scholarly journals Dose, Timing, and Type of Infant Antibiotic Use and the Risk of Childhood Asthma

2019 ◽  
Vol 70 (8) ◽  
pp. 1658-1665 ◽  
Author(s):  
Brittney M Donovan ◽  
Andrew Abreo ◽  
Tan Ding ◽  
Tebeb Gebretsadik ◽  
Kedir N Turi ◽  
...  
Keyword(s):  
Childhood Asthma ◽  
Clinical Decision Making ◽  
Antibiotic Prescription ◽  
Subsequent Development ◽  
Antibiotic Use ◽  
Healthy Children ◽  
Dependent Manner ◽  
Antibiotic Exposure ◽  
The Impact ◽  
Dose Dependent

Abstract Background Aspects of infant antibiotic exposure and its association with asthma development have been variably explored. We aimed to evaluate comprehensively and simultaneously the impact of dose, timing, and type of infant antibiotic use on the risk of childhood asthma. Methods Singleton, term-birth, non–low-birth-weight, and otherwise healthy children enrolled in the Tennessee Medicaid Program were included. Infant antibiotic use and childhood asthma diagnosis were ascertained from prescription fills and healthcare encounter claims. We examined the association using multivariable logistic regression models. Results Among 152 622 children, 79% had at least 1 antibiotic prescription fill during infancy. Infant antibiotic use was associated with increased odds of childhood asthma in a dose-dependent manner, with a 20% increase in odds (adjusted odds ratio [aOR], 1.20 [95% confidence interval {CI}, 1.19–1.20]) for each additional antibiotic prescription filled. This significant dose-dependent relationship persisted after additionally controlling for timing and type of the antibiotics. Infants who had broad-spectrum-only antibiotic fills had increased odds of developing asthma compared with infants who had narrow-spectrum-only fills (aOR, 1.10 [95% CI, 1.05–1.19]). There was no significant association between timing, formulation, anaerobic coverage, and class of antibiotics and childhood asthma. Conclusions We found a consistent dose-dependent association between antibiotic prescription fills during infancy and subsequent development of childhood asthma. Our study adds important insights into specific aspects of infant antibiotic exposure. Clinical decision making regarding antibiotic stewardship and prevention of adverse effects should be critically assessed prior to use during infancy.

scholarly journals Prenatal antibiotic exposure and childhood asthma: a population-based study

2018 ◽  
Vol 52 (1) ◽  
pp. 1702070 ◽  
Author(s):  
Keely Loewen ◽  
Barret Monchka ◽  
Salaheddin M. Mahmud ◽  
Geert 't Jong ◽  
Meghan B. Azad
Keyword(s):  
Childhood Asthma ◽  
Cox Regression ◽  
Antibiotic Use ◽  
Population Based ◽  
Sensitivity Analyses ◽  
Antibiotic Exposure ◽  
Physician Billing ◽  
Increased Risk ◽  
Before And After ◽  
The Impact

Antibiotic use during infancy alters gut microbiota and immune development and is associated with an increased risk of childhood asthma. The impact of prenatal antibiotic exposure is unclear. We sought to characterise the association between prenatal antibiotic exposure and childhood asthma.We performed a population-based cohort study using prescription records, hospitalisation records and physician billing claims from 213 661 mother–child dyads born in Manitoba, Canada between 1996 and 2012. Associations were determined using Cox regression, adjusting for maternal asthma, postnatal antibiotics and other potential confounders. Sensitivity analyses evaluated maternal antibiotic use before and after pregnancy.36.8% of children were exposed prenatally to antibiotics and 10.1% developed asthma. Prenatal antibiotic exposure was associated with an increased risk of asthma (adjusted hazard ratio (aHR) 1.23, 95% CI 1.20–1.27). There was an apparent dose response (aHR 1.15, 95% CI 1.11–1.18 for one course; aHR 1.26, 95% CI 1.21–1.32 for two courses; and aHR 1.51, 95% CI 1.44–1.59 for three or more courses). Maternal antibiotic use during 9 months before pregnancy (aHR 1.27, 95% CI 1.24–1.31) and 9 months postpartum (aHR 1.32, 95% CI 1.28–1.36) were similarly associated with asthma.Prenatal antibiotic exposure was associated with a dose-dependent increase in asthma risk. However, similar associations were observed for maternal antibiotic use before and after pregnancy, suggesting the association is either not directly causal, or not specific to pregnancy.

scholarly journals Inhibition of p38 Mitogen-Activated Protein Kinase Impairs Mayaro Virus Replication in Human Dermal Fibroblasts and HeLa Cells

