Detection of PD-L1-Expressing Myeloid Cell Clusters in the Hyaluronan-Enriched Stroma in Tumor Tissue and Tumor-Draining Lymph Nodes.

Expression of the transmembrane protein PD-L1 is frequently upregulated in cancer. Because PD-L1-expressing cells can induce apoptosis or anergy of T lymphocytes through binding to the PD1 receptor, the PD-L1-mediated inhibition of activated PD1+ T cells is considered a major pathway for tumor immune escape. However, the mechanisms that regulate the expression of PD-L1 in the tumor microenvironment are not fully understood. Analysis of organotypic tumor tissue slice cultures, obtained from mice with implanted syngeneic tumors (MBT2 bladder tumors in C3H mice, Renca kidney, and CT26 colon tumors in BALB/c mice), as well as from patients with cancer, revealed that tumor-associated hyaluronan (HA) supports the development of immunosuppressive PD-L1+ macrophages. Using genetically modified tumor cells, we identified epithelial tumor cells and cancer-associated mesenchymal fibroblast-like cells as a major source of HA in the tumor microenvironment. These HA-producing tumor cells, and particularly the vimentin-positive fibroblast-like cells of bone marrow origin, directly interact with tumor-recruited myeloid cells to form large stromal congregates/clusters that are highly enriched for both HA and PD-L1. Furthermore, similar cell clusters composed of HA-producing fibroblast-like cells and PD-L1+ macrophages were detected in tumor-draining, but not in distant, lymph nodes. Collectively, our findings indicate that the formation of multiple large HA-enriched stromal clusters that support the development of PD-L1-expressing APCs in the tumor microenvironment and draining lymph nodes could contribute to the immune escape and resistance to immunotherapy in cancer.

Antitumor activity of solamargine in mouse melanoma model: relevance to clinical safety.

Melanoma is the most aggressive type of skin cancer, and thus it is important to develop new drugs for its treatment. The present study aimed to examine the antitumor effects of solamargine a major alkaloid heteroside present in Solanum lycocarpum fruit. In addition solamargine was incorporated into nanoparticles (NP) of yttrium vanadate functionalized with 3-chloropropyltrimethoxysilane (YVO4:Eu3+:CPTES:SM) to determine antitumor activity. The anti-melanoma assessment was performed using a syngeneic mouse melanoma model B16F10 cell line. In addition, systemic toxicity, nephrotoxic, and genotoxic parameters were assessed. Solamargine, at doses of 5 or 10 mg/kg/day administered subcutaneously to male C57BL/6 mice for 5 days, decreased tumor size and frequency of mitoses in tumor tissue, indicative of a decrease in cell proliferation. Treatments with YVO4:Eu3+:CPTES:SM significantly reduced the number of mitoses in tumor tissue, associated with no change in tumor size. There were no apparent signs of systemic toxicity, nephrotoxicity, and genotoxicity initiated by treatments either with solamargine alone or plant alkaloid incorporated into NP. The animals treated with YVO4:Eu3+:CPTES:SM exhibited significant increase in spleen weight accompanied by no apparent histological changes in all tissues examined. In addition, animals treated with solamargine (10 mg/kg/day) and YVO4:Eu3+:CPTES:SM demonstrated significant reduction in hepatic DNA damage which was induced by tumor growth. Therefore, data suggest that solamargine may be considered a promising candidate in cancer therapy with no apparent toxic effects.

A robust method of nuclei isolation for single-cell RNA sequencing of solid tissues from the plant genus Populus.

