scholarly journals A New Natural Defense Against Airborne Pathogens

QRB Discovery ◽  
2020 ◽  
Vol 1 ◽  
Author(s):  
David Edwards ◽  
Anthony Hickey ◽  
Richard Batycky ◽  
Lester Griel ◽  
Michael Lipp ◽  
...  
Keyword(s):  
Primary Source ◽  
Face Mask ◽  
Nasal Delivery ◽  
Nasal Administration ◽  
Swine Model ◽  
Upper Airways ◽  
Suppression Effect ◽  
High Particle ◽  
Natural Defense ◽  
Human Airways

AbstractWe propose the nasal administration of calcium-enriched physiological salts as a new hygienic intervention with possible therapeutic application as a response to the rapid and tenacious spread of COVID-19. We test the effectiveness of these salts against viral and bacterial pathogens in animals and humans. We find that aerosol administration of these salts to the airways diminishes the exhalation of the small particles that face masks fail to filter and, in the case of an influenza swine model, completely block airborne transmission of disease. In a study of 10 human volunteers (5 less than 65 years and 5 older than 65 years), we show that delivery of a nasal saline comprising calcium and sodium salts quickly (within 15 min) and durably (up to at least 6 h) diminishes exhaled particles from the human airways. Being predominantly smaller than 1 μm, these particles are below the size effectively filtered by conventional masks. The suppression of exhaled droplets by the nasal delivery of calcium-rich saline with aerosol droplet size of around 10 μm suggests the upper airways as a primary source of bioaerosol generation. The suppression effect is especially pronounced (99%) among those who exhale large numbers of particles. In our study, we found this high-particle exhalation group to correlate with advanced age. We argue for a new hygienic practice of nasal cleansing by a calcium-rich saline aerosol, to complement the washing of hands with ordinary soap, use of a face mask, and social distancing.

scholarly journals Short Onset and Enhanced Analgesia Following Nasal Administration of Non-Controlled Drugs in Nanovesicular Systems

Pharmaceutics ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 978
Author(s):  
Elka Touitou ◽  
Hiba Natsheh ◽  
Shatha Boukeileh ◽  
Rania Awad
Keyword(s):  
Lipid Bilayers ◽  
Analgesic Effect ◽  
Drug Level ◽  
Nasal Delivery ◽  
Nasal Administration ◽  
Mice Model ◽  
Noninvasive Treatment ◽  
New Approach ◽  
Controlled Drugs ◽  
Peak Value

Nasal nanovesicular delivery systems (NVS) containing the noncontrolled analgesic drugs Ketoprofen, Butorphanol or Tramadol, incorporated in a phospholipid nanovesicular carrier, were designed and investigated. The systems were first characterized for their physicochemical properties. Due to their composition, comprising propylene glycol as a lipid bilayers fluidizer, these systems contain soft vesicles. Pharmacokinetic profiles of Tramadol in plasma and brain and of Ketoprofen in plasma were also assessed. The analgesic effect of each of the three tested drugs was evaluated in the acetic acid mice model for pain. One important result obtained in this work is that the concentration of Tramadol in rats’ plasma and brain increased rapidly after administration, reaching a peak value 10 min after administration with a Cmax of 2 to 5 folds greater than that for the oral or nasal non-vesicular treatments, respectively. In the case of Ketoprofen, the peak of the drug level in plasma was measured 10 min post nasal administration in NVS. The Cmax was three-fold higher relative to oral administration of this drug. In the experiment testing analgesia, a rapid and improved analgesia was observed for the tested drugs when delivered nasally in the nanocarrier. On the other hand, a weaker analgesic effect was observed for oral and nasal control systems. This new approach suggests that nasal delivery of non-controlled drugs in soft nanovesicles may open the way for better and noninvasive treatment of severe pain.

