Vitamin A supplementation for the prevention of chronic lung disease in premature infants: A cost-utility analysis.

INTRODUCTION: Despite the growing evidence on efficacy, little is known regarding the efficiency of Vitamin A supplementation to decrease the probability of chronic lung disease (CLD) in preterm infants. This study aims to determine the cost-utility of Vitamin A to prevent CLD in preterm infants in Colombia. METHODS: A decision tree model was used to estimate the cost and quality-adjusted life-years (QALYs) of Vitamin A supplementation in preterm infants. Multiple sensitivity analyses were conducted to evaluate the robustness of the model. Cost-effectiveness was evaluated at a willingness-to-pay value of US$5180. RESULTS: Vitamin A was associated with lower costs and higher QALYs. The expected annual cost per patient with Vitamin A was US$1579 (95% CI US$1555-US$1585) and without Vitamin A was US$1913 (95% CI US$1891-US$1934). The QALYs per person estimated with Vitamin A was 0.66 (95% CI 0.66-0.67) and without Vitamin A was 0.61 (95% CI 0.60-0.61). This position of absolute dominance (Vitamin A has lower costs and higher QALYs than without Vitamin A) is unnecessary to estimate the incremental cost-effectiveness ratio. CONCLUSION: Our economic evaluation shows that Vitamin A is cost-effective to reduce the incidence rate of CLD in premature infants in Colombia. Our study provides evidence that should be used by decision-makers to improve clinical practice guidelines.

Amelioration of cyclophosphamide toxicity via modulation of metabolizing enzymes by avocado (Persea americana) extract.

OBJECTIVES: Cyclophosphamide (CPA) is highly effective in treating several human tumours and autoimmune disorders; but, it triggers deleterious side effects. Avocado, Persea americana (Mill.), is a widely consumed fruit with pronounced nutritional and medicinal value. Though many studies examined the protective mechanisms of natural products against CPA toxicity, almost none investigated the modulation of CPA metabolism as a potential underlying mechanism for protection. Here, we investigated the modulating effect of avocado extract (AE) on certain CPA metabolizing enzymes and its correlation with the extent of CPA-induced pulmonary toxicity and urotoxicity. METHODS: Rats received oral AE (0.9 g/kg body weight/day) 7 days before a single CPA injection (150 mg/kg body weight) and continued AE intake for 2, 7 or 28 days to study three phases of CPA-induced urotoxicity and pulmonary toxicity. KEY FINDINGS: CPA acutely elevated then reduced hepatic microsomal cytochrome P450 2B6 (CYP2B6) content and significantly suppressed bladder and lung glutathione-S-transferase activity. Furthermore, CPA elevated lung myeloperoxidase activity, DNA content and hydroxyproline level and bladder blood content. AE ameliorated CPA-induced derangements through suppression of CYP2B6 and myeloperoxidase and augmentation of glutathione-S-transferase activity in CPA-treated rats. CONCLUSIONS: AE modulation of CPA metabolizing enzymes and potential anti-inflammatory effect may mitigate CPA-induced toxicity.

Essential sufficiency of zinc, ω-3 polyunsaturated fatty acids, vitamin D and magnesium for prevention and treatment of COVID-19, diabetes, cardiovascular diseases, lung diseases and cancer.

Despite the development of a number of vaccines for COVID-19, there remains a need for prevention and treatment of the virus SARS-CoV-2 and the ensuing disease COVID-19. This report discusses the key elements of SARS-CoV-2 and COVID-19 that can be readily treated: viral entry, the immune system and inflammation, and the cytokine storm. It is shown that the essential nutrients zinc, ω-3 polyunsaturated fatty acids (PUFAs), vitamin D and magnesium provide the ideal combination for prevention and treatment of COVID-19: prevention of SARS-CoV-2 entry to host cells, prevention of proliferation of SARS-CoV-2, inhibition of excessive inflammation, improved control of the regulation of the immune system, inhibition of the cytokine storm, and reduction in the effects of acute respiratory distress syndrome (ARDS) and associated non-communicable diseases. It is emphasized that the non-communicable diseases associated with COVID-19 are inherently more prevalent in the elderly than the young, and that the maintenance of sufficiency of zinc, ω-3 PUFAs, vitamin D and magnesium is essential for the elderly to prevent the occurrence of non-communicable diseases such as diabetes, cardiovascular diseases, lung diseases and cancer. Annual checking of levels of these essential nutrients is recommended for those over 65 years of age, together with appropriate adjustments in their intake, with these services and supplies being at government cost. The cost:benefit ratio would be huge as the cost of the nutrients and the testing of their levels would be very small compared with the cost savings of specialists and hospitalization.

