Oxygen Uptake Efficiency Slope in South American Healthy Adults: COMPREHENSIVE REFERENCE VALUES AND INTERNATIONAL COMPARISONS.

PURPOSE: The purpose of this study is to provide comprehensive reference values for oxygen uptake efficiency slope (OUES) in healthy adults. International heterogeneity was also explored through published databases. METHODS: A cross-sectional study was conducted with treadmill cardiopulmonary exercise testing (CPX) from a Brazilian healthy adult sample, in which absolute OUES and values normalized by weight and body surface area (BSA) were calculated. Data were stratified by sex and age group. Prediction equations were calculated using age and anthropometric variables. International data were pooled and differences were explored using factorial analysis of variance or the t test, as appropriate. The OUES age-related patterns were calculated using regression analysis. RESULTS: A total of 3544 CPX were included (1970 males and 1574 females) and the age ranged from 20-80 yr. Males had higher values than females for OUES, OUES/kg, and OUES/BSA. Lower values were found with aging and the data followed a quadratic regression curve. Reference value tables and predictive equations were provided for absolute and normalized OUES in both sexes. International comparisons of absolute OUES values among Brazilian, European, and Japanese data revealed substantial heterogeneity. The OUES/BSA measure minimized the discrepancies between Brazilian and European data. CONCLUSIONS: Our study provided comprehensive OUES reference values in a large healthy adult sample from South America with a wide age range and included absolute and normalized values. Differences observed between Brazilian and European data were reduced in the BSA-normalized OUES.

Uncontrolled pain in critically ill patients and acute kidney injury: a hypothesis-generating cohort study.

BACKGROUND: In critically ill patients, acute pain occurs frequently, causes sympathetic activation, release of inflammatory mediators, and potential organ dysfunction, with the kidneys potentially sensitive to inflammation-mediated injury. This study aimed to explore the association between acute pain in critically ill patients and the occurrence of acute kidney injury (AKI). METHODS: Data from a retrospective cohort of adult patients admitted between June 2013 and June 2016 to the Intensive Care Unit (ICU) of a tertiary hospital in São Paulo, Brazil, were analyzed. The main exclusion criteria were ICU length of stay < 48 h, coma, and prior kidney dysfunction. The outcome (AKI) was defined as an elevation in the baseline serum creatinine level of ≥ 0.3 mg/dl and/or > 50% at any time after the first 48 h in the ICU. Multivariable logistic regression and hierarchical cluster analysis were performed. RESULTS: The isolated incidence of pain was 23.6%, and the incidence of pain duration > 5 days was 10.6%. AKI occurred in 31.7% of the cohort. In multivariable logistic analysis, duration of pain > 5 days (OR 5.25 CI 2.19-12.57 p < 0.01) and mechanical ventilation (MV) ≥ 3 days (OR 5.5 CI 2.3-13.5 p < 0.01) were the variables with positive association with AKI. The hierarchical cluster analysis reinforced the relation between AKI, MV and duration of pain. CONCLUSIONS: Pain is an especially important issue in critically ill patients and in this exploratory study it appears to be associated with AKI development. The search for more rigorous pain control in ICU is crucial and can influence organ dysfunction.

Reference Standards for Cardiorespiratory Fitness in Brazil: A POOLED ANALYSIS AND OVERVIEW OF HETEROGENEITY IN NATIONAL AND INTERNATIONAL STUDIES.

PURPOSE: This study aimed to propose reference standards for cardiorespiratory fitness (CRF) for Brazil from a pooled analysis and to compare peak oxygen uptake (V˙ o2peak ) in Brazilian, United States (US), and Norwegian samples, exploring possible national and international differences. METHODS: Reference values for treadmill V˙ o2peak in three different Brazilian regions were assessed from previous publications. We analyzed available samples to assess possible differences, generate weighted average data for Brazil, and compared them with US and Norwegian data. RESULTS: Brazilian reference values had a lower V˙ o2peak value for the Northeast region and a higher V˙ o2peak value for the Southeast region for all sex and age groups. International comparisons with the Brazilian pooled data (n = 26661) revealed higher values for the Norwegian sample (n = 3810) and lower values for the US sample (n = 16278). The observed heterogeneity in CRF is possibly related to differences in anthropometric (weight, height) and socioeconomic factors, which differed among the samples. Also, Brazilian data showed a curvilinear V˙ o2peak age reduction trend rather than the linear characteristic commonly utilized, and the regression curves were different from those for US and Norwegian data. CONCLUSION: This study provides new CRF reference standards for Brazil. After pooling data from three Brazilian regions, a comparison revealed notable differences between regions, evidencing a negative gradient from Southern to Northern regions. Similarly, the international comparisons between Brazil, US, and Norway data revealed CRF heterogeneity, with differences in the V˙ o2peak values and in the age relationship patterns. These findings reinforce the importance of using national- or regional-specific V˙ o2peak reference values, ensuring proper CRF evaluation.