Viruses ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1156
Author(s):  
Madelaine Sugasti-Salazar ◽  
Yessica Y. Llamas-González ◽  
Dalkiria Campos ◽  
José González-Santamaría
Keyword(s):  
Protein Expression ◽  
Hela Cells ◽  
Plaque Assay ◽  
Dermal Fibroblasts ◽  
Dependent Manner ◽  
Human Dermal Fibroblasts ◽  
Mitogen Activated Protein ◽  
Mayaro Virus ◽  
The Impact ◽  
Dose Dependent

Mayaro virus (MAYV) hijacks the host’s cell machinery to effectively replicate. The mitogen-activated protein kinases (MAPKs) p38, JNK, and ERK1/2 have emerged as crucial cellular factors implicated in different stages of the viral cycle. However, whether MAYV uses these MAPKs to competently replicate has not yet been determined. The aim of this study was to evaluate the impact of MAPK inhibition on MAYV replication using primary human dermal fibroblasts (HDFs) and HeLa cells. Viral yields in supernatants from MAYV-infected cells treated or untreated with inhibitors SB203580, SP600125, U0126, or Losmapimod were quantified using plaque assay. Additionally, viral protein expression was analyzed using immunoblot and immunofluorescence. Knockdown of p38⍺/p38β isoforms was performed in HDFs using the PROTACs molecule NR-7h. Our data demonstrated that HDFs are highly susceptible to MAYV infection. SB203580, a p38 inhibitor, reduced MAYV replication in a dose-dependent manner in both HDFs and HeLa cells. Additionally, SB203580 significantly decreased viral E1 protein expression. Similarly, knockdown or inhibition of p38⍺/p38β isoforms with NR-7h or Losmapimod, respectively, affected MAYV replication in a dose-dependent manner. Collectively, these findings suggest that p38 could play an important role in MAYV replication and could serve as a therapeutic target to control MAYV infection.

scholarly journals Comparison of Different Methods for Extracting the Astaxanthin from Haematococcus pluvialis: Chemical Composition and Biological Activity

Molecules ◽  
2021 ◽  
Vol 26 (12) ◽  
pp. 3569
Author(s):  
Yicheng Tan ◽  
Zhang Ye ◽  
Mansheng Wang ◽  
Muhammad Faisal Manzoor ◽  
Rana Muhammad Aadil ◽  
...  
Keyword(s):  
High Pressure ◽  
Biological Activity ◽  
Chemical Composition ◽  
Haematococcus Pluvialis ◽  
Activity Analysis ◽  
Cell Disruption ◽  
Dependent Manner ◽  
Dpph Activity ◽  
The Impact ◽  
Dose Dependent

In this study, the impact of different cell disruption techniques (high-pressure micro fluidization (HPMF), ionic liquids (ILs), multi-enzyme (ME), and hydrochloric acid (HCl)) on the chemical composition and biological activity of astaxanthin (AST) obtained from Haematococcus pluvialis was investigated. Results indicated that all cell disruption techniques had a significant effect on AST composition, which were confirmed by TLC and UPC2 analysis. AST recovery from HCl (HCl-AST) and ILs (ILs-AST) cell disruption techniques was dominant by free and monoesters AST, while AST recovery from HPMF (HPMF-AST) and ME (ME-AST) cell disruption techniques was composed of monoesters, diesters, and free AST. Further biological activity analysis displayed that HCl-AST showed the highest ABTS and DPPH activity, while ILs-AST showed better results against the ORAC assay. Additionally, ILs-AST exhibits a stronger anti-proliferation of HepG2 cells in a dose-dependent manner, which was ascribed to AST-induced ROS in to inhibit the proliferative of cancer cells.

Post-Exercise Protein Ingestion Increases Whole Body Leucine Balance in a Dose-Dependent Manner in Healthy Children

2016 ◽  
Vol 48 ◽  
pp. 442
Author(s):  
Kimberly A. Volterman ◽  
Daniel R. Moore ◽  
Peter Breithaupt ◽  
Elizabeth Offord-Cavin ◽  
Leonidas G. Karagounis ◽  
...  
Keyword(s):  
Whole Body ◽  
Healthy Children ◽  
Dependent Manner ◽  
Post Exercise ◽  
Protein Ingestion ◽  
Dose Dependent

scholarly journals Does Curcumin Have a Role in the Interaction between Gut Microbiota and Schistosoma mansoni in Mice?

