Expression of CD34 and CD146 vascular markers contributes to the immunological function of the human palatine tonsil.

The fundamental function of the palatine tonsil is the immune response to airborne and foodborne pathogenic agents. Small blood vessels have an important role in the provision of a special microenvironment in which the immune response occurs. In this study, we investigated the expression of vascular markers CD34 and CD146 and basal lamina marker - type IV collagen - in the small blood vessels of the human palatine tonsil in the context of their role in the immunological function of the tonsil. The tonsils were collected after tonsillectomy from ten patients with chronic tonsillitis, aged 18-28 years. Five-µm-thick paraffin sections were routinely stained with haematoxylin and eosin, while the studied markers (CD34, CD146 and type IV collagen) were detected immunohistochemically using LSAB2/HRP method. CD34 was expressed equally in the capillaries within and below the crypt epithelium, in lymphoid follicles and in high endothelial venules localized para- and interfollicularly. CD146 molecule was expressed on the luminal surface of endothelial cells in the capillaries of the crypt epithelium, while its expression in high endothelial venules was seen on the luminal and lateral surfaces of the cuboidal endothelial cells. In contrast to the basal lamina of intraepithelial capillaries, where collagen IV-immunopositivity is mostly seen as a continuing line, the basal lamina of high endothelial venules was seen as a two- or three-layered structure beneath the cuboidal endothelial cells. The specifics of expression of CD34, CD146, and type IV collagen confirm the morphofunctional specialization of endothelium in crypt epithelium capillaries, and also in endothelium of high endothelial venules, which is directly associated with the role of these vessels in the immune function of the tonsil.

Ultrastructure of the human palatine tonsil and its functional significance.

The human palatine tonsils represent a mucosa-associated lymphoid tissue with a significant function in mucosal protection against alimentary and airborne pathogens. The ultrastructure of different morphological compartments in the human palatine tonsil was studied in eighteen tonsils obtained from the patients who had undergone elective tonsillectomy due to chronic tonsillitis. The tonsillar specimens were analyzed by scanning and transmission electron microscopy. The results showed the presence of tight junctions between superficial epithelial cells of the oropharyngeal tonsillar surface. The crypt epithelium is a sponge-like structure infiltrated by non-epithelial cells, mostly lymphocytes, and is characterized by the presence of small pores - microcrypts occupied by large microvillus cells and/or lymphocytes. Antigen-presenting Langerhans cells with typical intracytoplasmic Birbeck granules were also found in the crypt epithelium. The lymphoid follicles are composed of lymphocytes and two types of non-lymphoid follicular cells: small fibroblast-like cells and large cells, morphologically consistent with antigen-bearing follicular dendritic cells or macrophages. The interfollicular areas consisted of a dense network of reticular cells and reticular fibers; many lymphocytes were interspersed between the reticular fibers. In addition to arterioles and high endothelial venules in the interfollicular lymphoid tissue, some fenestrated capillaries were seen intraepithelially and subepithelially. The complex ultrastructure of the human palatine tonsil provides a microenvironment necessary for antigen uptake, antigen processing and immune response.

Pharmacogenetics may Influence Tacrolimus Daily Dose, but not Urinary Tubular Damage Markers in the Long-Term Period after Renal Transplantation.

BACKGROUND: The primary goal of this study was to evaluate the influence of cytochrome P450 (CYP) 3A5 (6986A>G) and ABCB1 (3435C>T) polymorphisms on tacrolimus (TAC) dosage regimen and exposure. Second, we evaluated the influence of TAC dosage regimen and the tested polymorphisms on renal oxidative injury, as well as the urinary activities of tubular ectoenzymes in a long-term period after transplantation. Also, we aimed to determine the association between renal oxidative stress and tubular damage markers in the renal transplant patients. METHODS: The study included 72 patients who were on TAC based immunosuppression. Allele-specific PCR was used for polymorphism determination. We measured the urinary thiobarbituric acid reactive substances (TBARS) and reactive carbonyl derivates (RCD) in order to evaluate oxidative injury, as well as the urinary activities of ectoenzymes (N-acetyl-ß-D-glucosaminidase, aminopeptidase N and dipeptidyl peptidase IV) to evaluate tubular damage. RESULTS: The carriers of CYP 3A5*1 allele required statistically higher daily doses of TAC than CYP *3/*3 carriers, as well as the carriers of C allele of ABCB1 gene compared to those with TT genotype. Also, there were no differences in TBARS, RCD and the activities of ectoenzymes between the patients' genotypes. Our results showed significant correlations between urinary TBARS and RCD and the ectoenzymes' activities. CONCLUSIONS: Our findings suggest that CYP 3A5 and ABCB1 3435 polymorphism may affect TAC daily doses, but not the drug's tubular toxicity. Furthermore, tubular damage may be associated with increased renal oxidative stress.

