Biomedical subjects

M A Martins

Publications and source records attributed to M A Martins.

At least 19 recordsLinked to original sources

PubMed2006

Early stages of Ascaris suum induce airway inflammation and hyperreactivity in a mouse model.

The inflammatory and functional changes that occur in murine lung after infection with 2500 infective Ascaris suum eggs were studied in this work. A sequential influx of neutrophils, mononuclear cells and eosinophils occurred into airways concomitantly with migration of larvae from liver to the lungs. Histological analysis of the lung showed a severe intra-alveolar haemorrhage at the peak of larval migration (day 8) and the most intense inflammatory cell infiltrate on day 14. Ascaris L3 were found in alveolar spaces and inside bronchioles on day 8. The number of eosinophils was elevated in the blood on days 8 and 14. The peak of eosinophil influx into the lung was at day 14, as indicated by the high levels of eosinophil peroxidase activity, followed by their migration into the airways. The antibody response against egg and larval antigens consisted mainly of IgG1 and IgM, and also of IgE and anaphylactic IgG1, that cross-reacted with adult worm antigens. Total IgE levels were substantially elevated during the infection. Measurement of lung mechanical parameters showed airway hyperreactivity in infected mice. In conclusion, the murine model of A. suum infection mimics the Th2-induced parameters observed in pigs and humans and can be used to analyse the immunoregulatory properties of this helminth.

Anaphylaxis↗

PubMed2006

Incorrect use of thromboprophylaxis for venous thromboembolism in medical and surgical patients: results of a multicentric, observational and cross-sectional study in Brazil.

OBJECTIVES: Although effective strategies for the prevention of venous thromboembolism (VTE) are widely available, a significant number of patients still develop VTE because appropriate thromboprophylaxis is not correctly prescribed. We conducted this study to estimate the risk profile for VTE and the employment of adequate thromboprophylaxis procedures in patients admitted to hospitals in the state of São Paulo, Brazil. METHODS: Four hospitals were included in this study. Data on risk factors for VTE and prescription of pharmacological and non-pharmacological thromboprophylaxis were collected from 1454 randomly chosen patients (589 surgical and 865 clinical). Case report forms were filled according to medical and nursing records. Physicians were unaware of the survey. Three risk assessment models were used: American College of Chest Physicians (ACCP) Guidelines, Caprini score, and the International Union of Angiololy Consensus Statement (IUAS). The ACCP score classifies VTE risk in surgical patients and the others classify VTE risk in surgical and clinical patients. Contingency tables were built presenting the joined distribution of the risk score and the prescription of any pharmacological and non-pharmacological thromboprophylaxis (yes or no). RESULTS: According to the Caprini score, 29% of the patients with the highest risk for VTE were not prescribed any thromboprophylaxis. Considering the patients under moderate, high or highest risk who should be receiving prophylaxis, 37% and 29% were not prescribed thromboprophylaxis according to ACCP (surgical patients) and IUAS risk scores, respectively. In contrast, 27% and 42% of the patients at low risk of VTE, according to Caprini and IUAS scores, respectively, had thromboprophylaxis prescribed. CONCLUSION: Despite the existence of several guidelines, this study demonstrates that adequate thromboprophylaxis is not correctly prescribed: high-risk patients are under-treated and low-risk patients are over-treated. This condition must be changed to insure that patients receive adequate treatment for the prevention of thromboembolism.

Anticoagulants↗

PubMed2005

Thymus involution in alloxan diabetes: analysis of mast cells.

We previously reported that alloxan-induced diabetes results in reduction in the number and reactivity of mast cells at different body sites. In this study, the influence of diabetes on thymic mast cells was investigated. Thymuses from diabetic rats showed marked alterations including shrinkage, thymocyte depletion, and increase in the extracellular matrix network, as compared to those profiles seen in normal animals. Nevertheless, we noted that the number and reactivity of mast cells remained unchanged. These findings indicate that although diabetes leads to critical alterations in the thymus, the local mast cell population is refractory to its effect. This suggests that thymic mast cells are under a different regulation as compared to those located in other tissues.

