Brazilian Green Propolis' Artepillin C and Its Acetylated Derivative Activate the NGF-Signaling Pathways and Induce Neurite Outgrowth in NGF-Deprived PC12 Cells.

Artepillin C is the most studied compound in Brazilian Green Propolis and, along with its acetylated derivative, displays neurotrophic activity on PC12 cells. Specific inhibitors of the trkA receptor (K252a), PI3K/Akt (LY294002), and MAPK/ERK (U0126) signaling pathways were used to investigate the neurotrophic mechanism. The expression of proteins involved in axonal and synaptic plasticity (GAP-43 and Synapsin I) was assessed by western blotting. Additionally, physicochemical properties, pharmacokinetics, and drug-likeness were evaluated by the SwissADME web tool. Both compounds induced neurite outgrowth by activating the NGF-signaling pathways but through different neuronal proteins. Furthermore, in silico analyses showed interesting physicochemical and pharmacokinetic properties of these compounds. Therefore, these compounds could play an important role in axonal and synaptic plasticity and should be further investigated.

Unconventional and conventional Pickering emulsions: Perspectives and challenges in skin applications.

Pickering emulsions are free from molecular and classical surfactants and are stabilized by solid particles, creating long-term stability against emulsion coalescence. Additionally, these emulsions are both environmentally and skin-friendly, creating new and unexplored sensorial perceptions. Although the literature mostly describes conventional emulsions (oil-in-water), there are unconventional emulsions (multiple, oil-in-oil and water-in-water) with excellent prospects and challenges in skin application as oil-free systems, permeation enhancers and topical drug delivery agents, with various possibilities in pharmaceutical and cosmetic products. However, up to now, these conventional and unconventional Pickering emulsions are not yet available as commercial products. This review brings to the discussion some important aspects such as the use of phases, particles, rheological and sensorial perception, as well as current trends in the development of these emulsions.

Doxycycline inhibits dopaminergic neurodegeneration through upregulation of axonal and synaptic proteins.

Doxycycline (DOX) is a widely used antibiotic that is able to cross the blood-brain barrier. Several studies have shown its neuroprotective effect against neurodegeneration and have associated it with antioxidant, anti-apoptotic, and anti-inflammatory mechanisms. We have recently demonstrated that DOX mimics nerve growth factor (NGF) signaling in PC12 cells. However, the involvement of this mechanism in the neuroprotective effect of DOX is unknown. Axonal degeneration and synaptic loss are key events at the early stages of neurodegeneration, and precede the neuronal death in neurodegenerative diseases, including Parkinson's disease (PD). Therefore, the regeneration of the axonal and synaptic network might be beneficial in PD. The effect of DOX in PC12 cells treated with the Parkinsonian neurotoxin 1-methyl-4-phenylpyridinium (MPP+) was addressed. Doxycycline reduced the inhibition of neuritogenesis induced by MPP+, even in cells deprived of NGF. The mechanism involved the upregulation of GAP-43, synapsin I, ß-III-tubulin, F-actin, and neurofilament-200, proteins that are associated with axonal and synaptic plasticity. Considering the role of axonal degeneration and synaptic loss at the initial stages of PD, the recent advances in early diagnosis of neurodegeneration, and the advantages of drug repurposing, doxycycline is a promising candidate to treat PD.

Baccharin from Brazilian green propolis induces neurotrophic signaling pathways in PC12 cells: potential for axonal and synaptic regeneration.

Neurodegenerative diseases are characterized by progressive loss of the structure and function of specific neuronal populations, and have been associated with reduced neurotrophic support. Neurotrophins, like NGF (nerve growth factor), are endogenous proteins that induce neuritogenesis and modulate axonal growth, branching, and synapsis; however, their therapeutic application is limited mainly by low stability, short half-life, and inability to cross the blood-brain barrier (BBB). Small neurotrophic molecules that have suitable pharmacokinetics and are able to cross the BBB are potential candidates for neuroprotection. Baccharin is a bioactive small molecule isolated from Brazilian green propolis. In the present study, we investigated the neurotrophic and neuroprotective potential of baccharin in the PC12 cell neuronal model. We used pharmacological inhibitors (K252a, LY294002, and U0126), and ELISA (phospho-trkA, phospho-Akt, and phospho-MEK) to investigate the involvement of trkA receptor, PI3k/Akt pathway, and MAPK/Erk pathway, respectively. Additionally, we evaluated the expression of axonal (GAP-43) and synaptic (synapsin I) proteins by western blot. The results showed that baccharin induces neuritogenesis in NGF-deprived PC12 cells, through activation of trkA receptor and the downstream signaling cascades (PI3K/Akt and MAPK/ERK), which is the same neurotrophic pathway activated by NGF in PC12 cells and neurons. Baccharin also induced the expression of GAP-43 and synapsin I, which mediate axonal and synaptic plasticity, respectively. Additionally, in silico predictions of baccharin showed favorable physicochemical properties, pharmacokinetics, drug-likeness, and medicinal chemistry friendliness. Altogether, these findings suggest that baccharin is a promising neurotrophic agent whose therapeutic application in neurodegeneration should be further investigated.

