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The purpose of the present study was to examine myocardial antioxidant and oxidative stress changes in male and female rats in the presence of physiological sex hormone concentrations and after castration. Twenty-four 9-week-old Wistar rats were divided into four groups of 6 animals each: 1) sham-operated females, 2) castrated females, 3) sham-operated males, and 4) castrated males. When testosterone and estrogen levels were measured by radioimmunoassay, significant differences were observed between the castrated and control groups (both males and females), demonstrating the success of castration. Progesterone and catalase levels did not change in any group. Control male rats had higher levels of glutathione peroxidase (50%) and lower levels of superoxide dismutase (SOD, 14%) than females. Control females presented increased levels of SOD as compared to the other groups. After castration, SOD activity decreased by 29% in the female group and by 14% in the male group as compared to their respective controls. Lipid peroxidation (LPO) was assessed to evaluate oxidative damage to cardiac membranes by two different methods, i.e., TBARS and chemiluminescence. LPO was higher in male controls compared to female controls when evaluated by both methods, TBARS (360%) and chemiluminescence (46%). Castration induced a 200% increase in myocardial damage in females as determined by TBARS and a 20% increase as determined by chemiluminescence. In males, castration did not change LPO levels. These data suggest that estrogen may have an antioxidant role in heart muscle, while testosterone does not.

The purpose of the present study was to investigate the effects of experimental diabetes on the oxidant and antioxidant status of latissimus dorsi (LD) muscles of male Wistar rats (220 ± 5 g, N = 11). Short-term (5 days) diabetes was induced by a single injection of streptozotocin (STZ, 50 mg/kg, iv; glycemia >300 mg/dl). LD muscle of STZ-diabetic rats presented higher levels of thiobarbituric acid reactive substances (TBARS) and chemiluminescence (0.36 ± 0.02 nmol/mg protein and 14706 ± 1581 cps/mg protein) than LD muscle of normal rats (0.23 ± 0.04 nmol/mg protein and 7389 ± 1355 cps/mg protein). Diabetes induced a 92% increase in catalase and a 27% increase in glutathione S-transferase activities in LD muscle. Glutathione peroxidase activity was reduced (58%) in STZ-diabetic rats and superoxide dismutase activity was similar in LD muscle of both groups. A positive correlation was obtained between catalase activity and the oxidative stress of LD, as evaluated in terms of TBARS (r = 0.78) and by chemiluminescence (r = 0.89). Catalase activity also correlated inversely with glutathione peroxidase activity (r = 0.79). These data suggest that an increased oxidative stress in LD muscle of diabetic rats may be related to skeletal muscle myopathy.

Objectives: We aimed to analyze the episodes of esophageal food bolus impaction (EFI) occurred over a time of 15 years in children admitted to a large pediatric emergency department (PED), documenting their clinical presentation, underlying pathology, management, biopsy rate, and follow-up visits. Additionally, to combine our institutional experience with the existing literature, a comprehensive review was conducted., Methods: We reviewed the medical records of all children presenting to our PED with EFI from 2010 to 2024. The comprehensive review was guided by the Preferred Reporting Items for Systematic Reviews and Meta-Analysis statement for systematic reviews. Electronic databases including PubMed/Medline and EMBASE were screened. The data obtained was synthesized to map out the actual status and current literature on pediatric EFI., Results: We identified 54 cases of EFI. Overall, 22 patients (41%) had underlying pathology. Previous episodes were reported in 14 cases (26%). Urgent endoscopy was performed in 31 cases (57%). The presence of underlying pathology was associated with the need for endoscopic removal (p = 0.013), as well as the history of previous episodes (p = 0.016). Biopsies were performed in 14 cases (26%). Pediatric gastroenterologists showed a higher rate of performed biopsies compared to surgeons, as well as higher rate of follow-up visits. An underlying disease was found during later clinical follow-up in 5 out of 54 cases of EFI (9%). A comprehensive review of 16 studies revealed high rates of underlying pathology and low rates of biopsies and follow-up visits among children with EFI., Conclusion: Increased vigilance in identifying underlying pathologies in children with EFI is crucial. The importance of performing biopsies, regardless of prior anatomical conditions, and the need for ongoing follow-up to ensure timely and accurate diagnoses should be addressed through shared protocols., (© 2024 European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Background and Aims: Upper endoscopy (UE) procedures (EGD and ERCP) are an established standard of care in pediatric gastroenterology. The Pediatric Endoscopy Quality Improvement Network (PEnQuIN) recently published its pediatric-specific endoscopy quality guidelines. This study, initiated by the Italian Society of Pediatric Gastroenterology, Hepatology and Nutrition, aims to evaluate the adherence of Italian pediatric endoscopy centers (PECs) to these established quality standards., Methods: Conducted between April 2019 and March 2021, this nationwide study used a smartphone-based app approach. Data encompassing pediatric endoscopy facilities, patient profiles, endoscopy indications, 17 procedure-related PEnQuIN indicators, and a patient satisfaction questionnaire (Group Health Association of America-9) were systematically collected., Results: A comprehensive analysis of 3582 procedures from 24 centers revealed that 2654 (76%) were UEs. The majority of centers (75%) involved >1 operator, with 9 centers incorporating adult endoscopists, responsible for 5% of UEs. Overall, adherence to quality standards was good; however, areas of improvement include suboptimal reporting of sedation details, adherence to disease-specific guidelines, and patient satisfaction questionnaire completeness (56%). The adverse event rate aligned with literature standards (1%), and patient satisfaction was generally high. A noteworthy observation was a 30% decreased monthly reporting rate and a shift in disease-specific patterns after the COVID-19 outbreak., Conclusions: Pediatric UE practices in Italy adhere well to established quality standards. Emphasizing the adoption of disease-specific guidelines is crucial for optimizing resources, enhancing diagnostic accuracy, and minimizing unnecessary procedures. Prioritizing patient satisfaction is important for immediate enhancements in practice as well as for future research endeavors., Competing Interests: Disclosure All authors disclosed no financial relationships., (Copyright © 2024 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