Single-cell transcriptome analysis has been extensively applied in humans and animal models to uncover gene expression heterogeneity between the different cell types of a tissue or an organ. It demonstrated its capability to discover key regulatory elements that determine cell fate during developmental programs. Single-cell analysis requires the isolation and labeling of the messenger RNA (mRNA) derived from each cell. These challenges were primarily addressed in mammals by developing microfluidic-based approaches. For plant species whose cells contain cell walls, these approaches have generally required the generation of isolated protoplasts. Many plant tissues' secondary cell wall hinders enzymatic digestion required for individual protoplast isolation, resulting in an unequal representation of cell types in a protoplast population. This limitation is especially critical for cell types located in the inner layers of a tissue or the inner tissues of an organ. Consequently, single-cell RNA sequencing (scRNA-seq) studies using microfluidic approaches in plants have mainly been restricted to Arabidopsis roots, for which well-established procedures of protoplast isolation are available. Here we present a simple alternative approach to generating high-quality protoplasts from plant tissue by characterizing the mRNA extracted from individual nuclei instead of whole cells. We developed the protocol using two different plant materials with varying cellular complexity levels and cell wall structure, Populus shoot apices, and more lignified stems. Using the 10× Genomics Chromium technology, we show that this procedure results in intact mRNA isolation and limited leakage, with a broad representation of individual cell transcriptomes.

Cytotoxic and chemosensitizing effects of glycoalkaloidic extract on 2D and 3D models using RT4 and patient derived xenografts bladder cancer cells.

Glycoalkaloids have been widely demonstrated as potential anticancer agents. However, the chemosensitizing effect of these compounds with traditional chemotherapeutic agents has not been explored yet. In a quest for novel effective therapies to treat bladder cancer (BC), we evaluated the chemosensitizing potential of glycoalkaloidic extract (GE) with cisplatin (cDDP) in RT4 and PDX cells using 2D and 3D cell culture models. Additionally, we also investigated the underlying molecular mechanism behind this effect in RT4 cells. Herein, we observed that PDX cells were highly resistant to cisplatin when compared to RT4 cells. IC50 values showed at least 2.16-folds and 1.4-folds higher in 3D cultures when compared to 2D monolayers in RT4 cells and PDX cells, respectively. GE + cDDP inhibited colony formation (40%) and migration (28.38%) and induced apoptosis (57%) in RT4 cells. Combination therapy induced apoptosis by down-regulating the expression of Bcl-2 (p < 0.001), Bcl-xL (p < 0.001) and survivin (p < 0.01), and activating the caspase cascade in RT4 cells. Moreover, decreased expression of MMP-2 and 9 (p < 0.01) were observed with combination therapy, implying its effect on cell invasion/migration. Furthermore, we used 3D bioprinting to grow RT4 spheroids using sodium alginate-gelatin as a bioink and evaluated the effect of GE + cDDP on this system. Cell viability assay showed the chemosensitizing effect of GE with cDDP on bio-printed spheroids. In summary, we showed the cytotoxicity effect of GE on BC cells and also demonstrated that GE could sensitize BC cells to chemotherapy.

Author Correction: Characterization and printability of Sodium alginate -Gelatin hydrogel for bioprinting NSCLC co-culture.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Characterization and printability of Sodium alginate -Gelatin hydrogel for bioprinting NSCLC co-culture.

3D bioprinting improves orientation of in vitro tumor models by offering layer by layer positioning of cancer cells and cancer associated fibroblasts (CAFs) which can replicate tumor microenvironment. Aim of this study was to develop a sodium alginate -gelatin (SA-GL) hydrogel by optimizing rheological parameters to print non-small cell lung cancer (NSCLC) patient derived xenograft (PDX) cells and lung CAFs co-cultures. SA-GL hydrogels were prepared, and rheological properties were evaluated. Both the cells were mixed with the hydrogel and printed using INKREDIBLE bioprinter. Hydrogels prepared with 3.25% and 3.5% (w/v) SA and 4% (w/v) GL showed higher printability and cell viability. A significant decline in viscosity with shear rate was observed in these hydrogels suggesting the shear thinning property of hydrogels. Spheroid size distribution after 15 days was in the diameter range of 50-1100 µm. Up-regulation of vimentin, α-SMA and loss of E-cadherin in co-culture spheroids confirmed cellular crosstalk. This study demonstrates that rheological optimization of SA-GL hydrogel enhances printability and viability of NSCLC PDX and CAF co-culture which allows 3D co-culture spheroid formation within the printed scaffold. Therefore, this model can be used for studying high throughput drug screening and other pre-clinical applications.

Assessing the cytotoxic potential of glycoalkaloidic extract in nanoparticles against bladder cancer cells.

