In Silico and In Vitro Analysis of Sulforaphane Anti-Candida Activity.

Oropharyngeal candidiasis/candidosis is a common and recurrent opportunistic fungal infection. Fluconazole (FLZ), one of the most used and effective antifungal agents, has been associated with a rise of resistant Candida species in immunocompromised patients undergoing prophylactic therapy. Sulforaphane (SFN), a compound from cruciferous vegetables, is an antimicrobial with yet controversial activities and mechanisms on fungi. Herein, the in silico and antifungal activities of SFN against C. albicans were investigated. In silico analyzes for the prediction of the biological activities and oral bioavailability of SFN, its possible toxicity and pharmacokinetic parameters, as well as the estimates of its gastrointestinal absorption, permeability to the blood-brain barrier and skin, and similarities to drugs, were performed by using different software. SFN in vitro anti-Candida activities alone and in combination with fluconazole (FLZ) were determined by the broth microdilution method and the checkerboard, biofilm and hyphae formation tests. Amongst the identified probable biological activities of SFN, nine indicated an antimicrobial potential. SFN was predicted to be highly absorbable by the gastrointestinal tract, to present good oral availability, and not to be irritant and/or hepatotoxic. SFN presented antifungal activity against C. albicans and prevented both biofilm and hyphae formation by this microorganism. SFN was additive/synergistic to FLZ. Overall, the data highlights the anti-Candida activity of SFN and its potential to be used as an adjuvant therapy to FLZ in clinical settings.

Decrease in CD8+CD45+CCR7+CD62L+ T cells in individuals vaccinated with Sinovac-CoronaVac following COVID-19 infection.

Vaccines induce antibodies, but T cell responses are also important for protection against Coronavirus disease 2019. Here, we analyzed the frequency of memory T cells in infected and/or vaccinated individuals and observed a decrease in central memory T cells in individuals who were vaccinated following COVID-19 infection.

Cinnamaldehyde Increases the Survival of Mice Submitted to Sepsis Induced by Extraintestinal Pathogenic Escherichia coli.

Several natural products have been investigated for their bactericidal potential, among these, cinnamaldehyde. In this study, we aimed to evaluate the activity of cinnamaldehyde in the treatment of animals with sepsis induced by extraintestinal pathogenic E. coli. Initially, the E. coli F5 was incubated with cinnamaldehyde to evaluate the minimum inhibitory and minimum bactericidal concentration. Animal survival was monitored for five days, and a subset of mice were euthanized after 10 h to evaluate histological, hematological, and immunological parameters, as well as the presence of bacteria in the organs. On the one hand, inoculation of bacterium caused the death of 100% of the animals within 24 h after infection. On the other hand, cinnamaldehyde (60 mg/kg) was able to keep 40% of mice alive after infection. The treatment significantly reduced the levels of cytokines in serum and peritoneum and increased the production of cells in both bone marrow and spleen, as well as lymphocytes at the infection site. Cinnamaldehyde was able to reduce tissue damage by decreasing the deleterious effects for the organism and contributed to the control of the sepsis and survival of animals; therefore, it is a promising candidate for the development of new drugs.

Pic-Producing Escherichia coli Induces High Production of Proinflammatory Mediators by the Host Leading to Death by Sepsis.

Escherichia coli is an important pathogen responsible for a variety of diseases. We have recently shown that Pic, a serine protease secreted by E. coli, mediates immune evasion by the direct cleavage of complement molecules. The aim of this study was to investigate the action of a Pic-producing bacteria in a murine model of sepsis. Mice were infected with Pic-producing E. coli (F5) or F5∆pic mutant. Animal survival was monitored for five days, and a subset of mice was euthanized after 12 h for sample acquisition. The inoculation of Pic-producing bacteria induced 100% death within 24 h. The colony forming units count in the organs was significantly higher in F5. Hematological analysis showed a decrease of total leukocytes. Nitric oxide and cytokines were detected in serum, as well as on peritoneal lavage of the F5 group in higher levels than those detected in the other groups. In addition, immunophenotyping showed a decrease of activated lymphocytes and macrophages in the F5 group. Therefore, Pic represents an important virulence factor, allowing the survival of the bacterium in the bloodstream and several organs, as well as inducing a high production of proinflammatory mediators by the host, and concomitantly a cellular immunosuppression, leading to sepsis and death.