A prolactin-dependent sexually dimorphic mechanism of migraine chronification

Cephalalgia ◽  
2021 ◽  
pp. 033310242110398
Author(s):  
Daigo Ikegami ◽  
Edita Navratilova ◽  
Xu Yue ◽  
Aubin Moutal ◽  
Caroline M Kopruszinski ◽  
...  
Keyword(s):  
Trigeminal Ganglion ◽  
Medication Overuse ◽  
Medication Overuse Headache ◽  
Nasal Delivery ◽  
Nasal Administration ◽  
Dopamine Receptor Agonist ◽  
Sexually Dimorphic ◽  
Down Regulation ◽  
Female Mice ◽  
Cutaneous Allodynia

Objective Determination of possible sex differences in mechanisms promoting migraine progression and the contribution of prolactin and the prolactin long (PRLR-L) and short (PRLR-S) receptor isoforms. Background The majority of patients with chronic migraine and medication overuse headache are female. Prolactin is present at higher levels in women and increases migraine. Prolactin signaling at the PRLR-S selectively sensitizes nociceptors in female rodents, while expression of the PRLR-L is protective. Methods Medication overuse headache was modeled by repeated sumatriptan administration in male and female mice. Periorbital and hindpaw cutaneous allodynia served as a surrogate of migraine-like pain. PRLR-L and PRLR-S isoforms were measured in the trigeminal ganglion with western blotting. Possible co-localization of PRLR with serotonin 5HT1B and 5HT1D receptors was determined with RNAscope. Cabergoline, a dopamine receptor agonist that inhibits circulating prolactin, was co-administered with sumatriptan. Nasal administration of CRISPR/Cas9 plasmid was used to edit expression of both PRLR isoforms. Results PRLR was co-localized with 5HT1B or 5HT1D receptors in the ophthalmic region of female trigeminal ganglion. A single injection of sumatriptan increased serum PRL levels in female mice. Repeated sumatriptan promoted cutaneous allodynia in both sexes but down-regulated trigeminal ganglion PRLR-L, without altering PRLR-S, only in females. Co-administration of sumatriptan with cabergoline prevented allodynia and down-regulation of PRLR-L only in females. CRISPR/Cas9 editing of both PRLR isoforms in the trigeminal ganglion prevented sumatriptan-induced periorbital allodynia in females. Interpretation We identified a sexually dimorphic mechanism of migraine chronification that involves down-regulation of PRLR-L and increased signaling of circulating prolactin at PRLR-S. These studies reveal a previously unrecognized neuroendocrine mechanism linking the hypothalamus to nociceptor sensitization that increases the risk of migraine pain in females and suggest opportunities for novel sex-specific therapies including gene editing through nasal delivery of CRISPR/Cas9 constructs.

FORMULATION AND IN-VITRO EVALUATION OF ZOLMITRIPTAN IN SITU GEL FOR NASAL ADMINISTRATION

INDIAN DRUGS ◽  
2013 ◽  
Vol 50 (12) ◽  
pp. 54-58
Author(s):  
P. H Patil ◽  
◽  
V. S Belgamwar ◽  
D. A Patel ◽  
S. J. Surana
Keyword(s):  
Evaluation Studies ◽  
Methyl Cellulose ◽  
Nasal Delivery ◽  
Nasal Administration ◽  
Histopathological Study ◽  
In Situ Gel ◽  
In Vitro Evaluation ◽  
Effective Delivery

The aim of present investigation was formulation and in-vitro evaluation of in situ gel for the nasal delivery of zolmitriptan. The in situ gel was prepared by temperature induced gelation technique using Pluronic with mucoadhesive polymer hydroxy propyl methyl cellulose K4 M in different ratios. The in situ gels so prepared were characterized and from the evaluation studies, batch PH2 was optimized and further subjected for stability studies at 30±2°C and 60±5% RH for 90 days. These formulations retained good stability at accelerated conditions and also did not show any remarkable damage to nasal mucosa in histopathological study. Owing to these properties it can be used as an effective delivery system for the nasal route.

scholarly journals Hemagglutinin Cleavability, Acid Stability, and Temperature Dependence Optimize Influenza B Virus for Replication in Human Airways

2019 ◽  
Vol 94 (1) ◽  
Author(s):  
Manon Laporte ◽  
Annelies Stevaert ◽  
Valerie Raeymaekers ◽  
Talitha Boogaerts ◽  
Inga Nehlmeier ◽  
...  
Keyword(s):  
Membrane Fusion ◽  
Human Population ◽  
Influenza A ◽  
Influenza B Virus ◽  
Influenza B ◽  
Upper Airways ◽  
Acid Stability ◽  
Viral Hemagglutinin ◽  
B Virus ◽  
Human Airways

