Biomedical subjects

M M Teixeira

Publications and source records attributed to M M Teixeira.

At least 37 records · Page 2Linked to original sources

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

Leukotriene B(4) induces nitric oxide synthesis in Trypanosoma cruzi-infected murine macrophages and mediates resistance to infection.

The production of nitric oxide (NO) by gamma interferon (IFN-gamma)-activated macrophages is a major effector mechanism during experimental Trypanosoma cruzi infection. In addition to IFN-gamma, chemoattractant molecules, such as platelet-activating factor (PAF) and CC chemokines, may also activate macrophages to induce NO and mediate the killing of T. cruzi in an NO-dependent manner. Here we investigated the ability of leukotriene B(4) (LTB(4)) to induce the production of NO by macrophages infected with T. cruzi in vitro and whether NO mediated LTB(4)-induced parasite killing. The activation of T. cruzi-infected but not naive murine peritoneal macrophages with LTB(4) induced the time- and concentration-dependent production of NO. In addition, low concentrations of LTB(4) acted in synergy with IFN-gamma to induce NO production. The NO produced mediated LTB(4)-induced microbicidal activity in macrophages, as demonstrated by the inhibitory effects of an inducible NO synthase inhibitor. LTB(4)-induced NO production and parasite killing were LTB(4) receptor dependent and were partially blocked by a PAF receptor antagonist. LTB(4) also induced significant tumor necrosis factor alpha (TNF-alpha) production, and blockade of TNF-alpha suppressed LTB(4)-induced NO release and parasite killing. A blockade of LTB(4) or PAF receptors partially inhibited IFN-gamma-induced NO and TNF-alpha production but not parasite killing. Finally, daily treatment of infected mice with CP-105,696 was accompanied by a significantly higher level of blood parasitemia, but not lethality, than that seen in vehicle-treated animals. In conclusion, our results suggest a role for LTB(4) during experimental T. cruzi infection. Chemoattractant molecules such as LTB(4) not only may play a major role in leukocyte migration into sites of inflammation in vivo but also, in the event of an infection, may play a relevant role in the activation of recruited leukocytes to kill the invading microorganism in an NO-dependent manner.

Animals↗

PubMed2002

Temozolomide in second-line treatment after prior nitrosurea-based chemotherapy in glioblastoma multiforme: experience from a Portuguese institution.

Temozolomide is a new cytotoxic alkylating agent that has recently been approved in Portugal for the treatment of recurrent high-grade glioma. From September 1999 to March 2001, 16 patients with recurrent glioblastoma multiforme who had prior nitrosurea-based chemotherapy [procarbazine, carmustine, vincristine (PCV)] were given temozolomide 150-200 mg/m2/day for 5 days every 28-day cycle. The estimated 1-year survival rate was 16% and the median overall survival was 6.5 months. Despite the small sample size, the overall survival achieved with temozolomide was similar to that of other reports. These promising data suggest that randomized trials should be undertaken to assess its use in first-line therapy its inclusion in combined chemotherapy regimes and its effectiveness with concurrent radiotherapy.

Adult↗

PubMed2001

Blockade of PAF receptors controls interleukin-8 production by regulating the activation of neutrophil CD11/CD18.

The production of interleukin-8 by neutrophils in response to particulate stimuli may play a role in the recruitment and activation of further neutrophils in an inflammatory reaction. Here, we have evaluated the sequence of early events leading to interleukin-8 production by phagocytosing neutrophils. Kinetic experiments showed that the phagocytosis of zymosan particles by human neutrophils was rapid in onset. In contrast, interleukin-8 production was more protracted and only detectable 6 h later. Nevertheless, inhibition of phagocytosis with cytochalasins B or D suppressed the late interleukin-8 production. Activation of neutrophils with zymosan failed to enhance CD11/CD18 expression on the neutrophil surface but led to an increase in the expression of an activation-dependent epitope on CD11/CD18. Pretreatment with the platelet-activating factor (PAF) receptor antagonist, UK-74505 (4-(2-chlorophenyl)-1,4-dihydro-3-ethoxycarbonyl-6-methyl-2-[4-(2-methylimidazol[4,5-c]pyrid-1-yl)phenyl]-5-[N-(2-pyridyl)carbamoyl]pyridine), significantly blocked the increase in the expression of the activation epitope, resulting in inhibition of the phagocytosis of zymosan and interleukin-8 production. In conclusion, the activation of neutrophils with zymosan leads to the activation of PAF receptors and this is followed by activation of CD11/CD18, phagocytosis of zymosan particles and subsequent interleukin-8 release.

