Characterization and In Vivo Assay of Allantoin-Enriched Pectin Hydrogel for the Treatment of Skin Wounds.

This work describes a liquid allantoin-enriched pectin hydrogel with hydrophilic behavior that is supported by the presence of functional groups related to healing efficacy. A topical study shows the effect of the hydrogel application on surgically induced skin wound healing in a rat model. Contact angle measurements confirm hydrophilic behavior (11.37°), while Fourier-transform infrared spectroscopy indicates the presence of functional groups related to the healing effectiveness (carboxylic acid and amine groups). Allantoin is distributed on the surface and inside the amorphous pectin hydrogel surrounded by a heterogeneous distribution of pores. This promotes wound drying with better interaction between the hydrogel and cells involved in the wound healing process. An experimental study with female Wistar rats indicates that the hydrogel improves wound contraction, reducing around 71.43% of the total healing time and reaching total wound closure in 15 days.

Chromatographic Techniques and Pharmacological Analysis as a Quality Control Strategy for Serjania triquetra a Traditional Medicinal Plant.

Serjania triquetra is a medicinal plant widely used in traditional medicine for the treatment of urinary tract diseases, renal affections, and its complications. The population can buy this plant in folk markets as a raw material mixed with several herbal remedies or as a health supplement. On the market, two commercial presentations were found for the vegetal material; one had a bulk appearance and the other was marketed wrapped in cellophane bags (HESt-2, HESt-3). Nevertheless, the plant has not been exhaustively investigated and quality control techniques have not been developed. This research aimed to realize a phytochemical study using an authentic, freshly collected sample as a reference for S. triquetra (HESt-1), using the compounds identified. A method for the determination of preliminary chromatographic fingerprinting was developed. Additionally, the vasorelaxant effect from three samples was evaluated with ex vivo rat models. Thus, three hydroalcoholic extracts (HESt-1, HESt-2, and HESt-3) were prepared by maceration. A total of nine compounds were fully identified from HESt-1 after the extract was subjected to open-column chromatography. Seven metabolites were detected by gas chromatography, while ursolic acid (UA) and allantoin were isolated and identified using UPLC-MS and NMR, respectively. Three extracts were analyzed for their chromatographic fingerprint by UPLC-MS. Biological activity was explored by ex vivo rat aorta ring model to evaluate vasorelaxant activity. All extracts showed a vasorelaxant effect in a concentration-dependent and endothelium-dependent manner. S. triquetra vascular activity may be attributed to UA and allantoin compounds previously described in the literature for this activity.

Selected ruminal variables and purine urinary excretion rate of steers subjected to feeding, fasting, and re-feeding conditions.

The effects of feeding, fasting, and re-feeding on the ruminal profile of growing cattle were studied. Ruminal fluid and urine samples were obtained from 12 crossbred steers weighing approximately 300 kg during the following periods: 11 h of normal feeding (postprandial period), 48 consecutive hours of fasting, and followed by 48 h of re-feeding. Fasting promotes changes in the ruminal profile, such as an increase in ruminal pH, reduction in the number of rumen protozoa and bacteria, and decrease in the urinary excretion of allantoin; however, it does not change the urinary uric acid excretion rate. The overall mean ruminal pH was higher during fasting (7.53±0.27) in comparison to those at normal feeding (6.72±0.25) and re-feeding (6.62±0.31) (p⟨0.05). During re-feeding, the ruminal profile returned to normal, except for the protozoa count, which despite a slight increase only after 48 h of re-feeding, did not recover to baseline values.

Coaxial fibers of poly(styrene-co-maleic anhydride)@poly(vinyl alcohol) for wound dressing applications: Dual and sustained delivery of bioactive agents promoting fibroblast proliferation with reduced cell adherence.

