Search

PURPOSE: Professionals who work with rehabilitation of the hand usually assess performance components as their main outcome measures. Intervention is aimed at normalization of deficits of these components, with the expectation that the integrity of the structures and functions of the body will revert to improvements in the client's functional performance. The objectives of this study were to describe changes in patients who received rehabilitation in a Brazilian public hospital after having suffered hand injuries due to workplace accidents, and to examine the relations between performance components and levels of functioning. METHODS: Observational cross-sectional study was used. A convenience sample was selected, including 42 patients assessed at service admission and at discharge. Assessed characteristics included grip strength, wrist and finger range of movement (ROM), sensitivity, and self-perceptions of functional performance (COPM). Statistical procedures included correlations between performance components and COPM scores and differences on selected variables at admission and discharge. RESULTS: Significant improvements in all assessed functional components. COPM values increased more than 100% after intervention (effect size d = 1.996 for performance and d = 1.553 for satisfaction) demonstrating improvements in both domains. Low correlations between grip strength and COPM scores were found only at admission (r = 0.314; p = 0.045). When the relationship between gains in strength and COPM scores at discharge were examined, significant correlations were found with the performance (r = 0.324; p = 0.039) and satisfaction (r = 0.0326; p = 0.038) subscales. CONCLUSIONS: Results of this study provide evidence for functional gains in clients treated in a rehabilitation service and supply information about the relation between specific components and functional performance. [ABSTRACT FROM AUTHOR]

OBJECTIVES: To describe workers who returned to work after a hand injury and to analyze the factors associated with this outcome three years after discharge from rehabilitation. METHODS: An observational, cross-sectional study was carried out with triangulation of quantitative and qualitative methods. The quantitative analysis used a database with sociodemographic, functional and clinical information on 35 individuals who were classified into two groups (return/no return to work). Multivariate analysis was conducted using the CART (Classification and Regression Tree) algorithm to assess the predictive value of four models, thereby identifying workers who had returned or not returned to work. Using the results from the statistical analysis, a semi-structured form was prepared for interviews, which were conducted with seven workers randomly selected from the sample. RESULTS: Out of the 35 workers who participated in this study, 30 returned and five did not return to work. The majority were male, married and of low educational level, and the mean age was 37 years. The variables with the greatest predictive power were grip strength, occupational performance scores, occupational category and age. The qualitative analysis confirmed the multifactorial nature of the return to work and demonstrated that the presence of a professional to follow-up the process, adjustments to the workstation and working hours (to enable treatment continuity) and also accident benefits may contribute to a successful return. CONCLUSIONS: This study showed the complexity of the return to work by workers with hand injuries, highlighting a number of factors associated with this outcome and the importance of individualized assessment centered on the worker. [ABSTRACT FROM AUTHOR]

Tetracycline (TC) is a widely used antibiotic, and evaluating its interaction with humic substances (HS) that act as a complexing agent in the environment is essential to understanding the availability of this contaminant in the environment. This study evaluated the interaction between HS and TC using different spectroscopic techniques, theoretical studies, and biological assays simulating environmental conditions. TC interacts with HS, preferably by electrostatic forces, with a binding constant of 9.2 × 10 3 M -1 (30 °C). This process induces conformational changes in the superstructure, preferably in the HS, like protein fraction. Besides, studies using the 8-anilino-1-naphthalene sulfonate (ANS) probe indicated that the antibiotic alters the hydrophobicity degree on HS's surface. Synchronized fluorescence shows that the TC interaction occurs preferentially with the protein-like fraction of soil organic matter (K SV = 26.28 ± 1.03 M -1 ). The TC epitope was evaluated by 1 H NMR and varied according to the pH (4.8 and 9.0) of the medium, as well as the main forces responsible for the stabilization of the HS-TC complex. The molecular docking studies showed that the formation of the HS-TC complex is carried out spontaneously (ΔG = -7.1 kcal mol -1 ) and is stabilized by hydrogen bonds and electrostatic interactions, as observed in the experimental spectroscopic results. Finally, biological assays indicated that HS influenced the antimicrobial activity of TC. Thus, this study contributed to understanding the dynamics and distribution of TC in the environment and HS's potential in the remediation of antibiotics of this class in natural systems, as these can have adverse effects on ecosystems and human health., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

