Equivalent biodiversity area: A novel metric for No Net Loss success in Brazil's changing biomes.

This study presents a new method to incorporate the No Net Loss (NNL) principle within corporate Environmental, Social, and Governance (ESG) frameworks. This principle aims to ensure that biodiversity losses from human activities are fully offset. In this context, we tackle two main challenges: managing epistemic uncertainties in environmental modeling and accurately assessing compensatory areas needed to replace lost habitats. Focusing on Brazil's diverse biomes, which are undergoing rapid changes, we highlight the role of expert opinion surveys in addressing the uncertainties of the InVEST Habitat Quality, a model that simulates changes in landscape integrity under different land use scenarios. Our analysis across three of Brazil's regions - Caatinga Semi-arid, Cerrado Savanna, and Atlantic Forest - leverages open-source data to reveal substantial habitat losses due to activities like wind farm development, mining, and intensive agriculture, leading to a widespread decline in habitat quality. We introduce the Equivalent Biodiversity Area (EBA) metric to support NNL and Net Gain of Biodiversity efforts, measured in hectares. Findings show a reduction in EBA across all studied areas, highlighting the need for effective compensation strategies. Such strategies should merge Legal Reserves and ecological restoration into ESG policies, encourage landholder collaboration, and align with larger environmental efforts, such as watershed revitalization and Biodiversity Credits markets.

Topical formulation containing chitosan-chamomile microparticles in cutaneous wound healing in rats.

Objective: The aim of this research was to evaluate the efficacy of a topical formulation containing chitosan-chamomile microparticles in cutaneous healing in rats. Method: Male Wistar rats (n=57) were randomly distributed into three groups: treatment; vehicle; and control. Evaluations were performed on days 2, 7 and 14 after the surgical procedure using skin lesion photography, and histological and biochemical analyses. Results: The results showed that there was no difference in the healing index and in the histological analysis of the inflammatory infiltrate among groups. Fibrogenesis was more significant in the group treated with the test formulation at day 7, and angiogenesis was greater in the vehicle and chamomile groups at day 2. The quantification of hydroxyproline showed a higher amount of collagen in the group treated with chamomile, mainly at day 14, although the histological quantification of collagen showed no difference between the groups. Conclusion: From the results of this study, it can be concluded that the formulation, although it had no effect on the healing time, improved the quality of the cicatricial tissue formed with a greater quantity of fibroblasts and collagen.

Photoprotective effect of solid lipid nanoparticles of rutin against UVB radiation damage on skin biopsies and tissue-engineered skin.

Solid lipid nanoparticles (SLNs) containing rutin were prepared to enhance their photochemopreventive effect on the skin. SLNs were produced by the hot melt microemulsion technique. Two 3D skin models: ex vivo skin explants and 3D tissue engineering skin were used to evaluate the photochemopreventive effect of topical formulations containing rutin SLNs, against ultraviolet B (UVB) radiation, inducing sunburn cells, caspase-3, cyclobutane pyrimidine dimers, lipid peroxidation, and metalloproteinase formation. The rutin SLNs presented average size of 74.22 ± 2.77 nm, polydispersion index of 0.16 ± 0.04, encapsulation efficiency of 98.90 ± 0.25%, and zeta potential of -53.0 ± 1.61 mV. The rutin SLNs were able to efficiently protect against UVB induced in the analysed parameters in both skin models. Furthermore, the rutin SLNs inhibited lipid peroxidation and metalloproteinase formation. These results support the use of rutin SLNs as skin photochemopreventive agents for topical application to the skin.

Dynamics of Growth and Egg Traits in Three Dietary Balanced Protein Scenarios Applied for Laying Hens.

