Potentiating-antibiotic activity and absorption, distribution, metabolism, excretion and toxicity properties (ADMET) analysis of synthetic thiadiazines against multi-drug resistant (MDR) strains.

BACKGROUND: Thiadiazines are heterocyclic compounds that contain two nitrogen atoms and one sulfur atom in their structure. These synthetic molecules have several relevant pharmacological activities, such as antifungal, antibacterial, and antiparasitic. OBJECTIVES: The present study aimed to evaluate the possible in vitro and in silico interactions of compounds derived from thiadiazines. METHODS: The compounds were initially synthesized, purified, and confirmed through HPLC methodology. Multi-drug resistant bacterial strains of Staphylococcus aureus 10 and Pseudomonas aeruginosa 24 were used to evaluate the direct and modifying antibiotic activity of thiadiazine derivatives. ADMET assays (absorption, distribution, metabolism, excretion, and toxicity) were conducted, which evaluated the influence of the compounds against thousands of macromolecules considered as bioactive targets. RESULTS: There were modifications in the chemical synthesis in carbon 4 or 3 in one of the aromatic rings of the structure where different ions were added, ensuring a variability of products. It was possible to observe results that indicate the possibility of these compounds acting through the cyclooxygenase 2 mechanism, which, in addition to being involved in inflammatory responses, also acts by helping sodium reabsorption. The amine group present in thiadiazine analogs confers hydrophilic characteristics to the substances, but this primary characteristic has been altered due to alterations and insertions of other ligands. The characteristics of the analogs generally allow easy intestinal absorption, reduce possible hepatic toxic effects, and enable possible neurological and anti-inflammatory action. The antibacterial activity tests showed a slight direct action, mainly of the IJ23 analog. Some compounds were able to modify the action of the antibiotics gentamicin and norfloxacin against multi-drug resistant strains, indicating a possible synergistic action. CONCLUSIONS: Among all the results obtained in the study, the relevance of thiadiazine analogs as possible coadjuvant drugs in the antibacterial, anti-inflammatory, and neurological action with low toxicity is clear. Need for further studies to verify these effects in living organisms is not ruled out.

Meldrum's acid derivates are MepA efflux pump inhibitors: In vitro and in silico essays.

Efflux pumps are proteins capable of expelling antibiotics from bacterial cells, have emerged as a major mechanism of bacterial resistance. In the ongoing pursuit to overcome and reduce bacterial resistance, novel substances are being explored as potential efflux pump inhibitors. Meldrum's acid, a synthetic molecule widely studied for its role in synthesizing bioactive compounds, holds promise in this regard. Therefore, the objective of this study is to evaluate the antibacterial activity of three derivatives of Meldrum's acid and assess their ability to inhibit efflux mechanisms, employing both in silico and in vitro approaches. The antibacterial activity of the derivatives was assessed using a broth microdilution testing method. Surprisingly, the derivatives did not exhibit direct antibacterial activity on their own. However, they displayed a significant effect in enhancing the efficacy of antibiotics, suggesting a potential role in potentiating their effects. Furthermore, fluorescence emission assays using ethidium bromide indicated that the derivatives could potentially block efflux pumps, as they exhibited fluorescence levels comparable to the positive control. To further investigate their inhibitory capacity, molecular docking studies were conducted in silico, revealing binding interactions similar to ciprofloxacin and carbonyl cyanide 3-chlorophenylhydrazone, known efflux pump inhibitors. These findings highlight the potential of Meldrum's acid derivatives as effective inhibitors of efflux pumps. By targeting these mechanisms, the derivatives offer a promising avenue to enhance the effectiveness of antibiotics and combat bacterial resistance. This study underscores the importance of exploring novel strategies in the fight against bacterial resistance and provides valuable insights into the potential of Meldrum's acid derivatives as efflux pump inhibitors. Further research and exploration in this field are warranted to fully exploit their therapeutic potential.

