SARS-CoV-2 (COVID-19) en pacientes con algún grado de inmunosupresión

BackgroundIt is not clear whether patients with some degree of immunosuppression have worse outcomes in SARS-CoV-2 infection, compared to healthy people.ObjectiveTo carry out a narrative review of the information available on infection by SARS-CoV-2 in immunosuppressed patients, especially patients with cancer, transplanted, neurological diseases, primary and secondary immunodeficiencies.ResultsPatients with cancer and recent cancer treatment (chemotherapy or surgery) and SARS-CoV-2 infection have a higher risk of worse outcomes. In transplant patients (renal, cardiac and hepatic), with neurological pathologies (multiple sclerosis [MS], neuromyelitis optica [NMODS], myasthenia gravis [MG]), primary immunodeficiencies and infection with human immunodeficiency virus (HIV) in association with immunosuppressants, studies have shown no tendency for worse outcomes.ConclusionGiven the little evidence we have so far, the behaviour of SARS-CoV-2 infection in immunosuppressed patients is unclear, but current studies have not shown worse outcomes, except for patients with cancer.     

Anti-inflammatory and analgesic activities of the ethanolic extracts from Zanthoxylum riedelianum (Rutaceae) leaves and stem bark

We have evaluated the anti-inflammatory and analgesic properties of the leaves (LCE) and stem bark (BCE) crude extracts of Zanthoxylum riedelianum (Rutaceae). Different fractions of the stem bark extract (hexane, BCEH; dichloromethane, BCED; ethyl acetate, BCEE; and lyophilized aqueous residual, BCEW) were also investigated. We studied the effects of the extracts and fractions using the rat paw oedema test induced by carrageenan, dextran, histamine or nystatin; the mouse abdominal constriction test; the mouse hot-plate test (only for LCE and BCE); and the mouse formalin test. Both extracts and all BCE fractions displayed anti-inflammatory activity in the carrageenan-induced oedema model, but not for dextran, histamine or nystatin. Considering the analgesic models, both extracts showed antinociceptive activity, but BCE was more active than LCE in models of central pain. All BCE fractions showed significant inhibition in the abdominal constriction test and in both phases of the formalin test. When BCED was submitted to phytochemical procedures it led to the isolation of six lignans (sesamin, methylpluviatolide, dimethylmatairesinol, piperitol-4(')-O-(gamma),(gamma)-dimethylallyl ether, kaerophyllin and hinokinin), and a triterpene (lupeol). Inhibition of cyclooxygenase and its metabolites may have been involved in the mechanism of action of this plant, considering previous studies reporting the anti-inflammatory and analgesic activity for the identified lignans, as well as anti-inflammatory activity for lupeol.     

Effect of Baccharis dracunculifolia D.C. (Asteraceae) extracts and its isolated compounds on macrophage activation

Baccharis dracunculifolia D.C. (Asteraceae), a shrub which grows wild in Brazil, is the main botanical source of Brazilian green propolis. Since Brazilian propolis shows an immunomodulatory activity, the goal of this work was to evaluate the action of B. dracunculifolia extracts and some of its isolated compounds on reactive oxygen intermediate (H(2)O(2)) production by macrophages obtained from male BALB/c mice. The results showed that the leaf (Bd-L) (25, 50, and 100 microg mL(-1)), leaf rinse (Bd-LR) (25 microg mL(-1)), and the root (Bd-R) (25 microg mL(-1)) extracts enhanced H2O2 release by macrophages. A phytochemical study of the root and leaves of B. dracunculifolia was carried out. The chromatographic fractionation of Bd-R, using several techniques, afforded the isolation of baccharis oxide (1), friedelanol (2), viscidone (11), 11-hydroxy-10,11-dihydro-euparin (12), and 6hydroxy-tremetona (13), while Bd-LR gave the following isolated compounds: baccharis oxide (1), friedelanol (2), isosakuranetin (3), aromadendrin-4'-methyl ether (4), dihydrocumaric acid (5), baccharin (6), hautriwaic acid lactone (7), hautriwaic acid acetate (8), drupanin (9), and cumaric acid (10). Among the isolated compounds, baccharis oxide (1) and friedelanol (2) increased H2O2 production at a concentration of 100 microM. This is the first time that the presence of compounds 7, 8, 12, and 13 in B. dracunculifolia has been reported. Based on these results it is suggested that the crude extracts and some isolated compounds from B. dracunculifolia display an immunomodulatory action.     