Germinated Rhynchosia nulubilis Fermented with Lactobacillus pentosus SC65 Reduces Particulate Matter Induced Type II Alveolar Epithelial Apoptotic Cell Death.

Particulate matter (PM) is a significant environmental pollutant that promotes respiratory diseases, including lung injury and inflammation, by inducing oxidative stress. Rhynchosia nulubilis (black soybean) is traditionally used to prevent chronic respiratory disease via inducing antioxidant and anti-inflammatory effects. To investigate the effects of Lactobacillus pentosus SC65 fermented GR (GR-SC65) and Pediococcus pentosaceus ON81A (GR-ON81A) against PM-induced oxidative stress and cell death in A549 cells, we performed the 2-7-dichlorodihydrofluorescein diacetate and cell counting kit-8 assays, as well as Hoechst 33342 and propidium iodide staining and western blotting. GR-SC65 showed the highest total polyphenolic contents and 1,1-diphenyl-2-picrylidrazil radical scavenging activity among lactic acid bacteria-fermented GRs (p < 0.001 vs. GR). Four soy peptides, ß-conglycinin breakdowns (INAENNQRNF, ISSEDKPFN, LAFPGSAQAVEK, and LAFPGSAKDIEN), were detected in GR-SC65, but not in GR. In GR-SC65, PM-induced A549 cell death was less than that observed in GR-ON81A and GR (p < 0.001 vs. PM-treated group). GR-SC65 significantly decreased intracellular reactive oxidative species (ROS) when compared with PM (*** p < 0.001 vs. PM). GR-SC65 decreased the levels of BAX, active caspase-9, -3, and poly ADP-ribose polymerase (PARP) proteins (#p < 0.01, ###p < 0.001 vs. PM), while increasing the level of BCL-2 protein, a mitochondrial anti-apoptotic protein (###p < 0.001 vs. PM). Our findings indicate that GR-SC65 inhibited PM-induced cell death by suppressing the levels of ROS, active caspase-9 and -3, and PARP proteins, while enhancing the level of BCL-2 protein in type II alveolar epithelial A549 cells. Therefore, GR-SC65 might be a potential therapeutic and preventive agent against PM-induced lung injury.

Perioperative breathing training to prevent postoperative pulmonary complications in patients undergoing laparoscopic colorectal surgery: A randomized controlled trial.

OBJECTIVE: The aim of this study was to determine whether perioperative breathing training reduces the incidence of postoperative pulmonary complications in patients undergoing laparoscopic colorectal surgery. DESIGN: A randomized controlled trial. SETTING: University hospital. SUBJECTS: A total of 240 patients undergoing laparoscopic colorectal surgery participated in this study. INTERVENTION: The enrolled patients were randomized into an intervention or control group. Patients in the intervention group received perioperative breathing training, including deep breathing and coughing exercise, balloon-blowing exercise, and pursed lip breathing exercise. The control group received standard perioperative care without any breathing training. MAIN MEASURES: The primary endpoint was the incidence of postoperative pulmonary complications. The secondary objectives were to evaluate the effect of perioperative breathing training on arterial oxygenation, incidence of other postoperative complications, patient satisfaction, length of stay, and hospital charges. RESULTS: The incidence of postoperative pulmonary complications in the breathing training group was lower than that in the control group (5/120 [4%] vs 14/120 [12%]; RR 0.357, 95%CI 0.133-0.960; P = 0.031). In addition, PaO2 and arterial oxygenation index on the first and fourth days after surgery were significantly higher in the breathing training group than in the control group (P < 0.001). In addition, patients with breathing training had shorter length of stay (6d [IQR 5-7] vs 8d [IQR 7-9]), lower hospital charges (7761 ± 1679 vs 8212 ± 1326), and higher patient satisfaction (9.46 ± 0.65 vs 9.21 ± 0.47) than those without. CONCLUSION: Perioperative breathing training may reduce the incidence of postoperative pulmonary complications and preserve of arterial oxygenation after laparoscopic colorectal surgery.

Preoperative physiotherapy is cost-effective for preventing pulmonary complications after major abdominal surgery: a health economic analysis of a multicentre randomised trial.