The objective of this study was to evaluate laying hens from 8 to 102 weeks old, regarding their changes in performance, body composition, and egg components produced in three scenarios of nutrition. Three treatments designed to contain different levels of balanced protein (BP) were randomly assigned to the experimental units, performing ten replicates per treatment with 20 birds each. A standard feed was formulated to meet hen requirements and the ideal ratio between essential amino acids. Then, two experimental feeds were formulated to contain 20% above or below the dietary BP used in the standard feed. The responses evaluated were cumulated feed intake (g), daily feed intake (g/day), body weight (g), body composition (g of protein, fat, and ash), hen-housed egg production (%/hen-housed), egg production (%), egg weight (g), egg mass (g), and egg components (percentages of yolk, albumen, and eggshell). The dietary BP influenced the body composition, egg production, egg weight, and egg mass of white laying hens. The increase in dietary BP was related to an increase in body contents and egg weight, whereas hens consuming the low dietary balanced protein presented a lower body weight, leaner, and produced smaller eggs.

Spray-dried bacterial cellulose nanofibers: A new generation of pharmaceutical excipient intended for intestinal drug delivery.

Defibrillation of bacterial cellulose by ultra-refining was efficient to release nanofibers (BCNF) which were spray dried with the matrices formers mannitol (MN), maltodextrin or hydroxypropylmethylcellulose. The best microsystem comprised the association of BCNF and MN, so the selected microparticles were loaded with diclofenac sodium or caffeine. Depending on the proportion of BCNF, the nanofibers collapse promoted by spray drying can occur onto surface or into microparticles core, leading to different release behaviors. Samples showed pH-dependent drug release, so the microsystem developed with the lowest BCNF concentration showed important trend to gastroresistance. Caffeine was spray dried as a free drug and for this reason it was devoid of any control over release rates. The set of results showed BCNF can be considered an interesting and potential pharmaceutical excipient for lipophilic drugs. Beyond that, BCNF association with MN can lead to novel enteric drug delivery systems based on natural polymers.

Different levels of selenomethionine on the meat quality and selenium deposition in tissue of finishing pigs.

The aim of the study was to verify the influence of selenomethionine (SM) supplementation on performance, carcass yield, characteristics of meat quality and Se tissue deposition of finishing pigs. A total of 128 hybrid pigs with an average weight of 76 kg were distributed in randomized blocks according to body weight in eight treatments and eight replicates. The experimental treatments were two Se levels from sodium selenite-SS (0.3 and 0.6 ppm), four Se levels from SM (0.3, 0.4, 0.5 and 0.6 ppm) and two combinations of SS with SM (SS 0.15 + SM 0.15 ppm and SS 0.3 + SM 0.3 ppm) providing 0.3 and 0.6 ppm Se in the diet respectively. The feeds were based on corn and soya bean meal. After 30 days on test, were analysed the performance indices and the pigs were slaughtered at commercial slaughterhouse. The cold carcass yield, the physicochemical characteristics of the loin meat and the Se content in muscle and liver were evaluated. There was no significant difference in performance indices (p > .05); however, there was a linear effect on the increase in pig carcass yield by increasing SM (p < .05). The use of SM solely or combined with SS provided higher Se deposition in muscle compared to SS (p < .05). The highest Se deposition in muscle occurred for SM at 0.4 ppm (p < .05). The SS provided higher Se deposition in liver (p < .05). The SM presented best results for meat quality compared to other sources (p < .05). The level of 0.4 ppm Se promoted the best results for the indices of yellow, luminosity, cooking loss and pH (p < .05). The use of SM at any level promotes higher oxidation stability of pig meat (p < .05). The supplementation of SM at a level of 0.4 ppm promotes better physicochemical characteristics and higher Se deposition on swine meat.

Supplementation of selenomethionine at different ages and levels on meat quality, tissue deposition, and selenium retention in broiler chickens.

