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1.
Poult Sci ; 95(1): 53-61, 2016 Jan.
Article in English | MEDLINE | ID: mdl-26574038

ABSTRACT

The objective of this study was to investigate the effects of 1) spray dried blood cells rich in histidine and 2) pure histidine added to feed on the antioxidant status and concentration of carnosine related components in the blood and breast meat of female turkeys. The experiment was performed on 168 Big7 turkey females randomly assigned to 3 dietary treatments: control; control with the addition of 0.18% L-histidine (His); and control with the addition of spray dried blood cells (SDBC). Birds were raised for 103 d on a floor with sawdust litter, with drinking water and feed ad libitum. The antioxidant status of blood plasma and breast muscle was analyzed by ferric reducing ability (FRAP) and by 2,2-Azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) and 1,1-Diphenyl-2-picrylhydrazyl (DPPH) radicals scavenging ability. The activity of antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) was analyzed in the blood and breast meat, with the content of carnosine and anserine quantified by HPLC. Proximate analysis as well as amino acid profiling were carried out for the feed and breast muscles. Growth performance parameters also were calculated. Histidine supplementation of the turkey diet resulted in increased DPPH radical scavenging capacity in the breast muscles and blood, but did not result in higher histidine dipeptide concentrations. The enzymatic antioxidant system of turkey blood was affected by the diet with SDBC. In the plasma, the SDBC addition increased both SOD and GPx activity, and decreased GPx activity in the erythrocytes. Feeding turkeys with an SDBC containing diet increased BW and the content of isoleucine and valine in breast muscles.


Subject(s)
Anserine/metabolism , Antioxidants/metabolism , Carnosine/metabolism , Diet/veterinary , Histidine/metabolism , Meat/analysis , Turkeys/metabolism , Animal Feed/analysis , Animal Nutritional Physiological Phenomena , Animals , Anserine/blood , Blood Cells/chemistry , Carnosine/blood , Dietary Supplements/analysis , Female , Food, Preserved/analysis , Histidine/analysis , Muscle, Skeletal/chemistry , Oxidation-Reduction , Random Allocation , Turkeys/blood
2.
Acta Physiol Hung ; 101(4): 461-70, 2014 Dec.
Article in English | MEDLINE | ID: mdl-25201708

ABSTRACT

Carnosine is a dipeptide formed from the amino acids ß-alanine and histidine and found in large amounts in the brain and muscle, especially fast twitch muscle. Carnosine has an antioxidant role and accounts for about 10% of the muscle's ability to buffer the H+ ions produced by high intensity exercise. Due to the interesting role of carnosine, the aim of the study was observe the effects of carnosine intake on pro-antioxidant status in highly trained athletes exposed to intense exercise.Fourteen male athletes from the Polish national kayak and canoe teams participated in placebo-controlled and cross-over study. The athletes were supplemented with 4 g/d carnosine for 14 days. Blood samples were collected before and 30 min, 24 h and 48 h after 2000 m exercise trial. In blood, hydrogen peroxide (H2O2), nitric oxide (NO), markers of RO/NS activity 8-isoprostanes and 3-nitrotyrosine, total (GSHt) and oxidised glutathione (GSSG), antioxidant status (APO) and superoxide dismutase (SOD) were determined. There were not observed statistically significant differences in exercise-induced changes in H2O2 and NO concentrations and SOD activity after carnosine intake. However, carnosine prevented an increase in 8-isoprostanes, 3-nitrotyrosine and GSSG concentrations as well as elevated redox status (GSHt-2GSSG)/GSSG at post-exercise period.Although, oral supplementation with 4 g carnosine did not affect RO/NS generation, it significantly attenuated exercise-induced glutathione loss, reduced oxidation/nitration markers concentration and SOD activity. These results suggest that carnosine could provide antioxidative protection for highly trained athletes.


Subject(s)
Antioxidants/administration & dosage , Athletes , Carnosine/administration & dosage , Dietary Supplements , Muscle, Skeletal/drug effects , Oxidative Stress/drug effects , Physical Endurance , Biomarkers/blood , Cross-Over Studies , Dinoprost/analogs & derivatives , Dinoprost/blood , Glutathione/blood , Humans , Hydrogen Peroxide/blood , Lactic Acid/blood , Male , Muscle, Skeletal/metabolism , Nitric Oxide/blood , Poland , Superoxide Dismutase/blood , Time Factors , Tyrosine/analogs & derivatives , Tyrosine/blood , Young Adult
3.
Arch Gerontol Geriatr ; 59(2): 485-90, 2014.
Article in English | MEDLINE | ID: mdl-24880197

