Chitosan and Chitooligosaccharides: Antifungal Potential and Structural Insights.

Chitosan is a cationic polysaccharide derived from chitin deacetylation. This polysaccharide and its oligosaccharides have many biological activities and can be used in several fields due to their favorable characteristics, such as biodegradability, biocompatibility, and nontoxicity. This review aims to explore the antifungal potential of chitosan and chitooligosaccharides along with the conditions used for the activity and mechanisms of action they use to kill fungal cells. The sources, chemical properties, and applications of chitosan and chitooligosaccharides are discussed in this review. It also addresses the threat fungi pose to human health and crop production and how these saccharides have proven to be effective against these microorganisms. The cellular processes triggered by chitosan and chitooligosaccharides in fungal cells, and prospects for their use as potential antifungal agents are also examined.

Antibacterial and antifungal action of CTAB-containing silica nanoparticles against human pathogens.

New antibiotic agents are urgently needed worldwide to combat the increasing tolerance and resistance of pathogenic fungi and bacteria to current antimicrobials. Here, we looked at the antibacterial and antifungal effects of minor quantities of cetyltrimethylammonium bromide (CTAB), ca. 93.8 mg g-1, on silica nanoparticles (MPSi-CTAB). Our results show that MPSi-CTAB exhibits antimicrobial activity against Methicillin-resistant Staphylococcus aureus strain (S. aureus ATCC 700698) with MIC and MBC of 0.625 mg mL-1 and 1.25 mg mL-1, respectively. Additionally, for Staphylococcus epidermidis ATCC 35984, MPSi-CTAB reduces MIC and MBC by 99.99% of viable cells on the biofilm. Furthermore, when combined with ampicillin or tetracycline, MPSi-CTAB exhibits reduced MIC values by 32- and 16-folds, respectively. MPSi-CTAB also exhibited in vitro antifungal activity against reference strains of Candida, with MIC values ranging from 0.0625 to 0.5 mg mL-1. This nanomaterial has low cytotoxicity in human fibroblasts, where over 80% of cells remained viable at 0.31 mg mL-1 of MPSi-CTAB. Finally, we developed a gel formulation of MPSi-CTAB, which inhibited in vitro the growth of Staphylococcus and Candida strains. Overall, these results support the efficacy of MPSi-CTAB with potential application in the treatment and/or prevention of infections caused by methicillin-resistant Staphylococcus and/or Candida species.

Pharmacist-led medication reconciliation in emergency hospital services in Brazil: A scoping review.

OBJECTIVE: This scoping review aimed to map the evidence of pharmacist-led  medication reconciliation in hospital emergency services in Brazil. METHOD: We performed a scoping review by searching electronic databases LILACS, Pubmed, Embase, CINAHL, Scopus, Web of Science, Clinical  trials, REBEC e Cochrane and conducting a manual search to identify studies published up to 20 October 2021. Studies that addressed pharmacist-led medication reconciliation in hospital emergency  services in Brazil, regardless of clinical conditions, and outcomes evaluated,  were included. RESULTS: A total of 168 studies were retrieved, with three matching the inclusion criteria. Most studies performed pharmacist-led medication reconciliation at emergency department admissions, but it was not  the primary pharmaceutical attribution in this setting. Medication errors were identified during the medication reconciliation process, being drug  omission the most reported. Studies did not describe the concerns in collecting the best medication history from patients and the humanistic,  economic, and clinical outcomes of pharmacist-led medication reconciliation. Conclusions: This scoping review revealed the lack of evidence about the  pharmacist-led medication reconciliation process in the emergency setting in  Brazil. The findings suggest the need for future studies in this context.

OBJETIVO: Documentar la evidencia de la conciliación de medicamentos dirigida  por farmacéuticos en los servicios de emergencia  hospitalarios en Brasil.Método: Se realizó una revisión sistemática exploratoria de bases de datos  electrónicas LILACS, Pubmed, Embase, CINAHL, Scopus, Web of Science,  Clinical Trials, REBEC y Cochrane para identificar estudios publicados hasta el  20 de octubre de 2021. Los estudios incluidos abordaban la conciliación de  medicamentos dirigida por farmacéuticos en los servicios de emergencia  hospitalarios en Brasil, independientemente de las condiciones clínicas y los  resultados evaluados. RESULTADOS: Se recuperaron un total de 168 estudios, tres de los cuales cumplieron los criterios de inclusión. La mayoría de los estudios  realizaban la conciliación de la medicación dirigida por el farmacéutico en las admisiones al servicio de urgencias, pero ésta no era la principal atribución farmacéutica en ese contexto. Los errores de medicación fueron  identificados durante el proceso de conciliación de medicamentos, siendo la omisión de medicamentos el error más reportado. Los estudios no hacían referencia a la importancia de recabar un historial farmacológico lo más completo posible ni a los resultados humanísticos, económicos y clínicos de la  conciliación de medicamentos dirigida por farmacéuticos. CONCLUSIONES: Esta revisión sistemática exploratoria reveló la falta de evidencia sobre el proceso de conciliación de medicamentos dirigido por  farmacéuticos en los servicios de urgencias de Brasil. Los hallazgos sugieren la  necesidad de seguir investigando sobre este asunto.