The antibiotic doxycycline mimics the NGF signaling in PC12 cells: A relevant mechanism for neuroprotection.

Doxycycline has been used as antibiotic since the 1960s. Recently, studies have shown that doxycycline is neuroprotective in models of neurodegenerative diseases and brain injuries, mainly due to anti-inflammatory and anti-apoptotic effects. However, it is not known if doxycycline has neurotrophic potential, which is relevant, considering the role of axonal degeneration at the early stages of neurodegeneration in Alzheimer's disease, Amyotrophic Lateral Sclerosis and Parkinson's disease as well as in normal aging. Axons are preceded by the formation of neurites, the hallmark of the neuronal differentiation induced by neurotrophins like NGF. Therefore, the modulation of neurotrophin receptors aimed at formation and regeneration of axons has been proposed as a strategy to delay the progression of neurodegeneration and has gained relevance as new techniques for early diagnosis arise. Based on these premises, we investigated the potential of doxycycline to mimic the effects of Nerve Growth Factor (NGF) with focus on the signaling pathways and neuronal modulators of neurite initiation, growth and branching. We used PC12 cells, a neuronal model widely employed to study the neurotrophic pathways and mechanisms induced by NGF. Results showed that doxycycline induced neurite outgrowth via activation of the trkA receptor and the downstream signaling pathways, PI3K/Akt and MAPK/ERK, without inducing the expression of NGF. Doxycycline also increased the expression of GAP-43, synapsin I and NF200, proteins involved in axonal and synaptic plasticity. Altogether, these data demonstrate, for the first time, the neurotrophic potential of doxycycline, which might be useful to restore the neuronal connectivity lost at the initial phase of neurodegeneration.

The Neurotrophic-Like Effect of Carvacrol: Perspective for Axonal and Synaptic Regeneration.

Carvacrol (CARV) is a phytochemical widely used as flavoring, preservative, and fragrance in food and cosmetic industries. CARV is able to cross the blood-brain barrier (BBB) and has demonstrated protective potential against neurodegenerative diseases by several mechanisms, including antioxidant, anti-inflammatory, anticholinesterase, and antiapoptotic effects. However, it is not known whether CARV is able to modulate axonal and synaptic plasticity, crucial events in cognition, memory, and learning. Abnormalities in axonal and synaptic plasticity, low levels of neurotrophins, and bioenergetic failure have been associated with the pathogenesis of neurodegenerative diseases, including Parkinson's (PD) and Alzheimer's diseases (ADs). Small lipophilic molecules with neurotrophic activity might be able to restore the axonal and synaptic networks that are lost in neurodegenerative processes. Therefore, this study investigated the neurotrophic potential of CARV in PC12 cell-based neuronal model. Carvacrol induced neurite outgrowth by activating the NGF high-affinity trkA receptor and the downstream PI3K-AKT and MAPK-ERK pathways, without depending on NGF. In addition, CARV increased the expression of proteins involved in neuronal plasticity (ß-tubulin III, F-actin, 200-kDa neurofilament, GAP-43 and synapsin-I) and improved bioenergetics (AMPKα, p-AMPKα, and ATP). Our study showed, for the first time, a promising neurotrophic mechanism of CARV that could be beneficial in neurodegenerative and neurological diseases.

Cyclodextrin and TiF4 Nanocomplex on Enamel Demineralization.