QUESTION: Is preoperative physiotherapy cost-effective in reducing postoperative pulmonary complications (PPC) and improving quality-adjusted life years (QALYs) after major abdominal surgery? DESIGN: Cost-effectiveness analysis from the hospitals' perspective within a multicentre randomised controlled trial with concealed allocation, blinded assessors and intention-to-treat analysis. PARTICIPANTS: Four hundred and forty-one adults awaiting elective upper abdominal surgery attending pre-anaesthetic clinics at three public hospitals in Australia and New Zealand. INTERVENTIONS: The experimental group received an information booklet and a 30-minute face-to-face session, involving respiratory education and breathing exercise training, with a physiotherapist. The control group received the information booklet only. OUTCOME MEASURES: The probability of cost-effectiveness and incremental net benefits was estimated using bootstrapped incremental PPC and QALY cost-effectiveness ratios plotted on cost-effectiveness planes and associated probability curves through a range of willingness-to-pay amounts. Cost-effectiveness modelling utilised 21-day postoperative hospital cost audit data and QALYs estimated from Short Form-Six Domain health utilities and mortality to 12 months. RESULTS: Preoperative physiotherapy had 95% probability of being cost-effective with an incremental net benefit to participating hospitals of A$4,958 (95% CI 10 to 9,197) for each PPC prevented, given that the hospitals were willing to pay $45,000 to provide the service. Cost-utility for QALY gains was less certain. Sensitivity analyses strengthened cost-effectiveness findings. Improved cost-effectiveness and QALY gains were detected when experienced physiotherapists delivered the intervention. CONCLUSIONS: Preoperative physiotherapy aimed at preventing PPCs was highly likely to be cost-effective from the hospitals' perspective. For each PPC prevented, preoperative physiotherapy is likely to cost the hospitals less than the costs estimated to treat a PPC after surgery. Potential QALY gains require confirmation. TRIAL REGISTRATION: ACTRN12613000664741.

Spirometry in Occupational Health-2020.

: Spirometry in the occupational health setting plays a critical role in the primary, secondary, and tertiary prevention of workplace-related lung disease. Recognizing the central role of spirometry in workplace respiratory programs, the American College of Occupational and Environmental Medicine (ACOEM) developed three spirometry position statements in the past two decades, which summarized advances of particular relevance to occupational health practice. However, since these statements were published, there have been important developments in federal regulations and in official American Thoracic Society recommendations which affect occupational spirometry testing. This 2020 ACOEM guidance statement incorporates these spirometry testing changes into its recommendations to provide current information for all users of spirometry test results, from those who perform or supervise testing to those who only interpret or review results.

Modified-BEP Chemotherapy in Patients With Germ-Cell Tumors Treated at a Comprehensive Cancer Center.

OBJECTIVES: Bleomycin, etoposide, and cisplatin (BEP) is the most common and successful chemotherapy regimen for germ-cell tumor (GCT) patients, accompanied by a bleomycin-induced dose-dependent lung toxicity in certain patients. In an attempt to reduce bleomycin-toxicity, we developed a modified-BEP (mBEP) regimen. MATERIALS AND METHODS: Between August 2008 and February 2018, 182 unselected mainly testicular GCT patients (39 with adjuvant purpose and 143 with curative purpose) received a tri-weekly 5-day hospitalization schedule with bleomycin 15 U intravenous (IV) push on day 1 and 10 U IV continuous infusion over 12 hours on days 1 to 3, cisplatin 20 mg/m IV, and etoposide 100 mg/m IV on days 1 to 5. Pulmonary toxicity was assessed through chest computed tomography scan and clinical monitoring. RESULTS: Median number of mBEP cycles was 3 (range: 1 to 4). In the curative setting, according to the International Germ Cell Cancer Collaborative Group (IGCCCG) prognostic system, 112, 21, and 9 patients had good-risk, intermediate-risk, and poor-risk class, respectively; 66 (46%) patients had complete response (CR), 67 (47%) had partial response (52 of whom became CR afterwards), 6 (4%) had stable disease (that in 3 became CR afterwards), 3 (2%) progressed, and 1 (1%) died of brain stroke. At a median follow-up of 2.67 years (interquartile range: 1.23-5.00 y), 1 and 5-year overall survival and progression-free survival were 99% and 95%, and 90% and 88%, respectively. In the entire patient population, there was grade 3/4 neutropenia in 92 patients (51%), febrile neutropenia in 11 patients (6%), grade 1/2 nausea in 74 patients (41%), and no death due to pulmonary toxicity. CONCLUSION: In GCT patients, our mBEP-schedule would suggest an effective treatment modality without suffering meaningful pulmonary toxicity.

The Use of Regional or Local Anesthesia for Carotid Endarterectomies May Reduce Blood Loss and Pulmonary Complications.

