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Introduction: Breastfeeding has unique health benefits. Exclusive breastfeeding is recommended during the first six months of life and should be maintained during complementary feeding. Alternatively, infant formulas, which are designed to mimic human breastmilk to promote similar metabolic and growth profiles, can be used. This study aimed to assess the opinion of Portuguese paediatricians with expertise in nutrition on the composition, benefits and indications of commercialised infant formulas., Material and Methods: A survey based on the Delphi method with application of a questionnaire developed by a scientific committee was issued to a panel of paediatricians with expertise in nutrition. An initial questionnaire that included 65 items covering 11 areas was administered in two rounds., Results: Twenty-one experts participated, and the final response rate was 87.5%. The panel was in agreement in 68.3% of the enquired items, namely that infant formulas should be used only when breastfeeding is not possible. Notwithstanding, the opinion of the panel was heterogeneous on a number of issues, particularly those related to the advantages and indications of 'special' or modified infant formulas (partially hydrolysed formulas and anti-colic, anti-constipation and anti-regurgitation formulas) and of young child formulas ('growing-up formulas')., Discussion: A wide consensus was recorded on the nutritional quality, food safety and indications attributed to commercialized infant formulas., Conclusion: The opinion of Portuguese experts was consensual in most of the enquired topics. The absence of consensus was mostly related to issues that remain under debate in the literature and lack robust scientific evidence.

Background: To achieve recommended nutrient intakes in preterm infants, the target fortification method of human milk (HM) was proposed as an alternative to standard fortification method. We aimed to compare assumed energy and macronutrient intakes based on standard fortified HM with actual intakes relying on measured composition of human milk (HM), in a cohort of HM-fed very preterm infants., Methods: This study is a secondary retrospective analysis, in which assumed energy and macronutrient contents of daily pools of own mother's milk (OMM) from 33 mothers and donated HM (DHM) delivered to infants were compared with the measured values using a mid-infrared HM analyzer. A fortification method consisting of modular protein and/or fat supplements added to standard fortified HM was used to provide the minimum recommended daily intakes of energy 110 Kcal/kg and protein up to 4.0 g/kg. Assumed nutrient intakes were compared with actual nutrient intakes from full enteral feeding to 35 weeks plus 6 days postmenstrual age, using the Wilcoxon matched-pairs signed ranks test., Results: The composition of 1181 samples of daily pools of HM were measured. For 90.2% of study days, infants were exclusively fed OMM and in remaining days fed OMM plus DHM. Comparing with reported preterm OMM composition, measured protein concentration was significantly lower, and energy and other macronutrient concentrations were lower only from the second to third postnatal week. Using fortified HM, the actual median daily intakes of energy, protein, and fat were significantly lower (113.3 vs. 120.7 Kcal/kg, 4.45 vs. 4.73 g/kg, and 4.96 vs. 5.35 g/kg, respectively) and the actual protein-to-energy ratio (PER) significantly higher than what was assumed (4.2 vs. 4.0), without differences in carbohydrate intake., Conclusions: When fortifying the HM, we used conservative target intakes trying not to exceed the osmolarity recommended for infant feeds. Actual energy, protein and fat intakes in OMM were significantly lower than assumed. This resulted in inadequate intake using our fortification method, that did not compensate the suboptimal measured energy and macronutrient contents of OMM delivered. Further studies comparing assumed with the gold standard target fortification are needed to determine safe upper limits of assumed fortification., Competing Interests: Parents or guardians of all infants gave their informed consent before inclusion in the study, and the study was conducted in accordance with the tenets of the Declaration of Helsinki.Not applicable.The authors declare no conflict of interest. The funding sponsors had no role in the design of the study, in the collection, analyses, or interpretation of data, in the writing of the manuscript and in the decision to publish the findings.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Naphthoquinones and 1,2,3-triazoles are structural pharmacophore that is known to impart several cancer cells. This work shows a synthetic methodology to obtain hybrid molecules involving naphthoquinone and triazol scaffold as multiple ligands. A simple and efficient synthetic route was used to prepare a series of sixteen compounds being eight 2-(1-aryl-1H-1,2,3-triazol-4-yl)-2,3-dihydronaphtho[1,2 b]furan-4,5-diones and eight 2-(1-aryl-1H-1,2,3-triazol-4-yl)-2,3-dihydronaphtho[2,3-b]furan-4,9-diones. These compounds were tested in MDA-MB231, Caco-2 and Calu-3 human cancer cells, and among them 7a was the most selective compound on Caco-2 cells, the most sensitized cell line in this study. In silico study suggest that the blockage of topoisomerase I and IIα may be one of the mechanisms of action responsible for the cytotoxic effect of 7a in Caco-2 cells., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

Objective: To determine the associations of measured protein, energy, and protein-to-energy (PER) intakes with body composition in human milk (HM)-fed preterm infants., Study Design: Neonates born at < 33 gestational weeks were eligible. Standard fortification method with modular supplements was used and the HM composition was measured. The weight gain velocity was calculated, and body composition was assessed by air displacement plethysmography at 40 weeks' postmenstrual age (PMA). The fat mass percentage and fat mass index were used as indicators of adiposity, with convenience cut-offs ≤ -1 and ≥ + 1 z -scores for low and high adiposity, respectively., Results: Thirty-three infants were included (median [interquartile range] gestational age: 30 [28-31] weeks; birth weight: 1.175 [1.010-1.408] g); 36.4 and 84.8% did not receive the minimum recommended protein and energy intakes, respectively. Weight gain velocity showed positive weak-to-moderate correlations with nutrient intakes. Overall, no correlations between nutrient intakes and body composition were found. Infants with lower adiposity received lower energy, protein, and PER intakes, while those with higher adiposity received lower energy intake but higher PER intake., Conclusion: Overall, no correlations of nutrient intakes with body composition were found; however, differences in nutrient intakes were found between infants with lower and higher adiposity at term PMA., Competing Interests: None., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

The associations between enteric pathogenic parasites and growth in infants in São Tomé were explored using a refined anthropometric approach to recognize early growth faltering. A birth cohort study was conducted with follow-up to 24 months of age. Microscopic examination for protozoa and soil-transmitted helminths was performed. Anthropometric assessments included: z-scores for weight-for-length (WLZ), length-for-age (LAZ), weight (WAVZ) and length velocities (LAVZ), length-for-age difference (LAD), and wasting and stunting risk (≤-1 SD). Generalized additive mixed effects regression models were used to explore the associations between anthropometric parameters and enteric parasitic infections and cofactors. A total of 475 infants were enrolled, and 282 completed the study. The great majority of infants were asymptomatic. Giardia lamblia was detected in 35.1% of infants in at least one stool sample, helminths in 30.4%, and Cryptosporidium spp. in 14.7%. Giardia lamblia and helminth infections were significantly associated with mean decreases of 0.10 in LAZ and 0.32 in LAD, and of 0.16 in LAZ and 0.48 in LAD, respectively. Cryptosporidium spp. infection was significantly associated with a mean decrease of 0.43 in WAVZ and 0.55 in LAVZ. The underestimated association between subclinical parasitic enteric infections and mild growth faltering in infants should be addressed in public health policies., Competing Interests: The authors declare no conflict of interest.