Objectives: We aimed to appraise the real-life efficacy of Crohn's disease exclusion diet (CDED) coupled with partial enteral nutrition (PEN) in inducing clinical and biochemical remission at disease onset and in patients with loss of response to biologics and immunomodulators., Methods: We retrospectively gathered data of patients aged less than 18 years of age with a diagnosis of Crohn's disease (CD), who received CDED coupled with PEN at a tertiary level pediatric inflammatory bowel disease center., Results: Sixty-six patients were identified. Forty (60.6%) started CDED plus PEN at disease onset and 26 (39.4%) received CDED with PEN as add-on therapy. Forty-six (69.7%) patients achieved clinical remission (weighted Pediatric Crohn's Disease Activity Index < 12.5) at the end of phase 1, 44 (66.7%) normalized c-reactive protein levels (<0.5 mg/dL) and 18 (27.2%) patients normalized calprotectin levels (<150 µg/g). Nine of 19 (47.3%) of patients with clinically severe disease (defined by Physician Global Assessment) achieved clinical remission at the end of phase I. Patients with extraintestinal manifestations had statistically lower clinical response rates to the dietary regimen (p = 0.018). Among patients who received CDED + PEN as add-on treatment, a previous successful course of Exclusive Enteral Nutrition was associated with statistically higher clinical remission rates at Week 8 (p = 0.026). Clinical response at Week 4 was an independent predictor of clinical remission and fecal calprotectin normalization at Week 8 (p = 0.002)., Conclusion: CDED with PEN confirmed its efficacy in a real-life setting, proving to be effective also in refractory patients and those with severe disease. Early clinical response predicts clinical remission at the end of phase 1., (© 2024 The Author(s). Journal of Pediatric Gastroenterology and Nutrition published by Wiley Periodicals LLC on behalf of European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Background: The study aimed to assess the longitudinal impact of endoscopic healing (EH) and histological healing (HH) in a cohort of paediatric patients affected by ulcerative colitis (UC)., Methods: This was a retrospective single-centre longitudinal study. 86 children with UC who underwent endoscopic re-assessment while in clinical and biochemical remission were included. Partial EH was defined as a Mayo Endoscopic Subscore (MES) of 1 and complete EH was defined as a MES of 0. HH was defined as the absence of active inflammation in all biopsies. The cumulative incidence of clinical relapse was evaluated during follow-up., Results: At the second endoscopic re-evaluation, 59 (68.6%) patients achieved EH (MES ≤1). Of these patients, 39 (66%) achieved complete EH. 20 of the 39 patients who achieved complete EH attained complete HH. Patients who achieved partial and complete EH showed higher recurrence-free survival rates compared to those who did not (p < 0.01 and p < 0.01, respectively). Amongst patients with complete EH, those who achieved complete HH had lower recurrence rates when compared to patients who still showed microscopic inflammation (p = 0.049)., Conclusion: Achievement of EH and HH is associated with fewer disease relapses, with patients achieving HH showing longer relapse-free survival rates., Competing Interests: Conflict of interest Paolo Lionetti has served as a speaker and as an advisory board member for AbbVie, Janssen, and Sandoz. All the other authors have no conflict of interest to declare., (Copyright © 2023. Published by Elsevier Ltd.)

