The Potential Use of Cyclosporine Ultrafine Solution Pressurised Metered-Dose Inhaler in the Treatment of COVID-19 Patients

Introduction: Serious COVID-19 respiratory problems start when the virus reaches the alveolar level, where type II cells get infected and die. Therefore, virus inhibition at the alveolar level would help prevent these respiratory complications. Method: A literature search was conducted to collect physicochemical properties of small molecule compounds that could be used for the COVID-19 treatment. Compounds with a low melting point were selected along with those soluble in ethanol, hydrogen-bond donors, and acceptors. Results : There are severe acute respiratory syndrome coronavirus inhibitors with physicochemical properties suitable for the formulation as an ultrafine pressurised metered-dose inhaler (pMDI). Mycophenolic acid, Debio 025, and cyclosporine A are prime candidates among these compounds. Cyclosporine A (hereafter cyclosporine) is a potent SARS-CoV-2 inhibitor, and it has been used for the treatment of COVID-19 patients, demonstrating an improved survival rate. Also, inhalation therapy of nebulised cyclosporine was tolerated, which was used for patients with lung transplants. Finally, cyclosporine has been formulated as a solution ultrafine pMDI. Although vaccine therapy has been started in most countries, inhalation therapies with non-immunological activities could minimise the spread of the disease and be used in vaccine-hesitant individuals. Conclusion: Ultrafine pMDI formulation of cyclosporine or Debio 025 should be investigated for the inhalation therapy of COVID-19.

THE EFFECTIVESS OF EVALUATION OF OSTEOPATHIC SUPPORT OF PATIENTS SUFFERING FROM THE DISTURBED OCCLUSION AT THE DENTAL ALVEOLAR LEVEL

The eff ectiveness of simultaneous use of braces and methods of osteopathic correction was evaluated while treating 48 patients suff ering from occlusion disorders at the dental alveolar level. The indicators of osteopathic status, situational anxiety, and satisfaction with the aesthetic result of treatment were studied. It was found that the most typical somatic dysfunctions were the dysfunctions of the bones of the skull base, facial skull, cervical spine, chest, and of internal organs of the chest and neck. The inclusion of methods of osteopathic correction in the comprehensive treatment resulted in the better mobility of the structures of the skull, cervical spine, and chest, a decreased anxiety level and, consequently, an increased satisfaction with the aesthetic result of treatment.

A new mode of mechanical ventilation: positive + negative synchronized ventilation

Often, in supporting patients suffering from severe respiratory diseases with mechanical ventilation, obstacles are encountered due to pulmonary and/or thoracic alterations, reductions in the ventilable lung parenchyma, increases in airway resistance, alterations in thoraco-pulmonary compliance, advanced age of the subjects. All this involves difficulties in finding the right ventilation parameters and an adequate driving pressure to guarantee sufficient ventilation. Therefrom, new mechanical ventilation techniques were sought that could help overcome the aforementioned obstacles. A new mode of mechanical ventilation is being presented, i.e., a Positive + Negative Synchronized Ventilation (PNSV), characterized by the association and integration of two pulmonary ventilators; one acting inside the chest with positive pressures and one externally with negative pressure. The peculiarity of this combination is the complete synchronization, which takes place with specific electronic modifications. The PNSV can be applied both in a completely non-invasive and invasive way and, therefore, be used both in acute care wards and in ICU. The most relevant effect found, due to the compensation of opposing pressures acting on the chest, is that, during the entire inspiratory act created by the ventilators, the pressure at the alveolar level is equal to zero even if adding together the two ventilators’ pressures; thus, the transpulmonary pressure is doubled. The application of this pressure for 1 hour on elderly patients suffering from severe acute respiratory failure, resulted in a significant improvement in blood gas analytical and clinical parameters without any side effects. An increased pulmonary recruitment, including posterior lung areas, and a reduction in spontaneous ventilatory rate have also been demonstrated with PNSV. This also paves the way to the search for the best ventilatory treatment in critically ill or ARDS patients. The compensation of intrathoracic pressures should also lead, although not yet proven, to an improvement in venous return, systolic and cardiac output. In the analysis of the study in which this method was applied, the total transpulmonary pressure delivered was the sum of the individual pressures applied by the two ventilators. However, this does not exclude the possibility of reducing the pressures of the two machines to modulate a lower but balanced total transpulmonary pressure within the chest.

Health risk of radon exposure

Introduction. Radon is a chemical element of increased interest to the scientific community due to its implications in the etiology of bronchopulmonary cancer. Pollution of indoor air with radon causes serious effects on health, due to alpha radiation emitted following the process of disintegration into isotopes that together with dust particles, dust enters the alveolar level. Material and methods. This study was based on the analysis of bibliographic sources within the PubMed and Google Scholar platforms. The relevant articles for the study were chosen analogously to the research objectives, interest in publications attesting to the problem of residential radon, its implications in the etiology of lung cancer and the synergism between radon and tobacco. Results. Radon is attributed a significant role in indoor air pollution, has a share of about 50% of total exposure to ionizing radiation and is the second leading cause of death from lung cancer internationally. The synergism between radon and tobacco causes an increased effect in triggering the processes of damage at the cellular level, by disturbing translation and transcription. In the Republic of Moldova, the problem is current; the level of residential radioactivity caused by radon exceeds European and national standards in about half of cases. Conclusions. It is imperative to continuously monitor radon concentrations in the country's homes, set benchmarks, update national rules and implement an effective strategy to reduce the negative effects of radon exposure.