Hepcidin and iron metabolism disorders in patients with chronic kidney disease.

BACKGROUND/AIM: [corrected] Hepcidin may play a pathogenetic role in iron metobolism disorders. The aim of this study was to determine the correlation between hepcidin concentration and parameters of iron metabolism in patients with different stage of chronic kidney disease (CKD). METHODS: The study involved 104 patients with CKD: 64 on hemodialysis (HD) and 40 patients in pre-dialysis stadium (pre-HD) with adequate erythropoetin therapy and iron supplementation. The HD group was divided in four subgroups according to the level of serum ferritin (up to 100; 100-199; 200-499 and over 500 ng/mL). Parameters of anemia, iron status, in flamation and hepcidin level were evaluated. RESULTS: The HD patients had a significantly lower eritrocyte count, erythrocytes indexes, hemoglobin and transferrin saturation and significantly higher iron, ferritin, hepcidin and total iron binding capacity (TIBC). The HD subgroups up to 199 ng/mL of serum feritin had lower high-sensitivity C-reactive protein (hsCRP), iron and higher unbuffered iron binding capacity (UIBC), transferrin saturation and TIBC compared to the HD subgroups over 200 ng/mL. The lowest and the highest ferritin subgroups had the highest hepcidin level and it showed significant correlation with ferritin. CONCLUSION: Hepcidin may serve as a marker for better diagnosing and monitoring anemia and iron metabolism disorders in CKD.

Histomorphological and clinical study of primary and secondary glomerulopathies in Southeast Serbia (20-year period of analysis).

BACKGROUND/AIM: Epidemiological studies of renal biopsies have been performed to follow up the incidence of glomerular diseases on a specified territory and to compare the obtained results with results from other regions. The aim of this study was to analyze the frequency of certain histopathophysiological types of glomerular diseases on the territory of Southeast Serbia. METHODS: In a 20-year period (1986-2006), 316 kidney biopsies were performed in patients with clinical signs of impaired renal function, in Southeast Serbia. On average 1.6 biopsies were made per year per 100 000 inhabitants. RESULTS: Biopsies of adult patients represented 88% of all biopsies, biopsies in children (aged under 18 years) represented 8%, while biopsies of elderly patients (more than 60 years) represented 4% of all biopsies. The predominance of male patients was described with male/female ratio of 1.4. The most frequent clinical manifestation in patients at the time of biopsy were nephrotic syndrome (42.5%), and asymptomatic proteinuria and/or hemamuria (31.3%) and nephritic syndrome (14.9%). The most common glomerular disease was IgA nephropathy with an incidence of 21.5% of total biopsy diagnosed glomerulopathies, followed by: membranous glomerulonephritis (12.6%), focal segmental proliferative and sclerosing glomerulonephritis (10.7%), lupus nephritis (8.4%), nephroangiosclerosis (7.0%), mesangio-proliferative glomerulonephritis (6.1%), minimal change disease (2.8%), mesangiocapillary glomerulonephritis (2.3%). CONCLUSION: The frequency of certain histopathologic findings significantly correlated with data from studies that we used for comparison, with the exception of minimal change disease whose incidence in our study was smaller.

Schizophrenia is associated with increased levels of serum Fas and FasL.