Background: The aim of the present study was to investigate outcomes of anti-TNF-alpha (ATA) withdrawal in selected pediatric patients with inflammatory bowel disease who achieved clinical remission and mucosal and histological healing (MH and HH)., Methods: A retrospective analysis was performed on children and adolescents affected by Crohn disease (CD) and ulcerative colitis (UC) who were followed up at 2 tertiary referral centers from 2008 through 2018. The main outcome measure was clinical relapse rates after ATA withdrawal., Results: One hundred seventy patients received scheduled ATA treatment; 78 patients with CD and 56 patients with UC underwent endoscopic reassessment. We found that MH was achieved by 32 patients with CD (41%) and 30 patients with UC (53.6%); 26 patients with CD (33.3%) and 22 patients with UC (39.3%) achieved HH. The ATA treatment was suspended in 45 patients, 24 affected by CD and 21 by UC, who all achieved concurrently complete MH (Simplified Endoscopic Score for CD, 0; Mayo score, 0, respectively) and HH. All the patients who suspended ATA shifted to an immunomodulatory agent or mesalazine. In contrast, 17 patients, 8 with CD and 9 with UC, continued ATA because of growth needs, the persistence of slight endoscopic lesions, and/or microscopic inflammation. Thirteen out of 24 patients with CD who suspended ATA experienced disease relapse after a median follow-up time of 29 months, whereas no recurrence was observed among the 9 patients with CD who continued treatment (P = 0.05). Among the patients with UC, there were no significant differences in relapse-free survival among those who discontinued ATA and those who did not suspend treatment (P = 0.718)., Conclusions: Despite the application of rigid selection criteria, ATA cessation remains inadvisable in CD. In contrast, in UC, the concurrent achievement of MH and HH may represent promising selection criteria to identify patients in whom treatment withdrawal is feasible., (© 2021 Crohn’s & Colitis Foundation. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objectives: Mucosal healing (MH) and histological healing (HH) have been recently proposed as a novel treatment target for inflammatory bowel disease (IBD). The aim of the present study was to evaluate real-life achievement of such outcomes in a cohort of pediatric patients with IBD treated with anti-TNF-alpha (ATA) agents., Methods: A retrospective analysis was performed on patients affected by IBD who received ATA and were followed up at two referral centers. Incidence and cumulative rates for MH and HH for each group were calculated., Results: Of 170 (105 Crohn's disease [CD] and 65 ulcerative colitis [UC]) patients, 78 with CD and 56 with UC underwent endoscopic re-assessment during the study period. MH was achieved by 32 CD (41%) and 30 UC (53.6%) patients; 26 CD (33.3%) and 22 UC (39.3%) patients achieved HH. MH incidence rate was 19.1/1000 and 47/1000 person-months, whereas HH incidence rate was 15.5/1000 and 34.7/1000 person-months for CD and UC, respectively. Remission at the end of induction was associated with higher MH and HH rates (HR: 2.43, P = 0.049 and HR: 2.94, P = 0.046, respectively) in CD. In UC, adalimumab was associated with lower MH and HH rates (HR: 0.16, P = 0.004 and HR: 0.07, P = 0.003)., Conclusions: We reported a real-life experience arising from a large cohort of pediatric IBD who received ATA scheduled treatment. Less than half of patients with CD and only a little >50% of UC patients achieved MH. Microscopical inflammation was observed in 18.8% CD and 26.7% UC patients who achieved MH. Overall, MH and HH rates appear lower compared to previously published data., Competing Interests: The authors report no conflict of interest to declare., (Copyright © 2021 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Background: The emergence of SARS-CoV-2 pandemic has upset health systems around the world and caused immeasurable losses and costs. Until a vaccine will become available, the recommended prevention measures remain physical distancing and enhanced hygiene., Methods and Findings: The proteic structure external to the virus is the main target that may eventually lead to reduce or block its replication in the upper airways. We developed a protocol based of repeated steam inhalation cycles aimed at reducing the risk of progression to full blown infection if performed soon after contagion. The protocol has been used in a single-center open label trial on ten infected asymptomatic or pauci-symptomatic health care professionals., Conclusions: The promising results we obtained with this easily accessible, non-invasive and inexpensive procedure should prompt controlled trials., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background and Objective: Acute severe colitis (ASC) is a potentially life-threatening event. Optimal timing for second-line treatment in children is mainly based on the clinical score Pediatric Ulcerative Colitis Activity Index. The aim of our study was to evaluate the potential role of bowel ultrasound scan (BUS) in predicting the need of second-line therapy in ASC., Methods: Patients younger than 18 years admitted to a single tertiary referral center with ASC were included. We retrospectively reviewed medical records collecting clinical and BUS data. Colonic wall thickness (CWT), loss of colonic wall stratification (CWS), presence of hyperechoic lymph nodes, and colonic wall flow evaluated at power Doppler were assessed at BUS performed within the third day of hospitalization., Results: Sixty-nine ASC episodes from 52 different patients were identified. CWT showed significantly higher values in patients who required second-line therapy (5.14 vs 3.69 mm; P < 0.001). Loss of CWS was present in 17 of 36 (47.2%) of steroid-resistant ASC versus only 1 of 33 of those responding to intravenous corticosteroids (P < 0.001, sensitivity = 47%, specificity = 97%). Using a receiver operating characteristic curve, a cut-off of 3.4 mm was individuated for CWT to predict steroid treatment failure, showing a sensitivity of 92% and a specificity of 52%. The multivariable binary logistic regression analysis identified thickened colonic wall (CWT >3.4 mm) and loss of CWS as independent predictors of steroid resistance., Conclusions: BUS is a noninvasive, easily accessible, and cost-effective resource that may identify at an early stage first-line therapy failure in pediatric ASC.