The aim of this study was to assess the effect of a newly developed nanocomplex formed of hydroxypropyl-b-cyclodextrin and 1% titanium tetrafluoride (TiF4) after distinct complexation periods (12/72 h) on demineralization of bovine enamel in vitro. Enamel blocks (n=60) were allocated in different groups: Mili-Q water, hydroxypropyl-b-cyclodextrin, 1% TiF4, hydroxypropyl-b-cyclodextrin + 1% TiF4 after 12 h of complexation and hydroxypropyl-b-cyclodextrin + 1% TiF4 after 72 h of complexation. The samples were evaluated by surface microhardness, cross-sectional microhardness and micro-CT. Scanning electron microscopy and energy dispersive X-ray spectrometry (SEM/EDX) were also obtained. Hydroxypropyl-b-cyclodextrin + 1% TiF4 after 12 h complexation resulted in lower percentage of surface microhardness loss compared to Mili-Q water, hydroxypropyl-b-cyclodextrin, 1% TiF4 and hydroxypropyl-b-cyclodextrin + 1% TiF4 after 72 h of complexation group, with a large effect size (from 1.307 to 2.943) and high power (84.9 to 99%). All groups resulted in similar integrated mineral loss (ΔZ) obtained by both internal microhardness and micro-CT techniques. Enamel treated with TiF4 and TiF4 + hydroxypropyl-b-cyclodextrin groups showed a TiO2 glaze-layer, while EDX evaluation identified Ti. The solution containing the inclusion complex of hydroxypropyl-b-cyclodextrin + TiF4 with 12 h of complexation period demonstrated a significant ability to reduce surface demineralization of sound enamel under an artificial cariogenic challenge.

Cyclodextrin and TIF4 nanocomplex on enamel demineralization

Abstract The aim of this study was to assess the effect of a newly developed nanocomplex formed of hydroxypropyl-b-cyclodextrin and 1% titanium tetrafluoride (TiF4) after distinct complexation periods (12/72 h) on demineralization of bovine enamel in vitro. Enamel blocks (n=60) were allocated in different groups: Mili-Q water, hydroxypropyl-b-cyclodextrin, 1% TiF4, hydroxypropyl-b-cyclodextrin + 1% TiF4 after 12 h of complexation and hydroxypropyl-b-cyclodextrin + 1% TiF4 after 72 h of complexation. The samples were evaluated by surface microhardness, cross-sectional microhardness and micro-CT. Scanning electron microscopy and energy dispersive X-ray spectrometry (SEM/EDX) were also obtained. Hydroxypropyl-b-cyclodextrin + 1% TiF4 after 12 h complexation resulted in lower percentage of surface microhardness loss compared to Mili-Q water, hydroxypropyl-b-cyclodextrin, 1% TiF4 and hydroxypropyl-b-cyclodextrin + 1% TiF4 after 72 h of complexation group, with a large effect size (from 1.307 to 2.943) and high power (84.9 to 99%). All groups resulted in similar integrated mineral loss (ΔZ) obtained by both internal microhardness and micro-CT techniques. Enamel treated with TiF4 and TiF4 + hydroxypropyl-b-cyclodextrin groups showed a TiO2 glaze-layer, while EDX evaluation identified Ti. The solution containing the inclusion complex of hydroxypropyl-b-cyclodextrin + TiF4 with 12 h of complexation period demonstrated a significant ability to reduce surface demineralization of sound enamel under an artificial cariogenic challenge.

Resumo O objetivo deste estudo foi avaliar o efeito da 1-etil-3- (3-dimetilaminopropil) carbodiimida (EDC) na resistência de união de pinos de fibra de vidro em canais radiculares obturados com diferentes cimentos endodônticos. Setenta e oito pré-molares inferiores foram obturados com três cimentos endodônticos (n=26): Endofill (END), AH Plus (AHP) e Endosequence BC Sealer (EBS). Após o preparo do espaço para pino, dois subgrupos formaram-se conforme a cimentação dos pinos (n=13): com EDC e sem EDC (controle - CON). Os espécimes foram submetidos ao teste pull-out, classificação do modo de falha e avaliação da superfície do canal radicular por microscopia eletrônica de varredura após o deslocamento. Quanto à força de resistência de união, uma diferença estatisticamente significativa ocorreu entre os subgrupos EDC e CON apenas no END (p=0,001). Não foi detectada diferença entre os subgrupos CON (p=0,339). Contudo, no subgrupo EDC, o AHP apresentou maiores valores (END versus AHP: p=0,001; AHP versus EBS: p=0,016). Acerca da classificação dos modos de falha, o escore 1 (≥50% de cimento) foi o mais comumente observado, exceto para END + EDC. Restos de cimentos endodônticos e cimentos resinosos foram encontrados no terço cervical, mas sem diferença estatística (p=0,269), enquanto no terço médio, houve diferença (p=0,004). Em conclusão, o EDC diminui a resistência de união quando associado ao cimento END, sem alterar o modo de falha entre o cimento resinoso e o pino de fibra de vidro. O melhor desempenho foi observado quanto o EDC foi usado com o cimento AHP.

