Homeopathic treatments modify inflammation but not behavioral response to influenza antigen challenge in BALB/c mice

Homeopathy ◽  
2016 ◽  
Vol 105 (03) ◽  
pp. 257-264 ◽  
Author(s):  
Camila Monteiro Siqueira ◽  
Priscila Dias Motta ◽  
Thayná Neves Cardoso ◽  
Cideli de Paula Coelho ◽  
Ana Flavia Popi ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Virus Antigen ◽  
Behavioral Changes ◽  
Antigen Challenge ◽  
Male Adult ◽  
Influenza Hemagglutinin ◽  
Adult Mice ◽  
Series Of Experiments ◽  
Cell Balance ◽  
Time Point

Background: Influenza affects thousands of people worldwide every year, motivating the development of new therapies. In this work, the effects of two homeopathic preparations (influenza biotherapies and thymulin) were chosen following two different rationales: isotherapy and endo-isotherapy models. The homeopathic effects were evaluated individually considering the inflammatory and behavioral responses against influenza virus antigen were studied in BALB/c mice.Methods: Male adult mice were treated orally and blindly for 21 days with highly diluted influenza virus or with thymulin, and were divided in two sets of experiments. The first series of experiments aimed to describe their behavior, using an open field (OF) device. In the second series, mice were challenged subcutaneously with influenza hemagglutinin antigen (7 μg/200 μl) at day 21. At day 42, behavior and inflammation response were evaluated.Results: No behavioral changes were seen in OF tests at any time point after treatments. Flow cytometry and morphometry revealed significant changes in T and B cell balance after influenza antigen challenge, varying according to treatment.Conclusion: The results show that both homeopathic treatments induced subtle changes in acquired immune anti-viral response regulation. A deeper understanding of the mechanism could elucidate their possible use in influenza epidemiological situations.

scholarly journals Next generation methodology for updating HA vaccines against emerging human seasonal influenza A(H3N2) viruses

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
James D. Allen ◽  
Ted M. Ross
Keyword(s):  
Influenza Virus ◽  
Immune Responses ◽  
Influenza A ◽  
Seasonal Influenza ◽  
Influenza Viruses ◽  
Next Generation ◽  
Virus Infections ◽  
Wild Type ◽  
Influenza Hemagglutinin ◽  
H3n2 Influenza

AbstractWhile vaccines remain the best tool for preventing influenza virus infections, they have demonstrated low to moderate effectiveness in recent years. Seasonal influenza vaccines typically consist of wild-type influenza A and B viruses that are limited in their ability to elicit protective immune responses against co-circulating influenza virus variant strains. Improved influenza virus vaccines need to elicit protective immune responses against multiple influenza virus drift variants within each season. Broadly reactive vaccine candidates potentially provide a solution to this problem, but their efficacy may begin to wane as influenza viruses naturally mutate through processes that mediates drift. Thus, it is necessary to develop a method that commercial vaccine manufacturers can use to update broadly reactive vaccine antigens to better protect against future and currently circulating viral variants. Building upon the COBRA technology, nine next-generation H3N2 influenza hemagglutinin (HA) vaccines were designed using a next generation algorithm and design methodology. These next-generation broadly reactive COBRA H3 HA vaccines were superior to wild-type HA vaccines at eliciting antibodies with high HAI activity against a panel of historical and co-circulating H3N2 influenza viruses isolated over the last 15 years, as well as the ability to neutralize future emerging H3N2 isolates.

Broadly-neutralizing antibodies that bind to the influenza hemagglutinin stalk domain enhance the effectiveness of neuraminidase inhibitors via Fc-mediated effector functions

2021 ◽  
Author(s):  
Ali Zhang ◽  
Hanu Chaudhari ◽  
Yonathan Agung ◽  
Michael D'Agostino ◽  
Jann Ang ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Neutralizing Antibodies ◽  
Influenza Virus Infection ◽  
Dependent Manner ◽  
Neuraminidase Inhibitors ◽  
Immune Effector ◽  
Effector Cells ◽  
Individual Level ◽  
Influenza Hemagglutinin ◽  
Stalk Domain