Assessment of Quercetin Antiemetic Properties: In Vivo and In Silico Investigations on Receptor Binding Affinity and Synergistic Effects.

Quercetin (QUA), a flavonoid compound, is ubiquitously found in plants and has demonstrated a diverse range of biological activities. The primary objective of the current study is to assess the potential antiemetic properties of QUA using an in vivo and in silico approach. In this experiment, 4-day-old chicks were purchased to induce emesis by orally administering copper sulfate pentahydrate (CuSO4·5H2O) at a dose of 50 mg/kg (orally). Domperidone (DOM) (6 mg/kg), Hyoscine (HYS) (21 mg/kg), and Ondansetron (OND) (5 mg/kg) were treated as positive controls (PCs), and distilled water and a trace amount of Tween 80 mixture was employed as a negative control (NC). QUA was given orally at two distinct doses (25 and 50 mg/kg). Additionally, QUA (50 mg/kg) and PCs were administered separately or in combination to assess their antagonistic or synergistic effects on the chicks. The binding affinity of QUA and referral ligands towards the serotonin receptor (5HT3), dopamine receptors (D2 and D3), and muscarinic acetylcholine receptors (M1-M5) were estimated, and ligand-receptor interactions were visualized through various computational tools. In vivo findings indicate that QUA (25 and 50 mg/kg) has a significant effect on reducing the number of retches (16.50 ± 4.65 and 10.00 ± 4.19 times) and increasing the chick latency period (59.25 ± 4.75 and 94.25 ± 4.01 s), respectively. Additionally, QUA (50 mg/kg) in combination with Domperidone and Ondansetron exhibited superior antiemetic effects, reducing the number of retches and increasing the onset of emesis-inducing time. Furthermore, it is worth noting that QUA exhibited the strongest binding affinity against the D2 receptor with a value of -9.7 kcal/mol through the formation of hydrogen and hydrophobic bonds. In summary, the study found that QUA exhibited antiemetic activity in chicks, potentially by interacting with the D2 receptor pathway.

Sclareol exerts synergistic antidepressant effects with quercetin and caffeine, possibly suppressing GABAergic transmission in chicks.

This study evaluated the effects of sclareol (SCL) with or without caffeine (CAF) and quercetin (QUR) using in-vivo and in-silico studies. For this, 5-day-old chicks weighing between 45 and 48 g were randomly divided into five groups and treated accordingly. The chicks were monitored to compare the occurrence, latency, and duration of sleep as well as the loss and gain of righting reflex in response to SCL-10 mg/kg, CAF-10 mg/kg, and QUR-50 mg/kg using a thiopental sodium (TS)-induced sleeping model. Data were analyzed by one-way ANOVA followed by t-Student-Newman-Keuls' as a posthoc test at 95% confidence intervals with multiple comparisons. An in-silico study was also performed to investigate the possible antidepressant mechanisms of the test and/or standard drugs with different subunits of GABAA receptors. In comparison to the SCL, CAF, and QUR individual groups, SCL+CAF+QUR significantly increased the latency while decreasing the length of sleep. The incidence of loss and gain of the righting reflex was also modulated in the combination group. SCL showed better interaction with GABAA (α2 and α5) subunits than QUR with α2, α3, and α5. All these compounds showed stronger interactions with the GABAA receptor subunits than the standard CAF. Taken together, SCL, CAF, and QUR reduced the TS-induced righting reflex and sleeping time in the combination group more than in the individual treatments. SCL may show its antidepressant effects, possibly through interactions with GABAA receptor subunits.

Chemical composition and antibacterial effects of Etlingera elatior (Jack) R.M. Smith against Staphylococcus aureus efflux pumps.