OBJECTIVE: This study proposed to use the nanotechnology to deliver glycoalkaloidic extract (AE) to bladder cancer cells, evaluating their activity in 2D and 3D models and the biological mechanism of cell death. METHODS: NPs were prepared by nanoprecipitation method using polylactic acid (PLA) and characterized considering their size, charge, particle concentration and stability. The cytotoxicity was evaluated in 2D and 3D model, and the apoptosis and cell cycle were investigated using flow cytometry. KEY FINDINGS: NPs loading AE (NP-AE) had diameter around 125 ± 6 nm (PdI <0.1) and negative charge. The encapsulation efficiency of SM and SS was higher than 85% for both compounds. The obtained formulation showed a significant in-vitro cytotoxic effect against RT4 cells in a dose-dependent manner with IC50 two fold lower than the free AE. The cytotoxic effect of NP-AE was mediated by apoptosis and cell cycle arrested in the S phase. RT4 cells cultured under 3D conditions exhibited a higher resistance to the treatments (IC50 ~ three fold higher than in 2D cell culture). CONCLUSION: The NP-AE might be a promising nanocarrier to load and deliver glycoalkaloids against bladder cancer.

Chemosensitizing Effect of Cernumidine Extracted from Solanum cernuum on Bladder Cancer Cells in Vitro.

Cernumidine (CER) is a guanidinic alkaloid isolated from Solanum cernuum leaves. In this work, we investigated the cytotoxicity, chemosensitizing effect of cernumidine to cisplatin (cDDP) and the possible mechanism of action of the combination on bladder cancer cells. Cernumidine showed cytotoxicity and could sensitize bladder cancer cells to cisplatin. The combination of CER+cDDP inhibited cell migration on T24 cells. CER+cDDP down-regulated MMP-2/9 and p-ERK1/2, while it increased EGFR activity corroborating the observed cell migration inhibition. Down-regulation of Bcl-2 and up-regulation pro-apoptotic Bax and further depletion of the mitochondrial membrane potential (ΔΨm) indicates that mitochondria play a central role in the combination treatment inducing the mitochondrial signaling pathway of apoptosis in T24 cells. Our data showed that the alkaloid cernumidine is worthy of further studies as a chemosensitizing agent to be used in complementary chemotherapy.

Comparative Analysis of 3D Bladder Tumor Spheroids Obtained by Forced Floating and Hanging Drop Methods for Drug Screening.

Introduction: Cell-based assays using three-dimensional (3D) cell cultures may reflect the antitumor activity of compounds more accurately, since these models reproduce the tumor microenvironment better. Methods: Here, we report a comparative analysis of cell behavior in the two most widely employed methods for 3D spheroid culture, forced floating (Ultra-low Attachment, ULA, plates), and hanging drop (HD) methods, using the RT4 human bladder cancer cell line as a model. The morphology parameters and growth/metabolism of the spheroids generated were first characterized, using four different cell-seeding concentrations (0.5, 1.25, 2.5, and 3.75 × 104 cells/mL), and then, subjected to drug resistance evaluation. Results: Both methods generated spheroids with a smooth surface and round shape in a spheroidization time of about 48 h, regardless of the cell-seeding concentration used. Reduced cell growth and metabolism was observed in 3D cultures compared to two-dimensional (2D) cultures. The optimal range of spheroid diameter (300-500 µm) was obtained using cultures initiated with 0.5 and 1.25 × 104 cells/mL for the ULA method and 2.5 and 3.75 × 104 cells/mL for the HD method. RT4 cells cultured under 3D conditions also exhibited a higher resistance to doxorubicin (IC50 of 1.00 and 0.83 µg/mL for the ULA and HD methods, respectively) compared to 2D cultures (IC50 ranging from 0.39 to 0.43). Conclusions: Comparing the results, we concluded that the forced floating method using ULA plates was considered more suitable and straightforward to generate RT4 spheroids for drug screening/cytotoxicity assays. The results presented here also contribute to the improvement in the standardization of the 3D cultures required for widespread application.

Protective effects of Solanum cernuum extract against chromosomal and genomic damage induced by methyl methanesulfonate in Swiss mice.