Pic-producing escherichia coli induces high production of proinflammatory mediators by the host leading to death by sepsis

Escherichia coli is an important pathogen responsible for a variety of diseases. We have recently shown that Pic, a serine protease secreted by E. coli, mediates immune evasion by the direct cleavage of complement molecules. The aim of this study was to investigate the action of a Pic-producing bacteria in a murine model of sepsis. Mice were infected with Pic-producing E. coli (F5) or F5?pic mutant. Animal survival was monitored for five days, and a subset of mice was euthanized after 12 h for sample acquisition. The inoculation of Pic-producing bacteria induced 100% death within 24 h. The colony forming units count in the organs was significantly higher in F5. Hematological analysis showed a decrease of total leukocytes. Nitric oxide and cytokines were detected in serum, as well as on peritoneal lavage of the F5 group in higher levels than those detected in the other groups. In addition, immunophenotyping showed a decrease of activated lymphocytes and macrophages in the F5 group. Therefore, Pic represents an important virulence factor, allowing the survival of the bacterium in the bloodstream and several organs, as well as inducing a high production of proinflammatory mediators by the host, and concomitantly a cellular immunosuppression, leading to sepsis and death

Pic-producing escherichia coli induces high production of proinflammatory mediators by the host leading to death by sepsis

Escherichia coli is an important pathogen responsible for a variety of diseases. We have recently shown that Pic, a serine protease secreted by E. coli, mediates immune evasion by the direct cleavage of complement molecules. The aim of this study was to investigate the action of a Pic-producing bacteria in a murine model of sepsis. Mice were infected with Pic-producing E. coli (F5) or F5?pic mutant. Animal survival was monitored for five days, and a subset of mice was euthanized after 12 h for sample acquisition. The inoculation of Pic-producing bacteria induced 100% death within 24 h. The colony forming units count in the organs was significantly higher in F5. Hematological analysis showed a decrease of total leukocytes. Nitric oxide and cytokines were detected in serum, as well as on peritoneal lavage of the F5 group in higher levels than those detected in the other groups. In addition, immunophenotyping showed a decrease of activated lymphocytes and macrophages in the F5 group. Therefore, Pic represents an important virulence factor, allowing the survival of the bacterium in the bloodstream and several organs, as well as inducing a high production of proinflammatory mediators by the host, and concomitantly a cellular immunosuppression, leading to sepsis and death

High incidence of rhinovirus infection in children with community-acquired pneumonia from a city in the Brazilian pre-Amazon region.

Community-acquired pneumonia (CAP) is the leading cause of child death worldwide. Viruses are the most common pathogens associated with CAP in children, but their incidence varies greatly. This study investigated the presence of respiratory syncytial virus (RSV), adenovirus, human rhinovirus (HRV), human metapneumovirus (HMPV), human coronavirus (HCoV-OC43 and HCoV-NL63), and influenza A virus (FluA) in children with CAP and the contributing risk factors. Here, children with acute respiratory infections were screened by pediatrics; and a total of 150 radiographically-confirmed CAP patients (aged 3 months to 10 years) from two clinical centers in Sao Luis, Brazil were recruited. Patient's clinical and epidemiological data were recorded. Nasopharyngeal swab and tracheal aspirate samples were collected to extract viral nucleic acid. RSV, adenovirus, rhinovirus, FluA, HMPV, HCoV-OC43, and HCoV-NL63 were detected by real-time polymerase chain reaction. The severe CAP was associated with ages between 3 and 12 months. Viruses were detected in 43% of CAP patients. Rhinovirus infections were the most frequently identified (68%). RSV, adenovirus, FluA, and coinfections were identified in 14%, 14%, 5%, and 15% of children with viral infection, respectively. Rhinovirus was associated with nonsevere CAP (P = .014); RSV, FluA, and coinfections were associated with severe CAP (P < .05). New strategies for prevention and treatment of viral respiratory infections, mainly rhinovirus and RSV infections, are necessary.

Targeting the Immune System with Plant Lectins to Combat Microbial Infections.

