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Background: Enhanced influenza vaccines are the best option for the elderly. In 2021, Argentina introduced the MF59-adjuvanted inactivated influenza vaccine (aIIV) for individuals aged 65 years. and above, in the national immunization program. High dose inactivated influenza vaccine (HD-IIV) is also currently registered. This study evaluates the clinical and economic outcomes of these noted enhanced influenza vaccines for the elderly in Argentina., Methods: Using a static decision-tree model and adopting the payer's perspective during an average influenza season, the analysis incorporated influenza epidemiological data from pre-pandemic Argentinian seasons (2014-2019), strain distribution, vaccination uptake, influenza-related costs and Quality-Adjusted Life-Years (QALYs) gained. Results include two relative vaccine effectiveness (rVE) scenarios from two published meta-analyses, due to reported rVE variability, although without statistical significance expected between enhanced vaccines. Vaccination acquisition costs were obtained from aIIV manufacturer, while HD-IIV costs were estimated using local (Argentinian private sector) and international public sector data (Europe). This assessment considered one GDP per-capita (US$13,696) as a cost-effectiveness threshold and included multiple sensitivity analysis., Results: With an expected lower vaccine cost and non-significant higher rVE for aIIV vs HD-IIV (3.2 %), aIIV generated 41.4 QALYs gained and US$8.7 M savings to the Argentinean public health system. In this scenario aIIV resulted as a dominant strategy over HD-IIV. On a second scenario, where HD-IIV has a non-significant higher rVE compared to aIIV (15.9 % and 13.9 % for HD-IIV and aIIV, respectively, both vs standard-dose IIV), HD-IIV would only result cost-effective compared to aIIV if its public price is up to 25 % the incremental cost in relation to the standard-dose IIV acquisition price., Conclusions: In Argentina, the use of enhanced influenza vaccines in the elderly can increase vaccine effectiveness, reduce mortality and disease-related costs. Based on comparable effectiveness, the economic advantage of aIIV over HD-IIV confirms the current vaccination strategy employing aIIV in Argentina., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Analia Uruena reports financial support was provided by Seqirus Srl. Analia Uruena reports a relationship with Seqirus Inc. that includes: speaking and lecture fees. Analia Uruena reports a relationship with Merck Sharp & Dohme Corp that includes: speaking and lecture fees. Analia Uruena reports a relationship with Takeda Pharmaceutical Company Limited that includes: speaking and lecture fees. Analia Uruena reports a relationship with GSK that includes: consulting or advisory. Analia Uruena reports a relationship with Takeda Pharmaceutical Company Limited that includes: consulting or advisory. Analia Uruena reports a relationship with Seqirus Inc. that includes: consulting or advisory. Analia Uruena reports a relationship with Sociedad Argentina de Vacunologia y Epidemiologia that includes: board membership. Joaquin Mould Quevedo reports a relationship with Seqirus Inc. that includes: employment and equity or stocks. Carolina Saenz reports a relationship with Seqirus Inc. that includes: employment. Jose Luis Montes reports a relationship with Seqirus Inc. that includes: employment. Norberto Giglio reports a relationship with Argentine Society of Pediatrics that includes: board membership. Norberto Giglio reports a relationship with Ricardo Gutierrez Children's Hospital that includes: board membership. Norberto Giglio reports a relationship with Global Vaccines Data Network that includes: board membership. Norberto Giglio reports a relationship with GSK that includes: consulting or advisory and speaking and lecture fees. Norberto Giglio reports a relationship with Seqirus Inc. that includes: consulting or advisory and speaking and lecture fees. Norberto Giglio reports a relationship with Takeda Pharmaceutical Company Limited that includes: consulting or advisory and speaking and lecture fees. Norberto Giglio reports a relationship with Sanofi Pasteur Inc. that includes: consulting or advisory and speaking and lecture fees. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors. Published by Elsevier Ltd.)

