Flow cytometry diagnosis in myelodysplastic syndrome: Current practice in Latin America and comparison with other regions of the world.

BACKGROUND: Flow cytometry (FC) is a valuable tool for the diagnosis of myelodysplastic syndromes (MDS). We present results of a survey carried out to evaluate FC current practice for MDS diagnosis in Latin America (LA), focusing on markers used and characteristics of the clinical diagnostic report. Compliance to IMDSflow recommendations was also evaluated. These practices were then compared with those used in other countries. METHODS: An online survey was sent through the Grupo Latino-Americano de Mielodisplasia to LA cytometrists and other international scientific societies. RESULTS: 91 responses from 15 LA countries were received. The median of the number of markers used was 20 ± 4.5, but only 8.1% of participants adopted the complete panel proposed by the International/European LeukemiaNet Working Group (IMDSflow). We received 140 eligible answers from regions other than LA (66 Europe, 59 USA-Canada, 8 Oceania, 6 Asia and 1 Africa). LA utilized more markers for MDS diagnosis than USA/Canada (p = 0.006), but similar to Europe. The use of MDS scoring systems differed among regions: 10.3% in LA, 0% USA/Canada and 25.7% Europe reported the "Ogata score". Finally, 52.0% of all participants included a general interpretation statement in the final report about the consistency of the FC results with MDS diagnosis, with no statistical differences between regions. CONCLUSIONS: This survey shows a low compliance with the IMDSflow recommendations and a scarce use of the scoring systems proposed in the literature. However, the number of surface markers used is high. We will work to develop a FC consensus for MDS diagnosis adapted to the clinical practice requirements in LA.

Normal variation of bone marrow B-cell precursors according to age - reference ranges for studies in myelodysplastic syndromes in Brazil.

BACKGROUND: Normal B lymphoid maturation occurs in bone marrow (BM) throughout life, but immature B-cell progenitors (BCPs) are more numerous in children than in adults. To assess the normal values according to age became important as BCPs are decreased in myelodysplastic syndromes and have been considered an important diagnostic and prognostic feature in these clonal disorders. METHODS: in a multicenter retrospective study from the Brazilian Group of Flow Cytometry we analyzed the variation of BCPs in normal BM according to age and technical peculiarities of each laboratory. We analysed of 45 BM donors and 89 cases examined for elucidation of transitory reactive cytopenias presenting a normal BM immunophenotyping. BCPs were enumerated as CD19+ /CD34+ /CD45dim /CD10+ cells (panel 1) or CD19+ /CD34+ /CD45dim cells (panel 2) among the total nucleated non-erythroid cells and as percentage of CD34+ cells. RESULTS: we included 134 cases. Panel 1 was applied in 88 cases and panel 2 was used in 46. Age range: 10 months to 89 years. In a multiple regression, % BCPs/total nucleated cells was an exponential function of age. Age explained alone 49.4% of the variance, while 'panel used' explained 1.8% and 'laboratory' explained 0.7%. Age explained only 24.9% of the variance of BCPs/CD34+ cells. CONCLUSIONS: in normal individuals, BM B-cell precursors varied mainly according to age, but were also dependent on technical peculiarities of operators and equipments. Analysis by phenotype and as percentage of total nucleated cells was more accurate and less susceptible to variation than evaluating % BCPs/total CD34+ cells. © 2017 International Clinical Cytometry Society.

Diagnosis of chronic lymphoproliferative disorders by flow cytometry using four-color combinations for immunophenotyping: A proposal of the brazilian group of flow cytometry (GBCFLUX).

BACKGROUND: Multiparametric flow cytometry (MFC) is a powerful tool for the diagnosis of hematological malignancies and has been useful for the classification of chronic lymphoproliferative disorders (CLPD) according to the WHO criteria. Following the purposes of the Brazilian Group of Flow Cytometry (GBCFLUX), the aim of this report was to standardize the minimum requirements to achieve an accurate diagnosis in CLPDs, considering the different economic possibilities of the laboratories in our country. Most laboratories in Brazil work with 4-fluorescence flow cytometers, which is why the GBCFLUX CLPD Committee has proposed 4-color monoclonal antibody (MoAb) panels. METHODS/RESULTS: Panels for screening and diagnosis in B, T and NK lymphoproliferative disorders were developed based on the normal differentiation pathways of these cells and the most frequent phenotypic aberrations. Important markers for prognosis and for minimal residual disease (MRD) evaluation were also included. The MoAb panels presented here were designed based on the diagnostic expertise of the participating laboratories and an extensive literature review. CONCLUSION: The 4-color panels presented to aid in the diagnosis of lymphoproliferative neoplasms by GBCFLUX aim to provide clinical laboratories with a systematic, step-wise, cost-effective, and reproducible approach to obtain an accurate immunophenotypic diagnosis of the most frequent of these disorders. © 2016 International Clinical Cytometry Society.