BACKGROUND: A growing body of evidence suggests that the apoptotic process is dysregulated in schizophrenia. However, only a few studies have evaluated apoptotic markers in vivo in patients or their cell cultures. METHODS: Serum concentrations of Fas receptor (Fas/APO-1) and Fas ligand (FasL) were measured by ELISA techniques. The differences were tested according to the patients' demographic, clinical and drug treatment characteristics. The clinical accuracy of the examined markers was assessed using receiver operating characteristic (ROC) curve analysis. RESULTS: In this case-controlled study both sFas/APO-1 and FasL were significantly higher in the patients with schizophrenia than in the controls. An increase in apoptotic markers was independent of the symptomatology, drug treatment, heredity, the first onset of the disease, the duration of the psychotic disease as well as the tobacco abuse. A significant negative correlation between the duration of the disease and sFasL concentration was found. At the same time, a significant positive correlation was found between sFasL and lymphocyte caspase-3 activity. ROC curve analysis showed that sFasL was the most strongly associated with the presence of schizophrenia. CONCLUSIONS: We can conclude that the extrinsic apoptotic pathway is dysregulated in schizophrenia and sFasL may be a clinically useful disease predictor.

Lipoprotein(a) Is the Best Single Marker in Assessing Unstable Angina Pectoris.

This study evaluated whether statin therapy changed a diagnostic validity of lipid and inflammatory markers in ischemic heart disease (IHD) patients. Levels of lipids, lipoproteins, apolipoproteins, inflammatory markers, and atherogenic indexes were determined in 49 apparently healthy men and women, 82 patients having stable angina pectoris (SAP), 80 patients with unstable angina (USAP), and 106 patients with acute ST-elevation myocardial infarction (STEMI) treated or not treated with statins. Diagnostic accuracy of markers was determined by ROC curve analysis. Significantly lower apoA-I in all statin-treated groups and significantly higher apoB in statin-treated STEMI group compared to non-statin-treated groups were observed. CRP showed the best ROC characteristics in the assessment of STEMI patients. Lp(a) is better in the evaluation of SAP and USAP patients, considering that Lp(a) showed the highest area under the curve (AUC). Regarding atherogenic indexes, the highest AUC in SAP group was obtained for TG/apoB and in USAP and STEMI patients for TG/HDL-c. Statins lowered total cholesterol, LDL-c, and TG but fail to normalize apoA-I in patients with IHD.

Beta2-microglobulin and alpha1-microglobulin as markers of Balkan endemic nephropathy, a worldwide disease.

BACKGROUND: Urine beta2-microglobulin (beta2-MG) was mainly used as a tubular marker of Balkan endemic nephropathy (BEN) but recently alpha1-microglobulin (alpha1-MG) was proposed for the diagnosis of BEN. In this study, the potential of urine beta2-MG, alpha1-MG, albumin, and total protein in the differentiation of BEN from healthy persons and patients with glomerulonephritis (GN) and nephrosclerosis (NS) was examined. METHODS: This study involved 47 patients with BEN, 36 with GN, 11 with NS, 30 healthy subjects from BEN families, and 46 healthy subjects from non-BEN families. RESULTS: In BEN patients area under the curve (AUC) for urine beta2-MG (0.828) and alpha1-MG (0.782) was higher than for urine albumin (0.740), but in GN patients AUC for urine protein (0.854) and albumin (0.872) was significantly higher than for the two low molecular weight proteins. AUC for all four urinary markers in NS patients was significantly lower than in BEN patients, ranging between 500 and 595. Median urine beta2-MG excretion in BEN patients was 17.5 times higher than in GN patients and 18.3 times higher than in controls; median alpha1-MG excretion was higher only 3.0 and 2.25 times, respectively. In the differentiation of BEN from healthy controls, beta2-MG had higher sensitivity and specificity at the cutoff levels (p < 0.001) than alpha1-MG (p < 0.05). In the differentiation of BEN from GN, beta2-MG was the best marker. CONCLUSION: All four urinary markers can be used for the differential diagnosis of BEN, beta2-MG being the best. Like in aristolochic acid nephropathy, beta2-MG seems to be an early marker of tubular damage in BEN.