In environmental systems, the soil is a principal route of contamination by various potentially toxic species. Roxarsone (RX) is an arsenic (V) organic compound used to treat parasitic diseases and as an additive for animal fattening. When the animal excretes RX, the residues may lead to environmental contamination. Due to their physicochemical properties, the soil's humic substances (HS) are important in species distribution in the environment and are involved in various specific interaction/adsorption processes. Since RX, an arsenic (V) compound, is considered an emerging contaminant, its interaction with HS was evaluated in simulated environmental conditions. The HS-RX interaction was analyzed by monitoring intrinsic HS fluorescence intensity variations caused by complexation with RX, forming non-fluorescent supramolecular complexes that yielded a binding constant K b (on the order of 10 3 ). The HS-RX interaction occurred through static quenching due to complex formation in the ground state, which was confirmed by spectrophotometry. The process was spontaneous (ΔG < 0), and the predominant interaction forces were van der Waals and hydrogen bonding (ΔH < 0 and ΔS < 0), with an electrostatic component evidenced by the influence of ionic strength in the interaction process. Structural changes in the HS were verified by synchronized and 3D fluorescence, with higher variation in the region referring to the protein-like fraction. In addition, metal ions (except ions Cu(II)) favored HS-RX interaction. When interacting with HS, the RX epitope was suggested by 1 H NMR, which indicated that the entire molecule interacts with the superstructure. An enzyme inhibition assay verified the ability to reduce the alkaline phosphatase activity of free and complexed RX (RX-HS). Finally, this work revealed the main parameters associated with HS and RX interaction in simulated environmental conditions, thus, providing data that may help our understanding of the dynamics of organic arsenic-influenced soils., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Cardiac adaptation to conditioning in horses was evaluated after empirical training based on trainers' experience. Twelve purebred Arabian horses, aged (mean ± SD) 28.42 ± 3.75 months, which did not perform any type of exercise prior to the research, were submitted to treadmill conditioning for six weeks. The conditioning program was based on the velocity run by the horse at which the blood lactate concentration, determined in an incremental exercise test (IET), reached 2 mmol/L (V 2 ). The velocity at which the blood lactate concentration reached 4 mmol/L (V 4 ) was also determined. The echocardiograms were performed at rest with pulsed-wave and tissue Doppler imaging in B- and M-modes. All procedures were carried out before and after the conditioning period. The results showed increases in V 2 (from 5.2 ± 0.3 to 6.7 ± 0.4 m/s) and V 4 (from 5.8 ± 0.4 to 7.6 ± 0.5 m/s) ( p < 0.0001). There were also increases in the left ventricle internal diameter at diastole (LVIDd), left ventricle mass (LV mass), and stroke volume (SV), while no changes were observed in the LV free wall thickness and mean and relative wall thicknesses. The conditioning protocol, which was completed by all horses, proved to be safe and efficient, as it improved the aerobic capacity of the animals. Finally, the cardiac remodeling that occurred was mainly associated with the effect of physical training.