ABSTRACT

The aim of this study was to investigate the potential beneficial effects of dietary anserine and carnosine (CRC) supplementation on cognitive functioning and physical activity of the elderly. The fifty-six subjects (65+) were allocated to the CRC group or placebo group at a 1:1 ratio. The double-blind procedure was used. Data were collected at the baseline and after 13-weeks of supplementation. In the follow up procedure fifty one subjects took part. Chicken meat extract (CME) containing 40% of CRC components (2:1 ratio of anserine to carnosine) was administered 2.5 g per day which allowed to rich the level of 1g CRC in dipeptides supplement. The cognitive function, physical capacity, body measurements, blood pressure and heart rate (HR) were assessed. After supplementation Body Mass Index (BMI) decreased significantly (p<0.05) in the CRC group performance comparing the placebo group. In two of six Senior Fitness Test the scores increased significantly (p<0.05) in CRC group comparing to the placebo group. The perceived exertion differed significantly (p<0.05) at the baseline and after follow up at the CRC group. The mean values of the Short Test of Mental Status (STMS) scores showed the significant (p<0.04) increase only in CRC group, in the subscores of construction/copying, abstraction and recall. Conducted anserine and carnosine supplementation in the elderly brings promising effects on cognitive functioning and physical capacity of participants. However, further studies are needed.


Subject(s)
Anserine/administration & dosage , Carnosine/administration & dosage , Cognition Disorders/drug therapy , Cognition/drug effects , Dietary Supplements , Physical Fitness , Aged , Aged, 80 and over , Double-Blind Method , Female , Humans , Male , Poland , Surveys and Questionnaires , Treatment Outcome
4.
Pol J Vet Sci ; 16(2): 283-91, 2013.
Article in English | MEDLINE | ID: mdl-23971196

ABSTRACT

Aim of the study was to evaluate the effect of immunization of hens with bovine vaccines (C, R, T) on the course of IgY antibodies production against selected bovine E. coli strains, rota- and coronaviruses in egg yolk in farm conditions. The hens (40 individuals per group) were vaccinated twice, subcutaneously in four week interval and eggs were harvested once a week. Control group consisted of eggs sampled from non-vaccinated hens located in neighbouring cages. The antibody activity was measured by ELISA. All used vaccines induced the rise of IgY antibody in egg yolks. Based on the duration and the highest level of IgY antibody against bovine alimentary tract pathogens C vaccine was further used in next two trials for vaccination of 1000 hens each time. Double immunization seems to be enough in mounting response against examined pathogens for several weeks. Immunization with C vaccine allowed to harvest eggs with satisfactory levels of E. coli, rotavirus and coronavirus IgY antibodies which may be used to evaluate their protective effect by oral administration in calves.


Subject(s)
Antibodies, Bacterial/immunology , Antibodies, Viral/immunology , Egg Proteins/immunology , Escherichia coli O157/immunology , Gastrointestinal Diseases/veterinary , Rotavirus/immunology , Animals , Antibodies, Bacterial/metabolism , Antibodies, Viral/metabolism , Cattle , Coronavirus/immunology , Gastrointestinal Diseases/microbiology , Immunoglobulins/immunology , Time Factors
5.
Br Poult Sci ; 54(4): 454-65, 2013.
Article in English | MEDLINE | ID: mdl-23768017

ABSTRACT

1. The objective of this study was to investigate how a diet containing spray-dried blood cells (SDBC) (4%) with or without zinc (Zn) would affect the concentration of two histidine heterodipeptides and the antioxidant status of broiler blood and breast muscles. 2. The study was carried out on 920 male Flex chickens randomly assigned to 4 dietary treatments: I - control, II - diet I with SDBC, III - diet I with SDBC and supplemented with Zn and IV - diet I supplemented with L-histidine. Birds were raised on floor littered with wood shavings, given free access to water and fed ad libitum. Performance indices were measured on d 1, 21 and 42. 3. The activity of antioxidant enzymes superoxide dismutase, catalase and glutathione peroxidase was analysed in plasma, erythrocytes and muscle tissue. The total antioxidant capacity of plasma and breast muscles was measured by 2,2-azinobis-(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS) and 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging ability, as well as by ferric reducing antioxidant power (FRAP). Carnosine/anserine content of meat and plasma were determined using HPLC. Diets and breast muscles were analysed for amino acid profile and selected microelement content. 4. Histidine supplementation of the diet increased glutathione peroxidase activity in plasma and superoxide dismutase activity in erythrocytes. Moreover, the addition of SDBC or pure histidine in the diet increased histidine dipeptide content and activated enzymatic and non-enzymatic antioxidant systems in chicken blood and muscles. However, it led to lower growth performance indices. 5. The enrichment of broiler diets with Zn increased the antioxidant potential and the activity of superoxide dismutase in plasma, which was independent of the histidine dipeptide concentration. Zn supplementation combined with SDBC in a broiler diet led to the increase of superoxide dismutase and glutathione peroxidase activity, but it did not affect the radical-scavenging or ferric iron reduction abilities of muscles.