The conserved hemagglutinin stalk domain is an attractive target for broadly effective antibody-based therapeutics and next generation universal influenza vaccines. Protection provided by hemagglutinin stalk binding antibodies is principally mediated through activation of immune effector cells. Titers of stalk-binding antibodies are highly variable on an individual level, and tend to increase with age as a result of increasing exposures to influenza virus. In our study, we show that stalk-binding antibodies cooperate with neuraminidase inhibitors to protect against influenza virus infection in an Fc-dependent manner. These data suggest that the effectiveness of neuraminidase inhibitors is likely influenced by an individual's titers of stalk-binding antibodies, and that neuraminidase inhibitors may enhance the effectiveness of future stalk-binding monoclonal antibody-based treatments.

scholarly journals Impairment of Ca2+ release in single Xenopusmuscle fibers fatigued at varied extracellular P O 2

2000 ◽  
Vol 88 (5) ◽  
pp. 1743-1748 ◽  
Author(s):  
Creed M. Stary ◽  
Michael C. Hogan
Keyword(s):  
Skeletal Muscle ◽  
Muscle Fibers ◽  
Rapid Onset ◽  
Skeletal Muscle Fibers ◽  
Significant Difference ◽  
Force Recovery ◽  
Series Of Experiments ◽  
Initial Peak ◽  
Time Point ◽  
Text Condition

We tested the hypothesis that the mechanisms involved in the more rapid onset of fatigue when O2 availability is reduced in contracting skeletal muscle are similar to those when O2 availability is more sufficient. Two series of experiments were performed in isolated, single skeletal muscle fibers from Xenopus laevis. First, relative force and free cytosolic Ca2+concentrations ([Ca2+]c) were measured simultaneously in single fibers ( n = 6) stimulated at increasing frequencies (0.25, 0.33, 0.5, and 1 Hz) at an extracellular[Formula: see text] of either 22 or 159 Torr. Muscle fatigue (force = 50% of initial peak tension) occurred significantly sooner ( P < 0.05) during the low- (237 ± 40 s) vs. high-[Formula: see text]treatments (280 ± 38 s). Relative [Ca2+]c was significantly decreased from maximal values at the fatigue time point during both the high- (72 ± 4%) and low-[Formula: see text] conditions (78 ± 4%), but no significant difference was observed between the treatments. In the second series of experiments, using the same stimulation regime as the first, fibers ( n = 6) exposed to 5 mM caffeine immediately after fatigue demonstrated an immediate but incomplete relative force recovery during both the low- (89 ± 4%) and high-[Formula: see text] treatments (82 ± 3%), with no significant difference between treatments. Additionally, there was no significant difference in relative [Ca2+]c between the high- (100 ± 12% of prefatigue values) and low-[Formula: see text] treatments (108 ± 12%) on application of caffeine. These results suggest that in isolated, single skeletal muscle fibers, the earlier onset of fatigue that occurred during the low-extracellular[Formula: see text] condition was modulated through similar pathways as the fatigue process during the high and involved a decrease in relative peak [Ca2+]c.

scholarly journals Mapping person-to-person variation in viral mutations that escape polyclonal serum targeting influenza hemagglutinin

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Juhye M Lee ◽  
Rachel Eguia ◽  
Seth J Zost ◽  
Saket Choudhary ◽  
Patrick C Wilson ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Viral Evolution ◽  
Surface Protein ◽  
Viral Escape ◽  
Viral Neutralization ◽  
Influenza Hemagglutinin ◽  
Human Sera ◽  
Order Of Magnitude ◽  
Amino Acid Mutations ◽  
Major Surface

A longstanding question is how influenza virus evolves to escape human immunity, which is polyclonal and can target many distinct epitopes. Here, we map how all amino-acid mutations to influenza’s major surface protein affect viral neutralization by polyclonal human sera. The serum of some individuals is so focused that it selects single mutations that reduce viral neutralization by over an order of magnitude. However, different viral mutations escape the sera of different individuals. This individual-to-individual variation in viral escape mutations is not present among ferrets that have been infected just once with a defined viral strain. Our results show how different single mutations help influenza virus escape the immunity of different members of the human population, a phenomenon that could shape viral evolution and disease susceptibility.

scholarly journals Peptide Aggregation Induced Immunogenic Rupture (PAIIR)