The prevalence of chronic and acute wounds, as well as the complexity of their treatment represent a great challenge for health systems around the world. In this context, the development of bioactive wound dressings that release active agents to prevent infections and promote wound healing, appears as the most promising solution. In this work, we develop an antibacterial and biocompatible wound dressing material made from coaxial electrospun fibers of poly(styrene-co-maleic anhydride) and poly(vinyl alcohol) (PSMA@PVA). The coaxial configuration of the fibers consists of a shell of poly (styrene-co-maleic anhydride) containing a variable concentration of silver nanoparticles (AgNPs) 0.1-0.6 wt% as antibacterial agent, and a core of PVA containing 1 wt% allantoin as healing agent. The fibers present diameters between 0.72 and 1.7 µm. The release of Ag+ in a physiological medium was studied for 72 h, observing a burst release during the first 14 h and then a sustained and controlled release during the remaining 58 h. Allantoin release curves showed significant release only after 14 h. The meshes showed an antibacterial activity against Pseudomonas aeruginosa and Bacillus subtilis that correlates with the amount of AgNPs incorporated and the release rate of Ag+. Indeed, meshes containing 0.3 and 0.6 wt% of AgNPs showed a 99.99% inhibition against both bacteria. The adherence and cell viability of the meshes were evaluated in mouse embryonic fibroblasts NIH/3T3, observing a significant increase in cell viability after 72 h of incubation accompanied by a reduced adhesion of fibroblasts that decreased in the presence of the active agents. These results show that the material prepared here is capable of significantly promoting fibroblast cell proliferation but without strong adherence, which makes it an ideal material for wound dressings with non-adherent characteristics and with potential for wound healing.

Physiological impact of flavonoids on nodulation and ureide metabolism in legume plants.

Legume plants from Fabaceae family (phylogenetic group composed by three subfamilies: Caesalpinioideae, Mimosoideae, and Papilionoideae) can fix atmospheric nitrogen (N2) into ammonia (NH3) by the symbiotic relationship with rhizobia bacteria. These bacteria respond chemotactically to certain compounds released by plants such as sugars, amino acids and organic acids. Root secretion of isoflavonoids acts as inducers for nod genes in rhizobia and ABC transporters and ICHG (isoflavone conjugates hydrolyzing beta-glucosidase) at apoplast are related to the exudation of genistein and daidzein in soybean roots. Biological nitrogen fixation (BNF) occurs inside the nodule by the action of nitrogenase enzyme, which fixes N2 into NH3, which is converted into ureides (allantoin and allantoic acid). In this review, we bring together the latest findings on flavonoids biosynthesis and ureide metabolism in several legume plant species. We emphasize how flavonoids induce nod genes in rhizobia, affecting chemotaxis, nodulation, ureide production, growth and yield of legume plants. Mainly, isoflavonoids daidzein and genistein are responsible for nod genes activation in the rhizobia bacteria. Flavonoids also play an important role during nodule organogenesis by acting as auxin transporter inhibitors in root cells, especially in indeterminate nodules. The ureides are the main N transport form in tropical legumes and they are catabolized in leaves and other sink tissues to produce amino acids and proteins needed for plant growth and yield.

Determination of Ureides Content in Plant Tissues.

The ureides allantoin and allantoate are the main organic nitrogen compounds transported in several legumes, predominantly from N2 fixation. Moreover, recent studies point out a remarkable role for allantoin during several stress responses of plants other than legumes. The goal of this protocol is to determine ureides concentration in different plant tissues. Ureides are extracted from plant material by boiling it in phosphate buffer. The allantoin and allantoate present in the supernatants are subjected to alkaline-acidic hydrolysis to glyoxylate. The glyoxylate is converted into glycoxylic acid phenylhydrazone, that is then oxidized to red-colored 1,5-diphenylformazan. The absorbance of supernatants is measured using a spectrophotometer at 520 nm. Ureides concentration can be inferred by using a glyoxylate calibration curve. Ureide quantification of different tissues of Arabidopsis thaliana and soybean plants were carried out following this protocol.

Film Dressings Based on Hydrogels: Simultaneous and Sustained-Release of Bioactive Compounds with Wound Healing Properties.

This research proposes the rational modeling, synthesis and evaluation of film dressing hydrogels based on polyvinyl alcohol crosslinked with 20 different kinds of dicarboxylic acids. These formulations would allow the sustained release of simultaneous bioactive compounds including allantoin, resveratrol, dexpanthenol and caffeic acid as a multi-target therapy in wound healing. Interaction energy calculations and molecular dynamics simulation studies allowed evaluating the intermolecular affinity of the above bioactive compounds by hydrogels crosslinked with the different dicarboxylic acids. According to the computational results, the hydrogels crosslinked with succinic, aspartic, maleic and malic acids were selected as the best candidates to be synthesized and evaluated experimentally. These four crosslinked hydrogels were prepared and characterized by FTIR, mechanical properties, SEM and equilibrium swelling ratio. The sustained release of the bioactive compounds from the film dressing was investigated in vitro and in vivo. The in vitro results indicate a good release profile for all four analyzed bioactive compounds. More importantly, in vivo experiments suggest that prepared formulations could considerably accelerate the healing rate of artificial wounds in rats. The histological studies show that these formulations help to successfully reconstruct and thicken epidermis during 14 days of wound healing. Moreover, the four film dressings developed and exhibited excellent biocompatibility. In conclusion, the novel film dressings based on hydrogels rationally designed with combinatorial and sustained release therapy could have significant promise as dressing materials for skin wound healing.