Background: Cholestasis is a common complication in infants receiving prolonged parenteral nutrition (PN). We studied the effects of two intravenous lipid emulsions composed with either 30% soybean oil, 30% medium-chain triglycerides (MCT), 25% olive oil, and 15% fish oil (SMOF) or with 50% MCT and 50% soybean oil n-6 (MCT/SOY) on the incidence of cholestasis in surgical term and near-term neonates., Methods: A single-center, double-blinded, randomized controlled trial compared the incidence of cholestasis using either SMOF or MCT/SOY in neonates born at gestational age ≥34 weeks undergoing major surgery. The primary outcome was the incidence of conjugated serum bilirubin >1 mg/dL. Other liver enzymes were assessed as secondary outcomes. A post-hoc analysis assessed serum triglycerides levels. Odds ratios were estimated by mixed-effects regression models., Results: Enrollment was prematurely interrupted because the MCT/SOY became unavailable, thus 49 infants (SMOF 22, MCT/SOY 27) completed the study. The exposure (time on PN, cumulative dose of lipids) was similar in both groups. Similar cumulative incidence rates were found for elevated conjugated bilirubinemia and other liver enzymes. Hypertriglyceridemia >250 mg/dL (12/49) was more frequent in MCT/SOY (37.0%, 95% CI 21.53-55.77) than in SMOF (9.1%, 95% CI 2.53-27.81, p = 0.024). Triglyceridemia at the first assessment (median 8 postnatal days) was significantly higher with MCT/SOY than with SMOF (181 vs. 134 mg/dL, p = 0.006). Over the whole study period, mean triglyceride concentration was 36.5 mg/dL higher with MCT/SOY compared with SMOF (p = 0.013)., Conclusion: Both emulsions had similar effects on the incidence of cholestasis and markers of liver integrity, but MCT/SOY induced higher serum triglyceride concentrations., Trial Registration: ClinicalTrials.gov, NCT02633384., (Copyright © 2017 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved.)

Introduction: The resting energy expenditure (REE) evolution after liver transplantation is not fully understood., Objective: To assess longitudinally the REE evolution in adults undergoing liver transplantation, in association with other nutritional measurements that characterize the metabolic profile., Methods: A single-center cohort of consecutive end-stage liver disease patients with indication for liver transplantation was recruited. REE, subjective global assessment (SGA), handgrip strength and body composition measurements were assessed before transplantation (T0) and at median nine (T1) and 36 (T2) days after transplantation. Mixed effects regression models were used for analysis., Results: Fifty-six patients with a mean age of 53.7 (8.5) years were included; 87.5% were males. In T0, 41% of patients were normometabolic, 37.5% were hypometabolic and 21.4% were hypermetabolic. After transplantation, the mean REE decreased progressively in patients initially hypermetabolic and the opposite occurred in those initially hypometabolic. The REE evolution was positively associated with body weight (β = 9.6, p < 0.001) and energy intake (β= 13.6, p = 0.005) in the whole sample; it was positively associated with body weight (β= 7.1, p = 0.018) and percentage of energy intake from lipids (β= 18.9, p = 0.003) in initially hypometabolic patients, and positively associated with body weight (β= 14.1, p < 0.001) and negatively associated with SGA-undernourishment (β = -171, p = 0.007) in initially normometabolic patients., Conclusion: Different REE evolutions after liver transplantation are associated with the preoperative metabolic status. In patients initially hypometabolic, the REE evolution is positively associated with body weight and percentage of energy intake from lipids, and in those initially normometabolic, it is positively associated with body weight and negatively associated with SGA-undernourishment.

The cumulative effect of repeated asymptomatic enteric infections on intestinal barrier is not fully understood in infants. We aimed to evaluate the association between previous enteric parasitic infections and intestinal inflammation and permeability at 24-months of age, in asymptomatic infants of São Tomé Island. A subset of infants from a birth cohort, with intestinal parasite evaluations in at least four points of assessment, was eligible. Intestinal inflammatory response and permeability were assessed using fecal S100A12 and alpha-1-antitrypsin (A1AT), respectively. The cutoff <-1SD for weight-for-length and length-for-age was used to define wasting and stunting. Multivariable linear regression analysis explored if cumulative enteric parasitic infections explained variability of fecal biomarkers, after adjusting for potential confounders. Eighty infants were included. Giardia duodenalis and soil-transmitted helminths (STH) were the most frequent parasites. The median (interquartile range) levels were 2.87 μg/g (2.41-3.92) for S100A12 and 165.1 μg/g (66.0-275.6) for A1AT. Weak evidence of association was found between S100A12 levels and G. duodenalis (p = 0.080) and STH infections (p = 0.089), and between A1AT levels and parasitic infection of any etiology (p = 0.089), at 24-months of age. Significant associations between A1AT levels and wasting (p = 0.006) and stunting (p = 0.044) were found. Previous parasitic infections were not associated with fecal biomarkers at 24 months of age. To summarize, previous asymptomatic parasitic infections showed no association with intestinal barrier dysfunction. Notwithstanding, a tendency toward increased levels of the inflammatory biomarker was observed for current G. duodenalis and STH infections, and increased levels of the permeability biomarker were significantly associated with stunting and wasting.

