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International Journal of Molecular... Jun 2021FcRn plays a major role in regulating immune homeostasis, but it is also able to transport biologics across cellular barriers. The question of whether FcRn could be an... (Meta-Analysis)
Meta-Analysis
FcRn plays a major role in regulating immune homeostasis, but it is also able to transport biologics across cellular barriers. The question of whether FcRn could be an efficient transporter of biologics across the nasal epithelial barrier is of particular interest, as it would allow a less invasive strategy for the administration of biologics in comparison to subcutaneous, intramuscular or intravenous administrations, which are often used in clinical practice. A focused systematic review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. It was registered on the international prospective register of systematic reviews PROSPERO, which helped in identifying articles that met the inclusion criteria. Clinical and preclinical studies involving FcRn and the nasal delivery of biologics were screened, and the risk of bias was assessed across studies using the Oral Health Assessment Tool (OHAT). Among the 12 studies finally included in this systematic review (out of the 758 studies screened), 11 demonstrated efficient transcytosis of biologics through the nasal epithelium. Only three studies evaluated the potential toxicity of biologics' intranasal delivery, and they all showed that it was safe. This systematic review confirmed that FcRn is expressed in the nasal airway and the olfactory epithelium, and that FcRn may play a role in IgG and/or IgG-derived molecule-transcytosis across the airway epithelium. However, additional research is needed to better characterize the pharmacokinetic and pharmacodynamic properties of biologics after their intranasal delivery.
Topics: Animals; Biological Products; Biological Transport; Biomarkers; Drug Delivery Systems; Gene Expression; Histocompatibility Antigens Class I; Humans; Nasal Mucosa; Protein Binding; Receptors, Fc; Transcytosis
PubMed: 34204226
DOI: 10.3390/ijms22126475 -
Rhinology Jun 2021Unlike other respiratory viruses, SARS-CoV-2 causes anosmia without sinonasal inflammation. Here we systematically review the effects of the 7 known human coronaviruses...
BACKGROUND
Unlike other respiratory viruses, SARS-CoV-2 causes anosmia without sinonasal inflammation. Here we systematically review the effects of the 7 known human coronaviruses on olfaction to determine if SARS-CoV-2 distinctly affects the olfactory system.
METHOD
PubMed, EMBASE, Web of Science, bioRxiv, medRxiv and DOAJ were searched for studies describing pathophysiological, immunohistochemical, cytological and clinical data.
RESULTS
49 studies were included. Common cold coronaviruses lead to sinonasal inflammation which can cause transient and chronic loss of smell. MERS-CoV entry receptors were not found in the nasal mucosa and it did not impair olfaction. SARS-CoV-1 had low affinity for its receptor ACE2, limiting olfactory effects. Anosmia is frequent in SARS-CoV-2 infections. SARS-CoV-2’s entry factors ACE2 and TMPRSS2 are expressed in the nasal respiratory epithelium and olfactory supporting cells. SARS-CoV-2 appeared to target the olfactory cleft while diffuse nasal inflammation was not observed. Damage of the olfactory epithelium was observed in animal models. Alternative receptors such as furin and neuropilin-1 and the similarity of viral proteins to odourant receptors could amplify olfactory impairment in SARS-CoV-2 infection.
CONCLUSIONS
The pathophysiology of anosmia in SARS-CoV-2 infection is distinct from other coronaviruses due to preferentially targeting olfactory supporting cells. However, SARS-CoV-2 does not cause sinonasal inflammation in spite of preferred entry factor expression in the nasal respiratory epithelium. This raises doubts about the attention given to ACE2. Alternative receptors, odourant receptor mimicry and other as yet unknown mechanisms may be crucial in the pathogenesis of anosmia in SARS-CoV-2 infection. Further studies are warranted to investigate infection mechanisms beyond ACE2.