Investigation of oxidative stress in patients with chronic tonsillitis.

OBJECTIVES: Oxidative stress has been implicated in numerous pathological conditions including chronic tonsillitis. The aim of this study was to assess levels of lipid peroxidation, evidenced by formation of thiobarbituric acid reactive substance (TBARS), level of total sulfhydryl groups (TSH), and carbonyl content in patients with tonsillar hypertrophy (TH) and recurrent tonsillitis (RT), before and after tonsillectomy. METHODS: In this study the serum and tonsillar tissue levels of TBARS, TSH and carbonyl content were investigated in 35 patients with TH and RT, before and 1 month after the operation, compared to 30 age-matched controls. RESULTS: In both TH and RT groups, a significantly higher serum TBARS levels were observed before and 4 weeks after tonsillectomy in comparison with healthy subjects. The serum level in TH patients after operation was even higher compared to the levels before. There was statistically significant difference in serum TSH levels between patients with RT before operation compared to the control group. After tonsillectomy the serum levels of TSH were higher compared to control groups and TH and RT patients before operation. Carbonyl content was attenuated only in TH patients after tonsillectomy. In tonsillar tissue, significantly lower level of glutathione content (GSH) has been observed in RT related to TH patients. CONCLUSIONS: Oxidative stress, in patients with tonsillar hypertrophy and recurrent tonsillitis, is still present 1 month after the removal of tonsillar tissue. Antioxidant therapy, during the recovery period after tonsillectomy, could be optional treatment.

Oxidative stress parameters as possible urine markers in patients with diabetic nephropathy.

OBJECTIVE: Reactive oxygen species play a crucial role in the pathogenesis of diabetic nephropathy (DN). The present study was performed to assess oxidative stress parameters-thiobarbituric acid reactive substances (TBARS), reactive carbonyl derivates (RCDs), and total sulfhydryl groups (TSHGs)-in serum and urine of patients with DN. METHODS: All parameters were determined in patients with type 2 and type 1 diabetes mellitus and microalbuminuria (DMT2-MIA, DMT1-MIA, respectively) and patients with type 2 diabetes mellitus and macroalbuminuria (DMT2-MAA) compared to healthy controls. RESULTS: Serum and urine TBARS levels were higher in all patients with DN and microalbiminuria compared to the control group. RCD levels significantly increased in serum of patients with DMT2 relative to the controls as well as in urine of patients with DMT2-MAA and DMT1-MIA. In all groups of patients, TSHGs decreased in serum but not in urine of patients with DMT2-MAA. CONCLUSION: Urine TBARS, RCDs, and TSHGs could be proposed as possible markers for oxidative damage of kidney in DN.

Diagnostic value of the aminopeptidase N, N-acetyl-beta-D-glucosaminidase and dipeptidylpeptidase IV in evaluating tubular dysfunction in patients with glomerulopathies.

AIM: The aim of the present study was to investigate the value of the urine cell glycoprotein 1 (PC-1), aminopeptidase N (APN), N-acetyl-beta-D-glucosaminidase (NAGA), and dipeptidylpeptidase IV (DPP IV) in the evaluation of tubular damage in patients with primary glomerulonephritis, diabetic nephropathy, and lupus nephritis. SUBJECTS AND METHODS: PC-1, APN, NAGA, and DPP IV activities were determined in serum, urine, and lymphocytes of 178 subjects, including 10 patients with membranous nephropathy, 38 with IgA nephropathy, 29 with lupus nephritis, 51 with diabetic nephropathy, and 50 control subjects. RESULTS: Urinary PC-1 excretion in IgA nephropathy group was significantly higher (p < 0.05) than in controls. Urinary NAGA excretion was markedly (p < 0.01) higher in membranous nephropathy group, and APN excretion in diabetic nephropathy group was significantly higher (p < 0.01) than in healthy controls. Urinary APN activity was significantly (p < 0.01) higher in both type 1 and type 2 diabetic patients with microalbuminuria, as well as urinary NAGA and DPP IV activities in type 2 diabetics with microalbuminuria (p < 0.01 and p < 0.05, respectively) compared to controls. Serum PC-1 and APN activities were significantly higher than the control level in membranous nephropathy group, as well as serum PC-1 and DPP IV activities in IgA nephropathy patients (p < 0.05). However, significantly lower serum DPP IV and APN activity was observed in type 2 diabetics with microalbuminuria compared to controls (p < 0.05). CONCLUSION: Damage of tubules in primary glomerulonephritis, lupus nephritis, and diabetic nephropathy is accompanied by a release of several tubular enzymes, with possible diagnostic and prognostic significance. Increased serum PC-1, APN, and DPP IV activities could be also of diagnostic significance.

