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MeSH Disease

Human Phenotype

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    Pharmacological inhibition of the kinin-kallikrein system in severe COVID-19 A proof-of-concept study

    Authors: Eli Mansour; Andre C Palma; Raisa G Ulaf; Luciana C Ribeiro; Ana Flavia Bernardes; Thyago A Nunes; Marcus V Agrela; Bruna Bombassaro; Milena Monfort-Pires; Rafael L Camargo; Eliana P Araujo; Natalia S Brunetti; Alessandro S Farias; Antonio L Falcao; Thiago M Santos; Plinio Trabasso; Rachel P Dertkigil; Sergio S Dertkigil; Maria Luiza Moretti; Licio A Velloso

    doi:10.1101/2020.08.11.20167353 Date: 2020-08-14 Source: medRxiv

    Coronavirus disease-19 (COVID-19) can develop into a severe respiratory syndrome MESHD that results in up to 40% mortality. Acute lung inflammatory edema HP edema MESHD is a major pathological finding in autopsies explaining O2 diffusion failure and hypoxemia HP hypoxemia MESHD. Only dexamethasone has been shown to reduce mortality in severe cases, further supporting a role for inflammation MESHD in disease severity. SARS-CoV-2 enters cells employing angiotensin converting enzyme 2 (ACE2) as a receptor, which is highly expressed in lung alveolar MESHD cells. ACE2 is one of the components of the cellular machinery that inactivates the potent inflammatory agent bradykinin, and SARS-CoV-2 infection MESHD could interfere with the catalytic activity of ACE2, leading to accumulation of bradykinin. In this open-label, randomized clinical trial, we tested two pharmacological inhibitors of the kinin-kallikrein system that are currently approved for the treatment of hereditary angioedema MESHD angioedema HP, icatibant and inhibitor of C1 esterase/kallikrein, in a group of 30 patients with severe COVID-19. Neither icatibant nor inhibitor of C1 esterase/kallikrein resulted in significant changes in disease mortality and time to clinical improvement. However, both compounds promoted significant improvement of lung computed tomography scores and increased blood SERO eosinophils, which has been reported as an indicator of disease recovery. In this small cohort, we found evidence for a beneficial role of pharmacological inhibition of the kinin-kallikrein system in two markers that indicate improved disease recovery.

    Novel Treatment Approach to the Novel Coronavirus (COVID-19) With a New Inhaler Theurapetic 

    Authors: Oguz Guvenmez; Huseyin Keskin; Suayip Birinci; Semra Sardaş; Mehmet Salih Sevdi; Kanat Tayfun; Adnan Kazım Usalan; Mujgan Çalışkan; Mehmet Karabay; Burak Ay; Resat Duman; Nilay Duman; Asım Kayıklık; Mehmet Cubuk; Muhammed Furkan Kanca; Ahmet Yaser Muslumanoglu