The arsenal of drugs available to treat infections caused by eukaryotic and prokaryotic microbes has been declining exponentially due to antimicrobial resistance phenomenon, leading to an urgent need to develop new therapeutic strategies. Host-directed immunotherapy has been reported as an attractive option to treat microbial infections. It consists in the improvement of host defenses by increasing the expression of inflammatory mediators and/or controlling of inflammation-induced tissue injury. Although the in vitro antimicrobial and immunomodulatory activities of lectins have been extensively demonstrated, few studies have evaluated their in vivo effects on experimental models of infections. This review aims to highlight the experimental use of immunomodulatory plant lectins to improve the host immune response against microbial infections. Lectins have been used in vivo both prophylactically and therapeutically resulting in the increased survival of mice under microbial challenge. Other studies successfully demonstrated that lectins could be used in combination with parasite antigens in order to induce a more efficient immunization. Therefore, these plant lectins represent new candidates for management of microbial infections. Furthermore, immunotherapeutic studies have improved our knowledge about the mechanisms involved in host-pathogen interactions, and may also help in the discovery of new drug targets.

Phytochemical Characterization of Terminalia catappa Linn. Extracts and Their antifungal Activities against Candida spp.

Terminalia catappa Linn bark is used to treat dysentery by various populations in Southeast Asian countries, and its leaves have also been used in traditional medicine to treat hepatitis in India and the Philippines. Here, the antifungal actions of crude hydro-alcoholic extract (TcHE) and fractions from T. catappa leaves were assessed via the agar diffusion and microdilution tests on Candida reference strains and clinical isolates from patients with acquired immunodeficiency syndrome (AIDS). Additionally, the potential cytotoxic effects of TcHE were assessed on cultured human peripheral blood mononuclear cells (PBMC). T. catappa fractions and sub-fractions were analyzed by gas chromatography coupled to mass spectrometry with electron impact (GC/MS/EI), high-performance liquid chromatography coupled to mass spectrometry "electrospray" ionization in positive mode (HPLC/MS/MS/ESI+) and hydrogen nuclear magnetic resonance (1HNMR). TcHE and its fractions were able to inhibit the growth of all tested Candida strains with the n-butanol (FBuOH) fraction presenting the best antifungal activity. Testing of different FBuOH sub-fractions (SF) showed that SF10 was the most active against Candida spp. Fractioning of SF10 demonstrated that 5 out of its 15 sub-fractions were active against Candida spp., with SF10.5 presenting the highest activity. Chemical analysis of SF10 detected hydrolysable tannins (punicalin, punicalagin), gallic acid and flavonoid C-glycosides. Overall, the results showed that T. catappa L. leaf extract, fractions and sub-fractions were antifungal against Candida spp. and may be useful to treat diseases caused by this fungus.

In vitro Effects of Lemongrass Extract on Candida albicans Biofilms, Human Cells Viability, and Denture Surface.

The purpose of this study was to investigate whether immersion of a denture surface in lemongrass extract (LGE) has effects on C. albicans biofilms, human cell viability and denture surface. Minimal inhibitory concentration (MIC) and minimal fungicidal concentration (MFC) were performed for LGE against C. albicans. For biofilm analysis, discs were fabricated using a denture acrylic resin with surface roughness standardization. C. albicans biofilms were developed on saliva-coated discs, and the effects of LGE at MIC, 5XMIC, and 10XMIC were investigated during biofilm formation and after biofilm maturation. Biofilms were investigated for cell counting, metabolic activity, and microscopic analysis. The cytotoxicity of different concentrations of LGE to peripheral blood mononuclear cells (PBMC) was analyzed using MTT. The effects of LGE on acrylic resin were verified by measuring changes in roughness, color and flexural strength after 28 days of immersion. Data were analyzed by ANOVA, followed by a Tukey test at a 5% significance level. The minimal concentration of LGE required to inhibit C. albicans growth was 0.625 mg/mL, while MFC was 2.5 mg/mL. The presence of LGE during biofilm development resulted in a reduction of cell counting (p < 0.05), which made the MIC sufficient to reduce approximately 90% of cells (p < 0.0001). The exposure of LGE after biofilm maturation also had a significant antifungal effect at all concentrations (p < 0.05). When compared to the control group, the exposure of PBMC to LGE at MIC resulted in similar viability (p > 0.05). There were no verified differences in color perception, roughness, or flexural strength after immersion in LGE at MIC compared to the control (p > 0.05). It could be concluded that immersion of the denture surface in LGE was effective in reducing C. albicans biofilms with no deleterious effects on acrylic properties at MIC. MIC was also an effective and safe concentration for use.

Anti-Inflammatory Effects of a Pomegranate Leaf Extract in LPS-Induced Peritonitis.