The aim of the present study was to verify the effect of selenomethionine (SM) supplementation in the diet of chickens on performance, carcass yield, apparent retention, meat quality, and selenium (Se) deposition in tissues. In the first experiment, 2,100 day-old male chicks from the Hubbard Flex strain were randomly distributed in 84 plots with 12 treatments and 7 replicates. The treatments consisted of SM (1,600 ppm) supplementation at levels of 0.3 and 0.5 ppm in substitution of sodium selenite (45.7%) in different preslaughter phases. In the second experiment, 224 day-old male chicks from Hubbard Flex strain were randomly distributed in 28 metabolic cages. Poultry were distributed in 4 treatments with 7 replicates (8 poultry) in the experimental period from 1 to 21 D and experimental plot with 4 poultry aged from 22 to 42 D. Treatments consisted of 4 SM addition levels (0.3, 0.4, 0.5, and 0.6 ppm). In both experiments, the performance (1 to 21 and 1 to 42 D), carcass yield and cuts, apparent retention of Se (33 to 35 D), physical and chemical characteristics of the breast meat were evaluated: objective color, drip loss (DL), cooking loss (CL), pH, peroxide value, and Se deposition in tissues. In experiment I, it was found that SM at 0.3 ppm improved the weight gain and feed conversion of 1 to 42 D. The use of SM at 0.5 ppm resulted in lower DL and CL. The highest Se deposition in muscles was obtained using the SM at 0.5 ppm of 1 to 42 D. Using the SM at 0.5 ppm, only in the last week there was a deposition similar to the use of SM at 0.3 ppm of 1 to 42 D. In experiment II, it can be observed that increased SM levels provided lower DL and lower pH values. Se deposition in tissues of broiler chickens increased linearly at the SM level from 0.3 to 0.6 ppm.

Fluidized Bed Hot-Melt Granulation as a Tool to Improve Curcuminoid Solubility.

Curcumin is the main bioactive component of Curcuma longa L. and has recently aroused growing interest from the scientific community. Unfortunately, the medicinal properties attributed to curcuminoids are impaired by their low oral bioavailability or low solubility in aqueous solutions. Many strategies have been studied to improve curcumin solubility; however, the preparation of granules using hydrophilic materials has never been attempted. The aim of this work was to develop curcumin granules by fluidized bed hot-melt granulation using the hydrophilic carrier Gelucire® 50:13. A two-level factorial design was used to verify the influence of Gelucire® 50:13 and lactose contents found in the granules on their size, morphology, bulk and tapped densities, flow, moisture content, and water activity. The granules obtained were also evaluated by differential scanning calorimetry, thermogravimetric analysis, X-ray powder diffraction, and infrared spectrometry. The curcumin solubility and dissolution rates in water were determined by liquid chromatography. The best formulation provides an increase of curcumin solubility of 4642-fold and 3.8-fold compared to the physical mixture. The dissolution tests showed a maximum drug release from granules after 45 min of 70% at pH 1.2 and 80% at pH 5.8 and 7.4, while for non-granulated curcumin, the release was below 20% in all pH. The solid-state characterization and solubility measurement showed good stability of granules over 9 months. The results attest that the fluidized bed hot-melt granulation with hydrophilic binders is an attractive and promising alternative to obtain solid forms of curcumin with enhanced bioavailability.

Triterpene saponins from Billia rosea.

Five previously undescribed triterpene saponins, billiosides A-E, and a known analogue, were isolated from the seeds of Billia rosea (Planch. & Linden) C. Ulloa & P. Jørg. Their structures were elucidated on the basis of extensive 1D and 2D NMR experiments (1H, 13C, DEPT, COSY, TOCSY, NOESY, ROESY, HSQC, and HMBC) and mass spectrometry as (3ß,21ß,22α)-3-[(2-O-ß-D-glucopyranosyl-O-[α-L-arabinopyranosyl-(1 â†’ 4)]-ß-D-glucopyranosyl)oxy]-21-[((2E,6S)-2,6-dimethyl-6-hydroxyocta-2,7-dienoyl)oxy]-22-(acetyloxy)-24-hydroxyolean-12-en-28-oic acid, (3ß,21ß,22α)-3-[(2-O-ß-D-galactopyranosyl-ß-D-glucopyranosyl)oxy]-21,22-dihydroxyolean-12-en-28-yl O-α-L-arabinopyranosyl-(1 â†’ 4)-ß-D-glucopyranoside, (3ß,21ß,22α)-3-[(2-O-ß-D-galactopyranosyl-O-[α-L-arabinopyranosyl-(1 â†’ 4)]-ß-D-xylopyranosyl)oxy]-21,22-dihydroxyolean-12-en-28-yl O-ß-D-glucopyranoside, (3ß,21ß,22α)-3-[(2-O-ß-D-galactopyranosyl-O-[α-L-arabinopyranosyl-(1 â†’ 4)]-ß-D-glucopyranosyl)oxy]-21,22-dihydroxyolean-12-en-28-yl O-ß-D-glucopyranoside, (3ß,21ß,22α)-3-[(2-O-ß-D-galactopyranosyl-O-[α-L-arabinopyranosyl-(1 â†’ 4)]-ß-D-glucopyranosyl)oxy]-21,22-dihydroxyolean-12-en-28-yl O-ß-D-glucopyranosyl-(1 â†’ 6)-ß-D-glucopyranoside, and dipteroside A. Billiosides B and C exhibited moderate effects when tested as hepatic glucose-6-phosphatase inhibitors and as glucose intestinal absorption inhibitors, using in situ rat intestinal segments.