CD11 Antigens↗

PubMed2001

Classification of trypanosomatids from fruits and seeds using morphological, biochemical and molecular markers revealed several genera among fruit isolates.

Trypanosomatids are widespread in several plant families and although most isolates have been classified as Phytomonas, other trypanosomatid genera can also infect plants. In order to assess the natural occurrence of non-Phytomonas trypanosomatids in plants we characterized 21 new trypanosomatid cultures, 18 from fruits and three from seeds of 17 plant species. The trypanosomatids from fruit and seeds were compared in terms of morphological, growth, biochemical and molecular features. The high diversity among the isolates permitted the classification of the new flagellates into the genera Crithidia and Leptomonas as well as Phytomonas. The data showed that natural fruit infection with non-Phytomonas trypanosomatids is more common than usually thought, being detected in 43% of the fruit isolates.

Animals↗

PubMed2001

Stem cell factor-induced leukotriene B4 production cooperates with eotaxin to mediate the recruitment of eosinophils during allergic pleurisy in mice.

The understanding of the mechanisms underlying eosinophil recruitment in vivo may aid in the development of novel strategies for the treatment of allergic disorders. In this study, we investigated the role of chemokines in the cascade of events leading to eosinophil recruitment in a stem cell factor (SCF)- and leukotriene B(4) (LTB(4))-dependent allergic pleurisy model in mice. The intrapleural administration of the eosinophil-active chemokines eotaxin, RANTES, and macrophage-inflammatory protein 1alpha (MIP-1alpha) induced a time- and dose-dependent eosinophil recruitment. Pretreatment with anti-eotaxin, but not anti-RANTES or anti-MIP-1alpha, blocked the recruitment of eosinophils following Ag challenge of sensitized animals, and significant eotaxin immunoreactivity was detected in the pleural cavity of these animals. Similarly, only the anti-eotaxin inhibited the eosinophil recruitment induced by injection of SCF in naive animals. However, blockade of SCF did not inhibit the release of eotaxin after Ag challenge of sensitized mice. Akin to its effects on SCF and in the allergic reaction, eotaxin-induced eosinophil recruitment was blocked by the LTB(4) receptor antagonist CP105696. Nevertheless, SCF, but not eotaxin, appeared to regulate the endogenous release of LTB(4) after Ag challenge. Finally, we show that low doses of eotaxin synergized with LTB(4) to induce eosinophil recruitment in the pleural cavity. Overall, the present results show that eotaxin and SCF-induced LTB(4) cooperate to induce eosinophil recruitment into sites of allergic inflammation. Cooperation between inflammatory mediators must be an important phenomenon in vivo, explaining both the ability of lower concentrations of mediators to induce a full-blown functional response and the effectiveness of different strategies at inhibiting these responses.

Animals↗

PubMed2001

Cardiac autonomic denervation and functional response to neurotoxins during acute experimental Chagas' disease in rats.

Severe cardiac autonomic denervation occurs in the acute Chagas' disease in rats. The present study aims at verifying whether this denervation was accompanied by impairment of heart function. Scorpionic (Tityus serrulatus) crude venom was used for neurotransmitter release in isolated hearts (Langendorff's preparation). In control hearts, the venom induced significant bradycardia followed by tachycardia. In infected animals, despite the severe (sympathetic) or moderate (parasympathetic) cardiac denervation, the venom provoked similar bradycardia but the tachycardia was higher. The hearts of infected animals beat at significantly lower rate. Atropine prevented this lower rate. Our results demonstrated sympathetic dysfunction during the acute phase of Trypanosoma cruzi infection in rats, the parasympathetic function being spared.

Acetylcholine↗

PubMed2001

Trypanosoma vivax: characterization of the spliced-leader gene of a Brazilian stock and species-specific detection by PCR amplification of an intergenic spacer sequence.

