Chemical Characterization and Biological Activities of Jandaíra Stingless Bee Products (Melipona subnitida, Ducke, 1911): A Brief Review.

Melipona subnitida (Ducke, 1911), a species of stingless bee, popularly known as Jandaíra, has a wide distribution in the Brazilian Northeast region, being an important pollinator of the Caatinga biome. This bee produces products such as honey, geopropolis, pollen (saburá) and wax that are traditionally used for therapeutic purposes and some studies report the biological properties, as well as its chemical composition. This review aimed to select, analyze and gather data published in the literature focusing on the chemical profile and bioactivities described for M. subnitida products. Data collection was carried out through the Capes Journal Portal platform, using the following databases: Web of Science, Scopus, and PubMed. Original articles published in English and Portuguese were included, with no time limitation. The chemical composition of M. subnitida products has been investigated through chromatographic analysis, demonstrating the presence of a variety of phenolic compounds, such as flavonoids and phenylpropanoids, among other classes of secondary metabolites. These products also have several biological activities, including antioxidant, healing, antinociceptive, anti-inflammatory, antidepressant, antidyslipidemic, antiobesity, antifungal, antibacterial and prebiotic. Among the biological activities reported, the antioxidant activity was the most investigated. These data show that products derived from the stingless bee M. subnitida have promising bioactive compounds. This review provides useful information about the bioactivities and chemical profile of Melipona subnitida bee products, and a direction for future research, which should focus on understanding the mechanisms of action associated with the already elucidated pharmacological activities, as well as the bioactive properties of the main isolate's constituents identified in the chemical composition of these products.

Evaluation of the antibacterial and inhibitory activity of the MepA efflux pump of Staphylococcus aureus by riparins I, II, III, and IV.

The efflux pump mechanism contributes to the antibiotic resistance of widely distributed strains of Staphylococcus aureus. Therefore, in the present work, the ability of the riparins N-(4-methoxyphenethyl)benzamide (I), 2-hydroxy-N-[2-(4-methoxyphenyl)ethyl]benzamide (II), 2, 6-dihydroxy-N-[ 2-(4-methoxyphenyl)ethyl]benzamide (III), and 3,4,5-trimethoxy-N-[2-(4-methoxyphenethyl)benzamide (IV) as potential inhibitors of the MepA efflux pump in S. aureus K2068 (fluoroquinolone-resistant). In addition, we performed checkerboard assays to obtain more information about the activity of riparins as potential inhibitors of MepA efflux and also analyzed the ability of riparins to act on the permeability of the bacterial membrane of S. aureus by the fluorescence method with SYTOX Green. A molecular coupling assay was performed to characterize the interaction between riparins and MepA, and ADMET (absorption, distribution, metabolism, and excretion) properties were analyzed. We observed that I-IV riparins did not show direct antibacterial activity against S. aureus. However, combination assays with substrates of MepA, ciprofloxacin, and ethidium bromide (EtBr) revealed a potentiation of the efficacy of these substrates by reducing the minimum inhibitory concentration (MIC). Furthermore, increased EtBr fluorescence emission was observed for all riparins. The checkerboard assay showed synergism between riparins I, II, and III, ciprofloxacin, and EtBr. Furthermore, riparins III and IV exhibited permeability in the S. aureus membrane at a concentration of 200 µg/mL. Molecular docking showed that riparins I, II, and III bound in a different region from the binding site of chlorpromazine (standard pump inhibitor), indicating a possible synergistic effect with the reference inhibitor. In contrast, riparin IV binds in the same region as the chlorpromazine binding site. From the in silico ADMET prediction based on MPO, it could be concluded that the molecules of riparin I-IV present their physicochemical properties within the ideal pharmacological spectrum allowing their preparation as an oral drug. Furthermore, the prediction of cytotoxicity in liver cell lines showed a low cytotoxic effect for riparins I-IV.

Efflux Pump (QacA, QacB, and QacC) and ß-Lactamase Inhibitors? An Evaluation of 1,8-Naphthyridines against Staphylococcus aureus Strains.