Distribution of dipeptidyl peptidase IV in patients with chronic tonsillitis.

In the pathogeneses of recurrent tonsillitis (RT) and tonsillar hypertrophy (TH), different immunological mechanisms are involved. Dipeptidyl peptidase IV (DPP IV) and aminopeptidase N (APN) participate in the regulation of the immune response during inflammation. In this study, the localization of DPP IV and the enzymatic activities of DPP IV and APN in 32 patients, 13 with RT and 19 with TH, who underwent tonsillectomy were investigated. The localization of DPP IV in tonsils was studied using histochemical and immunohistochemical methods. The enzymatic activities of DPP IV and APN in tonsillar lymphocytes and the patients' sera were determined kinetically at 37 degrees C using Gly-Pro-p-nitroanilide (for DPP IV) and Ala-p-nitroanilide (for APN) as chromogenic substrates. In samples from both RT and TH patients, DPP IV was found to localize mainly in extrafollicular areas of tonsillar tissue in a pattern corresponding to the T-cell distribution. Significantly higher (P < 0.001) levels of DPP IV and APN activities in sera from patients with TH than in sera from patients with RT were found. A correlation of DPP IV activities in sera and tonsillar lymphocytes from patients with TH was also found (r = 0.518; P < 0.05). Moreover, the results show that DPP IV and APN activities in sera decreased significantly with age. Tonsillar lymphocytes demonstrated a wide range of DPP IV and APN activities, without significant differences between the investigated groups. The results of this study show that the localization of DPP IV does not depend on the type of tonsillitis, whereas the variety in levels of DPP IV and APN activities in sera of patients with TH and RT suggests different patterns of participation of antigen-stimulated tonsils in the immune system.

Ethanol inhibitory effect on rat kidney brush border aminopeptidases.

BACKGROUND/AIM: Confusing data have been reported about the effect of ethanol or its metabolic products on blood pressure. The pressor agent, angiotensin II (Ang II), is found to be susceptible to degradation by different enzymes known as angiotensinases. We have studied the effects of ethanol and L-NAME, an inhibitor of nitric oxide synthase, consumption on rat serum and kidney ectoenzymes: aminopeptidase N (APN) and aminopeptidase A (APA). METHODS: Enzymatic activity of both enzymes was determined spectrophotometrically in serum and 10% homogenates of the rat kidney cortex using appropriate chromogenic substrates. RESULTS: After 2 weeks of treatment with ethanol and L-NAME, blood urea and creatinine levels were significantly increased. The activities of APN (EC 3.4.11.2) and APA (EC 3.4.11.7) were reduced in serum as well as in kidney tissue during this period. L-NAME significantly attenuated activities of both enyzmes. Ethanol and L-NAME given simultaneously did not have an additional effect on the activity of investigated enzymes. CONCLUSION: Hypertension caused by chronic ethanol treatment as well as L-NAME administration could be associated with the reduction of APN and APA activity. Possible ethanol- and L-NAME-mediated inhibition of angiotensins degrading aminopeptidases could potentiate their effects on blood pressure.

Effects of aerobic exercise on microalbuminuria and enzymuria in type 2 diabetic patients.