Background: Thimerosal (TM) is an organic mercury compound used as a preservative in many pharmacological inputs. Mercury toxicity is related to structural and functional changes in macromolecules such as hemoglobin (Hb) in erythrocytes (Ery)., Method: Human Hb and Ery were used to evaluate O 2 uptake based on the TM concentration, incubation time, and temperature. The influence of TM on the sulfhydryl content, production of reactive oxygen species (ROS), and membrane fragility was also evaluated. Raman spectra and atomic force microscopy (AFM) profiles for Ery in the presence and absence of TM were calculated, and docking studies were performed., Results: At 37 °C, with 2.50 μM TM (higher concentration) and after 5 min of incubation in Hb and Ery, we observed a reduction in O 2 uptake of up to 50 %, while HgCl 2 , which was used as a positive control, showed a reduction of at least 62 %. Total thiol assays in the presence of NEM (thiol blocker) quantified the preservation of almost 60 % of free SH in Ery. Based on the Raman spectrum profile from Ery-TM, structural differences in the porphyrinic ring and the membrane lipid content were confirmed. Finally, studies using AFM showed changes in the morphology and biomechanical properties of Ery. Theoretical studies confirmed these experimental results and showed that the cysteine (Cys) residues present in Hb are involved in the binding of TM., Conclusion: Our results show that TM binds to human Hb via free Cys residues, causing conformation changes and leading to harmful effects associated with O 2 transport., (Copyright © 2022 Elsevier GmbH. All rights reserved.)

Toxicological effects of 25H-NBOMe and 25H-NBOH recreational drugs on zebrafish embryos and larvae at the end of 96 h exposure period were demonstrated. 25H-NBOH and 25H-NBOMe caused high embryo mortality at 80 and 100 µg mL -1 , respectively. According to the decrease in the concentration tested, lethality decreased while non-lethal effects were predominant up to 10 and 50 µg mL -1 of 25H-NBOH and 25H-NBOMe, respectively, including spine malformation, egg hatching delay, body malformation, otolith malformation, pericardial edema, and blood clotting. We can disclose that these drugs have an affinity for DNA in vitro using biophysical spectroscopic assays and molecular modeling methods. The experiments demonstrated that 25H-NBOH and 25H-NBOMe bind to the unclassical major groove of ctDNA with a binding constant of 27.00 × 10 4 M -1 and 5.27 × 10 4 M -1 , respectively. Furthermore, these interactions lead to conformational changes in the DNA structure. Therefore, the results observed in the zebrafish embryos and DNA may be correlated., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2021 The Author(s).)

Tetracycline (TC), oxytetracycline (OTC), and chlortetracycline (CTC) interactions with the allergenic milk protein casein (CAS) were here evaluated simulating food conditions. The antibiotics assessed interact with CAS through static quenching and form non-fluorescent complexes. At 30 °C, the binding constant (K b ) varied from 0.05 to 1.23 × 10 6 M -1 . Tetracycline interacts with CAS preferably through electrostatic forces, while oxytetracycline and chlortetracycline interactions occur by hydrogen bonds and van der Waals forces. The interaction process is spontaneous, and the magnitude of interaction based on K b values, followed the order: TC < CTC < OTC. The distances between the donor (protein) and the receptors (TC, OTC, and CTC) were determined by Förster resonance energy transfer (FRET) and varied from 3.67 to 4.08 nm. Under natural feeding conditions, the citrate decreased the affinity between TC and CAS; a similar effect was observed for OTC in the presence of Ca(II), Fe(III) and lactose. Synchronized and three-dimensional (3D) fluorescence studies indicated alterations in the original protein conformation due to the interaction process, which may influence allergenic processes. In addition, complexation with CAS modulated the antimicrobial activity of CTC against S. aureus , demonstrated that the interaction process possibly alters the biological properties of antibiotics and the own protein, in the food conditions.Communicated by Ramaswamy H. Sarma.