Introduction: Portuguese population is drifting away from the Mediterranean diet-like pattern. In this context, the current nutritionalstatus of women of childbearing age and of pregnant Portuguese women and their growing fetuses is critically reviewed., Material and Methods: A narrative critical review was performed on recent published high quality studies assessing diet and nutritional status of women of childbearing age and pregnant women and its influence on the nutritional status of their offspring., Results: Data from five multinational ecological studies that included Portugal, two national official surveys on food availability, seven national studies on the diet and nutritional status of women of childbearing age and pregnant women, and five national studies on the effect of nutritional maternal factors on their growing fetuses were selected and analyzed. The prevalence of overweight/obesity has dramatically increased in Portuguese women of childbearing age and pregnant women, associated with the described trend of low adherence to Mediterranean diet. Variations in energy and macronutrients intakes during pregnancy seem to have no significantly impact on the nutritional status of growing fetuses. On contrary, pre-pregnancy overweight/obesity has been associated with increased offspring adiposity at birth, and an excessive gestational weight gain may be associated with offspring's overweight status in childhood. Factors potentially contributing to low adherence to the Mediterranean diet, deserving further investigation, include European Union agriculture policies that have implemented the production of non-Mediterranean food groups at low cost, and insufficient financial capacity to afford foods of quality reported by Portuguese population., Conclusion: Retrieving traditional Mediterranean dietary habits should be incorporated into strategies for prevention and treatment ofoverweight/obesity in Portugal, especially in women of childbearing age.

Background: This study aimed to determine factors associated with body composition changes shortly after liver transplantation (LTx), including the influence of immunosuppressive agents. The combined resting energy expenditure (REE) and handgrip strength provided a valuable assessment in data interpretation of body composition., Methods: This observational single-center study included a cohort of consecutive end-stage liver disease patients with indications for LTx over 2 years. Cyclosporine was preferred for diabetic, hepatitis C-infected, and human immunodeficiency virus-infected patients per the transplant center protocol. Subjective Global Assessment, handgrip strength, multifrequency bioelectrical impedance analysis, and REE measurements were collected. The assessments were performed before LTx (T0) and at medians of 9 (T1) and 36 (T2) days after LTx. The fat mass index (FMI) and lean mass index (LMI) were surrogates of adiposity and skeletal muscle, respectively. Multiple linear regression analysis was used., Results: Fifty-six patients with a mean age of 53.7 (8.5) years were included; 87.5% were men. Preoperative Subjective Global Assessment undernourishment (β-estimate = 17.9; P = 0.004) and of drug addiction absence (β estimate = 14.6; P = 0.049) were associated with FMI increase. Higher REE at T1 (per 100 kcal) was associated with LMI increase (β estimate = 1.70; P = 0.012) and body cell mass increase (β estimate = 1.60; P = 0.049). The cyclosporine-based regimen was associated with FMI decrease (β estimate = -25.64; P < 0.001) and LMI increase (β estimate = 23.76; P < 0.001) when compared with a tacrolimus-based regimen. Steroids did not affect body composition., Conclusions: The cyclosporine-based regimen was independently associated with decreased adiposity and increased skeletal muscle compared with the tacrolimus-based regimen. Future randomized controlled trials are needed to confirm these findings.

Objective: An early and accurate recognition of success in treating obesity may increase the compliance of obese children and their families to intervention programs. This observational, prospective study aimed to evaluate the ability and the time to detect a significant reduction of adiposity estimated by body mass index (BMI), percentage of fat mass (%FM), and fat mass index (FMI) during weight management in prepubertal obese children., Methods: In a cohort of 60 prepubertal obese children aged 3-9 years included in an outpatient weight management program, BMI, %FM, and FMI were monitored monthly; the last two measurements were assessed using air displacement plethysmography. The outcome measures were the reduction of >5% of each indicator and the time to achieve it., Results: The rate of detection of the outcome was 33.3% (95% CI: 25.9-41.6) using BMI, significantly lower (p<0.001) than either 63.3% using %FM (95% CI: 50.6-74.8) or 70.0% (95% CI: 57.5-80.1) using FMI. The median time to detect the outcome was 71 days using FMI, shorter than 88 days using %FM, and similar to 70 days using BMI. The agreement between the outcome detected by FMI and by %FM was high (kappa 0.701), but very low between the success detected by BMI and either FMI (kappa 0.231) or %FM (kappa 0.125)., Conclusions: FMI achieved the best combination of ability and swiftness to identify reduction of adiposity during monitoring of weight management in prepubertal obese children., (Copyright © 2016 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.)

This systematic review discusses data on the dietary intake of preschool children living in the Mediterranean countries of the European Union, including the comparison with a Mediterranean-like diet and the association with nutritional status. Specifically, data from the multinational European Identification and Prevention on Dietary and life style induced health effects in children and infants (IDEFICS) study and national studies, such as the Estudo do Padrão Alimentar e de Crescimento Infantil (EPACI) study and Geração XXI cohort in Portugal, ALimentando la SAlud del MAñana (ALSALMA) study in Spain, Étude des Déterminants pré-et postnatals précoces du développement et de la santé de l'ENfant (EDEN) cohort in France, Nutrintake 636 study in Italy, and Growth, Exercise and Nutrition Epidemiological Study in preSchoolers (GENESIS) cohort in Greece, were analyzed. In the majority of countries, young children consumed fruit and vegetables quite frequently, but also consumed sugared beverages and snacks. High energy and high protein intakes mainly from dairy products were found in the majority of countries. The majority of children also consumed excessive sodium intake. Early high prevalence of overweight and obesity was found, and both early consumption of energy-dense foods and overweight seemed to track across toddler and preschool ages. Most children living in the analyzed countries showed low adherence to a Mediterranean-like diet, which in turn was associated with being overweight/obese. Unhealthier diets were associated with lower maternal educational level and parental unemployment. Programs promoting adherence of young children to the traditional Mediterranean diet should be part of a multi-intervention strategy for the prevention and treatment of pediatric overweight and obesity.

Very preterm infants (<32 weeks' gestation) are at high risk for impaired skeletal development because of factors that limit the provision of extrauterine nutrients. Cumulative net deficiencies of calcium, phosphorus, docosahexaenoic acid (DHA), and arachidonic acid (ARA) are evident in these infants after prolonged administration of total parenteral nutrition (TPN). This is significant because minerals as well as metabolites of DHA and ARA are important modulators of bone cell differentiation, lengthening of bone, and bone matrix deposition. Furthermore, diets containing only precursors of DHA and ARA result in suboptimal skeletal growth. With the emergence of new intravenous lipid emulsions, it is important to understand the impact of fatty acids on bone metabolism in the third trimester in order to optimize the provision of TPN in very preterm infants. The purpose of this review is to evaluate current evidence regarding intravenous lipid emulsions and bone metabolism in very preterm infants receiving prolonged TPN and to identify areas of research needed., (© The Author(s) 2015. Published by Oxford University Press on behalf of the International Life Sciences Institute. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

A novel RFX6 homozygous missense mutation was identified in an infant with Mitchell-Riley syndrome. The most common features of Mitchell-Riley syndrome were present, including severe neonatal diabetes associated with annular pancreas, intestinal malrotation, gallbladder agenesis, cholestatic disease, chronic diarrhea, and severe intrauterine growth restriction. Perijejunal tissue similar to pancreatic tissue was found in the submucosa, a finding that has not been previously reported in this syndrome. This case associating RFX6 mutation with structural and functional pancreatic abnormalities reinforces the RFX6 gene role in pancreas development and β-cell function, adding information to the existent mutation databases.