Multidrug resistance is a significant health problem worldwide, with increasing mortality rates, especially in the last few years. In this context, a consistent effort has been made to discover new antibacterial agents, and evidence points to natural products as the most promising source of bioactive compounds. This research aimed to characterize the antibacterial effect of the essential oil of Etlingera elatior (EOEE) and its major constituents against efflux pump-carrying Staphylococcus aureus strains. The essential oil was extracted from fresh inflorescences by hydrodistillation. Chemical analysis was performed using gas chromatography coupled to mass spectrometry (GC-MS) and gas chromatography equipped with a flame ionization detector (GC-FID). The strains RN-4220, 1199B, IS-58, and 1199 of S. aureus were used to evaluate the antibacterial activity and the inhibition of efflux pumps. A total of 23 compounds were identified, including dodecanal and 1-dodecanol as major compounds. EOEE and dodecanal showed weak activity against the strains, while 1-dodecanol inhibited bacterial growth at low concentrations, indicating strong antibacterial activity. In addition, this compound potentiated the activity of norfloxacin against S. aureus 1199. In conclusion, 1-dodecanol was identified as the most effective compound of EOEE, showing significant potential to be used in antibacterial drug development.

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.

Antibacterial activity and anxiolytic-like effect of Ziziphus joazeiro Mart. leaves in adult zebrafish (Danio rerio).

Ziziphus joazeiro Mart. is an endemic plant of the Caatinga that presents a great socioeconomic importance for the Northeast and Semiarid Region of Brazil. In view of this, this study aimed to evaluate the antibacterial activity and anxiolytic-like effects of Ziziphus joazeiro Mart leaves in adult zebrafish (Danio rerio). The characterization of the main classes of metabolites was performed through chemical reactions. The antibacterial and antibiotic potentiating activity was evaluated by broth microdilution assays. The 96 h acute toxicity, open field test and anxiety models test was evaluated in vivo on adult zebrafish. The results obtained in the phytochemical prospection evidenced the presence of flobabenic tannins, leucoanthocyanidins, flavonois, flavonones, catechins, alkaloids, steroids, and triterpenoids. EEFZJ did not show antibacterial activity for all microorganism tested (MIC ≥ 1024 µg/mL), but reduced the concentration required for bacterial growth inhibition in combination with gentamicin and norfloxacin against multidrug-resistant strains of S. aureus (SA10) and E. coli (EC06), exhibiting synergistic effect with these antibiotics (p<0.0001). In the tests in vivo, EEFZJ was found to be nontoxic, performing reduced locomotor activity and demonstrated an anxiolytic-like effect in adult zebrafish via GABAergic and Serotoninergic systems (5-HT1, 5-HT2A/2C and 5-HT3A/3B).

Antibacterial Activity of the Essential Oil of Piper tuberculatum Jacq. Fruits against Multidrug-Resistant Strains: Inhibition of Efflux Pumps and ß-Lactamase.

Antimicrobial resistance has become a growing public health concern in recent decades, demanding a search for new effective treatments. Therefore, this study aimed to elucidate the phytochemical composition and evaluate the antibacterial activity of the essential oil obtained from the fruits of Piper tuberculatum Jacq. (EOPT) against strains carrying different mechanisms of antibiotic resistance. Phytochemical analysis was performed using gas chromatography-mass spectrometry (GC/MS). The antibacterial activity of EOPT and its ability to inhibit antibiotic resistance was evaluated through the broth microdilution method. The GC-MS analysis identified 99.59% of the constituents, with ß-pinene (31.51%), α-pinene (28.38%), and ß-cis-ocimene (20.22%) being identified as major constituents. The minimum inhibitory concentration (MIC) of EOPT was determined to assess its antibacterial activity against multidrug-resistant strains of Staphylococcus aureus (IS-58, 1199B, K2068, and K4100). The compound showed a MIC of ≥ 1024 µg/mL, suggesting a lack of intrinsic antibacterial activity. However, when the EOPT was associated with antibiotics and EtBr, a significant decrease in antibiotic resistance was observed, indicating the modulation of efflux pump activity. This evidence was corroborated with the observation of increased fluorescent light emission by the bacterial strains, indicating the involvement of the NorA and MepA efflux pumps. Additionally, the significant potentiation of ampicillin activity against the S. aureus strain K4414 suggests the ß-lactamase inhibitory activity of EOPT. These results suggest that the essential oil from P. tuberculatum fruits has antibiotic-enhancing properties, with a mechanism involving the inhibition of efflux pumps and ß-lactamase in MDR S. aureus strains. These findings provide new perspectives on the potential use of EOPT against antibiotic resistance and highlight the importance of Piper species as sources of bioactive compounds with promising therapeutic activities against MDR bacteria. Nevertheless, further preclinical (in vivo) studies remain necessary to confirm these in vitro-observed results.