Introduction: Cow's milk protein allergy (CMPA) is the most frequent food allergy in early childhood. For those infants requiring breastmilk substitutes, formulas with extensively hydrolyzed proteins (EHF), should be the treatment of choice. As there are limited data showing the progression of initial symptoms in infants newly diagnosed with CMPA who are treated with EHF with added synbiotics, the main objective of this study was to evaluate the resolution of symptoms in said infants after 4 weeks of treatment. As a secondary objective this study aimed to assess the impact of the treatment on the family's quality of life., Materials and Methods: observational, longitudinal, prospective, and multicentric real-world evidence study. The intervention phase (EHF with synbiotics) lasted 28 days and was completed by 65 patients. Treating physicians registered child´s anthropometry, Infant Gastrointestinal Symptoms Questionnaire (IGSQ-13) and CoMiSS (Cow´s Milk Allergy Symptoms Score) both at baseline and after 28 days of treatment. During treatment, caregivers reported child´s regurgitation and stools, PO-SCORAD (Patient Oriented Scoring of Atopic Dermatitis) and FAQL-PB (Family Quality of Life-Parental Burden). Data were collected using Google Forms and analyzed through the STATA program., Results: 95.4% of the patients showed an improvement or disappearance of the overall initial symptoms after 4 weeks of treatment. Gastrointestinal symptoms improved or disappeared in 92% of patients ( p  < 0.05) while dermatological symptoms improved or disappeared in 87.5% of patients ( p  < 0.05). The median CoMiSS at baseline was 9, with 21 patients exceeding the cut-off point of 12. After 4 weeks of treatment, the median dropped to 3, and no patient exceeded the 12-cut-off point ( p  = 0.000). At baseline, patients had a PO-SCORAD of 11.5 (interquartile range 1-23) that went to 1.0 (interquartile range 1-6) at day 28 ( p  = 0.000). The treatment diminished stool frequency ( p  < 0.05), improved stool consistency ( p  = 0.004) and decreased the frequency of regurgitation in infants with CMPA ( p  = 0.01). The percentage of patients who no longer had any episode of regurgitation increased from 11% to 31% on day 28 ( p  = 0.003). At baseline, 13% of patients cried more than 3 h per day, while at day 28 that percentage dropped to 3% ( p  = 0.03). An improvement in the infants' sleep pattern was also appreciated with the treatment. At study onset, 56% of the families reported feeling very overwhelmed, a percentage that dropped to 17% after 28 days of treatment ( p  < 0.05). The small percentage of families who did not feel overwhelmed at study onset (17%), grew to 43% on day 28 ( p  < 0.05)., Conclusions: The use of an EHF with synbiotics for the management of infants diagnosed with or suspected to have CMPA suggested a good safety profile, an adequate infant growth, and improvement of overall, gastrointestinal, and dermatological symptoms. It also suggested a lower daily frequency of regurgitations and stools, and an improvement in stool consistency, sleeping pattern, and quality of life of the infant and his family., Competing Interests: Unrestricted grant was provided by Nutricia Bago to support this research study. It is important to note that Nutricia Bago had no involvement or influence in the study design, data collection, analysis, interpretation, or the decision to publish the findings. We declare no conflicting interests that could compromise the integrity, objectivity, or impartiality of the study., (© 2023 Soria, Del Compare, Sallaberry, Martín, Aprigliano, Hermida, Carosella, Gruenberg, Monsell, Micone, Maciero, Giglio.)

Background: Quadrivalent cell-based influenza vaccines (QIVc) avoid egg-adaptive mutations and can be more effective than traditional quadrivalent egg-based influenza vaccines (QIVe). This analysis compared the cost-effectiveness of QIVc and QIVe in Argentinian populations < 65 years old from the payer and societal perspectives. Methods: A static decision tree model compared the costs and health benefits of vaccination with QIVc vs. QIVe using a one-year time horizon. The relative vaccine effectiveness of QIVc vs. QIVe was assumed to be 8.1% for children and 11.4% for adults. An alternative high egg-adaptation scenario was also assessed. Model inputs were sourced from Argentina or the international literature. Deterministic and probabilistic sensitivity analyses were performed. Results: Compared to QIVe, QIVc would prevent 17,857 general practitioner visits, 2418 complications, 816 hospitalizations, and 12 deaths per year. From the payers’ perspective, the incremental cost-effectiveness ratio per quality-adjusted life years gained was USD12,214 in the base case and USD2311 in the high egg-adaptation scenario. QIVc was cost-saving from the societal perspective in both scenarios. Conclusions: QIVc in Argentina would be cost-effective relative to QIVe. The potential health benefits and savings would be even higher in high egg-adaptation seasons.

