Enhancing the Furosemide Permeability by Papain Minitablets Through a Triple Co-culture In Vitro Intestinal Cell Model.

The administration of medicines by the oral route is the most used approach for being very convenient. Although it is the most popular, this route also has absorption, and consequently, bioavailability limitations. In this sense, several pharmacotechnical strategies have been used to improve drug absorption, one of which is the use of permeation promoters. Papain is a very versatile plant enzyme that can be used as a permeation promoter of various active compounds. This study aimed to evaluate the safety of papain and the formulation of native papain minitablets to promote in vitro permeation of furosemide through an innovative biomimetic triple co-culture model of Caco-2, HT29-MTX, and Raji cells. Regarding permeation, furosemide and metaprolol concentrations are determined with HPLC; those are used to calculate Papp. Monolayer integrity was evaluated using TEER and Lucifer Yellow. In the presence of papain, TEER decreased two-fold and the Papp of furosemide increased six-fold. The results suggest that native papain minitablets can be used as therapeutic adjuvants to enhance the permeation of drugs significantly improving bioavailability.

ZnO:SBA-15 Nanocomposites for Potential Use in Sunscreen: Preparation, Properties, Human Skin Penetration and Toxicity.

AIM: We evaluated the effects of the incorporation of zinc oxide (ZnO) nanoparticles in a mesoporous matrix, aiming to improve the textural, structural and morphological properties and verify their safety so that they can be applied in sunscreen cosmetics. MATERIALS AND METHODS: ZnO nano-particles were incorporated into an ordered mesoporous silica matrix known as Santa Barbara Amorphous-15 (SBA-15), using post-synthesis methodology. The resulting nanocomposites were characterized using X-ray diffraction, small angle X-ray scattering, N2 adsorption-desorption isotherms, Fourier transform infrared spectroscopy, scanning electron microscopy and predicted in vitro sun protector factor (SPF) estimation. Effectiveness and safety were evaluated by antimicrobial activity, in vitro cell toxicity and non-invasive multi-photon tomography with fluorescence lifetime imaging. RESULTS: The structure of the nanocomposites was similar to that of SBA-15, with little perturbation caused by ZnO incorporation. Nanocomposites had an increased in vitro SPF, reduced cytotoxic activity and favourable antimicrobial properties compared to ZnO. ZnO:SBA-15 nanocomposites exhibited no measurable toxicity when applied to human skin in vivo. CONCLUSION: Due to their suitable physicochemical properties and improved safety compared to bare ZnO nanoparticles, the ZnO:SBA-15 nanocomposites show promise for use in cosmetic applications.

Hydroboration of Terminal Olefins with Pinacolborane Catalyzed by New Mono(2-Iminopyrrolyl) Cobalt(II) Complexes.

The 5-substituted 2-aryliminopyrrolyl ligand precursors of the type 5-R-2-[ N-(2,6-diisopropylphenyl)formimino]-1 H-pyrrole (R = 2,6-Me2-C6H3 (1a), 2,4,6-iPr3-C6H2 (1b), 2,4,6-Ph3-C6H3 (1c; reported in this work), anthracen-9-yl (1d), CPh3 (1e; reported in this work)) were treated with K[N(SiMe3)2] in toluene to yield the respective 5-R-2-[ N-(2,6-diisopropylphenyl)formimino]pyrrolyl potassium salts 2a-e in high yields. The paramagnetic 15-electron Co(II) complexes of the type [Co{κ2 N,N'-5-R-NC4H2-2-C(H)═N(2,6-iPr2-C6H3)}(Py)Cl] (3a-e; Py = pyridine) were prepared by salt metathesis of CoCl2(Py)4 with the respective potassium salts 2a-e in moderate to good yields. When the CoCl2(THF)1.5 precursor was combined with the in situ prepared sodium salt of ligand precursor 1b, the trinuclear complex [Co{κ2 N, N'-5-(2,4,6-iPr3-C6H2)-NC4H2-2-C(H)═N(2,6-iPr2-C6H3)}(µ-Cl)]2[(µ-Cl)2Co(THF)2] (4) was obtained in high yields. Complexes 3a-e have high-spin electronic configurations both in solution and in the solid state. X-ray diffraction studies of complexes 3a,e confirmed distorted tetrahedral coordination geometries. Complex 4, on the other hand, is a linear trinuclear Co(II)-Co(II)-Co(II) complex with two terminal distorted tetrahedral four-coordinate sites and a central octahedral six-coordinate site, all in the high-spin state, S = 3/2, as confirmed by the magnetization measurements and DFT calculations. Solid-state magnetic measurements in both complexes 3a and 4 point to paramagnetic behavior with a significant contribution of spin-orbit coupling. Additionally, intramolecular antiferromagnetic coupling of the adjacent cobalt atoms is observed in 4. The Co(II) family 3a-d, on activation with K(HBEt3), catalyzed the hydroboration of several α-olefins with pinacolborane, in good to high yields (50-80%). This system almost exclusively yielded the anti-Markovnikov (a-Mk) addition product, except when styrene was used, where the selectivity in the Markovnikov (Mk) product increased with increasing steric bulkiness of the 5-R-2-iminopyrrolyl substituent, with the a-Mk:Mk molar ratio varying from 2.33:1 (3a, R = 2,6-Me2-C6H3) to 0.75:1 (3c, R = 2,4,6-Ph3-C6H3). Preliminary mechanistic studies indicate that the activation by K(HBEt3) gave rise to a Co(I) species, the catalyst system likely following an oxidative addition pathway.