The preeclampsia condition alters external potassium-evoked contraction of human umbilical vessels.

INTRODUCTION: Pre-eclampsia (PE) is a disease of high incidence in parturients, that adversely affects both mother and fetus. Although PE prevalence is high, there are few studies on literature describing its etiology or its mechanism of action. Thus, the aim of this study was to elucidate PE-induced alterations of contractile reactivity in umbilical vessels. METHOD: Segments of human umbilical artery (HUA) and human umbilical vein (HUV) from neonates of normotensive or PE parturients were obtained and contractile responses measured with a myograph. The segments were allowed to stabilize (2 h) under 1.0, 2.0 and 3.0 g force (gf) at pre-stimulation and, then, were stimulated with high isotonic K+ concentrations ([K+]o; 10-120 mM). RESULTS: All preparations responded to increases in isotonic K+ concentrations. In HUA and HUV of neonates of normotensive parturients, and in HUV of neonates of PE parturients, the contraction saturated at nearly 50 mM [K+]o, while in HUA of neonates of PE parturients, saturation occurred at 30 mM [K+]o. Additionally, several differences between contractile responses of HUA and HUV from neonates of normotensive parturients and those from neonates of parturients with PE were observed. PE alters the contractile response of the HUA and HUV to increased [K+]o, and its contractile modulation by the pre-stimulus basal tension. Moreover, in HUA of PE, reactivity is decreased for 2.0 and 3.0 gf basal tensions and increased for 1.0 gf; in the HUV of PE condition, it is increased for all basal tensions. DISCUSSION: In conclusion, PE promotes several alterations in HUA and HUV contractile reactivity, vessels in which important circulatory alterations are known to occur.

Antifungal Effect and Inhibition of the Virulence Mechanism of D-Limonene against Candida parapsilosis.

Yeasts from the Candida parapsilosis complex are clinically relevant due to their high virulence and pathogenicity potential, such as adherence to epithelial cells and emission of filamentous structures, as well as their low susceptibility to antifungals. D-limonene, a natural compound, emerges as a promising alternative with previously described antibacterial, antiparasitic, and antifungal activity; however, its mechanisms of action and antivirulence activity against C. parapsilosis complex species have not been elucidated. Therefore, in the present study, we aimed to evaluate the antifungal and antivirulence action, as well as the mechanism of action of D-limonene against isolates from this complex. D-limonene exhibited relevant antifungal activity against C. parapsilosis complex yeasts, as well as excellent antivirulence activity by inhibiting yeast morphogenesis and adherence to the human epithelium. Furthermore, the apoptotic mechanism induced by this compound, which is not induced by oxidative stress, represents an important target for the development of new antifungal drugs.

Modification of Antibiotic Activity by Fixed Oil of the Artocarpus heterophyllus Almond against Standard and Multidrug-Resistant Bacteria Strains.