One-dose universal varicella vaccination (UVV) was introduced in the Argentinian National Immunization Program in July 2015. This study examined the impact of one-dose UVV on varicella incidence and mortality in Argentina. Incidence and mortality data were obtained from official databases for pre-UVV (January 2008-June 2015) and post-UVV (July 2015-December 2019) periods. Time series analyses with autoregressive integrated moving average (ARIMA) modeling predicted varicella incidence and mortality in absence of UVV in the target (aged 1-4 years) and overall population. Predicted and observed values post-UVV were compared to estimate UVV impact. Mean annual incidence rates per 100,000 reduced from 1999 (pre-UVV) to 1122 (post-UVV) in the target population and from 178 to 154 in the overall population. Significant declines in incidence were observed, reaching reductions of 83.9% (95% prediction interval [PI]: 58.9, 90.0) and 69.1% (95% PI: 23.6, 80.7) in the target and overall populations, respectively, during peak months (September-November) post-UVV. Decreasing trends in mortality rate from 0.4 to 0.2 per 1,000,000 population were observed. Over the last four years, one-dose UVV has significantly reduced varicella burden of disease in Argentina. Continuous efforts to improve vaccination coverage rates and long-term follow-up are needed to better understand the benefits of the UVV program.

The burden of seasonal influenza disease in Argentina is considerable. The cost-effectiveness of trivalent (TIV) versus quadrivalent influenza vaccine (QIV) in Argentina was assessed. An age-stratified, static, decision-tree model compared the costs and benefits of vaccination for an average influenza season. Main outcomes included: numbers of influenza cases; general practitioner (GP) visits; complicated ambulatory cases; hospitalizations; deaths averted; and costs per quality-adjusted life years (QALYs) gained. Epidemiological data from Argentina for 2014-2019 were used to determine the proportion of A and B strain cases, and the frequency of mismatch between vaccine and circulating B strains. To manage uncertainty, one-way and probabilistic sensitivity analyses were performed. Switching from TIV to QIV would prevent 19,128 influenza cases, 16,164 GP visits, 2440 complicated ambulatory cases, 524 hospitalizations, and 82 deaths. Incremental cost-effectiveness ratios (ICERs) per QALY were 13,590 and 11,678 USD from the payer's and societal perspectives, respectively. The greatest health benefits and direct medical cost savings would occur in ≥ 65-year-olds. One-way sensitivity analyses demonstrated the principal drivers of ICER to be vaccine acquisition costs, environmental B strain predominance, and B strain mismatch. Introducing QIV in Argentina would be beneficial and cost-effective relative to TIV, particularly in older adults.

Serological risk factors are the most important determinant in predicting unsuccessful pregnancy in obstetric antiphospholipid antibodies syndrome (OAPS) despite conventional treatment. It is not clear if changes in the profile of antiphospholipid antibodies (aPL) during pregnancy modify the risk associated with a poor response to conventional treatment. The aim of our study was to compare the value of a serological tag for aPL obtained before and during the first trimester of pregnancy to predict the response to conventional treatment. We carefully selected 97 pregnancies in women who were included in our study only if they were diagnosed with OAPS prior to a new pregnancy (basal serological risk), retested for aPL during the first trimester of pregnancy (serological risk during pregnancy), and treated with conventional therapy. High baseline serological risk was associated with pregnancy failure in 62.1% of cases (18/29) and predicted 82.5% of pregnancy outcomes with conventional treatment: OR = 16.9, CI = 5.5-52.1, p < 0.001. High serological risk during pregnancy was associated with pregnancy failure in 86.3% of cases (19/22) and predicted 91.8% of pregnancy outcomes with conventional treatment: OR = 88.7, CI = 19.4-404.8, p < 0.001. According to these results, we found that risk categorization performed during pregnancy was better in predicting pregnancy outcome (82.5 vs. 91.8%). Moreover, risk categorization during pregnancy had an increased specificity regarding the prediction: 84.9% at baseline and 95.9% during pregnancy (p = 0.024). Our findings suggest that it is important to perform aPL during the first trimester of pregnancy since that is the best time to establish the serological risk factors.