Background: Thalidomide is an effective therapy in children with inflammatory bowel disease refractory to standard treatments, but thalidomide-induced peripheral neuropathy (TiPN) limits its long-term use. We aimed to investigate the risk factors and the outcome of TiPN in children with inflammatory bowel disease., Methods: Within a retrospective multicenter cohort study, we evaluated prevalence and evolution of TiPN. Clinical data and candidate genetic profiles of patients with and without TiPN were compared with detect predisposing factors., Results: One hundred forty-two patients were identified. TiPN was found in 72.5% of patients (38.7% clinical and instrumental alterations, 26.8% exclusive electrophysiological anomalies, and 7.0% exclusive neurological symptoms). Median TiPN-free period of treatment was 16.5 months; percentage of TiPN-free patients was 70.0% and 35.6% at 12 and 24 months of treatment, respectively. The risk of TiPN increased depending on the mean daily dose (50-99 mg/d adjusted hazard ratio 2.62; 95% confidence interval [CI], 1.31-5.21; 100-149 mg/d adjusted hazard ratio 6.16; 95% CI, 20.9-13.06; >150 mg/d adjusted hazard ratio 9.57; 95% CI, 2.6-35.2). Single nucleotide polymorphisms in ICAM1 (rs1799969) and SERPINB2 (rs6103) genes were found to be protective against TiPN (odds ratio 0.15; 95% CI, 0.03-0.82 and 0.36; 95% CI, 0.14-0.88, respectively). TiPN was the cause of drug suspension in 41.8% of patients. Clinical symptoms resolved in 89.2% of cases, whereas instrumental alteration persisted in more than half of the patients during a short follow-up., Conclusions: In children with inflammatory bowel disease, TiPN is common but mild and generally reversible. Cumulative dose seems to be the most relevant risk factor, whereas polymorphisms in genes involved in neuronal inflammation may be protective.

In 2013, four Italian Gastroenterological Societies (the Italian Society of Paediatric Gastroenterology, Hepatology and Nutrition, the Italian Society of Hospital Gastroenterologists and Endoscopists, the Italian Society of Endoscopy, and the Italian Society of Gastroenterology) formed a joint panel of experts with the aim of preparing an official statement on transition medicine in Gastroenterology. The transition of adolescents from paediatric to adult care is a crucial moment in managing chronic diseases such as celiac disease, inflammatory bowel disease, liver disease and liver transplantation. Improved medical treatment and availability of new drugs and surgical techniques have improved the prognosis of many paediatric disorders, prolonging survival, thus making the transition to adulthood possible and necessary. An inappropriate transition or the incomplete transmission of data from the paediatrician to the adult Gastroenterologist can dramatically decrease compliance to treatment and prognosis of a young patient, particularly in the case of severe disorders. For these reasons, the Italian gastroenterological societies decided to develop an official shared transition protocol. The resulting document discusses the factors influencing the transition process and highlights the main points to accomplish to optimize compliance and prognosis of gastroenterological patients during the difficult transition from childhood to adolescence and adulthood., (Copyright © 2015 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

We aimed to assess the current knowledge on continuous versus intermittent bolus feeding in preterm infants. We found that existing evidence does not support the firm recommendation of one strategy among the many alternatives. However, although many areas remain to be investigated, it is probable that continuous feeding might be advantageous compared to intermittent feeding in favoring the faster establishment of full enteral feeding, and decreasing the risk of hypoxic-ischemic gut damage in preterm neonates in critical condition, especially SGA infants, by limiting their gastrointestinal oxygen requirement., (© 2013 Elsevier Ireland Ltd. All rights reserved.)