Subject(s)
Antioxidants/metabolism , Chickens/growth & development , Chickens/metabolism , Dipeptides/metabolism , Histidine/metabolism , Muscles/drug effects , Zinc/metabolism , Animal Feed/analysis , Animals , Diet/veterinary , Dietary Supplements/analysis , Male , Muscles/metabolism , Oxidation-Reduction , Zinc/administration & dosage
6.
J Anim Physiol Anim Nutr (Berl) ; 97(3): 586-98, 2013 Jun.
Article in English | MEDLINE | ID: mdl-22533382

ABSTRACT

One-day-old chickens were fed mixtures containing different raw materials (fish by-products meal, porcine blood cells meal, blood meal, wheat gluten, fodder yeast), as a source of histidine and ß-alanine - components of carnosine. Control birds were administered a feed mixture, in which soy bean meal was the main protein source. The bodyweight, feed consumption and conversion, antioxidant characteristics and histidine dipeptides content in blood and muscles, and also amino acid composition of chicken meat on day 34 post-hatch were recorded. The best (p < 0.05) performance and feed conversion were observed in chickens fed mixture containing porcine blood cells meal. In blood plasma of control chickens, a significantly (p < 0.01) higher ability to scavenge DPPH radicals was found. However, the highest catalase activity in erythrocytes was determined in chickens fed mixtures with blood by-products. Insignificant differences in both carnosine and anserine levels in plasma between treatments were noted. Breast muscles from control birds were characterized by lower activity of glutathione peroxidase (GPx), superoxide dismutase (SOD) and catalase (CAT) (p < 0.05; p < 0.01), than those from chickens fed blood by-products. Improved ability to reduce ferric ions (FRAP) (p < 0.01) and carnosine content in meat from chickens fed blood cell meal were recorded. No direct relations between amino acids content in feed mixtures and in meat were observed.


Subject(s)
Animal Feed/analysis , Antioxidants/metabolism , Chickens/blood , Dietary Proteins/analysis , Histidine/chemistry , Muscle, Skeletal/physiology , Animal Nutritional Physiological Phenomena , Animals , Antioxidants/chemistry , Chickens/metabolism , Diet/veterinary , Histidine/metabolism , Male
7.
Transplant Proc ; 43(8): 3000-3, 2011 Oct.
Article in English | MEDLINE | ID: mdl-21996210

ABSTRACT

INTRODUCTION: Nowadays, renal allografts continue to be lost at the rate of 2% to 4% per year beyond the first year after transplantation due to chronic allograft injury. Excessive accumulation of extracellular matrix results from overproduction and/or defective degradation by proteolytic enzymes, among which metalloproteinases (MMPs) play a major role. The aim of this study was to assess the role of MMPs in renal transplant recipients (RTR) in the context of allograft injury or proteinuria. MATERIALS AND METHODS: Plasma and urine MMP-2 and MMP-9 and tissue inhibitors of metalloproteinases (TIMPs) were assessed by enzyme-linked immunoassay in 150 RTR including 66% males with an overall mean age of 49.2±11.5 years. The subjects were examined at a mean of 73.4±41.2 months (range=12-240) after kidney transplantation. Thirty-seven healthy volunteers including 54% male with an overall mean age of 48.4±14.1 years served as a control group. RESULTS: Renal transplant recipients displayed significantly decreased plasma MMP-2 activity compared with healthy controls (P<.000) probably due to increased inhibitory plasma (p) TIMP-2 activity (P=.0029), and lower plasma MMP-2:TIMP-2 index (P<.0001). Plasma MMP-9 and pTIMP-1 activities were twofold increased in RTR compared with controls (P=.0015 and P<.000) but with a nearly stable plasma MMP-9:TIMP-1 index (P=NS). There was no difference between RTR and controls according to urine (u) MMP-2 activity, but uMMP-9 was increased in RTR compared with healthy controls (P=.0032). Urine MMP-9 potential was probably diminished by increased uTIMPs (uTIMP-2, P=.017; uTIMP-1, P=.000), which contributed to graft impairment or proteinuria. CONCLUSION: Our study revealed profibrotic MMP/TIMP constellations in RTR that show an imbalance in plasma MMP-2 and MMP-9 with increased plasma and urinary TIMPs. The net proteolytic potential of increased plasma and urinary MMP-9 may be diminished significantly by enhanced plasma and urine TIMP activities.