Topics: Angiotensin-Converting Enzyme 2; Animals; COVID-19; Humans; Peptidyl-Dipeptidase A; SARS-CoV-2
PubMed: 34091654
DOI: 10.4193/Rhin20.610 -
American Journal of Rhinology & Allergy May 2021Post-viral olfactory dysfunction is a common cause of both short- and long-term smell alteration. The coronavirus pandemic further highlights the importance of...
BACKGROUND
Post-viral olfactory dysfunction is a common cause of both short- and long-term smell alteration. The coronavirus pandemic further highlights the importance of post-viral olfactory dysfunction. Currently, a comprehensive review of the neural mechanism underpinning post-viral olfactory dysfunction is lacking.
OBJECTIVES
To synthesize the existing primary literature related to olfactory dysfunction secondary to viral infection, detail the underlying pathophysiological mechanisms, highlight relevance for the current COVID-19 pandemic, and identify high impact areas of future research.
METHODS
PubMed and Embase were searched to identify studies reporting primary scientific data on post-viral olfactory dysfunction. Results were supplemented by manual searches. Studies were categorized into animal and human studies for final analysis and summary.
RESULTS
A total of 38 animal studies and 7 human studies met inclusion criteria and were analyzed. There was significant variability in study design, experimental model, and outcome measured. Viral effects on the olfactory system varies significantly based on viral substrain but generally include damage or alteration in components of the olfactory epithelium and/or the olfactory bulb.
CONCLUSIONS
The mechanism of post-viral olfactory dysfunction is highly complex, virus-dependent, and involves a combination of insults at multiple levels of the olfactory pathway. This will have important implications for future diagnostic and therapeutic developments for patients infected with COVID-19.
Topics: Animals; COVID-19; Humans; Olfaction Disorders; Olfactory Bulb; Olfactory Mucosa; Olfactory Pathways; SARS-CoV-2; Species Specificity; Post-Acute COVID-19 Syndrome
PubMed: 32915650
DOI: 10.1177/1945892420957853 -
Head and Neck Pathology Mar 2021To review the data regarding the expression of angiotensin converting enzyme-2 (ACE2) and transmembrane protease serine-2 (TMPRSS2) in head and neck tissue. Scopus,...
To review the data regarding the expression of angiotensin converting enzyme-2 (ACE2) and transmembrane protease serine-2 (TMPRSS2) in head and neck tissue. Scopus, Cochrane Library, Medrxiv, Google Scholar and PubMED/MEDLINE were searched by four independent investigators for studies investigating ACE2 or TMPRSS2 expressions in head and neck tissues. The following outcomes were considered: sample origin (animal versus human); detection method; anatomical location and cell types. PRISMA checklist and modified population, intervention, comparison, outcome, timing and setting (PICOTS) framework were used to perform the review. Of the 24 identified studies, 17 met our inclusion criteria. Thirteen studies were conducted during the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic. ACE2 and TMPRSS2 were expressed in oral, pharyngeal, sinusonasal human mucosa. The following cell types expressed ACE2: basal, apical, goblet, minor salivary, and endothelial cells. TMPRSS2 was found in goblet and apical respiratory cells. ACE2 and TMPRSS2 were found in the olfactory region, especially in sustentacular non-neural and neural stem cells. Animal studies suggested that ACE2 expression may vary regarding age. There was an important heterogeneity between studies in the methods used to detect ACE2 and TMPRSS2, leading to a potential identification bias. The SARS-CoV-2 receptors, ACE2 and TMPRSS2, are both expressed in many head and neck tissues, enabling the viral entry into the host organism.
Topics: Angiotensin-Converting Enzyme 2; Animals; COVID-19; Head; Humans; Neck; SARS-CoV-2; Serine Endopeptidases
PubMed: 32816230
DOI: 10.1007/s12105-020-01212-5 -
Acta Otorrinolaringologica Espanola 2020There is debate as to whether olfactory dysfunction should be considered a symptom of COVID-19 infection, given the implications for managing the symptom itself, for...