Effects of propolis crude hydroalcoholic extract on chromosomal aberrations induced by doxorubicin in rats

Propolis has been reported to display a broad spectrum of biological activities such as anticancer, antioxidant, anti-inflammatory, antibiotic and antifungal properties, among others. There is great interest not only in the determination of the chemical composition of propolis but also in the understanding of the mechanisms related to its therapeutic actions. In this respect, the aim of the present investigation was to study the influence of both simultaneous (6, 12 and 24 mg/kg b. w.) and subacute (12 mg/kg b. w.) treatment with a crude hydroalcoholic extract of propolis on the frequency of chromosome aberrations induced by the chemotherapeutic agent doxorubicin (DXR) in Wistar rat bone marrow cells. HPLC analysis of the crude extract allowed the quantification of the phenolic compounds: caffeic acid, P-coumaric acid, aromadendrin 4'-methyl ether, 3-prenyl- P-coumaric acid (drupanin), isosakuranetin, kaempferide, 3,5-diprenyl- P-coumaric acid (artepellin C), baccharin and 2,2-dimethyl-6-carboxyethenyl-2 H-1-benzopyran. A total of 100 metaphase cells/animal were analyzed for chromosome aberration frequency and 1000 cells/animal were counted to obtain the mitotic index. The results showed that the dose of 12 mg propolis/kg b. w., administered either as a single dose or as subacute treatment, caused a statistically significant decrease in the frequency of chromosome damage induced by DXR compared to the group treated only with DXR. This reduction might be, in part, due to the presence of phenolic compounds in the studied propolis, which are able to capture free radicals produced by chemotherapeutic agents such as DXR.     

Constituents of Oxandra cf. xylopioides with anti-inflammatory activity

A new triterpenoid (1) derived from 24-methylcycloartanol was isolated from the leaves of Oxandra cf. xylopioides. An unusual structure of the new compound was assigned as 1, for which the name berenjenol is proposed, on the basis of the spectroscopic data of the natural product and of its derivatives 2 and 3. The leaves also afforded the known monoterpene isoespintanol (4). Compounds 1 and 4 significantly reduced the paw edema induced by carrageenan by 64% and 43%, at 3 h, respectively. Moreover, 4 reduced IL-1 beta production by 72% at 100 microM and reduced IL-1 beta mRNA synthesis.     

Effects of kefir fractions on innate immunity

Innate immunity that protects against pathogens in the tissues and circulation is the first line of defense in the immune reaction, where macrophages have a critical role in directing the fate of the infection. We recently demonstrated that kefir modulates the immune response in mice, increasing the number of IgA+ cells in the intestinal and bronchial mucosa and the phagocytic activity of peritoneal and pulmonary macrophages. The aim of this study was to further characterize the immunomodulating capacity of the two fractions of kefir (F1: solids including bacteria and F2: liquid supernatant), by studying the cytokines produced by cells from the innate immune system: peritoneal macrophages and the adherent cells from Peyer's patches. BALB/c mice were fed either kefir solid fraction (F1) or kefir supernatant (F2) for 2, 5 or 7 consecutive days. The number of cytokine (IL-1alpha, IFNgamma, TNFalpha, IL-6 and IL-10) producing cells was determined on peritoneal macrophages and adherent cells from Peyer's patches. Both kefir fractions (F1 and F2) induced similar cytokine profiles on peritoneal macrophages (only TNFalpha and IL-6 were up-regulated). All cytokines studied on adherent cells from Peyer's patches were enhanced after F1 and F2 feeding, except for IFNgamma after F2 administration. Moreover, the percentage of IL-10+cells induced by fraction F2 on adherent cells from Peyer's patches was significantly higher than the one induced by fraction F1. Different components of kefir have an in vivo role as oral biotherapeutic substances capable of stimulating immune cells of the innate immune system, to down-regulate the Th2 immune phenotype or to promote cell-mediated immune responses against tumours and also against intracellular pathogenic infections.     