Solanum cernuum Vell is a Brazilian shrub or small tree, restricted to Southeast states of the country. The leaves are commercialized as "panacéia" and indicated for the treatment of urinary disorders, gonorrhea, scabies, skin diseases and as desobstruent, diuretic and antiarrhythmic. The hydroalcholic extract is active in the treatment of gastric ulcer. The aim of this study was to evaluate the genotoxic and antigenotoxic potential of S. cernuum hydroalcoholic extract (SC) in Swiss mice by micronucleus and comet assays. The animals were treated by gavage with the doses of 500, 1000 and 2000mg/kg body weight (b.w.). For antigenotoxicity assessment, the doses of 15, 30, 60, 120 and 240mg/kg b.w SC were administered simultaneously with the mutagen methyl methanesulfonate (MMS, 40mg/kg b.w., i.p.). The results showed that the SC was not genotoxic in both micronucleus and comet assays. On the other hand, the treatment with the lowest dose of SC (15mg/kg b.w.) plus MMS showed a statistically significant reduction in the frequency of micronuclei compared to treatment only with MMS. For the comet assay, significant reduction in extensions of DNA damage was observed in all treatments with SC combined with MMS in comparison with only MMS. The antigenotoxic activity observed for the SC may be due to the antioxidant potential of the compounds present in the extract such as guanidine alkaloids and flavonoids.

Antigenotoxic and Antioxidant Properties of Solanum cernuum and Its Alkaloid, Cernumidine.

Solanum cernuum VE. has been used extensively for the treatment of urinary disorders, gonorrhea and skin infections; cernumidine is a major component of S. cernuum (SC) hydroalcoholic extract. The micronucleus test in V79 cells was used to evaluate the genotoxic and antigenotoxic potential of SC and cernumidine. For antigenotoxicity assessment, methyl methanesulfonate (MMS, 44 µg/mL) and hydrogen peroxide (H2O2, 3.5 µg/mL) were added as inducers of chromosome damage. Antioxidant activity was evaluated by the 2,2-diphenyl-1-picrylhydrazyl (DPPH) test. Significantly higher frequencies of micronuclei were observed in cell cultures treated with SC concentrations of 160 and 320 µg/mL in comparison with the negative control, demonstrating a genotoxic effect. There was no significant difference in the frequency of micronuclei between cell cultures treated with a combination of SC and MMS and those treated only with MMS. On the other hand, a significant reduction in the frequency of micronuclei was observed for V79 cells treated with SC or cernumidine plus H2O2 compared to those treated only with H2O2. Furthermore, SC and cernumidine were able to scavenge free radicals in the DPPH assay. Thus, the protective effect of SC and cernumidine against H2O2 can be attributed to antioxidant activity.

Gastroprotective activity of the hydroethanolic extract and isolated compounds from the leaves of Solanum cernuum Vell.

ETHNOPHARMACOLOGICAL RELEVANCE: Solanum cernuum Vell. (Solanaceae) is a Brazilian medicinal plant, traditionally known as "panaceia". Its folk name is probably due to its wide range of applications in traditional medicine including the treatment of ulcers. AIM OF THE STUDY: To evaluate the gastroprotective activities of the hydroethanolic extract (ESC) of S. cernuum and its major isolated compounds using in vivo gastric ulcer models. MATERIAL AND METHODS: The ESC extract was obtained by maceration followed by percolation of the dried and powdered leaves of S. cernuum in ethanol:water (7:3). The major compounds in the extract were isolated by applying various preparative chromatographic techniques. The gastroprotective activity was evaluated in mice using different gastric ulcer-induced models. The anti-Helicobacter pylori activity was performed using the agar-well diffusion and broth microdilution methods. RESULTS: The ESC extract showed gastroprotective effects in the assay of acute gastric ulcer-induced by HCl/EtOH, nonsteroidal anti-inflammatory drug, and acetic acid-induced chronic ulcer protocols. The results also demonstrated that the gastroprotection induced by ESC extract is related to the activity of nitric oxide and endogenous sulfhydryls, which are important gastroprotective factors. The ESC extract and the alkaloid cernumidine did not show activity against H. pylori in the concentrations tested. CONCLUSIONS: The present study showed that the crude extract of S. cernuum possessed gastroprotective activity which corroborating the traditional use of this plant for the treatment of gastric ulcers. The isolated flavonoids, quercitrin and afzelin as well as the phenylpropanoid, isoferulic acid are suggested to be the compounds responsible for the gastroprotective activity of S. cernuum extract.