Association of myelin peptide with vitamin D prevents autoimmune encephalomyelitis development.

Multiple sclerosis is a chronic, inflammatory and demyelinating disease of the central nervous system (CNS). As there is no cure for this disease, new therapeutic strategies and prophylactic measures are necessary. We recently described the therapeutic activity of the association between myelin oligodendrocyte glycoprotein peptide (MOG) and active vitamin D3 (VitD) against experimental autoimmune encephalomyelitis (EAE). The objective of this work was to evaluate the prophylactic potential of this association in EAE. C57BL/6 mice were vaccinated with MOG in the presence of VitD and then subjected to EAE induction. Animals were euthanized 7 and 19days after disease induction and the following parameters were evaluated: body weight, clinical score, inflammatory process in the CNS, amount of dendritic cells (DCs) and regulatory T cells in the spleen and cytokine production by spleen and CNS cell cultures. Vaccination with MOG associated with VitD determined a drastic reduction in clinical score, body weight loss, CNS inflammation, DCs maturation and also in the production of cytokines by CNS and spleen cell cultures. Collectively, our data indicate that this association prevents EAE development. A similar effect from specific self-antigens associated with VitD is expected in other autoimmune conditions and deserves to be experimentally appraised.

Bacille Calmette-Guérin/DNAhsp65 prime-boost is protective against diabetes in non-obese diabetic mice but not in the streptozotocin model of type 1 diabetes.

Type I diabetes is a disease caused by autoimmune destruction of the beta cells in the pancreas that leads to a deficiency in insulin production. The aim of this study was to evaluate the prophylactic potential of a prime-boost strategy involving bacille Calmette-Guérin (BCG) and the pVAXhsp65 vaccine (BCG/DNAhsp65) in diabetes induced by streptozotocin (STZ) in C57BL/6 mice and also in spontaneous type 1 diabetes in non-obese diabetic (NOD) mice. BCG/DNAhsp65 vaccination in NOD mice determined weight gain, protection against hyperglycaemia, decreased islet inflammation, higher levels of cytokine production by the spleen and a reduced number of regulatory T cells in the spleen compared with non-immunized NOD mice. In the STZ model, however, there was no significant difference in the clinical parameters. Although this vaccination strategy did not protect mice in the STZ model, it was very effective in NOD mice. This is the first report demonstrating that a prime-boost strategy could be explored as an immunomodulatory procedure in autoimmune diseases.

A series of structurally novel heterotricyclic alpha-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate receptor-selective antagonists.

BACKGROUND AND PURPOSE: A new class of heterotricyclic glutamate analogues recently was generated by incorporating structural elements of two excitotoxic marine compounds, kainic acid and neodysiherbaine A. Rather than acting as convulsants, several of these 'IKM' compounds markedly depressed CNS activity in mice. Here, we characterize the pharmacological profile of the series with a focus on the most potent of these molecules, IKM-159. EXPERIMENTAL APPROACH: The pharmacological activity and specificity of IKM compounds were characterized using whole-cell patch clamp recording from neurons and heterologous receptor expression systems, in combination with radioligand binding techniques. KEY RESULTS: The majority of the IKM compounds tested reduced excitatory synaptic transmission in neuronal cultures, and IKM-159 inhibited synaptic currents from CA1 pyramidal neurons in hippocampal slices. IKM-159 inhibited glutamate-evoked whole-cell currents from recombinant GluA2- and GluA4-containing alpha-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate (AMPA) receptors most potently, whereas kainate and NMDA receptor currents were not reduced by IKM-159. Antagonism of steady-state currents was agonist concentration dependent, suggesting that its mechanism of action was competitive, although it paradoxically did not displace [(3)H]-AMPA from receptor binding sites. IKM-159 reduced spontaneous action potential firing in both cultured hippocampal neurons in control conditions and during hyperactive states in an in vitro model of status epilepticus. CONCLUSIONS AND IMPLICATIONS: IKM-159 is an AMPA receptor-selective antagonist. IKM-159 and related nitrogen heterocycles represent structurally novel AMPA receptor antagonists with accessible synthetic pathways and potentially unique pharmacology, which could be of use in exploring the role of specific populations of receptors in neurophysiological and neuropathological processes.

