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Abstract Cervical cancer stands as a prevalent gynaecologic malignancy affecting women globally, often linked to persistent human papillomavirus infection. Biomarkers associated with cervical cancer, including VEGF-A, VEGF-B, VEGF-C, VEGF-D, and VEGF-E, show upregulation and are linked to angiogenesis and lymphangiogenesis. This research aims to employ in-silico methods to target tyrosine kinase receptor proteins—VEGFR-1, VEGFR-2, and VEGFR-3, and identify novel inhibitors for Vascular Endothelial Growth Factors receptors (VEGFRs). A comprehensive literary study was conducted which identified 26 established inhibitors for VEGFR-1, VEGFR-2, and VEGFR-3 receptor proteins. Compounds with high-affinity scores, including PubChem ID—25102847, 369976, and 208908 were chosen from pre-existing compounds for creating Deep Learning-based models. RD-Kit, a Deep learning algorithm, was used to generate 43 million compounds for VEGFR-1, VEGFR-2, and VEGFR-3 targets. Molecular docking studies were conducted on the top 10 molecules for each target to validate the receptor-ligand binding affinity. The results of Molecular Docking indicated that PubChem IDs—71465,645 and 11152946 exhibited strong affinity, designating them as the most efficient molecules. To further investigate their potential, a Molecular Dynamics Simulation was performed to assess conformational stability, and a pharmacophore analysis was also conducted for indoctrinating interactions.

An unprecedented global social and economic impact as well as a significant number of fatalities have been brought on by the coronavirus disease 2019 (COVID-19), produced by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Acute SARS-CoV-2 infection can, in certain situations, cause immunological abnormalities, leading to an anomalous innate and adaptive immune response. While most patients only experience mild symptoms and recover without the need for mechanical ventilation, a substantial percentage of those who are affected develop severe respiratory illness, which can be fatal. The absence of effective therapies when disease progresses to a very severe condition coupled with the incomplete understanding of COVID-19’s pathogenesis triggers the need to develop innovative therapeutic approaches for patients at high risk of mortality. As a result, we investigate the potential contribution of promising combinatorial cell therapy to prevent death in critical patients.

Protozoal diseases, such as leishmaniasis, malaria, African sleeping sickness, Chagas disease, amoebiasis, giardiasis, cryptococcosis, and toxoplasmosis (among others), affect and/or have the potential to infect more than one billion people worldwide [...]

Cancer is a multifactorial disease that continues to increase. Lignans are known to be important anticancer agents. However, due to the structural diversity of lignans, it is difficult to associate anticancer activity with a particular subclass. Therefore, the present study sought to evaluate the association of lignan subclasses with antitumor activity, considering the genetic profile of the variants of the selected targets. To do so, predictive models were built against the targets tyrosine-protein kinase ABL (ABL), epidermal growth factor receptor erbB1 (EGFR), histone deacetylase (HDAC), serine/threonine-protein kinase mTOR (mTOR) and poly [ADP-ribose] polymerase-1 (PARP1). Then, single nucleotide polymorphisms were mapped, target mutations were designed, and molecular docking was performed with the lignans with the best predicted biological activity. The results showed more anticancer activity in the dibenzocyclooctadiene, furofuran and aryltetralin subclasses. The lignans with the best predictive values of biological activity showed varying binding energy results in the presence of certain genetic variants.

Chalcones are direct precursors in the biosynthesis of flavonoids. They have an α,β-unsaturated carbonyl system which gives them broad biological properties. Among the biological properties exerted by chalcones, their ability to suppress tumors stands out, in addition to their low toxicity. In this perspective, the present work explores the role of natural and synthetic chalcones and their anticancer activity in vitro reported in the last four years from 2019 to 2023. Moreover, we carried out a partial least square (PLS) analysis of the biologic data reported for colon adenocarcinoma lineage HCT-116. Information was obtained from the Web of Science database. Our in silico analysis identified that the presence of polar radicals such as hydroxyl and methoxyl contributed to the anticancer activity of chalcones derivatives. We hope that the data presented in this work will help researchers to develop effective drugs to inhibit colon adenocarcinoma in future works.