Alloxan↗

PubMed2005

Effect of salbutamol on pulmonary responsiveness in chronic pulmonary allergic inflammation in guinea pigs.

Beta-2-agonists have been widely used by asthmatic subjects to relieve their obstructive symptoms. However, there are reports that continuous use could lead to loss of bronchial protection and exacerbation of asthma symptoms. We evaluated the effect of two regimens of salbutamol administration (twice and five times a week) in a model of chronic airway inflammation in male Hartley guinea pigs (protocol starting weight: 286 +/- 30 g) induced by repeated exposures to aerosols of ovalbumin (OVA). After sensitization, guinea pigs were exposed to aerosols of 0.1 mg/ml salbutamol solution twice a week (OVA + S2x, N = 7) or five times a week (OVA + S5x, N = 8). We studied allergen-specific (OVA inhalation time) and -nonspecific (response to methacholine) respiratory system responsiveness. Seventy-two hours after the last OVA challenge, guinea pigs were anesthetized and tracheostomized, respiratory system resistance and elastance were measured and a dose-response curve to inhaled methacholine chloride was obtained. Specific IgG1 was also quantified by the passive cutaneous anaphylactic technique. OVA-sensitized guinea pigs (N = 8) showed reduction of the time of OVA exposure before the onset of respiratory distress, at the 5th, 6th and 7th exposures (P < 0.001). The OVA + S2x group (but not the OVA + S5x group) showed a significant increase in OVA inhalation time. There were no significant differences in pulmonary responsiveness to methacholine among the experimental groups. OVA + S2x (but not OVA + S5x) animals showed a decrease in the levels of IgG(1)-specific anaphylactic antibodies compared to the OVA group (P < 0.05). Our results suggest that, in this experimental model, frequent administration of beta(2)-agonists results in a loss of some of their protective effects against the allergen.

Adrenergic beta-Agonists↗

PubMed2005

A novel hot-plate test sensitive to hyperalgesic stimuli and non-opioid analgesics.

It is widely accepted that the classical constant-temperature hot-plate test is insensitive to cyclooxygenase inhibitors. In the current study, we developed a variant of the hot-plate test procedure (modified hot-plate (MHP) test) to measure inflammatory nociception in freely moving rats and mice. Following left and right hind paw stimulation with a phlogogen and vehicle, respectively, the animals were placed individually on a hot-plate surface at 51 degrees C and the withdrawal latency for each paw was determined simultaneously in measurements performed at 15, 60, 180, and 360 min post-challenge. Plantar stimulation of rats (250 and 500 microg/paw) and mice (125-500 microg/paw) with carrageenan led to a rapid hyperalgesic response of the ipsilateral paw that reached a plateau from 15 to 360 min after challenge. Pretreatment with indomethacin (4 mg/kg, i.p.) inhibited the phenomenon at all the times analyzed. Similarly, plantar stimulation of rats and mice with prostaglandin E2 (0.5 and 1 microg/paw) also resulted in rapid hyperalgesia which was first detected 15 min post-challenge. Finally, we observed that the MHP test was more sensitive than the classical Hargreaves' test, being able to detect about 4- and 10-fold lower doses of prostaglandin E2 and carrageenan, respectively. In conclusion, the MHP test is a simple and sensitive method for detecting peripheral hyperalgesia and analgesia in rats and mice. This test represents a low-cost alternative for the study of inflammatory pain in freely moving animals.

Animals↗

PubMed2005

Chelating effect of novel pyrimidines in a model of aluminum intoxication.