Objective: To evaluate the effect of prepregnancy body mass index (BMI), energy and macronutrient intakes during pregnancy, and gestational weight gain (GWG) on the body composition of full-term appropriate-for-gestational age neonates., Study Design: This is a cross-sectional study of a systematically recruited convenience sample of mother-infant pairs. Food intake during pregnancy was assessed by food frequency questionnaire and its nutritional value by the Food Processor Plus (ESHA Research Inc, Salem, OR). Neonatal body composition was assessed both by anthropometry and air displacement plethysmography. Explanatory models for neonatal body composition were tested by multiple linear regression analysis., Results: A total of 100 mother-infant pairs were included. Prepregnancy overweight was positively associated with offspring weight, weight/length, BMI, and fat-free mass in the whole sample; in males, it was also positively associated with midarm circumference, ponderal index, and fat mass. Higher energy intake from carbohydrate was positively associated with midarm circumference and weight/length in the whole sample. Higher GWG was positively associated with weight, length, and midarm circumference in females., Conclusion: Positive adjusted associations were found between both prepregnancy BMI and energy intake from carbohydrate and offspring body size in the whole sample. Positive adjusted associations were also found between prepregnancy overweight and adiposity in males, and between GWG and body size in females., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Objective: To evaluate the practices of neonatal parenteral nutrition (PN) compounding in Portugal and the agreement to the recommendations from the Spanish Consensus on Compounding of Parenteral Nutrition Mixtures 2008., Methods: Survey based on an electronic questionnaire on PN preparation emailed, between July and October 2009, to the pharmacists or nurses responsible for preparing neonatal PN in the 50 public and private Portuguese hospitals with neonatal special care units., Results: From the 30 hospitals where neonatal PN was prepared, 22 (73%) responded to the questionnaire. In 76.7% hospitals the PN was prepared in the hospital pharmacy and the remaining in the neonatal unit. In most hospitals the PN was only prepared in the working days. In half of cases the professional responsible for the preparation received the prescription in electronic support. The problems related with interpretation and validations of the prescriptions were not unusual (14-41%). Most of the Portuguese hospitals referred practices in agreement with the main recommendations from the Spanish Consensus regarding the documentation, equipment and facilities, human resources and labeling. In relation to PN admixtures, most hospitals follow the recommendations on deadlines to use, protection from light, use of terminal filters for infusion, and physical and chemical control by visual inspection and microbiological control., Conclusions: The results from this study provide a good insight of the practice of preparation of neonatal NP in Portugal. The comparison with the Spanish Consensus contributes to identify weaknesses., (Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.)

Introduction: The use of guidelines for neonatal parenteral nutrition (PN) improves its clinical efficiency and the safety of prescription., Objective: To evaluate the practices of neonatal parenteral nutrition prescription in Portugal, and the adherence to the National Consensus on neonatal PN (2008)., Methods: A questionnaire based on a multiple choice response on parenteral nutrition prescription was conducted, and sent to the coordinators of the 50 public and private Portuguese neonatal special care units, 25 being level III and 25 level II., Results: Parenteral nutrition was prescribed in 32 neonatal units, 23 of which (71.9%) responded to the questionnaire. Of the respondents, 19 (82.6%) refer to follow the National Consensus, the remaining following local guidelines; 17 (73.9%) of units referred to using an electronic based system for prescription. In preterm neonates, most mentioned: administering judiciously the fluid intake during the first post-natal week; starting amino acids from the first post-natal day with 1.5-3g/kg/d, increasing up to 3-4g/kg/d; starting lipids from the first three post-natal days with 1g/kg/d, increasing up to 3g/kg/d; administering 40-70mg/kg/d of calcium and of phosphorus with the fixed calcium:phosphorus ratio of 1.7: 1 (mg:mg); and estimating the osmolality of the solutions, and weekly monitoring of serum triglycerides, blood urea, serum phosphorus and liver function., Conclusions: The high response rate is probably representative of the practice of PN prescription in Portugal. Most of the units used the National Consensus on neonatal PN as a reference, thus contributing to better nutritional support for neonates., (Copyright © 2012 Asociación Española de Pediatría. Published by Elsevier Espana. All rights reserved.)

Fibroblasts colonization into injured areas during wound healing (WH) is responsible for skin remodelling and is also involved in the modulation of inflammation, as fibroblasts are immunologically active. Herein, we aimed to determine neurotensin effect on the immunomodulatory profile of fibroblasts, both in homeostatic and inflammatory conditions. Neurotensin mediated responses occurred through NTR1 or NTR3 receptors, while under inflammatory conditions NTR1 expression increase seemed to modulate neurotensin responses. Among different immunomodulatory genes, CCL11, IL-8, and IL-6 were the most expressed genes, while CCL4 and EGF were the less expressed genes. After neurotensin exposure, IL-8 mRNA expression was increased while CCL11 was decreased, suggesting a proinflammatory upregulation and chemoattractant ability downregulation of fibroblasts. Under inflammatory conditions, gene expression was significantly increased. After neurotensin exposure, CCL4 and IL-6 mRNA expression were decreased while CCL11 was increased, suggesting again a decrease in the chemoattractant capacity of fibroblasts and in their proinflammatory status. Furthermore, the expression of EGF, a crucial growth factor for skin cells proliferation and WH, was increased in all conditions. Overall, neurotensin, released by nerve fibers or skin cells, may be involved in the decrease of the chemotaxis and the proinflammatory status in the proliferation and remodelling phases of WH.