The present study proposed the synthesis of a novel acridine derivative not yet described in the literature, chemical characterization by NMR, MS, and IR, followed by investigations of its antileishmanial potential. In vitro assays were performed to assess its antileishmanial activity against L. amazonensis strains and cytotoxicity against macrophages through MTT assay and annexin V-FITC/PI, and the ability to perform an immunomodulatory action using CBA. To investigate possible molecular targets, its interaction with DNA in vitro and in silico targets were evaluated. As results, the compound showed good antileishmanial activity, with IC50 of 6.57 (amastigotes) and 94.97 (promastigotes) µg mL−1, associated with non-cytotoxicity to macrophages (CC50 > 256.00 µg mL−1). When assessed by flow cytometry, 99.8% of macrophages remained viable. The compound induced an antileishmanial effect in infected macrophages and altered TNF-α, IL-10 and IL-6 expression, suggesting a slight immunomodulatory activity. DNA assay showed an interaction with the minor grooves due to the hyperchromic effect of 47.53% and Kb 1.17 × 106 M−1, and was sustained by docking studies. Molecular dynamics simulations and MM-PBSA calculations propose cysteine protease B as a possible target. Therefore, this study demonstrates that the new compound is a promising molecule and contributes as a model for future works.

The World Health Organization classifies Leishmania as one of the 17 “neglected diseases” that burden tropical and sub-tropical climate regions with over half a million diagnosed cases each year. Despite this, currently available anti-leishmania drugs have high toxicity and the potential to be made obsolete by parasite drug resistance. We chose to analyze organoselenides for leishmanicidal potential given the reduced toxicity inherent to selenium and the displayed biological activity of organoselenides against Leishmania. Thus, the biological activities of 77 selenoesters and their N-aryl-propanamide derivatives were predicted using robust in silico models of Leishmania infantum, Leishmania amazonensis, Leishmania major, and Leishmania (Viannia) braziliensis. The models identified 28 compounds with >60% probability of demonstrating leishmanicidal activity against L. infantum, and likewise, 26 for L. amazonesis, 25 for L. braziliensis, and 23 for L. major. The in silico prediction of ADMET properties suggests high rates of oral absorption and good bioavailability for these compounds. In the in silico toxicity evaluation, only seven compounds showed signs of toxicity in up to one or two parameters. The methodology was corroborated with the ensuing experimental validation, which evaluated the inhibition of the Promastigote form of the Leishmania species under study. The activity of the molecules was determined by the IC50 value (µM); IC50 values < 20 µM indicated better inhibition profiles. Sixteen compounds were synthesized and tested for their activity. Eight molecules presented IC50 values < 20 µM for at least one of the Leishmania species under study, with compound NC34 presenting the strongest parasite inhibition profile. Furthermore, the methodology used was effective, as many of the compounds with the highest probability of activity were confirmed by the in vitro tests performed.

Parasitic diseases remain as unresolved health issues worldwide. While for some parasites the treatments involve drug combinations with serious side effects, for others, chemical therapies are inefficient due to the emergence of drug resistance. This urges the search for novel antiparasitic agents able to act through multiple mechanisms of action. Here, we report the first multi-target model based on quantitative structure-activity relationships and a multilayer perceptron neural network (mt-QSAR-MLP) to virtually design and predict versatile inhibitors of proteins involved in the survival and/or infectivity of different pathogenic parasites. The mt-QSAR-MLP model exhibited high accuracy (>80%) in both training and test sets for the classification/prediction of protein inhibitors. Several fragments were directly extracted from the physicochemical and structural interpretations of the molecular descriptors in the mt-QSAR-MLP model. Such interpretations enabled the generation of four molecules that were predicted as multi-target inhibitors against at least three of the five parasitic proteins reported here with two of the molecules being predicted to inhibit all the proteins. Docking calculations converged with the mt-QSAR-MLP model regarding the multi-target profile of the designed molecules. The designed molecules exhibited drug-like properties, complying with Lipinski’s rule of five, as well as Ghose’s filter and Veber’s guidelines.