Long time ago aluminum (Al) was considered as a non-toxic element and its use had no restrictions. However, over the last two decades, scientific publications have indicated that Al is a toxic element. In line with this, aluminum accumulation in the organism is associated with a variety of human pathologies. Efficient therapeutics approach to treat Al intoxication are still not available, but there is a consensus that chelation therapy is the procedure to be used. However, the development of new chelating agents are highly desirable to improve the efficacy of the treatment of Al intoxication. The present study evaluates the chelating effect of two novel pyrimidines: 4-tricloromethyl-1-H-pyrimidin-2-one (THP) and (4-methyl-6-trifluoromethyl-6-pyrimidin-2-il)-hydrazine (MTPH) in a mice model of aluminum intoxication and compares their efficacy with those of desferrioxamine (DFO), a classical agent used for treat Al accumulation. The animals were exposed to aluminum by gavage (0.1 mmol aluminum/kg/day) 5 days/week for 4 weeks. At the end of this period, DFO was injected i.p. and the novel pyrimidines were given by gavage at 0.2 mmol/kg/day for five consecutive days. Aluminum concentration in tissues (brain, liver, kidney and blood) was determined by graphite furnace atomic absorption spectroscopy (GFAAS). The results showed that when administered by gavage, aluminum accumulated in the brain, kidney and liver of mice. MTPH was able to decrease aluminum levels in aluminum plus citrate animal groups, whereas THP was inefficient for this purpose. However, the novel pyrimidines used in this study were unable to surpass the aluminum chelating property of DFO. Thus, new studies must be performed utilizing other chelating agents which can decrease aluminum toxicity.

Aluminum↗

PubMed2005

Modulation of murine experimental asthma by Ascaris suum components.

BACKGROUND: We have recently isolated two distinct components from Ascaris suum adult worms with different effects on the immune system: the allergenic protein of A. suum (APAS-3), which induces IgE antibody production, and suppressive protein of A. suum (PAS-1), which inhibits humoral and cellular immune responses induced by unrelated antigens. In this study, we investigated the immunomodulatory effect of PAS-1 on a murine model of asthma induced by APAS-3. METHODS: BALB/c mice were immunized twice with APAS-3 or APAS-3 plus PAS-1 by the intraperitoneal and subcutaneous route (on days 0 and 7) and challenged twice with the same antigens intranasally (days 14 and 21). Two days after the last challenge, the allergic airway inflammation was evaluated by cellular migration, eosinophil peroxidase (EPO) activity, cytokine and chemokine production and pulmonary mechanical parameters. RESULTS: The allergenic properties of APAS-3 were confirmed by the stimulation of anaphylactic IgE and IgG1 antibody production and eosinophilic airway inflammation and hyper-responsiveness. On the other hand, PAS-1-treated mice showed a marked suppression of cellular migration and EPO activity that correlated well with a significant reduction in the levels of IL-4, IL-5, eotaxin and RANTES in the bronchoalveolar lavage (BAL) fluid. In contrast, considerable amounts of IL-10 were observed in the BAL fluid of PAS-1-treated mice. Airway hyper-responsiveness was obtained in APAS-3-immunized mice, but the conductance of the respiratory system was restored to normal values in the presence of PAS-1. CONCLUSION: These results indicate that A. suum allergenic protein APAS-3 induces a T helper 2-type immune response and, consequently, eosinophilic airway inflammation and hyper-responsiveness. Moreover, the modulatory protein PAS-1 has a marked suppressive effect on this response, and the inhibition of cytokine (IL-4, IL-5) and chemokine (eotaxin and RANTES) release, probably because of the presence of IL-10, may contribute to this effect.

Allergens↗

PubMed2005

Pulmonary amoebiasis presenting as superior vena cava syndrome.

Pulmonary amoebiasis without liver involvement occurs sporadically as a result of haematogenous spread from a primary site, the colon. The case history is presented of a patient who developed superior vena cava syndrome due to a pulmonary amoebic abscess without liver involvement. He was initially suspected of having a neoplasm but a combination of tests including histological examination of the H&E stained excised tissue, immunofluorescence using anti-Entamoeba histolytica antibodies, and serology confirmed the diagnosis of amoebiasis. To our knowledge this is the first description of pulmonary amoebiasis presenting as superior vena cava syndrome.