Aim: To obtain reference values for bone strength assessed early after birth for term and preterm neonates in Portugal., Methods: Speed of sound (SOS) (m/s) was measured using the quantitative ultrasound method in a systematic sample of appropriate-for-gestationalage term and preterm neonates, within the first two and five days after birth, respectively. Homogeneity of values between genders and between gestational age groups was assessed., Results: A sample of 158 neonates was enrolled, 34 full-term and 124 preterm (26-41 weeks of gestation), birth weights of 595g-4195g, 84 males (53.2%) and 20 twins (10.8%). The mean of the SOS significantly increases with gestational age. Reference values of SOS for gestational age groups are provided as 10th, 25th, 50th, 75th and 90th centiles without gender distinction., Conclusion: Reference values for SOS early after birth are made available for term and preterm appropriate-for-gestational age neonates, reflecting the intrauterine bone status, a baseline for follow-up studies on bone strength in Portugal.

Background: Upper arm anthropometry has been used in the nutritional assessment of small infants, but it has not yet been validated as a predictor of regional body composition in this population., Objective: Validation of measured and derived upper arm anthropometry as a predictor of arm fat and fat-free compartments in preterm infants., Methods: Upper arm anthropometry, including the upper arm cross-sectional areas, was compared individually or in combination with other anthropometric measurements, with the cross-sectional arm areas measured by magnetic resonance imaging, in a cohort of consecutive preterm appropriate-for-gestational-age neonates, just before discharge., Results: Thirty infants born with (mean +/- SD) a gestational age of 30.7 +/- 1.9 weeks and birth weight of 1,380 +/- 325 g, were assessed at 35.4 +/- 1.1 weeks of corrected gestational age, weighing 1,785 +/- 93 g. None of the anthropometric measurements are reliable predictors (r(2) < 0.56) of the measurements obtained by magnetic resonance imaging, individually or in combination with other anthropometric measurements., Conclusion: Both measured anthropometry and derived upper arm anthropometry are inaccurate predictors of regional body composition in preterm appropriate-for-gestational-age infants., ((c) 2008 S. Karger AG, Basel.)

Maximal blood lactate steady state concentration (MLSS) and anaerobic threshold (AT) have been shown to accurately predict long distance events performance and training loads, as well, in human athletes. Horse endurance races can take up to 160 km and, in practice, coaches use the 4 mM blood lactate concentration, a human based fixed concentration to establish AT, to predict training loads to horse athletes, what can lead to misleading training loads. The lactate minimum speed (LMS) protocol that consists in an initial elevation in blood lactate level by a high intensity bout of exercise and then establishes an individual equilibrium between lactate production and catabolism during progressive submaximal efforts, has been proposed as a nonfixed lactate concentration, to measure individual AT and at the same time predicts MLSS for human long distance runners and basketball players as well. The purpose of this study was to determine the reliability of the LMS protocol in endurance horse athletes. Five male horses that were engaged on endurance training, for at least 1 year of regular training and competition, were used in this study. Animals were submitted to a 500 m full gallop to determine each blood lactate time to peak (LP) after these determinations, animals were submitted to a progressive 1000 m exercise, starting at 15 km h(-1) to determine LMS, and after LMS determination animals were also submitted to two 10,000 m running, first at LMS and then 10% above LMS to test MLSS accuracy. Mean LP was 8.2+/-0.7 mM at approximately 5.8+/-6.09 min, mean LMS was 20.75+/-2.06 km h(-1) and mean heart rate at LMS was 124.8+/-4.7 BPM. Blood lactate remained at rest baseline levels during 10,000 m trial at LMS, but reached a six fold significantly raise during 10% above LMS trial after 4000 and 6000 m (p<0.05) and (p<0.01) after 8000 and 10,000 m. In conclusion, our adapted LMS protocol for horse athletes proposed here seems to be a reliable method to state endurance horse athletes LT and MLSS.

Aim: To assess the degree of discomfort caused by length measurement in neonates, performed with one or both lower limbs extended, on the first and second day after birth, with either one or both lower limbs extended., Methods: Healthy full-term neonates were systematically sampled during the months of February and March 2004. Crown-heel length was measured, using a 1-mm precision neonatometer, at approximately 8 h and 32 h after birth, with one and both lower limbs extended. The Neonatal Facial Coding System was used to assess discomfort during measurements. Data were analysed by parametric and non-parametric tests as appropriate., Results: Whatever the measurement technique, discomfort scores are significantly higher during the length measurement than at baseline. Whenever length measurements are performed, discomfort scores are significantly higher when extending both lower limbs rather than one lower limb (p < 0.006). The measured length is greater with one lower limb extended; however, the difference decreases over time, being 0.19 cm (95% CI 0.1-0.3; p < 0.001) at approximately 32 h of age. No significant differences in length were found between measurements at approximately 8 or 32 h, regardless of the technique used. The best correlation between length measurements with one or both lower limbs extended was observed at approximately 32 h after birth (r = 0.98)., Conclusion: Measuring crown-heel length is a distressful procedure for the neonate. Measurements with one lower limb extended result in less discomfort than when both lower limbs are extended, without decreasing the accuracy.

The availability of newer, more sophisticated and versatile bronchoscopes has expanded the spectrum and scope of the indications for bronchoscopy in the newborn infant both for diagnostic and therapeutic purposes. The aim of this study was to carry out a retrospective analysis of the bronchoscopies performed on newborn infants, and to review the indications of this procedure in this age group. Sixty-three patients were submitted to 67 bronchoscopies in a period of 13 years, allowing the diagnosis of 45 anomalies and malformations of the tracheo-bronchial tree, and the performance of 24 bronchoalveolar lavages. In six cases, endoscopic removal of secretions helped to resolve resistant atelectasia, while in another case, with esophageal atresia, intra-operative definition of the fistula tract was possible through catheterisation of the fistula with the bronchoscope. The flexible bronchoscope was preferred for diagnosis by direct visualisation, and the rigid bronchoscope for some diagnostic and therapeutic procedures. Stridor, unexplained cyanosis, hemoptysis, persistent or recurrent pulmonary images, difficulties in the intubation or extubation, and persistent disturbances in ventilation are among the main indications for bronchoscopy in the newborn infant. Bronchoscopy also allows the performance of subsidiary techniques, such as bronchoalveolar lavage, biopsy and laser therapy.