Immune reconstitution in HIV-1 infected patients treated for two years with highly active antiretroviral therapy

The aim of this paper was to evaluate the immune reconstitution of HIV-1 patients subjected to highly active antiretroviral therapy (HAART) for two years or more according to CD45RA and CD45RO cell count; determination of IL-2, IFN-gamma, IL-4, IL-10 and TNF-alpha serum levels; CD4+ T and CD8+ T lymphocyte count; and plasma viral load (VL) determination. For this purpose, a cross sectional study was carried out in the Tropical Diseases Area, Botucatu School of Medicine, São Paulo State University, UNESP, Botucatu, São Paulo, Brazil. Between June 2001 and April 2002, 37 HIV-1 infected patients were evaluated, 13 with treatment indication but untreated (G1), 9 subjected to HAART for 5-7 months (G2), and 15 treated for two years or more (G3); both treated groups used medication regularly and without failure. Forty-nine normal individuals were studied as controls (GC-1 and GC-2). There was a tendency (p<0.10) for the predominance of two nucleoside reverse transcriptase inhibitors (NRTI) associated with one non-nucleoside reverse transcriptase inhibitor (NNRTI) regimen in G2; and two NRTI associated with a protease inhibitor (PI) in G3. Statistical differences between groups were seen for CD45RA (G1<[G3=GC-2]; p<0.05) and CD45RO (G1[G2=G3]; p<0.001), TNF-alpha serum determination ([G1>G3; G2=intermediate]>GC-1; p<0.001), IL-2 (G1<[G2=G3=GC-1]; p<0.01), IFN-gamma ([G1=GC-1]<[GC-2=G3]; p<0.001), IL-4 and IL-10 ([G1=G2=G3]>GC-1; p<0.001), serum cytokine profiles, with a higher proportion of subtype 2 in G1 and mature subtype 0 in G2 and G3 (p<0.005). There was no statistical difference for CD8+ T lymphocyte counts (G1=G2=G3; p<0.50). Consistency was seen between positive correlations of profile 1 definer cytokines (IL-2 and IFN-gamma), CD45RA and CD45RO cells, and CD4+ T lymphocyte counts and between positive correlations of profile 2 definer cytokines (IL-4 and IL-10) with TNF-alpha, and VL. The negative correlations were also consistent as they expressed the inverse of the positives. The variables with the highest number of correlations were IL-2, IFN-gamma, and VL, followed by CD45RA and CD45RO cells, and IL-10...

Glomerular size in renal dysplasia secondary to obstructive uropathy: a further exploration of the fetal lamb model.

BACKGROUND/PURPOSE: Creating an obstructive uropathy early in glomerulogenesis would produce multicystic dysplastic kidneys (MCDK). Measuring the mean planar area of the glomeruli (GMPA) may clarify the pathogenesis of MCDK. METHODS: Fetal lambs at 60 days' gestation had their left ureter ligated and were delivered by cesarian section at 145 days' gestation. Kidney weight and length were recorded. GMPA in 3 zones (outer, middle, inner) of the sectioned kidney was measured using a computerized planimeter. The obstructed kidneys were compared with contralateral unobstructed kidneys. The unpaired Student's t test was used to determine significance. RESULTS: One ewe miscarried. Four of 5 (80%) 60-day lambs survived. All had dysplastic kidneys. Mean kidney weights were 4.3 +/- 0.84 g in MCDK and 16.8 +/- 3.6 g in controls (P< .05). The GMPA of the outer, middle, and inner zones of the MCDK were 2.7 x 10(-3) mm2, 3.2 x 10(-3) mm2, and 4.0 x 10(-3) mm2, respectively. Controls were 2.8 x 10(-3) mm2, 4.4 x 10(-3) mm2, and 6.0 x 10(-3) mm2. The glomeruli of 60-day fetal kidneys were 3.0 x 10(-3) mm2, 6.1 x 10(-3) mm2, and 11.0 x 10(-3) mm2. MCDK had smaller glomeruli in the inner and middle zones than controls. CONCLUSION: Fetal glomeruli appear to grow from the inner zone of the kidney. Early urinary tract obstruction stops this growth.

[Diagnosis--serodiagnosis of alpha herpesviruses].