Treatment of pain and fever remains an important challenge for modern medicine. Non-steroidal anti-inflammatory drugs (NSAIDs) are the pharmacological options most often used, but their frequent use exposes the patient to serious side effects and dangerous drug interactions. In this context, thiophene derivatives are promising therapeutic alternatives. In this study, we evaluated the in vivo and in silico antinociceptive and antipyretic properties of RMD86, a thiophene derivative. At 100 mg/kg, RMD86 induced no significant changes in the motor coordination of mice in the Rotarod test. At 25, 50, and 100 mg/kg RMD86 significantly reduced the number of abdominal contortions induced by acetic acid (antinociceptive activity) in mice when compared to the control. In the formalin test, for the first phase, there was a reduction in licking times at doses of 50 and 100 mg/kg. In the second phase, reduction occurred at all doses. In the hot plate test, RMD86 (at 100 mg/kg) increased latency time in the first 30 min. For antipyretic activity, RMD86, when compared to the reference drug acetaminophen (250 mg/kg), significantly reduced pyrexia at 30, 60, and 120 min, at dosages of 25, 50 and 100 mg/kg. Molecular docking studies revealed that RMD86 presents a greater number of interactions and lower energy values than both the co-crystallized ligand and the reference drug (meloxicam) against COX-1 and COX-2 isoenzymes. The results give evidence of the analgesic and antipyretic properties like NSAIDs suggesting its potential for pain therapy.

A series of coumarin derivatives and isosteres were synthesized from the reaction of triflic intermediates with phenylboronic acids, terminal alkynes, and organozinc compounds through palladium-catalyzed cross-coupling reactions. The in vitro cytotoxic effect of the compounds was evaluated against two non-small cell lung carcinoma (NSCLC) cell lines (A-549 and H2170) and a normal cell line (NIH-3T3) using cisplatin as a reference drug. Additionally, the effects of the most promising coumarin derivative (9f) in reversing the epithelial-to-mesenchymal transition (EMT) in IL-1β-stimulated A549 cells and in inhibiting the EMT-associated migratory ability in A549 cells were also evaluated. 9f had the greatest cytotoxic effect (CC50 = 7.1 ± 0.8 and 3.3 ± 0.5 μM, respectively against A549 and H2170 cells) and CC50 value of 25.8 µM for NIH-3T3 cells. 9f inhibited the IL-1β-induced EMT in epithelial cells by inhibiting the F-actin reorganization, attenuating changes in the actin cytoskeleton reorganization, and downregulating vimentin in A549 cells stimulated by IL-1β. Treatment of A549 cells with 9f at 7 µM for 24 h significantly reduced the migration of IL-1β-stimulated cells, which is a phenomenon confirmed by qualitative assessment of the wound closure. Taken together, our findings suggest that coumarin derivatives, especially compound 9f, may become a promising candidate for lung cancer therapy, especially in lung cancer promoted by NSCLC cell lines.

In this study, films of chitosan and 2-amino-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carbonitrile (6CN), a 2-aminothiophene derivative with great pharmacological potential, were prepared as a system for a topical formulation. 6CN-chitosan films were characterized by physicochemical analyses, such as Fourier-transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), X-ray diffraction (XRD), and scanning electronic microscopy (SEM). Additionally, the antifungal potential of the films was evaluated in vitro against three species of Candida (C. albicans, C. tropicalis, and C. parapsilosis). The results of the FTIR and thermal analysis showed the incorporation of 6CN in the polymer matrix. In the diffractogram, the 6CN-chitosan films exhibited diffraction halos that were characteristic of amorphous structures, while the micrographs showed that 6CN particles were dispersed in the chitosan matrix, exhibiting pores and cracks on the film surface. In addition, the results of antifungal investigation demonstrated that 6CN-chitosan films were effective against Candida species showing potential for application as a new antifungal drug.

In 2017, for the first time in six years, the number of cinemas in Spain has increased, although the high cost of digitization has forced the disappearance of cinema as a cultural offer in many parts of Spain. The birth of citizen initiatives that bet on an alternative exhibition model with the purpose of reconverting the neighborhood cinemas threatened in spaces for cultural diffusion. In this context, to describe the different business models adopted by self-managed cinema initiatives that emerged in recent years and integrated in CineArte, Network of Independent Cinemas for Culture and Art is the main objective of the paper. It is concluded that the majority of these are defined as non-profit cinemas managed through associations whose partners, sometimes also owners, direct the project, financed by membership dues and ticket sales.