The bacterial species Staphylococcus aureus presents a variety of resistance mechanisms, among which the expression of ß-lactamases and efflux pumps stand out for providing a significant degree of resistance to clinically relevant antibiotics. The 1,8-naphthyridines are nitrogen heterocycles with a broad spectrum of biological activities and, as such, are promising research targets. However, the potential roles of these compounds on bacterial resistance management remain to be better investigated. Therefore, the present study evaluated the antibacterial activity of 1,8-naphthyridine sulfonamides, addressing their ability to act as inhibitors of ß-lactamases and efflux pump (QacA/B and QacC) against the strains SA-K4414 and SA-K4100 of S. aureus. All substances were prepared at an initial concentration of 1024 µg/mL, and their minimum inhibitory concentrations (MIC) were determined by the broth microdilution method. Subsequently, their effects on ß-lactamase- and efflux pump-mediated antibiotic resistance was evaluated from the reduction of the MIC of ethidium bromide (EtBr) and ß-lactam antibiotics, respectively. The 1,8-naphthyridines did not present direct antibacterial activity against the strains SA-K4414 and SA-K4100 of S. aureus. On the other hand, when associated with antibiotics against both strains, the compounds reduced the MIC of EtBr and ß-lactam antibiotics, suggesting that they may act by inhibiting ß-lactamases and efflux pumps such as QacC and QacA/B. However, further research is required to elucidate the molecular mechanisms underlying these observed effects.

Antibacterial activity of eugenol on the IS-58 strain of Staphylococcus aureus resistant to tetracycline and toxicity in Drosophila melanogaster.

The indiscriminate use of antibiotics contributes significantly to the selection of bacteria resistant to several antibiotics. Among the resistance mechanisms are the Efflux Pumps which are responsible for extruding solutes from the cell cytoplasm through proteins in the cell membrane. Because of this, new strategies are needed to control multidrug-resistant pathogenic strains. In this way, the objective of this study was to evaluate the antibacterial activity of eugenol by inhibition of TetK Efflux Pump in strains of Staphylococcus aureus resistant to Tetracycline, in addition to evaluating its toxicity in Drosophila melanogaster. To determine the Minimum Inhibitory Concentration (MIC), the broth microdilution method was used. The modulated effect of antibiotic and Ethidium Bromide associated with eugenol in subinhibitory concentrations (MIC/8) was evaluated. To evaluate the toxic effect of eugenol on D. melanogaster, fumigation tests were used, in which the parameters of mortality and damage to the locomotor system were evaluated. The results showed that eugenol has no direct activity in S. aureus, with an MIC ≥1024 µg/mL. However, it demonstrated that the synergistic potential when associated with Tetracycline, reducing the MIC of the antibiotic, already associated with Ethidium Bromide, had an antagonistic effect. When the toxicity in D. melanogaster was evaluated, eugenol demonstrated a non-toxic profile, since it presented EC50: 2036 µL/mL in 48 h of exposure. In conclusion, eugenol had no relevant direct effect against S. aureus, however, it potentialized the action of the antibiotic by decreasing its MIC.

Anti-inflammatory effect, antibiotic potentiating activity against multidrug-resistant strains of Escherichia coli and Staphylococcus aureus, and evaluation of antibiotic resistance mechanisms by the ibuprofen derivative methyl 2-(-4-isobutylphenyl)propanoate.

The prevalence of multidrug-resistant (MDR) bacteria and the limited efficacy of current available antibiotics cause every year approximately 700 000 deaths per year. This study aimed to evaluate the anti-inflammatory effect and antibacterial potential of the ibuprofen derivative Methyl 2-(-4-isobutylphenyl)propanoate (MET-IBU). The molecular structure of MET-IBU was confirmed by Nuclear Magnetic Resonance (NMR) and, Attenuated Total Reflectance Fourier Transform Infrared spectroscopy (ATR-FTIR) spectroscopy. Our in vivo study using adult zebrafish model demonstrated that the ibuprofen derivative MET-IBU also possesses anti-inflammatory effect, and in vitro antibacterial activity assays showed that in the association of ampicillin, norfloxacin, and gentamicin with MET-IBU occurred reduction in the minimum inhibitory concentration (MIC) for MDR bacterial strains of Escherichia coli 06 and Staphylococcus aureus 10, indicating a potentiating in the growth inhibition of these pathogenic bacteria. Regarding the strain of Staphylococcus aureus K2068 (overexpressing mepA gene), a potentiation of ethidium bromide was found in the association with MET-IBU, indicating the action of this compound on the efflux pump mechanism present in this strains. This result corroborates the molecular docking study that indicated a high affinity of the MET-IBU with the MepA efflux pump. It was also noticed an antibiotic potentiating activity in the association MET-IBU with norfloxacin against strains of Staphylococcus aureus 1199B (overexpressing norA gene) when compared to the norfloxacin control. This enhanced antibiotic effect of MET-IBU is associated with a second resistance mechanism, which is due to the modification in the topoisomerase enzyme. These results bring attention to the ibuprofen derivative MET-IBU as possible candidate for the development of new options for the treatment of bacterial infections with protective anti-inflammatory action.