Pharmacometabolomics of Meglumine Antimoniate in Patients With Cutaneous Leishmaniasis.

Control of cutaneous leishmaniasis (CL) in the Americas is dependent on chemotherapy with parenteral pentavalent antimonials. High rates of treatment failure urge the search for predictive and prognostic markers of therapeutic responsiveness. In this study, we aimed to identify biomarkers of therapeutic response during treatment with meglumine antimoniate (MA). We conducted untargeted metabolomic profiling of plasma samples from CL patients (n = 39; 25 who cured and 14 who did not cure), obtained before and at the end of treatment. Exposure to MA induced metabolic perturbations primarily reflecting alteration in long-chain fatty acid ß-oxidation and energy production. Allantoin, N-acetylglutamine, taurine, and pyruvate were significantly more abundant in samples from patients who responded to treatment, and were predictive and prognostic of treatment outcome in this patient cohort (AUC > 0.7). In an ex vivo model of infection, allantoin but not taurine enhanced the MA-dependent killing of intracellular Leishmania (Viannia) panamensis. Our results support the participation of metabolites mediating antioxidant and wound healing responses in clinical cure of CL, revealing relationships between metabolism and immune responses in the outcome of antileishmanial treatment.

Allantoin reduces cell death induced by cisplatin: possible implications for tumor lysis syndrome management.

Massive lysis of tumor mass in cancer patients under chemotherapy regimens generates high levels of uric acid, leading to what is known as tumor lysis syndrome (TLS). Rasburicase, a recombinant urate oxidase, converts urate to allantoin, which is readily excreted by the kidneys. Even though there is a high production of allantoin from urate in cancer patients following rasburicase treatment, there are no studies on how allantoin excess could interfere with chemotherapy. We have evaluated allantoin interference with cisplatin efficiency on the lung cancer cell line H460 in vitro. The cells were treated with cisplatin (33 µM), with or without allantoin, for 48 h, in the presence or absence of UV light, and N-acetyl-L-cysteine (NAC) for 24 h. Cell viability, cell cycle, ROS production, apoptosis and immunoblot assays were performed. We showed that allantoin reduced the apoptosis induced by cisplatin in the H460 cell line. However, the activity of carboplatin and oxaliplatin, betulinic acid, TIBA, UV and H2O2 was not affected by allantoin. NMR spectroscopy showed that allantoin reduces cisplatin activity through direct interaction with cisplatin.

Effect of allantoin on experimentally induced gastric ulcers: Pathways of gastroprotection.

Gastric ulcer affects people worldwide, and its inefficacy and recurrence have fueled the search for new therapeutic strategies. Despite the well-known use of allantoin in medicines and cosmetic products, its effect has not yet been studied with regard to gastric ulcer. Hence, the aim of the present study was to explore the pharmaco-mechanistic efficacy of allantoin against commonly harmful agents that cause injuries to the stomach. Ethanol, indomethacin, and stress-induced gastric ulcer models were adopted, in addition to pylorus ligature, a quantification of vascular permeability, glutathione (GSH), gastric adhered mucus, prostaglandin (PGE2), pro-inflammatory cytokines levels, myeloperoxidase (MPO), and catalase (CAT) activities. The gastric lesions were examined by gross, histological, and ultrastructural features. The results showed that treatment with allantoin (60mg/kg, per oral) reduced the gastric ulcer formation in all models. Furthermore, allantoin reduced the parameters of gastric acid secretion and attenuated both the vascular permeability and MPO activity. The levels of pro-inflammatory cytokines were also reduced, accompanied by a restoration of CAT activity and GSH levels. Notably, allantoin treatment preserved the gastric-adhered mucus and PGE2 levels after ethanol administration. Microscopic and ultrastructural analysis revealed that allantoin maintained tissue integrity and prevented morphological changes in cells caused by ethanol. In summary, we demonstrated for the first time that allantoin possesses gastroprotective activity through anti-inflammatory, anti-oxidative, antisecretory, and cytoprotective mechanisms. The antisecretory and cytoprotective mechanisms are probably associated with an increase in PGE2 levels.

