Pathophysiology and possible treatments for olfactory-gustatory disorders in patients affected by COVID-19.

SARS-CoV-2 infects host cells mainly through the interaction between the virus's Spike protein and the viral receptors namely Angiotensin-Converting Enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2). Both are highly expressed in the gastrointestinal tract, in the nasal and bronchial epithelium, as well as in the type II alveolar epithelial cells. The aim of this review is to report the evidences from the scientific literature on the pathophysiology and the available treatments for olfactory-gustatory disorders in patients with COVID-19. The mechanisms involved in these disorders are still unclear and studies on specific therapies are scarce. However, it has been hypothesized that a decrease in the sensitivity of the sensory neurons as well as the co-expression of ACE2 and TMPRSS2 in the alveolar epithelial cells are the main causes of olfactory-gustatory disorders. The possible mechanisms described in the literature for changes in taste perception in patients with COVID-19 include olfactory disorders and a competitive activity of COVID-19 on ACE2 receptors in the taste buds. In addition, SARS-CoV-2 can bind to sialic acid receptors in the taste buds. In general, evidences show that there is no specific treatment for olfactory-taste disorders induced by SARS-CoV-2, even though some treatments have been used and have shown some promising results, such as olfactory training, intranasal application of sodium citrate and vitamin A, as well as systemic use of omega-3 and zinc. Corticosteroids have also been used as a pharmacological approach to treat patients with olfactory dysfunction with some contradictory results. The knowledge of the mechanisms by which SARS-CoV-2 influences the sensory systems and how effective therapies can treat the loss of smell and taste will have important implications on the understanding and clinical management of olfactory-taste disorders.

N-acylhydrazone Derivative-Loaded Cellulose Acetate Films: Thermoanalytical, Spectroscopic, Mechanical and Morphological Characterization.

Cellulose acetate (ACT) is one of the most important cellulose derivatives due to its biodegradability and low toxicity, presenting itself as one of the main substitutes for synthetic materials in the development of wound dressing films. The incorporation of a N-acylhydrazonic derivative (JR19), with its promising anti-inflammatory activity, may represent an alternative for the treatment of skin wounds. This work aims to develop and to physicochemically and mechanically characterize ACT films containing JR19. The films were prepared using the 'casting' method and further characterized by thermoanalytical and spectroscopic techniques. In addition, mechanical tests and morphological analysis were performed. Thermogravimetry (TG) and differential scanning calorimetry (DSC) analyses showed that the thermal events attributed to excipients and films were similar, indicating the absence of physical incompatibilities between ACT and JR19. Infrared spectroscopy showed that JR19 was incorporated into ACT films. The characteristic band attributed to C≡N (2279 to 2264 cm-1) was observed in the spectra of JR19, in that of the physical mixture of JR19/ACT, and, to a lesser extent, in the spectra of JR19 incorporated into the ACT film, suggesting some interaction between JR19 and ACT. X-ray diffraction (XRD) evidenced the suppression of the crystallinity of JR19 (diffraction peaks at 8.54°, 12.80°, 14.09°, 16.08°, 18.19°, 22.65°, 23.59°, 24.53°, 25.70°, 28.16° and 30.27°2θ) after incorporation into ACT films. The mechanical tests indicated the adequate integrity of the films and their resistance to bending. The morphological characterization showed JR19 crystals along with a homogeneously distributed porous structure throughout the surface of the films with an average diameter of 21.34 µm and 22.65 µm of the films alone and of those incorporating JR19F, respectively. This study was able to characterize the ACT films incorporating JR19, showing their potential to be further developed as wound healing dressings.