Adult↗

PubMed2004

Patient and physician evaluation of the severity of acute asthma exacerbations.

We studied the ability of patients not experienced in the use of peak expiratory flow meters to assess the severity of their asthma exacerbations and compared it to the assessment of experienced clinicians. We also evaluated which data of physical examination and medical history are used by physicians to subjectively evaluate the severity of asthma attacks. Fifty-seven adult patients (15 men and 42 women, with a mean (+/- SD) age of 37.3 +/- 14.5 years and 24.0 +/- 17.9 years of asthma symptoms) with asthma exacerbations were evaluated in a University Hospital Emergency Department. Patients and physicians independently evaluated the severity of the asthma attack using a linear scale. Patient score, physician score and forced expiratory volume at the first second (FEV1) were correlated with history and physical examination variables, and were also considered as dependent variables in multiple linear regression models. FEV1 correlated significantly with the physician score (rho = 0.42, P = 0.001), but not with patient score (rho = 0.03; P = 0.77). Use of neck accessory muscles, expiratory time and wheezing intensity were the explanatory variables in the FEV1 regression model and were also present in the physician score model. We conclude that physicians evaluate asthma exacerbation severity better than patients and that physician's scoring of asthma severity correlated significantly with objective measures of airway obstruction (FEV1). Some variables (the use of neck accessory muscles, expiratory time and wheezing intensity) persisted as explanatory variables in physician score and FEV1 regression models, and should be emphasized in medical schools and emergency settings.

Acute Disease↗

PubMed2004

Comparison of glucocorticoid and cysteinyl leukotriene receptor antagonist treatments in an experimental model of chronic airway inflammation in guinea-pigs.

BACKGROUND: Leukotriene receptor antagonists have been demonstrated in several studies to possess bronchodilating and anti-inflammatory properties in asthma. However, there are few experimental studies performed to compare the effects of anti-leukotrienes and glucocorticoids, most used anti-inflammatory agents in asthma. In the present study, we evaluated the effects of treatment with dexamethasone or montelukast on eosinophil and mononuclear cell recruitment in an experimental model of allergen-induced chronic airway inflammation in guinea-pigs (GP). METHODS: GP were submitted to increasing concentrations of aerosols of ovalbumin (OVA) twice a week for 4 weeks. After 2 weeks, animals were treated daily with dexamethasone, montelukast or saline solution. After this period, GP were anaesthetized, tracheostomized, mechanically ventilated and challenged with OVA aerosol. RESULTS: Maximal changes of respiratory system resistance and elastance induced by OVA challenge were attenuated by dexamethasone (P<0.001), but not by montelukast treatment. Neither dexamethasone nor montelukast significantly influenced bronchial oedema formation. Dexamethasone but not montelukast induced a decrease in mononuclear cells in airways (P<0.001). Eosinophil infiltration in the bronchial wall was reduced by both dexamethasone and montelukast (P<0.005). Only dexamethasone treatment reduced the levels of exhaled nitric oxide (P<0.025). CONCLUSION: Although leukotriene receptor antagonist treatment reduces eosinophil accumulation induced by multiple antigen challenges, glucocorticoid treatment attenuates both eosinophil and mononuclear cell infiltration.

Acetates↗

PubMed2004

Influence of socioeconomic conditions on air pollution adverse health effects in elderly people: an analysis of six regions in São Paulo, Brazil.