In vitro and in vivo evaluation of the delivery of topical formulations containing glycoalkaloids of Solanum lycocarpum fruits.

The glycoalkaloids solasonine (SN) and solamargine (SM) have been studied for their antiparasitic, antifungal, and anticancer properties, especially in vitro and in vivo against non-melanoma skin cancer. Thus, the alkaloidic extract of Solanum lycocarpum, which contains approximately 45% each of SN and SM, was used to define the best experimental conditions for in vitro and in vivo assays. The in vitro assays were performed with the Franz cell diffusion porcine skin model to evaluate the effects of different pHs and the presence of monoolein, ethoxydiglycol or ethanol penetration enhancers on the skin penetration and retention of SN and SM after 3, 6, 9 and 12h of exposure. The in vivo assay was performed on hairless mice with the formulation selected in the in vitro assays. The results showed that pH 6.5 was optimal for SM penetration. The formulation containing 5% alkaloidic extract, 5% propylene glycol, 5% monoolein and a hydroxyethyl cellulose gel base (Natrosol) (pH 6.5) was optimal for the delivery of SN and SM into the skin, and this formulation is potentially useful for the topical therapy of several skin disorders.

Distinctive histopathology and modulation of cytokine production during oral and intraperitoneal Trypanosoma cruzi Y strain infection.

Acute Chagas disease outbreaks are related to the consumption of food or drink contaminated by triatomine feces, thus making oral infection an important route of transmission. Both vector-borne and oral infections trigger important cardiac manifestations in the host that are related to a dysregulated immune response. The aims of this work were to evaluate possible alterations of lymphocyte CD4+/CD8+ sub-populations, Th1 and Th2 cytokines, nitrite concentrations and cardiac histopathology. One group of male Wistar rats was intraperitoneally infected (I.P.) with 1×105 metacyclic trypomastigotes of the T. cruzi Y strain, and another group of Wistar rats was orally infected (O.I.) with 8×105 metacyclic trypomastigotes of the same strain. The intraperitoneal infection triggered statistically enhanced parasite and peritoneal macrophage numbers, increased concentrations of NO and IL-12 and elevated cardiac inflammatory foci when compared with the oral infection. However, proliferation of CD4+ and CD8+ T cells were not statistically different for oral and intraperitoneal routes.

Protective actions of melatonin against heart damage during chronic Chagas disease.

Chronic cardiomyopathy is the most important clinical form of Chagas disease, and it is characterised by myocarditis that is associated with fibrosis and organ dysfunction. Alternative treatment options are important tools to modulate host immune responses. The main goal of this work was to evaluate the anti-inflammatory actions of melatonin during the chronic phase of Chagas disease. TNF-α, IL-10 and nitrite concentrations were evaluated as predictive factors of immune modulation. Creatine phosphokinase-MB (CK-MB), cardiac inflammatory foci and heart weight were assessed to evaluate the efficacy of the melatonin treatment. Male Wistar rats were infected with 1×10(5) blood trypomastigotes of the Y strain of Trypanosoma cruzi and kept untreated for 60 days to mimic chronic infection. After this period, the rats were orally treated with melatonin 50mg/kg/day, and the experiments were performed 90, 120, and 180 days post-infection. Melatonin treatment significantly increased the concentration of IL-10 and reduced the concentrations of NO and TNF-α produced by cardiomyocytes. Furthermore, it led to decreased heart weight, serum CK-MB levels and inflammatory foci when compared to the untreated and infected control groups. We conclude that melatonin therapy is effective at protecting animals against the harmful cardiac inflammatory response that is characteristic of chronic T. cruzi infection.

In vitro leishmanicidal and cytotoxic activities of the glycoalkaloids from Solanum lycocarpum (Solanaceae) fruits.