Nature as a source of drugs for ophthalmology / Natureza como fonte de drogas para oftalmologia

ABSTRACT Nature has always provided an unlimited source of biologically-active compounds. Since the beginning of mankind, humans have sought resources in fauna and flora to treat eye diseases. However, it was only after the Industrial Revolution that extracts of plants and substances of animal origin could be used safely, as has been determined by controlled interventional studies. Two major challenges faced by ocular pharmacology are the following: developing drugs that are able to reduce blindness due to glaucoma; and controlling the pain associated with eye surgery. The search for a drug that effectively lowers intraocular pressure and controls the progression of glaucoma has led to the development of various ocular hypotensive agents, such as physostigmine from the Physostigma venenosum plant. The anesthetic properties of cocaine, extracted from Erythroxylon coca, finally enabled surgical procedures in the eye. Several new natural compounds have been investigated in an attempt to identify substances with the potential to provide additional benefits to eye tissue and vision. Emerging evidence of anti-inflammatory, wound-healing, antimicrobial, antioxidant, antitumor, and antiangiogenic properties attributed to plant extracts and animal tissues has encouraged more investment in research in this area. Despite technological advances in synthesizing drugs, the pharmaceutical industry still seeks new active compounds from natural sources as well as from revisiting already-established naturally derived compounds. Although a large number of naturally-occurring compounds is known, this review article focuses on the bioactive substances with scientifically-proven benefits for ocular tissues.

RESUMO A natureza sempre se forneceu uma fonte inesgotável compostos biologicamente ativos. Desde o início da humanidade, os homens buscaram recursos na fauna e flora para tratar as doenças oculares. Porém, foi somente após a Revolução Industrial que extratos de plantas e substâncias de origem animal puderam ser utilizados com segurança, como foi determinado por estudos controlados de intervenção. Dois grandes desafios enfrentados pela farmacologia foram: desenvolver drogas capazes de reduzir a cegueira pelo glaucoma; e controlar a dor associada à cirurgia ocular. A busca por uma droga que efetivamente reduza a pressão intraocular e controle a progressão do glaucoma levou ao desenvolvimento de diversos hipotensores oculares, como a physostigmine da planta Physostigma venenosum. As propriedades anestésicas da cocaína, extraídas da Erythroxylon coca, finalmente permitiram procedimentos cirúrgicos no olho. Vários novos compostos naturais foram investigados na tentativa de identificar substâncias com potencial para fornecer benefícios adicionais ao tecido ocular e à visão. Evidências emergentes de propriedades anti-inflamatórias, de cicatrização de feridas, antimicrobianas, antioxidantes, antitumorais e antiangiogênicas atribuídas a extratos de plantas e tecidos animais estimularam mais investimentos em pesquisas nessa área. Apesar dos avanços tecnológicos na síntese de drogas, a indústria farmacêutica ainda busca novos princípios ativos a partir de fontes naturais, bem como revisita drogas derivadas já estabelecidas. Embora um grande número de compostos que ocorrem naturalmente seja conhecido, este artigo de revisão concentra-se nas substâncias bioativas com benefícios cientificamente comprovados para os tecidos oculares.

Nature as a source of drugs for ophthalmology.

Nature has always provided an unlimited source of biologically-active compounds. Since the beginning of mankind, humans have sought resources in fauna and flora to treat eye diseases. However, it was only after the Industrial Revolution that extracts of plants and substances of animal origin could be used safely, as has been determined by controlled interventional studies. Two major challenges faced by ocular pharmacology are the following: developing drugs that are able to reduce blindness due to glaucoma; and controlling the pain associated with eye surgery. The search for a drug that effectively lowers intraocular pressure and controls the progression of glaucoma has led to the development of various ocular hypotensive agents, such as physostigmine from the Physostigma venenosum plant. The anesthetic properties of cocaine, extracted from Erythroxylon coca, finally enabled surgical procedures in the eye. Several new natural compounds have been investigated in an attempt to identify substances with the potential to provide additional benefits to eye tissue and vision. Emerging evidence of anti-inflammatory, wound-healing, antimicrobial, antioxidant, antitumor, and antiangiogenic properties attributed to plant extracts and animal tissues has encouraged more investment in research in this area. Despite technological advances in synthesizing drugs, the pharmaceutical industry still seeks new active compounds from natural sources as well as from revisiting already-established naturally derived compounds. Although a large number of naturally-occurring compounds is known, this review article focuses on the bioactive substances with scientifically-proven benefits for ocular tissues.

