scholarly journals Aging Regulates Post-Viral Asthmatic Airway Pathology

2021 ◽  
Author(s):  
Guy Hazan ◽  
Anna Eubanks ◽  
Carrie Gierasch ◽  
Jeffrey Atkinson ◽  
Carolyn Fox ◽  
...  
Keyword(s):  
Influenza A ◽  
Sendai Virus ◽  
Protective Effects ◽  
Independent Manner ◽  
Common Chronic Disease ◽  
Mhc Ii ◽  
Airway Pathology ◽  
Transcriptional Changes ◽  
High Level

Abstract Asthma is a common chronic disease of childhood, but for unknown reasons disease activity sometimes subsides as children mature. To understand why, we exposed mice across a range of ages to viral and allergic triggers of asthma exacerbations and airway pathology. We found that pathology induced by Sendai virus (SeV) or influenza A virus (IAV) occurred selectively in juvenile mice in a microbiome-independent manner, while the same phenotypes induced by allergens were insensitive to age. Age-specific responses to SeV included a juvenile bias towards type-2 airway inflammation that emerged early in infection and was lost with maturation. With aging, we observed progressive transcriptional changes to alveolar macrophages (AMs) including the acquisition of high-level MHC-II expression. Importantly, depleting AMs canceled the protective effects of maturity on post-viral airway pathology. Thus, aging of the lung-immune microenvironment influences chronic outcomes of respiratory viral infection and may help to explain childhood asthma remission.

scholarly journals The Global Architecture Shaping the Heterogeneity and Tissue-Dependency of the MHC Class I Immunopeptidome is Evolutionarily Conserved

2020 ◽  
Author(s):  
Peter Kubiniok ◽  
Ana Marcu ◽  
Leon Bichmann ◽  
Leon Kuchenbecker ◽  
Heiko Schuster ◽  
...  
Keyword(s):  
T Cell ◽  
Antigen Processing ◽  
Global Analysis ◽  
Primary Source ◽  
Independent Manner ◽  
Mhc I ◽  
Mhc Ii ◽  
Mouse Tissues ◽  
High Level

ABSTRACTUnderstanding the molecular principles that govern the composition of the mammalian MHC-I immunopeptidome (MHC-Ii) across different primary tissues is fundamentally important to predict how T cell respond in different contexts in vivo. Here, we performed a global analysis of the mammalian MHC-Ii from 29 and 19 primary human and mouse tissues, respectively. First, we observed that different HLA-A, -B and -C allotypes do not contribute evenly to the global composition of the MHC-Ii across multiple human tissues. Second, we found that peptides that are presented in a tissue-dependent and -independent manner share very distinct properties. Third, we discovered that proteins that were evolutionarily hyperconserved represent the primary source of the MHC-Ii at the organism-wide scale. Finally, we uncovered a remarkable antigen processing and presentation network that may drive the high level of heterogeneity of the MHC-Ii across different tissues in mammals. This study opens up new avenues toward a system-wide understanding of antigen presentation in vivo and may serve as ground work to understand tissue-dependent T cell responses in autoimmunity, infectious diseases and cancer.

Response to DDAVP in children with von Willebrand disease type 2

2009 ◽  
Vol 29 (02) ◽  
pp. 143-148 ◽  
Author(s):  
U. Budde ◽  
K. Beutel ◽  
W.-A. Hassenpflug ◽  
H. Hauch ◽  
T. Obser ◽  
...  
Keyword(s):  
Disease Type ◽  
Von Willebrand Disease ◽  
Molecular Defect ◽  
Variable Response ◽  
Functional Parameters ◽  
Functional Defect ◽  
Biologic Response ◽  
High Level ◽  
Von Willebrand

SummaryWe have prospectively evaluated the biologic response to desmopressin (DDAVP) in 28 children with type 2 von Willebrand disease (VWD) in correlation with the phenotype and the molecular defect of VWF. The diagnosis of VWD type 2 was mainly based on VWF functional parameters and/or an aberrant VWF multimer pattern. Seventeen different mutations were identified (6 of them novel). No response with respect to the functional parameters VWF:RCo and/or VWF:CB was seen in patients with severe abnormality of the VWF multimer pattern. One patient with VWD type 2A phenotype IIC Miami did not respond with respect to VWF:CB, but showed a good response of VWF:Ag and FVIII:C as expected. Interestingly he showed a persistently high level of VWF:Ag and FVIII:C up to 4 hours after DDAVP infusion. Patients with minor alterations of multimer structure and particular mutations responded well to DDAVP, whereas patients with normal multimer structure but a defect in platelet dependent functional parameters did not respond with VWF:RCo. Conclusion: Children with VWD type 2 show a variable response to desmopressin depending on the mutation that correlates with the functional defect and the presence or absence as well as the half-life of large VWF multimers. Our data emphasize the usefulness of DDAVP testing even in patients with VWD type 2, possibly with the exception of VWD type 2B.