Allantoin as an independent marker associated with carotid intima-media thickness in subclinical atherosclerosis

Allantoin is the main product of uric acid oxidation and was found to be augmented in atherosclerotic plaque in human autopsy and in animal models of atherosclerosis. Uric acid is abundant in human plasma and is prone to oxidation in inflammatory conditions such as atherosclerosis. In this study, we found a significant increase in plasma uric acid (P=0.002) and allantoin (P=0.025) in participants of the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) that presented common carotid intima-media thickness (c-IMT) within the 75th percentile (c-IMT≥P75). Multiple linear regression showed an association of c-IMT with uric acid (β=0.0004, P=0.014) and allantoin (β=0.018, P=0.008). This association was independent of age, the traditional risk factor LDL/HDL ratio, and non-traditional risk factors: pulse pressure, neck circumference, and the inflammatory marker myeloperoxidase. The independent and strong association of allantoin with c-IMT shows that it might be a useful marker, along with other traditional risk factors, to evaluate an early stage of atherosclerosis.

Allantoin accumulation mediated by allantoinase downregulation and transport by Ureide Permease 5 confers salt stress tolerance to Arabidopsis plants.

Allantoin, a metabolite generated in the purine degradation pathway, was primarily considered an intermediate for recycling of the abundant nitrogen assimilated in plant purines. More specifically, tropical legumes utilize allantoin and allantoic acid as major nodule-to-shoot nitrogen transport compounds. In other species, an increase in allantoin content was observed under different stress conditions, but the underlying molecular mechanisms remain poorly understood. In this work, Arabidopsis thaliana was used as a model system to investigate the effects of salt stress on allantoin metabolism and to know whether its accumulation results in plant protection. Plant seedlings treated with NaCl at different concentrations showed higher allantoin and lower allantoic acid contents. Treatments with NaCl favored the expression of genes involved in allantoin synthesis, but strongly repressed the unique gene encoding allantoinase (AtALN). Due to the potential regulatory role of this gene for allantoin accumulation, AtALN promoter activity was studied using a reporter system. GUS mediated coloration was found in specific plant tissues and was diminished with increasing salt concentrations. Phenotypic analysis of knockout, knockdown and stress-inducible mutants for AtALN revealed that allantoin accumulation is essential for salt stress tolerance. In addition, the possible role of allantoin transport was investigated. The Ureide Permease 5 (UPS5) is expressed in the cortex and endodermis of roots and its transcription is enhanced by salt treatment. Ups5 knockout plants under salt stress presented a susceptible phenotype and altered allantoin root-to-shoot content ratios. Possible roles of allantoin as a protectant compound in oxidative events or signaling are discussed.

Proteína microbiana e parâmetros sanguíneos de caprinos alimentados com torta de licuri / Microbial protein and blood parameters of goats fed with licury cake

O objetivo deste trabalho foi avaliar a síntese de proteína microbiana, ureia e glicose sanguíneas, em caprinos Boer alimentados com níveis de torta de licuri nas dietas. Utilizaram-se 20 caprinos machos não castrados ¾ Boer com peso vivo médio 18 kg distribuídos nos quatro tratamentos. Os animais foram mantidos em baias suspensas com um m2 e água a vontade. As dietas foram formuladas conforme o NRC (2007) e os ingredientes utilizados foram: 50% feno de Tifton-85 (Cynodon sp), milho moído, farelo de soja, suplemento vitamínico-mineral e torta de licuri. Os tratamentos foram: 1) 0% de adição (MS%) de torta de licuri na dieta, 2) 15% de adição de torta de licuri, 3) 30% de adição de torta de licuri e 4) 45% de adição de torta de licuri. O experimento teve a duração de 17 dias, sendo 10 dias de adaptação dos animais as dietas. A inclusão da torta de licuri na dieta de caprinos promoveu redução nos níveis de ureia e glicose nos caprinos. O volume urinário dos caprinos reduziu de forma linear com a inclusão de torta de licuri na dieta. A inclusão de torta de licuri nas dietas de caprinos promoveu redução linear na excreção de alantoína xantina e hipoxantina e derivados de purinas totais (PD) nas amostras das coletas totais de urina em resposta a inclusão da torta de licuri na dieta. Com base na produção de proteína microbiana e os parâmetros sanguíneos dos caprinos alimentados com torta de licuri, pode-se utilizar até 15% de inclusão na dieta.(AU)