Subject(s)
Kidney Transplantation/adverse effects , Kidney Transplantation/physiology , Kidney/injuries , Metalloproteases/metabolism , Tissue Inhibitor of Metalloproteinases/metabolism , Adult , Case-Control Studies , Chronic Disease , Female , Fibrosis , Graft Survival/physiology , Humans , Kidney/metabolism , Kidney/pathology , Male , Matrix Metalloproteinase 2/blood , Matrix Metalloproteinase 2/urine , Matrix Metalloproteinase 9/blood , Matrix Metalloproteinase 9/urine , Middle Aged , Tissue Inhibitor of Metalloproteinase-1/blood , Tissue Inhibitor of Metalloproteinase-1/urine , Tissue Inhibitor of Metalloproteinase-2/blood , Tissue Inhibitor of Metalloproteinase-2/urine , Transplantation, Homologous
8.
Int Angiol ; 28(3): 192-201, 2009 Jun.
Article in English | MEDLINE | ID: mdl-19506538

ABSTRACT

AIM: Evidence is accumulating for endothelial cell dysfunction as one of the main factors initiating vessel wall damage in SLE. Enhanced expression of endothelial adhesion molecules is suggested to play a crucial role in the pathogenesis of vasculitis, while the number of circulating endothelial cells (CECs) is believed to be a reliable marker of endothelial damage. It therefore seems relevant to investigate CECs counts and soluble markers of endothelial dysfunction in SLE patients with inflammatory microangiopathy. The aim of this study was to assess the number of CECs, including apoptotic CECs, as well as to determine serum levels of sVCAM-1, sICAM-1 and sE-selectin in patients with SLE-related vasculitis. METHODS: The study included 51 women with SLE, divided into 2 subgroups: I patients with severe disease activity according to SLEDAI score, developing vascular complications, such as central nervous system affection and/or vasculitis and/or glomerulonephritis, II patients with mild or moderate disease activity, without vascular complications. The control group consisted of 16 healthy female volunteers. CECs, including apoptotic CECs, were isolated using anti-CD146-coated immunomagnetic Dynabeads. Serum levels of sVCAM-1, sICAM-1 and sE-selectin levels were determined with ELISA. RESULTS: In patients with SLE, CEC counts were significantly higher than in healthy controls, and strongly correlated with disease activity assessed by SLEDAI score. The number of apoptotic CECs, as compared with healthy subjects, increased considerably only in subgroup I. Serum sVCAM-1 levels were notably increased in subgroup I in relation to subgroup II and in subgroup II in relation to the control group, while serum sICAM-1 and sE-selectin levels in both subgroups were comparable and significantly higher than those of healthy subjects. CONCLUSIONS: The study showed that the number of CECs increases in SLE and strongly correlates with disease activity, reaching maximum values at the stage of inflammatory microangiopathy-related complications. Severe SLE flares are characterized by enhanced endothelial cell apoptosis. Progressive increase in serum sVCAM-1 levels is connected with disease activity aggravation and development of lupus microangiopathy.


Subject(s)
Apoptosis , Cell Adhesion Molecules/blood , Endothelial Cells/pathology , Endothelium, Vascular/pathology , Lupus Erythematosus, Systemic/complications , Vasculitis/etiology , Adolescent , Adult , Biomarkers/blood , Case-Control Studies , Cell Count , E-Selectin/blood , Endothelial Cells/metabolism , Endothelium, Vascular/metabolism , Endothelium, Vascular/physiopathology , Enzyme-Linked Immunosorbent Assay , Female , Humans , Immunomagnetic Separation , Intercellular Adhesion Molecule-1/blood , Lupus Erythematosus, Systemic/blood , Lupus Erythematosus, Systemic/pathology , Lupus Erythematosus, Systemic/physiopathology , Middle Aged , Poland , Severity of Illness Index , Vascular Cell Adhesion Molecule-1/blood , Vasculitis/blood , Vasculitis/pathology , Vasculitis/physiopathology , Young Adult
9.
Transpl Immunol ; 18(3): 203-7, 2008 Jan.
Article in English | MEDLINE | ID: mdl-18047927

ABSTRACT

Chemokines induced during an acute immune alloresponse cause cellular infiltration of the allograft. These chemokines and cells are excreted with urine. The aim of the study was to assess the diagnostic utility of urinary excretion of monocyte chemotactic peptide-1 and certain cells involved in infiltration i.e. CD3+, CD64+ and HLA-DR+ cells. The study entailed 35 patients with acute renal rejection and 65 with a stable graft function. Urinary sediments were prepared by means of cytospin and stained with anti-CD3, anti-CD64, anti-HLA-DR labeled monoclonal antibodies. Urinary expression of MCP-1 was assayed by ELISA. In the patients with acute rejection MCP-1 level was ten-fold higher than in the patients with a stable graft function (6.1+/-3.4 vs 0.6+/-0.4 ng/mg creatinine). The number of CD3+ cells was over 5 times higher than in the non-rejection patients (13.4+/-4.6 vs 2.5+/-2.2). The number of HLA-DR+ cells was 6 times higher in the acute rejection patients (15.7+/-5.9 vs 2.5+/-2.7). The number of CD64+ cells was significantly increased in the patients during an acute rejection episode (p<0.0001). CD3+, HLA-DR+ and CD64+ cell counts strongly correlated with urine excretion of MCP-1. The counts of CD3+ and HLA-DR+ cells correlated with Banff score. The assessment of MCP-1 as well as CD3+, CD64+ and HLA-DR+ cells can provide a useful non-invasive device for the diagnosis of acute rejection. A sole assay of HLA-DR+ cell excretion provides enough specificity and sensitivity for the routine monitoring of patients after kidney transplantation, saving costs and time.