First report on the production of phytotoxic metabolites by Mycoleptodiscus indicus under optimized conditions of submerged fermentation.

An alternative to controlling weeds resistant to conventional herbicides is the isolation of new active principles. Fungi can produce phytotoxic metabolites that may be used in the development of new herbicides. The objectives of this study were: (1) isolate, select, and identify a fungus producer of phytotoxic metabolites and (2) optimize the culture conditions of this fungus in a low-cost culture medium, with the aim of increasing the phytotoxic effects of their metabolites in weeds and commercial plants. Fungi were isolated from the leaves of Conyza sp. with disease symptoms and selected according to the production of phytotoxic metabolites in solid and submerged fermentation in a low-cost culture medium. A Plackett-Burman Design and Central Composite Rotational Design were used to optimize the conditions of temperature, agitation, pH, and concentrations of glucose and yeast extract in submerged fermentation. The phytotoxic metabolites produced under optimal conditions were tested on 10 commercial plants and weeds that are difficult to control. Of the nine fungi isolated, Mycoleptodiscus indicus UFSM54 produced higher leaf lesions. The production of phytotoxic metabolites was optimized when the fungus was cultivated at 35°C, 50 rpm, and 1.5 g L-1 of glucose in submerged fermentation. The metabolites of M. indicus caused severe phytotoxic effects on germination and seedling growth, and enhanced lesion development on detached plant leaves. The present study is the first to report on the production of phytotoxic metabolites by M. indicus, a potential producer of bioherbicides.

Methodology for creating and validating object naming and semantic tests used by Verst-Maldaun Language Assessment during awake craniotomies.

Verst-Maldaun Language Assessment (VMLA) is a new intraoperative neuropsychological test (NT) within our local culture, e.g., native Portuguese speaking Brazilians. It aims to fill the specific need of an objective and dynamic approach for assessing the language network during awake craniotomies. The test includes object naming (ON) and semantic functions. This paper describes the process of validation, allowing for other centers to create their own language assessment. The validation process included 248 volunteers and the results were associated with age, gender and educational level (EL). The factor with the greatest impact was EL, followed by age. Intraoperative image learning by repetition is unlikely, since it is composed of 388 items and 70 combinations. The test will be available for free use under http://www.vemotests.com/ (beginning in February 2021).

Impact of Fat Graft Thickness and Harvesting Technique on Adipocyte Viability in a New Porcine Experimental Model: An Immunohistochemical Analysis.

BACKGROUND: Autologous fat grafting (AFG) has been employed in surgical practice as a filling method. However, controversies remain on the specifics of this technique. So far, few relevant experimental large animal studies have objectively assessed factors related to AFG integration. OBJECTIVES: This study utilized an experimental, medium-sized animal model to compare the feasibility of AFG collected employing 2 different techniques with instruments of distinct thicknesses. METHODS: Twenty minipigs (Sus scropha domesticus) were subjected to AFG harvesting via en bloc resection utilizing 3- (Group I) and 5-mm-diameter (Group II) round punch blades (PBs) and liposuction (LS) with 3- (Group III) and 5-mm-diameter cannulas (Group IV). Both samples were grafted intramuscularly (biceps femoralis). Hematoxylin and eosin staining was employed to identify intact adipocytes, fat necrosis, fibrosis, inflammation, and oil cysts. Immunohistochemical staining (perilipin-A, tumor necrosis factor alfa, and cluster of differentiation number 31) was utilized to quantify the feasibility of adipocytes, tissue necrosis, and neoangiogenesis, respectively. RESULTS: Hematoxylin and eosin analysis showed that fat necrosis and histiocyte presence were significantly lower in the AFG harvested utilizing a PB than in LS. For perilipin-A, a statistical difference was observed between subgroups I and III (P = 0.001) and I and IV (P = 0.004). Instrument diameter had no effect on graft integration in comparisons between groups II and III (P = 0.059) and II and IV (P = 0.132). CONCLUSIONS: In this experimental study, fat collected utilizing a PB demonstrated higher adipocyte viability than fat collected with LS. The diameter of the collection instruments, whether PB or LS, had no effect on graft integration.