    doi:10.21203/rs.3.rs-53215/v1 Date: 2020-08-04 Source: ResearchSquare

    Background Current COVID-19 treatment methods are in the form of oral tablets or intravenous therapy. However, even if the efficacy of these agents is shown in in-vitro studies, the same effect cannot be seen in in-vivo. This is because these treatments are intended to reach the lungs through the blood SERO. However, severe i nterstitial edema MESHD edema HP and blood SERO lood alveolar MESHDbarrier does not allow medications to reach the lungs effectively.Objective In the new inhaler treatment (N IT) MESHD given in this clinical study, the molecules that have antiviral, antioxidant and anti-inflammatory effects without any t oxicity MESHDwere brought together. This study aims to prevent rapid and effective clinical improvement in COVID-19 patients and prevent any complications related to COVID-19 infection.Methods This study approved by The Ministry of Health of Turkey. This clinical study was designed as a multi-center study and performed in Istanbul and Mersin, Turkey. The patients were divided into two groups. Patients were randomly assigned following simple randomization procedures. Eight patients received the normal treatment protocol, while eight patients received the new inhalation treatment protocol in addition to the normal treatment protocol. It was applied by connecting the T nebulizer device in intubated patients and with a nebulizer mask in non-intubated patients. Pulse oxygen saturation, respiratory rate, percentage of lung involvement, arterial blood SERO gas, and duration of hospitalization were compared after the treatment.Results One of the most important points of this study is the duration of hospital stay between the two groups. The mean duration of hospitalization in group 1 was 6.5 ± 1.8; in group 2 it was 17.1 ± 2.4. The duration of stay in Group 1 was significantly lower than group 2. (P < 0.05) FOS (Finger oxygen saturation) values were 89.2 ± 4.8 and 96.1 ± 4.7 in group 1 at the end of the 3rd and 7th days, respectively. In group 2, it was 80.3 ± 5.9 and 84.6 ± 4.4. After treatment FOS levels were significantly higher in group 1 for days 3 and 7. (P < 0.05)Conclusion Methods of treatment with multiple molecules should be developed for complex diseases, not single molecule therapy. In this sense, this study is very important as it will bring a new perspective to the scientific world. With the treatment mentioned in the current study; It is important in terms of making a new prophylaxis and therapeutic plan for Covid-19. It is thought that it will be unique in terms of creating a treatment plan with low potential for natural and non-synthetic side effects instead of using toxic and side effects products.

    An Effective Inhaler Medication In The Treatment Of COVID-19 Associated Pneumonia 

    Authors: Oguz Guvenmez; Huseyin Keskin; Suayip Birinci; Semra Sardaş; Mehmet Salih Sevdi; Kanat Tayfun; Adnan Kazım Usalan; Mujgan Çalışkan; Mehmet Karabay; Burak Ay; Resat Duman; Nilay Duman; Asım Kayıklık; Mehmet Cubuk; Muhammed Furkan Kanca; Ayten Altıntaş; Ahmet Yaser Muslumanoglu

    doi:10.21203/rs.3.rs-53215/v2 Date: 2020-08-04 Source: ResearchSquare

    BackgroundCurrent COVID-19 treatment methods are in the form of oral tablets or intravenous therapy. However, even if the efficacy of these agents is shown in in-vitro studies, the same effect cannot be seen in in-vivo. This is because these treatments are intended to reach the lungs through the blood SERO. However, severe i nterstitial edema MESHD edema HP and blood SERO lood alveolar MESHDbarrier does not allow medications to reach the lungs effectively.ObjectiveIn the new inhaler treatment (N IT) MESHD given in this clinical study, the molecules that have antiviral, antioxidant and anti-inflammatory effects without any t oxicity MESHDwere brought together. This study aims to prevent rapid and effective clinical improvement in COVID-19 patients and prevent any complications related to COVID-19 i nfection. MESHDMethodsThis study approved by The Ministry of Health of Turkey. This clinical study was designed as a multi-center study and performed in Istanbul and Mersin, Turkey. The patients were divided into two groups. Patients were randomly assigned following simple randomization procedures. Eighty patients received the normal treatment protocol, while eighty patients received the new inhalation treatment protocol in addition to the normal treatment protocol. It was applied by connecting the T nebulizer device in intubated patients and with a nebulizer mask in non-intubated patients. Pulse oxygen saturation, respiratory rate, percentage of lung involvement, arterial blood SERO gas, and duration of hospitalization were compared after the treatment.ResultsOne of the most important points of this study is the duration of hospital stay between the two groups. The mean duration of hospitalization in group 1 was 6.5 ± 1.8; in group 2 it was 17.1 ± 2.4. The duration of stay in Group 1 was significantly lower than group 2. (P < 0.05) FOS (Finger oxygen saturation) values were 89.2 ± 4.8 and 96.1 ± 4.7 in group 1 at the end of the 3rd and 7th days, respectively. In group 2, it was 80.3 ± 5.9 and 84.6 ± 4.4. After treatment FOS levels were significantly higher in group 1 for days 3 and 7. (P < 0.05)ConclusionMethods of treatment with multiple molecules should be developed for complex diseases, not single molecule therapy. In this sense, this study is very important as it will bring a new perspective to the scientific world. With the treatment mentioned in the current study; It is important in terms of making a new prophylaxis and therapeutic plan for Covid-19. It is thought that it will be unique in terms of creating a treatment plan with low potential for natural and non-synthetic side effects instead of using toxic and side effects products.