Artocarpus heterophyllus (jackfruit) is an evergreen tree distributed in tropical regions and is among the most studied species of the genus Artocarpus. The jackfruit almond has been highlighted in relation to phytochemical studies, biological properties, and application in the development of food products. This study aimed to analyze jackfruit fixed oil regarding chemical components, antibacterial property alone, and in association with antibiotics against standard and MDR bacteria strains. In the analysis of the oil by gas chromatography coupled to a flame ionization detector (GC-FID), a high content of saturated fatty acids (78.51%) was identified in relation to unsaturated fatty acids (17.07%). The main fatty acids identified were lauric acid (43.01%), myristic acid (11.10%), palmitic acid (6.95%), and oleic acid (15.32%). In the antibacterial analysis, broth microdilution assays were used. The oil presented minimum inhibitory concentration (MIC) ≥ 1024 µg/mL in antibacterial analysis for standard and MDR bacterial strains. The oil showed synergistic effects in the association with gentamicin, ofloxacin, and penicillin against MDR strains, with significant reductions in the MIC of antibiotics. The results suggest that the fixed oil of A. heterophyllus has fatty acids with the potential to synergistically modify antibiotic activity.

Anxiolytic-like Effect of Quercetin Possibly through GABA Receptor Interaction Pathway: In Vivo and In Silico Studies.

Scientific evidence suggests that quercetin (QUR) has anxiolytic-like effects in experimental animals. However, the mechanism of action responsible for its anxiolytic-like effects is yet to be discovered. The goal of this research is to assess QUR's anxiolytic effects in mouse models to explicate the possible mechanism of action. After acute intraperitoneal (i.p.) treatment with QUR at a dose of 50 mg/kg (i.p.), behavioral models of open-field, hole board, swing box, and light-dark tests were performed. QUR was combined with a GABAergic agonist (diazepam) and/or antagonist (flumazenil) group. Furthermore, in silico analysis was also conducted to observe the interaction of QUR and GABA (α5), GABA (ß1), and GABA (ß2) receptors. In the experimental animal model, QUR had an anxiolytic-like effect. QUR, when combined with diazepam (2 mg/kg, i.p.), drastically potentiated an anxiolytic effect of diazepam. QUR is a more highly competitive ligand for the benzodiazepine recognition site that can displace flumazenil (2.5 mg/kg, i.p.). In all the test models, QUR acted similar to diazepam, with enhanced effects of the standard anxiolytic drug, which were reversed by pre-treatment with flumazenil. QUR showed the best interaction with the GABA (α5) receptor compared to the GABA (ß1) and GABA (ß2) receptors. In conclusion, QUR may exert an anxiolytic-like effect on mice, probably through the GABA-receptor-interacting pathway.

GC-MS analysis, and evaluation of protective effect of Piper chaba stem bark against paracetamol-induced liver damage in Sprague-Dawley rats: Possible defensive mechanism by targeting CYP2E1 enzyme through in silico study.

The present study attempted to scrutinize the protective effect of the methanolic extract of P. chaba stem bark against paracetamol-induced hepatotoxicity in Sprague-Dawley rats, along with the gas chromatography-mass spectrometry (GC-MS) analysis to identify phytochemicals, which were further docked in the catalytic site of CYP2E1 and the MD simulation for system that plays a major role in the bio-activation of toxic substances that produce reactive metabolites, leading to hepatotoxicity. P. chaba stem methanol extract (250 and 500 mg/kg) were treated orally with the negative control and the negative control silymarin (50 mg/kg) groups. Phytochemical profiling was conducted using GC-MS. In in-silico studies, PyRx software was used for docking analysis and the stability of the binding mode in the target active sites was evaluated through a set of standard MD-simulation protocols using the Charmm 27 force field and Swiss PARAM. Co-administration of P. chaba at both doses with APAP significantly reduced the APAP-augmented liver marker enzymes ALT, AST, ALP, and LDH, along with serum albumin, globulin, hepatic enzymes, histopathological architecture, lipid profiles, total protein, and total bilirubin, and elevated the levels of MDA. The GC-MS analysis indicated that P. chaba extract is enriched in fatty acid methyl esters (46.23 %) and alkaloids (10.91 %) and piperine is represented as a main phytochemical. Among all the identified phytochemicals, piperine (-8.0 kcal/mol) was found to be more interacting and stable with the binding site of CYP2E1. Therefore, all of our findings may conclude that the P. chaba stem extract and its main compound, piperine, are able to neutralize APAP-induced hepatic damage.