Adverse reactions and adherence to capecitabine: A prospective study in patients with gastrointestinal cancer.

INTRODUCTION: Capecitabine is an oral anticancer drug which can cause some adverse reactions and the great challenge for its use is to ensure the medication adherence. The aim of this study was to analyze adverse reactions and adherence to capecitabine in patients with gastrointestinal cancer. METHODS: A prospective study was performed in a tertiary teaching hospital in Brazil. Outpatients undergoing capecitabine treatment for colorectal or gastric cancer were followed for three cycles of treatment. Patient demographic and clinical characteristics data were collected. Adverse reactions were analyzed using Common Terminology Criteria for Adverse Events (CTCAE) v.4. Adherence to capecitabine were evaluated using Morisky-Green and MedTake tests. Statistical analysis was conducted using Chi-square, Fisher's exact and McNemer tests. RESULTS: One hundred and four patients were enrolled in this study, with a mean age was 58.5 ± 10.9 years; 51.0% were men and 51.0% Caucasian. Nausea and diarrhea were the most frequently reported adverse reactions (82.7% and 62.5%, respectively), followed by vomiting (54.8%), fatigue (54.8%), and hand-foot syndrome (53.9%). Nausea and diarrhea were also the most severe adverse reactions. Most patients were adherent to capecitabine in all cycles of treatment using the Morisky-Green test. Adherence increased significantly between cycle 1 and cycle 2 by MedTake test (p < 0.001). Some demographic and clinical characteristics were associated with adverse reactions (e.g., age and nausea, gender and nausea and vomiting) and capecitabine adherence (e.g., marital status and educational level) as well as some adverse reactions were associated with capecitabine adherence (hand-foot syndrome and nausea). CONCLUSIONS: Clinical oncology pharmacists must provide patient information on the correct use of capecitabine, manage adverse reactions, and monitor adherence to treatment. Strategies to prevent non-adherence to capecitabine must be adopted to ensure the success of pharmacotherapy.

Effect of Carvacrol and Thymol on NorA efflux pump inhibition in multidrug-resistant (MDR) Staphylococcus aureus strains.

Undue exposure to antimicrobials has led to the acquisition and development of sophisticated bacterial resistance mechanisms, such as efflux pumps, which are able to expel or reduce the intracellular concentration of various antibiotics, making them ineffective. Therefore, inhibiting this mechanism is a promising way to minimize the phenomenon of resistance in bacteria. In this sense, the present study sought to evaluate the activity of the Carvacrol (CAR) and Thymol (THY) terpenes as possible Efflux Pump Inhibitors (EPIs), by determining the Minimum Inhibitory Concentration (MIC) and the association of these compounds in subinhibitory concentrations with the antibiotic Norfloxacin and with Ethidium Bromide (EtBr) against strains SA-1199 (wild-type) and SA-1199B (overexpresses NorA) of Staphylococcus aureus. In order to verify the interaction of the terpenes with the NorA efflux protein, an in silico molecular modeling study was carried out. The assays used to obtain the MIC of CAR and THY were performed by broth microdilution, while the Efflux Pump inhibitory test was performed by the MIC modification method of the antibiotic Norfloxacin and EtBr. docking was performed using the Molegro Virtual Docker (MVD) program. The results of the study revealed that CAR and THY have moderate bacterial activity and are capable of reducing the MIC of Norfloxacin antibiotic and EtBr in strains of S. aureus carrying the NorA efflux pump. The docking results showed that these terpenes act as possible competitive NorA inhibitors and can be investigated as adjuvants in combined therapies aimed at reducing antibiotic resistance.

Enhancement of the antibiotic activity by quercetin against Staphylococcus aureus efflux pumps.