SGLT-2 Inhibition: Novel Therapeutics for Reno-and Cardioprotection in Diabetes Mellitus

2019 ◽  
Vol 15 (5) ◽  
pp. 349-356 ◽  
Author(s):  
Angus Gill ◽  
Stephen P. Gray ◽  
Karin A. Jandeleit-Dahm ◽  
Anna M.D. Watson
Keyword(s):  
Sympathetic Nerve Activity ◽  
Diabetic Patients ◽  
Protective Effects ◽  
Preclinical Research ◽  
Type 2 Diabetic Patients ◽  
Nerve Activity ◽  
Current State ◽  
Glucose Reabsorption ◽  
Type 2 Diabetic

Background: The sodium glucose co-transporter 2 (SGLT2) is primarily located within S1 of the renal proximal tubule being responsible for approximately 90% of glucose re-uptake in the kidney. Inhibition of SGLT2 is an exciting new pharmacological approach for the reduction of blood glucose in type 2 diabetic patients via inhibition of tubular glucose reabsorption. In addition to lowering glucose, this group of drugs has shown significant cardiovascular and renal protective effects. Conclusion: This review aims to outline the current state of preclinical research and clinical trials for different SGLT2 inhibitors and outline some of the proposed mechanisms of action, including possible effects on sympathetic nerve activity, which may contribute to the unexpected beneficial cardiovascular and reno-protective effects of this class of compounds.

scholarly journals Analysis of Lipid Peroxidation by UPLC-MS/MS and Retinoprotective Effects of the Natural Polyphenol Pterostilbene

Antioxidants ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 168
Author(s):  
Isabel Torres-Cuevas ◽  
Iván Millán ◽  
Miguel Asensi ◽  
Máximo Vento ◽  
Camille Oger ◽  
...  
Keyword(s):  
Lipid Peroxidation ◽  
Diabetic Retinopathy ◽  
Redox Homeostasis ◽  
Ultra Performance Liquid Chromatography ◽  
Protective Effects ◽  
Diabetic Retina ◽  
Key Factor ◽  
Adrenic Acid ◽  
Diabetic Rabbits ◽  
High Level

The loss of redox homeostasis induced by hyperglycemia is an early sign and key factor in the development of diabetic retinopathy. Due to the high level of long-chain polyunsaturated fatty acids, diabetic retina is highly susceptible to lipid peroxidation, source of pathophysiological alterations in diabetic retinopathy. Previous studies have shown that pterostilbene, a natural antioxidant polyphenol, is an effective therapy against diabetic retinopathy development, although its protective effects on lipid peroxidation are not well known. Plasma, urine and retinas from diabetic rabbits, control and diabetic rabbits treated daily with pterostilbene were analyzed. Lipid peroxidation was evaluated through the determination of derivatives from arachidonic, adrenic and docosahexaenoic acids by ultra-performance liquid chromatography coupled with tandem mass spectrometry. Diabetes increased lipid peroxidation in retina, plasma and urine samples and pterostilbene treatment restored control values, showing its ability to prevent early and main alterations in the development of diabetic retinopathy. Through our study, we are able to propose the use of a derivative of adrenic acid, 17(RS)-10-epi-SC-Δ15-11-dihomo-IsoF, for the first time, as a suitable biomarker of diabetic retinopathy in plasmas or urine.

scholarly journals Type 1 Immunity Provides Optimal Protection against Both Mucosal and Systemic Trypanosoma cruzi Challenges

2002 ◽  
Vol 70 (12) ◽  
pp. 6715-6725 ◽  
Author(s):  
D. F. Hoft ◽  
C. S. Eickhoff
Keyword(s):  
Trypanosoma Cruzi ◽  
Neutralizing Antibody ◽  
Secretory Iga ◽  
Immune Memory ◽  
Interleukin 12 ◽  
Intracellular Pathogens ◽  
Protective Effects ◽  
Culture Techniques