Bioactive Natural Products for Chemical Control of Microorganisms: Scientific Prospecting (2001-2021) and Systematic Review.

The inappropriate use of synthetic antibiotics has become a global public health problem. Therefore, the study of new alternatives for the treatment of infectious diseases is relevant and natural bioactive products are on the rise. This study conducted a scientific prospection of bioactive natural products with promising applications in the chemical control of microorganisms. A systematic review of the most recent articles was performed according to the following three steps: (i) eligibility assessment, (ii) screening, and (iii) inclusion of articles and information extraction. There has been an increase in the number of scientific publications on bioactive natural products for microbial control in the CAPES and SciELO databases (2001-2021). Seventeen relevant articles were included, most of which focused on extracts. Ascorbic acid, chlorogenic acid, chrysin, and quercetin were the most cited compounds. Natural products were shown to be effective in inhibiting more than 30 microorganisms. A discussion was presented on the research trends.

Possible mechanisms involved in the neuroprotective effect of Trans,trans-farnesol on pilocarpine-induced seizures in mice.

This study aimed to investigate, through in vivo and in vitro methodologies, the effect of acute trans,trans-farnesol (12.5, 25, 50 or 100 mg/kg, p.o.) administration on behavioral and neurochemical parameters associated with pilocarpine-induced epileptic seizure (300 mg/kg, i.p.) in mice. The initial results showed that the compound in question presents no anxiolytic-like or myorelaxant effects, despite reducing locomotor activity in the animals at all doses tested. In addition, the lowest dose increased the latency to onset of the first epileptic seizure, and the time to death. In addition to decreasing the mortality percentage in mice submitted to the pilocarpine model. In this same model, pretreatment with the lowest dose of the compound decreased the hippocampal concentrations of thiobarbituric acid and nitrite, and partially restored striatal concentrations of noradrenaline, dopamine, and serotonin. Taken together, the results suggest that trans,trans-farnesol presents a central depressant effect which contributes to its antiepileptic action which, in turn, seems to be mediated by the antagonism of muscarinic cholinergic receptors, reduction of oxidative stress. and modulation of noradrenaline, dopamine and serotonin concentrations in the central nervous system.

Ethnomedicinal Uses, Phytochemistry, and Therapeutic Potentials of Litsea glutinosa (Lour.) C. B. Robinson: A Literature-Based Review.

Litsea glutinosa (Lour.) C. B. Robinson, belonging to the family Lauraceae, is a multipurpose and fast-growing evergreen or deciduous tree that has been traditionally used for numerous purposes such as treatment for diarrhea, dysentery, abdominal pain, indigestion, gastroenteritis, edema, traumatic injuries, colds, arthritis, asthma, diabetes, pain relief, and poignant sexual power. This study aimed to summarize the chemical reports, folk values, and phytopharmacological activities of L. glutinosa, based on available information screened from diverse databases. An up-to-date electronic-based search was accomplished to obtain detailed information, with the help of several databases such as Google Scholar, Scopus, SpringerLink, Web of Science, ScienceDirect, ResearchGate, PubMed, ChemSpider, Elsevier, BioMed Central, and the USPTO, CIPO, INPI, Google Patents, and Espacenet, using relevant keywords. Outcomes advocate that, up to the present time, alkaloids, glycosides, and terpenoids are abundant in, and the most bioactive constituents of, this natural plant. Results demonstrated that L. glutinosa has various remarkable biological activities, including antioxidant, anti-inflammatory, anti-microbial, anticancer, antipyretic, anti-diabetic, analgesic, hepatoprotective, and wound-healing activity. One study revealed that L. glutinosa exhibited significant aphrodisiac and anti-infertility activity. Nevertheless, no clinical studies have been cited. Taken together, L. glutinosa may be one of the significant sources of bioactive constituents that could potentially lead to different effective pharmacological activities. On the other hand, future research should focus on clinical studies and several toxicity evaluations, such as sub-chronic toxicity, teratogenicity, and genotoxicity.