Rheumatoid arthritis, arthrosis and gout, among other chronic inflammatory diseases are public health problems and represent major therapeutic challenges. Non-steroidal anti-inflammatory drugs (NSAIDs) are the most prescribed clinical treatments, despite their severe side effects and their exclusive action in improving symptoms, without effectively promoting the cure. However, recent advances in the fields of pharmacology, medicinal chemistry, and chemoinformatics have provided valuable information and opportunities for development of new anti-inflammatory drug candidates. For drug design and discovery, thiophene derivatives are privileged structures. Thiophene-based compounds, like the commercial drugs Tinoridine and Tiaprofenic acid, are known for their anti-inflammatory properties. The present review provides an update on the role of thiophene-based derivatives in inflammation. Studies on mechanisms of action, interactions with receptors (especially against cyclooxygenase (COX) and lipoxygenase (LOX)), and structure-activity relationships are also presented and discussed. The results demonstrate the importance of thiophene-based compounds as privileged structures for the design and discovery of novel anti-inflammatory agents. The studies reveal important structural characteristics. The presence of carboxylic acids, esters, amines, and amides, as well as methyl and methoxy groups, has been frequently described, and highlights the importance of these groups for anti-inflammatory activity and biological target recognition, especially for inhibition of COX and LOX enzymes.

The current treatments against Leishmania parasites present high toxicity and multiple side effects, which makes the control and elimination of leishmaniasis challenging. Natural products constitute an interesting and diverse chemical space for the identification of new antileishmanial drugs. To identify new drug options, an in-house database of 360 kauranes (tetracyclic diterpenes) was generated, and a combined ligand- and structure-based virtual screening (VS) approach was performed to select potential inhibitors of Leishmania major (Lm) pteridine reductase I (PTR1). The best-ranked kauranes were employed to verify the validity of the VS approach through LmPTR1 enzyme inhibition assay. The half-maximal inhibitory concentration (IC50) values of selected bioactive compounds were examined using the random forest (RF) model (i.e., 2β-hydroxy-menth-6-en-5β-yl ent-kaurenoate (135) and 3α-cinnamoyloxy-ent-kaur-16-en-19-oic acid (302)) were below 10 μM. A compound similar to 302, 3α-p-coumaroyloxy-ent-kaur-16-en-19-oic acid (302a), was also synthesized and showed the highest activity against LmPTR1. Finally, molecular docking calculations and molecular dynamics simulations were performed for the VS-selected, most-active kauranes within the active sites of PTR1 hybrid models, generated from three Leishmania species that are known to cause cutaneous leishmaniasis in the new world (i.e., L. braziliensis, L. panamensis, and L. amazonensis) to explore the targeting potential of these kauranes to other species-dependent variants of this enzyme.

Leishmaniasis is endemic in at least 98 countries. Due to the high toxicity and resistance associated with the drugs, we chose lignans as an alternative, due to their favorable properties of absorption, distribution, metabolism, excretion, and toxicity (ADMET). To investigate their leishmanicidal potential, the biological activities of a set of 160 lignans were predicted using predictive models that were built using data for Leishmania major and L. (Viannia) braziliensis. A combined analysis, based on ligand and structure, and several other computational approaches were used. The results showed that the combined analysis was able to select 11 lignans with potential activity against L. major and 21 lignans against L. braziliensis, with multitargeting effects and low or no toxicity. Of these compounds, four were isolated from the species Justicia aequilabris (Nees) Lindau. All of the identified compounds were able to inhibit the growth of L. braziliensis promastigotes, with the most active compound, (159) epipinoresinol-4-O-β-d-glucopyranoside, presenting an IC50 value of 5.39 µM and IC50 value of 36.51 µM for L. major. Our findings indicated the potential of computer-aided drug design and development and demonstrated that lignans represent promising prototype compounds for the development of multitarget drugs against leishmaniasis.