Box-Behnken analysis and storage of spray-dried collagenolytic proteases from Myceliophthora thermophila submerged bioprocess.

Enzymes do not have long-term storage stability in soluble forms, thus drying methods could minimize the loss of enzymatic activity, the spray dryer removes water under high temperatures and little time. The aims of this study were to improve the stability of enzymatic extract from Myceliophthora thermophila for potential applications in industry and to evaluate the best conditions to remove the water by spray drying technique. The parameters were tested according to Box-Behnken and evaluated by analysis of variance (ANOVA), all the parameters measured were found to influence the final enzyme activity and spray drying process yield ranged from 38.65 to 63.75%. Enzyme powders showed increased storage stability than extract and maintained about 100% of collagenolytic activity after 180 days of storage at 30°C. The results showed that the microbial enzymes maintained activity during the spray drying process and were stable during long-term storage; these are promising characteristics for industrial applications.

Topical Formulation Containing Beeswax-Based Nanoparticles Improved In Vivo Skin Barrier Function.

Lipid nanoparticles have shown many advantages for treatment/prevention of skin disorders with damaged skin barrier function. Beeswax is a favorable candidate for the development of nanosystems in the cosmetic and dermatological fields because of its advantages for the development of products for topical application. In the present study, beeswax-based nanoparticles (BNs) were prepared using the hot melt microemulsion technique and incorporated to a gel-cream formulation. The formulation was subsequently evaluated for its rheological stability and effect on stratum corneum water content (SCWC) and transepidermal water loss (TEWL) using in vivo biophysical techniques. BNs resulted in mean particle size of 95.72 ± 9.63 nm and zeta potential of -9.85 ± 0.57 mV. BN-loaded formulation showed shear thinning behavior, well adjusted by the Herschel-Bulkley model, and a small thixotropy index that were stable for 28 days at different temperatures. BN-loaded formulation was also able to simultaneously decrease the TEWL and increase the SCWC values 28 days after treatment. In conclusion, the novel beeswax-based nanoparticles showed potential for barrier recovery and open the perspective for its commercial use as a novel natural active as yet unexplored in the field of dermatology and cosmetics for treatment of skin diseases with damaged skin barrier function.

Curcumin suppresses inflammatory cytokines and heat shock protein 70 release and improves metabolic parameters during experimental sepsis.

CONTEXT: Curcumin has been reported to have anti-inflammatory, antioxidant and hypoglycaemic properties, besides reducing mortality in sepsis. OBJECTIVE: This study evaluates the biological activities of a curcumin dispersion formulated by spray-drying in experimental sepsis. MATERIALS AND METHODS: Male Wistar rats were subjected to sepsis by caecal ligation and puncture (CLP), controls were sham operated. The animals were treated with curcumin dispersion (100 mg/kg, p.o.) or water for 7 days prior to CLP and at 2 h after surgery. One group was used to analyze curcumin absorption through HPLC; another had the survival rate assessed during 48 h; and from a third group, blood was collected by decapitation to analyze metabolic and inflammatory parameters. RESULTS: The plasma curcumin levels reached 2.5 ng/mL at 4 h, dropped significantly (p < 0.001) at 6 h (1.2 ng/mL), and were undetectable at 24 h in both groups. Curcumin temporarily increased the survival rate of the septic rats by 20%. Moreover, it attenuated glycaemia (p < 0.05) and volemia (p < 0.05) alterations typically observed during sepsis, and decreased the levels of the proinflammatory cytokines IL-1ß and IL-6 in plasma (p < 0.001) and peritoneal lavage fluid (p < 0.05) of septic rats. Serum HSP70 levels were decreased (p < 0.01) at 24 h after CLP. DISCUSSION AND CONCLUSION: Our results show that the curcumin dispersion dose employed was not detrimental to the septic rats. In fact, it temporarily increased their survival rate, improved important metabolic parameters, reduced proinflammatory cytokines and HSP70 production.