The sequence of the spliced-leader gene repeat of a Brazilian Trypanosoma vivax stock from cattle showed high similarity to sequences of West African T. vivax in both intron and intergenic sequences. This is the first evidence based on DNA sequences of close-relatedness between Brazilian and West African T. vivax stocks. A T. vivax-specific diagnostic PCR assay based on spliced-leader gene intergenic sequences was able to amplify DNA from T. vivax stocks from South America (Brazil, Bolivia, and Colombia) and West Africa. Species-specificity of this method was confirmed by results obtained by testing 15 other trypanosomes, including other species and subspecies that can also infect cattle. The PCR assay developed presented high sensitivity, detecting the DNA content of only one parasite and also revealing T. vivax infection in asymptomatic animals without detectable parasitemia by microhematocrit or in Giemsa-stained blood smears. Use of crude preparations from field-blood samples collected on both filter paper and glass slides as DNA template suggested that this method could be useful for the diagnosis of T. vivax in large epidemiological studies.

Animals↗

PubMed2001

Modulation of chemokine production and inflammatory responses in interferon-gamma- and tumor necrosis factor-R1-deficient mice during Trypanosoma cruzi infection.

Infection with Trypanosoma cruzi causes a strong inflammatory reaction at the inoculation site and, later, in the myocardium. The present study investigates the role of cytokines as modulators of T. cruzi-induced chemokine expression in vivo and in vitro. In macrophage cultures, although the stimulation with interferon (IFN)-gamma increases the expression of IP-10, it blocks KC expression. Tumor necrosis factor (TNF)-alpha, on the other hand, potentiates KC, IP-10, macrophage inflammatory protein-1alpha, and JE/monocyte chemotatic protein-1 expression. Interleukin-10 and transforming growth factor-beta inhibited almost all chemokines tested. The role of IFN-gamma and TNF-alpha in chemokine modulation during infection was investigated in T. cruzi-infected IFN-gamma-deficient (GKO) or TNF-R1/p55-deficient (p55-/-) mice. The expression of chemokines detected in the inoculation site correlated with the infiltrating cell type observed. Although GKO mice had a delayed and intense neutrophilic infiltrate correlating with the expression of KC and macrophage inflammatory protein-2, none of the above was observed in p55-/- mice. The detection of infiltrating T cells, Mig, and IP-10 in the myocardium was observed in wild-type and p55-/-, but not in GKO mice. Together, these results suggest that the regulatory roles of IFN-gamma and TNF-alpha on chemokine expression may play a crucial role in the modulation of the inflammatory response during T. cruzi infection and mediate resistance to infection.

Animals↗

PubMed2001

Evidence for a direct action of Tityus serrulatus scorpion venom on the cardiac muscle.

The ability of toxins to activate the cardiovascular system plays an important role in the morbidity and lethality of the Tityus serrulatus scorpion envenoming. Most of the actions of the scorpion toxins are indirect and due to the release of adrenergic and cholinergic neurotransmitters. Accordingly, treatment following envenoming is targeted towards inhibition of adrenergic and cholinergic receptors. Here, we have sought evidence for a direct action of T. serrulatus venom on the isolated rat heart (Langendorff's method). We show that the bradycardia induced by T. serrulatus venom was completely blocked by atropine, a muscarinic receptor antagonist. Similarly, the increase in heart rate that follows the venom-induced bradycardia was totally inhibited by a beta(1)-adrenoceptor antagonist or by chemical sympathetic denervation with 6-hydroxydopamine. In contrast to these findings, the venom-induced increase in contractile force was not modified by beta(1)-adrenoceptor blockade or by chemical sympathetic denervation. The results clearly demonstrate that the chronotropic effects of T. serrulatus are dependent on neurotransmitter release, but the inotropic effects are not. The neurotransmitter-independent increase in contractility seems to be a direct action of the venom on cardiomyocytes. We suggest that this direct effect on cardiac fibers may play a role in the development of cardiac arrhythmias and contractility defects following envenoming with T. serrulatus scorpion.

Acetylcholine↗

PubMed2001

Evidence for a role of mast cells in the lung edema induced by Tityus serrulatus venom in rats.