There is debate as to whether olfactory dysfunction should be considered a symptom of COVID-19 infection, given the implications for managing the symptom itself, for diagnostic testing, and for implementing isolation measures. We undertook a systematic literature review of the articles indexed in PubMed on olfactory disorders in viral respiratory tract conditions, with special emphasis on COVID-19. The main objective was to find evidence of clinical interest to support the relationship between anosmia and COVID-19. Olfactory disorders in upper respiratory tract infections are frequent, most caused by obstruction due to oedema of the nasal mucosa. Occasionally, post-viral sensorineural olfactory dysfunction occurs, with a variable prognosis. The evidence on anosmia in COVID-19 patients is extremely limited, corresponding to a level 5 or D of the Centre for Evidence-Based Medicine. According to the various medical societies that have issued reports on the subject, it seems reasonable to apply isolation, hygiene and social distancing measures in patients with recent olfactory disorders as the only symptom, although the usefulness of diagnostic tests for this type of patient should be studied.
Topics: Betacoronavirus; COVID-19; COVID-19 Testing; Clinical Laboratory Techniques; Coronavirus Infections; Humans; Hygiene; Olfaction Disorders; Olfactory Mucosa; Pandemics; Patient Isolation; Pneumonia, Viral; Practice Guidelines as Topic; Prognosis; Quarantine; Respiratory Tract Infections; SARS-CoV-2; Virus Diseases
PubMed: 32466862
DOI: 10.1016/j.otorri.2020.04.003 -
International Forum of Allergy &... Jul 2018Interest in the pathophysiology and management of phantom smells has increased rapidly over the last decade. A PubMed search for the term "phantosmia" demonstrated a...
BACKGROUND
Interest in the pathophysiology and management of phantom smells has increased rapidly over the last decade. A PubMed search for the term "phantosmia" demonstrated a near-doubling of articles published on phantosmia within the past 7 years. We aimed to systematically review the literature on the management of phantosmia.
METHODS
The PubMed, EMBASE, and Cochrane databases were searched for articles published since January 1990, using terms combined with pertinent Boolean search operators. We included articles evaluating management of phantosmia written in the English language, with original data and a minimum of 6 months of follow-up, on at least 2 patients and with well-defined and measurable outcomes.
RESULTS
A total of 2151 unique titles were returned upon the initial search. Of these, 146 abstracts were examined, yielding 7 articles meeting the inclusion criteria. All articles were predominantly level 4 evidence. One prospective level 3 study was included. The studies included a total of 96 patients, with follow-up ranging from 6 months to 11 years. Endpoints were primarily based on subjective patient responses. Management options included observation and medical and surgical therapy. Olfactory mucosa excision was the only surgical intervention studied, with short-term symptomatic improvement in 10 of 11 patients. Forty-one patients were treated medically, which included antipsychotic, antimigraine, and antiseizure medications, transcranial stimulation, and topical cocaine application.
CONCLUSION
Despite increasing interest in the treatment of phantosmia and reports of successful therapies, there remains a paucity of data and lack of consensus regarding optimal management of this difficult condition.