Pharmacological screening of the phenolic compound caffeic acid using rat aorta, uterus and ileum smooth muscle.

Caffeic acid is a phenolic compound widely found in commonly consumed foods such as pears, apples and coffee, and is pharmacologically known for its antioxidant, anti-inflammatory and anti-asthmatic properties. However, its relaxant activity in the aorta, uterus and ileum smooth muscle has not been investigated. This study aimed to comparatively evaluate the effect of caffeic acid on smooth muscle from different organs (aorta, uterus and ileum), and the contractions of this different organ were induced by different agonists. The organ bath technique was used, where the organs were placed in different cuvettes with 10 mL of Tyrode solution for 1 h to stabilize, then, myometrial, intestinal strip and aortic ring contractions were evoked using different contractile agonists (KCl 60 mM, PHE 0.1 µM, OT 10-2 IU/mL, CCh 10-6 M and BaCl2 0.1-30 mM); increasing concentrations of caffeic acid (0.03-7 mM) were administered in the experimental preparations. In the presence of KCl (60 mM), caffeic acid caused relaxations with the following EC50 values: 2.7 ± 0.26 mM/mL (aorta), 5.7 ± 0.71 mM/mL (uterus) and 2.1 ± 0.39 mM/mL (ileum). When in the presence of different agonists, PHE (0.1 µM) for the aorta, OT (10-2 IU/mL) for the uterus and CCh (10-6 M) for the ileum, caffeic acid caused relaxations with EC50 values of: 2.7 ± 0.31 mM/mL; 2.2 ± 0.34 mM/mL and 2.0 ± 0.28 mM/mL, respectively. The inhibitory effect of caffeic acid on serotonergic (aorta and uterus) and muscarinic receptors (uterus and ileum), as well as its possible involvement with L-type Ca2+ channels, was also observed. This study reports the pharmacological characterization of caffeic acid on smooth muscle from different organs, for which caffeic acid was more potent in the ileum. A diverse understanding of its performance as a possible therapeutic product is attributed to its relaxant effect.

Pharmacological applications of farnesol (C15H26O): a patent review.

Introduction: Farnesol (C15H26O) is a sesquiterpene alcohol found in essential oils. This substance is reported to have different pharmacological activities such as antimicrobial, antitumor and antioxidant effects, as well as actions in different body systems.Areas covered: This study aimed to analyze pharmaceutical patents containing this substance in their formulations. Patent search was carried out through the WIPO (World Intellectual Property Organization), LatiPat and INPI (National Institute of Industrial Property) electronic banks using the following descriptors and combinations: 'farnesol', 'pharmaceutical product', 'pharmacology' and 'pharmacy'.Expert opinion: Primary research identified 54 patents, from which 17 were selected for the final analysis after applying the inclusion criteria. The selected patents referred to products presenting different pharmaceutical activities of interest such as the prevention and treatment of diseases affecting the dermis, central nervous and cardiovascular systems, diseases caused by different microorganisms and cancers, among others. A minority of the articles included in this review reported the type of farnesol isomer that was investigated, this becoming a major limitation for the development of future pharmaceutical products. With the completion of this study, farnesol presents itself as a potential agent with pharmacological application both in the prevention and treatment of different diseases.