Ultrasound influence on the solubility of solid dispersions prepared for a poorly soluble drug.

Solid dispersions have been successfully used to enhance the solubility of several poorly water soluble drugs. Solid dispersions are produced by melting hydrophilic carriers and mixing in the poorly water soluble drug. Supersaturation is obtained by quickly cooling the mixture until it solidifies, thereby entrapping the drug. The effects of using ultrasound to homogenize the molten carrier and drug mixture were studied. In particular, the increase in drug solubility for the resulting solid dispersions was analyzed. Piroxicam, which has very low water solubility, was used as a model drug. A full factorial design was used to analyze how sonication parameters affected the solubility and in vitro release of the drug. The results show that the use of ultrasound can significantly increase the solubility and dissolution rate of the piroxicam solid dispersion. Pure piroxicam presented a solubility of 13.3 µg/mL. A maximum fourfold increase in solubility, reaching 53.8 µg/mL, was observed for a solid dispersion sonicated at 19 kHz for 10 min and 475 W. The in vitro dissolution rate test showed the sonicated solid dispersion reached a maximum rate of 18%/min, a sixfold increase over the piroxicam rate of 2.9%/min. Further solid state characterization by thermal, X-ray diffraction and Fourier transform infrared analyses also showed that the sonication process, in the described conditions, did not adversely alter the drug or significantly change its polymorphic form. Ultrasound is therefore an interesting technique to homogenize drug/carrier mixtures with the objective of increasing the solubility of drugs with poor water solubility.

Improvement of enalapril maleate chemical stability by high shear melting granulation.

Enalapril maleate is a widely used drug, which is chemically unstable when mixed with excipients resulting in enalaprilat and diketopiperazine as the main degradation products. The preparation of enalapril sodium salt has been used to improve drug stability in solid dosage forms; however, product rejection is observed when the chemical reaction for obtaining the sodium salt is not completely finished before packaging. In this study, granules were prepared by melting granulation using stearic acid or glyceryl monostearate, with a view to developing more stable enalapril maleate solid dosage forms. The granules were prepared in a laboratory-scale high shear mixer and compressed in a rotary machine. Size distribution, flow properties, in vitro drug release and enalapril maleate chemical stability were evaluated and compared with data obtained from tablets prepared without hydrophobic binders. All formulations showed good physical properties and immediate drug release. The greatest improvement in the enalapril maleate stability was observed in formulations containing stearic acid. This study showed that hot melting granulation could be successfully used to prepare enalapril maleate granules which could substitute the in situ formation of enalapril sodium salt, since they provided better enalapril stability in solid dosage forms.

Impact of cross-linking and drying method on drug delivery performance of casein-pectin microparticles.

Pectin is a heteropolysaccharide which has been investigated for the development of colon-specific drug delivery systems. Polymers have been associated with pectin to reduce its aqueous solubility and improve the performance of drug delivery systems. Pectin-casein interaction is widely known in food research, but it has not been fully considered by pharmaceutical scientists. Thus, this study investigated the potential of casein-pectin microparticles as a drug delivery system and clarified the impact of cross-linking and drying methods on the in vitro release of indomethacin (IND) or acetaminophen (PCT) from microparticles. Microparticles were prepared by coacervation and dried by spray or spouted bed methods. Drug recovery, in vitro drug release, size, morphology, and the thermal and diffractometric properties of dried microparticles were determined. Spray-dried non-cross-linked microparticles were able to prolong IND release, and pectin was still degraded by pectinolytic enzymes. On the other hand, glutaraldehyde cross-linking prevented the enzymatic breakdown of pectin without improving IND release. Spouted bed drying reduced IND recovery from all microparticles when compared with spray drying, thus the successful spouted bed drying of microparticles depends on the chemical characteristics of both the drug and the polymer. Release data from PCT microparticles suggested that the microparticle formulation should be improved to bring about a more efficient delivery of water-soluble drugs. In conclusion, casein-pectin microparticles show great potential as a drug delivery system because casein reduces the water solubility of pectin. The drying method and cross-linking process had significant effects on the in vitro performance of these microparticles.