Objetive: To assess direct medical costs, outof-pocket expenses, and indirect costs in cases of hospitalizations for acute diarrhea among children <5 years of age at Hospital de Niños "Héctor Quintana" in the province of Jujuy during the period of rotavirus circulation in the Northwest region of Argentina., Methods: Cross-sectional study on diseaserelated costs. All children <5 years of age, hospitalized with the diagnosis of acute diarrhea and dehydration during the period of rotavirus circulation between May 1st and October 31st of 2013, were included. The assessment of direct medical costs was done by reviewing medical records whereas out-of-pocket expenses and indirect costs were determined using a survey. For the 95% confidence interval of the average cost per patient, a probabilistic bootstrapping analysis of 10 000 simulations by resampling was done., Results: One hundred and five patients were enrolled. Their average age was 18 months (standard deviation: 12); 62 (59%) were boys. The average direct medical cost, out-of-pocket expense, and lost income per case was ARS 3413.6 (2856.35-3970.93) (USD 577.59), ARS 134.92 (85.95-213.57) (USD 22.82), and ARS 301 (223.28-380.02) (USD 50.93), respectively. The total cost per hospitalization event was ARS 3849.52 (3298-4402.25) (USD 651.35)., Conclusions: The total cost per hospitalization event was within what is expected for Latin America. Costs are broken down into direct medical costs (significant share), compared to out-of-pocket expenses (3.5%) and indirect costs (7.8%)., (Sociedad Argentina de Pediatría)

Apixaban, a novel oral anticoagulant which has been approved for the prevention of stroke and systemic embolism in non-valvular atrial fibrillation, reduces both ischemic and haemorrhagic stroke and produces fewer bleedings than vitamin K antagonist warfarin. These clinical results lead to a decrease in health care resource utilization and, therefore, have a positive impact on health economics of atrial fibrillation. The cost-effectiveness of apixaban has been assessed in a variety of clinical settings and countries. However, data from emergent markets, as is the case of Argentina, are still scarce.We performed a cost-effectiveness analysis of apixaban versus warfarin in non-valvular atrial fibrillation (NVAF) in patients suitable for oral anticoagulation in Argentina. A Markov-based model including both costs and effects were used to simulate a cohort of patients with NVAF. Local epidemiological, resource utilization and cost data were used and all inputs were validated by a Delphi Panel of local experts. We adopted the payer's perspective with costs expressed in 2012 US Dollars.The study revealed that apixaban is cost-effective compared with warfarin using a willingness to pay threshold ranging from 1 to 3 per capita Gross Domestic Product (11558 - 34664 USD) with an incremental cost-effectiveness ratio of 786.08 USD per QALY gained. The benefit is primarily a result of the reduction in stroke and bleeding events.The study demonstrates that apixaban is a cost-effective alternative to warfarin in Argentina.

Maternal mortality is an important public health and human rights problem and reflects the effects of social determinants on women's health. Understanding the extent and causes of maternal death has been insufficient to achieve the Millennium Development Goals. This article proposes a model for a comprehensive approach to maternal mortality, covering seven areas: prioritization and definition of the problem, contextual description, methodological scope, knowledge management, innovation, implementation, and a monitoring and evaluation system. This model helps address problems associated with maternal mortality and severe maternal morbidity through early monitoring of potentially fatal complications in the reproductive process. Knowledge management is important for the reorientation of policies, programs, and health care. Interaction and synergies among people, communities, and actors in the health system should be strengthened in order to improve the results of health programs. More validated scientific information is needed on how actions should be implemented in different environments. It is essential to strengthen communication among research centers, cooperation agencies, and government organizations and to include them in programs and in the definition of a new women's health agenda in the Region of the Americas.

Objective: To analyse life-threatening obstetric complications that occurred in public hospitals in Argentina., Design: Multicentre collaborative cross-sectional study., Setting: Twenty-five hospitals included in the Perinatal Network of Buenos Aires Metropolitan Area., Population: Women giving birth in participating hospitals during a 1-year period., Methods: All cases of severe maternal morbidity (SMM) and maternal mortality (MM) during pregnancy (including miscarriage and induced abortion), labour and puerperium were included. Data were collected prospectively., Main Outcome Measures: Identification criteria, main causes and incidence of SMM; case-fatality rates, morbidity-mortality index and effective intervention's use rate., Results: A total of 552 women with life-threatening conditions were identified: 518 with SMM, 34 with MM. Identification criteria for SMM were case-management (48.9%), organ dysfunction (15.2%) and mixed criteria (35.9%). Incidence of SMM was 0.8% (95% confidence interval [95% CI] 0.73-0.87%) and hospital maternal death ratio was 52.3 per 100 000 live births (95% CI 35.5-69.1). Main causes of MM were abortion complications and puerperal sepsis; main causes of SMM were postpartum haemorrhage and hypertension. Overall case-fatality rate was 6.2% (95% CI 4.4-8.6): the highest due to sepsis (14.8%) and abortion complications (13.3%). Morbidity-mortality index was 15:1 (95% CI 7.5-30.8). Use rate of known effective interventions to prevent or treat main causes of MM and SMM was 52.3% (95% CI 46.9-57.7)., Conclusions: This study describes the importance of life-threatening obstetric complications that took place in public hospitals with comprehensive obstetric care and the low utilisation of known effective interventions that may decrease rates of SMM and MM. It also provides arguments that justify the need to develop a surveillance system for SMM., (© 2013 RCOG.)