The objective of this work was to evaluate the inhibitory effect of quercetin on S. aureus Efflux Pumps. The MIC of Quercetin was evaluated through the broth microdilution method, as well as the Efflux Pump inhibition assay through the method of reducing the antibiotic minimum inhibitory concentration as well as that of ethidium bromide. The in silico approach through bioinformatics was performed to demonstrate the molecular mechanism of interaction of the substrate and the binding cavity. The Quercetin inhibition concentration was not clinically relevant. With respect to the reversal of bacterial resistance effect by efflux pump inhibition, this effect was observed with the strains carrying the TetK and NorA pumps. Regarding the interaction between the Quercetin complex and the NorA pump, the extra stability was provided by hydrogen bonds produced by the hydroxyl group.

In vitro and in silico studies of chalcones derived from natural acetophenone inhibitors of NorA and MepA multidrug efflux pumps in Staphylococcus aureus.

Bacterial resistance induced by efflux pumps is a frequent concern in clinical treatments involving multi-resistant bacteria. Staphylococcus aureus is a microorganism responsible for several types of infections and has several strains carrying efflux pumps, among them are the strain 1199B (NorA overexpresser), and the strain K2068 (MepA overexpresser). In this work, four chalcones derived from Croton anisodontus with modifications in the B ring in their structures were tested regarding their ability to inhibit NorA and MepA efflux pumps. The efflux pump inhibition mechanism was tested with the ethidium bromide substrate in the presence and absence of standard efflux pump inhibitors. The minimum inhibitory concentration values were also compared to those of strains that do not overexpress these efflux pumps. In order to gain some insights about the efflux pump mechanisms of these chalcones, two homology models were created (NorA and MepA) for a docking procedure. In addition, the ADME properties (absorption, distribution, metabolism and excretion) were also evaluated. The tested chalcones promoted synergism of the norfloxacin antibiotic by inhibiting associated efflux pumps. All four tested chalcones appear to bind to the binding sites of the efflux pump models in the same fashion as other chalcones with efflux pump inhibition capabilities. It was also verified that the chalcones 1-4 are well absorbed in the intestine, but with a decrease in their bioavailability, resulting in a low volume of distribution in the blood plasma, in addition to having a mild CNS activity. However, the chalcone 3 and 4 were not toxic due to metabolic activation. Whereas the chalcones 1 and 2 present a mutagenic risk, depending on the oral dose administered. The tested chalcones have not antibacterial activity; however, they are capable of inhibiting efflux pumps for the 1199B and K2068 strains. They promoted synergism of the norfloxacin antibiotic by inhibiting associated efflux pumps, as well as other associated mechanisms.

Evaluation of Elaiophylin extracted from Streptomyces hygroscopicus as a potential inhibitor of the NorA efflux protein in Staphylococcus aureus: An in vitro and in silico approach.

Compounds capable of inhibiting the efflux pump mechanism are a promising alternative against bacterial resistance because, when combined with antibiotics, they can increase the effectiveness of these drugs by inhibiting active efflux. Elaiophylin, derived from Streptomyces hygroscopicus, is a natural antibiotic that exhibits a variety of biological activities, including antibacterial activity. However, its potential as an inhibitor of the bacterial efflux mechanism has not been investigated. This study evaluated the ability of Elaiophylin to inhibit the NorA efflux pump in Staphylococcus aureus strains. Therefore, tests were performed to obtain the Minimum Inhibitory Concentration (MIC) and to verify the ability of Elaiophylin to potentiate the MIC of the antibiotic Norfloxacin and Ethidium Bromide (EtBr), known substrates of NorA efflux. Real-time PCR and molecular docking assays were also performed to assess the potential of Elaiophylin against NorA. The strains SA-1199 (wild type) and SA-1199B (NorA over-expressed) of S. aureus were used for this study. The results showed that Elaiophylin significantly decreased the MIC of Norfloxacin and EtBr, increasing the activity of these substrates against S. aureus, which carries the efflux protein NorA. However, Elaiophylin provided a non-significant reduction in norA gene expression, however, molecular docking demonstrated a high binding affinity between Elaiophylin and NorA efflux protein, indicating that Elaiophylin can act as a potential NorA in S. aureus.

In Vitro and In Silico Inhibition of Staphylococcus aureus Efflux Pump NorA by α-Pinene and Limonene.