Herpes simplex virus(HSV) serodiagnosis concerns type-common diagnosis and type-specific diagnosis. Primary HSV infections can be diagnosed by type-common serological assays, and in the ideal case, in combination with virus isolation. HSV type 1 and HSV type 2 are very similar except for glycoprotein G(gG). This glycoprotein can be used to determine type-specific antibodies especially during initial non-primary infections. However, antibody response to gG is late compared to the response to type-common antibodies. A rapid diagnosis of acute varicella-zoster virus(VZV) infections are often needed in clinical settings and in these situations, diagnosis is performed by methods for rapid viral detection, and not by serology. Serological tests are usually used to screen for immunity against VZV.

A technique to replicate soft tissues around fixed restoration pontics on working casts.

When missing maxillary incisors are replaced, the patient's primary concern is usually esthetics. Depending on the patient's smile line and the display of the incisors, the esthetic zone may extend to the entire clinical crown and include the surrounding soft tissue. For these patients, the appearance and form of the soft tissue at the base of the pontics is as critical as the esthetics of the incisal edges of the restoration. A technique is presented to precisely transfer the soft tissue morphology of the pontic area to the working cast. This modified master cast allows the laboratory technician to fabricate restorations that will harmonize precisely with the soft tissues of the patient.

Role of the oxygen uptake efficiency slope in evaluating exercise tolerance.

OBJECTIVE: To investigate the interprotocol agreement of oxygen uptake efficiency slope (OUES). METHODS: 16 Japanese children and adolescents (10 boys and six girls) underwent two sessions of maximal exercise testing according to the following two treadmill protocols: the standard Bruce protocol and the rapidly increasing staged (RIS) protocol. Maximal oxygen uptake (VO2max), the ventilatory anaerobic threshold (VAT), and the OUES were obtained from the gas analysis data. Agreement between the protocols was tested by means of the Bland-Altman method. RESULTS: Interprotocol agreement was excellent for the OUES (limit of agreement, -18% to 17% of the mean value), slightly less good for VO2max (limit of agreement, -20% to 24% of the mean value), and poor for the VAT (limit of agreement, -31% to 31% of the mean value). CONCLUSION: These results confirm the clinical usefulness of the OUES as a measure of evaluating exercise tolerance in the paediatric population.

Lipoxygenase-1 from soybean seed inhibiting the activity of pancreatic lipase.

There are some similar characteristics in protein nature between the lipase inhibitor from soybean seed and soybean lipoxygenase-1 (LOX-1). Thus, the inhibiting protein for pancreatic lipase was prepared from defatted soybean meal by the procedure for the isolation of LOX-1 [Axelrod et al., Methods in Enzymology, 71, 441-451 (1981)]. The LOX-1 from soybean seed dose-dependently inhibited the release of fatty acid from a soybean oil emulsion, and the concentration of LOX-1 to cause half inhibition of the lipase activity was 3.2 x 10(-7) M. The LOX-1 obtained from E. coli transfected with a plasmid carrying the soybean LOX-1 gene also inhibited the lipase activity. However, the lipase-inhibiting activity by the LOX-1 was not affected by the presence of nordihydroguaiaretic acid, an inhibitor for LOX, in the reaction mixture. These results show that the soybean LOX-1 inhibits lipase activity regardless of its lipoxygenase activity.

Ventilatory control during exercise in normal children.

We investigated the relation between age and respiratory control during exercise in 80 children aged 6.4-17.6 y (42 male, age, 11.6 +/- 3.3 y; body weight, 41.3 +/- 14.7 kg; and 38 female, age, 12.6 +/- 2.7 y; body weight, 42.5 +/- 9.3 kg). Exercise tests were performed on a treadmill after a standard symptom-limited Bruce protocol. Data were analyzed separately for boys and girls. At rest and at peak exercise, the ratio of minute ventilation to carbon dioxide production (VE/VCO2), the ratio of effective alveolar ventilation to carbon dioxide production (VA/VCO2), the ratio of pulmonary dead space to tidal volume (Vd/Vt), and arterial PCO2 (PaCO2) were not correlated with age. At the exercise intensity of ventilatory anaerobic threshold, the PaCO2 increased, and the VA/VCO2 decreased, significantly with age, whereas the Vd/Vt was not related to age. Linear regression analysis demonstrated that the slope of the relationship between VE and VCO2 (deltaVE/deltaVCO2) and the slope of the relationship between VA and VCO2 (deltaVA/deltaVCO2) decreased with age. There were no gender differences in the regression slopes and the intercepts of the relationships. Results show that younger children breathe more during exercise to eliminate a given amount of CO2 to keep PaCO2 set point slightly but significantly lower than older children. This age dependence must be considered in investigating ventilatory control during exercise in children.