Thimerosal (TH), an organomercurial compound, is used as a preservative in vaccines and cosmetics. Its interaction with human hemoglobin (Hb) was investigated under physiological conditions using biophysical and biological assays, aiming to evaluate hazardous effects. TH interacts spontaneously with Hb (stoichiometry 2:1, ligand-protein), preferably by electrostatic forces, with a binding constant of 1.41 × 10 6  M -1 . Spectroscopic data allows to proposing that TH induces structural changes in Hg, through ethylmercury transfer to human Hb-Cys93 residues, forming thiosalicylic acid, which, in turn, interacts with the positive side of the amino acid in the Hb-HgEt adduct chain. As a consequence, inhibition of Hb-O 2 binding capacity up to 72% (human Hb), and 50% (human erythrocytes), was verified. Dose-dependent induction of TH forming advanced glycation end products (AGE) and protein aggregates (amyloids) was additionally observed. Finally, these results highlight the toxic potential of the use of TH in biological systems, with a consequent risk to human health., Competing Interests: Declaration of competing interest The authors declare no competing or financial interests., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Biophysical, theoretical and biological in vitro studies were carried out to evaluate the interaction of the main allergen protein of egg white (ovalbumin, OVA) with sulphonamides (SA): sulphathiazole (S1), sulfaquinoxaline (S2), sulfadimethoxine (S3) and sulfamethazine (S4). The binding constants for the OVA-SA supramolecular complexes ranged from 1.20 to 30.66 × 10 5  M -1 , observing the following order of affinity: S1 > S2 > S4 > S3. The preferential forces in the stabilization of the OVA complexes with S2 and S3 were hydrogen bonds and Van der Waals forces, whereas for OVA-S1 and OVAS4, were electrostatic interactions. Interaction process led to a change in the native structure of the protein, which may potentiate its natural allergenicity. Cations Ca(II), Mg(II) and Fe(III) favor the interaction of OVA with S1 and S2. The theoretical studies performed were consistent with the spectroscopic data. Finally, it was found that the interaction process for sulfonamides evaluated with OVA change the inhibition activity profile these antibiotics against strains of Escherichia coli ATCC 25922 and Bacillus megaterium APFSG3isox, but not the minimal inhibitory concentration values., (Copyright © 2019 Elsevier B.V. All rights reserved.)