Since the discovery of the first antibiotics, bacteria have acquired a variety of resistance mechanisms, with efflux pump (EP) being the most prominent mechanism for intracellular targeting drugs. These proteins have become efficient mechanisms of resistance to antibiotics in species such as Staphylococcus aureus and, therefore, have been identified as promising therapeutic targets in antibacterial drug development. Accordingly, evidence suggests that monoterpenes can act as EP inhibitors and can be useful in circumventing bacterial resistance. This study aimed to evaluate the effectiveness of monoterpenes α-pinene and limonene as EP inhibitors against a strain of S. aureus expressing NorA protein. The minimum inhibitory concentration (MIC) against the 1199B strain of S. aureus, which carries genes encoding efflux proteins associated with antibiotic resistance to norfloxacin, was assessed through the broth microdilution method. The results obtained served as a subsidy for the analysis of the NorA pump inhibition with norfloxacin and ethidium bromide. Docking techniques, in silico, were used to evaluate the interaction of monoterpenes with NorA. Both monoterpenes showed no clinically effective antibacterial activity. Nevertheless, these compounds were found to decrease the MICs of ethidium bromide and norfloxacin indicating EP inhibition, which was confirmed by molecular docking analyses. In conclusion, α-pinene and limonene showed promising antibiotic-enhancing properties in S. aureus 1199B strain, indicating that monoterpenes can be used in targeted drug development to combat antibiotic resistance associated with EP expression.

Clinical pharmacy in onco-hematology and bone marrow transplant: A valuable contribution to improving patient safety.

INTRODUCTION: It is known that clinical pharmacists intercept prescribing errors and contribute to patient safety in several medical specialties. The aim of this study was to identify, quantify and classify prescribing errors and pharmacist interventions carried out in onco-hematology and bone marrow transplant inpatient units. METHODS: This was a prospective and quantitative study, conducted from February 2018 to July 2018 in onco-hematology and bone marrow transplant inpatient units of a tertiary teaching hospital in Brazil. A pharmacist detected prescribing errors and performed interventions. The type and incidence of prescribing errors, error severity, type of pharmacist interventions, potential impact of interventions in patient care, and intervention acceptance rates were evaluated. RESULTS: A total of 1172 prescriptions were evaluated, 9% of them contained errors (total of 135 errors), and the most common error was related to prescribing the wrong dose (31.8%). Wrong dose and omission of drug were the two most frequent errors in onco-hematology, while wrong dose followed by inappropriate dilution were the most frequent in bone marrow transplantation. The pharmacist performed 135 interventions and the most common intervention was related to the treatment regimen (41.5%). Serious errors and very significant pharmacist interventions were the most frequent in both inpatient units. The acceptance rate of pharmacist interventions was high (90%). CONCLUSIONS: Clinical pharmacy improves patient safety and quality of care in onco-hematology and bone marrow transplant inpatient units.

Evaluation of Benzaldehyde as an Antibiotic Modulator and Its Toxic Effect against Drosophila melanogaster.

Products of natural origin remain important in the discovery of new bioactive molecules and are less damaging to the environment. Benzaldehyde is a product of the metabolism of plants, and similarly to oxygenated terpenes, it can have antibacterial activity against Staphylococcus aureus and toxic action against Drosophila melanogaster; we aimed to verify these activities. The broth microdilution tests determined the minimum inhibitory concentration (MIC) of benzaldehyde alone and in association with antibiotics and ethidium bromide (EtBr). Toxicity against Drosophila melanogaster was determined by fumigation tests that measured lethality and damage to the locomotor system. The results indicated that there was an association of norfloxacin and ciprofloxacin with benzaldehyde, from 64 µg/mL to 32 µg/mL of ciprofloxacin in the strain K6028 and from 256 µg/mL to 128 µg/mL of norfloxacin in the strain 1199B; however, the associations were not able to interfere with the functioning of the tested efflux pumps. In addition, benzaldehyde had a toxic effect on flies. Thus, the results proved the ability of benzaldehyde to modulate quinolone antibiotics and its toxic effects on fruit flies, thus enabling further studies in this area.

Non-coding RNAs: what are we missing?

Over the past two decades, the importance of small non-coding RNAs (sncRNAs) as regulatory molecules has become apparent in all three domains of life (archaea, bacteria, eukaryotes). In fact, sncRNAs play an important role in the control of gene expression at both the transcriptional and the post-transcriptional level, with crucial roles in fine-tuning cell responses during internal and external stress. Multiple pathways for sncRNA biogenesis and diverse mechanisms of regulation have been reported, and although biogenesis and mechanisms of sncRNAs in prokaryotes and eukaryotes are different, remarkable similarities exist. Here, we briefly review and compare the major sncRNA classes that act post-transcriptionally, and focus on recent discoveries regarding the ribosome as a target of regulation and the conservation of these mechanisms between prokaryotes and eukaryotes.