Objectives: The aim of the present study was to compare the effects of continuous and intermittent bolus milk feeding on splanchnic regional oxygenation (rSO₂S) in small-for-gestational age (SGA) and appropriate-for-gestational age (AGA) preterm infants., Methods: Infants with gestational age <32 weeks were prospectively studied by near-infrared spectroscopy. Each infant was given a milk bolus in ~10 minutes (intermittent feeding) followed after 3 hours by a 3-hour continuous feeding. rO₂S and splanchnic fractional oxygen extraction ratio (FOES [S = splanchnic]) were recorded 30 minutes before (T₀) and 30 minutes after the beginning of bolus feeding (T₁), 30 minutes before (T₂), at the end (T₃), and 30 minutes after the continuous feeding period (T₄)., Results: rSO2S increased at T₁ in both AGA and SGA groups, whereas FOES did not vary during the study period. Moreover, we found that rSO2S was higher and FOES was lower at T₁ and T₃ in the AGA than in the SGA group., Conclusions: Bolus milk feeding increases splanchnic oxygenation in both AGA and SGA infants, whereas continuous feeding does not. Splanchnic oxygenation is higher in AGA than in SGA infants both during bolus and continuous feeding. Continuous enteral feeding could help to limit the risk of hypoxic-ischemic gut damage in preterm infants in critical condition, especially in AGA infants.

The aim of this study was to evaluate the potential influence of endogenous ovarian hormones on cardiac oxidative stress in renovascular hypertension. Female Wistar rats (N = 10 per group) were divided among 4 groups: (i) normotensive control; (ii) hypertensive control; (iii) normotensive ovariectomized; and (iv) hypertensive ovariectomized rats. To induce hypertension, 2-kidney 1-clip (2K1C) Goldblatt's method was followed. Blood pressure (BP) was enhanced (25%) in 2K1C and it was not further altered in hypertensive ovariectomized animals. Lipid peroxidation (measured by thiobarbituric acid reactive substances; TBARS) increased in heart homogenates after ovariectomy (253%) and was additionally augmented when associated with hypertension (by 28%). Superoxide dismutase and catalase activities were similar in both hypertensive groups. Hypertension enhanced glutathione peroxidase activity (75%), but the association with ovariectomy prevented this change. Total radical trapping antioxidant potential (TRAP) decreased in hypertensive rats (34%) and was recovered when associated with ovariectomy. However, this adaptation seems not to be sufficient to avoid the increased oxidative damage in ovariectomized hypertensive animals. These results suggest a protective role for physiological ovarian hormones in the cardiac oxidative stress induced by 2K1C hypertension.

Objectives: Our aim was to evaluate whether single and multiple intubation-surfactant-extubation (INSURE) procedures have similar effects on the need of mechanical ventilation (MV) and occurrence of bronchopulmonary dysplasia (BPD) in extremely preterm infants., Methods: We studied infants of <30 weeks of gestation with respiratory distress syndrome (RDS) who were treated with single (FiO(2)>0.30 without need of MV) or multiple (FiO(2)>0.40 without need of MV) INSURE procedures., Results: Seventy-five infants were studied: 53 (71%) received single INSURE and 22 (29%) received multiple INSURE procedures. Infants in the single and multiple groups had similar rates of need of MV (15 vs. 23%) and occurrence of BPD (9 vs. 9%), although the latter were more immature and affected by more severe RDS (higher FiO(2), lower a/ApO(2), and pO(2)/FiO(2)) than the former., Conclusions: Single and multiple INSURE procedures were followed by similar respiratory outcome in a cohort of extremely preterm infants. Further studies are warranted to evaluate whether the multiple INSURE strategy enhances the success rate of INSURE in preventing the need of MV and the occurrence of BPD.

The possible correlation between the mean platelet volume (MPV) and the occurrence of bronchopulmonary dysplasia (BPD) and intraventricular hemorrhage (IVH) in a cohort of preterm infants was assessed. We studied infants with gestational age <30 weeks. Enrolled infants were divided into BPD and no-BPD groups and IVH and no-IVH groups. MPV was evaluated at birth and at 24 to 48 hours of life. MPV measured at birth was similar in BPD and no-BPD groups, but at 24 to 48 hours of life was higher in the BPD than in the no-BPD group (11.1 ± 0.9 versus 10.8 ± 0.9 fL, P = 0.033) and multivariate analysis demonstrated that MPV >11 fL increases (relative risk 1.40, 95% confidence interval 1.08 to 1.80) the risk of developing BPD. MPV was similar in infants with or without IVH. We concluded that high MPV in the first days of life is a risk factor for the development of BPD in extremely preterm infants. This might be because high MPV could favor inflammatory and oxidative lung damage. On the contrary, our data indicate that MPV is not associated with the development of IVH in our population., (© Thieme Medical Publishers.)