In the most severe cases of human poisoning by Tityus serrulatus, pulmonary edema is a frequent finding and can be the cause of death. Mast cells can release a range of mediators known to be involved in the development of lung edema following T. serrulatus venom injection. The present work was designed to investigate whether mast cells participated in the acute lung injury induced by T. serrulatus scorpion venom and could, thus, be an intermediate between neuropeptide release and activation of the inflammatory cascade. To this end, mast cells were depleted using compound 48/80. Pulmonary edema, as assessed by the levels of extravasation of Evans blue dye in the bronchoalveolar lavage and in the left lung, was completely inhibited in compound 48/80-treated animals. Moreover, the number of animals surviving 60min after injection of venom rose from 20 to 60%. Our results demonstrate an important role for mast cells in the development of lung injury and lethality following the intravenous administration of T. serrulatus venom.

Animals↗

PubMed2001

Spatial and temporal evolution of the levels of tritium in the Tagus River in its passage through Caceres (Spain) and the Alentejo (Portugal).

This work is the result of a collaboration between Spanish and Portuguese laboratories. The specific objective was to quantify the time evolution during 1994, 1995 and 1996 of the radioecological impact of the liquid releases of 3H from the Almaraz Nuclear Power Plant (ANPP) in the section of the Tagus River corresponding to Cáceres province in Spain and the Alentejo region in Portugal. We found that the temporal evolution of the levels of tritium depends on the management of the water held in the cooling reservoir of the ANPP and the presence of the dams that exist along the river. This management regime has a 12-month period. Also the movement of the mass of tritiated water (HTO) downriver was much faster during 1996 than 1995 or 1994 due to the hydrological differences between those years and consequently to the different amounts of water transferred between the reservoirs of the dams. From the hypothesis that hydrodynamically it is impossible to differentiate tritiated water from non-tritiated water, a model was constructed that satisfactorily reproduces the temporal evolution of the 3H in the zone of the Tagus River in which the exchange of water takes place, with the cooling reservoir of the Almaraz Nuclear Power Plant.

Fresh Water↗

PubMed2001

alpha(4) integrin-dependent eosinophil recruitment in allergic but not non-allergic inflammation.

1. Although anti-alpha(4) integrin mAbs reduce eosinophil accumulation in several models of allergic inflammation, it is not clear whether this occurs via a direct action to block eosinophil alpha(4) integrins or indirectly on another cell type. The role of alpha(4) integrins on the accumulation of (111)In-labelled eosinophils in allergic and non-allergic inflammation in guinea-pig skin was therefore investigated. 2. Intradermal injection of antigen in sensitized skin sites induced accumulation of (111)In-eosinophils that was reduced up to 70% by two anti-alpha(4) integrin mAbs. In contrast, accumulation of (111)In-eosinophils to intradermal chemoattractants was unaffected by the same mAbs. 3. Accumulation of (111)In-eosinophils in allergic and non-allergic conditions was partly inhibited by a low dose of an anti-beta(2) integrin mAb. In combination with anti-alpha(4) integrin mAb, responses were not further reduced suggesting that these adhesion pathways are not additive or synergic. 4. Pretreating skin sites with antiserum or contaminating LPS did not reveal an alpha(4) integrin dependent pathway for chemoattractant-induced (111)In-eosinophil accumulation. These data suggest that alpha(4) integrins are involved in the response to antigen in sensitized skin sites. 5. Pretreating (111)In-eosinophil with alpha(4) integrin mAb blocked their adhesion to fibronectin in vitro but did not inhibit their accumulation in allergic inflammation suggesting that the blocking effect in vivo was eosinophil independent. 6. These data support the concept that targeting alpha(4) integrins on cells other than eosinophils could control eosinophil accumulation and have therapeutic potential in allergic diseases such as asthma and atopic dermatitis.

Animals↗

PubMed2001

Pharmacological evidence for the activation of potassium channels as the mechanism involved in the hypotensive and vasorelaxant effect of dioclein in rat small resistance arteries.