O presente artigo tem como objetivo identificar na literatura evidências científicas acerca da utilização da educação em saúde na atenção básica como promotora de um envelhecimento saudável. Trata-se de uma revisão bibliográfica, desenvolvida nas bases de dados Literatura Latino-Americana em Ciências da Saúde (LILACS), Base de Dados de Enfermagem (BDENF) e na biblioteca eletrônica Scientific Electronic Library Online (SciELO), aplicando os descritores: Envelhecimento, Educação em Saúde e Atenção básica. Os descritores foram associados nas bases de dados utilizando o operador booleano “and”. Como critérios de inclusão, elegeram-se: trabalhos originais, publicados entre os anos de 2008 a 2017, nos idiomas inglês, português e espanhol, disponíveis online gratuitamente. Verificou-se que as ações educativas são compreendidas como necessárias para atenção ao idoso, embora os profissionais apontem dificuldades para realização das mesmas, como: falta de preparo para tratar da temática, descaso da gestão e falta de insumos. Conclui-se que ações educativas tem potencial para garantir melhoria na qualidade de vida dos idosos, tanto nos aspectos biológicos como nos psicossociais.

O presente trabalho teve por objetivo validar métodos por espectrofotometria UV-Vis e por CLAE para a análise quantitativa de um derivado do tiofeno, o 2-[(3,4-dicloro-benzilideno)-amino]-5,6-diidro-4H-ciclopen-ta[b]tiofeno-3-carbonitrila (5CN05) e aplicá-los no doseamento da molécula contida em microemulsões, Os métodos propostos foram validados conforme a Resolução 899/2003 da Agência Nacional de Vigilância Sanitária (ANVISA), O comprimento de onda de máxima absorção do fármaco 5CN05 foi detectado em ?max= 387nm, O método espectrofotométrico validado mostrou-se seletivo, apresentando linearidade na faixa de 3 a 16 µg.mL-1, coeficiente de correlação (r) igual a 0,9998 e limites de detecção e quantificação de 0,12 µg.mL-1 e 0,41 µg.mL-1, respectivamente, Para o método CLAE, observou-se linearidade na faixa de 0,1 a 3,0 µg.mL-1, r = 0,99915, limites de detecção e quantificação de 0,07 µg.mL-1 e 0,10 µg.mL-1 respectivamente, Para ambos os métodos, os parâmetros precisão, exatidão e robustez mostraram-se adequados para o uso pretendido, As metodologias propostas podem ser seguramente aplicadas para quantificação do 5CN05 em produtos farmacêuticos como microemulsões.

Fourteen arylsemicarbazone derivatives were synthesized and evaluated in order to find agents with potential anticancer activity. Cytotoxic screening was performed against K562, HL-60, MOLT-4, HEp-2, NCI-H292, HT-29 and MCF-7 tumor cell lines. Compounds 3c and 4a were active against the tested cancer cell lines, being more cytotoxic for the HL-60 cell line with IC50 values of 13.08 μM and 11.38 μM, respectively. Regarding the protein kinase inhibition assay, 3c inhibited seven different kinases and 4a strongly inhibited the CK1δ/ε kinase. The studied kinases are involved in several cellular functions such as proliferation, migration, cell death and cell cycle progression. Additional analysis by flow cytometry revealed that 3c and 4a caused depolarization of the mitochondrial membrane, suggesting apoptosis mediated by the intrinsic pathway. Compound 3c induced arrest in G1 phase of the cell cycle on HL-60 cells, and in the annexin V assay approximately 50% of cells were in apoptosis at the highest concentration tested (26 μM). Compound 4a inhibited cell cycle by accumulation of abnormal postmitotic cells at G1 phase and induced DNA fragmentation at the highest concentration (22 μM).

The Asteraceae, one of the largest families among angiosperms, is chemically characterised by the production of sesquiterpene lactones (SLs). A total of 1,111 SLs, which were extracted from 658 species, 161 genera, 63 subtribes and 15 tribes of Asteraceae, were represented and registered in two dimensions in the SISTEMATX, an in-house software system, and were associated with their botanical sources. The respective 11 block of descriptors: Constitutional, Functional groups, BCUT, Atom-centred, 2D autocorrelations, Topological, Geometrical, RDF, 3D-MoRSE, GETAWAY and WHIM were used as input data to separate the botanical occurrences through self-organising maps. Maps that were generated with each descriptor divided the Asteraceae tribes, with total index values between 66.7% and 83.6%. The analysis of the results shows evident similarities among the Heliantheae, Helenieae and Eupatorieae tribes as well as between the Anthemideae and Inuleae tribes. Those observations are in agreement with systematic classifications that were proposed by Bremer, which use mainly morphological and molecular data, therefore chemical markers partially corroborate with these classifications. The results demonstrate that the atom-centred and RDF descriptors can be used as a tool for taxonomic classification in low hierarchical levels, such as tribes. Descriptors obtained through fragments or by the two-dimensional representation of the SL structures were sufficient to obtain significant results, and better results were not achieved by using descriptors derived from three-dimensional representations of SLs. Such models based on physico-chemical properties can project new design SLs, similar structures from literature or even unreported structures in two-dimensional chemical space. Therefore, the generated SOMs can predict the most probable tribe where a biologically active molecule can be found according Bremer classification.