Characterization and antibacterial activity of the essential oil obtained from the leaves of Baccharis coridifolia DC against multiresistant strains.

Essential oils are secondary metabolites with immense pharmacological potential.These substances are abundantly produced by plants of the family Asteraceae, such as Baccharis coridifolia. Previous studies have demonstrated that this species has pharmacological properties that make it a promising source of new antibacterial agents. Therefore, the present study aimed to evaluate the antibacterial and antibiotic-modulating activity of Baccharis coridifolia essential oil against multidrug-resistant (MDR) strains. The phytochemical analysis was carried out by gas chromatography coupled to Mass Spectroscopy (GC/MS), and realized the Minimum Inhibitory Concentation (MIC) and antibiotic-modulation from the microdilution method in 96-well plates. It was revealed the presence of germacrene D (23.7%), bicyclogermacrene (17.1%), and (E)-caryophyllene (8.4%) as major components. The minimum inhibitory concentration of essential oil against strains of Pseudomonas aeruginosa (512 µg/mL) and Staphylococcus aureus (128 µg/mL) demonstrated clinically relevant antibacterial activity. In addition, the combination of subinhibitory doses of the oil with conventional antibiotics showed synergism, indicating potentiation of the antibacterial effect. In conclusion, the essential oil of Baccharis coridifolia (EOBc) presented antibacterial and antibiotic-modulating activities that place this species as a source of molecules useful in the fight against bacterial resistance.

Do 1,8-naphthyridine sulfonamides possess an inhibitory action against Tet(K) and MsrA efflux pumps in multiresistant Staphylococcus aureus strains?

Naphthyridines represent a class of heterocyclic compounds formed by two condensed aromatic rings. This study aimed to evaluate the antibacterial activity and in vitro inhibition of efflux resistance mechanisms of a series of 1,8-naphthyridine sulfonamides against strains carrying Tet(K) and MsrA efflux pumps. The efflux pump inhibitory capacity was evaluated by analyzing synergistic effects between 1,8-naphthyridine sulfonamides and standard antibiotics, as well as ethidium bromide. The following 1,8-naphthyridines were used: 4-methyl-N-(5-chloro-1,8-naphthyridin-2-yl)-benzenesulfonamide (Naph 1); 2,5-Dichloro-N-(5-chloro-1,8-naphthyridin-2-yl)-benzenesulfonamide (Naph 2); 2,3,4-trifluoro-N-(5-chloro-1,8-naphthyridin-2-yl)benzenesulfonamide (Naph 7); 3-trifluoromethyl-N-(5-chloro-1,8-naphthyridin-2-yl)-benzenesulfonamide (Naph 9). The 1,8-naphthyridine sulfonamide derivatives possessed a potential Tet(K) and MsrA efflux pump inhibitory action.

Evaluation of the Antibacterial Activity and Efflux Pump Reversal of Thymol and Carvacrol against Staphylococcus aureus and Their Toxicity in Drosophila melanogaster.

The antibacterial activity and efflux pump reversal of thymol and carvacrol were investigated against the Staphylococcus aureus IS-58 strain in this study, as well as their toxicity against Drosophila melanogaster. The minimum inhibitory concentration (MIC) was determined using the broth microdilution method, while efflux pump inhibition was assessed by reduction of the antibiotic and ethidium bromide (EtBr) MICs. D. melanogaster toxicity was tested using the fumigation method. Both thymol and carvacrol presented antibacterial activities with MICs of 72 and 256 µg/mL, respectively. The association between thymol and tetracycline demonstrated synergism, while the association between carvacrol and tetracycline presented antagonism. The compound and EtBr combinations did not differ from controls. Thymol and carvacrol toxicity against D. melanogaster were evidenced with EC50 values of 17.96 and 16.97 µg/mL, respectively, with 48 h of exposure. In conclusion, the compounds presented promising antibacterial activity against the tested strain, although no efficacy was observed in terms of efflux pump inhibition.

Atypical virulence of Leptospira kirschneri serogroup Icterohaemorrhagiae isolated from capybaras (Hydrochoerus hydrochaeris) in hamster model.