Characterization and effect of nanocomplexed fluoride solutions on the inhibition of enamel demineralization created by a multispecies cariogenic biofilm model.

OBJECTIVES: The aim of this study was to assess the in vitro caries preventive effect of nanocomplexed solutions of hydroxypropyl-ß-cyclodextrin and γ-cyclodextrin associated with titanium tetrafluoride (TiF4) after different complexation times (12 or 72 h). MATERIALS AND METHODS: Enamel blocks were randomly distributed in 9 groups (n = 11): negative control, hydroxypropyl-ß-cyclodextrin, γ-cyclodextrin, TiF4, hydroxypropyl-ß-cyclodextrin:TiF4 12 h, hydroxypropyl-ß-cyclodextrin:TiF4 72 h, γ-cyclodextrin:TiF4 12 h, γ-cyclodextrin:TiF4 72 h, and NaF (positive control). The solutions were applied for 1 min and the blocks were exposed to a biofilm model. Nanocompounds were characterized by differential scanning calorimetry and X-ray powder diffraction. The percentage of surface microhardness loss (%SML), mineral density changes (ΔZ), lesion depth, surface morphology (scanning electron microscopy-SEM), and chemical characterization (energy-dispersive spectroscopy-EDS) were assessed. RESULTS: No oxidation was observed, and the formation of the nanocomplexes was evidenced by changes in the melting point compared to pure cyclodextrins and the loss of crystallinity of the materials. Hydroxypropyl-ß-cyclodextrin:TiF4 72 h resulted in lower %SML than negative control, hydroxypropyl-ß-cyclodextrin, γ-cyclodextrin, and TiF4 (p < 0.05). NaF differed from all groups (p < 0.05), except for hydroxypropyl-ß-cyclodextrin:TiF4 72 h (p = 0.83). ΔZ of hydroxypropyl-ß-cyclodextrin:TiF4 72 h was higher than negative control, hydroxypropyl-ß-cyclodextrin, γ-cyclodextrin, γ-cyclodextrin:TiF4 1 2 h, γ-cyclodextrin:TiF4 72 h, and NaF (p < 0.05) and similar to TiF4 and hydroxypropyl-ß-cyclodextrin:TiF4 12 h (p > 0.05). SEM/EDS detected Ti in the blocks subjected to TiF4-products. CONCLUSION: The hydroxypropyl-ß-cyclodextrin:TiF4 72 h solution showed caries preventive effect on the surface and subsurface of the enamel. CLINICAL RELEVANCE: A hydroxypropyl-ß-cyclodextrin nanosystem, in association with TiF4 after 72 h of complexation, may be a promising agent for the prevention of enamel demineralization.

A Synthetic Snake-Venom-Based Tripeptide Protects PC12 Cells from the Neurotoxicity of Acrolein by Improving Axonal Plasticity and Bioenergetics.

The synthetic peptide p-BTX-I is based on the native peptide (formed by glutamic acid, valine and tryptophan) isolated from Bothrops atrox venom. We have previously demonstrated its neuroprotective and neurotrophic properties in PC12 cells treated with the dopaminergic neurotoxin 1-methyl-4-phenylpyridinium (MPP+). Now, we have investigated the neuroprotective effects and mechanisms of p-BTX-I against the toxicity of acrolein in PC12 cells. Studies have demonstrated that acrolein might play an important role in the etiology of Alzheimer's disease (AD), which is characterized by neuronal and synaptic loss. Our results showed that not only acrolein reduced cell differentiation and cell viability, but also altered the expression of markers of synaptic communication (synapsin I), energy metabolism (AMPK-α, Sirt I and glucose uptake), and cytoskeleton (ß-III-tubulin). Treatment with p-BTX-I increased the percentage of differentiation in cells treated with acrolein and significantly attenuated cell viability loss, besides counteracting the negative effects of acrolein on synapsin I, AMPK-α, Sirt I, glucose uptake, and ß-III-tubulin. Additionally, p-BTX-I alone increased the expression of apolipoprotein E (apoE) gene, associated with the proteolytic degradation of ß-amyloid peptide aggregates, a hallmark of AD. Taken together, these findings demonstrate that p-BTX-I protects against acrolein-induced neurotoxicity and might be a tool for the development of novel drugs for the treatment of neurodegenerative diseases.

Caffeic Acid Phenethyl Ester (CAPE) Protects PC12 Cells Against Cisplatin-Induced Neurotoxicity by Activating the AMPK/SIRT1, MAPK/Erk, and PI3k/Akt Signaling Pathways.