Subject(s)
Chemokine CCL2/urine , Graft Rejection/diagnosis , Graft Rejection/urine , Kidney Transplantation/immunology , Urine/cytology , Adult , Aged , Biomarkers/urine , CD3 Complex/analysis , Creatinine/urine , Female , HLA-DR Antigens/analysis , Humans , Male , Middle Aged , Receptors, IgG/immunology , Receptors, IgG/metabolism
10.
Article in English | MEDLINE | ID: mdl-14535055

ABSTRACT

Prematurity is of one of the main causes of neonatal morbidity and mortality. Clinical observations show, that periodontitis in pregnant women can be a direct risk factor for preterm labor, with a greater influence rate compared to other risk factors. The aim of the study was to asses the relationship between periodontal diseases and PLBW in the population of women from the Lower Silesian Region (Poland), and the evaluation of prostaglandin E2 (PGE2), interleukin-1 beta (IL-1 beta) levels in gingival cervicular (GCF) and blood serum in women with PLBW and women giving birth on time as well as secretion of these proinflammatory mediators in whole blood after bacterial lipopolysaccharide stimulation. The study group consisted of 84 women with PLBW (39.2% primiparous), aged 17-41 (mean 27.57). The controls were 44 women (47.7% primiparous) aged 16-38 (mean 26.36) who gave birth on time to a normal birthweight baby. PGE2 and IL-1 beta concentrations in serum and GCF were determined by means of immunoenzymatic method (EIA). In the studied population women over 28 years and exposed to medical risk factors had more frequent PLBW occurrence probability. In primiparous over 28 there is 4 times greater probability of preterm labor, and in case of the severe and generalized periodontitis presence there is 3.9 times higher possibility of PLBW compared to women with healthy periodontium. In all women with PLBW there is a significantly higher PGE2 and IL-1 beta concentration in GCF, and in primiparous also PGE2 level in blood serum, compared to controls.


Subject(s)
Dinoprostone/metabolism , Infant, Low Birth Weight , Infant, Premature , Interleukin-1/metabolism , Periodontal Diseases/physiopathology , Adolescent , Adult , Case-Control Studies , Chronic Disease , Dinoprostone/blood , Female , Gingival Crevicular Fluid/metabolism , Humans , Infant, Newborn , Inflammation Mediators/blood , Inflammation Mediators/physiology , Interleukin-1/blood , Lipopolysaccharides/pharmacology , Periodontal Diseases/classification , Periodontal Index , Pregnancy , Risk Factors , Statistics, Nonparametric
12.
Res Exp Med (Berl) ; 199(5): 295-307, 2000 Apr.
Article in English | MEDLINE | ID: mdl-10815758

ABSTRACT

We have previously documented amelioration of rat autologous anti-GBM nephritis with the antiproteolytic drugs epsilon-aminocaproic acid (EACA) and aprotinin, given from the day of induction or later in the course of disease. In the present study we investigated potential mechanisms of this effect by assessing interactions of the drugs with proteinase-dependent generation of superoxide anion in glomeruli, and their influence on both GBM degradation in vitro and activity of glomerular proteolytic enzymes. Release of O2- by enzymatically disrupted glomeruli, isolated from nephritic control or EACA/aprotinin-treated rats, was measured with the ferricytochrome reduction method and its activity was correlated with proteinuria and glomerular cellularity at the early phase of the disease. The hydroxyproline release assay was used to quantitate degradation of rat GBM in vitro by leukocyte proteinases stimulated by phorbol myristate acetate (PMA), in the presence or absence of EACA and aprotinin. Finally, the activities of elastase, cathepsins B and L, and plasmin, together with collagenase-like activity, were assessed fluorimetrically in homogenates of glomeruli isolated from control and antiproteolytic-drug-treated nephritic rats. EACA and aprotinin notably inhibited production of superoxide by nephritic glomeruli (by 47% and 66%, respectively), and this effect was not significantly correlated with proteinuria or glomerular hypercellularity at the early stage of disease. On the other hand, generation of O2- by glomeruli of untreated nephritic rats was notably correlated with total glomerular cell counts and numbers of macrophages infiltrating glomeruli. PMA-stimulated neutrophils and macrophages caused degradation of isolated rat GBM in vitro, markedly attenuated in the presence of EACA (P<0.0005) and, to a lesser extent, by addition of aprotinin (P<0.01). The activity of elastase was significantly reduced in glomeruli of nephritic rats treated with EACA or aprotinin (both P<0.001), while activities of remaining proteinases were not appreciably affected. The beneficial influence of proteinase inhibitors on rat anti-GBM disease may be due, at least in part, to abrogation of superoxide generation in nephritic glomeruli. EACA and aprotinin also have potential to interfere with digestion of GBM, and both these effects may be related to suppression of glomerular elastase.