STUDY OBJECTIVE: To evaluate if the effects of particulate matter (PM(10)) on respiratory mortality of elderly people are affected by socioeconomic status. DESIGN: Time series studies. The daily number of elderly respiratory deaths were modelled in generalised linear Poisson regression models controlling for long term trend, weather, and day of the week, from January 1997 to December 1999, in six different regions of São Paulo City, Brazil. The regions were defined according to the proximity of air pollution monitoring stations. Three socioeconomic indicators were used: college education, monthly income, and housing. MAIN RESULTS: For a 10 micro g/m(3) increase in PM(10), the percentage increase in respiratory mortality varied from 1.4% (95% CI 5.9 to 8.7) to 14.2% (95% CI 0.4 to 28.0). The overall percentage increase in the six regions was 5.4% (95% CI 2.3 to 8.6). The effect of PM(10) was negatively correlated with both percentage of people with college education and high family income, and it was positively associated with the percentage of people living in slums. CONCLUSIONS: These results suggest that socioeconomic deprivation represents an effect modifier of the association between air pollution and respiratory deaths.

Aged↗

PubMed2004

Down-regulation of mast cell activation and airway reactivity in diabetic rats: role of insulin.

Hormones play a modulating role in allergic inflammation. An inverse relationship between atopy and diabetes mellitus was reported. The mechanisms regulating this interaction are not completely understood. This study examined whether insulin influences mast cell activation following antigen challenge in rats. The experimental design included alloxan-induced diabetic rats and matching controls. Experiments were performed 30 days after alloxan injection. The animals were sensitised by s.c. injection of ovalbumin (OA) and aluminium hydroxide. OA-induced airway contraction, morphometric analysis of airway mast cells and tissue histamine quantification were evaluated in the isolated main bronchus and intrapulmonary bronchus upon exposure to antigen in vitro. Relative to controls, a reduced contraction to OA was observed in bronchial segments isolated from diabetic rats. This was accompanied by a 50% reduction in the number of degranulated mast cells and in histamine release. A complete recovery of the impaired responses was observed under the influence of insulin. In conclusion, the data suggested that insulin might modulate the controlling of mast cell degranulation; therefore, the early-phase response to antigen provocation, which represents a new insight into a better understanding of the mechanisms, accounted for the decreased risk of asthma among type-1 diabetic patients.

Animals↗

PubMed2003

Immunoglobulin E is not required for but enhances airway inflammation and hyperresponsiveness.

The aim of this study was to investigate the role of immunoglobulin E (IgE) in the late phase reaction (LPR) of murine experimental asthma. Our model consisted of an implant of DNP-conjugated, heat-coagulated hen's egg white (DNP-EWI), followed 14 days later by an intratracheal challenge with aggregated DNP-ovalbumin. Airway inflammation was analyzed 48 h after challenge and compared with a similarly immunized group of mice with highly suppressed humoral response due to anti-micro and anti-delta antibody treatment. Total number of cells in the bronchoalveolar lavage (BAL) (with predominance of eosinophils) and EPO activity in the lung homogenate were increased in the DNP-EWI-immunized group compared with immunosuppressed or nonimmunized mice. However, the cellular infiltration and EPO activity observed in the immunosuppressed group were still significantly above those obtained in the nonimmunized group, indicating that inhibition of antibody production did not completely prevent the inflammatory manifestations in BAL and lung. Airway hyperresponsiveness to methacoline was obtained in DNP-EWI-immunized mice, but the respiratory mechanical parameters returned to normal levels in the immunosuppressed group. When these mice were reconstituted with monoclonal anti-DNP antibodies, only IgE, but not IgG1, restored lung inflammation and decreased the conductance of the respiratory system, therefore, increasing hyperresponsiveness. These results indicate that antibodies are not essential for induction of LPR in the lung. However, IgE enhances pulmonary inflammation and hyperresponsiveness.

Animals↗

PubMed2003

Impact of clinical experience on quantification of clinical signs at physical examination.