Small airway function in Finnish COVID-19 survivors

Follow-up studies of COVID-19 patients have found lung function impairment up to six months after initial infection, but small airway function has not previously been studied. Patients (n = 20) hospitalised for a severe SARS-CoV-2 infection underwent spirometry, impulse oscillometry, and multiple measurements of alveolar nitric oxide three to six months after acute infection. None of the patients had small airway obstruction, nor increased nitric oxide concentration in the alveolar level. None of the patients had a reduced FEV1/FVC or significant bronchodilator responses in IOS or spirometry. In conclusion, we found no evidence of inflammation or dysfunction in the small airways.

Correlating Local Volumetric Tissue Strains with Global Lung Mechanics Measurements

The mechanics of breathing is a fascinating and vital process. The lung has complexities and subtle heterogeneities in structure across length scales that influence mechanics and function. This study establishes an experimental pipeline for capturing alveolar deformations during a respiratory cycle using synchrotron radiation micro-computed tomography (SR-micro-CT). Rodent lungs were mechanically ventilated and imaged at various time points during the respiratory cycle. Pressure-Volume (P-V) characteristics were recorded to capture any changes in overall lung mechanical behaviour during the experiment. A sequence of tomograms was collected from the lungs within the intact thoracic cavity. Digital volume correlation (DVC) was used to compute the three-dimensional strain field at the alveolar level from the time sequence of reconstructed tomograms. Regional differences in ventilation were highlighted during the respiratory cycle, relating the local strains within the lung tissue to the global ventilation measurements. Strains locally reached approximately 150% compared to the averaged regional deformations of approximately 80–100%. Redistribution of air within the lungs was observed during cycling. Regions which were relatively poorly ventilated (low deformations compared to its neighbouring region) were deforming more uniformly at later stages of the experiment (consistent with its neighbouring region). Such heterogenous phenomena are common in everyday breathing. In pathological lungs, some of these non-uniformities in deformation behaviour can become exaggerated, leading to poor function or further damage. The technique presented can help characterize the multiscale biomechanical nature of a given pathology to improve patient management strategies, considering both the local and global lung mechanics.

Covidaemia and its implications

Coronavirus disease 2019 (COVID-19) pandemic has taught many lessons to the medical fraternity. Academicians and the general population have been through phases of anxiety, panic, and trail and errors. The growing assumption at the onset of the pandemic that COVID infection may spread by blood has not found its roots deep enough for any clinical consequences. As all the symptoms of COVID relate to its local invasion at the alveolar level and its immunological sequelae, this article discusses the possibilities with the research available over the last 10 months. So far, the plasma viral load detected by reverse transcriptase polymerase chain reaction (RT-PCR) seems immaterial in comparison to the viral concentration from nasopharyngeal swabs. So the recommendations to prefer caesarean section for positive mothers, deferring blood donations by COVID patients, frequent antigen testing from blood serum and body fluids like breast milk or amniotic fluid, may really need to be given a second thought. Also, this article concludes about giving up the panic around the viremia-related possibility of vertical transmission from mother to fetus and other clinical implications of testing of blood for the same. This will help in saving the resources heavily to be used only selectively. Newborns in neonatal intensive care unit (NICU) may be permitted to be handled without gloves and using simple practices of handwashing, saving further resources and reducing neonatal infections.

Características y especialización de la respuesta inmunitaria en la COVID-19 y posibles tratamientos profilácticos

Characteristics and Specialization of the Immune Response in COVID-19 Abstract The outbreak of coronavirus pneumonia in Wuhan, China, became a pandemic on March 11, 2020. It has caused almost 4 million confirmed cases worldwide, with more than 270,000 deaths. Coronavirus is an enveloped RNA virus of the β-coronavirus genus distributed in birds, humans, and other mammals. The World Health Organization has named the new disease COVID-19. The scientific community is look http://doi.org/10.22201/fm.24484865e.2020.63.4.02 8 8 Revista de la Facultad de Medicina de la UNAM | ing for evidence that can lead to a better understanding of the infection and the immune response (IR), prognostic and therapeutic predictors, effective treatments and vaccines. The objective of this review was to compile updated scientific evidence of the IR to COVID-19, in order to guide professionals with solutions that have a clinical impact. The most important elements involve innate immunity with failures in the interferon system in the early stages of the infection and a sustained increase in proinflammatory interleukins. This can end in a potentially fatal cytokine storm. The infiltration of neutrophils and macrophages at the alveolar level, accompanied by neutrophilia, is very characteristic. Lymphopenia is evident at the adaptive immunity level, that, depending on the degree, can indicate the severity of the disease. Understanding the temporal sequence of the IR is crucial for choosing the appropriate and effective therapies, especially when selecting which type of anti-inflammatory drugs can be used and the frequency of the dosage. Due to the fact that it is difficult to determine when they will be clearly beneficial, not harmful to the IR and not too late, due to the irreversibility of the process. Key words: COVID-19; coronavirus; immune response

MAP kinase dysregulation by Coronaviruses

An opinion on what may cause complications displayed by the current coronavirus whereby it seems MAP kinase is 'overworking' in the process of virulence. Although the virus is completely inactivated in the presence of known chemicals such as acetone and zinc it is by accessing the lungs that it manages to cause respiratory distress. The virus is quite an amphiphilic molecule which makes its absorption easy to achieve particularly at an alveolar level where gas exchange occurs; however this amphilicity has been reached by mimicking human genome rather than by its own developmental sophistication. There is a wide range of therapeutic options for map kinase regulations. Some antimalarials and low dose aspirin even have demonstrated modest activity and according to recent news they have helped in difficult cases but prompt antiviral management should be addressed prior to the skyrocketing immune phase where the body may fail to recognise itself and self-attack. By targeting the virus initially the map kinase may react non-disproportionately.