Condicionantes do ambiente hospitalar de trabalho e sua influência nas atividades dos profissionais de saúde: um estudo de caso / Conditions of the hospital work environment and its influence on professional health activities: a study case

O ambiente hospitalar possui uma série de fatores que geram insalubridade podendo provocar sofrimento psicológicos aos profissionais que nele atuam. Dentre as profissões existentes nesse ambiente, a enfermagem é apontada, como uma profissão que apresenta alto nível de estresse ocupacional. De forma menos frequente, mas não menos importante, outras categorias profissionais também sofrem prejuízos decorrentes do estresse decorrente da operacionalização das atividades hospitalares. Objetivou-se identificar os condicionantes que influenciam as atividades profissionais de trabalhadores no ambiente hospitalar por meio das três dimensões Job Stress Scale (JSS). Trata-se de um estudo transversal, do tipo estudo de caso, desenvolvido com 63 profissionais de um Hospital Pólo, na Região do Cariri, Ceará. Foi realizada análise descritiva por meio de frequências absolutas e relativas para as variáveis categóricas. Este trabalho obedeceu a Resolução 466/2012 do Conselho Nacional de Saúde, respeitando os princípios da Bioética. Foi evidenciado que os profissionais entrevistados não enfrentam muitos problemas com relação ao ambiente de trabalho, pois quando questionados sobre se tem um ambiente calmo e agradável onde trabalham, 77,7% (49 profissionais) responderam que concordam ou concordam mais que discordam. De modo geral, pode-se afirmar que a situação de trabalho para os profissionais do referido hospital, mostrou-se satisfatória na opinião dos mesmos, indicando necessidade de atenção com relação ao desgaste por esgotamento para garantir maior satisfação profissional e impactar de forma positiva nos serviços ofertados pelo Estabelecimento de Assistência à Saúde ­ EAS.

The hospital environment has a series of factors that generate unhealthiness and can cause psychological suffering to the professionals who work in it. Among the existing professions in this environment, nursing is pointed out, as a profession that presents a high level of occupational stress. Less frequently, but not less important, other professional categories also suffer losses due to the stress resulting from the operationalization of hospital activities. The objective was to identify the conditions that influence the professional activities of workers in the hospital environment through the three dimensions Job Stress Scale (JSS). This is a cross­sectional study, of the case study type, developed with 63 professionals from a Pólo Hospital, in the Cariri Region, Ceará. Descriptive analysis was performed using absolute and relative frequencies for categorical variables. This work followed Resolution 466/2012 of the National Health Council, respecting the principles of Bioethics. It was evidenced that the interviewed professionals do not face many problems in relation to the work environment, because when asked if they have a calm and pleasant environment where they work, 77.7% (49 professionals) answered that they agree or agree more than they disagree. In general, it can be said that the work situation for the professionals of the hospital was satisfactory in their opinion, indicating the need for attention in relation to exhaustion to ensure greater professional satisfaction and positively impact the services offered by Health Care Establishment ­ HCE.

Toxicological and pharmacologic effects of farnesol (C15H26O): A descriptive systematic review.

The objective of the present study was to perform a systematic review (SR) composed of preclinical and clinical studies which investigated the toxicological and pharmacologic effects of farnesol [Molecular formula: C15H26O; IUPAC: (3,7,11-Trimethyl-2,6,10-dodecatrien-1-ol]. This SR was performed according to PRISMA guidelines. Literature research was performed using PubMed, MEDLINE, Scopus and Web of Science databases using the descriptor combinations: "farnesol and pharmacological effect" and "farnesol and toxicology". The inclusion criteria used were original articles from preclinical and clinical studies investigating the pharmacological and toxicological effects of farnesol, published between January 1960 and December 2017 which were written in English, Portuguese and Spanish. Primary research identified 414 articles, from which 76 articles were selected for final analysis following the inclusion criteria. After grouping, 51.32 and 22.37% of the articles investigated the antimicrobial and antitumor effect, respectively. Methodological biases have been observed both in pre-clinical studies with non-human animals and in clinical trials, mainly in group allocation and blinding. This SR is the first study developed to compile the studies concerning the pharmacological and toxicological effects of farnesol. This study concludes that farnesol possesses different pharmacological and toxicological features, which permit its use as an active or a coadjuvant drug.