OBJECTIVE: Over 150,000 carotid endarterectomy (CEA) procedures are performed each year. Perioperative anesthetic management may be complex due to multiple patient and procedure-related risk factors. The authorsaimed to determine whether the use of general anesthesia (GA), when compared with regional anesthesia (RA), would be associated with reduced perioperative morbidity and mortality in patients undergoing a CEA. DESIGN: Retrospective analysis of the American College of Surgeons National Surgical Quality Improvement Program (NSQIP) database. SETTING: The authors evaluated patients undergoing a CEA at multiple university- and community-based settings. PARTICIPANTS: A total of 43,463 patients were identified; 22,845 patients were propensity matched after excluding for missing data. INTERVENTIONS: The study population was divided into 2 groups: patients undergoing RA or GA. The RA group included regional anesthesia performed by the anesthesiologist or surgeon, monitored anesthesia care, and local infiltration. METHODS: The primary endpoint was 30-day mortality. Secondary endpoints included surgical site infection, pulmonary complications, return to the operating room, acute kidney injury, cardiac arrest, urinary tract infection, myocardial infarction, thromboembolism, perioperative transfusion, sepsis, and days to discharge. MEASUREMENTS AND MAIN RESULTS: Younger age, Hispanic ethnicity, body mass index <18.5, dyspnea, chronic obstructive pulmonary disease, and smoking history were associated with receiving GA. Patients with low hematocrit and low platelets were more likely to get RA. There was no mortality difference. GA was associated with a significantly higher rate of perioperative transfusions (p = 0.037) and perioperative pneumonia (p = 0.027). CONCLUSION: The use of RA over GA in CEA is associated with decreased risk of postoperative pneumonia and a reduced need for perioperative blood transfusions.

Cold-inducible RNA-binding protein-derived peptide C23 attenuates inflammation and tissue injury in a murine model of intestinal ischemia-reperfusion.

BACKGROUND: Cold-inducible RNA-binding protein is a novel damage-associated molecular pattern that causes inflammation. C23, a short peptide derived from cold-inducible RNA-binding protein, has been found to have efficacy in blocking cold-inducible RNA-binding protein's activity. We hypothesized that C23 reduces inflammation and tissue injury induced by intestinal ischemia-reperfusion. METHODS: Male C57BL/6 mice were subjected to 60 minutes of intestinal ischemia by clamping the superior mesenteric artery. Immediately after reperfusion, either normal saline (vehicle) or C23 peptide (8 mg/kg body weight) was injected intraperitoneally. Four hours after reperfusion, blood, intestinal, and lung tissues were collected for analysis of inflammatory and tissue injury parameters. RESULTS: Cold-inducible RNA-binding protein levels in the intestinal tissues were significantly increased following intestinal ischemia-reperfusion. Histologic examination of the intestine revealed a significant reduction in injury score in the C23 group by 48% as compared with the vehicles after intestinal ischemia-reperfusion. The serum levels of lactate dehydrogenase and aspartate aminotransferase were increased in animals that underwent vehicle-treated intestinal ischemia-reperfusion, whereas C23-treated animals exhibited significant reductions by 48% and 53%, respectively. The serum and intestinal tissue levels of tumor necrosis factor α were elevated in vehicle-treated intestinal ischemia-reperfusion mice but decreased by 72% and 69%, respectively, in C23-treated mice. Interleukin-6 mRNA levels in the lungs were reduced by 86% in the C23-treated group in comparison to the vehicle-treated group after intestinal ischemia-reperfusion. Expression of macrophage inflammatory protein 2 and level of myeloperoxidase activity in the lungs were dramatically increased after intestinal ischemia-reperfusion and significantly reduced by 91% and 25%, respectively, in the C23-treated group. CONCLUSION: C23 has potential to be developed into a possible therapy for reperfusion injury after mesenteric ischemia and reperfusion.

Propolis Protects Endotoxin Induced Acute Lung and Liver Inflammation Through Attenuating Inflammatory Responses and Oxidative Stress.

Propolis is a natural bee product, and it has many effects, including antioxidant, anti-inflammatory, antihepatotoxic, and anticancer activity. In this study, we aimed to explore the potential in vivo anti-inflammatory, antioxidant, and antiapoptotic properties of propolis extract on lipopolysaccharide (LPS)-induced inflammation in rats. Forty-two, 3- to 4-month-old male Sprague Dawley rats were used in six groups. LPS (1 mg/kg) was administered intraperitoneally to rats in inflammation, inflammation + propolis30, and inflammation+propolis90 groups. Thirty milligram/kilogram and 90 mg/kg of propolis were given orally 24 h after LPS injection. After the determination of the inflammation in lung and liver tissues by 18F-fluoro-deoxy-d-glucose-positron emission tomography (18FDG-PET), samples were collected. The levels of malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), nitric oxide (NO), and DNA fragmentation were determined. The decrease of MDA levels in inflammation + propolis30 and inflammation + propolis90 groups was determined compared to the inflammation group in lung and liver tissues. The increase of SOD% inhibition in inflammation + propolis90 group was determined in liver, lung, and hemolysate compared to the inflammation group. Increased CAT activities in inflammation + propolis30 and inflammation + propolis90 groups were observed in liver tissue and hemolysate compared to inflammation group. In lung tissue, NO levels were lower in inflammation group compared to the control group, but DNA fragmentation levels were higher. 18F-FDG uptake of tissues in inflammation + propolis30 and inflammation + propolis90 groups was decreased compared to the inflammation group. In conclusion, the data of this study indicate that the propolis application may serve as a potential approach for treating inflammatory diseases through the effect of reducing inflammation and free oxygen radical production.