Peripheral sensory neuropathy (PSN) is a well-known side effect of cisplatin characterized by axonal damage. In the early stage of neurotoxicity, cisplatin affects proteins that modulate neurite outgrowth and neuroplasticity, without inducing mitochondrial damage or apoptosis. There are no preventive therapies for cisplatin-induced peripheral neuropathy; therefore, measures to improve axonal growth and connectivity would be beneficial. Caffeic acid phenethyl ester (CAPE) is a bioactive component of propolis with neurotrophic and neuroprotective activities. We have recently showed that CAPE protects against cisplatin-induced neurotoxicity by activating NGF high-affinity receptors (trkA) and inducing neuroplasticity. We have now assessed other potential early targets of cisplatin and additional mechanisms involved in the neuroprotection of CAPE. Cisplatin reduced axonal cytoskeletal proteins (F-actin and ß-III-tubulin) without inducing oxidative damage in PC12 cells. It also reduced energy-related proteins (AMPK α, p-AMPK α, and SIRT1) and glucose uptake. At this stage of neurotoxicity, glutamate excitotoxicity is not involved in the toxicity of cisplatin. CAPE attenuated the downregulation of the cytoskeleton and energy-related markers as well as SIRT1 and phosphorylated AMPK α. Moreover, the neuroprotective mechanism of CAPE also involves the activation of the neurotrophic signaling pathways MAPK/Erk and PI3k/Akt. The PI3K/Akt pathway is involved in the upregulation of SIRT1 induced by CAPE, but not in the upregulation of cytoskeletal proteins. Altogether, these findings suggest that the neuroprotective effect of CAPE against cisplatin-induced neurotoxicity involves both (a) a neurotrophic mechanism that mimics the mechanism triggered by the NGF itself and (b) a non-neurotrophic mechanism that upregulates the cytoskeletal proteins.

Development and Characterization of Dapsone Cocrystal Prepared by Scalable Production Methods.

In this study, the formation of caffeine/dapsone (CAF/DAP) cocrystals by scalable production methods, such as liquid-assisted grinding (LAG) and spray drying, was investigated in the context of the potential use of processed cocrystal powder for pulmonary delivery. A CAF/DAP cocrystal (1:1 M ratio) was successfully prepared by slow evaporation from both acetone and ethyl acetate. Acetone, ethyl acetate, and ethanol were all successfully used to prepare cocrystals by LAG and spray drying. The powders obtained were characterized by X-ray diffractometry (XRD), differential scanning calorimetry (DSC), thermogravimetry (TGA), and Fourier transform infrared spectroscopy (FTIR). Laser diffraction analysis indicated a median particle size (D50) for spray-dried powders prepared from acetone, ethanol, and ethyl acetate of 5.4 ± 0.7, 5.2 ± 0.1, and 5.1 ± 0.0 µm respectively, which are appropriate sizes for pulmonary delivery by means of a dry powder inhaler. The solubility of the CAF/DAP cocrystal in phosphate buffer pH 7.4, prepared by spray drying using acetone, was 506.5 ± 31.5 µg/mL, while pure crystalline DAP had a measured solubility of 217.1 ± 7.8 µg/mL. In vitro cytotoxicity studies using Calu-3 cells indicated that the cocrystals were not toxic at concentrations of 0.1 and of 1 mM of DAP, while an in vitro permeability study suggested caffeine may contribute to the permeation of DAP by hindering the efflux effect. The results obtained indicate that the CAF/DAP cocrystal, particularly when prepared by the spray drying method, represents a possible suitable approach for inhalation formulations with applications in pulmonary pathologies.

Antileishmanial Thioureas: Synthesis, Biological Activity and in Silico Evaluations of New Promising Derivatives.