Expansion and phenotypic changes of mouse bone marrow mesenchymal cells cultured with FGF-2 and facial nerve-conditioned medium / Expansión y cambios fenotípicos de células mesenquimales de médula ósea de ratón cultivadas con FGF-2 y medio condicionado por el nervio facial

Mesenchymal cells (MCs) exhibit great regenerative potential due to their intrinsic properties and ability to restore tissue function, either directly through transdifferentiation or indirectly through paracrine effects. This study aimed to evaluate morphometric and phenotypic changes in MCs grown with facial nerve-conditioned medium in the presence or absence of fibroblast growth factor 2 (FGF-2). For quantitative phenotypic analysis, the expression of GFAP, OX-42, MAP-2, β-tubulin III, NeuN, and NF-200 was analyzed by immunocytochemistry. Cells cultured with facial nerve-conditioned medium in the presence of FGF-2 expressed GFAP, OX-42, MAP-2, β-tubulin III, NeuN, and NF-200. On average, the area and perimeter of GFAP-positive cells were higher in the group cultured with facial nerve-conditioned medium compared to the group cultured with conditioned medium and FGF-2 (p=0.0001). This study demonstrated the plasticity of MCs for neuronal and glial lineages and opens up new research perspectives in cell therapy and trans.differentiation.

Las células mesenquimales (CM) exhiben un gran potencial regenerativo debido a sus propiedades intrínsecas y la capacidad de restaurar la función del tejido, ya sea directamente, a través de la transdiferenciación, o indirectamente, a través de efectos parácrinos. Este estudio tuvo como objetivo evaluar los cambios morfométricos y fenotípicos en CM cultivadas con medio condicionado por nervio facial en presencia o ausencia de factor de crecimiento de fibroblastos 2 (FGF-2). Para el análisis fenotípico cuantitativo, se analizó la expresión de GFAP, OX-42, MAP-2, β-tubulina III, NeuN y NF-200 mediante inmunocitoquímica. Las células cultivadas con medio condicionado por el nervio facial en presencia de FGF-2 expresaban GFAP, OX-42, MAP-2, β-tubulina III, NeuN y NF-200. En promedio, el área y el perímetro de las células positivas para GFAP fueron mayores en el grupo cultivado con medio condicionado por el nervio facial en comparación con el grupo cultivado con medio acondicionado y FGF-2 (p = 0,0001). Este estudio demostró la plasticidad de CM para linajes neuronales y gliales y abre nuevas perspectivas de investigación en terapia celular y transdiferenciación.

Phytochemical Analysis by HPLC-HRESI-MS and Anti-Inflammatory Activity of Tabernaemontana catharinensis.

Tabernaemontana catharinensis (Apocynaceae) has been popularly used by folk medicine because of its anti-inflammatory, analgesic, and antiophidic properties. This study aims to analyze the flavonoids composition of the hydroethanolic extract and of the ethyl acetate (EtOAc) and butanol (BuOH) fractions of T. catharinensis leaves, as well as to evaluate their anti-inflammatory activity using in vivo models. The phytochemical profile, determined by High-Performance Liquid Chromatography-High-Resolution Electrospray Ionization-Mass Spectrometry (HPLC-HRESI-MS), showed the presence of flavonoids mainly having an isorhamnetin nucleus. The anti-inflammatory activity was evaluated in carrageenan-induced paw edema (pre- and post-treatment) with oral administration of a T. catharinensis hydroethanolic extract (50, 100, and 150 mg/kg) and of organic fractions (50 mg/kg). The extract and fractions showed antiedematogenic activity by decreasing myeloperoxidase (MPO) production. In the zymosan-air-pouch model, the extract and fractions inhibited leukocyte migration and significantly decreased the levels of various proteins, such as MPO, interleukin (IL)-1ß, and tumor necrosis factor (TNF)-α. The cytotoxicity was evaluated by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, which revealed no cytotoxicity of the extract and the fractions. These results suggest that the hydroethanolic extract and organic fractions of T. catharinensis leaves have sufficient anti-inflammatory activity to support the popular use of this plant in the treatment of inflammatory disorders.