Subject(s)
Aminocaproic Acid/therapeutic use , Anti-Glomerular Basement Membrane Disease/drug therapy , Aprotinin/therapeutic use , Kidney Glomerulus/drug effects , Serine Proteinase Inhibitors/therapeutic use , Animals , Anti-Glomerular Basement Membrane Disease/metabolism , Basement Membrane/drug effects , Basement Membrane/metabolism , Endopeptidases/metabolism , Hydroxyproline/metabolism , Kidney Glomerulus/metabolism , Macrophages, Peritoneal/drug effects , Macrophages, Peritoneal/enzymology , Male , Neutrophils/drug effects , Neutrophils/enzymology , Rats , Rats, Wistar , Superoxides/metabolism
14.
Pol Arch Med Wewn ; 99(5): 390-7, 1998 May.
Article in Polish | MEDLINE | ID: mdl-9816888

ABSTRACT

We analysed the occurrence of anti-neutrophil cytoplasmic antibodies (ANCA) in sera of 191 patients with glomerulonephritis (76 females and 115 males) by the standard indirect immunofluorescence method (IIF). The presence of ANCA was demonstrated in sera of 4.4% (8/181) patients with idiopathic glomerulonephritis (GN) and in 30% (3/10) of patients with rapidly progressive glomerulonephritis (RPGN), as a form of renal limited vasculitis. In the experimental part of our study we analysed the influence of GN ANCA-negative sera on the neutrophil function in vitro and compared with the effect of ANCA-positive sera (titre > or = 4:40) from systemic vasculitis (SV) patients with renal involvement. The activation of neutrophils was established by reactive oxygen species (ROS) production and the ability of superoxide anion to reduce ferrocytochrome c. Among 30 ANCA-negative GN sera 20% (6/30) revealed the ability to activate neutrophils isolated from healthy donor. Remaining ANCA-negative GN sera and all sera from normal healthy individuals (negative control group) did not affect the neutrophil function and did not induce the superoxide anion production. Their effect was similar to the second negative reference system without serum. Only 33% (3/9) of high titre ANCA-positive sera (> or = 1:40) from SV patients were able to activate neutrophils and to produce the superoxide anion with following ferrocytochrome c reduction, but the effect of activation was most powerfully expressed (three times greater than by GN ANCA-negative sera). The remaining ANCA-positive sera and all SV ANCA-negative sera did not affect the neutrophil function in vitro. These experimental data indicate that the presence of ANCA in GN sera is not necessary to induce neutrophil activation in vitro. On the other hand the influence of the SV ANCA-positive sera was most powerful expressed, although only 33% of sera were able to activate neutrophils in vitro. Our results indicate that not always ANCA presence in serum was connected with the ability to neutrophil activation in vitro. It is possible that in ANCA-negative sera other factors were able to activate neutrophils in vitro, but the effect of activation was markedly lower.


Subject(s)
Antibodies, Antineutrophil Cytoplasmic/blood , Glomerulonephritis/immunology , Granulocytes/immunology , Vasculitis/immunology , Adult , Female , Fluorescent Antibody Technique , Humans , Lymphocyte Activation/immunology , Male
15.
J Intern Med ; 243(3): 215-22, 1998 Mar.
Article in English | MEDLINE | ID: mdl-9627159

ABSTRACT

OBJECTIVES: As tubulointerstitial damage is regarded secondary to glomerular injury in primary glomerulopathies, we assessed lesions to renal tubulointerstitium in recently diagnosed primary glomerular diseases and evaluated their impact on progression of the disease during the first 2 years after diagnosis. DESIGN: A nonrandomized prospective study assessing tubulointerstitial morphometry at diagnosis, markers of tubular function within the next 6 months and progression of the disease (creatinine clearance) during 24 months' follow-up. SETTING: Single tertiary referral centre. SUBJECTS: Forty-six patients with primary glomerular disease, the diagnostic oligobiopsy performed within 2 months of the onset of clinical symptoms. INTERVENTIONS: All patients were subjected to antiinflammatory/immunosuppressive treatment. MAIN OUTCOME MEASURES: Alterations in results of tubulointerstitial morphometry and tubular function tests, correlations between these variables and parameters of nephrosis/renal function, selection of the most accurate predictor of disease progression within 24 months after diagnostic biopsy. RESULTS: Function of proximal tubules, markedly deteriorated at the time of diagnosis, significantly improved 6 months later (urinary beta2-microglobulin: P < 0.0025), along with reduction in proteinuria (P < 0.00125). No appreciable alterations in function of distal tubules were noted. Morphometric indices revealing interstitial expansion and tubular atrophy significantly correlated with creatinine clearance at 6 months (P = 0.032) and were the best predictors of deteriorating renal function at 24 months. Excretion of beta2-microglobulin at the time of diagnosis was the best marker for impairment of glomerular filtration 6 months later. CONCLUSIONS: Significant damage to cortical tubulointerstitium occurs concurrently with glomerular injury in primary glomerulopathies and may predict the clinical course of the disease already in its initial phase.