Spirituality alleviates the burden on family members caring for patients receiving palliative care exclusively.

BACKGROUND: Spirituality can give meaning to life, providing support and guidance in complex situations. Despite its importance in palliative care, the role of spirituality for family caregivers of patients under exclusive palliative care has not received enough attention in the literature. We aimed to address the correlation between spirituality and the emotional burden of family members of patients under exclusive palliative care. METHODS: This transversal study was conducted in a tertiary private teaching hospital, in São Paulo, Brazil. The study comprised family members of patients receiving palliative care exclusively. Only one caregiver who cared for the patient for at least 2 months was invited to participate. Family members answered the following questionnaires: WHOQOL spirituality, religiousness and personal beliefs (SRPB), Zarit Burden Interview (ZBI) and Self-Reporting Questionnaire (SRQ-20). They were excluded if patients were residing in a Long Stay Institution. Continuous variables were expressed by median and quartiles and analyzed with the Kruskal-Wallis test with Muller-Dunn post-test adjusted by Bonferroni or with the Mann-Whitney test for two groups. We used multivariable linear regression to identify independent predictors of caregiver burden. RESULTS: A total of 178 family members were interviewed in a median of 8 [4-13.25] days after patient admission. Almost 40% of families presented high score of burden. Faith and Meaning in Life were the facets that scored the highest, with a median of 4.50 [4.00-5.00] for both facets. There was an inverse correlation between Zarit score and all of the WHOQOL-SRPB facets, indicating that the lower the spirituality, the greater the emotional burden. Inner peace was the strongest protective factor associated with burden. CONCLUSIONS: Psycho-socio-spiritual interaction can improve the coping ability of family caregivers of patients under exclusive palliative care, addressing a critical gap in the provision of holistic palliative care services.

KLOTHO polymorphisms and age-related outcomes in community-dwelling older subjects: The São Paulo Ageing & Health (SPAH) Study.

Defective KLOTHO gene expression in mice led to a syndrome resembling human ageing. This study evaluated three KLOTHO polymorphisms, namely G395A, C1818T, and C370S, in an elderly population (mean age of 73 years) and their associations with ageing-related outcomes (cardiovascular events, kidney function, osteoporosis, sarcopenia) and mortality. Estimated glomerular filtration rates (eGFR) was lower in subjects with 1818TT (P = 0.047) and 370SS (P = 0.046) genotypes. The 1818TT genotype (P = 0.006) and 1818T allele were associated with higher frequency of myocardial infarction (MI) (CC:1.7% vs. CT + TT:7.0%; P = 0.002). The 370SS genotype was associated with lower stroke frequency (P = 0.001). MI (OR 3.35 [95% CI: 1.29-8.74]) and stroke (OR 3.64 [95% CI: 1.48-8.97]) were associated with mortality. Regarding MI, logistic regression showed 1818T allele was a risk factor for death-related MI (OR 4.29 [95% CI: 1.60-11.52]; P = 0.003), while 370C was protective (OR 0.03 [95% CI: 0.01-0.08]; P < 0.001). Regarding stroke, the 395A and 370C alleles were protective factors (respectively: OR 0.28 [95% CI: 0.20-0.80]; P = 0.018; OR 0.10 [95% CI: 0.05-0.18]; P < 0.001). This is the first study to determine potential associations between common ageing-related outcomes/mortality and KLOTHO polymorphisms. The 1818T allele was a risk factor for MI-related death. The 395A and 370C alleles were protective factors for stroke-related death in elderly from community.

Causes of nasoenteral tube obstruction in tertiary hospital patients.