Effect of stearic acid on enalapril stability and dissolution from multiparticulate solid dosage forms.

Enalapril maleate (EM) is a widely used anti-hypertensive drug which is unstable when mixed with excipients. Enalaprilate and diketopiperazine (DPK) are the main degradation products of enalapril. The in situ preparation of enalapril sodium salt (NaE) has been used to improve drug stability in dosage forms; however, gas release and product rejection ensue when the chemical reaction for obtaining the sodium salt is not completely finished before packaging. This study evaluated the effect of stearic acid (SA) on enalapril stability in microcrystalline cellulose (MCC) pellets containing EM or NaE. MCC pellets containing SA were prepared by the extrusion-spheronization technique and characterized. Enalapril stability and dissolution were then evaluated. DPK and enalaprilate formation were reduced by the addition of SA in pellets containing EM. The overall enalapril degradation in these formulations was lower when compared with pellets containing EM or even NaE prepared without SA. The immediate-release characteristic was maintained by the addition of 5% crospovidone to all the formulations tested. The incorporation of SA into NaE pellets resulted in unexpected enalapril degradation, caused by the interaction of these compounds, as suggested by a thermal analysis of the SA-NaE binary mixture. The findings presented here showed that formulations containing SA could substitute the formation of NaE, since they provide better enalapril stability in solid dosage forms. In addition, it is suggested that the stabilization effects would be observed for other N-carboxyalkyl dipeptide analogs with angiotensin converting enzyme inhibition activity, since these new entities share the same degradation pathway of enalapril.

Curcumin reduces cisplatin-induced neurotoxicity in NGF-differentiated PC12 cells.

The potential neuroprotective benefits of curcumin against cisplatin neurotoxicity were investigated. Curcumin is a polyphenol derived from the rhizome of Curcuma longa whose pharmacological effects include antioxidant, anti-inflammatory and anti-cancer properties. Cisplatin is a potent chemotherapeutic drug with activity against a wide variety of tumors, although it has notorious side effects. Cisplatin neurotoxicity is clinically evident in patients that have undergone a full course of chemotherapy and develop a peripheral neuropathy that may affect the treatment regimen and the patient's qualify of life. In this study, we examined whether curcumin can protect against cisplatin neurite outgrowth inhibition in PC12 cells, which is an indicator of the protective potential against neuropathy. We also investigated whether curcumin affects cisplatin effectiveness by analyzing the modulation of p53 gene expression and its effect on cisplatin cytotoxicity in HepG2 tumor cells. Non-cytotoxic concentrations of curcumin reduced in vitro neurotoxicity of cisplatin in PC12 cells. The treatment of PC12 cells with cisplatin (10µg/mL) significantly reduced neurite outgrowth. The tested concentration of curcumin (1.0 and 10µg/mL) did not result in neurite toxicity but nevertheless diminished cisplatin-induced inhibition of neurite outgrowth by up to 50% (p<0.05). Our results indicate that curcumin does not compromise cisplatin's anticancer activity. Curcumin neither suppressed p53 mRNA transcription nor protected tumor cells against cisplatin cytotoxicity. These results indicate that curcumin may reduce cisplatin-induced neurotoxicity, and clinical studies should potentially be considered.

Chitosan microparticles for sustaining the topical delivery of minoxidil sulphate.