Pathogens ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 767
Author(s):  
Assmaa Anter ◽  
Mohamed Abd El-Ghany ◽  
Marwa Abou El Dahab ◽  
Noha Mahana
Keyword(s):  
Schistosoma Mansoni ◽  
Intestinal Microbiota ◽  
Bacterial Species ◽  
Therapeutic Effects ◽  
Dependent Manner ◽  
Pseudomonas Sp ◽  
E Coli ◽  
Predominant Species ◽  
The Impact ◽  
Dose Dependent

There is strong correlation between changes in abundance of specific bacterial species and several diseases including schistosomiasis. Several studies have described therapeutic effects of curcumin (CUR) which may arise from its regulative effects on intestinal microbiota. Thus, we examined the impact of CUR on the diversity of intestinal microbiota with/without infection by Schistosoma mansoni cercariae for 56 days. Enterobacteriaceae was dominating in a naive and S. mansoni infected mice group without CUR treatment, the most predominant species was Escherichia coli with relative density (R.D%) = 80.66% and the least one was Pseudomonas sp. (0.52%). The influence of CUR on murine microbiota composition was examined one week after oral administration of high (40) and low (20 mg/kg b.w.) CUR doses were administered three times, with two day intervals. CUR induced high variation in the Enterobacteriaceae family, characterized by a significant (p < 0.001) reduction in E. coli and asignificant (p < 0.001) increase in Pseudomonas sp. in both naïve and S. mansoni-infected mice, compared to untreated mice, in a dose-dependent manner. Additionally, our study showed the effects of high CUR doses on S. mansoni infection immunological and parasitological parameters. These data support CUR’s ability to promote Pseudomonas sp. known to produce schistosomicidal toxins and offset the sequelae of murine schistosomiasis.

Evidence that estrogen receptor β enhances MMP-13 promoter activity in HIG-82 cells and that this enhancement can be influenced by ligands and involves specific promoter sites

2007 ◽  
Vol 85 (3) ◽  
pp. 326-336 ◽  
Author(s):  
Ting Lu ◽  
Yamini Achari ◽  
Jerome B. Rattner ◽  
David A. Hart
Keyword(s):  
Estrogen Receptor ◽  
Promoter Activity ◽  
Estrogen Receptor Β ◽  
Mrna Levels ◽  
Dependent Manner ◽  
Connective Tissues ◽  
Matrix Metalloproteinase 13 ◽  
Promoter Construct ◽  
The Impact ◽  
Dose Dependent

Degradation of articular cartilage is characteristic of osteoarthritis, and matrix metalloproteinase-13 (MMP-13) has been implicated in this condition. Estrogen receptors (ERs) are present in connective tissues, indicating these tissues' potential responsiveness to estrogen. We based this study on the hypothesis that estrogen receptor β (ERβ) can modulate MMP-13 promoter activity. Transfection of cells with ERβ constructs led to the induction of the endogenous MMP-13 gene, as evidenced by increased mRNA levels. The results also indicated that MMP-13 promoter construct activity in the HIG-82 cell line significantly increased when ERβ was present, and that estrogen downregulated this response in a dose-dependent manner. ERβ was shown to enhance MMP-13 expression somewhat more strongly than ERα, and the impact of a number of selective ER modulators (tamoxifen, raloxifene, and ICI 182,780) on ERβ enhancement of promoter activity was found to be significantly less than that of estrogen. Furthermore, transcription regulatory sites in the MMP-13 promoter, specifically AP-1 and PEA-3, were shown to act in conjunction to mediate ERβ effects. Thus, ERβ likely influences MMP-13 promoter expression in normal and disease processes.

scholarly journals Outbreak of murine infection withClostridium difficileassociated with the administration of a pre- and peri-natal methyl-donor diet

2019 ◽  
Author(s):  
Theresa Mau ◽  
Samantha S. Eckley ◽  
Ingrid L. Bergin ◽  
Katie Saund ◽  
Jason S. Villano ◽  
...  
Keyword(s):  
Clostridium Difficile ◽  
Control Diet ◽  
Antibiotic Use ◽  
Antibiotic Exposure ◽  
Murine Models ◽  
Outbreak Strain ◽  
Methyl Donor ◽  
Diet Intervention ◽  
Ribotype 027 ◽  
The Impact