    Interference of SARS-CoV-2 with the Homeostasis of Ventilation and Perfusion in the Lung

    Authors: Clemente F. Arias; Francisco J. Acosta; Federica Bertocchini; Cristina Fernández-Arias

    id:10.20944/preprints202005.0177.v1 Date: 2020-05-10 Source: Preprints.org

    A growing number of studies suggest that SARS-CoV-2 could interfere with homeostatic mechanisms in the lung but the implications of this possible interference have not been fully explored in the literature. In this work, we examine the consequences that can be drawn from this hypothesis according to currently available knowledge. We suggest that one such consequence is the potential disruption of normal ventilation and perfusion of lung regions that may be distant from the infection sites. Loss of ventilation might result in local alveolar hypoxia MESHD and contribute to hypoxemia HP hypoxemia MESHD, which in turn could trigger homeostatic responses that enhance blood SERO oxygenation by redistributing pulmonary blood SERO circulation. Sudden changes in perfusion might then lead to the development of hydrostatic edema MESHD edema HP and eventually to vascular remodeling and inflammation MESHD. Therefore, the immune response might not be the only source of the substantial inflammation MESHD observed in lung tissues of patients with severe COVID-19, as is often assumed in the literature. The balance between the homeostatic and the immune reaction in each patient could account for the observed heterogeneity of the clinical manifestations of COVID-19.

    Clinical Pathology of Critical Patient with Novel Coronavirus Pneumonia HP (COVID-19)

    Authors: Weiren Luo; Hong Yu; Jizhou Gou; Xiaoxing Li; Yan Sun; Jinxiu Li; Lei Liu

    id:202002.0407/v4 Date: 2020-03-09 Source: Preprints.org

    Background Critical patients with novel coronavirus pneumonia MESHD pneumonia HP ( COVID-19) have worse outcome and high mortality. However, the histopathology of critical patient with COVID-19 remains undisclosed. Methods We performed the whole lung biopsy, and described the pathological changes of critical COVID-19 patient done with transplant by HE staining, immunohistochemistry and special staining observed under the microscopy. Findings The whole lungs displayed diffuse congestive appearance and partly haemorrhagic necrosis MESHD on gross examination. The haemorrhagic necrosis MESHD was prominently present in outer edge of the right lower lung. The cut surfaces of the lung displayed severe congestive and haemorrhagic changes. The main pathological changes showed massive pulmonary interstitial fibrosis MESHD, and partly hyaline degeneration MESHD, variable degrees of hemorrhagic pulmonary infarction MESHD. Small vessels hyperplasia MESHD, vessel wall thickening, lumen stenosis, occlusion and microthrombosis MESHD formation. Focal monocytes, lymphocytes and plasma SERO cells infiltrating into pulmonary HP interstitium. Bronchiolitis HP Bronchiolitis MESHD and alveolitis with proliferation, atrophy MESHD, desquamation MESHD and squamous MESHD metaplasia of epithelial cells. Atrophy MESHD, vacuolar degeneration, proliferation, desquamation MESHD and squamous MESHD metaplasia in alveolar epithelial MESHD cells. Alveolar MESHD cavity congestion was prominent, and contained mucus, edema HP edema MESHD fluid, desquamated epithelial cells, and inflammatory cells. We also found several multinucleate giant cells and intracytoplasmic viral inclusion bodies. Special stains including Masson stain, sirius red staining, reticular fibers staining indicated massive pulmonary interstitial fibrosis MESHD. Immunohistochemistry showed positive for immunity cells including CD3, CD4, CD8, CD20, CD79a, CD5, CD38 and CD68. Interpretation We demonstrate the pathological findings of critical patient with COVID-19, which might provide a deep insight of the pathogenesis and severity of this disease.

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MeSH Disease
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