The objective of this study was to determine the ideal level of licury cake in the diet of Boer goats through microbial synthesis estimated based on the presence of purine derivatives in the urine and on blood urea and glucose parameters. Twenty uncastrated one-year-old ¾ Boer goats with an average body weight of 18 kg were distributed in a completely randomized design. Each animal was confined to a one m2 suspended stall with access to water ad libitum. The diets were formulated in accordance with the NRC (2007), and the ingredients were: 50% Tifton-85 (Cynodon sp) hay, corn meal, soybean meal, premixed vitamin and mineral supplement, and licury cake. The treatments were: 1) 0% of the goats total diet composed of licury cake (DM basis), 2) 15% of the total diet composed of licury cake, 3) 30% of the diet composed of licury cake, and 4) 45% of the diet composed of licury cake. The experiment lasted for 17 days. The first 10 days were used to adapt the animals to the diets and facilities. The inclusion of the licury cake in the goats diets reduced the levels of blood nitrogen and glucose. Urinary excretion decreased linearly with the inclusion of licury cake in the diet. The inclusion of licury cake in the goats diets also caused a linear reduction in the excretion of allantoin, xanthine and hypoxanthine and total purine derivative (PD) in urine samples. Based on the microbial protein production and blood parameters of goats fed with licury cake, up to 15% of the goat diet may be composed of licury cake.(AU)

Proteína microbiana e parâmetros sanguíneos de caprinos alimentados com torta de licuri / Microbial protein and blood parameters of goats fed with licury cake

O objetivo deste trabalho foi avaliar a síntese de proteína microbiana, ureia e glicose sanguíneas, em caprinos Boer alimentados com níveis de torta de licuri nas dietas. Utilizaram-se 20 caprinos machos não castrados ¾ Boer com peso vivo médio 18 kg distribuídos nos quatro tratamentos. Os animais foram mantidos em baias suspensas com um m2 e água a vontade. As dietas foram formuladas conforme o NRC (2007) e os ingredientes utilizados foram: 50% feno de Tifton-85 (Cynodon sp), milho moído, farelo de soja, suplemento vitamínico-mineral e torta de licuri. Os tratamentos foram: 1) 0% de adição (MS%) de torta de licuri na dieta, 2) 15% de adição de torta de licuri, 3) 30% de adição de torta de licuri e 4) 45% de adição de torta de licuri. O experimento teve a duração de 17 dias, sendo 10 dias de adaptação dos animais as dietas. A inclusão da torta de licuri na dieta de caprinos promoveu redução nos níveis de ureia e glicose nos caprinos. O volume urinário dos caprinos reduziu de forma linear com a inclusão de torta de licuri na dieta. A inclusão de torta de licuri nas dietas de caprinos promoveu redução linear na excreção de alantoína xantina e hipoxantina e derivados de purinas totais (PD) nas amostras das coletas totais de urina em resposta a inclusão da torta de licuri na dieta. Com base na produção de proteína microbiana e os parâmetros sanguíneos dos caprinos alimentados com torta de licuri, pode-se utilizar até 15% de inclusão na dieta.

The objective of this study was to determine the ideal level of licury cake in the diet of Boer goats through microbial synthesis estimated based on the presence of purine derivatives in the urine and on blood urea and glucose parameters. Twenty uncastrated one-year-old ¾ Boer goats with an average body weight of 18 kg were distributed in a completely randomized design. Each animal was confined to a one m2 suspended stall with access to water ad libitum. The diets were formulated in accordance with the NRC (2007), and the ingredients were: 50% Tifton-85 (Cynodon sp) hay, corn meal, soybean meal, premixed vitamin and mineral supplement, and licury cake. The treatments were: 1) 0% of the goat’s total diet composed of licury cake (DM basis), 2) 15% of the total diet composed of licury cake, 3) 30% of the diet composed of licury cake, and 4) 45% of the diet composed of licury cake. The experiment lasted for 17 days. The first 10 days were used to adapt the animals to the diets and facilities. The inclusion of the licury cake in the goat’s diets reduced the levels of blood nitrogen and glucose. Urinary excretion decreased linearly with the inclusion of licury cake in the diet. The inclusion of licury cake in the goat’s diets also caused a linear reduction in the excretion of allantoin, xanthine and hypoxanthine and total purine derivative (PD) in urine samples. Based on the microbial protein production and blood parameters of goats fed with licury cake, up to 15% of the goat diet may be composed of licury cake.