Leishmaniasis is a neglected tropical disease caused by protozoan parasites belonging to the genus Leishmania. Currently, the drugs available for treatment of this disease present high toxicity, along with development of parasite resistance. In order to overcome these problems, efforts have been made to search for new and more effective leishmanicidal drugs. The aim of this study was to synthesize and investigate the leishmanicidal effect of N,N'-disubstituted thioureas against Leishmania amazonensis, with evaluation of their in silico pharmacokinetics and toxicity profiles. Our results showed that different thioureas could be obtained in high to moderate yields using simple reaction conditions. Nine thiourea derivatives (3e, 3i, 3k, 3l, 3p, 3q, 3v, 3x and 3z) were active against parasite promastigotes (IC50 21.48-189.10 µM), with low cytotoxicity on mice peritoneal macrophages (CC50>200 µM), except for thiourea 3e (CC50=49.22 µM). After that, the most promising thioureas (3k, 3l, 3p, 3q and 3v) showed IC50 ranging from 70 to 150 µM against L. amazonensis amastigotes in infected macrophages. Except for thiourea 3p, the leishmanicidal activity of the derivatives were independent of nitric oxide (NO) production. Thioureas 3q and 3v affected promastigotes cell cycle without disturbing the mitochondrial membrane potential. Furthermore, our derivatives showed satisfactory theoretical absorption, distribution, metabolism, excretion, toxicity (ADMET) properties. These data indicate that thiourea derivatives are good candidates as leading compounds for the development of new leishmanicidal drugs.

Evaluation of the cytotoxicity and phototoxicity of Caryocar brasiliense supercritical carbon dioxide extract.

BACKGROUND: Caryocar brasiliense Camb (Pequi) is a typical Brazilian Cerrado fruit tree. Its fruit is used as a vitamin source for culinary purposes and as a source of oil for the manufacture of cosmetics. C. brasiliense supercritical CO2 extracts exhibit antimicrobial activity against the bacteria Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus and also possess antioxidant activity. This study was designed to evaluate the in vitro cytotoxicity and phototoxicity of the supercritical CO2 extract obtained from the leaves of this species. METHODS: In vitro cytotoxicity and phototoxicity of C. brasiliense supercritical CO2 extracts were assessed using a tetrazolium-based colorimetric assay (XTT) and Neutral Red methods. RESULTS: We found that the C. brasiliense (Pequi) extract obtained by supercritical CO2 extraction did not present cytotoxic and phototoxic hazards. CONCLUSIONS: This finding suggests that the extract may be useful for the development of cosmetic and/or pharmaceutical products.

Acaricidal properties of the formulations based on essential oils from Cymbopogon winterianus and Syzygium aromaticum plants.

The cattle tick, Rhipicephalus (Boophilus) microplus, has caused serious harm to livestock raising in Brazil, considering the costs of controlling it, loss of revenue due to smaller production of milk and meat, and damage to leather, in addition to transmitting diseases. The use of medicinal plants is considered an alternative to the recurring resistance to chemicals. Due to the need for efficient alternatives with less environmental impact, this study aimed to develop contact formulations with essential oils from the Java citronella (Cymbopogon winterianus) and clove (Syzygium aromaticum) plants and to assess in vitro the effects in different stages of the tick cycle. In the present study, concentrations from 0.5-15.0% of the essential oils incorporated in the formulations were used. The ticks from different geographical areas were treated with those formulations, and their effects on the production levels of eggs, on the larvae hatching, and their efficiency on ticks were assessed. The obtained results were compared with other commercial acaricidal products. After the 20th day of treatment, the formulations with citronella essential oil had 2.09-55.51% efficiency, depending on the concentration of the oil incorporated. The efficiency of the treatment with formulations containing clove essential oil was higher, from 92.47-100%. The results showed the acaricidal effects of the formulations tested when compared to commercial chemical products. In vivo studies should be performed in order to assess the efficiency of those formulations in the fields, aiming to use these products as an alternative for controlling cattle ticks.

Caryocar brasiliense supercritical CO2 extract possesses antimicrobial and antioxidant properties useful for personal care products.

BACKGROUND: The cosmetic and pharmaceutical industries have an increasing interest in replacing synthetic antimicrobials in dermatological products due to increased microbial resistance to conventional antimicrobial agents. Pequi (Caryocar brasiliense) is a native fruit tree of the Brazilian Cerrado, specifically used in cosmetics, in the food industry, and for medicinal purposes. Leishmanicidal and antifungal activities have been reported previously. This study was designed to evaluate the antimicrobial and antioxidant activities of a C. brasiliense extract obtained by supercritical CO2 extraction. METHODS: The minimum inhibitory concentrations (MICs) against Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus were determined by the classical microdilution method. Antiseptic activity against these organisms was evaluated by the plate diffusion method. The antioxidant potential of the extract was evaluated using a method based on the oxidation of 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS). The extract's chemical profile was analyzed for the presence of alkaloids, saponins, anthraquinones, steroids, tannins, flavonoids, and phenolic compounds according to standard colorimetric methods. RESULTS: The C. brasiliense supercritical CO2 extract exhibits antimicrobial activity against all bacteria tested. It also possesses antioxidant activity, when compared to a vitamin E standard. CONCLUSIONS: The C. brasiliense supercritical CO2 extract may be useful for the development of personal care products, primarily for antiseptic skin products that inactivate, reduce, prevent, or arrest the growth of microorganisms with the inherent intent to mitigate or prevent disease as well as products that minimize damage caused by free radicals.