Inclusion Complexes of Copaiba (Copaifera multijuga Hayne) Oleoresin and Cyclodextrins: Physicochemical Characterization and Anti-Inflammatory Activity.

Complexation with cyclodextrins (CDs) is a technique that has been extensively used to increase the aqueous solubility of oils and improve their stability. In addition, this technique has been used to convert oils into solid materials. This work aims to develop inclusion complexes of Copaifera multijuga oleoresin (CMO), which presents anti-inflammatory activity, with ß-cyclodextrin (ß-CD) and hydroxypropyl-ß-cyclodextrin (HP-ß-CD) by kneading (KND) and slurry (SL) methods. Physicochemical characterization was performed to verify the occurrence of interactions between CMO and the cyclodextrins. Carrageenan-induced hind paw edema in mice was carried out to evaluate the anti-inflammatory activity of CMO alone as well as complexed with CDs. Physicochemical characterization confirmed the formation of inclusion complex of CMO with both ß-CD and HP-ß-CD by KND and SL methods. Carrageenan-induced paw edema test showed that the anti-inflammatory activity of CMO was maintained after complexation with ß-CD and HP-ß-CD, where they were able to decrease the levels of nitrite and myeloperoxidase. In conclusion, this study showed that it is possible to produce inclusion complexes of CMO with CDs by KND and SL methods without any change in CMO's anti-inflammatory activity.

Anti-inflammatory activity of aqueous extract and bioactive compounds identified from the fruits of Hancornia speciosa Gomes (Apocynaceae).

BACKGROUND: Hancornia speciosa Gomes (Apocynaceae), popularly known as "mangabeira," has been used in folk medicine to treat inflammatory disorders, hypertension, dermatitis, diabetes, liver diseases and gastric disorders. Although the ethnobotany indicates that its fruits can be used for the treatment of ulcers and inflammatory disorders, only few studies have been conducted to prove such biological activities. This study investigated the anti-inflammatory properties of the aqueous extract of the fruits of H. speciosa Gomes as well as its bioactive compounds using in vivo experimental models. METHODS: The bioactive compounds were identified by High Performance Liquid Chromatography coupled with diode array detector (HPLC-DAD) and Liquid Chromatography coupled with Mass Spectrometry (LC-MS). The anti-inflammatory properties were investigated through in vivo tests, which comprised xylene-induced ear edema, carrageenan-induced peritonitis and zymosan-induced air pouch. The levels of IL-1ß, IL-6, IL-12 and TNF-α were determined using ELISA. RESULTS: Rutin and chlorogenic acid were identified in the extract as the main secondary metabolites. In addition, the extract as well as rutin and chlorogenic acid significantly inhibited the xilol-induced ear edema and also reduced the cell migration in both carrageenan-induced peritonitis and zymosan-induced air pouch models. Reduced levels of cytokines were also observed. CONCLUSION: This is the first study that demonstrated the anti-inflammatory activity of the extract of H. speciosa fruits against different inflammatory agents in animal models, suggesting that its bioactive molecules, especially rutin and chlorogenic acid are, at least in part, responsible for such activity. These findings support the widespread use of Hancornia speciosa in popular medicine and demonstrate that its aqueous extract has therapeutical potential for the development of herbal drugs with anti-inflammatory properties.

Evaluation of chitosan gel with 1% silver sulfadiazine as an alternative for burn wound treatment in rats.