Topics: Antipsychotic Agents; Cocaine; Humans; Olfaction Disorders; Olfactory Mucosa; Phantom Limb; Smell; Transcranial Magnetic Stimulation
PubMed: 29485754
DOI: 10.1002/alr.22108 -
Scientific Reports Jan 2018There are considerable disagreements on the application of olfactory ensheathing cells (OEC) for spinal cord injury (SCI) rehabilitation. The present meta-analysis was... (Meta-Analysis)
Meta-Analysis Review
There are considerable disagreements on the application of olfactory ensheathing cells (OEC) for spinal cord injury (SCI) rehabilitation. The present meta-analysis was designed to investigate the efficacy of OEC transplantation on motor function recovery and neuropathic pain alleviation in SCI animal models. Accordingly, all related studies were identified and included. Two independent researchers assessed the quality of the articles and summarized them by calculating standardized mean differences (SMD). OEC transplantation was shown to significantly improve functional recovery (SMD = 1.36; 95% confidence interval: 1.05-1.68; p < 0.001). The efficacy of this method was higher in thoracic injuries (SMD = 1.41; 95% confidence interval: 1.08-1.74; p < 0.001) and allogeneic transplants (SMD = 1.53; 95% confidence interval: 1.15-1.90; p < 0.001). OEC transplantation had no considerable effects on the improvement of hyperalgesia (SMD = -0.095; 95% confidence interval: -0.42-0.23; p = 0.57) but when the analyses were limited to studies with follow-up ≥8 weeks, it was associated with increased hyperalgesia (SMD = -0.66; 95% confidence interval: -1.28-0.04; p = 0.04). OEC transplantation did not affect SCI-induced allodynia (SMD = 0.54; 95% confidence interval: -0.80-1.87; p = 0.43). Our findings showed that OEC transplantation can significantly improve motor function post-SCI, but it has no effect on allodynia and might lead to relative aggravation of hyperalgesia.
Topics: Animals; Cell Transplantation; Humans; Neuralgia; Olfactory Bulb; Olfactory Mucosa; Spinal Cord Injuries
PubMed: 29321494
DOI: 10.1038/s41598-017-18754-4 -
The Journal of Craniofacial Surgery May 2017The aim of this study was to perform a systematic review of the treatment of nasal bone fractures. The search terms ("nasal bone fracture" AND complication) and ("nasal... (Review)
Review
The aim of this study was to perform a systematic review of the treatment of nasal bone fractures. The search terms ("nasal bone fracture" AND complication) and ("nasal bone fracture" AND [anosmia OR olfaction OR olfactory nerve OR smell]) and (anosmia AND ["nasal preparation" OR "nasal antiseptics"]) were used to search PubMed and SCOPUS. Of the 500 titles, 40 full papers were reviewed. One paper was excluded, and 3 mined papers were added. Ultimately, 12 papers were analyzed. The overall deformity rate was 10.4% ± 4.8%. No significant differences were found between patients who underwent closed reduction (14.7% ± 7.3%) and those who underwent open reduction (9.4% ± 4.4%), between those who underwent local anesthesia (5.8% ± 4.5%), and those who underwent general anesthesia (8.8% ± 3.8%), or between those who received timely treatment (5.7%) and those whose treatment was delayed (9.0%). Septal deviation occurred in 10.0% of patients as a sequela of nasal bone fracture. The nasal obstruction rate was 10.5% ± 5.3%. Fewer patients of nasal obstruction occurred in the open reduction patients (6.9% ± 4.4%) than in the closed reduction patients (15.2%). One patient of epiphora and 1 patient of diplopia were reportedAmong the 77 patients with nasal bone fractures, 29 (37.7% ± 11.3%) complained of olfactory disturbances. No significant associations were found between the type of fracture and the presence of olfactory disturbances. It is recommended for providers to explain to patients that approximately one-tenth of nasal bone fractures exhibit deformity, septal deviation, or nasal obstruction after surgery. Surgeons should take considerable care to avoid the olfactory mucosa during reduction surgery.