PURPOSE: Although physical examination is a fundamental component of medical decision making, relatively few studies have evaluated how physicians quantify clinical signs and whether different methods of assessment have different effects on clinical practice. OBJECTIVES: To evaluate a possible impact of clinical experience when attending physicians, medical residents and medical students quantify qualitative signs of physical examination in a teaching hospital. SETTING: Hospital das Clínicas, University of São Paulo, Brazil. SUBJECTS: A total of 244 randomly selected physicians and medical students completed a reliable and consistent eight-item questionnaire. MAIN OUTCOME MEASURES: To compare how they quantified clinical signs of cyanosis, anaemia, jaundice, oedema and dehydration, why they used the method(s) they described, and whether the method used could affect diagnosis, further testing or patient management. A chi-square test was used to calculate differences between the groups. RESULTS: Whilst the majority of those surveyed tended to use a four-level evaluation for these clinical signs, attending staff physicians were more likely to employ two-level evaluations than were residents or medical students. For all five signs, attending physicians' use of dichotomous evaluations was significantly higher than that of residents or medical students: anaemia (P = 0.004), cyanosis (P < 0.001), oedema (P = 0.005), dehydration (P < 0.001) and jaundice (P = 0.002). CONCLUSION: Although medical students and residents are routinely taught to use a four-level evaluation for these clinical signs, many of those surveyed tend to abandon this experience for a dichotomous approach. Given that the clinicians in this survey tended not to change their initial approach to a patient based on the intensity of this semi-quantitative method, increased emphasis on teaching dichotomous approach evaluations in medical school should be encouraged.

Brazil↗

PubMed2003

Kinetics of eosinophil and IgE-mast cell changes following infection with Angiostrongylus costaricensis in Wistar rats.

Human abdominal angiostrongyliasis is a severe eosinophilic disease caused by Angiostrongylus costaricensis. Previous studies have demonstrated that wild rodents are critically involved as definitive hosts to this nematode in nature. In this study, we have evaluated the susceptibility of Wistar rats (Rattus norvegicus) to A. costaricensis infection. Kinetics of parasitological and pathological changes, including the number of adult worms recovered from mesenteric arteries, and of IgE, mast cell and eosinophil levels in several compartments have been assessed. The oral inoculation of third-stage larvae (L3) into adult Wistar rats led to a marked accumulation of worms in the branches of the mesenteric arteries 25 and 50 days post-inoculation. Intense bone marrow eosinophilia ranging from 7 to 50 days was accompanied by marked accumulation of eosinophils in the blood, peritoneal and bronchoalveolar spaces. Eosinophilic periarteritis, oedema and granuloma in the intestinal and lung tissues were also histologically evident. Total serum IgE and specific anti-parasite IgE peaked at 25 days post-infection, as measured by ELISA and by the passive cutaneous anaphylaxis test, respectively. At that time point, there was a drastic reduction in the number of intact mast cells in the peritoneal effluent. These findings indicate that Wistar rats are permissive to A. costaricensis infection. IgE-mast cell activation and massive tissue eosinophil infiltration are marked features in the process and are likely to play a crucial role in the immune-response evoked by this parasite.

Angiostrongylus↗

PubMed2002

Exhaled nitric oxide collected with two different mouthpieces: a study in asthmatic patients.

Techniques for collecting exhaled nitric oxide (ENO) recommend the use of antibacterial filters of 0.3 m. The aim of the present study was to compare the measurements of ENO obtained with two different filtering devices. Air samples from 17 asthmatic and 17 non-asthmatic subjects were collected by a recommended off-line technique using two different mouthpieces: 1) the Sievers disposable tool (A) under a breathing pressure of 18 cmH2O, and 2) a mouthpiece containing a HEPA filter (B) under a breathing pressure of 12 cmH2O. The nitric oxide samples were collected into an impermeable reservoir bag. Values for ENO were compared using two-way repeated measures ANOVA followed by the Tukey test. Agreement was assessed by Bland-Altman analysis. ENO values obtained with mouthpieces A and B were comparable for asthmatic (mean +/- SEM, 42.9 +/- 6.9 vs 43.3 +/- 6.6 ppb) and non-asthmatic (13.3 +/- 1.3 vs 13.7 +/- 1.1 ppb) subjects. There was a significant difference in ENO between asthmatics and non-asthmatics using either mouthpiece A (P<0.001) or B (P<0.001). There was a positive correlation between mouthpiece A and mouthpiece B for both groups. The Bland-Altman limits of agreement were considered to be acceptable. Mouthpiece B was less expensive than A, and these data show that it can be used without compromising the result. Our data confirm reports of higher ENO values in the presence of airway inflammation.