Folk medicine suggests that pomegranate (peels, seeds and leaves) has anti-inflammatory properties; however, the precise mechanisms by which this plant affects the inflammatory process remain unclear. Herein, we analyzed the anti-inflammatory properties of a hydroalcoholic extract prepared from pomegranate leaves using a rat model of lipopolysaccharide-induced acute peritonitis. Male Wistar rats were treated with either the hydroalcoholic extract, sodium diclofenac, or saline, and 1 h later received an intraperitoneal injection of lipopolysaccharides. Saline-injected animals (i. p.) were used as controls. Animals were culled 4 h after peritonitis induction, and peritoneal lavage and peripheral blood samples were collected. Serum and peritoneal lavage levels of TNF-α as well as TNF-α mRNA expression in peritoneal lavage leukocytes were quantified. Total and differential leukocyte populations were analyzed in peritoneal lavage samples. Lipopolysaccharide-induced increases of both TNF-α mRNA and protein levels were diminished by treatment with either pomegranate leaf hydroalcoholic extract (57 % and 48 % mean reduction, respectively) or sodium diclofenac (41 % and 33 % reduction, respectively). Additionally, the numbers of peritoneal leukocytes, especially neutrophils, were markedly reduced in hydroalcoholic extract-treated rats with acute peritonitis. These results demonstrate that pomegranate leaf extract may be used as an anti-inflammatory drug which suppresses the levels of TNF-α in acute inflammation.

Late incomplete apposition after drug-eluting stent implantation: incidence and potential for adverse clinical outcomes

Aim Late acquired incomplete stent apposition (ISA) has been documented after drug-eluting stent (DES) implantation; However, its clinical consequences of late ISA after implantation sirolimus - (SES) or paclitaxel-eluting stent (PES) in a non-elected population. Methods and Results From our database, we analysed 195 consecutive patients who underwent DES placetement(175 with SES and 20 with PES) into native artery lesions and had serial intravascular ultrasound studies (IVUS) performed at index procedure and after 6-8 months. They were clinically followed for 29 +- 15 mounths (median of 24.3 months, interquartile range 18.1 - 31.6 months. They were clinically followed for a separation of at least one stent strut from the vessel wall in a segment without a side-branch and where the immediate post-implantation IVUS revealed complete apposition of stent struts...

Ineficácia do diltiazem na prevençäo da reestenose após angioplastia coronária / Inefficacy of Diltiazem in the Prevention of Restenosis Following Coronary Angioplasty

PURPOSE--To evaluate the efficacy of diltiazem in preventing restenosis after balloon angioplasty (PTCA). METHODS--Eighty-nine patients who were undergone to successful PTCA, were divided them in 2 groups (G): A) 44 patients (50 per cent ) who received diltiazem (180 mg tid) immediately after PTCA and were kept on it for 6 months); B) 45 patients (50 per cent ) who received placebo. Fifty two lesions were dilated in GA and 54 in GB. Patients were excluded from analysis for several reasons, including: necessity of diltiazem or others calcium channel blockers use; heart failure, bradicardia, AV block of any degree, PTCA to chronic total occlusion, ostial lesions and AMI less than 30 days prior to PTCA. Patients were randomized to either the active drug or placebo in a double blind fashion. Restenosis was defined as a 50 per cent lesion. Patients underwent late angiography either at 6 months or sooner if clinically indicated. RESULTS--Both G were similar to age > 70 years (A = 7 per cent vs B = 4 per cent -p = NS), sex (A = 13 per cent vs B = 11 per cent -p = NS), stable angina (A = 43 per cent vs B = 51 per cent ), unstable angina (A = 57 per cent vs B = 49 per cent -p = NS) and single vessel (A = 91 per cent vs B = 87 per cent -p = NS) or multivessel (A = 9 per cent vs B = 13 per cent -p = NS) PTCA. We studied 39/44 (89 per cent ) patients in GA and 43/45 (96 per cent ) in GB (p = NS). We observed restenosis in 17/39 (43 per cent ) in GA and 16/43 (37 per cent ) in GB (p = NS). The restenosis rate per lesion was 39 per cent in GA and 31 per cent in GB (p = NS). CONCLUSION--Diltiazem was ineffective in the prevention of restenosis following PTCA