Fifty 2-[(arylidene)amino]-4,5-cycloalkyl[b]thiophene-3-carbonitrile derivatives were screened for their in vitro antifungal activities against Candida krusei and Cryptococcus neoformans. Based on experimentally determined minimum inhibitory concentration (MIC) values, we conducted computer-aided drug design studies [molecular modelling, chemometric tools (CPCA, PCA, PLS) and QSAR-3D] that enable the prediction of three-dimensional structural characteristics that influence the antifungal activities of these derivatives. These predictions provide direction with regard to the syntheses of new derivatives with improved biological activities, which can be used as therapeutic alternatives for the treatment of fungal infections.

The novel 2-aminothiophene derivative 2-amino-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carbonitrile (6CN) has shown potential anti-proliferative activity in human cancer cell lines. However, the poor aqueous solubility of 6CN impairs its clinical use. This work aimed to develop binary 6CN-β-cyclodextrin (βCD) systems with the purpose of increasing 6CN solubility in water and therefore, to improve its pharmacological activity. The 6CN-βCD binary systems were prepared by physical mixing, kneading and rotary evaporation methods and further characterized by FTIR, XRD, DSC, TG and SEM. In addition, molecular modeling and phase solubility studies were performed. Finally, MTT assays were performed to investigate the cytostatic and anti-proliferative effects of 6CN-βCD binary systems. The characterization results show evident changes in the physicochemical properties of 6CN after the formation of the binary systems with βCD. In addition, 6CN was associated with βCD in aqueous solution and the solid state, which was confirmed by molecular modeling and the aforementioned characterization techniques. Phase solubility studies indicated that βCD forms stable 1:1 complexes with 6CN. The MTT assay demonstrated the cytostatic and anti-proliferative activities of 6CN-βCD binary systems and therefore, these might be considered as promising candidates for new anticancer drugs.

Uno de los objetivos de un curso básico de hidráulica del flujo libre en canales es el análisis de perfiles del flujo gradualmente variado. Este trabajo proporciona una estrategia de enseñanza-aprendizaje que puede mejorar la práctica universitaria docente de la hidráulica. Es bien conocida la gráfica profundidad contra energía específica (y-E) para describir e interpretar la hidráulica del flujo libre. Se propone complementarla con la gráfica profundidad contra pendiente de energía (y-sf). A partir de las comparaciones gráficas se ilustran los conceptos de flujo subcrítico (y>ycrítica, vynormal, vOne objective of an introductory course of open-channel flow is the analysis of gradually varied flow profiles. This paper shows a teaching-learning strategy that might improve the university practices for teaching hydraulics. It is well known the depth-specific energy curve (y-E) for describing and interpreting open-channel flow hydraulics. It is proposed to complement that curve with the depth-energy slope curve (y-sf). By using a graphic comparison, it aims to illustrate the concepts of the subcritical (y>ycritical, vynormal, v

This paper analyzes the relationship between bank credit policies and their ex-post performance. Literature review reveals that, sometimes, credit markets can be affected by a stronger endogenous component that usually assumed. We propose that the growth speed of the bank credit portfolio in expansive cycles is related to its ex-post performance once the recession cycle begins. The analysis outcomes refl ect a strong relation between the speed in the expansion of the credit and a poorer behaviour of the benefi ts, returns and insolvencies.