The hypotensive and vasorelaxant effect of dioclein in resistance mesenteric arteries was studied in intact animals and isolated vessels, respectively. In intact animals, initial bolus administration of dioclein (2.5 mg kg(-1)) produced transient hypotension accompanied by an increase in heart rate. Subsequent doses of dioclein (5 and 10 mg kg(-1)) produced hypotensive responses with no significant change in heart rate. N(G)-nitro-L-arginine methyl ester (L-NAME) did not affect the hypotensive response. In endothelium-containing or -denuded vessels pre-contracted with phenylephrine, dioclein (5 and 10 mg kg(-1) produced a concentration-dependent vasorelaxation (IC(50)=0.3+/-0.06 and 1.6+/-0.6 microM, respectively) which was not changed by 10 microM indomethacin. L-NAME (300 microM) produced a shift to the right. Dioclein was without effect on contraction of vessels induced by physiological salt solution (PSS) containing 50 mM KCl and the concentration dependence of dioclein's effect on phenylephrine induced contraction was shifted to the right in vessels bathed in PSS containing 25 mM KCl. Tetraethylammonium (10 mM) and BaCl(2) (1 mM) increased the IC(50) for dioclein-induced vasorelaxation without affecting the maximal response (E(max)). Charybdotoxin (100 nM), 4-aminopyridine (1 mM) and iberiotoxin (100 nM) increased the IC(50) and reduced the E(max). Apamin (1 microM) reduced the E(max) without affecting the IC(50). Dioclein produced a hyperpolarization in smooth muscle of mesenteric arteries with or without endothelium (7.7+/-1.4 mV and 12.3+/-3.6 mV, respectively). In conclusion dioclein lowered arterial pressure probably through a decrease in peripheral vascular resistance. The underling mechanism implicated in the vasorelaxant effect of dioclein appears to be the opening of K(Ca) and Kv channels and subsequent membrane hyperpolarization.

4-Aminopyridine↗

PubMed2001

Modulation of eotaxin formation and eosinophil migration by selective inhibitors of phosphodiesterase type 4 isoenzyme.

1. This study was undertaken to investigate the possible contribution of the blockade of eotaxin generation to the anti-eosinophilotactic effect of phosphodiesterase (PDE) type 4 inhibitors. In some experiments, the putative synergistic interaction between PDE type 4 inhibitors and the beta2-agonist salbutamol was also assessed. 2. Sensitized guinea-pigs aerosolized with antigen (5% ovalbumin, OVA) responded with a significant increase in eotaxin and eosinophil levels in the bronchoalveolar lavage fluid (BALF) at 6 h. Eosinophil recruitment was inhibited by both PDE type 4 inhibitors rolipram (5 mg kg(-1), i.p.) and RP 73401 (5 mg kg(-1), i.p.) treatments. In contrast, only rolipram inhibited eotaxin production. 3. Sensitized rats intrapleurally challenged (i.pl.) with antigen (OVA, 12 microg cavity(-1)) showed a marked eosinophil infiltration at 24 h, preceded by eotaxin generation at 6 h. Intravenous administration of a rabbit anti-mouse eotaxin antibody (0.5 mg kg(-1)) significantly reduced allergen-evoked eosinophilia in this model. 4. Local pretreatment with rolipram (40 microg cavity(-1)) or RP 73401 (40 microg cavity(-1)) 1 h before challenge reduced eosinophil accumulation evaluated in the rat pleural effluent, but only the former was active against eotaxin generation. The inhibitors of PDE type 3 (SK&F 94836) and type 5 (zaprinast) failed to alter allergen-evoked eosinophil recruitment in rats. 5. Local injection of beta2-agonist salbutamol (20 microg cavity(-1)) inhibited both eosinophil accumulation and eotaxin production following pleurisy. The former was better inhibited when salbutamol and rolipram were administered in combination. 6. Treatment with rolipram and RP 73401 dose-dependently inhibited eosinophil adhesion and migration in vitro. These effects were clearly potentiated by salbutamol at concentrations that had no effect alone. 7. Our findings indicate that although rolipram and RP 73401 are equally effective in inhibiting allergen-induced eosinophil infiltration only the former prevents eotaxin formation, indicating that PDE 4 inhibitors impair eosinophil accumulation by mechanisms independent of eotaxin production blockade.

3',5'-Cyclic-AMP Phosphodiesterases↗

PubMed2001

Effects of inhibition of PDE4 and TNF-alpha on local and remote injuries following ischaemia and reperfusion injury.