Avaliação da toxicidade aguda e da atividade cicatrizante dos extratos etanólicos das folhas e raízes da Memora nodosa (Silva Manso) Miers (Bignoniaceae) / Evaluation of acute and healing activity of ethanol extracts of Memora nodosa (Silva Manso) Miers (Bignoniaceae) leaves and roots

Memora nodosa (Silva Manso) Miers é uma espécie da flora do Cerrado cujas folhas e caules são utilizados popularmente no tratamento de feridas e úlceras externas, enquanto as raízes são empregadas para dores abdominais e no tratamento da sarna. O objetivo desse trabalho foi avaliar a toxicidade aguda dos extratos etanólicos das folhas e raízes nas doses de 2000 e 5000 mg kg-1 em ratos e camundongos e a atividade cicatrizante das soluções aquosas contendo 2% desses extratos em feridas cutâneas em ratos. A contração das bordas das feridas foi avaliada por análises histológicas e morfométricas após 4, 7 e 14 dias de tratamento e por reação imunohistoquímica após 7 dias de tratamento. Os extratos etanólicos das folhas e raízes não apresentaram toxicidade na dose de 2000 mg kg-1 para ratos e camundongos e na dose de 5000 mg kg-1 para ratos. Nos camundongos, a dose de 5000 mg kg-1 dos extratos das folhas e raízes provocou alterações histológicas no fígado. Não foram observadas diferenças significativas na contração das feridas entre os grupos tratados com os extratos das folhas e das raízes e o controle após 4 e 7 dias de tratamento. Após 14 dias de tratamento, 50% dos animais tratados com o extrato das raízes apresentaram reepitelização total das feridas e reconstrução parcial dos anexos. A alantoína, isolada do extrato etanólico da raiz, pode ser considerada como um dos metabólitos secundários responsáveis pela aceleração da reepitelização.

Memora nodosa (Silva Manso) Miers is a Brazilian Cerrado species whose leaves and stems are commonly used to treat external wounds and ulcers and the roots are used for abdominal pain and to treat scabies. The purpose of this study was to evaluate the acute toxicity of ethanol extracts from the leaves and roots of M. nodosa at 2000 and 5000 mg kg-1 doses in rats and mice and to evaluate the healing activity of aqueous solutions containing 2% of these extracts on skin wounds in rats. The contraction of the wounds was evaluated by histological and morphometric analysis after 4, 7 and 14 days of treatment and by immunohistochemistry analysis after 7 days of treatment. The ethanol extracts of leaves and roots presented no toxicity at a 2000 mg kg-1 dose for rats and mice, and at a 5000 mg kg-1 dose for rats. Histological changes in the liver of mice were verified with a 5000 mg kg-1 dose of the leaf and root extracts. Macroscopic and histological differences were not observed in the contraction of wounds between the groups treated with leaf and root extracts and the control group after 4 and 7 days of treatment. After 14 days of treatment, 50% of the animals treated with the root extract presented total re-epithelialization of wounds and partial reconstruction of the annexes. Allantoin, isolated from the root ethanol extract, can be considered one of the secondary metabolites responsible for accelerating re-epithelialization.

Parâmetros da fermentação ruminal e concentração de derivados de purina de vacas em lactação alimentadas com castanha de caju / Ruminal fermentative parameters and concentration of purine derivatives in lactating dairy cows fed cashew nut

Avaliaram-se os parâmetros de fermentação ruminal e a concentração de derivados de purinas na urina de vacas leiteiras alimentadas com teores crescentes de castanha de caju na dieta. Foram utilizadas oito vacas Holandesas multíparas, sendo quatro fistuladas no rúmen, com produção média de 28±4kg de leite/dia. O delineamento experimental adotado foi o quadrado latino 4x4, com parcelas subdivididas para os parâmetros ruminais e duplo para determinação dos derivados de purina. Os tratamentos avaliados consistiram na inclusão de 0; 8; 16 e 24% de castanha de caju moída na porção concentrada da dieta. O comportamento do pH ruminal foi semelhante entre as dietas avaliadas segundo os tempos após alimentação. A concentração média de nitrogênio amoniacal foi 12,70mg/100mL de líquido ruminal. Os valores médios de acetato e butirato apresentaram padrão linear de resposta, contudo a relação acetato:propionato não foi alterada pela adição do coproduto. As excreções de derivados de purina na urina não variaram significativamente (P>0,05) com a adição de castanha de caju. A inclusão de castanha de caju não afetou os parâmetros de fermentação ruminal nem as concentrações de derivados de purinas; dessa forma, pode ser recomendada como alternativa potencial na alimentação de vacas leiteiras em lactação.