The spinal anti-inflammatory mechanism of motor cortex stimulation: cause of success and refractoriness in neuropathic pain?

BACKGROUND: Motor cortex stimulation (MCS) is an effective treatment in neuropathic pain refractory to pharmacological management. However, analgesia is not satisfactorily obtained in one third of patients. Given the importance of understanding the mechanisms to overcome therapeutic limitations, we addressed the question: what mechanisms can explain both MCS effectiveness and refractoriness? Considering the crucial role of spinal neuroimmune activation in neuropathic pain pathophysiology, we hypothesized that modulation of spinal astrocyte and microglia activity is one of the mechanisms of action of MCS. METHODS: Rats with peripheral neuropathy (chronic nerve injury model) underwent MCS and were evaluated with a nociceptive test. Following the test, these animals were divided into two groups: MCS-responsive and MCS-refractory. We also evaluated a group of neuropathic rats not stimulated and a group of sham-operated rats. Some assays included rats with peripheral neuropathy that were treated with AM251 (a cannabinoid antagonist/inverse agonist) or saline before MCS. Finally, we performed immunohistochemical analyses of glial cells (microglia and astrocytes), cytokines (TNF-α and IL-1ß), cannabinoid type 2 (CB2), µ-opioid (MOR), and purinergic P2X4 receptors in the dorsal horn of the spinal cord (DHSC). FINDINGS: MCS reversed mechanical hyperalgesia, inhibited astrocyte and microglial activity, decreased proinflammatory cytokine staining, enhanced CB2 staining, and downregulated P2X4 receptors in the DHSC ipsilateral to sciatic injury. Spinal MOR staining was also inhibited upon MCS. Pre-treatment with AM251 blocked the effects of MCS, including the inhibitory mechanism on cells. Finally, MCS-refractory animals showed similar CB2, but higher P2X4 and MOR staining intensity in the DHSC in comparison to MCS-responsive rats. CONCLUSIONS: These results indicate that MCS induces analgesia through a spinal anti-neuroinflammatory effect and the activation of the cannabinoid and opioid systems via descending inhibitory pathways. As a possible explanation for MCS refractoriness, we propose that CB2 activation is compromised, leading to cannabinoid resistance and consequently to the perpetuation of neuroinflammation and opioid inefficacy.

Luminescent Di- and Trinuclear Boron Complexes Based on Aromatic Iminopyrrolyl Spacer Ligands: Synthesis, Characterization, and Application in OLEDs.