BACKGROUND/OBJECTIVES: Obstruction of the nasoenteral tube is one of the complications of enteral nutrition therapy, and its causes and frequency of occurrence are not well understood. To evaluate the causes of enteral nutrition feeding tube obstruction. To study the time elapsed between the beginning of the nutrition therapy and the obstruction of the tube. SUBJECTS/METHODS: This was a retrospective cohort study of 1170 patients aged 18 years or older who were hospitalized at Sírio-Libanês Hospital between January 2015 and October 2017, and who were undergoing enteral nutrition therapy delivered using an infusion pump through a nasogastric or nasoenteral tube. The study population included 683 (58%) men and 487 (42%) women. The median age was 79 years. Of these, 1084 patients received enteral nutrition and medication through the feeding tube, and 86 received medication alone. Variables investigated as causes of feeding tube obstruction were the administration of medication through the tube, type of diet, and use of symbiotics. RESULTS: Obstruction rates were 4% for up to 40 days of observation and 8% for the total observation time. The time for obstruction of 10% of the tubes in patients receiving rivaroxaban, linagliptin, metformin, and nystatin was 16, 19, 20, and 28 days, respectively. CONCLUSIONS: The main cause of nasoenteral tube obstruction (odds ratio) was the combination of metformin (2.0), nystatin (3.1), linagliptin (4.3), rivaroxaban (2.4), and a high-protein diet (1.9). Overall, proper tube care and strict compliance with tubal drug delivery guidelines can result in low tube obstruction rates.

Correction: Mental health and quality of life outcomes in family members of patients with chronic critical illness admitted to the intensive care units of two Brazilian hospitals serving the extremes of the socioeconomic spectrum.

[This corrects the article DOI: 10.1371/journal.pone.0221218.].

Spectrum of clinical and radiographic findings in patients with diagnosis of H1N1 and correlation with clinical severity.

BACKGROUND: The aim of this study was to evaluate the correlation between clinical and imaging findings with a worse clinical outcome in patients with a confirmed diagnosis of H1N1 influenza A virus. METHODS: Patients with a positive viral test for influenza A H1N1 in 2016 and chest radiography (CR) and/or computed tomography (CT) results had clinical and imaging data reviewed. Hospitalization, admission to the intensive care unit or death were defined as worse clinical outcomes. The association between clinical and imaging features and the worse outcome was calculated in a logistical regression model. RESULTS: Eighty of 160 (50%) patients were men, with a mean age of 43 ± 19 years. The most common symptoms were as follows: flu-like symptoms 141/160 (88%), dyspnea (25/160, 17%), and thoracic pain (7/160, 5%). Abnormalities on CR were detected in 8/110 (7%) patients, and 43/59 (73%) patients had an abnormal CT. The following variables were associated with worse clinical outcomes: the presence of diabetes mellitus (DM), hypertension, dyspnea, thoracic pain, abnormal CR or CT regardless of the type of finding, CT with consolidation or ground glass opacity. CONCLUSIONS: The presence of DM, hypertension, dyspnea, thoracic pain, or an abnormal CR or CT on admission were associated with worse clinical outcomes in patients with H1N1 influenza A virus infection. Thus, the use of readily accessible clinical and imaging features on admission may have a role in the evaluation of patients with H1N1 infection.

Mental health and quality of life outcomes in family members of patients with chronic critical illness admitted to the intensive care units of two Brazilian hospitals serving the extremes of the socioeconomic spectrum.

Chronic critical illness (CCI) is a relevant clinical, social and financial health issue. The aim of this study was to compare the mental outcomes (symptoms of anxiety and depression) and quality of life outcomes of the family members of patients with CCI from different socioeconomic backgrounds who were admitted to one of the intensive care units (ICUs) in two Brazilian hospitals, one private and one public. It is a prospective study involving a public hospital that serves a low-income population and a tertiary private hospital that serves a high-income population. Family members of patients with CCI answered the Hospital Anxiety and Depression Scale (HADS) and The World Health Organization Quality of Life-WHOQOL-bref questionnaires. They responded to the European Quality of life Five Dimension three Level (EuroQol-5D-3L) and the Activities of Daily Living (ADL) questionnaires on behalf of the patients at three time points: during the ICU stay, 30 and 90 days after the patient was discharged. We used logistic regression models to evaluate the main predictors of a binary outcome regarding symptoms of anxiety and depression. We enrolled 186 patients with CCI. Many patients from public hospitals who were independent became dependent for their ADLs at 90 days (41.7% versus 14.3%, p = 0.03). At 30 days, family members from public hospital had worse impact on all domains of WHOQOL-bref compared with families from private hospital. At 90-days, the difference persists in the physical domain, worse for families from public hospital (p = 0.006). The symptoms of depression at 30-days (p = 0.008) and at 90-days (p = 0.013) were worse in the public hospital. CCIs affected quality of life and the emotional condition of family members, especially in families with fewer resources when the patients became more dependent. Family members with higher education were more likely to experience depression, while depression was associated with cohabiting with the patient in low-income families.