Inspiratory muscle training is associated with decreased postoperative pulmonary complications: Evidence from randomized trials.

OBJECTIVE: To determine whether preoperative inspiratory muscle training was associated with a significant difference in the rate of postoperative pulmonary adverse outcomes in patients undergoing cardiothoracic or upper abdominal surgery using trial sequential analysis to correct for the risk of random errors. METHODS: We systematically reviewed the Excerpta Medica database, PubMed, Web of Science, Cumulative Index to Nursing and Allied Health Literature, and Cochrane Central Register of Controlled Trials for randomized controlled trials evaluating inspiratory muscle training before cardiothoracic or upper abdominal surgery. Outcome measures included postoperative pulmonary complications, length of hospital stay, maximum inspiratory pressure, and quality of life. A random-effects model was used to estimate relative risks with 95% confidence intervals (CIs). We used trial sequential analysis to calculate a diversity-adjusted required information size for meta-analysis. RESULTS: Thirteen randomized controlled trials were included in the meta-analysis for a total of 784 patients. Compared with the standard care group, the inspiratory muscle training group exhibited significantly decreased postoperative pulmonary complications (risk ratio, 0.59; 95% CI, 0.47-0.74). Trial sequential analysis indicated that the cumulative Z curve crossed both the conventional boundary and the trial sequential monitoring boundary for benefit. The length of hospital stay was reduced in the inspiratory muscle training group (mean difference, -1.15 days; 95% CI, -2.10 to 0.20), and the maximum inspiratory pressure was significantly improved at the end of the preoperative training (mean difference, 13.66; 95% CI, 3.88-23.44). The quality of life outcome was unavailable in most of the studies. CONCLUSIONS: Preoperative inspiratory muscle training resulted in significantly improved maximum inspiratory pressure and was associated with decreased postoperative pulmonary complications.

Immunization with Pseudomonas aeruginosa outer membrane vesicles stimulates protective immunity in mice.

Pseudomonas aeruginosa is an opportunistic pathogen responsible for a wide range of severe nosocomial and community acquired infections, these infections are major health problems for cystic fibrosis patients and immune-compromised individuals. The emergence of multidrug-resistant isolates highlights the need to develop alternative strategies for treatment of P. aeruginosa infections. Outer membrane vesicles (OMVs) are spherical nanometer-sized proteolipids that are secreted from numerous of pathogenic Gram-negative bacteria, and a number of studies have confirmed the protective efficacy for use of OMVs as candidate vaccines. In this study, OMVs from P. aeruginosa (PA_OMVs) were isolated, formulated with aluminum phosphate adjuvant and used as a vaccine in a mouse model of acute lung infection. The results confirmed that active immunization with PA_OMVs was able to reduce bacterial colonization, cytokine secretion and tissue damage in the lung tissue, thus protecting mice from lethal challenge of P. aeruginosa. Cytokines assay validated that immunization with PA_OMVs was efficient to induce a mixed cellular immune response in mice. Further, high level of specific antibodies was detected in mice immunized with PA_OMVs, and results from opsonophagocytic killing assay and passive immunization suggested that humoral immune response may be critical for PA_OMVs mediated protection. These findings demonstrated that PA_OMVs may be served as a novel candidate vaccine for the prevention of P. aeruginosa infection.

Effects of a liquefied petroleum gas stove intervention on pollutant exposure and adult cardiopulmonary outcomes (CHAP): study protocol for a randomized controlled trial.