Increased serum concentrations of type IV collagen and laminin associated with granulosa cell tumour of the ovary.

A 65 year old woman presented with an ovarian mass. Ultrasonography and computed tomography findings, and an increased serum oestrogen concentration were suggestive of an oestrogen producing ovarian tumour. The tumour was removed surgically and weighed 460 g. The pathological diagnosis was adult-type granulosa cell tumour. Strong immunohistochemical staining specific for type IV collagen and laminin was observed, and these components were localised to the pericellular region of the granulosa cells. The serum concentrations of these basement membrane components (measured by radioimmunoassay) were very high before surgery, but decreased rapidly thereafter. Serial measurement of type IV collagen and laminin, in conjunction with other tumour markers and oestrogen concentrations, might be helpful in evaluating prognosis of ovarian granulosa cell tumours, in detecting metastatic or recurrent lesions and in monitoring response to treatment.

[Changes in coagulation and fibrinolytic factors observed during heparin-urokinase-pulse combined therapy for nephritis resistant to conventional treatment in children].

Coagulation and fibrinolytic factors in the blood were measured during heparin-urokinase (UK)-pulse combined therapy in order to investigate the background for the availability of the therapy. Five patients with nephritis resistant to conventional treatment were treated with this combined therapy (heparin: 350-450 U/kg day, continuously i.v. during the therapy; UK: 5000 IU/kg/2 hrs, i.v., two times a day, for 3 days = 1 Kur; methylprednisolone 20 mg/kg/2hrs, d.i.v., for 3 days = 1 Kur; 3 Kurs of UK and 3 Kurs of pulse were alternately administered). 1) Blood levels of alpha 2-plasmin inhibitor (alpha 2-PI) antigen were decreased and those of alpha 2-plasmin inhibitor.plasmin complex (alpha 2-PI. PmC) were elevated during 3 Kurs of UK administration. Accordingly, activation of the fibrinolytic system was confirmed during the combined therapy, suggesting that both alpha 2-PI and alpha 2-PI.PmC were relevant in monitoring the fibrinolytic state in blood. 2) Both tissue-plasminogen activator (t-PA) and plasminogen activator inhibitor-1 (PAI-1) levels were sustained continuously in the elevated levels in the blood during both UK administration and pulse therapy. This movement of t-PA and PAI-1 was independent of that of the other fibrinolytic factors, such as alpha 2-PI,alpha 2-PI.PmC and plasminogen. 3) Inflammatory reactants such as fibrinogen, alpha 2-PI,alpha 2-macroglobulin and alpha 1-antitrypsin decreased more significantly during this heparin-urokinase-pulse combined therapy than during our previous combined therapy consisting of only heparin and urokinase. Therefore, we conclude that the anti-inflammatory effect was reinforced by adding the pulse therapy and that the combined therapy had some effect on the release of t-PA from vascular endothelial cells.

The binding site for fucose-binding proteins of Lotus tetragonolobus is a prognostic marker for transitional cell carcinoma of the human urinary bladder.

BACKGROUND: Carbohydrate signals are important in tumor metastasis. METHODS: Expression of binding sites for fucose-binding proteins (FBP) of Lotus tetragonolobus were immunohistochemically analyzed in patients with transitional cell carcinoma. RESULTS: The survival of patients with invasive bladder cancer was associated with the degree of expression of FBP binding sites. Overall actuarial 5-year survival and cancer-corrected 5-year survival rates were much worse in patients with strong expression of FBP binding sites than in those with no or weak expression (P < 0.001 and P < 0.05, respectively). Strong expression of FBP binding sites in patients with Stage T3-4 disease or disease beyond Stage T2 with lymphatic permeation also was correlated with increased disease progression. Autopsies revealed that FBP binding sites were strongly expressed in all primary tumors with metastasis and in most of the metastatic tissues. CONCLUSION: The degree of expression of FBP binding sites correlates with the increased metastatic potential of bladder cancer and with poor patient survival times.

[Analysis of the electrical charge of albumin in idiopathic nephrotic syndrome by isoelectric focusing].