Aim: To assess the current practices existing in Italy for the management of jaundice in preterm infants as preliminary achievement to a call for national guidelines and establishment of a kernicterus registry., Methods: A questionnaire (in Supporting Information online) was sent to the 109 level III neonatal units in Italy to ascertain existing guidelines for total bilirubin monitoring and treatment of hyperbilirubinaemia in preterm infants and occurrence of kernicterus., Results: There was a 61% (67/109) response rate. Eighty-five per cent of responding units had either written guidelines coming from different literature sources or locally developed. The monitoring of bilirubin varied greatly in timing before, during and after jaundice development. Phototherapy and exchange transfusion were given to 56.0 ± 21.0% and 0.2 ± 0.4% of admitted preterm infants in participating centres. Five cases of kernicterus in preterm infants and eleven cases in term infants were documented over the last 10 years., Conclusion: The management of hyperbilirubinaemia in preterm infants is not uniform in Italy and would benefit from shared national guidance together with establishment of a kernicterus registry to guide therapy., (© 2011 The Author(s)/Acta Paediatrica © 2011 Foundation Acta Paediatrica.)

Background: Multiprobe near infrared spectroscopy (NIRS) has been used to study regional cerebral (rSO(2)C), splanchnic (rSO(2)S), and renal (rSO(2)R) tissue oxygenation in newborns. We used this method to study the effects of red blood cell (RBC) transfusions in anemic preterm infants to assess if thresholds for transfusions were appropriate for recognizing a clinical condition permitting tissue oxygenation improvement., Study Design and Methods: Multiprobe NIRS (INVOS 5100, Somanetics) was applied during transfusion to 15 preterm infants with symptomatic anemia of prematurity (hematocrit level of <25%). rSO(2)C, rSO(2)S, and rSO(2)R were recorded at selected times, and then fractional oxygen cerebral extraction ratio [FOEC: (SaO(2)-rSO(2)C)/SaO(2)], fractional oxygen splanchnic extraction ratio [FOES: (SaO(2)-rSO(2)S)/SaO(2)], fractional oxygen renal extraction ratio [FOER: (SaO(2)-rSO(2)R)/SaO(2)], cerebrosplanchnic oxygenation ratio [CSOR: (rSO(2)S/rSO(2)C)], and cerebrorenal oxygenation ratio [CROR: (rSO(2)R/rSO(2)C)] were calculated. In addition, we used Doppler ultrasonography for evaluating cerebral blood flow (CBF), splanchnic blood flow (SBF), and renal blood flow (RBF) velocity., Results: rSO(2)C, rSO(2)S, and rSO(2)R significantly increased during transfusions, while FOEC, FOES, and FOER decreased. CSOR and CROR increased during transfusions. CBF velocity decreased during the study period, while SBF and RBF velocities did not vary., Conclusion: RBC transfusions performed at used thresholds permitted an increase in cerebral, splanchnic, and renal oxygenation. The associated decreases in oxygen tissue extraction might suggest that transfusions were well timed for preventing tissue hypoxia or too early and theoretically prooxidant. Further studies could help to clarify this issue.

The INSURE (Intubation-surfactant-extubation) method has been found to reduce the need for MV, the duration of respiratory support, and the need for surfactant in preterm infants with respiratory distress syndrome (RDS). However, this method fails in some patients. We demonstrated that a birth weight <750 g, pO2/FiO2 <218, and a/ApO2 < 0.44 at the first blood gas analysis were independent risk factor for INSURE failure in infants with gestational age <30 weeks. Moreover, we demonstrated that INSURE treatment can be repeated being the respiratory outcome similar in infants treated with single or multiple INSURE procedures. Thus, it is possible that the multiple INSURE strategy might decrease the failure rate of INSURE and increase its effectiveness in preventing the need for mechanical ventilation (MV).

Surfactant treatment has been demonstrated to decrease pneumothorax and mortality in preterm infants. Natural surfactants are better than synthetic surfactants. Early rescue treatment with surfactant is better than late treatment, whereas the role of surfactant prophylaxis is under re-evaluation due to the actual large diffusion of antenatal steroid and nasal continuous positive airway pressure treatment which have changed the clinical characteristics of preterm infants with respiratory distress syndrome. It is possible that in the next future anti-inflammatory and anti-oxidant properties of exogenous natural surfactants may be improved through their combination with adequate agents with the aim of counteracting the pathogenetic role of inflammatory and oxidative lung injury injuries in the development of brochopulmonary dysplasia.

