COVID-19 and Pulmonary Angiogenesis: The Possible Role of Hypoxia and Hyperinflammation in the Overexpression of Proteins Involved in Alveolar Vascular Dysfunction.

COVID-19 has been considered a vascular disease, and inflammation, intravascular coagulation, and consequent thrombosis may be associated with endothelial dysfunction. These changes, in addition to hypoxia, may be responsible for pathological angiogenesis. This research investigated the impact of COVID-19 on vascular function by analyzing post-mortem lung samples from 24 COVID-19 patients, 10 H1N1pdm09 patients, and 11 controls. We evaluated, through the immunohistochemistry technique, the tissue immunoexpressions of biomarkers involved in endothelial dysfunction, microthrombosis, and angiogenesis (ICAM-1, ANGPT-2, and IL-6, IL-1ß, vWF, PAI-1, CTNNB-1, GJA-1, VEGF, VEGFR-1, NF-kB, TNF-α and HIF-1α), along with the histopathological presence of microthrombosis, endothelial activation, and vascular layer hypertrophy. Clinical data from patients were also observed. The results showed that COVID-19 was associated with increased immunoexpression of biomarkers involved in endothelial dysfunction, microthrombosis, and angiogenesis compared to the H1N1 and CONTROL groups. Microthrombosis and vascular layer hypertrophy were found to be more prevalent in COVID-19 patients. This study concluded that immunothrombosis and angiogenesis might play a key role in COVID-19 progression and outcome, particularly in patients who die from the disease.

COVID-19 and Lung Mast Cells: The Kallikrein-Kinin Activation Pathway.

Mast cells (MCs) have relevant participation in inflammatory and vascular hyperpermeability events, responsible for the action of the kallikrein-kinin system (KKS), that affect patients inflicted by the severe form of COVID-19. Given a higher number of activated MCs present in COVID-19 patients and their association with vascular hyperpermeability events, we investigated the factors that lead to the activation and degranulation of these cells and their harmful effects on the alveolar septum environment provided by the action of its mediators. Therefore, the pyroptotic processes throughout caspase-1 (CASP-1) and alarmin interleukin-33 (IL-33) secretion were investigated, along with the immunoexpression of angiotensin-converting enzyme 2 (ACE2), bradykinin receptor B1 (B1R) and bradykinin receptor B2 (B2R) on post-mortem lung samples from 24 patients affected by COVID-19. The results were compared to 10 patients affected by H1N1pdm09 and 11 control patients. As a result of the inflammatory processes induced by SARS-CoV-2, the activation by immunoglobulin E (IgE) and degranulation of tryptase, as well as Toluidine Blue metachromatic (TB)-stained MCs of the interstitial and perivascular regions of the same groups were also counted. An increased immunoexpression of the tissue biomarkers CASP-1, IL-33, ACE2, B1R and B2R was observed in the alveolar septum of the COVID-19 patients, associated with a higher density of IgE+ MCs, tryptase+ MCs and TB-stained MCs, in addition to the presence of intra-alveolar edema. These findings suggest the direct correlation of MCs with vascular hyperpermeability, edema and diffuse alveolar damage (DAD) events that affect patients with a severe form of this disease. The role of KKS activation in events involving the exacerbated increase in vascular permeability and its direct link with the conditions that precede intra-alveolar edema, and the consequent DAD, is evidenced. Therapy with drugs that inhibit the activation/degranulation of MCs can prevent the worsening of the prognosis and provide a better outcome for the patient.

Chemical Compounds and Biologic Activities: A Review of Cedrela Genus.

The genus Cedrela P. Browne, which belongs to the Meliaceae family, has eighteen species. Trees of this genus are of economic interest due to wood quality, as well as being the focus of studies because of relevant biologic activities as in other Meliaceae species. These activities are mainly related to limonoids, a characteristic class of compounds in this family. Therefore, the aim of this review is to perform a survey of the citations in the literature on the Cedrela genus species. Articles were found on quantitative and qualitative phytochemical studies of the Cedrela species, revealing the chemical compounds identified, such as aliphatics acid and alcohol, flavonoids, tocopherol, monoterpenes, sesquiterpenes, triterpenes, cycloartanes, steroids, and limonoids. Although some activities were tested, the majority of studies focused on the insecticidal, antifeedant, or insect growth inhibitor activities of this genus. Nonetheless, the most promising activities were related to their antimalarial and antitripanocidal effects, although further investigations are still needed.

Comparative study of Polypropylene versus Parietex composite®, Vicryl® and Ultrapro® meshes, regarding the formation of intraperitoneal adhesions.