This work aimed to evaluate the inhibition of Candida rugosa lipase by five guanylhydrazone derivatives through biological, biophysical and theoretical studies simulating physiologic conditions. The compound LQM11 (IC 50  = 14.70 μM) presented the highest inhibition against the enzyme. Therefore, for a better understanding of the interaction process, spectroscopic and theoretical studies were performed. Fluorescence and UV-vis assays indicate a static quenching mechanism with non-fluorescent supramolecular complex formation and changing the native protein structure. The binding process was spontaneous (ΔG < 0) and electrostatic forces (ΔH < 0 and ΔS > 0) played a preferential role in stabilizing the complex ligand-lipase. The compounds were classified as non-competitive inhibitors using orlistat as a reference in competition studies. Based on the 1 H NMR assays it was possible to propose the sites of ligand (epitope) that bind preferentially to the enzyme and the theoretical studies were consistent with the experimental results. Finally, LQM11 was efficient as a lipase inhibitor of the crude intestinal extract of larvae of Rhynchophorus palmarum, an important agricultural plague, showing potential for control of this pest. Within this context, the real potential of this biotechnological application deserves further studies., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Considering the need for the development of new antitumor drugs, associated with the great antitumor potential of thiophene and thiosemicarbazonic derivatives, in this work we promote molecular hybridization approach to synthesize new compounds with increased anticancer activity., Objective: Investigate the antitumor activity and their likely mechanisms of action of a series of N-substituted 2-(5-nitro-thiophene)-thiosemicarbazone derivatives., Methods: Methods were performed in vitro (cytotoxicity, cell cycle progression, morphological analysis, mitochondrial membrane potential evaluation and topoisomerase assay), spectroscopic (DNA interaction studies), and in silico studies (docking and molecular modelling)., Results: Most of the compounds presented significant inhibitory activity; the NCIH-292 cell line was the most resistant, and the HL-60 cell line was the most sensitive. The most promising compound was LNN-05 with IC50 values ranging from 0.5 to 1.9 µg.mL-1. The in vitro studies revealed that LNN-05 was able to depolarize (dose-dependently) the mitochondrial membrane, induceG1 phase cell cycle arrest noticeably, promote morphological cell changes associated with apoptosis in chronic human myelocytic leukaemia (K-562) cells, and presented no topoisomerase II inhibition. Spectroscopic UV-vis and molecular fluorescence studies showed that LNN compounds interact with ctDNA forming supramolecular complexes. Intercalation between nitrogenous bases was revealed through KI quenching and competitive ethidium bromide assays. Docking and Molecular Dynamics suggested that 5-nitro-thiophene-thiosemicarbazone compounds interact against the larger DNA groove, and corroborating the spectroscopic results, may assume an intercalating interaction mode., Conclusion: Our findings highlight 5-nitro-thiophene-thiosemicarbazone derivatives, especially LNN-05, as a promising new class of compounds for further studies to provide new anticancer therapies., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Acridines are considered an important class of compounds due to their wide variety of biological activities. In this work, we synthesized four acridine derivatives (1-4) and evaluated their biological activity against the Plasmodium falciparum W2 line, as well as studied the interaction with ctDNA and HSA using spectroscopic techniques and molecular docking. The acridine derivative 2 (IC 50  = 0.90 ± 0.08 μM) was more effective against P. falciparum than primaquine (IC 50  = 1.70 ± 0.10 μM) and similar to amsacrine (IC 50  = 0.80 ± 0.10 μM). In the fluorescence and UV-vis assays, it was verified that the acridine derivatives interact with ctDNA and HSA leading to a non-fluorescent supramolecular complex formation. The non-covalent binding constants ranged from 2.09 to 7.76 × 10 3  M -1 , indicating moderate interaction with ctDNA. Through experiments with KI, fluorescence contact energy transfer and competition assays were possible to characterize the main non-covalent binding mode of the acridines evaluated with ctDNA as intercalation. The binding constants obtained showed a high linear correlation with the IC 50 values against the antimalarial activity, suggesting that DNA may be the main biological target of these molecules. Finally, HSA interaction studies were performed and all evaluated compounds bind to the site II of the protein. The less active compounds (1 and 3) presented the highest affinity to HSA, indicating that the interaction with carrier protein can affect the (bio)availability of these compounds to the biological target., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Haemonchus contortus is a gastrointestinal nematode that is responsible for high mortality rates in ruminant herds. The resistance of nematodes to synthetic anthelmintics is widespread and requires a continuous search for new bioactive molecules, such as proteins. The objective of this study was to evaluate the anthelmintic potential of a protease purified from the latex of Ficus benjamina against H. contortus . Fresh latex was collected from plants via small incisions in the green stems, the rubber was removed by centrifugation, and the latex protein extract (LPE) was obtained. After LPE fractionation with ammonium sulfate and chromatography of the fraction containing the highest proteolytic activity on CM-cellulose, a cysteine protease (FbP) was purified. FbP has a molecular mass of approximately 23.97 kDa, and its proteolytic activity was stable between pH 6.0 and pH 10 and over a broad temperature range, with optimum activity at 60 °C. FbP inhibited both the development and exsheathment of H. contortus larvae, with 50% effective concentrations of 0.26 and 0.79 mg/mL, respectively. We conclude that this cysteine protease from F. benjamina latex with anthelmintic activity against H. contortus could be a promising alternative for the development of products for use in parasite control programmes.

The interaction between bovine serum albumin (BSA) and thimerosal (TM), an organomercury compound widely employed as a preservative in vaccines, was investigated simulating physiological conditions and using different spectroscopic techniques. The results, employing molecular fluorescence showed the interaction occurs by static quenching through electrostatic forces (ΔH < 0 and ΔS > 0), spontaneously (ΔG = -4.40 kJ mol -1 ) and with a binding constant of 3.24 × 10 3  M -1 . Three-dimensional fluorescence studies indicated that TM causes structural changes in the polypeptide chain of the BSA, confirmed by circular dichroism that showed an increase in α-helix (from 43.9 to 47.8%) content after interaction process. Through synchronized fluorescence and employing bilirubin as a protein site marker, it was confirmed the preferential interaction of TM in the subdomain IB of BSA. The interaction mechanism proposed in this work is based on the reaction of TM with BSA through of free Cys34 residue, forming the adduct BSA-HgEt with the thiosalicylic acid release, which possibly interacts electrostatically with positive side chain amino acids of the modified protein. Finally, it was proven that both TM and EtHgCl accelerate the protein fibrillation kinetics in 42 and 122%, respectively, indicating the toxicity of these compounds in biological systems., (Copyright © 2018 Elsevier B.V. All rights reserved.)