Introduction: The scientific activity performed by doctors, whilst working in central hospitals, should be the major setting for clinical research. The purpose of this retrospective study was to measure the scientific activity and clinical research carried out by the medical staff at the central Hospital Dona Estefania., Methods: Between 1993 and 2002 (ten years) the abstracts included in the Hospital Dona Estefania's Scientific Year Book were analyzed. The type of studies, the number of communications and publications, and the scientific production (based on the ratio of number of studies per doctor in each specialty and subspecialty) were determined., Results: During the ten years analyzed, 1821 studies were included and 49.7% of them were considered to be clinical research; the mean annual scientific production of the Hospital was 182 studies, 165 communications and 24.5 publications. During the year of 2002, 312 doctors in 24 specialties and subspecialties were considered, with a mean ratio per doctor of 0.73 studies, including 0.29 research studies., Conclusions: The Scientific Year Book was an extremely useful tool to directly measure the scientific activity and research of doctors working at the Hospital, including published and unpublished papers. As yet, there is no similar national study available to compare the obtained results. Nonetheless, the analyzed scientific activity, particularly the clinical research, appears to be insufficient considering that the analyzed scientific production belongs to a central hospital. The excessive clinical work and the negligible value for research considered in the Portuguese national regulations for contracting doctors for the permanent staff of central hospitals may have contributed towards the poor motivation of doctors in research found in this study.

Unlabelled: A predictive equation of osmolarity that correlates closely with the measured osmolality was determined. Taking into account that an osmometer is not available in most clinical settings, the proposed equation appears to provide a quick and simple osmolarity calculation of neonatal parenteral nutrition solutions., Objective: We measured the osmolalities of neonatal parenteral nutrition (PN) solutions to determine if these values may be predicted by a simple equation for calculation of their osmolarity values., Methods: The osmolalities of 101 consecutive different final PN admixtures, prepared for 36 neonates, were measured by the freezing point depression method. The respective intra-assay and interassay coefficients of variation were always <2.1%. Linear multivariate regression analysis was used to determine a predictive equation of osmolarity that correlates closely with the value of measured osmolality., Results: The mean (SD) osmolality of the final PN admixtures was 749.7 (165.4) mOsm/kg. The best-fitted equation, with a coefficient of discrimination R2 = .95 (R2 = .90 for samples between 500 and 1000 mOsm/L) is osmolarity (mOsm/L) = (nitrogen x 0.8) + (glucose x 1.235) + (sodium x 2.25) + (phosphorus x 5.43)-50, with the concentration of components in mmol/L. Adapting the equation in our daily practice, using g/L for glucose and amino acids, mg/L for phosphorus, and mEq/L for sodium, the equation is osmolarity (mOsm/L) = (amino acid x 8) + (glucose x 7) + (sodium x 2) + (phosphorus x 0.2) - 50, with a similar R2., Conclusions: Taking into account that an osmometer is not available in most clinical settings, the proposed equation appears to provide a quick and simple osmolarity calculation of neonatal PN solutions, thus allowing more accurate decisions to be taken regarding the choice of route and rate of administration of PN solutions.

We examined intra- and extracellular H(2)O(2) and NO formation during contractions in primary rat skeletal muscle cell culture. The fluorescent probes DCFH-DA/DCFH (2,7-dichlorofluorescein-diacetate/2,7-dichlorofluorescein) and DAF-2-DA/DAF-2 (4,5-diaminofluorescein-diacetate/4,5-diaminofluorescein) were used to detect H(2)O(2) and NO, respectively. Intense electrical stimulation of muscle cells increased the intra- and extracellular DCF fluorescence by 171% and 105%, respectively, compared with control nonstimulated cells (p <.05). The addition of glutathione (GSH) or Tiron prior to electrical stimulation inhibited the intracellular DCFH oxidation (p <.05), whereas the addition of GSH-PX + GSH inhibited the extracellular DCFH oxidation (p <.05). Intense electrical stimulation also increased (p <.05) the intra- and extracellular DAF-2 fluorescence signal by 56% and 20%, respectively. The addition of N(G)-nitro-L-arginine (L-NA) completely removed the intra- and extracellular DAF-2 fluorescent signal. Our results show that H(2)O(2) and NO are formed in skeletal muscle cells during contractions and suggest that a rapid release of H(2)O(2) and NO may constitute an important defense mechanism against the formation of intracellular (*)OH and (*)ONOO. Furthermore, our data show that DCFH and DAF-2 are suitable probes for the detection of ROS and NO both intra- and extracellularly in skeletal muscle cell cultures.

The reaction of trans-[Ru(NH(3))(4)P(OEt)(3)NO](3+) and mitochondria was investigated through differential pulse polarography and fluorimetry. The nitrosyl complex undergoes one-electron reduction centered on the NO ligand site. The reaction between the mitochondrial reductor and trans-[Ru(NH(3))(4)P(OEt)(3)NO](3+) exhibits a second order specific rate constant calculated as k=2 x 10(1) M(-1) s(-1). The reduced species, trans-[Ru(NH(3))(4)P(OEt)(3)NO](2+), quickly releases NO, yielding trans-[Ru(NH(3))(4)P(OEt)(3)H(2)O](2+). The low toxicities of both trans-[Ru(NH(3))(4)P(OEt)(3)(NO)](2+) and trans-[Ru(NH(3))(4)P(OEt)(3)H(2)O](2+) and its ability to release NO after reductive activation in a biological medium make the nitrosyl compound a useful model of a hypotensive drug.

The malarial parasite Plasmodium vivax causes disease in humans, including chronic infections and recurrent relapses, but the course of infection is rarely fatal, unlike that caused by Plasmodium falciparum. To investigate differences in pathogenicity between P. vivax and P. falciparum, we have compared the subtelomeric domains in the DNA of these parasites. In P. falciparum, subtelomeric domains are conserved and contain ordered arrays of members of multigene families, such as var, rif and stevor, encoding virulence determinants of cytoadhesion and antigenic variation. Here we identify, through the analysis of a continuous 155,711-base-pair sequence of a P. vivax chromosome end, a multigene family called vir, which is specific to P. vivax. The vir genes are present at about 600-1,000 copies per haploid genome and encode proteins that are immunovariant in natural infections, indicating that they may have a functional role in establishing chronic infection through antigenic variation.

Cytoadhesion of parasitized red blood cells (PRBCs) to vascular endothelial cells (sequestration) and binding of unparasitized RBCs to PRBCs (rosetting) are virulence factors of Plasmodium falciparum, the species responsible for lethal human malaria. Variant antigens involved in both phenomena have been identified as products of the multicopy var gene family. In this review, progress in the understanding of molecular mechanisms of sequestration is summarized, in particular, concerning the structure of var gene products related to specificity of binding to endothelial receptors, and the origin of var gene diversity.