New bis- and tris(iminopyrrole)-functionalized linear (1,2-(HNC4 H3 -C(H)N)2 -C6 H4 (2), 1,3-(HNC4 H3 -C(H)N)2 -C6 H4 (3), 1,4-(HNC4 H3 -C(H)N)2 -C6 H4 (4), 4,4'-(HNC4 H3 -C(H)N)2 -(C6 H4 -C6 H4 ) (5), 1,5-(HNC4 H3 C-(H)N)2 -C10 H6 (6), 2,6-(HNC4 H3 C-(H)N)2 -C10 H6 (7), 2,6-(HNC4 H3 C-(H)N)2 -C14 H8 (8)) and star-shaped (1,3,5-(HNC4 H3 -C(H)N-1,4-C6 H4 )3 -C6 H3 (9)) π-conjugated molecules were synthesized by the condensation reactions of 2-formylpyrrole (1) with several aromatic di- and triamines. The corresponding linear diboron chelate complexes (Ph2 B[1,3-bis(iminopyrrolyl)-phenyl]BPh2 (10), Ph2 B[1,4-bis(iminopyrrolyl)-phenyl]BPh2 (11), Ph2 B[4,4'-bis(iminopyrrolyl)-biphenyl]BPh2 (12), Ph2 B[1,5-bis(iminopyrrolyl)-naphthyl]BPh2 (13), Ph2 B[2,6-bis(iminopyrrolyl)-naphthyl]BPh2 (14), Ph2 B[2,6-bis(iminopyrrolyl)-anthracenyl]BPh2 (15)) and the star-shaped triboron complex ([4',4'',4'''-tris(iminopyrrolyl)-1,3,5-triphenylbenzene](BPh2 )3 (16)) were obtained in moderate to good yields, by the treatment of 3-9 with B(C6 H5 )3 . The ligand precursors are non-emissive, whereas most of their boron complexes are highly fluorescent; their emission color depends on the π-conjugation length. The photophysical properties of the luminescent polyboron compounds were measured, showing good solution fluorescence quantum yields ranging from 0.15 to 0.69. DFT and time-dependent DFT calculations confirmed that molecules 10 and 16 are blue emitters, because only one of the iminopyrrolyl groups becomes planar in the singlet excited state, whereas the second (and third) keeps the same geometry. Compound 13, in which planarity is not achieved in any of the groups, is poorly emissive. In the other examples (11, 12, 14, and 15), the LUMO is stabilized, narrowing the gap between the highest occupied molecular orbital and the lowest unoccupied molecular orbital (HOMO-LUMO), and the two iminopyrrolyl groups become planar, extending the size of the π-system, to afford green to yellow emissions. Organic light-emitting diodes (OLEDs) were fabricated by using the new polyboron complexes and their luminance was found to be in the order of 2400 cd m(-2) , for single layer devices, increasing to 4400 cd m(-2) when a hole-transporting layer is used.

Development of papain containing pellets produced by extrusion-spheronization: an operational stage approach.

The performance of the standardized extrusion-spheronization technique, operational conditions, formulation parameters and storage of the final product over the bioactivity of papain containing pellets has been evaluated to obtain an insight into the potential of the technique for the manufacture of solid protein formulations. The pellets produced were assayed in terms of biological activity - monitored at each operational stage using N-benzoyl-dl-arginine ρ-nitroanilide as a substrate, and according to the physical properties - evaluated by means of size distribution, apparent density and friability. The produced pellets presented adequate physical and mechanical properties. Monitoring biological activity at each production stage revealed that the most critical steps corresponded to drying and storage, with bioactivity decay ranging from 5 to 30% and 5 to 20% for each process. Dry mixing and extrusion did not hold any influence over papain activity, while wet massing decreased the bioactivity by approximately 0-5% and the spheronization 0-2%. The results varied as a function of the experimental conditions and formulation components. In conclusion, the extrusion--spheronization technique was suitable to produce solid multiparticulate dosage forms for papain, considering the possibility to originate pellets with relatively low bioactivity decay. However, weak points of the technique corresponded to the wet massing and drying stages as well as storage.

Tunable fluorophores based on 2-(N-arylimino)pyrrolyl chelates of diphenylboron: synthesis, structure, photophysical characterization, and application in OLEDs.