The beta-lapachone is a product obtained from the Ipê Roxo tree [Tabebuia avellandae], which has proved its excellent antineoplasic potential acting through a particular mechanism of apoptosis against various cancer types. This study aims at determining the identity card of beta-lapachone by means of physico-chemical and pharmaco-technical characterization. A purifying process has been performed, as well as the isolation of a contaminant, its isomer alpha-lapachone. A stability study was also performed, determining the ideal storing conditions for beta-lapachone, essential for the ongoing pre-formulation studies for obtaining the different classic pharmaceutical forms and modified release systems.

Semisynthetic and commercial coumarins were investigated for their antibacterial and adjuvant properties with antibiotic agents against norfloxacin, erythromycin, and tetracycline resistant Staphylococcus aureus as based on efflux mechanisms. The coumarins and certain commercial antibiotics had their Minimum Inhibitory Concentrations determined by broth microdilution assay against resistant S. aureus strains which overexpress efflux pump proteins. For evaluation of the modulatory activity, the antibiotics MICs were determined in the presence of the coumarin derivatives at subinhibitory concentration. Although the coumarins did not display relevant antibacterial activity (MIC ≥ 128 µg/mL), they did modulate the antibiotics activities. Various coumarins, especially the alkylated derivatives in combination with antibiotics at subinhibitory concentrations, modulated antibiotic activity, reducing the MIC for tetracycline and norfloxacin by 2 to 8 times. Polar Surface Area (PSA) studies were performed and the fact that the presence of apolar groups is an important factor for the modulatory activity of coumarins was corroborated. Docking on the Penicillin-Binding Protein from MRSA identified that 18 is a potential ligand presenting low Ebinding. The results indicate that coumarin derivatives modulated antibiotic resistance and may be used as potential antibiotic adjuvants, acting by bacterial efflux pump inhibition in S. aureus.

Cancer is a major public health problem with limited success of available treatments, pointing to the need for new strategies to be developed. Phosphoethanolamine exhibits broad antitumor activity in a variety of tumor cells and potent inhibitor effects on tumor progress in vivo. Once-used organophosphates inhibit acetylcholinesterase (AChE), resulting in toxic effects to the user. As this group is present in phosphoethanolamine, we perform prediction of the in silico metabolism of phosphoethanolamine and submit this series to a docking study on AChE. A total of 10 metabolites were indicated by the prediction, including ammonia and hydroxylamine, which were not included in the study. Using a group of 8 organophosphorus whose pIC50 values ranged from 5.92 to 9.47 as template, we observed that no compound present in the phosphoethanolamine series had a binding energy lower than that of organophosphorus, suggesting that the series has low inhibitory power on AChE. In light of this, we conclude that phosphoethanolamine and its predicted metabolites do not significantly inhibit AChE to cause a cholinergic crisis. This finding highlights the importance of investigating this compound as lead for potential anticancer agents.

Background. For hand surgery, brachial plexus blocks provide effective anesthesia but produce undesirable numbness. We hypothesized that distal peripheral nerve blocks will better preserve motor function while providing effective anesthesia. Methods. Adult subjects who were scheduled for elective ambulatory hand surgery under regional anesthesia and sedation were recruited and randomly assigned to receive ultrasound-guided supraclavicular brachial plexus block or distal block of the ulnar and median nerves. Each subject received 15 mL of 1.5% mepivacaine at the assigned location with 15 mL of normal saline injected in the alternate block location. The primary outcome (change in baseline grip strength measured by a hydraulic dynamometer) was tested before the block and prior to discharge. Subject satisfaction data were collected the day after surgery. Results. Fourteen subjects were enrolled. Median (interquartile range [IQR]) strength loss in the distal group was 21.4% (14.3, 47.8%), while all subjects in the supraclavicular group lost 100% of their preoperative strength, P = 0.001. Subjects in the distal group reported greater satisfaction with their block procedures on the day after surgery, P = 0.012. Conclusion. Distal nerve blocks better preserve motor function without negatively affecting quality of anesthesia, leading to increased patient satisfaction, when compared to brachial plexus block.