Subject(s)
Glomerulonephritis/pathology , Kidney Glomerulus/pathology , Kidney Tubules/pathology , Adolescent , Adult , Aged , Disease Progression , Female , Glomerulonephritis/physiopathology , Humans , Kidney Function Tests , Male , Middle Aged , Prospective Studies
16.
Nephrol Dial Transplant ; 12(4): 707-12, 1997 Apr.
Article in English | MEDLINE | ID: mdl-9140998

ABSTRACT

BACKGROUND: Some preliminary observations suggest that predisposition to a particular type of glomerulonephritis (GN) may be connected with the genetically determined charge of the glomerular capillary wall. A correlation between erythrocyte surface and the glomerular capillary wall charges has also been observed. The purpose of this study was to verify and extend previous investigations. Therefore we measured erythrocyte and platelet surface charge from patients with idiopathic membranous and mesangial GN as well as idiopathic membranoproliferative GN and lupus nephritis. METHODS: The erythrocyte and platelet surface charge was determined by the binding of the cationic dye, alcian blue (AB). A fresh alcoholic AB solution was made for each experiment, which were run in batches of four, each including cells from a healthy person and from patients each with a different type of GN. RESULTS: In patients with idiopathic membranous and membranoproliferative GN, a significant decrease in the erythrocyte and platelet charges was observed irrespective of their clinical state (remission or nephrotic syndrome). Erythrocyte charge was decreased despite the normal amount of membranous sialic acid. In contrast, patients with idiopathic mesangial GN, in complete or partial remission, exhibited normal erythrocyte and platelet surface charges. Exclusively in this type of GN, the appearance of nephrotic proteinuria was associated with a slight decrease, the erythrocyte charge, which was not statistically significant (P > 0.1). A reduction in the negative erythrocyte charge in lupus nephritis was less in magnitude than in idiopathic membranous or membranoproliferative GN, and occurred independently of the level of daily proteinuria, whereas the platelet charge was normal. CONCLUSION: The decrease of the erythrocyte and platelet charge in idiopathic membranous and mebranoproliferative GN seems to be a pre-morbid feature.


Subject(s)
Blood Platelets/metabolism , Erythrocyte Membrane/metabolism , Glomerulonephritis/blood , Adolescent , Adult , Aged , Alcian Blue , Case-Control Studies , Cell Membrane/metabolism , Coloring Agents , Electrochemistry , Female , Glomerulonephritis, Membranoproliferative/blood , Glomerulonephritis, Membranous/blood , Humans , Lupus Nephritis/blood , Male , Membrane Potentials , Middle Aged , Nephrotic Syndrome/blood , Proteinuria/blood , Surface Properties
17.
Nephrol Dial Transplant ; 11(1): 32-9, 1996 Jan.
Article in English | MEDLINE | ID: mdl-8649650