Seventy-nine adults with Plasmodium vivax malaria, from the Porto Velho area of Rond nia (western Amazon region, Brazil), gave informed consent to participate in a blind, clinical study of two regimens of treatment with chloroquine (CQ) and primaquine. The effectiveness of the 'classical' regimen (CQ for 3 days, followed by primaquine for 14 days) was compared with that of a 'short' regimen in which the two drugs were given simultaneously for 5 days. There were no cases of recrudescence indicative of CQ resistance (i.e. within 30 days of the first treatment dose) among the 73 patients who each completed a full, supervised course of treatment. However, 10 cases of apparent relapse were observed (all > 60 days after first treatment dose), representing 6.5% (2/31) of the patients who completed 60 days of follow-up after the classical treatment and 26.7% (8/30) of the short-regimen patients who completed the same period of follow-up. PCR-based comparison of parasitic DNA collected pre- and post-treatment was successful for eight of the 10 cases of apparent relapse and indicated that two such cases, both given the short regimen of treatment, were, in fact, probable cases of re-infection rather than of relapse. The results indicate that the classical schedule of treatment with chloroquine and primaquine was more effective at preventing relapses than the short regimen. However, since prolonged treatment with primaquine often produces side-effects that are severe enough to reduce compliance, the short schedule could be a useful alternative for malaria control in endemic areas of the Amazon region.

Given the potential of reactive oxygen species to damage intracellular proteins during subsequent bouts of muscle contractions, it was suggested that, when this production exceeds the antioxidant capacity, the preexisting antioxidant pathways may be complemented by the synthesis of the defense mechanism represented by heat shock proteins (HSPs), stress proteins with the function of repair and maintaining protein folding. To test this hypothesis, we analyzed reactive carbonyl derivatives in plasma and the expression of HSP72 and activities of enzymes from the oxidative and antioxidant defense systems in the soleus muscle of sedentary rats and rats trained by two protocols: continuous and intermittent. We analyzed all three groups at rest and 2 h after acute exercise. After 8 wk of training, the animals from both groups clearly demonstrated higher resistance to exercise. Both trained groups showed significantly higher citrate synthase, catalase, and glutathione reductase activities than the control group (P < 0.01). After acute exercise, catalase and glutathione reductase activities significantly decreased (P < 0.01) and plasma reactive carbonyl derivatives significantly increased (P < 0.05) in the sedentary group, suggesting an oxidative-stress condition as responsible for exhaustion in this group. Finally, after acute exercise, the induction of HSP72 expression occurred only in the sedentary group, suggesting that HSP72 acts as a complementary protective mechanism in exercise-induced oxidative stress.

Since the late 1970s pyrimethamine-sulfadoxine (PS; FansidarTM Hoffman-LaRoche, Basel) has been used as first line therapy for uncomplicated malaria in the Amazon basin. Unfortunately, resistance has developed over the last ten years in many regions of the Amazon and PS is no longer recommended for use in Brazil. In vitro resistance to pyrimethamine and cycloguanil (the active metabolite of proguanil) is caused by specific point mutations in Plasmodium falciparum dihydrofolate reductase (DHFR), and in vitro resistance to sulfadoxine has been associated with mutations in dihydropteroate synthase (DHPS). In association with a proguanil-sulfamethoxazole clinical trial in Brazil, we performed a nested mutation-specific polymerase chain reaction to measure the prevalence of DHFR mutations at codons 50, 51, 59, 108 and 164 and DHPS mutations at codons 436, 437, 540, 581 and 613 at three sites in the Brazilian Amazon. Samples from two isolated towns showed a high degree of homogeneity, with the DHFR Arg-50/Ile-51/Asn-108 and DHPS Gly-437/Glu-540/Gly-581 mutant genotype accounting for all infections in Peixoto de Azevedo (n = 15) and 60% of infections in Apiacás (n = 10), State of Mato Grosso. The remaining infections in Apiacás differed from this predominant genotype only by the addition of the Bolivia repeat at codon 30 and the Leu-164 mutation in DHFR. By contrast, 17 samples from Porto Velho, capital city of the State of Rondônia, with much in- and out-migration, showed a wide variety of DHFR and DHPS genotypes.

Dipyridamole (DIP), a coronary vasodilator, presents coactivator activity for a number of antitumor drugs as well as antioxidant activity in membrane systems. DIP and derivatives interact with membrane systems such as micelles, phospholipid monolayers and vesicles. The antioxidant effect of DIP and several derivatives upon iron-induced lipoperoxidation on mitochondria has been reported and a good correlation between the hydrophobicity and their protective effect was found (M.F. Nepomuceno et al., Free Radic. Biol. Med., 23 (1997) 1046-1054). In the present work an effort is made to better understand the role of DIP as inhibitor of Fe2+-induced lipid peroxidation in mitochondria. At low concentration, no significant effect on either state IV or state III respiration was found, discarding a possible direct interaction of DIP or RA-25 with the peripheral benzodiazepine receptor. The association constants for DIP and RA-25 in mitochondria were estimated, being 0.7 (mg/ml)-1 for DIP and 0.2 (mg/ml)-1 for RA-25. Oxygen consumption studies in the presence of FeSO4 showed that the antioxidant effect of DIP or RA-25 did not involved the initial step of Fe2+ oxidation. Our data strongly support the hypothesis that the antioxidant effect of both DIP and RA-25 is related to their partition in the lipid phase of the mitochondrial membrane and not to a specific interaction with membrane proteins. This protection may be due either to a direct inhibition of the propagation steps or a scavenger effect on the radicular species that would trigger the peroxidative process.

We report on a longitudinal study concerning the incidence of malaria in a riverine population (Portuchuelo) settled on the riverbanks of Rio Madeira, in the State of Rondonia, Brazil. We found the incidence of malaria to be seasonal, prevailing in the dry months of June and July. The Annual Parasite Index (API) was 292/1000 inhabitants, almost three times that of the state of Rondonia for the same period. In contrast with other studied Rondonian populations, malaria in Portuchuelo was more prevalent in youngsters < 16 years old, particularly in the 0-1 year age group. Adults were relatively spared, particularly those over 50 years. Besides being indicative of indoor transmission, these facts may suggest the existence of a certain degree of acquired resistance to infection and/or of lessened symptoms in older people. Riverine populations are spread over the entire Amazon region where most of its members were born. Due to the permanent presence of malaria among riverine populations, we are proposing that they may act as perennial reserves of malaria and, therefore, as sources of infection for migrants or eventual settlers at their vicinity. To date, the opposite view has been generally held. Anopheles darlingi, the main vector species in the area, is essentially sylvatic, which contributes to make the control of malaria highly problematic. The only hopes for control rest on permanent surveillance and the prompt treatment of patients, which are also problematic considering the vastness of the Amazon region and the remoteness of some of its riverine settlements.