Objective: To assess the risk of adverse perinatal events of vaccination of pregnant women with an MF59 adjuvanted vaccine., Design: Cross sectional multicentre study., Setting: 49 public hospitals in major cities in Argentina, from September 2010 to May 2011., Participants: 30,448 mothers (7293 vaccinated) and their 30,769 newborns., Main Outcome Measure: Primary composite outcome of low birth weight, preterm delivery, or fetal or early neonatal death up to seven days postpartum., Results: Vaccinated women had a lower risk of the primary composite outcome (7.0% (n=513) v 9.3% (n=2160); adjusted odds ratio 0.80, 95% confidence interval 0.72 to 0.89). The propensity score analysis showed similar results. Adjusted odds ratios for vaccinated women were 0.74 (0.65 to 0.83) for low birth weight, 0.79 (0.69 to 0.90) for preterm delivery, and 0.68 (0.42 to 1.06) for perinatal mortality. These findings were consistent in further subgroup analysis. No significant differences in maternal outcomes were found., Conclusion: This large study using primary data collection found that MF59 adjuvanted A/H1N1 influenza vaccine did not result in an increased risk of adverse perinatal events and suggested a lower risk among vaccinated women. These findings should contribute to inform stakeholders and decision makers on the prescription of vaccination against influenza A/H1N1 in pregnant women.

Background: Argentina's population was heavily affected by the 2009 influenza pandemic, particularly children, in whom incidence of seasonal influenza is consistently high. Following the pandemic, Argentinean national recommendations for pediatric vaccination against A/H1N1 influenza were defined for all children aged up to five years, in line with programs implemented by national authorities elsewhere. Economic evaluations have found that vaccination programs for this population against seasonal influenza are cost-effective, if not cost-saving in many countries. Recently, Argentina decided to routinely vaccinate against influenza children aged 6-23 mo-old. But, the economic value of such strategies for the country has never been assessed., Methods: A model was developed to assess the value of four different vaccination strategies: (1) no pediatric vaccination; (2) vaccination of 6-23 mo-old children; (3) vaccination of 6-36 mo-old children; (4) vaccination of 6 mo-5 y-old children. We first estimated community health benefits of vaccination then we evaluated the economic and quality-of-life impact of these strategies on the population. Data used in the model come from surveillance networks, published literature, national databases and retrospective hospital-based data., Results: Pediatric influenza vaccination benefited not only children but also the overall community, due to decreased disease transmission. Our results showed that the recent decision by Argentina to vaccinate 6-23 mo-old children is cost-effective as would be the incremental vaccination of broader age groups., Conclusions: Results from this study are consistent with previous analyses in other countries confirming that implementing influenza pediatric vaccination programs can be highly cost-effective through individual- and community protection against the disease.