Increased urinary albumin excretion is a strong predictor for the development of overt diabetic nephropathy and overall cardiovascular morbidity and mortality in patients with type 2 diabetes. In a previous study, regular aerobic physical activity in overweight/obese patients with type 2 diabetes mellitus was found to have significant beneficial effects on glycemic control, insulin resistance, cardiovascular risk factors, and oxidative stress. The aim of the present study was to investigate the effects of aerobic exercise in the same cohort of type 2 diabetic patients on urinary albumin excretion, serum levels and urinary excretion of enzymes, tubular damage, and metabolic control markers in type 2 diabetic patients. Changes from baseline to 3 and 6 months of aerobic exercise were assessed for urinary albumin excretion, serum activities, and urinary excretion of N-acetyl-beta-D-glucosaminidase (NAGA), plasma cell glycoprotein 1 (PC-1) and aminopeptidase N (APN), as well as their association with insulin resistance, cardiovascular risk factors, and oxidative stress parameters in 30 male type 2 diabetic patients (aged 54.8 +/- 7.3 years, with a mean BMI of 30.8 +/- 3.0 kg/m2). Microalbuminuria was found in six (20%) diabetic patients at baseline, three of them (10%) after three months, and only one patient (3.33%) at the end of the study period. A significant correlation was found for urinary albumin excretion at baseline both with sulfhydryl-groups and catalase, but not for urinary albumin excretion with MDA and glutathione. The prevalence of microalbuminuria tended to decrease after six months of aerobic exercise in type 2 diabetic patients, independently of any improvement in insulin resistance and oxidative stress parameters. Neither between-group nor within-group changes were found for urinary PC-1, APN, and NAGA activity. Serum NAGA was significantly increased (p < 0.05) over the control level in diabetic patients at baseline, but it decreased to the normal level after six months of exercise. This study has shown that a six-month aerobic exercise, without any change in the medication, tended to decrease microalbuminuria without changing enzymuria. However, further studies are needed not only to confirm those findings, but to elucidate potential mechanisms that would clarify the beneficial effects of exercise.

Lymphocyte 5'-nucleotidase and aminopeptidase N activity in patients on maintenance hemodialysis treated with human recombinant erythropoietin and 1-alpha-D3.

BACKGROUND: Patients with end-stage renal disease (ESKD) present an immunodeficiency state paradoxically exacerbated by hemodialysis (HD) and associated with signs of T-cell activation. B cells are also activated in uremia, and this activation could be altered by erythropoietin therapy in HD patients. In this study, the effects of human recombinant erythropoietin (rHu-EPO) and 1-alpha-D3 treatments on lymphocyte immunomodulatory enzymes, aminopeptidase N (APN), and 5'-nucleotidase activity in patients on HD were investigated in hemodialysis patients before and after two-month treatment with s.c. rHu-EPO (15 patients, 2000-3000 U three times weekly) or oral 1-alpha-D3 (14 patients, 2 microg three times weekly). RESULTS: A two-month EPO treatment of 15 HD patients produced a rise in hemoglobin from 6.51 +/- 0.18 to 9.69 +/- 0.14 g/dL. Basal lymphocyte APN activity in HD patients was not significantly different from the level in healthy controls. Treatment of patients with rHu-EPO increased unstimulated lymphocyte APN activity to values significantly higher than those before treatment (p<0.05). A two-month pulse oral 1-alpha-D3 treatment of 14 HD patients increased hematocrit by 21% and raised hemoglobin from 7.11 +/- 0.32 to 8.80 +/- 0.39 g/dL. Unstimulated and Con A-stimulated lymphocyte APN activity after pulse oral 1-alpha-D3 was significantly increased (p<0.01 and p<0.05, respectively) from the pretreatment levels. In HD patients lymphocyte basal, Con A-, and PMA-stimulated 5'-nucleotidase activity was significantly higher (p<0.05) than it was in healthy controls. The two-month treatment with rHu-EPO or pulse oral 1-alpha D3 did not change the level of lymphocyte 5'-nucleotidase in these patients. CONCLUSIONS: This study demonstrated that a two-month treatment of HD patients with rHu-EPO or pulse oral 1-alpha D3 significantly increases activity of lymphocyte APN, important for cleavage of peptides and small proteins, which accumulate in the blood of ESKD patients. In HD patients lymphocyte ecto-5'-nucleotidase activity was significantly higher than that in healthy controls and was not changed after a two-month treatment with rHu-EPO or pulse oral 1-alpha D3. We speculate that oxidative stress activates 5'-nucleotidase and production of adenosine by lymphocytes of HD patients.