Early-life environmental events that disrupt the mother-pup relationship may induce profound long-lasting changes on several behavioral and neuroendocrine systems. The neonatal handling procedure, which involves repeated brief maternal separations followed by experimental manipulations, reduces sexual behavior and induces anovulatory estrous cycles in female rats. On the afternoon of proestrus, neonatally handled females show a reduced surge of luteinizing hormone (LH) and an increased content of gonadotropin-releasing hormone in the medial preoptic area (MPOA). In order to detect the possible causes for the reduced ovulation and sexual behavior, the present study aimed to analyze the effects of neonatal handling on noradrenaline (NA) and nitric oxide (NO) levels in the MPOA on the afternoon of proestrus. Neonatal handling reduced MHPG (NA metabolite) levels and MHPG/NA ratio in the MPOA, indicating decreased NAergic activity. Additionally, neonatal handling decreased NO levels, as measured by the metabolites (NO(x)), nitrite and nitrate in the same period. We may conclude that the neonatal handling procedure decreased activity of the NAergic and NOergic systems in the MPOA during proestrus, which is involved in the control of LH and FSH secretion, and this may possibly explain the anovulatory estrous cycles and reduced sexual behavior of the neonatally handled female rats., ((c) 2007 S. Karger AG, Basel)

Myocardial activity and gene expression of antioxidant defenses and oxidative damage were examined in an experimental model of pressure overload hypertrophy. Male Wistar rats were divided into abdominal aortic-banded or sham-operated groups. After 30 days, arterial pressure and heart rate were measured. Heart, lung, and liver were extracted and weighted to evaluate cardiac hypertrophy and pulmonary and hepatic congestion. Heart homogenates were prepared to quantify lipid peroxidation (LPO); the activities of superoxide dismutase (SOD), catalase (CAT), glutathione-S-transferase (GST), glutathione peroxidase (GPx) and glutathione reductase (GR); and Cu-Zn SOD and GST concentrations. Total glutathione (GSH) myocardial content was also measured. Arterial pressure (142 +/- 17 mmHg) and cardiac hypertrophy index (3.4 +/- 0.45 mg/g) were significantly increased (by 38% and 22%, respectively, p<0.0001) in the aortic-banded group. LPO was enhanced by 55% in the aortic-banded group (11891 +/- 766 cps/mg protein, p<0.001) compared with that in the controls. SOD activity and concentration were higher (40% and 38%, 15.15 +/- 1.03 U/mg protein, 49.187 pixels, respectively, p<0.05) in the aortic-banded group than in the controls. Aortic-banding induced a decrease by 28% in GST (48 +/- 10 pmol/min/mg protein, p<0.005), by 36% in GPx (38.2 +/- 9.5 nmol/min/mg protein, p<0.005), by 31% in GR activities (1.55 +/- 0.23 nmol/mg protein, p<0.0005), and by 43% in GSH content (0.13 +/- 0.02 nmol/mg protein, p<0.005). In conclusion, in this model it was observed that myocardial oxidative stress induces alterations in antioxidant enzyme activities and protein expression. The follow up of these parameters could afford an early therapeutical window to avoid heart failure progression.

In 8 trained subjects (T) and 9 untrained subjects (UT), lipid peroxidation (LPO), total antioxidant capacity (TRAP), superoxide dismutase, catalase, and glutathione peroxidase (GPx) activities were measured in the blood before and after three different intensities of exercise on the treadmill, determined from ventilatory threshold and maximal oxygen uptake data, obtained from a maximal aerobic power test. In plasma, LPO decreased from 3589 +/- 193 to 3274 +/- 223 cps x mg Hb(-1) (p < 0.05), and TRAP increased from 304 +/- 45 to 384 +/- 57 micromol x L(-1) trolox (p < 0.05) after high intensity exercise in T. GPx activity increased in the T group as compared to the UT group, after exercise in moderate (25.90 +/- 3.79 to 15.05 +/- 3.23 nM x min(-1) x mg protein(-1)) and high (21.75 +/- 4.91 to 12.1 +/- 2.46 nM x min(-1) x mg protein(-1)) intensities (p < 0.05). Superoxide dismutase activity increased after exercise at low (8.35 +/- 0.85 to 9.23 +/- 1.03 U SOD x mg protein(-1)) and moderate (8.89 +/- 0.98 to 10.44 +/- 0.86 U SOD x mg protein(-1)) intensity in UT (p < 0.05). There were no changes in catalase activity. These findings indicate that exercise in this model did not increase lipid peroxidation, probably because of the alterations in TRAP and enzymatic antioxidants.