PURPOSE: Evaluation of the rheological, biological and therapeutic properties of a new topical formulation consisting of chitosan gel containing 1% silver sulfadiazine, as an alternative for the treatment of burn wounds. METHODS: An experimental study was done with 21 Wistar rats divided into three groups. Group I was treated with chitosan gel without the antimicrobial, group II was treated with chitosan gel with 1% silver sulfadiazine and group III was treated with commercially available 1% silver sulfadiazine cream. RESULTS: Due to its pseudoplastic characteristic and good bioadhesiveness, the chitosan gels showed a satisfactory retention time over the wounds. No statistical difference was found in the amount of drug released from the chitosan gel and commercially available cream, as well as in the healing time among the groups. Wounds treated with chitosan gel with silver sulfadiazine showed a higher fibroblast production and a better angiogenesis than in the other groups, which are important parameters on the evolution of the healing process. CONCLUSION: The topical use of chitosan gel in association with silver sulfadiazine ameliorated the neovascularization and inflammatory reaction in burn wounds. This new formulation showed advantageous rheological properties and efficient release of the drug.

Evaluation of chitosan gel with 1 percent silver sulfadiazine as an alternative for burn wound treatment in rats / Avaliação do gel de quitosana contendo sulfadiazina de prata 1 por cento como alternativa para o tratamento de queimaduras em ratos

PURPOSE: Evaluation of the rheological, biological and therapeutic properties of a new topical formulation consisting of chitosan gel containing 1 percent silver sulfadiazine, as an alternative for the treatment of burn wounds. METHODS: An experimental study was done with 21 Wistar rats divided into three groups. Group I was treated with chitosan gel without the antimicrobial, group II was treated with chitosan gel with 1 percent silver sulfadiazine and group III was treated with commercially available 1 percent silver sulfadiazine cream. RESULTS: Due to its pseudoplastic characteristic and good bioadhesiveness, the chitosan gels showed a satisfactory retention time over the wounds. No statistical difference was found in the amount of drug released from the chitosan gel and commercially available cream, as well as in the healing time among the groups. Wounds treated with chitosan gel with silver sulfadiazine showed a higher fibroblast production and a better angiogenesis than in the other groups, which are important parameters on the evolution of the healing process. CONCLUSION: The topical use of chitosan gel in association with silver sulfadiazine ameliorated the neovascularization and inflammatory reaction in burn wounds. This new formulation showed advantageous rheological properties and efficient release of the drug.

OBJETIVO: Avaliar as propriedades reológicas, biológicas e terapêuticas de uma nova formulação de uso tópico, a partir de um gel de quitosana, contendo sulfadiazina de prata a 1 por cento, no tratamento de queimaduras. MÉTODOS: Foi realizado estudo experimental com 21 ratos Wistar distribuídos em três grupos de sete animais. As queimaduras dos animais do grupo I foram tratadas com gel de quitosana sem antimicrobiano, o grupo II foi tratado com gel de quitosana contendo sulfadiazina de prata 1 por cento e o grupo III foi tratado com creme de sulfadiazina de prata 1 por cento, comumente utilizado no tratamento de queimados. RESULTADOS: Devido às características pseudoplásticas e à boa bioadesividade, os géis de quitosana apresentaram um tempo de retenção satisfatório sobre as feridas. A liberação da sulfadiazina de prata, bem como o tempo de cicatrização, não foram estatisticamente diferentes. Feridas tratadas com o gel de quitosana contendo sulfadiazina de prata apresentaram uma maior produção de fibroblastos e uma melhor angiogênese, comparando-se com os outros grupos, fatores que indicaram uma maior evolução no processo de cicatrização. CONCLUSÃO: O uso tópico do gel de quitosana com sulfadiazina de prata a 1 por cento melhorou a neovascularização e a reação inflamatória em queimaduras e essa nova formulação mostrou boas propriedades reológicas associadas a eficiente liberação do fármaco.