Analysis of Variance↗

PubMed2002

Eosinophilic inflammation and airway hyper-responsiveness are profoundly inhibited by a helminth (Ascaris suum) extract in a murine model of asthma.

BACKGROUND: The increase of atopic disorders in developed countries has been associated with the decline of infectious diseases, including helminthic infections. We have already demonstrated that adult worm extracts from Ascaris suum (ASC) suppress the IgE antibody production against unrelated antigens. OBJECTIVE: Here we investigated the influence of ASC on the development of pulmonary eosinophilic inflammation in a murine model of asthma. METHODS: Heat-coagulated egg white alone (EWI) or mixed with ASC (EWI + ASC) was implanted subcutaneously in B10.A or C57BL/6 mice, and 14 days later they were challenged intratracheally with OVA or exposed to aerosolized OVA for 4 days. RESULTS: The suppressive effect of ASC was demonstrated on the accumulation of cells into airways, with reduction of eosinophil numbers and of eosinophil peroxidase activity in EWI + ASC-immunized mice. This effect correlated with a marked reduction of IL-5 and IL-4 levels in the BAL from C57BL/6 and B10. A mice, respectively, and of eotaxin in BAL and lung tissue from both strains. OVA-specific IgG1 and IgE levels were also impaired in serum and BAL from these mice. Airway hyper-reactivity to methacholine was obtained in B10. A mice sensitized with EWI, but the respiratory mechanical parameters returned to normal levels in EWI + ASC-immunized mice. CONCLUSION: These results indicate that ASC has a profound inhibitory effect on lung inflammation and hyper-responsiveness and that suppression of IL-5 or IL-4 and of eotaxin contributes to this effect.

Animals↗

PubMed2002

C-ANCA-positive IgG fraction from patients with Wegener's granulomatosis induces lung vasculitis in rats.

The aim of the present study was to analyse in rats the ability of C-ANCA-positive IgG fraction in triggering inflammatory response on pulmonary tissue. Wistar rats (n = 18) were injected via the the internal jugular vein with 20 mg of total C-ANCA-positive IgG fraction isolated from serum of three different Wegener's granulomatosis patients obtained before therapy. Similarly, control rats were treated with IgG fraction from two rheumatoid arthritis patients (n = 7), IgG from six normal human sera (n = 15) or saline (n = 18), respectively. Animals were sacrificed after 24h of injection for histological analysis of the lungs. Vasculitis and inflammatory infiltrate were consistently absent in rats injected with rheumatoid arthritis IgG or saline and in 14/15 of normal IgG treated animals. In contrast, marked vasculitis was observed in all 18 animals injected with C-ANCA-positive IgG fraction. The histological features were characterized by the presence of a perivascular pleomorphic cellular sheath, particularly around small vessels, endothelial adherence and diapedesis of polymorphonuclear leucocytes and presence of granuloma-like lesions. A dose-response relationship was observed between protein concentration of C-ANCA IgG sample and the intensity of the inflammatory response in the animals. In addition, IgG fraction with undetectable C-ANCA, obtained from one patient in remission after treatment, was not able to reproduce the pulmonary tissue alterations induced by its paired IgG that was positive for C-ANCA taken before therapy. The experimental model described herein may be useful to characterize more effectively the pathogenic mechanism of C-ANCA in Wegener's disease.

Adult↗