The parameters of rumen fermentation and the concentration of purine derivatives in the urine of dairy cows fed with increasing levels of cashew nut in the diet were evaluated. Eight multiparous holstein cows were used, being four rumen cannulated, with average production of 28±4kg of milk/day. The experimental design adopted was a 4x4 Latin square with split plots for the ruminal parameters and double for the determination of purine derivatives. The treatments consisted of the inclusion of 0; 8; 16 and 24% of cashew nut in the concentrate portion of the diet. The behavior of the ruminal pH was similar between the evaluated diets according to the time after feeding. The average concentration of ammonia nitrogen was 12.70mg/100mL of rumen fluid. The average values of acetate and butyrate showed a linear response, but the acetate:propionate ratio wasnot altered by the addition of the coproduct. The excretions of purine derivatives in urine did not differ significantly (P>0.05) with the addition of cashew nut. The inclusion of cashew nut did not affect ruminal fermentation parameters neither the concentrations of purine derivatives, so it can be recommended as a potential alternative for feeding dairy cows.

Parâmetros da fermentação ruminal e concentração de derivados de purina de vacas em lactação alimentadas com castanha de caju / Ruminal fermentative parameters and concentration of purine derivatives in lactating dairy cows fed cashew nut

Avaliaram-se os parâmetros de fermentação ruminal e a concentração de derivados de purinas na urina de vacas leiteiras alimentadas com teores crescentes de castanha de caju na dieta. Foram utilizadas oito vacas Holandesas multíparas, sendo quatro fistuladas no rúmen, com produção média de 28±4kg de leite/dia. O delineamento experimental adotado foi o quadrado latino 4x4, com parcelas subdivididas para os parâmetros ruminais e duplo para determinação dos derivados de purina. Os tratamentos avaliados consistiram na inclusão de 0; 8; 16 e 24% de castanha de caju moída na porção concentrada da dieta. O comportamento do pH ruminal foi semelhante entre as dietas avaliadas segundo os tempos após alimentação. A concentração média de nitrogênio amoniacal foi 12,70mg/100mL de líquido ruminal. Os valores médios de acetato e butirato apresentaram padrão linear de resposta, contudo a relação acetato:propionato não foi alterada pela adição do coproduto. As excreções de derivados de purina na urina não variaram significativamente (P>0,05) com a adição de castanha de caju. A inclusão de castanha de caju não afetou os parâmetros de fermentação ruminal nem as concentrações de derivados de purinas; dessa forma, pode ser recomendada como alternativa potencial na alimentação de vacas leiteiras em lactação.(AU)

The parameters of rumen fermentation and the concentration of purine derivatives in the urine of dairy cows fed with increasing levels of cashew nut in the diet were evaluated. Eight multiparous holstein cows were used, being four rumen cannulated, with average production of 28±4kg of milk/day. The experimental design adopted was a 4x4 Latin square with split plots for the ruminal parameters and double for the determination of purine derivatives. The treatments consisted of the inclusion of 0; 8; 16 and 24% of cashew nut in the concentrate portion of the diet. The behavior of the ruminal pH was similar between the evaluated diets according to the time after feeding. The average concentration of ammonia nitrogen was 12.70mg/100mL of rumen fluid. The average values of acetate and butyrate showed a linear response, but the acetate:propionate ratio wasnot altered by the addition of the coproduct. The excretions of purine derivatives in urine did not differ significantly (P>0.05) with the addition of cashew nut. The inclusion of cashew nut did not affect ruminal fermentation parameters neither the concentrations of purine derivatives, so it can be recommended as a potential alternative for feeding dairy cows.(AU)

Profile of wound healing process induced by allantoin / Perfil do processo de cicatrização induzido pela alantoína

PURPOSE: To evaluate and characterize the wound healing process profile induced by allantoin incorporated in soft lotion oil/water emulsion using the planimetric and histological methods. METHODS: Female Wistar rats (n=60) were randomly assigned to 3 experimental groups: (C) control group-without treatment; (E) group treated with soft lotion O/W emulsion excipients; (EA) group treated with soft lotion O/W emulsion containing allantoin 5 percent. The emulsions either containing or not allantoin were topically administered for 14 days and the wound area was evaluated by planimetry and by qualitative and quantitative histological analysis of open wound model. RESULTS: The data which were obtained and analyzed innovate by demonstrating, qualitatively and quantitatively, by histological analysis, the profile of healing process induced by allantoin. The results suggest that the wound healing mechanism induced by allantoin occurs via the regulation of inflammatory response and stimulus to fibroblastic proliferation and extracellular matrix synthesis. CONCLUSION: This work show, for the first time, the histological wound healing profile induced by allantoin in rats and demonstrated that it is able to ameliorate and fasten the reestablishment of the normal skin.(AU)