The state of the electrical charge of serum and urinary albumin was investigated in both the nephrotic and remission stage of idiopathic nephrotic syndrome (INS), using isoelectric focusing (IEF). 1) Both a b2 band (a main albumin band appearing at the site of isoelectric point: pI 4.7), and a b3 band (a more anionic albumin band than the b2 band) were detected commonly in all samples of urine and serum of INS patients in nephrotic and remission stages and of healthy volunteer controls even if the applied albumin in urine and serum amounted to 20 micrograms or 100 micrograms. 2) When applied albumin amounted to 20 micrograms, b1 bands (less anionic albumin bands than the b2 band) were detected between pI 4.7 and pI 6.5 in urine and in both serum and purified albumin fractionated from serum of INS patients in the nephrotic stage. However, b1 bands were not detected at all in the urine and serum of either INS patients in remission stage and healthy volunteer controls. 3) When applied albumin amounted to 100 micrograms, b1 bands were detected also in serum of healthy volunteer controls. From these results, it was confirmed that less anionic albumin existed also in the serum of healthy volunteer controls although the amount was extremely small.(ABSTRACT TRUNCATED AT 250 WORDS)

Expression of SSEA-1 carbohydrate antigen correlates with stage, grade and metastatic potential of transitional cell carcinoma of the bladder.

Expression of stage-specific embryonic antigen-1 (SSEA-1) was immunohistochemically analyzed in primary cancerous regions from transitional cell carcinoma of the bladder. Lymph node metastasis occurred in 14 (50%) of 28 patients with high expression of SSEA-1 antigen, but in only one (4%) of 23 patients with low or no expression. Of 36 invasive bladder carcinoma patients with no metastasis at operation, 8 (57%) of 14 with high expression of SSEA-1 antigen died of cancer or had metastasis, whereas 4 (18%) of 22 with low or no expression had progression of the disease. In addition, stage pT3b-4 tumors more frequently reacted with SSEA-1 MAb than stage pT1 tumors (p less than 0.01). Grade 2 or 3 tumors were also more reactive than grade 1 tumors, which were all unreactive except for one (p less than 0.01, respectively). Our data suggest that SSEA-1, which is a Le(x) antigen, correlates with stage and grade as well as metastatic phenotype of transitional cell carcinoma of the bladder.

Reactivity to fucose-binding proteins of Lotus tetragonolobus correlates with metastatic phenotype of transitional cell carcinoma of the bladder.

Expression of binding sites for fucose binding proteins (FBP) of Lotus tetragonolobus were immunohistochemically analyzed in surgically extirpated specimens from patients with transitional cell carcinoma of the bladder. The degree of expression of FBP binding sites in the primary cancerous region correlated with the occurrence of lymph node metastasis. Thus, lymph node metastases occurred in 15 of 34 cases with high expression of FBP binding sites, but did not in 17 cases with low or no FBP binding site expression. All metastatic lymph nodes strongly reacted with FBP. In addition, primary lesions at the pT3b or pT4 stage more frequently reacted with FBP as compared with those at the pTa, pT1 or pT2 stage. Although FBP is known to react both with Gal beta 1----4(Fuc alpha 1----3)GlcNAc and Fuc alpha 1----2Gal sequences, comparative staining of other carbohydrate markers revealed that the latter structure is not related with metastatic potential and stages.

Role for "uremic toxin" in the progressive loss of intact nephrons in chronic renal failure.

We studied the effect on the progression of glomerular sclerosis of two different experimental maneuvers, peritoneal dialysis and oral adsorbent, which remove circulating substances in different fashions. Munich-Wistar rats with established glomerular sclerosis, verified by renal biopsy analysis at seven weeks after subtotal nephrectomy, were treated for four weeks with either peritoneal dialysis (PD) or oral charcoal adsorbent (AST-120). Treatment was initiated at eight weeks. Rats were paired in treatment and control groups according to the similarity in the degree of sclerosis determined at biopsy with a minimum of 50 glomeruli analyzed. Systolic blood pressure and BUN and creatinine clearance, measured at seven to eight weeks, were not different among groups. In Group 2 rats, PD was performed with 1.5% dextrose for eight one-hour cycles, six days per week, while Group 1 control rats had zero indwelling time of the dialysate. Group 4 rats received AST-120, an oral adsorbent charcoal, mixed 5% by weight with standard rat chow and given ad libitum from 8 to 12 weeks after subtotal nephrectomy, while control Group 3 rats received only rat chow. Whole kidney GFR at 12 weeks was significantly higher in Group 2 PD versus Group 1 control (0.50 +/- 0.08 vs. 0.30 +/- 0.05 ml/min, P less than 0.05). There was no statistical difference for BUN and whole kidney creatinine or inulin clearance in Group 4 AST-120 treated versus Group 3 control rats. Light microscopic studies in autopsy specimens revealed that both PD and AST-120 attenuated progression of glomerular sclerosis.(ABSTRACT TRUNCATED AT 250 WORDS)