Leptospirosis is an important zoonotic disease and, in urban areas, rodents are considered the main reservoir of Leptospira to human hosts. It has been described that capybaras, the world largest rodent, also harbor and shed leptospires by urine. Although not virulent to their hosts, strains of rodent origin are virulent for the hamster. In this context we aim to investigate the virulence of Leptospira kirschneri strains of serogroup Icterohaemorrhagiae recovered from capybaras in Brazil in the hamster model. Five isolates of Leptospira recovered from asymptomatic capybaras were submitted to virulence tests following the suggested protocols and the 3Rs policy for experimental science. Briefly, 1 ml of 1 × 108 leptospires was inoculated intraperitoneally four times in one hamster for each strain. Four days after inoculation, a blood sample was collected via the gingival route for confirmation of blood culture infection. The infected animals were kept isolated in microisolators to observe clinical signs and monitored daily till day 21 post-inoculation. None strain caused acute disease in hamsters but were able to colonize their kidneys. The present study demonstrated that although Icterohaemorrhagiae strains are often reported as virulent, not all strains of that serogroup are indeed aggressive. Concluding, we report that strains of L. kirschneri serogroup Icterohaemorrhagiae recovered from healthy capybaras presented an atypical virulence to the hamster model, what reinforces that virulence is an intrinsic strains characteristic.

Parkia platycephala lectin enhances the antibiotic activity against multi-resistant bacterial strains and inhibits the development of Haemonchus contortus.

Lectins have been studied in the past few years as an alternative to inhibit the development of pathogenic bacteria and gastrointestinal nematodes of small ruminants. The development of new antibacterial and anthelmintic compounds is necessary owing to the increase in drug resistance among important pathogens. Therefore, this study aimed to evaluate the capacity of a glucose/mannose-binding lectin from Parkia platycephala seeds (PPL) to inhibit the development of Haemonchus contortus and to modulate antibiotic activity against multi-resistant bacterial strains, thereby confirming its efficacy when used in combination with gentamicin. PPL at the concentration of 1.2 mg/mL did not show inhibitory activity on H. contortus in the egg hatch test or the exsheathment assay. However, it did show significant inhibition of H. contortus larval development with an IC50 of 0.31 mg/mL. The minimum inhibitory concentration (MIC) obtained for PPL against all tested bacterial strains was not clinically relevant (MIC ≥ 1024 µg/mL). However, when PPL was combined with gentamicin, a significant increase in antibiotic activity was observed against S. aureus and E.coli multi-resistant strains. The inhibition of hemagglutinating activity by gentamicin (MIC = 50 mM) revealed that it may be interacting with the carbohydrate-binding site of PPL. It is this interaction between the antibiotic and lectin carbohydrate-binding site that may be responsible for the enhanced activity of gentamicin against multi-resistant strains. It can be concluded that PPL showed selective anthelmintic effect, inhibiting the development of H. contortus larvae and that it increased the effect of the antibiotic gentamicin against multi-resistant bacterial strains, thus constituting a potential therapeutic resource against resistant bacterial strains and H. contortus.

Clinical oncology pharmacist: Effective contribution to patient safety.

Management and prevention of problems related to oncology drugs are particularly important due to the excessive cost, high toxicity, and narrow therapeutic index of the antineoplastic drugs, in addition to the patients' state of health. Therefore, the presence of the pharmacist as a member of the multidisciplinary team is essential to contribute to patient safety. In this work, the interventions performed were identified, quantified, and classified to characterize the work of the clinical oncology pharmacist. This is a prospective and quantitative study, conducted over a period of six months in the outpatient oncology and chemotherapy clinic of the University Hospital of the University of Campinas, Brazil. A total of 3526 medical prescriptions were evaluated for the 780 patients seen and, among these prescriptions, 220 (6.24%) contained errors, representing 6.24% of the total number. The most common error was dose-related with 79 (22.83%) cases of overdosing. Wrong-patient medication error was the least reported (0.29%). Thirty drugs were involved in the pharmaceutical interventions, Carboplatin and Ondansetron being the most frequent. Thirteen types of potential errors were evaluated according to the method proposed by Cardinal and Fernandes. Two (15.38%) included interventions of indication, contraindication, and therapeutic efficacy of a drug. Five of them (38.46%) are related to the treatment regimen, and two (15.38%) were related to prevention of potential adverse events. Four interventions (30.77%) concerned technical interventions in injectable drugs such as dilution, compatibility, and administration time. Of the 346 interventions performed, 1 (0.29%) was classified as potentially lethal, 114 as serious (32.95%), 140 as significant (40.46%), and 91 as minor (26.30%).