Reactions of 2-(N-arylimino)pyrroles (HNC4H3C(H)=N-Ar) with triphenylboron (BPh3) in boiling toluene afford the respective highly emissive N,N'-boron chelate complexes, [BPh2 {κ(2)N,N'-NC4H3C(H)=N-Ar}] (Ar=C6H5 (12), 2,6-Me2-C6H3 (13), 2,6-iPr2-C6H3 (14), 4-OMe-C6H4 (15), 3,4-Me2-C6 H3 (16), 4-F-C6H4 (17), 4-NO2-C6H4 (18), 4-CN-C6H4 (19), 3,4,5-F3-C6H2 (20), and C6F5 (21)) in moderate to high yields. The photophysical properties of these new boron complexes largely depend on the substituents present on the aryl rings of their N-arylimino moieties. The complexes bearing electron-withdrawing aniline substituents 17-20 show more intense (e.g., ϕf =0.71 for Ar=4-CN-C6H4 (19) in THF), higher-energy (blue) fluorescent emission compared to those bearing electron-donating substituents, for which the emission is redshifted at the expense of lower quantum yields (ϕf=0.13 and 0.14 for Ar=4-OMe-C6H4 (15) and 3,4-Me2-C6H3 (16), respectively, in THF). The presence of substituents bulkier than a hydrogen atom at the 2,6-positions of the aryl groups strongly restricts rotation of this moiety towards coplanarity with the iminopyrrolyl ligand framework, inducing a shift in the emission to the violet region (λmax =410-465 nm) and a significant decrease in quantum yield (ϕf=0.005, 0.023, and 0.20 for Ar=2,6-Me2-C6H3 (13), 2,6-iPr2-C6H3 (14), and C6F5 (21), respectively, in THF), even when electron-withdrawing groups are also present. Density functional theory (DFT) and time-dependent DFT (TD-DFT) calculations have indicated that the excited singlet state has a planar aryliminopyrrolyl ligand, except when prevented by steric hindrance (ortho substituents). Calculated absorption maxima reproduce the experimental values, but the error is higher for the emission wavelengths. Organic light-emitting diodes (OLEDs) have been fabricated with the new boron complexes, with luminances of the order of 3000 cd m(-2) being achieved for a green-emitting device.

Effect of Makeup Use on Depressive Symptoms: An Open, Randomized and Controlled Trial.

INTRODUCTION: Depression is one of the most disabling diseases globally, with a high disease burden that generates high direct and indirect costs. The incidence of depression is twofold higher in adult women than in men. Biological and psychosocial factors constitute the pathophysiological bases of the condition and due to the complexity of the condition, current understanding is that the "treatment strategy must be multimodal". The objective of this study was to measure the effect of introducing the frequent use of makeup on improving depressive symptoms in adult women of medium-low purchasing power METHODS: Participants with the targeted profile who did not frequently use makeup were selected and randomised to receive (test group) or not (control group) stimuli and makeup products intended for encouraging the frequent use of makeup. The Zung Depression Self-Assessment Scale was used to assess depressive symptoms, with additional assessments on self-image perception using the mirror test and salivary cortisol level. RESULTS: The results demonstrated a sustained reduction in depressive symptoms (8.3 percentage points reduction in the Average Zung Index; P < 0.05), with a significant improvement in self-image perception (25% increase in the average score obtained in the mirror test; P < 0.05) and a specific influence on salivary cortisol levels (55% reduction in salivary cortisol concentration; P < 0.05) after the first makeup application. CONCLUSION: The results show that encouraging the frequent use of makeup, a practice that can be achieved by most people and which is simple and inexpensive to implement, can contribute to effective and sustainable improvement in the well-being and mental health of a significant portion of the population.

Neuroprotective effects of platinum nanoparticle-based microreactors in bicuculline-induced seizures.

Epilepsy designates a group of chronic brain disorders, characterized by the recurrence of hypersynchronous, repetitive activity, of neuronal clusters. Epileptic seizures are the hallmark of epilepsy. The primary goal of epilepsy treatment is to eliminate seizures with minimal side effects. Nevertheless, approximately 30% of patients do not respond to the available drugs. An imbalance between excitatory/inhibitory neurotransmission, that leads to excitotoxicity, seizures, and cell death, has been proposed as an important mechanism regarding epileptogenesis. Recently, it has been shown that microreactors composed of platinum nanoparticles (Pt-NP) and glutamate dehydrogenase possess in vitro and in vivo activity against excitotoxicity. This study investigates the in vivo effects of these microreactors in an animal model of epilepsy induced by the administration of the GABAergic antagonist bicuculline. Male Wistar rats were administered intracerebroventricularly (i.c.v.) with the microreactors or saline and, five days later, injected with bicuculline or saline. Seizure severity was evaluated in an open field. Thirty min after behavioral measurements, animals were euthanized, and their brains processed for neurodegeneration evaluation and for neurogenesis. Treatment with the microreactors significantly increased the time taken for the onset of seizures and for the first tonic-clonic seizure, when compared to the bicuculline group that did not receive the microreactor. The administration of the microreactors also increased the time spent in total exploration and grooming. Treatment with the microreactors decreased bicuculline-induced neurodegeneration and increased neurogenesis in the dorsal and ventral hippocampus. These observations suggest that treatment with Pt-NP-based microreactors attenuates the behavioral and neurobiological consequences of epileptiform seizure activity.