ABSTRACT Influenza A virus (IAV) and influenza B virus (IBV) cause yearly epidemics with significant morbidity and mortality. When zoonotic IAVs enter the human population, the viral hemagglutinin (HA) requires adaptation to achieve sustained virus transmission. In contrast, IBV has been circulating in humans, its only host, for a long period of time. Whether this entailed adaptation of IBV HA to the human airways is unknown. To address this question, we compared two seasonal IAVs (A/H1N1 and A/H3N2) and two IBVs (B/Victoria and B/Yamagata lineages) with regard to host-dependent activity of HA as the mediator of membrane fusion during viral entry. We first investigated proteolytic activation of HA by covering all type II transmembrane serine protease (TTSP) and kallikrein enzymes, many of which proved to be present in human respiratory epithelium. The IBV HA0 precursor is cleaved by a broader panel of TTSPs and activated with much higher efficiency than IAV HA0. Accordingly, knockdown of a single protease, TMPRSS2, abrogated spread of IAV but not IBV in human respiratory epithelial cells. Second, the HA fusion pH values proved similar for IBV and human-adapted IAVs (with one exception being the HA of 1918 IAV). Third, IBV HA exhibited higher expression at 33°C, a temperature required for membrane fusion by B/Victoria HA. This indicates pronounced adaptation of IBV HA to the mildly acidic pH and cooler temperature of human upper airways. These distinct and intrinsic features of IBV HA are compatible with extensive host adaptation during prolonged circulation of this respiratory virus in the human population. IMPORTANCE Influenza epidemics are caused by influenza A and influenza B viruses (IAV and IBV, respectively). IBV causes substantial disease; however, it is far less studied than IAV. While IAV originates from animal reservoirs, IBV circulates in humans only. Virus spread requires that the viral hemagglutinin (HA) is active and sufficiently stable in human airways. We resolve here how these mechanisms differ between IBV and IAV. Whereas human IAVs rely on one particular protease for HA activation, this is not the case for IBV. Superior activation of IBV by several proteases should enhance shedding of infectious particles. IBV HA exhibits acid stability and a preference for 33°C, indicating pronounced adaptation to the human upper airways, where the pH is mildly acidic and a cooler temperature exists. These adaptive features are rationalized by the long existence of IBV in humans and may have broader relevance for understanding the biology and evolution of respiratory viruses.

scholarly journals Quantifying Face Mask Comfort

2021 ◽  
Author(s):  
Esther Koh ◽  
Mythri Ambatipudi ◽  
DaLoria L. Boone ◽  
Julia B.W. Luehr ◽  
Alena Blaise ◽  
...  
Keyword(s):  
Multiple Linear Regression Model ◽  
Water Vapor Permeability ◽  
Primary Source ◽  
Face Mask ◽  
Machine Learning Algorithms ◽  
Critical Parameters ◽  
Vapor Permeability ◽  
Simple Analytical Expression ◽  
Air Resistance ◽  
Face Temperature

Face mask usage is one of the most effective ways to limit SARS-CoV-2 transmission, but a mask is only useful if user compliance is high. Through anonymous surveys, we show that mask discomfort is the primary source of noncompliance in mask wearing. Further, through these surveys, we identify three critical parameters that dictate mask comfort: air resistance, water vapor permeability, and face temperature change. To validate these parameters in a physiological context, we performed experiments to measure the respiratory rate and change in face temperature while wearing different types of commonly used masks. Finally, using values of these parameters from experiments and the literature, and surveys asking users to rate the comfort of various masks, three machine learning algorithms were trained and tested to generate overall comfort scores for those masks. Although all three models tested performed with an accuracy of approximately 70%, the multiple linear regression model also provides a simple analytical expression to predict the comfort scores for any face mask provided the input parameters. As face mask usage is crucial during the COVID-19 pandemic, the ability of this quantitative framework to predict mask comfort is likely to improve user experience and prevent discomfort-induced noncompliance.

scholarly journals Positive association of supersaturation effects in the human airways with influenza activity in subtropical climate: influenza seasons in Okinawa (2007-2012) – New method for analyzing and forecasting (first preliminary results)

2017 ◽  
Author(s):  
Aleksandr N Ishmatov
Keyword(s):  
Positive Association ◽  
Weather Conditions ◽  
Subtropical Climate ◽  
Upper Airways ◽  
Subtropical Zone ◽  
Additional Risk ◽  
Influenza Activity ◽  
Main Representative ◽  
Human Airways ◽  
Environmental Air