Increased urinary protein excretion in children from families with balkan endemic nephropathy.

BACKGROUND: Balkan endemic nephropathy (BEN) has not been described in children, however some previous studies of children from families with BEN have revealed abnormalities of the urinary tract including an increased urinary protein excretion. METHODS: In the present study, urinary excretion of total protein was studied in 703 healthy children, aged 9-13, from endemic and non-endemic settlements around the South Morava River. Since BEN is an environmentally induced disease, with possible seasonal variation of toxin(s), children were studied three times a year: in spring, autumn and winter, during a 3-year period. After a water load of 15 ml/kg body weight, a 3-hour urine sample was collected, from 7 to 10 a.m. RESULTS: Protein excretion in urine was highest in children from families with BEN compared with the excretion in children from the city, non-endemic villages, and those from non-endemic families living in the same settlements. This was the case during all three periods investigated in the second year of the study. In the autumn term of all three years of the study, protein excretion was significantly higher in children from families with BEN than in children from the city and from non- endemic families living in the same settlements. If the upper limit of protein excretion is set at 34 mg/mmol creatinine, then increased protein excretion in autumn was found in the first year of study in 9/229 children from endemic settlements and in only 4/474 children from non-endemic areas (p = 0.004); in the second year in 5/229 and 3/474 children (p = 0.069), and in the third year in 10/229 and 4/474 children (p = 0.002), respectively. CONCLUSIONS: We have presented evidence that children from families with BEN and endemic villages consistently excreted significantly more protein in the autumn, and in three seasons (spring, autumn, winter) in 1 year of our study. These results are consistent with seasonal variations in exposure to an environmental toxin(s).

Effect of polyamines on mesangial cell ecto-5'-nucleotidase and ecto-ATPase activity.

Polyamines were found to modulate the activity of several membrane-bound enzymes, participating in cell growth and differentiation. We have studied the effect of polyamines (spermidine, spermine and putrescine) on rat mesangial cell ectoenzymes: 5'-nucleotidase, Mg(2+)-ATPase and Ca(2+)-ATPase. Ecto-5'-nucleotidase activity was significantly increased after 48 h treatment with spermine and spermidine. Mg(2+)-ATPase was increased only after treatment with spermidine; however, Ca(2+)-ATPase was significantly increased after both spermine and spermidine treatment of mesangial cells. Culture of mesangial cells with putrescine did not change the activity of these ectoenzymes. Increased expression of mesangial cell ecto-ATPase and ecto-5'-nucleotidase after spermine and spermidine treatment could result in an increased production of adenosine, a powerful autacoid interesting with respect to a role of mesangial cells in inflammatory processes.

Increased expression of glomerular mesangial cell 5'-nucleotidase in membranous nephropathy.

It has been demonstrated in anti-Thy1 glomerulonephritis that extracellular adenine nucleotides have a significant pro-inflammatory activity, however, glomerular ATP/ADPase, which in concert with 5'-nucleotidase converts ATP/ADP, and AMP to anti-inflammatory adenosine had an anti-inflammatory role. We have studied distribution of 5'-nucleotidase and divalent cation-activated ATPase in kidney biopsies of 15 patients with glomerulonephritis. The major finding was an overexpression of 5'-nucleotidase in the mesangium of kidney from patients with membranous nephropathy. No change in 5'-nucleotidase expression was observed in other common forms of glomerulonephritis: IgA nephropathy, mesangioproliferative and mesangiocapillary glomerulonephritis. The distribution of Mg(2+)-ATPase in investigated specimens was similar to control distribution. Results obtained in this study indicate increased mesangial expression of 5'-nucleotidase in non-proliferative form of glomerulonephritis consistent to a role of mesangial cells in inflammatory processes.