ABSTRACT Chagas' disease results from infection with Trypanosoma cruzi, a protozoan parasite that establishes systemic intracellular infection after mucosal invasion. We hypothesized that ideal vaccines for mucosally invasive, intracellular pathogens like T. cruzi should induce mucosal type 2 immunity for optimal induction of protective secretory immunoglobulin A (IgA) and systemic type 1 immunity protective against intracellular replication. However, differential mucosal and systemic immune memory could be difficult to induce because of reciprocal inhibitory actions between type 1 and type 2 responses. To test our hypotheses, we investigated the protective effects of type 1 and type 2 biased vaccines against mucosal and systemic T. cruzi challenges. Intranasal vaccinations were given with recombinant interleukin-12 (IL-12)- and IL-4-neutralizing antibody (Ab) for type 1 immune bias, or recombinant IL-4 and gamma interferon-neutralizing Ab for type 2 immune bias. Cytokine RNA and protein studies confirmed that highly polarized memory immune responses were induced by our vaccination protocols. Survival after virulent subcutaneous T. cruzi challenge was used to assess systemic protection. Mucosal protection was assessed by measuring the relative inhibition of parasite replication in mucosal tissues early after oral T. cruzi challenge, using both PCR and quantitative culture techniques. As expected, only type 1 responses protected against systemic challenges (P < 0.01). However, contrary to our original hypothesis, type 1 responses optimally protected against mucosal challenges as well (P < 0.05). Type 1 and type 2 biased vaccines induced similar secretory IgA responses. We conclude that future vaccines for T. cruzi and possibly other mucosally invasive, intracellular pathogens should induce both mucosal and systemic type 1 immunity.

scholarly journals Metabolic syndrome in premenopausal and postmenopausal women with type 2 diabetes: loss of protective effects of premenopausal status

2014 ◽  
Vol 13 (1) ◽  
Author(s):  
Manouchehr Nakhjavani ◽  
Mehrnaz Imani ◽  
Mehrdad Larry ◽  
Arash Aghajani-Nargesi ◽  
Afsaneh Morteza ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Metabolic Syndrome ◽  
Postmenopausal Women ◽  
Protective Effects

Empagliflozin significantly attenuates QTc prolongation in rats due to sotalol

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
V.O Baris ◽  
B Dincsoy ◽  
E Gedikli ◽  
A Erdem
Keyword(s):  
Qt Prolongation ◽  
Control Group ◽  
Diabetic Patients ◽  
Protective Effects ◽  
Qtc Prolongation ◽  
Positive Effects ◽  
T Wave ◽  
Qt Intervals ◽  
Electrocardiogram Ecg

Abstract Introduction Sotalol (SOT) is a Class 3 antiarrhythmic drug and commonly used for various arrhythmia treatments. However; it can prolong QT interval and lead to malignant arrhythmias. Empagliflozin is a selective SGLT-2 inhibitor used in the treatment of Type 2 diabetes and has been shown to have positive effects on cardiovascular outcomes. Since the effect of empagliflozin (EMPA) on potassium channel activation is not yet known, there is no recommendation for the concomitant use of these drugs. Purpose In this study, we aimed to evaluate possible protective effects of empagliflozin in sotalol induced QT prolongation. Materials and methods Twenty-four male Wistar Alba rats were randomized into four groups. The first (control) group (n: 6) received only serum physiologic (1ml) via orogastric gavage (OG). The second (EMPA) group (n: 6) received EMPA (10 mg/kg) via OG. The third (SOT) group (n: 6) received SOT (80 mg/kg) via OG. The fourth (EMPA+SOT) group (n: 6) received EMPA (10 mg/kg) and SOT (80 mg/kg) via OG. Under anesthesia; PR, QT intervals and heart rate (HR) were measured and QTc value was also calculated at second hour on lead II using electrocardiogram (ECG). Results In the SOT group; QT intervals, T wave durations and QTc values were found to be statistically longer than the control group, whereas HR was found to be lower than the control group (p&lt;0.01). In the EMPA+SOT group; QT intervals, T wave durations and QTc values were significantly lower and HR was significantly higher compared to the SOT group (p&lt;0.001, p&lt;0.01, p&lt;0.001, p&lt;0.001 respectively) (Table) Conclusion In the present study, we detected that EMPA significantly ameliorates SOT induced QT prolongation. In addition to this, we have also shown that EMPA can be used safely with SOT in clinical practice. With more clinical trials, the routine use of EMPA may be suggested to prevent QTc prolongation in diabetic patients receiving SOT. Finally; our study indicates that EMPA can effect on potassium channels. Funding Acknowledgement Type of funding source: None

Consistently High Level of Cardiorespiratory Fitness and Incidence of Type 2 Diabetes

2017 ◽  
Vol 49 (10) ◽  
pp. 2048-2055 ◽  
Author(s):  
HARUKI MOMMA ◽  
SUSUMU S. SAWADA ◽  
I-MIN LEE ◽  
YUKO GANDO ◽  
RYOKO KAWAKAMI ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Cardiorespiratory Fitness ◽  
High Level
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