[Anesthesia for muscle biopsy to test susceptibility to malignant hyperthermia]. / Anestesia durante biópsia muscular para teste de suscetibilidade à hipertermia maligna.

INTRODUCTION: Malignant hyperthermia is an autosomal dominant pharmacogenetic disorder, characterized by hypermetabolic crisis triggered by halogenated anesthetics and/or succinylcholine. The standard method for diagnosing malignant hyperthermia susceptibility is the in vitro muscle contracture test in response to halothane-caffeine, which requires muscle biopsy under anesthesia. We describe a series of anesthetic procedures without triggering agents in malignant hyperthermia, comparing peripheral nerve block and subarachnoid anesthesia. METHOD: We assessed the anesthetic record charts of 69 patients suspected of malignant hyperthermia susceptibility who underwent muscle biopsy for in vitro muscle contracture in the period of 7 years. Demographic data, indication for malignant hyperthermia investigation, in vitro muscle contracture test results, and surgery/anesthesia/recovery data were analyzed. RESULTS: Sample with 34±13.7 years, 60.9% women, 65.2% of in vitro muscle contracture test positive. Techniques used: peripheral nerve blocks - lateral femoral and femoral cutaneous, latency 65±41minutes - (47.8%); subarachnoid anesthesia (49.3%), and total venous anesthesia (1.4%). There was 39.4% failure of peripheral nerve block and 11.8% of subarachnoid anesthesia. Adverse events (8.7%) occurred only with subarachnoid blockade (bradycardia, nausea, and transient neurological syndrome). All patients remained in the post-anesthesia care unit until discharge. Age and weight were significantly higher in patients with blockade failure (ROC cut-off point of 23.5 years and 59.5kg) and blockade failure was more frequent in the presence of increased idiopathic creatine kinase. CONCLUSION: Anesthesia with non-triggering agents has been shown to be safe in patients with malignant hyperthermia susceptibility. Variables such as age, weight, and history of increased idiopathic creatine kinase may be useful in selecting the anesthetic technique for this group of patients.

Age-based ultrasonographic criteria for diagnosis of autosomal dominant polycystic kidney disease in Persian cats.

OBJECTIVES: The aim of this study was to establish ultrasound criteria for the diagnosis of autosomal dominant polycystic kidney disease (ADPKD) in Persian cats. METHODS: Eighty-two Persian cats were assessed using renal ultrasound and genotyped for the C→A transversion in exon 29 of PKD1. The animals were also submitted to hematological characterization, serum biochemistry analyses and urinalysis. RESULTS: Age, sex and neutering status did not differ between ADPKD (n = 12) and non-ADPKD (n = 70) cats. After integrated molecular genetics/ultrasonographic analysis, the presence of at least one renal cyst was sufficient to establish a diagnosis of ADPKD in animals up to 15 months of age. Two or more cysts were required for diagnosis in cats aged 16-32 months, and at least three cysts warranted diagnosis of ADPKD in animals aged 33-49 months. Finally, four or more cysts led to diagnosis in cats aged 50-66 months. Although cats with ADPKD exhibited higher serum calcium levels than non-affected cats, hematological, urinalysis and other biochemical parameters did not differ between the two groups. CONCLUSIONS AND RELEVANCE: Integrated analyses of imaging and molecular genetics data enabled, for the first time, the establishment of age-based ultrasonographic criteria for the diagnosis of ADPKD in Persian cats. The development of imaging criteria is particularly relevant and useful in the clinical setting given the current limitations to access and the cost of molecular genetics-based diagnostic tests.

Oral Fludrocortisone Test for Salt-Sensitive Screening in Hypertensive Patients: A Randomized Crossover Trial.