Immunomodulating capacity of commercial fish protein hydrolysate for diet supplementation

Dietary proteins harbour bioactive peptides that can be released by a fermentation process. Fish proteins are a valuable and little-exploited source of potentially active biopeptides. The aim of this research was to evaluate the effects of a commercially available fermented fish protein concentrate (Seacure) (FPC) derived from a fermentation process, on the mucosal immune response in a murine model. BALB/c mice received the FPC or the non-fermented powder at different concentrations (0.20, 0.25 or 0.30mg/ml) for 2, 5 or 7 consecutive days. At the end of each feeding period, histological studies of the gut were carried out and the phagocytic activity of peritoneal macrophages, the number of IgA+ cells in the small intestine lamina propria and bronchial tissue and the number of IL-4+, IL-6+, IL-10+, IFNgamma+ and TNFalpha+ cells in the small intestine lamina propria were determined. Different accumulative doses of FPC did not induce any inflammatory immune response and the normal morphology of the small intestine was not affected. Phagocytic activity of peritoneal macrophages was enhanced following FPC administration at 0.3mg/ml for 7 consecutive days. The number of IgA+ cells increased in the small intestine lamina propria but not in the bronchial tissue. IL-4, IL-6 and IL-10 were all significantly increased in the lamina propria of the small intestine of animals that received FPC. At the same time, some pro-inflammatory cytokines such as IFNgamma and TNFalpha also increased, but the intestinal homoeostasis was maintained and no tissue damage was observed. We conclude that FPC is an immunomodulating food with a demonstrated capacity to enhance non-specific host defense mechanisms.     

Identification and distribution of mercury species in rat tissues following administration of thimerosal or methylmercury

Methylmercury (Met-Hg) is one the most toxic forms of Hg, with a considerable range of harmful effects on humans. Sodium ethyl mercury thiosalicylate, thimerosal (TM) is an ethylmercury (Et-Hg)-containing preservative that has been used in manufacturing vaccines in many countries. Whereas the behavior of Met-Hg in humans is relatively well known, that of ethylmercury (Et-Hg) is poorly understood. The present study describes the distribution of mercury as (-methyl, -ethyl and inorganic mercury) in rat tissues (brain, heart, kidney and liver) and blood following administration of TM or Met-Hg. Animals received one dose/day of Met-Hg or TM by gavage (0.5 mg Hg/kg). Blood samples were collected after 6, 12, 24, 48, 96 and 120 h of exposure. After 5 days, the animals were killed, and their tissues were collected. Total blood mercury (THg) levels were determined by ICP-MS, and methylmercury (Met-Hg), ethylmercury (Et-Hg) and inorganic mercury (Ino-Hg) levels were determined by speciation analysis with LC-ICP-MS. Mercury remains longer in the blood of rats treated with Met-Hg compared to that of TM-exposed rats. Moreover, after 48 h of the TM treatment, most of the Hg found in blood was inorganic. Of the total mercury found in the brain after TM exposure, 63% was in the form of Ino-Hg, with 13.5% as Et-Hg and 23.7% as Met-Hg. In general, mercury in tissues and blood following TM treatment was predominantly found as Ino-Hg, but a considerable amount of Et-Hg was also found in the liver and brain. Taken together, our data demonstrated that the toxicokinetics of TM is completely different from that of Met-Hg. Thus, Met-Hg is not an appropriate reference for assessing the risk from exposure to TM-derived Hg. It also adds new data for further studies in the evaluation of TM toxicity.     

Fungicide Activity of 5‐(4‐Chlorobenzylidene)‐(Z)‐2‐dimethylamino‐1,3‐thiazol‐4‐one against Cryptococcus Neoformans

The present work describes the synthesis and antifungal evaluation of new 5‐arylidene‐(Z)‐2‐dimethylamino‐1,3‐thiazol‐4‐ones 4a – f , obtained by the reaction of aromatic aldehydes 1 and rhodanine 2 followed by treatment with DMF. All compounds were tested against a panel of yeasts, hialohyphomycetes, and dermatophytes using the microbroth dilution method. Compounds 4a and 4c showed antifungal activity, with compound 4a being the most active one. Compound 4a demonstrated to be fungicidal rather than fungistatic and selective activity against Cryptococcus neoformans and dermatophytes. MIC₁₀₀, MIC₈₀, and MIC₅₀ of 4a were determined against a panel of clinical isolates of C. neoformans showing ranges of MICs between 2 and 16 μg/mL.