In the present work we investigated the effect of ovariectomy on acetylcholinesterase (AChE) activity and ganglioside content in cerebral cortex of female rats. We also studied the activity of butyrylcholinesterase (BuChE) in serum of these animals. Adult Wistar rats were divided into three groups: (1) naive females (control), (2) sham-operated females and (3) castrated females (ovariectomy). Thirty days after ovariectomy, rats were sacrificed by decapitation without anaesthesia. Blood was collected and the serum used for BuChE determination. Cerebral cortex was homogenized to determine AChE activity and extracted with chlorophorm:methanol for ganglioside evaluation. Results showed that rats subjected to ovariectomy presented a significant increase of AChE activity, but did not change the content and the profile of gangliosides in cerebral cortex when compared to sham or naive rats. BuChE activity was decreased in serum of rats ovariectomized. Our findings suggest that the alteration in the activity of brain AChE, as well as serum BuChE activity caused by ovariectomy may contribute to the impaired cognition and/or other neurological dysfunction found in post-menopausal women.

The purpose of the present study was to examine myocardial antioxidant and oxidative stress changes in male and female rats in the presence of physiological sex hormone concentrations and after castration. Twenty-four 9-week-old Wistar rats were divided into four groups of 6 animals each: 1) sham-operated females, 2) castrated females, 3) sham-operated males, and 4) castrated males. When testosterone and estrogen levels were measured by radioimmunoassay, significant differences were observed between the castrated and control groups (both males and females), demonstrating the success of castration. Progesterone and catalase levels did not change in any group. Control male rats had higher levels of glutathione peroxidase (50%) and lower levels of superoxide dismutase (SOD, 14%) than females. Control females presented increased levels of SOD as compared to the other groups. After castration, SOD activity decreased by 29% in the female group and by 14% in the male group as compared to their respective controls. Lipid peroxidation (LPO) was assessed to evaluate oxidative damage to cardiac membranes by two different methods, i.e., TBARS and chemiluminescence. LPO was higher in male controls compared to female controls when evaluated by both methods, TBARS (360%) and chemiluminescence (46%). Castration induced a 200% increase in myocardial damage in females as determined by TBARS and a 20% increase as determined by chemiluminescence. In males, castration did not change LPO levels. These data suggest that estrogen may have an antioxidant role in heart muscle, while testosterone does not.

The purpose of the present study was to investigate the effects of experimental diabetes on the oxidant and antioxidant status of latissimus dorsi (LD) muscles of male Wistar rats (220 +/- 5 g, N = 11). Short-term (5 days) diabetes was induced by a single injection of streptozotocin (STZ, 50 mg/kg, iv; glycemia >300 mg/dl). LD muscle of STZ-diabetic rats presented higher levels of thiobarbituric acid reactive substances (TBARS) and chemiluminescence (0.36 +/- 0.02 nmol/mg protein and 14706 +/- 1581 cps/mg protein) than LD muscle of normal rats (0.23 +/- 0.04 nmol/mg protein and 7389 +/- 1355 cps/mg protein). Diabetes induced a 92% increase in catalase and a 27% increase in glutathione S-transferase activities in LD muscle. Glutathione peroxidase activity was reduced (58%) in STZ-diabetic rats and superoxide dismutase activity was similar in LD muscle of both groups. A positive correlation was obtained between catalase activity and the oxidative stress of LD, as evaluated in terms of TBARS (r = 0.78) and by chemiluminescence (r = 0.89). Catalase activity also correlated inversely with glutathione peroxidase activity (r = 0.79). These data suggest that an increased oxidative stress in LD muscle of diabetic rats may be related to skeletal muscle myopathy.

Reactive oxygen species are formed in physiological and pathological conditions in mammalian tissues. Because of their high reactivity, they may interact with biomolecules, inducing oxidative injury. Increases in lipid peroxidation can result in oxidative damage to cellular membranes. Protection against oxidative damage is provided by enzymatic and non-enzymatic antioxidant defenses. Antioxidant enzyme activities and lipid peroxidation, as an index of oxidative stress injury, were evaluated in different seasons over one year in the heart and liver of rats, maintained on a 12 h light and dark cycle. Glutathione peroxidase and catalase activities, in both tissues, were maximal in the summer season. Lipid peroxidation in the heart was maximal in the spring as compared to the other seasons and it did not vary in the liver during the year. These findings suggest that any study of antioxidants or oxidative stress must take into account such seasonal variations for a more precise analysis of changes due to any pathological condition.