The cytotoxic activity of the pimarane diterpene annonalide (1) and nine of its semisynthetic derivatives (2-10) was investigated against the human tumor cell lines HL-60 (leukemia), PC-3 (prostate adenocarcinoma), HepG2 (hepatocellular carcinoma), SF-295 (glioblastoma) and HCT-116 (colon cancer), and normal mouse fibroblast (L929) cells. The preparation of 2-10 involved derivatization of the side chain of 1 at C-13. Except for 2, all derivatives are being reported for the first time. Most of the tested compounds presented IC 50 s below 4.0 μM, being considered potential antitumor agents. The structures of all new compounds were elucidated by spectroscopic analyses including 2D NMR and HRMS. Additionally, the interaction of annonalide (1) with ctDNA was evaluated using spectroscopic techniques, and the formation of a supramolecular complex with the macromolecule was confirmed. Competition assays with fluorescent probes (Hoechst and ethidium bromide) and theoretical studies confirmed that 1 interacts preferentially via DNA intercalation with stoichiometric ratio of 1:1 (1:ctDNA). The ΔG value was calculated as -28.24 kJ mol -1 , and indicated that the interaction process occurs spontaneously. Docking studies revealed that van der Walls is the most important interaction in 1-DNA and EB-DNA complexes, and that both ligands (1 and EB) interact with the same DNA residues (DA6, DA17 and DT19)., (Copyright © 2018. Published by Elsevier B.V.)

Twenty-five piperidines were studied as potential radical scavengers and antitumor agents. Quantitative interaction of compounds with ctDNA using spectroscopic techniques was also evaluated. Our results demonstrate that the evaluated piperidines possesses different abilities to scavenge the radical 2,2-diphenyl-1-picrylhydrazyl (DPPH) and the anion radical superoxide ( • O 2 - ). The piperidine 19 was the most potent radical DPPH scavenger, while the most effective to • O 2 - scavenger was piperidine 10 . In general, U251, MCF7, NCI/ADR-RES, NCI-H460 and HT29 cells were least sensitive to the tested compounds and all compounds were considerably more toxic to the studied cancer cell lines than to the normal cell line HaCaT. The binding mode of the compounds and ctDNA was preferably via intercalation. In addition, these results were confirmed based on theoretical studies. Finally, a linear and exponential correlation between interaction constant (K b ) and GI 50 for several human cancer cell was observed.

The interactions of tetracycline (TC), oxytetracycline (OTC) and chlortetracycline (CTC) with ovalbumin (OVA), the main allergen protein of egg white, were investigated by molecular spectroscopy and electrophoresis at three pH conditions (1.5, 4.6 and 7.4). Molecular and synchronous fluorescence, UV-vis spectroscopy, electrophoresis and 1 H NMR were used to study the interaction process. Tetracyclines interact with ovalbumin fluorescence by a static quenching mechanism with non-fluorescent complex formation changing the native protein structure. The binding constant (K b ) ranged from 2.11×10 4 to 58.4×10 4 Lmol -1 , and corresponding thermodynamic parameters were measured at different temperatures and pH values. The binding process was spontaneous (ΔG<0), and the magnitude of the interaction increased in the following order: TC