There are many theories of the seasonality of influenza for different climatic zones. But none of the known theories provides a clear explanation, especially for the tropical and subtropical climate. Here we have originally analyzed the association/connection of activity of seasonal influenza in Okinawa (subtropical zone) with the probability of occurring of supersaturation in the human airways when inhaling environmental air under specific weather conditions. We have shown for the first time that the effects of supersaturation in the human airways may be associated with main representative peaks of intensity/activity of influenza in Okinawa in the period of observation from Jan 2007 until Dec 2012 including 2009 pandemic. Our observation is the first one which clearly shows in the practice that the effect of supersaturation in the airways can be used for understanding and forecast the influenza activity in subtropical and tropical zones. Because the effect of supersaturation may lead to an additional risk of acidification of epithelial lining fluid in the local areas of the respiratory tract and to additional risk of deposition of infectious agents from inhaled air in the upper airways.

scholarly journals Upper Airway Cough Syndrome in Pathogenesis of Chronic Cough

2020 ◽  
pp. S35-S42
Author(s):  
M. Lucanska ◽  
A. Hajtman ◽  
V. Calkovsky ◽  
P. Kunc ◽  
R. Pecova
Keyword(s):  
Chronic Cough ◽  
Sensory Nerve ◽  
Upper Airway ◽  
Vagal Afferents ◽  
Upper Airways ◽  
Cough Reflex ◽  
Postnasal Drip ◽  
Common Causes ◽  
Lower Airways ◽  
Human Airways

Cough is one of the most important defensive reflexes. However, extensive non- productive cough is a harmful mechanism leading to the damage of human airways. Cough is initiated by activation of vagal afferents in the airways. The site of their convergence is particularly the nucleus of the solitary tract (nTS). The second-order neurons terminate in the pons, medulla and spinal cord and there is also the cortical and subcortical control of coughing. Upper airway cough syndrome (UACS) – previously postnasal drip syndrome - is one of the most common causes of chronic cough together with asthma and gastroesophageal reflux. The main mechanisms leading to cough in patients with nasal and sinus diseases are postnasal drip, direct irritation of nasal mucosa, inflammation in the lower airways, upper airway inflammation and the cough reflex sensitization. The cough demonstrated by UACS patients is probably due to hypersensitivity of the upper airways sensory nerve or lower airways sensory nerve, or a combination of both. Further studies are needed to clarify this mechanism.

scholarly journals Selective targeting of the TLR2/MyD88/NF-κB pathway reduces α-synuclein spreading in vitro and in vivo

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Debashis Dutta ◽  
Malabendu Jana ◽  
Moumita Majumder ◽  
Susanta Mondal ◽  
Avik Roy ◽  
...  
Keyword(s):  
Lewy Bodies ◽  
Selective Inhibition ◽  
Nasal Delivery ◽  
Nasal Administration ◽  
Interaction Domain ◽  
Selective Targeting ◽  
Nemo Binding Domain ◽  
Microglial Inflammation

AbstractPathways to control the spreading of α-synuclein (α-syn) and associated neuropathology in Parkinson’s disease (PD), multiple system atrophy (MSA) and dementia with Lewy bodies (DLB) are unclear. Here, we show that preformed α-syn fibrils (PFF) increase the association between TLR2 and MyD88, resulting in microglial activation. The TLR2-interaction domain of MyD88 (wtTIDM) peptide-mediated selective inhibition of TLR2 reduces PFF-induced microglial inflammation in vitro. In PFF-seeded A53T mice, the nasal administration of the wtTIDM peptide, NEMO-binding domain (wtNBD) peptide, or genetic deletion of TLR2 reduces glial inflammation, decreases α-syn spreading, and protects dopaminergic neurons by inhibiting NF-κB. In summary, α-syn spreading depends on the TLR2/MyD88/NF-κB pathway and it can be reduced by nasal delivery of wtTIDM and wtNBD peptides.

Pulmonary and systemic blood flow contributions to upper airways in canine lung

1988 ◽  
Vol 255 (5) ◽  
pp. H1130-H1135 ◽  
Author(s):  
S. A. Barman ◽  
J. L. Ardell ◽  
J. C. Parker ◽  
M. L. Perry ◽  
A. E. Taylor
Keyword(s):  
Blood Flow ◽  
Primary Source ◽  
Upper Airways ◽  
Systemic Blood Flow ◽  
Tracheal Cartilage ◽  
Blood Flows ◽  
Drainage Patterns ◽  
Isolated Lung ◽  
Anesthetized Dogs ◽  
The Right