Development and characterization of a new oral dapsone nanoemulsion system: permeability and in silico bioavailability studies.

BACKGROUND: Dapsone is described as being active against Mycobacterium leprae, hence its role in the treatment of leprosy and related pathologies. Despite its therapeutic potential, the low solubility of dapsone in water results in low bioavailability and high microbial resistance. Nanoemulsions are pharmaceutical delivery systems derived from micellar solutions with a good capacity for improving absorption. The aim of this work was to develop and compare the permeability of a series of dapsone nanoemulsions in Caco-2 cell culture against that of effective permeability in the human body simulated using Gastroplus™ software. METHODS AND RESULTS: The release profiles of the dapsone nanoemulsions using different combinations of surfactants and cosolvent showed a higher dissolution rate in simulated gastric and enteric fluid than did the dispersed dapsone powder. The drug release kinetics were consistent with a Higuchi model. CONCLUSION: This comparison of dapsone permeability in Caco-2 cells with effective permeability in the human body simulated by Gastroplus showed a good correlation and indicates potential improvement in the biodisponibility of dapsone using this new system.

Estirpes bacterianas-padrão, formas de obtenção de doação e sua manutenção em laboratórios de ensino e pesquisa / Estirpes standard bacterial strains, ways of obtaining donation and maintenance in teaching and research

Boas Práticas de Laboratório (BPL) referem-se ao sistema da qualidade que contribui para a garantia da qualidade dos resultados. Essas práticas incluem o uso de estipes padrão para o controle do desempenho de meios de cultura, corantes e de reações. Estirpes padrão ou bactérias de referência são culturas provenientes de uma coleção de culturas reconhecida nacional e/ou internacionalmente, acompanhadas de um certificado com a descrição de suas características fenotípicas e genotípicas e outras informações relevantes. A conservação de suas características originais e viabilidade são requisitos essenciais para a sua reprodução em processos industriais e em experimentos de pesquisa. O objetivo deste trabalho foi reunir e disponibilizar informações sobre as formas de obtenção de doação de estipes-padrão para laboratórios de ensino e pesquisa e sobre a sua manutenção. Foram reunidas informações por meio de pesquisa bibliográfica sobre instituições doadoras de estirpes padrão, e formas de reativação e manutenção. A disponibilização deste material possibilita o cumprimento das BPL e a qualidade em trabalhos desenvolvidos.

Good Laboratory Practices (GLP) refer to the quality system that contributes to guarantee the quality of research results, including the use of standard strains to control the performance of culture media, dyes, and reactions. Standard strains or reference bacteria are cultures originated from a collection of cultures nationally and/or internationally recognized, followed by a certificate describing their phenotypic and genotypic characteristics and other relevant information. The preservation of their original characteristics is one of the essential requirements for their viability, important for their reproduction in industrial processes and in pure and applied research experiments. The objective of this work was to compile and disseminate information on the ways of obtaining donation of standard strains to teaching and research laboratories and their maintenance in microbiological analysis laboratories. Through a bibliographic survey, information was compiled on institutions that donate reference material and on methods of standard strain reactivation and adequate maintenance. The availability of this material through donations and adequate maintenance according to laboratory conditions allow fulfilling GLP requirements and the quality of the works developed.

Official monitoring of the Brazilian Norm for Commercialization of Food for Nursling and Children of First Infancy, Rubber Nipples, Pacifiers, and Nursing Bottles - NBCAL / Monitoramento oficial da Norma Brasileira de Comercialização de Alimentos para Lactentes e Crianças de Primeira Infância, Bicos de borracha, chupetas e mamadeiras - NBCAL