The mitochondrial permeability transition was investigated under both oxidative and nonoxidative conditions. It was observed that dithiothreitol (DTT) was able to inhibit the permeability transition only when an oxidant, t-butylhydroperoxide, was used. Although cyclosporin A (CsA) showed also a partial protective effect under these conditions, it progressively lost its ability as the oxidant concentration was increased. Indeed, CsA and ADP were very effective under nonoxidative conditions where Ca2+ and Pi were used to induce the permeability transition, and no effect of DTT was observed. These results suggest that the Ca(2+)-dependent permeability transition pore opening is not directly dependent of dithiol oxidation. It was also shown here that CsA, independent of the presence of ADP, was able to restore the mitochondrial membrane electrical potential (delta psi) after the Ca(2+)-induced collapse. Moreover, carboxyatractyloside (CAT) did not prevent the effect of CsA, even when previously added, although it completely abolished the protective effect of ADP, indicating the participation of the ADP/ATP carrier on this process. The data with submitochondrial particles, besides providing further support to the existence of two distinct binding sites for Ca2+ in the mitochondrial inner membrane, with opposite effects on the pore opening probability, demonstrated, for the first time, that very low Ca2+ concentrations induced the permeability transition pore (PTP) opening in submitochondrial particles, an event fully prevented by CsA. The existence of such CsA-sensitive Ca(2+)-induced pore in submitochondrial particles also suggests that matrix cyclophilin is probably not the mediator of this process.

We describe here a new Plasmodium falciparum antigen, asparagine and aspartate rich protein 2 (PfAARP2) of 150 kDa, which is encoded by a unique gene on chromosome 1. PfAARP2 is first expressed 12 h post-invasion and accumulates in trophozoites and schizonts. Immunofluorescence studies indicate that PfAARP2 is translocated into the red blood cell cytoplasm. The central region of Pfaarp2 contains blocks of repetitions encoding asparagine and aspartate residues, which define a new family of related genes dispersed on different chromosomes, and two members of this family have also been identified. Interestingly, the non-repeated N- and C-termini of PfAARP2 display significant similarity to two yeast and human predicted proteins, and its possible function is discussed.

We have recently shown that an IgG preparation obtained from immune African donors was able to control Plasmodium falciparum multiplication in the blood of Thai patients, but had no inhibitory activity against the parasite in vitro. The same IgG preparation was passively transferred to Saimiri monkeys acutely infected with two different strains of P. falciparum, one of African origin and the other from French Guyana. A dose-dependent in vivo inhibition of parasite development was observed with both strains. The results justify the use of Saimiri monkeys for malaria vaccine trials and permit the introduction of new techniques for screening of candidate antigens for vaccines.

The squirrel monkey Saimiri sciureus is an experimental host for a range of human pathogens, and for the assessment of vaccine candidate antigens and vaccine strategies. This experimental host is thus particularly suitable for the follow-up of humoral responses. To understand some of the mechanisms that underlie the defense against experimental pathogens, there is a need of basic knowledge on cellular immune effectors also. The authors report here their experience in characterizing squirrel monkey blood T and B lymphocytes, and in studying in vitro induced activation and proliferation of T and B cells. Particular emphasis is given to the in vitro differentiation of squirrel monkey B cells into immunoglobulin secreting cells, with respect to Plasmodium falciparum antigens.

A monkey vaccination trial using a Plasmodium falciparum protein fraction containing antigens of 90-110 kDa is reported. The fraction was obtained by electroelution from preparative polyacrylamide gels. Three monkeys out of five resisted a heavy challenge dose of highly virulent parasites. Using specific antisera, several components of the fraction were identified, namely heat shock protein 90 (hsp90), Ag44/RhopH3, ABRA, 96tR/GBP130 and Pf96 protease. The fraction did not contain KAHRP, nor the SERP antigen. The antibody response of the monkeys was studied on these individual antigens purified by preparative immunoprecipitation. Surprisingly, hsp90 was found in the immunoprecipitates obtained with SERP antisera. Interestingly, the response to hsp90 correlated with protection, high antibody titres being found only in the protected monkeys. In contrast, no correlation with protection could be found for the response to the other antigens.

The activity of the mitochondrial inorganic pyrophosphatase from Saccharomyces cerevisiae was measured in the presence of increasing concentrations of magnesium and calcium. Calcium pyrophosphate (dissociation constant Kd = 1.9 microM) inhibited pyrophosphatase by competition with magnesium pyrophosphate (Kd = 50 microM). The small movements of calcium detected in mitochondria from yeast may be physiologically significant for the control of inorganic pyrophosphatase activity and the concentration of pyrophosphate in the matrix of yeast mitochondria.

The effect of cyclosporin A (CsA) or trifluoperazine (TFP) on lipid peroxidation and mitochondrial swelling was determined using liver mitochondria incubated with 30 microM Ca2+ and 250 microM t-butylhydroperoxide or 5 mM inorganic phosphate (P(i)). Lipid peroxidation was not modified by either 1 microM CsA or 40 microM TFP. These compounds presented a distinct effect on mitochondrial permeability. Under oxidative conditions, CsA only showed a transient protective effect whereas TFP completely inhibited mitochondrial swelling. Conversely, CsA was very efficient when Ca2+ and P(i) were used, a condition under which TFP was unable to prevent the swelling. These data are consistent with our previous results (M.F. Nepomuceno, D.V. Macedo and L. Pereira-da-Silva (1991). Brazilian Journal of Medical and Biological Research, 24: 833-836) showing that lipid peroxidation is one among other different components of the permeabilization process. The data suggest that lipid peroxidation is independent of swelling, occurring later than swelling, presumably when the mitochondrial reductant systems are depleted. The differential effects of CsA and TFP suggest that these compounds can be used as specific probes in the elucidation of the two distinct mechanisms responsible for mitochondrial swelling.