BACKGROUND: Biomass fuel smoke is a leading risk factor for the burden of disease worldwide. International campaigns are promoting the widespread adoption of liquefied petroleum gas (LPG) in resource-limited settings. However, it is unclear if the introduction and use of LPG stoves, in settings where biomass fuels are used daily, reduces pollution concentration exposure, improves health outcomes, or how cultural and social barriers influence the exclusive adoption of LPG stoves. METHODS: We will conduct a randomized controlled, field intervention trial of LPG stoves and fuel distribution in rural Puno, Peru, in which we will enroll 180 female participants aged 25-64 years and follow them for 2 years. After enrollment, we will collect information on sociodemographic characteristics, household characteristics, and cooking practices. During the first year of the study, LPG stoves and fuel tanks will be delivered to the homes of 90 intervention participants. During the second year, participants in the intervention arm will keep their LPG stoves, but the gas supply will stop. Control participants will receive LPG stoves and vouchers to obtain free fuel from distributors at the beginning of the second year, but gas will not be delivered. Starting at baseline, we will collect longitudinal measurements of respiratory symptoms, pulmonary function, blood pressure, endothelial function, carotid artery intima-media thickness, 24-h dietary recalls, exhaled carbon monoxide, quality-of-life indicators, and stove-use behaviors. Environmental exposure assessments will occur six times over the 2-year follow-up period, consisting of 48-h personal exposure and kitchen concentration measurements of fine particulate matter and carbon monoxide, and 48-h kitchen concentrations of nitrogen dioxide for a subset of 100 participants. DISCUSSION: Findings from this study will allow us to better understand behavioral patterns, environmental exposures, and cardiovascular and pulmonary outcomes resulting from the adoption of LPG stoves. If this trial indicates that LPG stoves are a feasible and effective way to reduce household air pollution and improve health, it will provide important information to support widespread adoption of LPG fuel as a strategy to reduce the global burden of disease. TRIAL REGISTRATION: ClinicalTrials.gov, ID: NCT02994680 , Cardiopulmonary Outcomes and Household Air Pollution (CHAP) Trial. Registered on 28 November 2016.

Melatonin protects against the pathological cardiac hypertrophy induced by transverse aortic constriction through activating PGC-1ß: In vivo and in vitro studies.

Melatonin, a circadian molecule secreted by the pineal gland, confers a protective role against cardiac hypertrophy induced by hyperthyroidism, chronic hypoxia, and isoproterenol. However, its role against pressure overload-induced cardiac hypertrophy and the underlying mechanisms remains elusive. In this study, we investigated the pharmacological effects of melatonin on pathological cardiac hypertrophy induced by transverse aortic constriction (TAC). Male C57BL/6 mice underwent TAC or sham surgery at day 0 and were then treated with melatonin (20 mg/kg/day, via drinking water) for 4 or 8 weeks. The 8-week survival rate following TAC surgery was significantly increased by melatonin. Melatonin treatment for 8 weeks markedly ameliorated cardiac hypertrophy. Compared with the TAC group, melatonin treatment for both 4 and 8 weeks reduced pulmonary congestion, upregulated the expression level of α-myosin heavy chain, downregulated the expression level of ß-myosin heavy chain and atrial natriuretic peptide, and attenuated the degree of cardiac fibrosis. In addition, melatonin treatment slowed the deterioration of cardiac contractile function caused by pressure overload. These effects of melatonin were accompanied by a significant upregulation in the expression of peroxisome proliferator-activated receptor-gamma co-activator-1 beta (PGC-1ß) and the inhibition of oxidative stress. In vitro studies showed that melatonin also protects against angiotensin II-induced cardiomyocyte hypertrophy and oxidative stress, which were largely abolished by knocking down the expression of PGC-1ß using small interfering RNA. In summary, our results demonstrate that melatonin protects against pathological cardiac hypertrophy induced by pressure overload through activating PGC-1ß.

Baicalein Attenuates Lung Injury Induced by Myocardial Ischemia and Reperfusion.

Baicalein is an active component of Scutellaria baicalensis Georgi, which has traditionally been used to treat cardiovascular diseases in China. In this study, we investigated if treatment with baicalein can attenuate the lung injury induced by myocardial ischemia and reperfusion (I/R). Myocardial I/R, induced by a 40-min occlusion of the left anterior descending coronary artery and a 3-h reperfusion, significantly increased histological damage and the wet-to-dry weight ratio of lungs in rats. The terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL)-positive nuclei and caspase-3 activation was significantly increased in the lungs. Serum and bronchoalveolar lavage fluid levels of tumor necrosis factor-[Formula: see text] (TNF-[Formula: see text]), interleukin-1[Formula: see text] (IL-1[Formula: see text]), and interleukin-6 (IL-6) were significantly elevated, as were TNF-[Formula: see text] levels in the lung. Intravenous administration with baicalein at doses of 3, 10, and 30[Formula: see text]mg/kg for ten minutes before myocardial I/R significantly reduced histological damage, the wet-to-dry weight ratio, and apoptosis in the lung. Baicalein also significantly inhibited the increase in levels of TNF-[Formula: see text], IL-1[Formula: see text], and IL-6. Moreover, baicalein increased Bcl-2 and decreased p53, Bax, and cytochrome [Formula: see text] in lungs. Phosphorylation of the prosurvival kinases, including Akt and extracellular signal-regulated kinases 1 and 2 (ERK1/2), was increased, while the phosphorylation of the pro-apoptotic mitogen-activated protein kinases, including p38 and c-Jun N-terminal kinase (JNK), was decreased. In conclusion, treatment with baicalein attenuates the lung injury induced by myocardial I/R. The mechanisms might be related to the limiting of apoptosis, possibly via the inhibition of both the extrinsic and intrinsic pathways of apoptosis, including the inhibition of TNF-[Formula: see text] production and modulation of pro- and anti-apoptotic signaling elements.