OBJETIVO: Avaliar e caracterizar o perfil cicatricial induzido pela alantoína incorporada em uma emulsão óleo/água, sob os aspectos planimétrico e histológico. MÉTODOS: Ratos Wistar fêmeas (n=60) foram agrupados aleatoriamente em três grupos experimentais grupo controle - sem tratamento (C); grupo tratado com emulsão pura (E); grupo tratado com emulsão contendo 5 por cento de alantoína (EA). As emulsões contendo ou não alantoína foram administradas topicamente durante 14 dias e a área da ferida foi avaliada por planimetria e por análise histológica qualitativa e quantitativa em modelo de ferida aberta. RESULTADOS: Na análise planimétrica não foi observado diferenças significativas entre os grupos experimentais. Os resultados da análise histológica sugerem que o mecanismo de cicatrização induzido pela alantoína ocorre via controle da resposta inflamatória e estímulos à proliferação fibroblástica e síntese de matrix extracelular de maneira mais intensa e rapidamente em relação aos grupos controles. CONCLUSÃO: Este trabalho mostra pela primeira vez o perfil histológico de cicatrização induzido pela alantoína em ratos, demonstrando ser capaz de melhorar e acelerar o processo de reconstituição da pele.(AU)

Profile of wound healing process induced by allantoin / Perfil do processo de cicatrização induzido pela alantoína

PURPOSE: To evaluate and characterize the wound healing process profile induced by allantoin incorporated in soft lotion oil/water emulsion using the planimetric and histological methods. METHODS: Female Wistar rats (n=60) were randomly assigned to 3 experimental groups: (C) control group-without treatment; (E) group treated with soft lotion O/W emulsion excipients; (EA) group treated with soft lotion O/W emulsion containing allantoin 5 percent. The emulsions either containing or not allantoin were topically administered for 14 days and the wound area was evaluated by planimetry and by qualitative and quantitative histological analysis of open wound model. RESULTS: The data which were obtained and analyzed innovate by demonstrating, qualitatively and quantitatively, by histological analysis, the profile of healing process induced by allantoin. The results suggest that the wound healing mechanism induced by allantoin occurs via the regulation of inflammatory response and stimulus to fibroblastic proliferation and extracellular matrix synthesis. CONCLUSION: This work show, for the first time, the histological wound healing profile induced by allantoin in rats and demonstrated that it is able to ameliorate and fasten the reestablishment of the normal skin.

OBJETIVO: Avaliar e caracterizar o perfil cicatricial induzido pela alantoína incorporada em uma emulsão óleo/água, sob os aspectos planimétrico e histológico. MÉTODOS: Ratos Wistar fêmeas (n=60) foram agrupados aleatoriamente em três grupos experimentais grupo controle - sem tratamento (C); grupo tratado com emulsão pura (E); grupo tratado com emulsão contendo 5 por cento de alantoína (EA). As emulsões contendo ou não alantoína foram administradas topicamente durante 14 dias e a área da ferida foi avaliada por planimetria e por análise histológica qualitativa e quantitativa em modelo de ferida aberta. RESULTADOS: Na análise planimétrica não foi observado diferenças significativas entre os grupos experimentais. Os resultados da análise histológica sugerem que o mecanismo de cicatrização induzido pela alantoína ocorre via controle da resposta inflamatória e estímulos à proliferação fibroblástica e síntese de matrix extracelular de maneira mais intensa e rapidamente em relação aos grupos controles. CONCLUSÃO: Este trabalho mostra pela primeira vez o perfil histológico de cicatrização induzido pela alantoína em ratos, demonstrando ser capaz de melhorar e acelerar o processo de reconstituição da pele.

Estudo clínico, monocego, da tolerabilidade cutânea e eficácia preventiva de assaduras de um produto tópico*, em condições reais de uso / A monoblind clinical trial study of cutaneous tolerability and preventive efficacy for diaper's rash os a topic product in real life or real use conditions

O uso crescente de produtos cosméticos tem sido cada vez mais comum em nosso meio, fazendo parte do receituário médico. O presente estudo tem por finalidade determinar a prevalência de reações adversas, em condições reais de uso, de um hidratante infantil contendo alantoína e alfa-bisabolol. Também foi avaliada a eficácia preventiva de assaduras.