Leishmaniasis is an infection caused by a protozoan parasite of the genus Leishmania and is the second most prevalent parasitic protozoal disease after malaria in the world. We report the in vitro leishmanicidal activity on promastigote forms of Leishmania amazonensis and cytotoxicity, using LLCMK2 cells, of the glycoalkaloids from the fruits of Solanum lycocarpum, determined by colorimetric methods. The alkaloidic extract was obtained by acid-base extraction; solamargine and solasonine were isolated by silica-gel chromatography, followed by reversed-phase HPLC final purification. The alkaloidic extract, solamargine, solasonine, as well as the equimolar mixture of the glycoalkaloids solamargine and solasonine displayed leishmanicidal activity against promastigote forms of L. amazonensis, whereas the aglycone solasodine was inactive. After 24 and 72 h of incubation, most of the samples showed lower cytotoxicities (IC50 6.5 to 124 µM) as compared to leishmanicidal activity (IC50 1.1 to 23.6 µM). The equimolar mixture solamargine/solasonine was the most active with an IC50 value of 1.1 µM, after 72 h. Likewise, solamargine was the most active after 24 h with an IC50 value of 14.4 µM, both in comparison with the positive control amphotericin B.

Immunomodulatory effect of the alkaloidic extract of Solanum lycocarpum fruits in mice infected with Schistosoma mansoni.

Schistosomiasis is a chronic disease caused by trematode flatworms of the genus Schistosoma; it accounts for more than 280,000 deaths annually. In this work we investigated the effect of the alkaloidic extract obtained by acid-base extraction of the dried fruits of Solanum lycocarpum on schistosomiasis. We used this extract at concentrations of 10, 20, and 40 mg/kg to treat mice infected with Schistosoma mansoni in different phases of the parasite cycle, and we compared its effect with that of the positive control praziquantel (60 mg/kg). We evaluated the results on the basis of the number of macrophages, eggs, and granulomas; we also assessed nitric oxide (NO) and interferon-gamma (IFN-γ) production. Animals treated with a daily dose of 10 or 20 mg/kg alkaloidic extract between the 37th and 41st day of infection showed increased number of macrophages, elevated NO and IFN-γ concentrations, and reduced number of eggs and granulomas in the liver. The alkaloidic extract of S. lycocarpum fruits displayed an immunomodulatory effect on mice infected with S. mansoni, so its potential to treat schistosomiasis deserves further studies.

A Validated Reverse Phase HPLC Analytical Method for Quantitation of Glycoalkaloids in Solanum lycocarpum and Its Extracts.

Solanum lycocarpum (Solanaceae) is native to the Brazilian Cerrado. Fruits of this species contain the glycoalkaloids solasonine (SN) and solamargine (SM), which display antiparasitic and anticancer properties. A method has been developed for the extraction and HPLC-UV analysis of the SN and SM in different parts of S. lycocarpum, mainly comprising ripe and unripe fruits, leaf, and stem. This analytical method was validated and gave good detection response with linearity over a dynamic range of 0.77-1000.00 µg mL(-1) and recovery in the range of 80.92-91.71%, allowing a reliable quantitation of the target compounds. Unripe fruits displayed higher concentrations of glycoalkaloids (1.04% ± 0.01 of SN and 0.69% ± 0.00 of SM) than the ripe fruits (0.83% ± 0.02 of SN and 0.60% ± 0.01 of SM). Quantitation of glycoalkaloids in the alkaloidic extract gave 45.09% ± 1.14 of SN and 44.37% ± 0.60 of SM, respectively.

Evaluation of the schistosomicidal activity of the steroidal alkaloids from Solanum lycocarpum fruits.