Pretreatment with the ALDH2 agonist Alda-1 reduces intestinal injury induced by ischaemia and reperfusion in mice.

Many studies demonstrate that activation of aldehyde dehydrogenase 2 (ALDH2) protects against oxidative stress via detoxification of cytotoxic aldehydes, and could attenuate cardiac, cerebral, lung and renal ischaemia-reperfusion (I/R) injuries. However, the effect of ALDH2 in intestinal I/R is unknown. The present study was set up to determine whether an ALDH2 agonist, Alda-1, could alleviate intestinal injury after gut I/R. In a mouse model of intestinal I/R injury, histological grading, proinflammatory cytokines, oxidative stress, cellular apoptosis, chemokine contents, ALDH2 activity, 4-hydroxy-trans-2-nonenal (4-HNE) and malondialdehyde (MDA) were evaluated. The results indicated that I/R treatment conferred elevation in pathological scores, proinflammatory cytokines, oxidative stress, cellular apoptosis and chemokine levels, accompanied by accumulated 4-HNE and MDA. No significant changes in ALDH2 activity were observed after I/R. However, Alda-1 pretreatment significantly decreased these injurious indicators, concomitant with up-regulated ALDH2 activity, and lessened 4-HNE and MDA accumulation. Taken together, our results implicate activation of ALDH2 by Alda-1 in the significant abatement intestinal I/R injury.

Vitamin A supplementation to prevent mortality and short- and long-term morbidity in very low birth weight infants.

BACKGROUND: Vitamin A is necessary for normal lung growth and the integrity of respiratory tract epithelial cells. Preterm infants have low vitamin A status at birth and this has been associated with an increased risk of developing chronic lung disease. OBJECTIVES: To evaluate supplementation with vitamin A on the incidence of death or neonatal chronic lung disease and long-term neurodevelopmental disability in very low birth weight (VLBW) infants compared with a control (placebo or no supplementation), and to consider the effect of the supplementation route, dose, and timing. SEARCH METHODS: For the original review and subsequent updates, we searched the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library), MEDLINE, Science Citation Index, and the Oxford Database of Perinatal Trials. The reference lists of relevant trials, paediatric and nutrition journals, and conference abstracts and proceedings were handsearched up to 2010.For the 2016 update, we used the standard search strategy of the Cochrane Neonatal Review group to search the Cochrane Central Register of Controlled Trials (CENTRAL 2016, Issue 4), MEDLINE via PubMed (1 May 2016), EMBASE (1 May 2016), and CINAHL (1 May 2016). We also searched clinical trials' databases, conference proceedings, and the reference lists of retrieved articles for randomised controlled trials and quasi-randomised trials. SELECTION CRITERIA: Randomised controlled trials comparing vitamin A supplementation with a control (placebo or no supplementation) or other dosage regimens in VLBW infants (birth weight ≤ 1500 grams or less than 32 weeks' gestation). DATA COLLECTION AND ANALYSIS: Two review authors screened the search results, extracted data, and assessed the trials for risk of bias. Results were reported as risk ratios (RR), risk differences (RD), and number needed to treat to benefit (NNTB), all with 95% confidence intervals (CI). Trialists were contacted for additional data. MAIN RESULTS: Eleven trials met the inclusion criteria. Ten trials (1460 infants) compared vitamin A supplementation with a control and one (120 infants) compared different regimens of vitamin A supplementation. Compared to the control group, vitamin A appeared to have a small benefit in reducing the risk of death or oxygen requirement at one month of age (typical RR 0.93, 95% CI 0.88 to 0.99; typical RD -0.05, 95% CI -0.10 to -0.01; NNTB 20, 95% CI 10 to 100; 6 studies, 1165 infants) and the risk of chronic lung disease (oxygen requirement) at 36 weeks' postmenstrual age (typical RR 0.87, 95% CI 0.77 to 0.99; typical RD -0.07, 95% CI -0.13 to -0.01; NNTB 11, 95% CI 6 to 100; 5 studies, 986 infants) (moderate-quality evidence). There was a marginal reduction of the combined outcome of death or chronic lung disease (typical RR 0.92, 95% CI 0.84 to 1.01; typical RD -0.05, 95% CI -0.11 to 0.01; 4 studies, 1089 infants). Neurodevelopmental assessment of 88% of the surviving infants in the largest trial showed no difference between the groups at 18 to 22 months of age, corrected for prematurity (low-quality evidence). There is no evidence to support different vitamin A dosing regimens. No adverse effects of vitamin A supplementation were reported, but it was noted that intramuscular injections of vitamin A were painful. AUTHORS' CONCLUSIONS: Whether clinicians decide to utilise repeat intramuscular doses of vitamin A to prevent chronic lung disease may depend upon the local incidence of this outcome and the value attached to achieving a modest reduction in the outcome balanced against the lack of other proven benefits and the acceptability of the treatment. Information on long-term neurodevelopmental status suggests no evidence of either benefit or harm from the intervention.