Thirty-nine Schiff bases were synthesized by performing microwave-assisted condensation of the corresponding aldehydes and aromatic amines. Their reactive nitrogen species (RNS) scavenging activity and inhibitory effects against cancer cell growth were then subsequently investigated. Additionally, the interaction between the calf thymus DNA (ctDNA) and selected Schiff bases was evaluated using fluorescence spectroscopy, and their binding parameters were determined. The yields of the various compounds ranged from moderate to excellent (43-99%) after only a 2-min reaction. The hydroxylated Schiff bases 2, 8, 15, 16, 18, 20, 29, 32, 34, and 37 were found to be potent scavengers of 2,2-diphenyl-1-picrylhydrazyl (DPPH) radicals with half-maximal scavenging concentration (SC 50 ) values lower than that of the positive control, resveratrol. The presence of hydroxyl substituents on the aromatic rings also proved essential to the cytotoxicity of the compounds. The binding constants (K b ) obtained using fluorescence spectroscopy ranged from 0.37 to 3.07×10 5 Lmol -1 , and were strongly influenced by the structure and hydroxylation degree. Schiff bases 3 and 8 showed promising cytotoxic activity, with half-maximal growth inhibitory (GI 50 ) values in the same order of magnitude as those exhibited by the reference drug, doxorubicin against various cell lines. Interestingly, these compounds also showed the highest K b , suggesting that the cytotoxic activity could be related to their interaction with the DNA of the tumor cells. The results of this study highlighted some Schiff bases as potential lead compounds for the design of new free radical scavengers and anticancer agents., (Copyright © 2017 Elsevier B.V. All rights reserved.)

The interaction of small molecules with DNA has been quite important, since this biomolecule is currently the major target for a wide range of drugs in clinical use or advanced clinical research phase. Thus, the present work aimed to assess the interaction process between the bioactive compound 11a-N-tosyl-5-carba-pterocarpan, (LQB-223), that presents antitumor activity, with DNA, employing spectroscopic techniques, electrophoresis, viscosity and theoretical studies. Through UV-vis and molecular fluorescence spectroscopy, it was possible to infer that the preferential quenching mechanism was static, characterized by non-fluorescent supramolecular complex formation between the LQB-223 and DNA. The binding constant was 1.94∙10 3 Lmol -1 (30°C) and, according to the thermodynamic parameters, the main forces involved in the interaction process are hydrophobic. Potassium iodide assay, competition with ethidium bromide, fluorescence contact energy transfer and melting temperature profile of DNA were employed to evaluate the binding mode. Except for KI assay, all results obtained indicated minor groove as the preferential binding mode of LQB-223 to DNA. These observations were supported by ionic strength assay, viscosity and molecular dynamics and docking studies. Finally, electrophoresis analysis demonstrated that the interaction does not promote DNA fragmentation, but it leads to variation in the migration profile after increasing the ligand concentration., (Copyright © 2016 Elsevier B.V. All rights reserved.)

A series of novel 1-(substituted phenyl)-3-(2-oxo-1,3,4-oxadiazol-5-yl) β-carbolines (4a-e) and the corresponding Mannich bases 5-9(a-c) were synthesized and evaluated for their in vitro antitumor activity against seven human cancer cell lines. Compounds of 4a-e series showed a broad spectrum of antitumor activity, with GI50 values lower than 15μM for five cell lines. The derivative 4b, having the N,N-dimethylaminophenyl group at C-1, displayed the highest activity with GI50 in the range of 0.67-3.20μM. A high selectivity and potent activity were observed for some Mannich bases, particularly towards resistant ovarian (NCI-ADR/RES) cell lines (5a, 5b, 6a, 6c and 9b), and ovarian (OVCAR-03) cell lines (5b, 6a, 6c, 9a, 9b and 9c). In addition, the interaction of compound 4b with DNA was investigated by using UV and fluorescence spectroscopic analysis. These studies indicated that 4b interact with ctDNA by intercalation binding., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