Solanum lycocarpum (Solanaceae), a Brazilian medicinal plant known as "wolf fruit," contains about 1.5% of glycoalkaloids in its dried fruits, consisting mainly of solamargine and solasonine. The present work reports the obtainment of the alkaloidic extract of the S. lycocarpum fruit by acid-base extraction and the isolation of the major alkaloid heterosides by chromatographic means, as well as the evaluation of their in vitro schistosomicidal activities. The in vitro schistosomicidal activities of the alkaloidic extract of S. lycocarpum fruits and its isolated steroidal alkaloids were undertaken against adult worms of Schistosoma mansoni. The alkaloidic extract (20, 32, and 50 µg mL(-1)), solasonine (50 µM), solamargine (32 and 50 µM), and equimolar mixture of glycoalkaloids (20, 32, and 50 µM) lead to the separation of all couple worms and extensive disruption on their teguments, such as sloughing, as well as their deaths within 24 h of incubation. In addition, the alkaloidic extract (10 and 15 µg mL(-1)), solasonine (50 µM), solamargine (10, 15, and 20 µM), and equimolar mixtures of glycoalkaloids (10 and 15 µM) reduced the development of eggs produced by the adult worms. Solamargine, containing the sugar chain moiety chacotriose, was more active than the solasonine, which contains solatriose sugar chain moiety. A synergistic effect was also observed for a mixture of solamargine and solasonine. Therefore, the alkaloidic extract of S. lycocarpum, and its major components, solamargine and solasonine, showed promising schistosomicidal activity.

Conhecimento, prática e atitude dos farmacêuticos hospitalares frente aos erros de medicação / Knowledge, attitude and practice of hospital pharmacists in the face of medication errors

A utilização de medicamentos é um processo complexo, que envolve vários serviços e setores. Os erros de medicação (EM) que acontecem durante o trabalho dos profissionais de saúde, podem gerar sérias consequências para os pacientes e para a organização hospitalar. Pelo fato do profissional farmacêutico avaliar a prescrição médica e dispensar o medicamento, ele pode contribuir para a ocorrência de um erro ou sua prevenção. Este estudo analisou no serviço de farmácia do Hospital Universitário/UFJF o conhecimento, a atitude e prática (CAP) dos farmacêuticos frente aos EM. Os dados foram obtidos através de um questionário do tipo CAP. Nos resultados foram apontados como responsáveis pelos EM tanto os fatores individuais (falta de atenção (6,34%), falta de conhecimento (5,98%), cansaço e estresse (5,63%)) como os fatores do sistema (excesso de trabalho (5,28%), falta de profissionais no setor (4,93%) e iluminação inadequada (3,52%)). Para minimizar tais erros os participantes da pesquisa destacaram: informatização da prescrição médica (13,45%), educação continuada, reciclagem e treinamento dos profissionais (13,45%). Em relação às providências tomadas após a ocorrência do erro, foram priorizadas nos questionários: orientação (32,15%), reuniões e debates sobre os erros, avaliação dos erros (28,57%) e notificação da ocorrência (25%). Os profissionais participantes desse estudo apresentam um conhecimento adequado sobre o assunto, uma atitude que não responsabiliza somente o indivíduo pelos EM, uma prática que transforma o erro em aprendizado e que previne muitas das ocorrências pela intervenção farmacêutica.

Drug use is a complex process that involves multiple services and health professionals. And medication errors (ME) are part of the work of these professionals, with serious consequences for patients and hospital organization. Due to the pharmacists to evaluate the prescription and dispense the drug, they can contribute to the error or prevent from occurring. Therefore, this work identified and analyzed the University Hospital/UFJF knowledge, attitude and practice (KAP) of hospital pharmacists in the face of ME. The data were obtained through a questionnaire. In results were identified as responsible for ME individual factors like inattention (6.34%), lack of knowledge (5.98%), fatigue, stress (5.63% ) as well as system factors: excess work (5.28%), inadequate lighting (4.93%) among other. Suggestions to minimize ME were also directed to the individual and the system: typed prescription (13.45%), continuing education, retraining and vocational training (13.45%) were the points highlighted by the participants. After the occurrence of the error, orientation (32.15%), meetings and discussions about the errors, evaluating them (28.57%), and notification of the occurrence (25%) were prioritized in questionnaires. This study showed that professionals in the Pharmacy Service of the University Hospital /UFJF have adequate knowledge on the subject, an attitude that not only the individual responsible for medication errors and a practice that transforms the learning and error that prevents some errors administration of drugs through pharmaceutical intervention