Given the hypothesis that microparticles can penetrate the skin barrier along the transfollicular route, this work aimed to obtain and characterise chitosan microparticles loaded with minoxidil sulphate (MXS) and to study their ability to sustain the release of the drug, attempting a further application utilising them in a targeted delivery system for the topical treatment of alopecia. Chitosan microparticles, containing different proportions of MXS/polymer, were prepared by spray drying and were characterised by yield, encapsulation efficiency, size and morphology. Microparticles selected for further studies showed high encapsulation efficiency (∼82%), a mean diameter of 3.0 µm and a spherical morphology without porosities. When suspended in an ethanol/water solution, chitosan microparticles underwent instantaneous swelling, increasing their mean diameter by 90%. Release studies revealed that the chitosan microparticles were able to sustain about three times the release rate of MXS. This feature, combined with suitable size, confers to these microparticles the potential to target and improve topical therapy of alopecia with minoxidil.

Antinociceptive and anti-inflammatory properties of 7-hydroxycoumarin in experimental animal models: potential therapeutic for the control of inflammatory chronic pain.

OBJECTIVES: In the present study we investigated the antinociceptive, anti-inflammatory and antipyretic effects of 7-hydroxycoumarin (7-HC) in animal models. METHODS: The effects of oral 7-HC were tested against acetic acid-induced writhing, formalin test, tail flick test, complete Freund's adjuvant (CFA)-induced hypernociception, carrageenan-induced paw oedema, lipopolysaccharide-induced fever and the rota rod test. KEY FINDINGS: 7-HC (3-60 mg/kg) produced a dose-related antinociception against acetic acid-induced writhing in mice and in the formalin test. In contrast, treatment with 7-HC did not prevent thermal nociception in the tail flick test. A single treatment with 7-HC, 60 mg/kg, produced a long-lasting antinociceptive effect against CFA-induced hypernociception, a chronic inflammatory pain stimulus. Notably, at 60 mg/kg per day over 4 days the administration of 7-HC produced a continuous antinociceptive effect against CFA-induced hypernociception. 7-HC (30-120 mg/kg) produced anti-inflammatory and antipyretic effects against carrageenan-induced inflammation and lipopolysaccharide-induced fever, respectively. Moreover, 7-HC was found to be safe with respect to ulcer induction. In the rota rod test, 7-HC-treated mice did not show any motor performance alterations. CONCLUSIONS: The prolonged antinociceptive and anti-inflammatory effects of 7-HC, in association with its low ulcerogenic activity, indicate that this molecule might be a good candidate for development of new drugs for the control of chronic inflammatory pain and fever.

Box-Behnken design for the optimization of an enantioselective method for the simultaneous analysis of propranolol and 4-hydroxypropranolol by CE.

An experimental design optimization (Box-Behnken design, BBD) was used to develop a CE method for the simultaneous resolution of propranolol (Prop) and 4-hydroxypropranolol enantiomers and acetaminophen (internal standard). The method was optimized using an uncoated fused silica capillary, carboxymethyl-beta-cyclodextrin (CM-beta-CD) as chiral selector and triethylamine/phosphoric acid buffer in alkaline conditions. A BBD for four factors was selected to observe the effects of buffer electrolyte concentration, pH, CM-beta-CD concentration and voltage on separation responses. Each factor was studied at three levels: high, central and low, and three center points were added. The buffer electrolyte concentration ranged from 25 to 75 mM, the pH ranged from 8 to 9, the CM-beta-CD concentration ranged from 3.5 to 4.5% w/v, and the applied run voltage ranged from 14 to 20 kV. The responses evaluated were resolution and migration time for the last peak. The obtained responses were processed by Minitab to evaluate the significance of the effects and to find the optimum analysis conditions. The best results were obtained using 4% w/v CM-beta-CD in 25 mM triethylamine/H3PO4 buffer at pH 9 as running electrolyte and 17 kV of voltage. Resolution values of 1.98 and 1.95 were obtained for Prop and 4-hydroxypropranolol enantiomers, respectively. The total analysis time was around of 15 min. The BBD showed to be an adequate design for the development of a CE method, resulting in a rapid and efficient optimization of the pH and concentration of the buffer, cyclodextrin concentration and applied voltage.