2021 ◽  
Author(s):  
Gokhan Gunay ◽  
Seren Hamsici ◽  
Handan Acar ◽  
Mark L. Lang ◽  
Gillian A. Lang ◽  
...  
Keyword(s):  
Immune Response ◽  
Membrane Damage ◽  
Cell Types ◽  
Peptide Aggregation ◽  
Vaccine Adjuvants ◽  
Humoral And Cellular Immunity ◽  
Influenza Hemagglutinin ◽  
Series Of Experiments ◽  
Molecular Patterns

Under the influence of stress and membrane damage, cells undergo immunogenic cell death (ICD), which involves the release of damage associated molecular patterns (DAMPs), natural adjuvants for enhancing an immune response. In the presence of an antigen, released DAMPs can determine the type and magnitude of the immune response, and therefore the longevity and efficacy of an antigen-specific immunity. In the last decade, the immune response effect of ICD has been shown, yet there is no tool that can induce controlled ICD with predictable results, regardless of the cell type. We designed a peptide-based tool, called [II], for controlled damage to cell membrane to induce ICD and DAMPs release. Herein we describe a series of experiments that determine that the mechanism of action of [II] includes a caspase-dependent ICD and subsequent release of immune stimulating DAMPs, on various cell types. Moreover, we tested the hypothesis that controlled DAMP release via [II] in vivo was associated with enhancement of antigen-specific adaptive immunity with influenza hemagglutinin (HA) subunit vaccine. HA and [II] showed significantly higher HA specific IgG1 and IgG2a antibodies, compared to HA-only immunized mice, while the peptide itself did not elicit antibodies. In this paper, we demonstrate the first peptide-aggregation induced immunogenic rupture (PAIIR) approach as vaccine adjuvants for increasing both humoral and cellular immunity. In consideration of its ability to enhance IgG2a responses that are associated with heterosubtypic influenza virus protection, PAIIR is a promising adjuvant to promote universal protection upon influenza HA vaccination.

Sleep apnea and effect of chemostimulation on breathing instability in mice

2003 ◽  
Vol 94 (2) ◽  
pp. 525-532 ◽  
Author(s):  
Akira Nakamura ◽  
Yasuichiro Fukuda ◽  
Tomoyuki Kuwaki
Keyword(s):  
Sleep Apnea ◽  
Eye Movement ◽  
Experimental Model ◽  
Molecular Basis ◽  
Slow Wave Sleep ◽  
Rapid Eye Movement Sleep ◽  
Body Plethysmography ◽  
Male Adult ◽  
Experimental Animals ◽  
Adult Mice

Sleep apnea occurs in humans and experimental animals. We examined whether it also arises in adult mice. Ventilation in male adult 129/Sv mice was recorded concomitantly by electroencephalograms and electromyograms for 6 h by use of body plethysmography. Apnea was defined as cessation of plethysmographic signals for longer than two respiratory cycles. While mice breathed room air, 32.3 ± 6.9 (mean ± SE, n = 5) apneas were observed during sleep but not in quiet awake periods. Sleep apneas were further classified into two types. Postsigh apneas occurred exclusively during slow-wave sleep (SWS), whereas spontaneous apneas arose during both SWS and rapid eye movement sleep. Compared with room air (9.1 ± 1.4/h of SWS), postsigh apneas were more frequent in hypoxia (13.7 ± 2.1) and less frequent in hyperoxia (3.6 ± 1.7) and hypercapnia (2.8 ± 2.1). Our data indicated that significant sleep apnea occurs in normal adult mice and suggested that the mouse could be a promising experimental model with which to study the genetic and molecular basis of respiratory regulation during sleep.

scholarly journals DISSOCIATION OF HEMAGGLUTINATING AND ANTIBODY-MEASURING CAPACITIES OF INFLUENZA VIRUS

1947 ◽  
Vol 85 (1) ◽  
pp. 1-7 ◽  
Author(s):  
Thomas Francis
Keyword(s):  
Influenza Virus ◽  
Specific Antibody ◽  
Serum Antibody ◽  
Allantoic Fluid ◽  
Virus Antigen ◽  
Normal Serum ◽  
Type B ◽  
Heat Stable ◽  
Labile Component ◽  
Type B Influenza Virus