This work aimed to evaluate advertisement of baby food, rubber nipples, pacifiers and nursing bottles through newspapers as well as on TV, radio, and the internet, in order to check whether the 'Brazilian Norm for Commercialization of Food for Nursling and Children of First Infancy, Rubber Nipples, Pacifiers and Nursing Bottles' (Norma Brasileira de Comercialização de Alimentos para Lactentes e Crianças de Primeira Infância, Bicos, Chupetas e Mamadeiras - NBCAL) has been complied. Samples of all the items above were acquired at discount and department stores to check whether labeling was in compliance with the NBCAL. The development of this research as well as the analyses of commercial promotion were carried out in Juiz de Fora - state of Minas Gerais, from May to July 2006, using convenient, non-representative sampling composed of 680 pieces of advertisement. The results obtained through descriptive statistics showed that 564 of the 680 samples analyzed, or 83.0 percent, did not meet the NBCAL. Irregularities were detected in 100 percent of the samples advertised on the media and found in hospitals and drugstores; in 70.1 percent of the samples purchased at supermarkets, in 37 percent of those from medical clinics and in 86.6 percent of those found on the internet. The evidences showed that monitoring must be carried out continuously and educational campaigns on the importance of breast-feeding for the full development of children must be addressed to mothers, the food industry and commercial establishments.

O presente trabalho teve como objetivo avaliar propagandas e publicidades impressas de alimentos infantis, bicos, chupetas e mamadeiras, além das veiculadas em rádio, TV e internet, para verificar o cumprimento da Norma Brasileira de Comercialização de Alimentos para Lactentes e Crianças de Primeira Infância (NBCAL). Também foi realizada a aquisição de bicos, mamadeiras e chupetas em "lojas de 1,99" e de departamento, para a verificação de rotulagem de acordo com a NBCAL. O desenvolvimento da pesquisa foi realizado no período de maio a julho de 2006, no município de Juiz de Fora, MG, mediante amostragem não representativa, de conveniência. A amostra constituiu-se de 680 peças publicitárias. Os resultados foram analisados pela estatística descritiva. Das 680 peças publicitárias analisadas, 564 (83,0 por cento) não cumpriram a NBCAL. Foram encontradas irregularidades em 100 por cento das amostras captadas em rádio, TV, jornais, revistas, hospitais e farmácias; em 70,1 por cento das amostras captadas em supermercados; em 37 por cento das amostras captadas em clínicas médicas e em 86,6 por cento das captadas na internet. Concluiu-se que há necessidade de intensificar o monitoramento em caráter contínuo e que as ações educativas relativas à importância do aleitamento materno devem ser direcionadas para as mães, indústrias produtoras e empresas que comercializam alimentos infantis.

Determinação do teor de cumarina no xarope de guaco armazenado em diferentes temperaturas / Coumarin content of guaco syrup stored at different temperatures

A produção magistral do xarope de guaco, obtido a partir do extrato fluido do guaco (Mikania glomerata Spreng., Asteraceae) e comercializada na Farmácia Universitária da UFJF/MG, gerou um projeto de pesquisa com o objetivo principal de estudar a estabilidade do produto acabado, tendo como ponto de referência a determinação do teor de cumarina das amostras armazenadas em diferentes temperaturas. O método aplicado para realizar a análise do teor de cumarina presente no xarope em estudo foi espectrometria no UV com comprimento de onda de 275,4 nm. Utilizou-se como veículo para efetuar as diluições da amostra uma mistura de metanol/água destilada, na proporção de 80 por cento v/v. A curva de calibração foi obtida diluindo-se 100 mg de cumarina padrão em 100 mL da solução descrito acima, obtendo-se sete concentrações distintas com variação de 2 µg a 20 µg. Os resultados obtidos demonstraram que a temperatura de armazenamento de 45 °C foi considerada ótima para desenvolver a conversão do isômero trans em cis com subseqüente conversão deste a cumarina. Os valores de cumarina encontrados na forma farmacêutica em estudo foram de 1,19 a 1,37 mg/mL, sendo que o valor mais alto refere-se às amostras armazenadas a 45°C durante seis meses.

The production of guaco syrup, obtained from guaco (Mikania glomerata Spreng., Asteraceae) fluid extract, and commercialized by the University Pharmacy of the Federal University of Juiz de Fora-MG, Brazil, led to a research project whose main aim was to study the stability of the finished product, with reference to the coumarin content of samples stored at different temperatures. UV spectrophotometry (275.4 nm) was used to assess the coumarin content of the study syrup. An 80 percent v/v methanol/distilled water mixture was used for sample dilution. The calibration curve was constructed by the dilution of 100 mg standard coumarin in 100 ml of the aforementioned solution, with seven distinct concentrations (ranging from 2 µg a 20 µg) being obtained. The results showed the 45 °C storage temperature to be optimum for the development of trans-cis isomerization, with subsequent conversion of the latter into coumarin. Coumarin content in the studied pharmaceutical presentation ranged from 1.19 to 1.37 mg/mL, the highest value corresponding to the samples stored at 45 °C for six months.