El 22 de diciembre de 2007, falleció el Sr. Dr. Francisco Mendoza Jaime, quien al momento de su partida ejercía la Jefatura del Servicio de Gastroenterología y Hepatología del Instituto Oncológico Nacional SOLCA, Guayaquil. Su sentido deceso es una irreparable pérdida, no sólo para sus familiares, amigos y esta Institución, sino para toda nuestra sociedad. El Doctor Mendoza nació el 30 de julio de 1953. Fue segundo hijo del matrimonio formado por el Doctor en Jurisprudencia, Ramón Tarciso Mendoza Mendoza y Doña Blanca Elena Jaime Ortiz. Luego de graduarse de bachiller en Humanidades Modernas, en la especialidad de Química y Biología, en enero de 1971, ingresó a la Facultad de Medicina de la Universidad Católica de Santiago de Guayaquil. Así inició su carrera universitaria, que culminó al obtener el Título de Doctor en Medicina y Cirugía, en Enero de 1979. En 1972, realizó un curso intensivo de inglés en la Universidad de Saint Louis, Missouri. Paralelamente realizaba sus prácticas hospitlarias en la Clínica Julián Coronel, donde bajo la dirección de los médicos de este centro privado, como el Dr. Eduardo Ortega Moreira y en especial, quien fue su Tutor, el Dr. Juan Tanca Campozano, planificó su estrategia para en el futuro ser un especialista en Gastroenterología y Hepatología. Finalmente cumplió el año de Medicatura Rural en la ciudad de Latacunga, en el periodo 1979-1980. Ayudado por sus familiares, viajó a París-Francia y fue admitido como asistente extranjero en el Servicio de Gastroenterología y Hepatología del Hospital Beaujon, bajo la supervisión de los Profesores Jean Pierre Benhamou y Serge Erlinger. Su tesis de postgrado de especialidad su tituló, “El quiste biliar y su prevalencia a la ecografía”. También realizó estudio de perfeccionamiento en endoscopia digestiva, en especial colonoscopía, en el Hospital Saint Lazare, en la misma ciudad de París, con el profesor Alain Bitoun. El 11 de septiembre de 1985, la “Faculté de Médicine Xavier Bichat de la Université de Paris VII”, le otorgó el diploma de Assistant Éxtranger (asistente extranjero) en el Service d’hépatogastroentérologie de I’hopital Beaujon”, firmado por el profesor Jean –Pierre Benhamou.

Este artículo tiene por objeto aplicar el transporte de cantidad de movimiento al flujo en canales como una metodología independiente de otros principios físicos. Así se subsana una carencia de la literatura técnica cuando aborda la interpretación adicional de fenómenos hidráulicos que habitualmente se tratan desde la conservación de la energía. Concluye acerca del comportamiento de la profundidad de flujo en un canal ante diversas condiciones de flujo o variaciones de la profundidad o en presencia de controles hidráulicos. Con la ayuda de la ecuación de transporte de cantidad de movimiento a lo largo de un canal se interpreta el comportamiento del tirante hidráulico en flujo uniforme, en flujo no uniforme con variación gradual y en algunos fenómenos locales de flujo rápidamente variado como ocurre en las transiciones y en el resalto hidráulico. Se obtienen las ecuaciones del resalto hidráulico para calcular la profundidad inicial y secuente, conocida una de las dos, en diversas secciones transversales del canal.

Se presenta la función fuerza específica en flujo libre en canales de sección generalizada, se estudian sus características principales, un criterio de flujo crítico y su conversión a función adimensional o reducida.

Major depressive disorder (MDD) is among the most prevalent neuropsychiatric disorders associated with HIV infection; however, its risks and neurobiologic correlates in diverse cultures are poorly understood. This study aimed to examine the frequency of MDD among HIV+ participants in southern Brazil. We hypothesized that the frequency and severity of MDD would be higher among individuals with HIV+ compared with HIV- and higher in HIV subtype B compared with C. Individuals with HIV (n = 39) as well as seronegative controls (n = 22) were enrolled in a cross-sectional, prospective, observational study. Current and lifetime history of MDD was diagnosed by MINI-Plus; symptom severity was assessed by Beck Depression Inventory-II (BDI-II). Current and past episodes of MDD were significantly more frequent in the HIV+ versus HIV- group: current MDD, 15 (38.5 %) vs. 0 (0 %), p = 0.0004; past MDD, 24 (61.5 %) vs. 3 (13.6 %), p = 0.0004. The median BDI-II score in the HIV+ group was significantly higher than that in the HIV- (13 (8-27.5) vs. 2.5 (1-5.5); p