ABSTRACT

BACKGROUND: Given the evidence accrued by other authors on beneficial effect of protease inhibitors on experimental immune nephritis, and following our preliminary report on abrogation of immune glomerulopathy in the rat by antifibrinolytic and antiproteolytic drug, epsilon-aminocaproic acid (EACA), we investigated the effect of this drug on the rat autologous anti-GBM nephritis. Along with the EACA we evaluated another protease inhibitor, aprotinin, an antagonist of serine proteases. METHODS: EACA (0.3g/kg) or aprotinin (5000 kallkrein inhibition units, KIU/kg) was administered intraperitoneally (t.i.d.) from day 0 (preventive protocol) or day 3 (therapeutic protocol) of autologous anti-GBM nephritis induced in Wistar rats. Proteinuria, creatinine clearance and renal histopathology were assessed as markers of disease activity, while glomerular fibrin deposits (immunoperoxidase staining) and standard parameters of coagulation/fibrinolysis of peripheral blood enabled insight into local and systemic haemostatic mechanisms. Glomerular binding of anti-GBM antibodies (immunofluorescence) and serum titres of autologus nephrotoxic antibodies (haemagglutination assay) represented conditions of immune induction of glomerulopathy. RESULTS: Our experiments indicated that EACA, and to a lesser extent also aprotinin, are capable of preventing proteinuria (EACA, reduction by 57.6%; aprotinin, reduction by 26.8%, compared to untreated nephritic rats, day 3 post-induction) and glomerular histopathological changes, without affecting endogenous creatinine clearance, otherwise depressed in this model of glomerulonephritis. More importantly, both drugs significantly ameliorated glomerular lesions and proteinuria, even when the treatment was initiated on day 3 post-induction, after the injury has begun (EACA reduced proteinuria by 32.0%, and aprotinin reduced it by 20.9% day 7). Administration of EACA and aprotinin at doses reducing glomerular injury did not cause appreciable fibrin deposition in glomeruli of nephritic rats, nor did it modify parameters of systemic coagulation and fibrinolysis in these animals, EACA and aprotinin did not interfere with serum titres of nephrotoxic antibody, nor with the intensity of its binding to the glomerular basement membrane in vivo. CONCLUSIONS: Antiproteolytic drugs utilized in our studies exert their beneficial effect on autologous anti-GBM nephritis through interference with inflammatory phase of the disease, while sparing its immune induction and mechanisms of coagulation/fibrinolysis.


Subject(s)
Aminocaproic Acid/therapeutic use , Antifibrinolytic Agents/therapeutic use , Aprotinin/therapeutic use , Glomerulonephritis/prevention & control , Proteinuria/prevention & control , Serine Proteinase Inhibitors/therapeutic use , Animals , Creatinine/metabolism , Disease Models, Animal , Dose-Response Relationship, Drug , Fibrinolysis/drug effects , Glomerulonephritis/immunology , Glomerulonephritis/metabolism , Male , Proteinuria/metabolism , Rats , Rats, Wistar
18.
Int Urol Nephrol ; 26(5): 579-86, 1994.
Article in English | MEDLINE | ID: mdl-7860209

ABSTRACT

A 64-year-old man presented with symptoms of systemic immune disease dominated by rapidly progressive glomerular injury with highly positive ANCA of cytoplasmic distribution. The clinical course was characterized by dependence upon the intensity of immunosuppression, which has finally led to development of fungal septicaemia and death. The post mortem examination revealed occult gastric cancer with regional lymphatic involvement and crescentic glomerulonephritis, while failing to substantiate clinical findings of systemic vasculitis. This is, to our knowledge, the first case of ANCA-positive glomerulonephritis accompanying visceral malignancy and as such raises the question of whether it results from a simple coincidence or a causal relationship.


Subject(s)
Adenocarcinoma/complications , Autoantibodies/analysis , Glomerulonephritis/complications , Stomach Neoplasms/complications , Adenocarcinoma/pathology , Antibodies, Antineutrophil Cytoplasmic , Glomerulonephritis/immunology , Glomerulonephritis/pathology , Humans , Kidney/pathology , Male , Middle Aged , Stomach Neoplasms/pathology
20.
Pol Arch Med Wewn ; 86(5): 290-7, 1991 Nov.
Article in Polish | MEDLINE | ID: mdl-1821024

ABSTRACT

UNLABELLED: The activity of the erythrocyte complement receptors type 1 (CR1) was measured in four groups: a control group--42 healthy persons, 18 patients with lupus nephritis (morphologic types: membranous, membranoproliferative, and proliferative), 16 patients with primary idiopathic membranous glomerulonephritis (GN), 20 patients with primary idiopathic membranoproliferative GN, and 23 chronic haemodialysis patients, in 20 of them the cause of the end-stage renal failure was primary idiopathic GN. The erythrocyte CR1 activity was determined by the immune adherence test. In the groups of the lupus nephritis and of the end-stage renal failure was observed a significant drop in erythrocyte CR1 activity. On the contrary the patients with primary idiopathic membranous and membranoproliferative GN exhibited a significantly greater erythrocyte CR1 activity than the normals. CONCLUSIONS: 1. The genetic predisposition to primary idiopathic GN is not reflected on the level of the erythrocyte CR1 system, what is distinct from the situation occurred in lupus nephritis, despite similarities in their immunopathogenesis. 2. The development of the end-stage renal failure in the course of primary idiopathic GN shows a inhibitory effect on erythrocyte CR1 activity.


Subject(s)
Complement C1/immunology , Erythrocyte Membrane/immunology , Glomerulonephritis, Membranoproliferative/blood , Glomerulonephritis, Membranous/blood , Lupus Nephritis/blood , Receptors, Complement/immunology , Adolescent , Adult , Complement C1/analysis , Female , Humans , Immune Adherence Reaction/methods , Male , Middle Aged , Receptors, Complement/analysis
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