AbstractBetween October 2016 and June 2017, a C57BL/6J mouse colony that was undergoing a pre- and peri-natal methyl-donor supplementation diet intervention to study the impact of parental nutrition on offspring susceptibility to disease was found to suffer from an epizootic of unexpected deaths. Necropsy revealed the presence of severe colitis, and further investigation linked these outbreak deaths to aClostridium difficilestrain of ribotype 027 we term 16N203.C. difficileinfection (CDI) is associated with antibiotic use in humans. Current murine models of CDI rely on antibiotic pretreatment to establish clinical phenotypes. In this report, theC. difficileoutbreak occurs in F1 mice linked to alterations in the parental diet. The diagnosis of CDI in the affected mice was confirmed by cecal/colonic histopathology, presence ofC. difficilebacteria in fecal/colonic culture, and detection ofC. difficiletoxins. F1 mice from parents fed the methyl-supplementation diet also had significantly reduced survival (p<0.0001) than F1 mice from parents fed the control diet. When we tested the 16N203 outbreak strain in an established mouse model of antibiotic-induced CDI, we confirmed that this strain is pathogenic. Our serendipitous observations from this spontaneous outbreak ofC. difficilein association with a pre- and perinatal methyl-donor diet suggest the important role diet may play in host defense and CDI risk factors.ImportanceClostridium difficileinfection (CDI) has become the leading cause of infectious diarrhea in hospitals worldwide, owing its preeminence to the emergence of hyperendemic strains, such as ribotype 027 (RT027). A major CDI risk factor is antibiotic exposure which alters gut microbiota, resulting in the loss of colonization resistance. Current murine models of CDI also depend on pretreatment of antibiotics of animals to establish disease. The outbreak we report here is unique in that the CDI occurred in mice with no antibiotic exposure and is associated to a pre- and peri-natal methyl-supplementation donor diet intervention study. Our investigation subsequently reveals that the outbreak strain we term 16N203 is an RT027 strain, and this isolated strain is also pathogenic in an established murine model of CDI (with antibiotics). Our report of this spontaneous outbreak offers additional insight into the importance of environmental factors, such as diet, and CDI susceptibility.

scholarly journals Quercetin mediated inhibition of Staphylococcus aureus biofilms and the impact of the isolate phenotype and genotype

2021 ◽  
Vol 42 (3) ◽  
pp. 615-624
Author(s):  
E.H. Eldrehmy ◽  
◽  
S.M. Abdel-Hafez ◽  
Y.S. Alghamdi ◽  
M.M. Soliman ◽  
...  
Keyword(s):  
Microtiter Plate ◽  
Antibiofilm Activity ◽  
Dependent Manner ◽  
Inhibition Rate ◽  
Pcr Assay ◽  
Gram Staining ◽  
Biofilm Production ◽  
Pcr Assays ◽  
The Impact ◽  
Dose Dependent

Aim: This study was designed to assess the antibiofilm activity of quercetin on characterized S. aureus isolates. Methodology: This study evaluated 36 S. aureus isolates, each of which was identified using Gram staining, culture, biochemical, and PCR assays. Isolates were cultured and their biofilm production was evaluated using Congo red agar (CRA) plates, microtiter plate tests and PCR, and the effects of quercetin were examined. Results: The CRA results revealed that eight (22.3%) S. aureus isolates were strongly positive for biofilm production and an additional 18 isolates (50%) showed moderate biofilm capacity. The remaining 10 isolates were negative (27.7%) for biofilm production. S. aureus isolates were divided into strong positive, intermediate, and negative groups, 27.8%, 44.5%, and 27.7%, respectively. Scanning electron microscopy showed that the biofilm-producing isolates appeared as aggregates of cells within a heavy matrix. In addition, PCR assay identified IcaA and IcaD (66.6% for both) biofilm production genes in most isolates and IcaC (61.1%), IcaB, FnbB (33.3% for both), and Fib (22.2%) in several other strains. Quercetin significantly inhibited biofilm activity in biofilm producing S. aureus isolates in a dose-dependent manner, with an inhibition rate of 29.6-87.7%. Interpretation: Biofilm production is dependent on Ica gene phenotype and strains with an IcaABCD or IcaABD phenotype produce more biofilm than strains with IcaAD phenotype. Quercetin significantly inhibited S. aureus biofilm production, irrespective of Ica phenotype.

scholarly journals Pilot investigation on the dose-dependent impact of irradiation on primary human alveolar osteoblasts in vitro

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Anna-Klara Amler ◽  
Domenic Schlauch ◽  
Selin Tüzüner ◽  
Alexander Thomas ◽  
Norbert Neckel ◽  
...  
Keyword(s):  
Bone Cells ◽  
Marker Gene ◽  
Marker Genes ◽  
Dependent Manner ◽  
Current Standard ◽  
Functional Changes ◽  
Standard Procedures ◽  
The Impact ◽  
Dose Dependent