Streptococcus pneumoniae continues to be the most important causative agent of invasive bacterial infections in children and is the most common cause of vaccine-preventable deaths in children less than 5 years of age. Due to some conditions in the Latin America region, economic assessments of pneumococcal conjugate vaccines (PCVs) have unique characteristics. First, distribution of S. pneumoniae serotypes, and thus coverage by vaccines that incorporate certain serotypes, varies within the region and compared with other parts of the world. Second, the mortality rate of pneumococcal infections in developing countries is significantly higher than in the US and Europe. Third, the economies of the Latin American region are very different from those of developed countries. For these reasons, the Pan American Health Organization (PAHO) is promoting the need for economic valuation studies of the impact of pneumococcal vaccines Latin America. Given the importance of pneumonia in the burden of pneumococcal disease in Latin America, the number of pneumonia cases prevented by the vaccine has a large impact on the economic valuation of PCVs, due to a strong correlation with numbers of deaths averted, quality-adjusted life-years (QALYs) gained or disability-adjusted life-years (DALYs) avoided. In terms of cost, analysis of impact on acute otitis media (short-term) and sequelae (long-term) show a significant and important expenditure avoided by vaccination. Cost-effectiveness is significantly modified by vaccine cost, mortality due to pneumonia, vaccine efficacy/effectiveness and herd immunity. Finally the validity of certain assumptions based on the uncertainty of the data should be considered in economic assessments of new PCVs. These include assumptions related to the impact on otitis media, estimates of efficacy/effectiveness based on measured antibody levels and the extrapolation to PCV10 and PCV13 of previous experience with PCV7., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Unlabelled: Due to the region's own conditions, universal vaccination with pneumococcal conjugate heptavalent vaccine (PCV-7) in Latin American countries is still controversial., Objective: To compare projected economic costs and health benefits associated with pneumococcal conjugate heptavalent vaccine as a routine immunization in healthy children in Argentina., Design: A decision analytic model of Markov simulated lifetime evolution of a birth cohort (n 696,451) was developed and compared costs and health benefits of pneumococcal disease in the presence and absence of vaccination., Main Outcome Measures: Cost per life year (LY) gained, reduce in diseases burden and costs of vaccination., Results: From the society's perspective, the incremental cost per LY gained was US$ 5599.42 and the purchase of the 4 doses of vaccine for the entire cohort with a cost of US$ 26.5 dose requires an investment of US$ 73,823,806.00. The model estimated that vaccination reduce the number of death by 159 cases of meningitis, 756 cases of bacteriemias 4594 cases of pneumonias about 84,769 cases of otitis media and 20 meningitis sequelae. The value of the cost per LY gained was considerably modified by the variation in the cost of the vaccine dose, efficacy/effectiveness of the vaccine for pneumonia the mortality from pneumonia and herd immunity., Conclusions: Our analysis predicted that routine vaccination of healthy infants <2 years could prevent an important number of pneumococcal infectious and reduce related mortality and morbidity. This strategic could be highly cost-effective in Argentina., (Copyright 2010 Elsevier Ltd. All rights reserved.)

Objective: To investigate the use of beneficial maternal and perinatal healthcare practices in a network of public maternity hospitals in Argentina., Method: A multicenter, prospective, descriptive study of 6661 deliveries in 9 hospitals. The use of 5 obstetric care practices that reduce maternal and perinatal morbidity and mortality was evaluated., Results: Median use rates for the selected practices were: continuous support for women during childbirth (17.9%); corticosteroids for preterm birth (35.3%); avoidance of episiotomy in primiparous women (41.2%); iron and folate supplementation (52.5%); active management of third stage of labor (93.5%)., Conclusion: There is limited use of the selected evidence-based maternal and perinatal practices in public hospitals in Argentina and a large variation in their use among and within hospitals. Efforts should be made to increase the use of these evidence-based practices.

The activity of matrix metalloproteinase (MMP)-9 was evaluated in placental tissue from healthy subjects (controls) and from patients with gestational and pre-existing diabetes mellitus (GDM and PDM, respectively). Compared with controls, MMP-9 activity was greater in placental tissue from patients with PDM and lower in placental tissue from patients with GDM. The modulatory role of nitric oxide (NO) and reactive oxygen species (ROS) on MMP-9 activity in placental tissue was evaluated. In healthy placenta, NO synthase inhibitors diminished MMP-9 activity, whereas NO donors enhanced it. The addition of xanthine/xanthine oxidase or hydrogen peroxide to placental incubates enhanced MMP-9 activity, while the addition of superoxide dismutase (SOD) diminished it. In placental tissue from patients with PDM, MMP-9 activity was stimulated by NO and by ROS. In placental tissue from patients with PDM, concentrations of nitrates/nitrites and thiobarbituric acid-reactive substances (TBARS) were enhanced, whereas SOD activity was decreased, suggesting that elevated concentrations of NO and ROS may be related to the enhanced MMP-9 concentrations found in these tissues. In placenta from GDM patients, in which a diminished concentration of MMP-9 were detected, nitrate/nitrite concentrations were increased, but placental MMP-9 activity did not change in the presence of either NO donors or inhibitors. The activity of MMP-9 in placental tissue from patients with GDM was stimulated by ROS donor systems and was inhibited by the addition of SOD; however, TBARS and SOD concentrations were unchanged in these tissues compared with controls. These findings demonstrate that placental MMP-9 activity is modulated by NO and ROS and that, in diabetic pathology, NO and ROS may determine changes in MMP-9 activity, which are probably involved in the structural and functional abnormalities of diabetic placental tissue.