The blood flow contributions and drainage patterns of the pulmonary and systemic circulations in the upper airways (trachea and main bronchi) were assessed in anesthetized dogs by injecting 15-micron radiolabeled microspheres into the right and left heart, respectively. After the animals were killed, the tracheal cartilage, tracheal muscle-mucosa, and main bronchi were excised. The tracheal cartilage and tracheal muscle-mucosa were divided into lower, middle, and upper segments for blood flow determinations. The pulmonary contribution to tracheal blood flow was very small, averaging only 0.6 +/- 0.3 ml.min-1.100 g-1 (means +/- SE), being higher in the lower segments. The systemic contribution to these same tracheal regions was significantly (P less than 0.05) higher, averaging 20.9 +/- 5.5 ml.min-1.100 g-1 (means +/- SE) and higher in the upper segments. The pulmonary and systemic circulations each contributed approximately 50% to the main bronchi blood flow, which averaged 11.2 +/- 4.2 ml.min-1.100 g-1 (means +/- SE). The pulmonary blood flow contribution alone to the trachea and main bronchi was also determined in subsequent experiments that utilized the isolated lung, and these blood flows were not significantly different from the pulmonary contribution measured in the intact lungs. The present results indicate that the systemic (bronchial) circulation is the primary source of tracheal blood flow and that both the pulmonary and systemic circulations may contribute approximately 50% of the blood flow to the main bronchi in dog lungs.

scholarly journals Evidence for influenza B virus hemagglutinin adaptation to the human host: high cleavability, acid-stability and preference for cool temperature

2019 ◽  
Author(s):  
Manon Laporte ◽  
Annelies Stevaert ◽  
Valerie Raeymaekers ◽  
Talitha Boogaerts ◽  
Inga Nehlmeier ◽  
...  
Keyword(s):  
Membrane Fusion ◽  
Human Population ◽  
Influenza A ◽  
Influenza B Virus ◽  
Influenza B ◽  
Upper Airways ◽  
Acid Stability ◽  
Viral Hemagglutinin ◽  
B Virus ◽  
Human Airways

AbstractInfluenza A virus (IAV) and influenza B virus (IBV) cause yearly epidemics with significant morbidity and mortality. When zoonotic IAVs enter the human population, the viral hemagglutinin (HA) requires adaptation to achieve sustained virus transmission. In contrast, IBV has been circulating in humans, its only host, for a long period of time. Whether this entailed adaptation of IBV HA to the human airways is unknown. To address this question, we compared seasonal IAV (A/H1N1 and A/H3N2) and IBV viruses (B/Victoria and B/Yamagata lineage) with regard to host-dependent activity of HA as the mediator of membrane fusion during viral entry. We first investigated proteolytic activation of HA, by covering all type II transmembrane serine protease (TTSP) and kallikrein enzymes, many of which proved present in human respiratory epithelium. Compared to IAV, the IBV HA0 precursor is cleaved by a broader panel of TTSPs and activated with much higher efficiency. Accordingly, knockdown of a single protease, TMPRSS2, was sufficient to abrogate spread of IAV but not IBV in human respiratory epithelial cells. Second, the HA fusion pH proved similar for IBV and human-adapted IAVs (one exception being HA of 1918 IAV). Third, IBV HA exhibited higher expression at 33°C, a temperature required for membrane fusion by B/Victoria HA. This indicates pronounced adaptation of IBV HA to the mildly acidic pH and cooler temperature of human upper airways. These distinct and intrinsic features of IBV HA are compatible with extensive host-adaptation during prolonged circulation of this respiratory virus in the human population.ImportanceInfluenza epidemics are caused by influenza A (IAV) and influenza B (IBV) viruses. IBV causes substantial disease, however it is far less studied than IAV. While IAV originates from animal reservoirs, IBV circulates in humans only. Virus spread requires that the viral hemagglutinin (HA) is active and sufficiently stable in human airways. We here resolve how these mechanisms differ between IBV and IAV. Whereas human IAVs rely on one particular protease for HA activation, this is not the case for IBV. Superior activation of IBV by several proteases should enhance shedding of infectious particles. IBV HA exhibits acid-stability and a preference for 33°C, indicating pronounced adaptation to the human upper airways, where the pH is mildly acidic and a cooler temperature exists. These adaptive features are rationalized by the long existence of IBV in humans, and may have broader relevance for understanding the biology and evolution of respiratory viruses.

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