Association Between Frequent Use of Makeup and Presence of Depressive Symptoms-Population-Based Observational Study, Including 2400 Participants.

INTRODUCTION: The increased prevalence of depression is a global phenomenon, with an estimated 320 million cases worldwide. In Brazil, the World Health Organization (WHO) estimated that there are about 12 million cases or more, mainly among adult women with lower socioeconomic status, leading to a high consumption of health resources. Studies suggest a positive association of measures related to appearance care on depressive symptoms, but usually with no objective methodology. This study aimed to estimate the prevalence of depressive symptoms in adult Brazilian women with lower purchasing power and to verify the association between the intensity of symptoms and the use of makeup. METHODS: A national sample of 2400 cases from all regions of the country, drawn randomly from an online panel representative of the Brazilian population, was studied using an online questionnaire accessible via computer or smartphone, from which the frequency of use of makeup was surveyed, and the Zung Depressive Self-Rating Scale was applied for the inventory of symptoms. RESULTS: A prevalence of 61.4% (0.59-0.63) of depressive symptoms was identified. The association between frequent use of makeup and a lower prevalence of cases with a Zung index suggestive of mild depression was confirmed. Association between frequent use of makeup and lower intensity of depressive symptoms was also identified among cases with a Zung index suggestive of absence of depression. Additionally, an association was identified between the habit of frequent use of makeup and higher economic class as well as the younger age group. CONCLUSION: The results suggest the hypothesis that use of makeup may contribute both to a lower prevalence of mild depression and less expressive symptoms when index of absence of depression is observed.

Flow cytometry as an alternative method to evaluate genotoxicity of natural cosmetic actives.

Alternative in vitro methods are important, as there is a call to ban the use of animals in cosmetics research. AIM: To suggest the expansion of the use of in vitro safety techniques recommended by the OECD guidelines and to propose the use of the automation of the in vitro mammalian micronucleus test method by flow cytometry to assess the genotoxic potential of Centella asiatica, Horse Chestnut, Witch Hazel, Blend, Ecoblend, and Caffeine extracts due to their widespread use in commercial products. METHODS: Flow cytometer analysis was performed using the Accuri™ C6 equipment and analyzed using the FlowJo software. Cytotoxicity tests followed OECD 129 guidelines and Phototoxicity followed OECD/GD 432 guidelines. RESULTS: The results showed that the cytotoxicity assay presented a decrease in cell viability when cells were exposed to Centella asiatica from a concentration of 5.0%, horse chestnut 2.5%, Witch hazel 2.5%, Blend 3.13%, and Caffeine 3%, while Ecoblend at the tested concentrations did not show cytotoxicity. In the phototoxicity test, the samples at the tested concentrations showed a PIF <2 being considered potentially non-phototoxic. Finally, in the genotoxicity automated assay, samples were considered potentially non-genotoxic. CONCLUSION: In vitro methods are of paramount importance for the development of pre-clinical tests and the use of test automation helps to reduce the time for analysis and dissemination of results, being a determining factor for the prospect of new compounds.

New copper(I) complexes of bulky 5-substituted-2-iminopyrrolyl ligands as catalysts for azide-alkyne cycloaddition.