Conciliación de medicamentos dirigida por farmacéuticos en los servicios de urgencias hospitalarias de Brasil: Revisión sistemática exploratoria / Pharmacist-led medication reconciliation in emergency hospital services in Brazil: A scoping review

Objetivo: Documentar la evidencia de la conciliación de medicamentos dirigida por farmacéuticos en los servicios de emergencia hospitalarios en Brasil.Método: Se realizó una revisión sistemática exploratoria de bases dedatos electrónicas LILACS, Pubmed, Embase, CINAHL, Scopus, Web ofScience, Clinical Trials, REBEC y Cochrane para identificar estudios publicados hasta el 20 de octubre de 2021. Los estudios incluidos abordabanla conciliación de medicamentos dirigida por farmacéuticos en los servicios de emergencia hospitalarios en Brasil, independientemente de lascondiciones clínicas y los resultados evaluados.Resultados: Se recuperaron un total de 168 estudios, tres de los cualescumplieron los criterios de inclusión. La mayoría de los estudios realizaban la conciliación de la medicación dirigida por el farmacéutico en lasadmisiones al servicio de urgencias, pero ésta no era la principal atribución farmacéutica en ese contexto. Los errores de medicación fueron identificados durante el proceso de conciliación de medicamentos, siendo laomisión de medicamentos el error más reportado. Los estudios no hacían referencia a la importancia de recabar un historial farmacológico lo máscompleto posible ni a los resultados humanísticos, económicos y clínicosde la conciliación de medicamentos dirigida por farmacéuticos.(AU)

Objective: This scoping review aimed to map the evidence of pharmacist-led medication reconciliation in hospital emergency services in Brazil.Method: We performed a scoping review by searching electronic databases LILACS, Pubmed, Embase, CINAHL, Scopus, Web of Science,Clinical trials, REBEC e Cochrane and conducting a manual search toidentify studies published up to 20 October 2021. Studies that addressedpharmacist-led medication reconciliation in hospital emergency servicesin Brazil, regardless of clinical conditions, and outcomes evaluated, wereincluded.Results: A total of 168 studies were retrieved, with three matching theinclusion criteria. Most studies performed pharmacist-led medicationreconciliation at emergency department admissions, but it was not theprimary pharmaceutical attribution in this setting. Medication errors wereidentified during the medication reconciliation process, being drug omission the most reported. Studies did not describe the concerns in collectingthe best medication history from patients and the humanistic, economic,and clinical outcomes of pharmacist-led medication reconciliation. Conclusions: This scoping review revealed the lack of evidence aboutthe pharmacist-led medication reconciliation process in the emergencysetting in Brazil. The findings suggest the need for future studies in thiscontext. (AU)

Plant antimicrobial peptides: An overview about classification, toxicity and clinical applications.

Antimicrobial peptides, also known as AMPs, are cationic and amphipathic molecules found in all living organisms, composing part of the defense mechanisms against various pathogens, including fungi, viruses, bacteria, and nematodes. AMPs derived from plants are the focus of this review because they have gained attention as alternative molecules to overcome pathogen resistance as well as new drugs to combat cancer. Plant AMPs are generally classified based on their sequences and structures, as thionins, defensins, hevein-like peptides, knottins, stable-like peptides, lipid transfer proteins, snakins, and cyclotides. Although there are studies reporting the toxicity of plant AMPs to nontarget cells or limitations of oral administration, synthetic AMPs with reduced toxicity or allergenicity, or greater resistance to peptidases can be designed by using different bioinformatics tools. Thus, this review provides information about the classification of plant AMPs, their characteristics, mechanisms of action, hemolytic and cytotoxic potential, possible applications in the medical field, and finally, the use of bioinformatics to help design synthetic AMPs with improved features.

Role of neutrophil-lymphocyte ratio as a predictive factor of glioma tumor grade: A systematic review.

Gliomas are the main type of intra-axial primary brain tumors. We performed a systematic review of studies on the neutrophil-to-lymphocyte ratio (NLR) and its role in the prognosis of patients with gliomas. An English-language literature-based search, using the PubMed and Biblioteca Virtual em Saúde databases, was conducted for papers published until May 2, 2020. The quality of the selected articles was stratified using the Newcastle-Ottawa scale's criteria. We found 137 publications for a query string. After applying the inclusion criteria, 13 articles were selected. Seven studies assessed overall survival and found high NLR values associated with poor overall survival. Six studies approached the issue of tumor grading and differential diagnosis and demonstrated that patients with high NLR values were diagnosed with high-grade gliomas. NLR is a low-cost method and an effective prognostic factor associated with tumor grading and OS in patients with gliomas.

Is neutrophil-lymphocyte ratio a useful tool for predicting outcome in subarachnoid hemorrhage? A systematic review.