1. The effects of phosphodiesterase (PDE)4 and TNF-alpha inhibition were assessed on the local and remote injuries following intestinal ischaemia and reperfusion (I/R) injury in rats. 2. The PDE4 inhibitor rolipram dose-dependently (1 - 10 mg kg(-1)) suppressed the local (intestine) and remote (lung) increases in vascular permeability and neutrophil recruitment following mild I/R injury. SB207499 (ariflo), a structurally-distinct PDE4 inhibitor, also suppressed the injuries following mild I/R injury. 3. In a severe model of I/R injury, treatment with rolipram (10 mg kg(-1)) partially reversed the local and remote increases in vascular permeability, neutrophil recruitment, intestinal haemorrhage and intestinal LTB(4) concentrations. The anti-TNF-alpha anti-serum was more effective than rolipram at inhibiting local and remote injuries and prevented the lethality associated with severe I/R. 4. Rolipram and anti-TNF-alpha prevented the increase in the concentrations of TNF-alpha in the lung and intestine, but rolipram only partially inhibited the elevation of this cytokine in serum. Rolipram had little effect on the increases of IL-1 beta concentrations in lung and serum, whereas treatment with anti-TNF-alpha markedly increased the concentration of this cytokine. Concentrations of IL-10 rose significantly in the lung and serum and these increases were blocked by rolipram or anti-TNF-alpha. 5. The capacity of PDE4 inhibitors to block the recruitment of neutrophils into tissues, the production of LTB(4) and of the pro-inflammatory cytokines TNF-alpha, IL-1 beta and IL-6 appear to underlie their anti-inflammatory effects in our model of I/R injury. Overall, PDE4 inhibition was less effective than inhibition of TNF-alpha for protection against I/R injury.

3',5'-Cyclic-AMP Phosphodiesterases↗

PubMed2001

Genetic variability of trypanosomatids isolated from phytophagous hemiptera defined by morphological, biochemical, and molecular taxonomic markers.

In the present study, we investigated the genetic variability among 49 new isolates of trypanosomatids from phytophagous Hemiptera by means of morphological characters, growth features, and biochemical (enzymes of ornithine-arginine cycle) and molecular markers (based on spliced-leader, and ribosomal genes). From 402 phytophagous insects dissected and examined for the presence of trypanosomatids, 228 species belonging to Pyrrhocoridae, Coreidae, Lygaeidae, and Pentatomidae families harbored trypanosomatids in their salivary glands, or digestive tubes. Among these insects, 211 carried promastigotes and only 17 had choanomastigote forms. The results show a strong association among morphology, growth features, and biochemical and molecular markers and reveal the genetic diversity of the isolates, which were assigned to Crithidia, Phytomonas, and Leptomonas; we found genetic polymorphism within all these genera, thus indicating high genetic variability among trypanosomatids from phytophagous insects.

Animals↗

PubMed2001

Gestational diabetes mellitus diagnosed with a 2-h 75-g oral glucose tolerance test and adverse pregnancy outcomes.

OBJECTIVE: To evaluate American Diabetes Association (ADA) and World Health Organization (WHO) diagnostic criteria for gestational diabetes mellitus (GDM) against pregnancy outcomes. RESEARCH DESIGN AND METHODS: This cohort study consecutively enrolled Brazilian adult women attending general prenatal clinics. All women were requested to undertake a standardized 2-h 75-g oral glucose tolerance test (OGTT) between their estimated 24th and 28th gestational weeks and were then followed to delivery. New ADA criteria for GDM require two plasma glucose values > or = 5.3 mmol/l (fasting), > or = 10 mmol/l (1 h), and > or = 8.6 mmol/l (2 h). WHO criteria require a plasma glucose > or = 7.0 mmol/l (fasting) or > or = 7.8 mmol/l (2 h). Individuals with hyperglycemia indicative of diabetes outside of pregnancy were excluded. RESULTS: Among the 4,977 women studied, 2.4% (95% CI 2.0-2.9) presented with GDM by ADA criteria and 7.2% (6.5-7.9) by WHO criteria. After adjustment for the effects of age, obesity, and other risk factors, GDM by ADA criteria predicted an increased risk of macrosomia (RR 1.29, 95% CI 0.73-2.18), preeclampsia (2.28, 1.22-4.16), and perinatal death (3.10, 1.42-6.47). Similarly, GDM by WHO criteria predicted increased risk for macrosomia (1.45, 1.06-1.95), preeclampsia (1.94, 1.22-3.03), and perinatal death (1.59, 0.86-2.90). Of women positive by WHO criteria, 260 (73%) were negative by ADA criteria. Conversely, 22 (18%) women positive by ADA criteria were negative by WHO criteria. CONCLUSIONS: GDM based on a 2-h 75-g OGTT defined by either WHO or ADA criteria predicts adverse pregnancy outcomes.

Adult↗