AbstractRadiotherapy of head and neck squamous cell carcinoma can lead to long-term complications like osteoradionecrosis, resulting in severe impairment of the jawbone. Current standard procedures require a 6-month wait after irradiation before dental reconstruction can begin. A comprehensive characterization of the irradiation-induced molecular and functional changes in bone cells could allow the development of novel strategies for an earlier successful dental reconstruction in patients treated by radiotherapy. The impact of ionizing radiation on the bone-forming alveolar osteoblasts remains however elusive, as previous studies have relied on animal-based models and fetal or animal-derived cell lines. This study presents the first in vitro data obtained from primary human alveolar osteoblasts. Primary human alveolar osteoblasts were isolated from healthy donors and expanded. After X-ray irradiation with 2, 6 and 10 Gy, cells were cultivated under osteogenic conditions and analyzed regarding their proliferation, mineralization, and expression of marker genes and proteins. Proliferation of osteoblasts decreased in a dose-dependent manner. While cells recovered from irradiation with 2 Gy, application of 6 and 10 Gy doses not only led to a permanent impairment of proliferation, but also resulted in altered cell morphology and a disturbed structure of the extracellular matrix as demonstrated by immunostaining of collagen I and fibronectin. Following irradiation with any of the examined doses, a decrease of marker gene expression levels was observed for most of the investigated genes, revealing interindividual differences. Primary human alveolar osteoblasts presented a considerably changed phenotype after irradiation, depending on the dose administered. Mechanisms for these findings need to be further investigated. This could facilitate improved patient care by re-evaluating current standard procedures and investigating faster and safer reconstruction concepts, thus improving quality of life and social integrity.

scholarly journals Hyperoxia Provokes Time- and Dose-Dependent Gut Injury and Endotoxemia and Alters Gut Microbiome and Transcriptome in Mice

2021 ◽  
Vol 8 ◽  
Author(s):  
Yunhang Li ◽  
Yuanfa Tao ◽  
Jingyu Xu ◽  
Yihuai He ◽  
Wen Zhang ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Transcriptome Analysis ◽  
Gut Microbiome ◽  
Control Group ◽  
Dependent Manner ◽  
Barrier Dysfunction ◽  
Necrosis Factor Alpha ◽  
Gut Dysbiosis ◽  
The Impact ◽  
Dose Dependent

Background: Oxygen therapy usually exposes patients to hyperoxia, which induces injuries in the lung, the heart, and the brain. The gut and its microbiome play key roles in critical illnesses, but the impact of hyperoxia on the gut and its microbiome remains not very clear. We clarified the time- and dose-dependent effects of hyperoxia on the gut and investigated oxygen-induced gut dysbiosis and explored the underlying mechanism of gut injury by transcriptome analysis.Methods: The C57BL/6 mice were randomly divided into the control group and nine different oxygen groups exposed to hyperoxia with an inspired O2 fraction (FiO2) of 40, 60, and 80% for 24, 72, and 168 h (7 days), respectively. Intestinal histopathological and biochemical analyses were performed to explore the oxygen-induced gut injury and inflammatory response. Another experiment was performed to explore the impact of hyperoxia on the gut microbiome by exposing the mice to hyperoxia (FiO2 80%) for 7 days, with the 16S rRNA sequencing method. We prolonged the exposure (up to 14 days) of the mice to hyperoxia (FiO2 80%), and gut transcriptome analysis and western blotting were carried out to obtain differentially expressed genes (DEGs) and signaling pathways related to innate immunity and cell death.Results: Inhaled oxygen induced time- and dose-dependent gut histopathological impairment characterized by mucosal atrophy (e.g., villus shortening: 80% of FiO2 for 24 h: P = 0.008) and enterocyte death (e.g., apoptosis: 40% of FiO2 for 7 days: P = 0.01). Administered time- and dose-dependent oxygen led to intestinal barrier dysfunction (e.g., endotoxemia: 80% of FiO2 for 72 h: P = 0.002) and potentiated gut inflammation by increasing proinflammatory cytokines [e.g., tumor necrosis factor alpha (TNF-α): 40% of FiO2 for 24 h: P = 0.003)] and reducing anti-inflammatory cytokines [Interleukin 10 (IL-10): 80% of FiO2 for 72 h: P &lt; 0.0001]. Hyperoxia induced gut dysbiosis with an expansion of oxygen-tolerant bacteria (e.g., Enterobacteriaceae). Gut transcriptome analysis identified 1,747 DEGs and 171 signaling pathways and immunoblotting verified TLR-4, NOD-like receptor, and apoptosis signaling pathways were activated in oxygen-induced gut injury.Conclusions: Acute hyperoxia rapidly provokes gut injury in a time- and dose-dependent manner and induces gut dysbiosis, and an innate immune response is involved in an oxygen-induced gut injury.

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