Topics: Humans; Nasal Bone; Nasal Obstruction; Nose Deformities, Acquired; Olfaction Disorders; Open Fracture Reduction; Skull Fractures; Tomography, X-Ray Computed
PubMed: 28468171
DOI: 10.1097/SCS.0000000000003482 -
European Journal of Neurology Feb 2016Phosphorylated α-synuclein (phosαSYN) containing inclusions in neurons (Lewy bodies, LB) and nerve terminals (Lewy neurites, LN), the pathological hallmark of... (Review)
Review
Phosphorylated α-synuclein (phosαSYN) containing inclusions in neurons (Lewy bodies, LB) and nerve terminals (Lewy neurites, LN), the pathological hallmark of Parkinson's disease (PD), are not confined to the central nervous system, but have also been reported in peripheral tissues. However, the usefulness of αSYN/phosαSYN detection in tissues accessible to biopsies as a reliable biomarker for prodromal PD remains unclear. A systematic review of studies using biopsies of skin, olfactory and gastrointestinal (GI) tissues was conducted to evaluate the sensitivity and specificity of both αSYN and phosαSYN staining in PD patients. Data analysis was hampered by the diversity of the methods used, e.g. choice of biopsy sites, tissue processing, staining protocols and evaluation of the findings. Tissue obtained from GI tract/salivary glands (13 post-mortem, 13 in vivo studies) yielded the highest overall sensitivity and specificity compared to skin (three post-mortem, eight in vivo studies) and olfactory mucosa/bulb (six post-mortem studies, one in vivo study). In contrast to phosαSYN, αSYN was more consistently detectable in peripheral tissues of healthy controls. GI tract/salivary glands appear to be the most promising candidate tissue for peripheral biopsy-taking. phosαSYN is considered as the marker of choice to delineate pathological aggregates from normal αSYN regularly found in peripheral neural tissues. However, the sensitivity and specificity of phosαSYN are not yet acceptable for using phosαSYN as a reliable peripheral biomarker for PD in clinical routine. Further refinement regarding the interpretation of the peripheral αSYN/phosαSYN burden and the phenotypical definition of peripheral LB/LN is needed to optimize screening methods for prodromal PD.
Topics: Biomarkers; Gastrointestinal Tract; Humans; Parkinson Disease; Salivary Glands; alpha-Synuclein
PubMed: 26100920
DOI: 10.1111/ene.12753 -
Journal of Affective Disorders Sep 2015There is an emerging interest in the use of cellular models to study psychiatric disorders. We have systematically reviewed the application of cellular models to... (Review)
Review
BACKGROUND
There is an emerging interest in the use of cellular models to study psychiatric disorders. We have systematically reviewed the application of cellular models to understand the biological basis of bipolar disorder (BD).
METHOD
Published scientific literature in MEDLINE, PsychINFO and SCOPUS databases were identified with the following search strategy: [(Lymphoblastoid OR Lymphoblast OR Fibroblast OR Pluripotent OR Olfactory epithelium OR Olfactory mucosa) AND (Bipolar disorder OR Lithium OR Valproate OR Mania)]. Studies were included if they had used cell cultures derived from BD patients.
RESULTS
There were 65 articles on lymphoblastoid cell lines, 14 articles on fibroblasts, 4 articles on olfactory neuronal epithelium (ONE) and 2 articles on neurons reprogrammed from induced pluripotent stem cell lines (IPSC). Several parameters have been studied, and the most replicated findings are abnormalities in calcium signaling, endoplasmic reticulum (ER) stress response, mitochondrial oxidative pathway, membrane ion channels, circadian system and apoptosis related genes. These, although present in basal state, seem to be accentuated in the presence of cellular stressors (e.g. oxidative stress--rotenone; ER stress--thapsigargin), and are often reversed with in-vitro lithium.
CONCLUSION
Cellular modeling has proven useful in BD, and potential pathways, especially in cellular resilience related mechanisms have been identified. These findings show consistency with other study designs (genome-wide association, brain-imaging, and post-mortem brain expression). ONE cells and IPSC reprogrammed neurons represent the next generation of cell models in BD. Future studies should focus on family-based study designs and combine cell models with deep sequencing and genetic manipulations.
Topics: Animals; Antipsychotic Agents; Apoptosis; Bipolar Disorder; Brain; Calcium; Humans; Ion Channels; Lithium Compounds; Lymphocytes; Mitochondria; Neurons; Oxidative Stress; Signal Transduction; Valproic Acid
PubMed: 26070045
DOI: 10.1016/j.jad.2015.05.037