of hookworm infections up to six months after the interventions. As the effects of the latrine campaign and a single mass treatment on the parasite load were only transient, no sustained impact on nutritional variables was observed.(ABSTRACT TRUNCATED AT 400 WORDS)

Carbamoylation of glomerular and tubular proteins in patients with kidney failure: a potential mechanism of ongoing renal damage.

BACKGROUND: Cyanate formed spontaneously from urea carbamoylates non-protonated amino groups of protein, irreversibly altering function, charge and structure. Carbamoylated proteins in renal tissue have not been examined hitherto. OBJECTIVES: To identify homocitrulline (epsilon-amino-carbamoyl-lysine), a result of in vivo carbamoylation by urea-derived cyanate, from patients with renal disease or in newly transplanted kidneys by immunohistochemistry. To evaluate enzymatic activity of carbamoylated and non-carbamoylated matrix metalloproteinase-2 and correlate this with renal tissue carbamoylated in vivo. DESIGN: Anti-homocitrulline antibody is specific for homocitrulline and was used to identify carbamoylation of epsilon-amino-lysine in renal biopsies from patients with elevated BUN, with isolated proteinuria, and as controls, from normal donors at time of transplantation. Enzymatic activity of matrix metalloproteinase-2 carbamoylated in vitro was evaluated. RESULTS: Homocitrulline was present in glomerular basement membrane (8/10), mesangium (8/10), tubular epithelium and cytoplasm (7/10) and Bowman's capsule (1/10) in patients with elevated BUN. The discordant patterns of glomerular and tubular localization of homocitrulline versus immune complexes indicated that the carbamoylated proteins were not a component of immune deposits but were modified proteins in renal tissue. No homocitrulline was found in transplanted kidneys (14/15) or in proteinuric patients (2/2). Enzymatic activity of both human and rat matrix metalloproteinase-2 was strongly inhibited in a dose-dependent fashion when incubated with cyanate. CONCLUSIONS: In situ carbamoylation in proteins occurred in kidneys of patients with renal dysfunction but not in normal newly transplanted kidneys. Decreased enzymatic activity of carbamoylated enzymes may alter specific renal regulatory mechanisms. Carbamoylated proteins with altered function and charge may represent a previously underestimated mechanism in renal pathophysiology.

Inoculation of pigs against Trichinella spiralis, using larval excretory-secretory antigens.

Pigs were inoculated with Trichinella spiralis excretory-secretory products derived from short-term in vitro maintenance of infective muscle larvae. Intraperitoneal administration of excretory-secretory products in Freund's complete adjuvant or aluminum hydroxide induced moderate, but variable, degrees of immunity to challenge exposure in a nondose-dependent manner; IM administration of products in Freund's incomplete adjuvant was less successful. Inoculated pigs harbored fewer adult worms, and the fecundity of female worms (numbers of newborn larvae shed in vitro) recovered after challenge exposure was significantly lower (alpha = 0.05) than the fecundity of females recovered from control pigs. The degree of resistance in inoculated pigs was directly related to serotiter against excretory-secretory antigens, as determined in an enzyme-linked immunosorbent assay.

[Role of matrix metalloproteinases in the progression of renal lesions]. / Rôle des métalloprotéases matricielles dans la progression des lésions rénales.

METALLOPROTEINASES: The progression to end-stage kidney disease is accompanied by accumulation of extracellular matrix (ECM) proteins. The degradation of ECM proteins occurs by the action of proteases, notably the matrix metalloproteinases (MMP). MMP can be classified into four major groups, such as interstitial collagenases, gelatinases, stromelysins, and membrane-type (MT)-MMP. MMP are also involved in the regulation of cell proliferation and possibly of apoptosis. In the kidney, MMP are synthesized by intrinsic glomerular cells and tubular epithelial cells. EXPERIMENTAL DATA: MMP and TIMP expression is well studied in a variety of kidney disorders, particularly in diabetes mellitus and in experimental glomerulonephritis. In diabetes mellitus, an increased plasma concentration of MMP-9 was found to represent the earliest marker of diabetic kidney disease. In anti-Thy 1.1 nephritis, a rat model of mesangial proliferative glomerulonephritis, an increase in proliferation of mesangial cells is associated with augmented expression of MMP-2 and accumulation of extracellular matrix proteins. These inflammatory features can be attenuated by a synthetic MMP inhibitor. ABNORMAL MMP AND TIMP REGULATION: The hypothesis that MMP play an important role in the progression of nephropathies is mainly based on the well known ability of MMP to degrade ECM components, on the association of altered MMP expression in a large number of kidney diseases, and on the ability of MMP-2 to induce or to sustain an inflammatory mesangial cell phenotype. However, since there are only few interventional or functional studies, uncertainty persists as to whether abnormal regulation of MMP and TIMP represents a cause or simply an effect of the respective renal diseases. A DUAL ROLE: In nephropathies, MMP appear to play a dual role as antifibrotic enzymes and as proinflammatory mediators. The exact biologic function in a given renal disorder may depend upon the level of net MMP activity and on the acuteness or the chronicity of the respective disease.

[A special case of swollen lower limb]. / Eine ungewöhnliche Ursache für Odeme der unteren Extremitäten!

We report on a case of a 31-year-old patient suffering from long-standing peripheral edema with severe hypoalbuminemia, but without proteinuria. Differential diagnosis, diagnostic work-up and the therapeutic options in this unusual case are discussed. The general practitioner must keep in mind a broad range of causes when seeing every-day-patients with peripheral edema, although the correct etiology can be found easily in most cases.