Five dinuclear copper(I) complexes of the type [Cu{κN,κN'-5-R-NC4H2-2-C(H)N(2,6-iPr2C6H3)}]2 (1a-e; R = 2,4,6-iPr3C6H2 (a), R = 2,6-Me2C6H3 (b), R = 3,5-(CF3)2C6H3 (c), R = 2,6-(OMe)2C6H2 (d), R = CPh3 (e)) were prepared by the reaction of the respective 5-R-2-iminopyrrolyl potassium salts KLa-e and [Cu(NCMe)4]BF4 in moderate yields. These new copper(I) complexes were characterized by NMR spectroscopy, elemental analysis and, in selected cases, by single crystal X-ray diffraction and their structural and electronic features further analyzed by DFT calculations and cyclic voltammetry, respectively. X-ray diffraction studies reveal dimeric Cu structures assembled by 2-iminopyrrolyl bridging ligands adopting a transoid conformation (complexes 1a and 1d), while complexes 1c and 1e displayed a cisoid conformation of those moieties, with respect to the Cu(I) centers. Additionally, VT-1H NMR and 1H-1H NOESY NMR experiments on complexes 1a-e exhibited complex fluxional processes in solution, assigned to a conformational inversion of the respective Cu2N4C4 metallacycles in all complexes but 1c, accompanied by a cisoid-transoid isomerization in the cases of complexes 1d,e. The Cu(I) complexes were also analyzed by cyclic voltammetry, where all complexes exhibit two oxidation processes, where the first oxidation is reversible, with the exception of 1b and 1c, which also show the highest oxidation potentials. The oxidation potentials follow clear trends related to the structural parameters of the complexes, in particular the Cu⋯Cu distance and the Cu2N4C4 macrocycles torsion angles. All new 5-substituted-2-iminopyrrolyl Cu(I) complexes 1a-e served as catalysts for azide-alkyne cycloaddition (CuAAC) reactions, being able to generate the respective 1,2,3-triazole products in yields as high as 82% and turnover frequencies (TOFs) as high as 859 h-1, after optimizing the conditions. The activity, as measured by the TOF, is in accordance with the oxidation potential of the corresponding complexes, the easier the oxidation, the higher the TOF value. Complex 1-H, where R = H, proved to be a poor catalyst for the same reactions, indicating that the 5-substitution in the ligand framework is crucial in stabilizing any potential catalytic species.

Aloe vera and copaiba oleoresin-loaded chitosan films for wound dressings: microbial permeation, cytotoxicity, and in vivo proof of concept.

Chitosan films are commonly used for wound dressing, provided that this polymer has healing, mucoadhesiveness and antimicrobial properties. These properties can be further reinforced by the combination of chitosan with polysaccharides and glycoproteins present in aloe vera, together with copaiba oleoresin's pharmacological activity attributed to sesquiterpenes. In this work, we developed chitosan films containing either aloe vera, copaiba oil or both, by casting technique, and evaluated their microbial permeation, antimicrobial activity, cytotoxicity, and in vivo healing potential in female adult rats. None of the developed chitosan films promoted microbial permeation, while the cytotoxicity in Balb/c 3 T3 clone A31 cell line revealed no toxicity of films produced with 2 % of chitosan and up to 1 % of aloe vera and copaiba oleoresin. Films obtained with either 0.5 % chitosan or 0.5 % copaiba oleoresin induced cell proliferation which anticipate their potential for closure of wound and for the healing process. The in vivo results confirmed that tested films (0.5 % copaiba-loaded chitosan film and 0.5 % aloe vera-loaded chitosan film) were superior to a commercial dressing film. For all tested groups, a fully formed epithelium was seen, while neoformation of vessels seemed to be greater in formulations-treated groups than those treated with the control. Our work confirms the added value of combining chitosan with aloe vera and copaiba oil in the healing process of wounds.

Lemongrass (Cymbopogon citratus)-incorporated chitosan bioactive films for potential skincare applications.

Circular economy, and concerns about environmental waste, is fostering the development of sustainable alternative products in a range of industries. In the dermo-cosmetic field, the market for sustainable anti-aging skincare products has increasingly grown over the last years. The innovation of this work was to develop chitosan films incorporating lemongrass essential oil (LEO) that could potentially be applied as a green cosmetic skin treatment due to their anti-oxidant and antimicrobial properties, using renewable and biodegradable materials. Different concentrations of LEO (i.e., 0.5, 1.0, and 1.5 % w/w) were formulated into chitosan filmogenic matrices, forming skincare bioactive films. Their antioxidant properties and water vapor permeability were strongly governed by the LEO concentration. Chitosan bioactive films containing 0.5 % LEO showed cellular viability over 70 %, while those with 1.5 % LEO had similar antioxidant capacity as NAC (N-acetyl-L-cysteine), used as the positive control to inactivate intracellular reactive oxygen species (ROS) in HaCat cells not treated with H2O2. The developed bioactive films showed activity against Escherichia coli and Staphylococcus aureus. Our LEO-loaded chitosan biofilms may be used as sheet masks with antioxidant and antimicrobial properties for skincare, with high flexibility and selected permeability, and without cytotoxic risks.