Preparations of Type B influenza virus, propagated in the embryonated egg and obtained in the form of allantoic fluid, were found after heating at 56°C. for 30 minutes to retain the capacity to agglutinate erythrocytes but no longer measured specific antibody when used as antigen in titrations of serum antibody. The dissociation of the two activities suggests the presence in such virus preparations of a complex virus antigen comprising, (1) a heat-stable component which agglutinates erythrocytes and reacts primarily with specific antibody; (2) a heat-labile component reacting with a factor of normal serum which ordinarily tends to inhibit the hemagglutinating activity of influenza virus. The relation of the reagents to other known serological activities of influenza virus is being studied.

scholarly journals Exogenous GLP-2 and IGF-I induce a differential intestinal response in IGF binding protein-3 and -5 double knockout mice

2012 ◽  
Vol 302 (8) ◽  
pp. G794-G804 ◽  
Author(s):  
Sangita G. Murali ◽  
Adam S. Brinkman ◽  
Patrick Solverson ◽  
Wing Pun ◽  
John E. Pintar ◽  
...  
Keyword(s):  
Relative Mass ◽  
Jejunal Mucosa ◽  
Double Knockout ◽  
Igf Binding Proteins ◽  
Male Adult ◽  
Adult Mice ◽  
Igf I ◽  
Igf Binding ◽  
Mucosal Growth ◽  
Igfbp 3

Glucagon-like peptide-2 (GLP-2) action is dependent on intestinal expression of IGF-I, and IGF-I action is modulated by IGF binding proteins (IGFBP). Our objective was to evaluate whether the intestinal response to GLP-2 or IGF-I is dependent on expression of IGFBP-3 and -5. Male, adult mice in six treatment groups, three wild-type (WT) and three double IGFBP-3/-5 knockout (KO), received twice daily intraperitoneal injections of GLP-2 (0.5 μg/g body wt), IGF-I (4 μg/g body wt), or PBS (vehicle) for 7 days. IGFBP-3/-5 KO mice showed a phenotype of lower plasma IGF-I concentration, but greater body weight and relative mass of visceral organs, compared with WT mice ( P < 0.001). WT mice showed jejunal growth with either IGF-I or GLP-2 treatment. In KO mice, IGF-I did not stimulate jejunal growth, crypt mitosis, sucrase activity, and IGF-I receptor (IGF-IR) expression, suggesting that the intestinotrophic actions of IGF-I are dependent on expression of IGFBP-3 and -5. In KO mice, GLP-2 induced significant increases in jejunal mucosal cellularity, crypt mitosis, villus height, and crypt depth that was associated with increased expression of the ErbB ligand epiregulin and decreased expression of IGF-I and IGF-IR. This suggests that in KO mice, GLP-2 action in jejunal mucosa is independent of the IGF-I system and linked with ErbB ligands. In summary, the intestinotrophic actions of IGF-I, but not GLP-2, in mucosa are dependent on IGFBP-3 and -5. These findings support the role of multiple downstream mediators for the mucosal growth induced by GLP-2.

scholarly journals The γδ T Lymphocytes of the Perinatal Murine Thymus

1995 ◽  
Vol 4 (2) ◽  
pp. 93-100 ◽  
Author(s):  
Michelle I. Zorbas ◽  
Roland Scollay
Keyword(s):  
T Cells ◽  
T Lymphocytes ◽  
Γδ T Cells ◽  
The Third ◽  
Adult Mice ◽  
Heat Stable ◽  
Heat Stable Antigen ◽  
Adult Thymus ◽  
Number Of Cells ◽  
Time Point

We have previously shown that the adult thymus contains three subsets of γδ T cells that can be defined by the expression of Thy-1 and heat-stable antigen (HSA). In this study, the number of cells in each of these thymic γδ populations was investigated at different stages throughout life. In adult mice, the populations stayed relatively constant, however, in contrast, there were major variations in them early in development. It was shown that only two of the γδ populations were present in the prenatal thymus, a major population of Thy-1+HSA-cells, and a smaller population of Thy-1+HSA-cells. However, after birth, most of the Thy-1+HSA-cells appear to loose the Thy-1 antigen, forming the third population of HSA-Thy-1-cells. The adult configuration of populations appeared to be established within the first week after birth. Therefore, whereas the γδ populations stayed relatively constant from this time point onwards, there were major variations early in development. Throughout life, most γδ thymocytes are CD4-CD8-, however, in the neonatal thymus, there are some CD4+and CD8+γδ thymocytes, and these are contained in the Thy-1+HSA-population.

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