Ruptured intracranial aneurysms, as the leading cause of spontaneous subarachnoid hemorrhage (aSAH), represents an emergency with high morbi-mortality. The comprehension of the underlying pathology that involves inflammatory and immune responses, through the neutrophil-to-lymphocyte ratio (NLR), could help to predict complications such as delayed cerebral ischemia (DCI) or rebleeding and the functional outcome. Systematic review of English-based literature through PubMed and Biblioteca Vitural em Saúde (BVS) to find papers discussing the use of NLR in the aSAH setting. Area-under-curve (AUC) of receiver operating characteristics (ROC), cutoff value, sensitivity, and specificity were retrieved. From 53 articles included, 4 papers were evaluated after exclusion criteria. Rebleeding could be predicted with a NLR cutoff value of 9.88 (sensitivity 72.3%, specificity 63.3%). The mean cutoff value for DCI was 12.85, with sensitivity 66.3% and specificity 75.8%. Finally, a worse 3-month functional outcome could be predicted with a mean sensitivity of 73.3% and a mean specificity of 54%. NLR is a new issue in scientific community, especially neurosurgery. The current understanding points to a multifactorial process after aSAH that emerges as alterations on the NLR. As a measurement readily available and cost-effect after admission of the patient, its use signals that patients that need expedite surgical treatment or more aggressive treatment for vasospasm. As other medical subspecialties already use this ratio to predict outcomes, the literature reviewed by this paper constitute the earliest clues that higher NLR predicts re-bleeding, DCI, and functional outcome.

Secretory production in Escherichia coli of a GH46 chitosanase from Chromobacterium violaceum, suitable to generate antifungal chitooligosaccharides.

A chitosanase (CvCsn46) from Chromobacterium violaceum ATCC 12472 was produced in Escherichia coli, purified, and partially characterized. When subjected to denaturing polyacrylamide gel electrophoresis, the enzyme migrated as two protein bands (38 and 36 kDa apparent molecular masses), which were both identified as CvCsn46 by mass spectrometry. The enzyme hydrolyzed colloidal chitosan, with optimum catalytic activity at 50 °C, and two optimum pH values (at pH 6.0 and pH 11.0). The chitosanolytic activity of CvCsn46 was enhanced by some ions (Ca2+, Co2+, Cu2+, Sr2+, Mn2+) and DTT, whereas Fe2+, SDS and ß-mercaptoethanol completely inhibited its activity. CvCsn46 showed a non-Michaelis-Menten kinetics, characterized by a sigmoidal velocity curve (R2 = 0.9927) and a Hill coefficient of 3.95. ESI-MS analysis revealed that the hydrolytic action of CvCsn46 on colloidal chitosan generated a mixture of low molecular mass chitooligosaccharides, containing from 2 to 7 hexose residues, as well as D-glucosamine. The chitosan oligomers generated by CvCsn46 inhibited in vitro the mycelial growth of Lasiodiplodia theobromae, significantly reducing mycelium extension and inducing hyphal morphological alterations, as observed by scanning electron microscopy. CvCsn46 was characterized as a versatile biocatalyst that produces well-defined chitooligosaccharides, which have potential to control fungi that cause important crop diseases.

Structural and functional features of a class VI chitinase from cashew (Anacardium occidentale L.) with antifungal properties.

A partial cDNA sequence from Anacardium occidentale CCP 76 was obtained, encoding a GH19 chitinase (AoChi) belonging to class VI. AoChi exhibits distinct structural features in relation to previously characterized plant GH19 chitinases from classes I, II, IV and VII. For example, a conserved Glu residue at the catalytic center of typical GH19 chitinases, which acts as the proton donor during catalysis, is replaced by a Lys residue in AoChi. To verify if AoChi is a genuine chitinase or is a chitinase-like protein that has lost its ability to degrade chitin and inhibit the growth of fungal pathogens, the recombinant protein was expressed in Pichia pastoris, purified and biochemically characterized. Purified AoChi (45 kDa apparent molecular mass) was able to degrade colloidal chitin, with optimum activity at pH 6.0 and at temperatures from 30 °C to 50 °C. AoChi activity was completely lost when the protein was heated at 70 °C for 1 h or incubated at pH values of 2.0 or 10.0. Several cation ions (Al3+, Cd2+, Ca2+, Pb2+, Cu2+, Fe3+, Mn2+, Rb+, Zn2+ and Hg2+), chelating (EDTA) and reducing agents (DTT, ß-mercaptoethanol) and the denaturant SDS, drastically reduced AoChi enzymatic activity. AoChi chitinase activity fitted the classical Michaelis-Menten kinetics, although turnover number and catalytic efficiency were much lower in comparison to typical GH19 plant chitinases. Moreover, AoChi inhibited in vitro the mycelial growth of Lasiodiplodia theobromae, causing several alterations in hyphae morphology. Molecular docking of a chito-oligosaccharide in the substrate-binding cleft of AoChi revealed that the Lys residue (theoretical pKa = 6.01) that replaces the catalytic Glu could act as the proton donor during catalysis.