Implementation of the three Rs in the human hazard assessment of Brazilian medicinal plants: an evaluation of the cytotoxic and genotoxic potentials of Dipteryx alata Vogel.

In Brazil, medicinal plants are widely used by the indigenous people, which leads to a constant requirement for toxicity tests to be performed on the plant extracts. Although the current Brazilian Directive 90/2004 on the preclinical toxicity testing of phytotherapeutics recommends only in vivo tests, some Brazilian researchers would like to change this situation by implementing the Three Rs in the toxicological testing of medicinal plants. The present study evaluated the cytotoxic and genotoxic potentials of bark extracts from Dipteryx alata Vogel, a medicinal plant of the Brazilian cerrado, by using CHO-K1 (Chinese hamster ovary) cells. An IC50 value was obtained, which corresponded to 0.16mg/ml of plant extract, and from this the equivalent LD50 was determined as 705mg/kg. In order to determine the genotoxic potential of the sample, the frequency of micronucleus formation was assessed. CHO-K1 cells were exposed, during targeted mitosis, to different concentrations of plant extract and cytochalasin B, in the presence and absence of an appropriate metabolic activation system (an S9 mix). The results obtained indicated that it might be possible to implement the Three Rs in assessing the potential human hazard of medicinal plants. The publication of such data can increase awareness of the Three Rs by showing how to optimise the management of animal use, if in vivo toxicological experiments are required.

Iminopyrrole derivatives containing electron-withdrawing substituents: the formation of dimers and supramolecular arrangements.

The crystal structures of two p-substituted phenylformiminopyrrole derivatives, namely 2-[(4-fluorophenyl)iminomethyl]pyrrole, C(11)H(9)FN(2), (1), and 2-[(1H-pyrrol-2-ylmethylidene)amino]benzonitrile, C(12)H(9)N(3), (2), bear F and C[triple-bond]N electron-withdrawing groups, respectively. Both structures feature two independent molecules in the asymmetric unit forming dimers via N-H...N hydrogen bonds. In the case of (1), each dimer interacts with two other dimers via C-H...F contacts, thus forming one-dimensional chains in the b direction, whereas in the case of (2), a weak C-H...N interaction connects the dimers in one-dimensional chains in the (110) direction.

Motor Cortex Stimulation Reversed Hypernociception, Increased Serotonin in Raphe Neurons, and Caused Inhibition of Spinal Astrocytes in a Parkinson's Disease Rat Model.

Persistent pain is a prevalent symptom of Parkinson's disease (PD), which is related to the loss of monoamines and neuroinflammation. Motor cortex stimulation (MCS) inhibits persistent pain by activating the descending analgesic pathways; however, its effectiveness in the control of PD-induced pain remains unclear. Here, we evaluated the analgesic efficacy of MCS together with serotonergic and spinal glial modulation in an experimental PD (ePD) rat model. Wistar rats with unilateral striatal 6-OHDA and MCS were assessed for behavioral immobility and nociceptive responses. The immunoreactivity of dopamine in the substantia nigra and serotonin in the nucleus raphe magnus (NRM) and the neuronal, astrocytic, and microglial activation in the dorsal horn of the spinal cord were evaluated. MCS, without interfering with dopamine loss, reversed ePD-induced immobility and hypernociception. This response was accompanied by an exacerbated increase in serotonin in the NRM and a decrease in neuronal and astrocytic hyperactivation in the spinal cord, without inhibiting ePD-induced microglial hypertrophy and hyperplasia. Taken together, MCS induces analgesia in the ePD model, while restores the descending serotonergic pathway with consequent inhibition of spinal neurons and astrocytes, showing the role of MCS in PD-induced pain control.

Effect of Chitosan and Aloe Vera Extract Concentrations on the Physicochemical Properties of Chitosan Biofilms.