Medicinal plants--prophylactic and therapeutic options for gastrointestinal and respiratory diseases in calves and piglets? A systematic review.

BACKGROUND: Gastrointestinal and respiratory diseases in calves and piglets lead to significant economic losses in livestock husbandry. A high morbidity has been reported for diarrhea (calves ≤ 35%; piglets ≤ 50%) and for respiratory diseases (calves ≤ 80%; piglets ≤ 40%). Despite a highly diverse etiology and pathophysiology of these diseases, treatment with antimicrobials is often the first-line therapy. Multi-antimicrobial resistance in pathogens results in international accordance to strengthen the research in novel treatment options. Medicinal plants bear a potential as alternative or additional treatment. Based on the versatile effects of their plant specific multi-component-compositions, medicinal plants can potentially act as 'multi-target drugs'. Regarding the plurality of medicinal plants, the aim of this systematic review was to identify potential medicinal plant species for prevention and treatment of gastrointestinal and respiratory diseases and for modulation of the immune system and inflammation in calves and piglets. RESULTS: Based on nine initial sources including standard textbooks and European ethnoveterinary studies, a total of 223 medicinal plant species related to the treatment of gastrointestinal and respiratory diseases was identified. A defined search strategy was established using the PRISMA statement to evaluate 30 medicinal plant species starting from 20'000 peer-reviewed articles published in the last 20 years (1994-2014). This strategy led to 418 references (257 in vitro, 84 in vivo and 77 clinical trials, thereof 48 clinical trials in veterinary medicine) to evaluate effects of medicinal plants and their efficacy in detail. The findings indicate that the most promising candidates for gastrointestinal diseases are Allium sativum L., Mentha x piperita L. and Salvia officinalis L.; for diseases of the respiratory tract Echinacea purpurea (L.) MOENCH, Thymus vulgaris L. and Althea officinalis L. were found most promising, and Echinacea purpurea (L.) MOENCH, Camellia sinensis (L.) KUNTZE, Glycyrrhiza glabra L. and Origanum vulgare L. were identified as best candidates for modulation of the immune system and inflammation. CONCLUSIONS: Several medicinal plants bear a potential for novel treatment strategies for young livestock. There is a need for further research focused on gastrointestinal and respiratory diseases in calves and piglets, and the findings of this review provide a basis on plant selection for future studies.

Dietary and pharmacological intervention to mitigate the cardiopulmonary effects of air pollution toxicity.

BACKGROUND: Exposure to air pollution contributes importantly to excess morbidity and mortality. And while regulatory actions under the "Clean Air Act" have saved millions of lives by improving air quality, there are still millions of people in the U.S. who live in areas where particulate air pollution (PM) levels exceed the U.S. Environmental Protection Agency's National Ambient Air Quality Standards. Therefore, apart from such localities working to attain such standards the protection of the health of public and in particular those at high risk might benefit from interventional strategies that would ameliorate air pollution's adverse health effects. Because inflammation and oxidative stress appear to mediate the health effects of air pollution, one interventional approach to consider is the use of dietary supplementation or medication with anti-inflammatory or antioxidant properties to block the biological responses that initiate the pathophysiological process that culminates in adverse health effects. SCOPE OF REVIEW: This article reviews the capability of dietary supplementation, such as antioxidant vitamins, polyunsaturated fatty acids, and medications as a strategy to mitigate air pollution-induced subclinical cardiopulmonary effects. MAJOR CONCLUSIONS: Antioxidant vitamins C and E protect the lungs against short-term ozone and PM exposure. Polyunsaturated fatty acids, such as fish oil and olive oil appear to offer protection against short-term air pollution-induced adverse cardiovascular responses. GENERAL SIGNIFICANCE: Taking dietary supplements or medications with antioxidant or anti-inflammatory properties has the potential to provide at least partial protection against air pollution-induced adverse health effects in those individuals who are known to be most susceptible, namely those with pre-existing respiratory and cardiovascular diseases. This article is part of a Special Issue entitled Air Pollution, edited by Wenjun Ding, Andrew J. Ghio and Weidong Wu.