BACKGROUND: Salt sensitivity is associated with an increased cardiovascular risk, but the gold standard method (diet cycles) requires 24-h urine samples and has poor patient compliance. OBJECTIVES: Test the hypothesis that oral fludrocortisone (0.4 mg per day for 7 days) is a good alternative in identifying salt-sensitive patients. METHODOLOGY: We conducted a randomized crossover study with 30 hypertensive individuals comprising the following steps: (1) washout; (2) phase A (low- and high-sodium diet cycles); (3) washout 2; (4) phase B (fludrocortisone test). Phase A and B steps were performed in a random way. Consistent with the literature, we found that 53.3% were salt-sensitive according to the reference test. Using the ROC curve, the fludrocortisone test defined salt sensitivity by a median blood pressure increase of ≥3 mmHg. A good accuracy of fludrocortisone in detecting salt sensitivity was observed (AUC: 0.732±0.065; p<0.001), with 80% sensitivity and 53% specificity. CONCLUSION: The fludrocortisone test is a good option for screening salt sensitivity in hypertensive patients. However, the low specificity prevents this test from being an ideal substitute to the labor-intensive diet cycles exam in the definition of salt sensitivity. This clinical trial is registered with NCT01453959.

Resistance exercise enhances oxygen uptake without worsening cardiac function in patients with systolic heart failure: a systematic review and meta-analysis.

Recent literature suggests that resistance training (RT) improves peak oxygen uptake ([Formula: see text] peak), similarly to aerobic exercise (AE) in patients with heart failure (HF), but its effect on cardiac remodeling is controversial. Thus, we examined the effects of RT and AE on [Formula: see text] peak and cardiac remodeling in patients with heart failure (HF) via a systematic review and meta-analysis. MEDLINE, EMBASE, Cochrane Library and CINAHL, AMEDEO and PEDro databases search were extracted study characteristics, exercise type, and ventricular outcomes. The main outcomes were [Formula: see text] peak (ml kg-1 min-1), LVEF (%) and LVEDV (mL). Fifty-nine RCTs were included. RT produced a greater increase in [Formula: see text] peak (3.57 ml kg-1 min-1, P < 0.00001, I 2 = 0%) compared to AE (2.63 ml kg-1 min-1, P < 0.00001, I 2 = 58%) while combined RT and AE produced a 2.48 ml kg-1 min-1 increase in [Formula: see text]; I 2 = 69%) compared to control group. Comparison among the three forms of exercise revealed similar effects on [Formula: see text] peak (P = 0.84 and 1.00, respectively; I 2 = 0%). AE was associated with a greater gain in LVEF (3.15%; P < 0.00001, I 2 = 17%) compared to RT alone or combined exercise which produced similar gains compared to control groups. Subgroup analysis revealed that AE reduced LVEDV (- 10.21 ml; P = 0.007, I 2 = 0%), while RT and combined RT and AE had no effect on LVEDV compared with control participants. RT results in a greater gain in [Formula: see text] peak, and induces no deleterious effects on cardiac function in HF patients.

Thoracoabdominal asynchrony: Two methods in healthy, COPD, and interstitial lung disease patients.

BACKGROUND: Thoracoabdominal asynchrony is the nonparallel motion of the ribcage and abdomen. It is estimated by using respiratory inductive plethysmography and, recently, using optoelectronic plethysmography; however the agreement of measurements between these 2 techniques is unknown. Therefore, the present study compared respiratory inductive plethysmography with optoelectronic plethysmography for measuring thoracoabdominal asynchrony to see if the measurements were similar or different. METHODS: 27 individuals (9 healthy subjects, 9 patients with interstitial lung disease, and 9 with chronic obstructive pulmonary disease performed 2 cycle ergometer tests with respiratory inductive plethysmography or optoelectronic plethysmography in a random order. Thoracoabdominal asynchrony was evaluated at rest, and at 50% and 75% of maximal workload between the superior ribcage and abdomen using a phase angle. RESULTS: Thoracoabdominal asynchrony values were very similar in both approaches not only at rest but also with exercise, with no statistical difference. There was a good correlation between the methods and the Phase angle values were within the limits of agreement in the Bland-Altman analysis. CONCLUSION: Thoracoabdominal asynchrony measured by optoelectronic plethysmography and respiratory inductive plethysmography results in similar values and has a satisfactory agreement at rest and even for different exercise intensities in these groups.

Exposure to fine particulate matter in the air alters placental structure and the renin-angiotensin system.