Angioplastia coronária com uso de duplo baläo em artéria de grande calibre (hugging balloons) / Coronary Angioplasty with the Double Balloon Technique in Large Lumen Artery (Hugging Balloon)

Em paciente do sexo masculino, com 73 anos de idade, foi realizada angioplastia em artéria coronária direita de grande calibre, com lesäo severa associada a trombo, utilizando-se 2 balöes, colocados lado a lado, e insuflados simultaneamente (técnica denominada Hugging Balloons), garantindo a obtençäo de lesäo residual pequena e boa evoluçäo hospitalar

In this case report the transluminal coronary angioplasty was performed in a oversized right coronary artery with a severe lesion with thrombus inside, using the Hugging balloon technique (two dilatation balloon catheters used simultaneously). This technique achieved minimal residual lesion and had a favorable clinical outcome of the patient

Cateterismo cardíaco ambulatorial: análise da experiência acumulada em 10 meses / Outpatient Cardiac Catheterization. Analysis of a 10 Month Experience

Objetivo - Identificar pacientes que se prestem à estratégia do cateterismo cardíaco ambulatorial, com base nos aspectos sociais, riscos e complicações, por um período de 24 h. Métodos - Dos 2.126 casos submetidos a ca-teterismo cardíaco, no Instituto Dante Pazzanese de Cardiologia, no período de setembro de 1990 a junho de 1991, excluíramse: a) aqueles com idade superior a 75 anos; b) os com síndromes isquêmicas agudas; c) os com descompensação cardíaca classe IV (NYHA); d) os estudados pela técnica femoral com sistemas introdutores de alto perfil; e) os submetidos à anestesia geral, estudos eletrofisiológicos ou biópsias endomiocárdicas. Após a realização do exame, seguia-se período de observação de 3 h e, na ausência de complicacões, os pacientes re-cebiam alta com orientação de retorno obrigatório no dia seguinte, para reavaliação clínica. As eventuais complicacões deste período foram anotadas. Resultados - Dos 719pacientes elegíveis, 68% eram do sexo masculino, e a idade média era de 55,3 anos. Sessenta e um por cento estavam em classefuncional I da NYHA e a maioria (80,8%) foi estudada pela via braquial. Em 83% dos casos realizou-se a coronariografia, dos quais, 52%exibiam aterosclerose coronária. Quatrocentos e quatorze casos não receberam alta, pela seguintes razões: 217 por término do exame após as 18 h, 111 por razões sócio-econômicas, 23 por recusa do médico assistente, 8 devido à lesão do tronco da coronária esquerda e 55 por complicacões diversas. Todos os 305 pacientes que receberam alta ambulatorial não mostraram qualquer complicação na avaliação clínica do dia seguinte. Conclusão - O cateterismo ambulatorial demonstrou ser seguro em pacientes selecionados, viabilizando grande número de exames, com relativa economia de leitos e outros recursos hospitalares

Purpose - To identify patients suitable for out-patient cardiac catheterization strategy, based on social aspects, risks and complications, for a 24 hour period. Methods - In a series of 2.126 cases submitted to cardiac catheterization at the Instituto Dante Pazzanese de Cardiologia, between September 1990 and June 1991, were excluded: a) those over 75 years of age; b) the acute ischemic syndroms; c) those in NYHA functional class IV; d) patients who used 7 or 8 French femoral angiographtc catheters; e) patients who had undergone general anesthesia, electrophysiological study or endomyocardial biopsy. After the procedure, the patients were observed for a 3 hour period and in the absence of any complication, they were discharged from the hospital, returning the next day for clinical evaluation. If any complication occurred it was registered. Results - In a cohort of 719 eligible patients, 68% were male, with a mean age of 55,3 years. Sixty one per cent were in NYHA functional class I and most of them (80,8%) were studied by the brachial approach. Eigthy-three per cent of the patients were submitted to coronary angiography, with 52% of them having coronary artery disease. Four hundred and fourteen patients were not discharged on the same day: 217 did not have their procedures finish after 6p.m., 111forsocial-economical reasons, 23 because of theirphysician's refuse, 8 because of left main coronary disease, 55 because of any kind of complication. All the 305 patients who were discharged on the same day, did not have shown any complication in the next day evaluation. Conclusion - Outpatient cardiac catheterization is a safe technique in selected patients, making possible the accomplishment of a greater number of procedures improving bed utilization and decreasing hospitalar costs