PURPOSE: To compare the polypropylene mesh (Marlex®) to Vicryl®, Parietex composite® and Ultrapro® meshes to assess the occurrence of adhesions in the intraperitoneal implantation. METHODS: Sixty Wistar rats were allocated into three groups: PP+V, in which all the animals received a polypropylene and a Vicryl® mesh; PP+PC, with the implantation of polypropylene and Parietex composite® meshes and PP+UP, in which there was implantation of polypropylene and Ultrapro®. Macroscopic analysis was performed 28 days later to assess the percentage of mesh area affected by adhesion. RESULTS: in the PP+ V group, the Vicryl® mesh showed lower adhesion formation (p=0.013). In the PP+PC, there were no differences between polypropylene and Parietex composite® (p=0.765). In the PP+UP group, Ultrapro® and polypropylene meshes were equivalent (p=0.198) . CONCLUSION: All the four meshes led to adhesions, with the Vicryl® mesh showing the least potential for its formation.

Comparative study of Polypropylene versus Parietex composite®, Vicryl® and Ultrapro® meshes, regarding the formation of intraperitoneal adhesions

Abstract Purpose: To compare the polypropylene mesh (Marlex®) to Vicryl®, Parietex composite® and Ultrapro® meshes to assess the occurrence of adhesions in the intraperitoneal implantation. Methods: Sixty Wistar rats were allocated into three groups: PP+V, in which all the animals received a polypropylene and a Vicryl® mesh; PP+PC, with the implantation of polypropylene and Parietex composite® meshes and PP+UP, in which there was implantation of polypropylene and Ultrapro®. Macroscopic analysis was performed 28 days later to assess the percentage of mesh area affected by adhesion. Results: in the PP+ V group, the Vicryl® mesh showed lower adhesion formation (p=0.013). In the PP+PC, there were no differences between polypropylene and Parietex composite® (p=0.765). In the PP+UP group, Ultrapro® and polypropylene meshes were equivalent (p=0.198) . Conclusion: All the four meshes led to adhesions, with the Vicryl® mesh showing the least potential for its formation.

Comparison between polypropylene and polypropylene with poliglecaprone meshes on intraperitoneal adhesion formation / Estudo comparativo entre tela de polipropileno e poliglecaprone com tela de polipropileno na formação de aderências intraperitoneais

ABSTRACT Objective: to compare intraperitoneal adhesion formation in rats when using polypropylene and polypropylene with poliglecaprone meshes. Methods: we used twenty male, Wistar rats, divided in two groups. In group 1, the rats received the polypropylene mesh on their right side and the polypropylene with poliglecaprone mesh on their left side. In group 2 the position of the meshes was inverted. After 30 days, we analyzed the presence or not of adhesion formation, including only those over the meshes. The findings undergone an analysis through the Mann-Whitney test, at a level of significance of p≤0.05. Results: all meshes presented adhesions. We verified that, for the polypropylene meshes, the percentage of their surface covered by adhesions varied from 10.5 to 100%, with an average of 34.07±24.21%, while for the polypropylene with poliglecaprone mesh, the percentage covered by adhesions varied between 8.5% and 100%, with an average of 44.7±32.85% (p=0.12). Conclusion: both meshes lead to adhesion formation, none being superior to the other.

RESUMO Objetivo: comparar a formação de aderências intraperitoneais em ratos, com o uso de tela de polipropileno e tela composta de polipropileno e poliglecaprone. Métodos: vinte ratos Wistar machos, foram alocados em dois grupos. No grupo 1 os ratos receberam tela de polipropileno no lado direito e tela de polipropileno e poliglecaprone no lado esquerdo. No grupo 2 inverteu-se a posição das telas. Analisou-se a presença ou não de aderências após 30 dias, sendo incluídas apenas aderências sobre as telas. Os resultados foram submetidos à análise estatística, adotando-se como nível de significância p≤0,05. Resultados: todas as telas se apresentaram com aderências. Verificou-se que, na tela de polipropileno, a porcentagem de superfície coberta por aderências variou entre 10,5 a 100%, com média 34,07±24,21% enquanto que na tela de polipropileno e poliglecaprone a porcentagem de tela coberta por aderências variou entre 8,5 a 100%, com média 44,7±32,85% (p=0,12) . Conclusão: ambas as telas dão origem às aderências, não havendo vantagem de aplicação no reparo intraperitoneal de uma em relação à outra.

Comparison between polypropylene and polypropylene with poliglecaprone meshes on intraperitoneal adhesion formation.

OBJECTIVE: to compare intraperitoneal adhesion formation in rats when using polypropylene and polypropylene with poliglecaprone meshes. METHODS: we used twenty male, Wistar rats, divided in two groups. In group 1, the rats received the polypropylene mesh on their right side and the polypropylene with poliglecaprone mesh on their left side. In group 2 the position of the meshes was inverted. After 30 days, we analyzed the presence or not of adhesion formation, including only those over the meshes. The findings undergone an analysis through the Mann-Whitney test, at a level of significance of p≤0.05. RESULTS: all meshes presented adhesions. We verified that, for the polypropylene meshes, the percentage of their surface covered by adhesions varied from 10.5 to 100%, with an average of 34.07±24.21%, while for the polypropylene with poliglecaprone mesh, the percentage covered by adhesions varied between 8.5% and 100%, with an average of 44.7±32.85% (p=0.12). CONCLUSION: both meshes lead to adhesion formation, none being superior to the other.