Chitosan films have been extensively studied as dressings in formulations for the treatment of chronic wounds. The incorporation of aloe vera (Aloe barbadensis Miller) into chitosan dressings could potentialize the healing process since aloe vera shows several pharmacological activities. This work aimed to evaluate the effect of aloe vera and chitosan concentrations on the physicochemical properties of the developed films. The films were obtained by casting technique and characterized with respect to their color parameters, morphology, barrier and mechanical properties, and thermal analysis. Results showed that the presence of aloe vera modified the films' color parameters, changed barrier properties, increased fluid handling capacity (FHC), and decreased water-vapor permeability (WVP). The reduced elongation at break resulted in more rigid films. Aloe vera concentration did not significantly change film properties, but the presence of this gel increased the films' stability at temperatures below 200 °C, showing similar behavior as chitosan films above 400 °C. The results suggest a crosslinking/complexation between chitosan and aloe vera, which combine appropriate physicochemical properties for application as wound dressing materials.

Prosopis juliflora as a new cosmetic ingredient: Development and clinical evaluation of a bioactive moisturizing and anti-aging innovative solid core.

Prosopis juliflora is an invasive plant distributed throughout the world and presents metabolites of interest for cosmetology. The aim of this work was to develop a new polysaccharide-based ingredient from P. juliflora and analyze its application in a solid core formulation that upon contact with water instantly forms a gel to improve moisturizing and anti-aging skin properties. Purified extracts by gel chromatography were characterized by NMR and LC-DAD-MS-MS. The in vitro and in vivo safety, antioxidant activity, formulation development and clinical evaluation were performed. The extract was characterized as containing an α-glucan and phenolics. It was non-cytotoxic, non-phototoxic and no skin reactions were observed in vivo. Antioxidant activity were present through different mechanisms. Clinical evaluation reinforced the potential of P. juliflora in skin hydration and microrelief improvement. This innovative form proved to be a prototype of a new product and the first study of an α-glucan as a cosmetic ingredient.

Neurochemical effects of motor cortex stimulation in the periaqueductal gray during neuropathic pain.

OBJECTIVE: Motor cortex stimulation (MCS) is a neurosurgical technique used to treat patients with refractory neuropathic pain syndromes. MCS activates the periaqueductal gray (PAG) matter, which is one of the major centers of the descending pain inhibitory system. However, the neurochemical mechanisms in the PAG that underlie the analgesic effect of MCS have not yet been described. The main goal of this study was to investigate the neurochemical mechanisms involved in the analgesic effect induced by MCS in neuropathic pain. Specifically, we investigated the release of γ-aminobutyric acid (GABA), glycine, and glutamate in the PAG and performed pharmacological antagonism experiments to validate of our findings. METHODS: Male Wistar rats with surgically induced chronic constriction of the sciatic nerve, along with sham-operated rats and naive rats, were implanted with both unilateral transdural electrodes in the motor cortex and a microdialysis guide cannula in the PAG and subjected to MCS. The MCS was delivered in single 15-minute sessions. Neurotransmitter release was evaluated in the PAG before, during, and after MCS. Quantification of the neurotransmitters GABA, glycine, and glutamate was performed using a high-performance liquid chromatography system. The mechanical nociceptive threshold was evaluated initially, on the 14th day following the surgery, and during the MCS. In another group of neuropathic rats, once the analgesic effect after MCS was confirmed by the mechanical nociceptive test, rats were microinjected with saline or a glycine antagonist (strychnine), a GABA antagonist (bicuculline), or a combination of glycine and GABA antagonists (strychnine+bicuculline) and reevaluated for the mechanical nociceptive threshold during MCS. RESULTS: MCS reversed the hyperalgesia induced by peripheral neuropathy in the rats with chronic sciatic nerve constriction and induced a significant increase in the glycine and GABA levels in the PAG in comparison with the naive and sham-treated rats. The glutamate levels remained stable under all conditions. The antagonism of glycine, GABA, and the combination of glycine and GABA reversed the MCS-induced analgesia. CONCLUSIONS: These results suggest that the neurotransmitters glycine and GABA released in the PAG may be involved in the analgesia induced by cortical stimulation in animals with neuropathic pain. Further investigation of the mechanisms involved in MCS-induced analgesia may contribute to clinical improvements for the treatment of persistent neuropathic pain syndromes.