A better comprehension of the prilocaine (PLC)-β-cyclodextrin (β-CD) complex liberation to membranes was provided by studying the architectural supramolecular arrangements of PLC, β-CD and egg phosphatidylcholine (EPC) liposomes, a membrane model. The topologies and possible interactions of mixtures of PLC, β-CD and EPC liposomes were investigated by nuclear magnetic resonances combining experimental (1)H-NMR (1D ROESY, STD and DOSY) at different pHs. The results indicate that in the mixture PLC/β-CD/EPC at pH 10 the PLC molecules are almost totally embedded into the liposomes and little interaction was observed between PLC and β-CD. However, at pH 5.5 not only was PLC imbedded in the EPC bilayer, but PLC was also interacting with β-CD. These results were rationalized as a spontaneous PLC release from β-CD to liposomes vesicles, whereas the PLC/EPC complex formation was higher at pH 10 than pH 5.5., (Copyright © 2011 John Wiley & Sons, Ltd.)

Objectives: To describe workers who returned to work after a hand injury and to analyze the factors associated with this outcome three years after discharge from rehabilitation., Methods: An observational, cross-sectional study was carried out with triangulation of quantitative and qualitative methods. The quantitative analysis used a database with sociodemographic, functional and clinical information on 35 individuals who were classified into two groups (return/no return to work). Multivariate analysis was conducted using the CART (Classification and Regression Tree) algorithm to assess the predictive value of four models, thereby identifying workers who had returned or not returned to work. Using the results from the statistical analysis, a semi-structured form was prepared for interviews, which were conducted with seven workers randomly selected from the sample., Results: Out of the 35 workers who participated in this study, 30 returned and five did not return to work. The majority were male, married and of low educational level, and the mean age was 37 years. The variables with the greatest predictive power were grip strength, occupational performance scores, occupational category and age. The qualitative analysis confirmed the multifactorial nature of the return to work and demonstrated that the presence of a professional to follow-up the process, adjustments to the workstation and working hours (to enable treatment continuity) and also accident benefits may contribute to a successful return., Conclusions: This study showed the complexity of the return to work by workers with hand injuries, highlighting a number of factors associated with this outcome and the importance of individualized assessment centered on the worker.

The development of an analytical method using 1H nuclear magnetic resonance (1H NMR) spectrometry to monitor cupuassu (Theobroma grandiflorum Spreng) bean fermentation, drying, and roasting processes is reported. The analysis of organic acids and alcohols of crude water extracts of cupuassu ground kernels were monitored by HPLC and 1H NMR spectroscopy. The residual protein signals caused deleterious effects on acid and alcohol quantifications. Therefore, the analytical procedures were optimized by sample cleanup and water suppression pulse sequences in order to obtain compatible data using HPLC and 1H NMR. The quantification of lactic acid, acetic acid, and 2,3-butanediol by NMR is 5- to 10-fold faster than by HPLC, with the advantage of providing the identification of several chemical species in a single experiment. Application of these analytical conditions to some cupuassu samples revealed that this methodology can be applied to the quality profiles of fermentation and roasting processes.

The effects of eugenol on the excitation-contraction coupling of the toad (Bufo paracnemis) sartorius were studied. Eugenol (0.1-2.5 mM) blocked the contracture induced by 80 mM K+. At 2.5 mM, it decreased the depolarization, induced by 80 mM K+, by 14 mV. This is not sufficient to explain the complete blockade of the potassium contracture. At higher concentrations (3-12 mM), eugenol induced contractures, without causing a depolarization of the membrane. Contractures were blocked by procaine and potentiated by caffeine and by cooling of the muscle. For concentrations of eugenol in the upper range of the dose-response curve (10 mM), the contracture was independent of the Ca++ concentration in the medium. At lower concentrations (5 mM), the contractures induced by eugenol were potentiated by divalent cations, in the order: Mg++ < Ba++ < Zn++ < Co++ < Ca++ < Mn++. We infer that the eugenol-induced contractures are caused, primarily, by a release of Ca++ from the sarcoplasmic reticulum and, secondarily, by a mechanism related to the presence of some divalent cations in the extracellular space.