METHODS: Female Wistar rats were exposed to filtered air (F) or to concentrated fine particulate matter (P) for 15 days. After mating, the rats were divided into four groups and again exposed to F or P (FF, FP, PF, PP) beginning on day 6 of pregnancy. At embryonic day 19, the placenta was collected. The placental structure, the protein and gene expression of TGFß1, VEGF-A, and its receptor Flk-1 and RAS were evaluated by indirect ELISA and quantitative real-time PCR. RESULTS: Exposure to P decreased the placental mass, size, and surface area as well as the TGFß1, VEGF-A and Flk-1 content. In the maternal portion of the placenta, angiotensin II (AngII) and its receptors AT1 (AT1R) and AT2 (AT2R) were decreased in the PF and PP groups. In the fetal portion of the placenta, AngII in the FP, PF and PP groups and AT2R in the PF and PP groups were decreased, but AT1R was increased in the FP group. VEGF-A gene expression was lower in the PP group than in the FF group. CONCLUSIONS: Exposure to pollutants before and/or during pregnancy alters some characteristics of the placenta, indicating a possible impairment of trophoblast invasion and placental angiogenesis with possible consequences for the maternal-fetal interaction, such as a limitation of fetal nutrition and growth.

Cardiac dysfunction in Pkd1-deficient mice with phenotype rescue by galectin-3 knockout.

Alterations in myocardial wall texture stand out among ADPKD cardiovascular manifestations in hypertensive and normotensive patients. To elucidate their pathogenesis, we analyzed the cardiac phenotype in Pkd1(cond/cond)Nestin(cre) (CYG+) cystic mice exposed to increased blood pressure, at 5 to 6 and 20 to 24 weeks of age, and Pkd1(+/-) (HTG+) noncystic mice at 5-6 and 10-13 weeks. Echocardiographic analyses revealed decreased myocardial deformation and systolic function in CYG+ and HTG+ mice, as well as diastolic dysfunction in older CYG+ mice, compared to their Pkd1(cond/cond) and Pkd1(+/+) controls. Hearts from CYG+ and HTG+ mice presented reduced polycystin-1 expression, increased apoptosis, and mild fibrosis. Since galectin-3 has been associated with heart dysfunction, we studied it as a potential modifier of the ADPKD cardiac phenotype. Double-mutant Pkd1(cond/cond):Nestin(cre);Lgals3(-/-) (CYG-) and Pkd1(+/-);Lgals3(-/-) (HTG-) mice displayed improved cardiac deformability and systolic parameters compared to single-mutants, not differing from the controls. CYG- and HTG- showed decreased apoptosis and fibrosis. Analysis of a severe cystic model (Pkd1(V/V); VVG+) showed that Pkd1(V/V);Lgals3(-/-) (VVG-) mice have longer survival, decreased cardiac apoptosis and improved heart function compared to VVG+. CYG- and VVG- animals showed no difference in renal cystic burden compared to CYG+ and VVG+ mice. Thus, myocardial dysfunction occurs in different Pkd1-deficient models and suppression of galectin-3 expression rescues this phenotype.

High and Low Salt Intake during Pregnancy: Impact on Cardiac and Renal Structure in Newborns.

INTRODUCTION: Previous studies from our laboratory demonstrated that dietary salt overload and salt restriction during pregnancy were associated with cardiac and renal structural and/or functional alterations in adult offspring. The present study evaluated renal and cardiac structure and the local renin-angiotensin system in newborns from dams fed high-, normal- or low-salt diets during pregnancy. METHODS: Female Wistar rats were fed low- (LS, 0.15% NaCl), normal- (NS, 1.3% NaCl) or high- (HS, 8% NaCl) salt diets during pregnancy. Kidneys and hearts were collected from newborns (n = 6-8/group) during the first 24 hours after birth to evaluate possible changes in structure using stereology. Protein expression of renin-angiotensin system components was evaluated using an indirect enzyme-linked immunosorbent assay (ELISA). RESULTS: No differences between groups were observed in total renal volume, volume of renal compartments or number of glomeruli. The transverse diameter of the nuclei of cardiomyocytes was greater in HS than NS males in the left and right ventricles. Protein expression of the AT1 receptor was lower in the kidneys of the LS than in those of the NS and HS males but not females. Protein expression of the AT2 receptor was lower in the kidneys of the LS males and females than in those of the NS males and females. CONCLUSION: High salt intake during pregnancy induced left and right ventricular hypertrophy in male newborns. Salt restriction during pregnancy reduced the expression of renal angiotensin II receptors in newborns.