Copaifera langsdorffii Oleoresin-Loaded Nanostructured Lipid Carrier Emulgel Improves Cutaneous Healing by Anti-Inflammatory and Re-Epithelialization Mechanisms.

The skin is essential to the integrity of the organism. The disruption of this organ promotes a wound, and the organism starts the healing to reconstruct the skin. Copaifera langsdorffii is a tree used in folk medicine to treat skin affections, with antioxidant and anti-inflammatory properties. In our study, the oleoresin of the plant was associated with nanostructured lipid carriers, aiming to evaluate the healing potential of this formulation and compare the treatment with reference drugs used in wound healing. Male Wistar rats were used to perform the excision wound model, with the macroscopic analysis of wound retraction. Skin samples were used in histological, immunohistochemical, and biochemical analyses. The results showed the wound retraction in the oleoresin-treated group, mediated by α-smooth muscle actin (α-SMA). Biochemical assays revealed the anti-inflammatory mechanism of the oleoresin-treated group, increasing interleukin-10 (IL-10) concentration and decreasing pro-inflammatory cytokines. Histopathological and immunohistochemical results showed the improvement of re-epithelialization and tissue remodeling in the Copaifera langsdorffii group, with an increase in laminin-γ2, a decrease in desmoglein-3 and an increase in collagen remodeling. These findings indicate the wound healing potential of nanostructured lipid carriers associated with Copaifera langsdorffii oleoresin in skin wounds, which can be helpful as a future alternative treatment for skin wounds.

Effects of dietary copper and zinc hydroxychloride supplementation on bone development, skin quality and hematological parameters of broilers chickens.

This study was carried out to evaluate the effects of supplementation with different levels of copper (Cu) and zinc (Zn), using two mineral sources (sulphate and hydroxy forms), on the bone characteristics, skin strength/elasticity, and haematological parameters of broilers. A total of 1792 1-day-old male Cobb-500 broiler chickens were randomly distributed among eight dietary treatments, using Cu sulphate (CSM) or hydroxychloride (CHC), and Zn sulphate (ZSM) or hydroxychloride (ZHC). The dietary treatments were as follows: (1) low-CSM/high-ZSM, (2) high-CSM/high-ZSM, (3) low-CHC/low-ZHC, (4) low-CHC/medium-ZHC, (5) low-CHC/high-ZHC, (6) high-CHC/low-ZHC, (7) high-CHC/medium-ZHC, and (8) high-CHC/high-ZHC. On Day 42, blood samples were collected from one bird/pen to analyze the haematological parameters. Finally, two birds/pen were slaughtered, and the tibia and femur were collected to analyze the quality of bone and skin. The means were subjected to ANOVA and, when significant, compared by Tukey's test (p < 0.05) or Dunnett's (p < 0.05) test. The haematological parameters were not influenced by mineral supplementation. However, the inclusion of low ZHC enhanced the skin strength compared to high ZHC (p = 0.046). Furthermore, the bone mineral density of the tibia proximal epiphysis, tibia ash and tibia mineral content were positively improved with supplementation of low-CHC/medium-ZHC compared to high-CHC/medium-ZHC. This study demonstrated that hydroxy compounds are potential alternatives for replacing sulphate supplements in broiler diets. Moreover, among the Cu and Zn levels, the low CHC (15 mg/kg) and medium ZHC (100 mg/kg) improved bone development and skin integrity, suggesting that the combination of Cu and Zn can be a nutritional strategy to prevent the incidence of leg disorders in broilers.

Randomized controlled clinical trial of ketoanalogues supplementation in dogs with chronic kidney disease / Estudo clínico randomizado controlado da suplementação de cetoanálogos em cães com doença renal crônica

The objective was to verify the effectiveness of ketoanalogues in dogs with Chronic Kidney Disease (CKD) stage 3. Controlled randomized clinical trial was performed with twenty dogs with CKD stage 3. Animals were subjected to: Group 1 (control): conventional therapy (CT) for CKD; Group 2: CT and 60mg/kg, OA, q48h of keto-supplementa; Group 3, CT and 60mg/kg, OA, q24h of keto-supplementa; and Group 4, CT and 120mg/kg, OA, q12h of keto-supplementa. All dogs received canine renal diet. Animals were evaluated at the beginning of therapy and after 15 and 30 days. Complete blood count (CBC), serum urea, creatinine, phosphorus, calcium, potassium and sodium and urine protein/creatinine (UPC) ratio were analyzed. The use of ketoanalogues in dogs with CKD stage 3 during the period of 30 days showed no efficacy, in any of the studies dosages, to improve signs and symptoms of the disease, improve the values of CBC, reduce serum urea and creatinine, normalize electrolytes or reduce UPC. It is concluded that the use of ketoanalogues does not impact the clinical outcomes in dogs with CKD stage 3.(AU)

O objetivo foi de verificar a eficácia da suplementação com cetoanálogos em cães com Doença Renal Crônica (DRC) grau 3. Um ensaio clínico controlado e randomizado foi realizado com 20 cães com DRC grau 3. Os animais foram divididos em 4 grupos: grupo 1 (controle): terapia convencional (TC) para DRC; grupo 2: TC e 60mg/kg, VO, q48h de cetoanálogoa; grupo 3: TC e 60mg/kg, VO, q24h de cetoanálogoa; e grupo 4, TC e 120mg/kg, VO, q12h de cetoanálogoa. Todos os cães receberam ração renal para cães. Os animais foram avaliados no início da terapia e após 15 e 30 dias. Hemograma completo, ureia, creatinina, fósforo, cálcio, potássio e sódio séricos e a razão proteína creatinina (RPC) urinária foram analisados. Foi verificado que o uso dos cetoanálogos em cães com DRC grau 3 durante 30 dias não mostrou eficácia, em nenhuma das dosagens utilizadas, em melhorar os sinais clínicos e sintomatologia da doença, os valores do hemograma e ureia e creatinina séricos, normalizar eletrólitos e reduzir RPC. Concluiu-se que o uso de cetoanálogos não impacta na melhora de sintomatologia clínica em cães com CKD grau 3. Como esse parece ser o primeiro ensaio clínico sobre cetoanálogos em cães com CKD, mais estudos podem ser necessários com maior acompanhamento e maiores grupos.(AU)

Citrus aurantium L. essential oil exhibits anxiolytic-like activity mediated by 5-HT(1A)-receptors and reduces cholesterol after repeated oral treatment.

BACKGROUND: The current treatments for anxiety disorders and depression have multiple adverse effects in addition to a delayed onset of action, which has prompted efforts to find new substances with potential activity in these disorders. Citrus aurantium was chosen based on ethnopharmacological data because traditional medicine refers to the Citrus genus as useful in diminishing the symptoms of anxiety or insomnia, and C. aurantium has more recently been proposed as an adjuvant for antidepressants. In the present work, we investigated the biological activity underlying the anxiolytic and antidepressant effects of C. aurantium essential oil (EO), the putative mechanism of the anxiolytic-like effect, and the neurochemical changes in specific brain structures of mice after acute treatment. We also monitored the mice for possible signs of toxicity after a 14-day treatment. METHODS: The anxiolytic-like activity of the EO was investigated in a light/dark box, and the antidepressant activity was investigated in a forced swim test. Flumazenil, a competitive antagonist of benzodiazepine binding, and the selective 5-HT(1A) receptor antagonist WAY100635 were used in the experimental procedures to determine the mechanism of action of the EO. To exclude false positive results due to motor impairment, the mice were submitted to the rotarod test. RESULTS: The data suggest that the anxiolytic-like activity observed in the light/dark box procedure after acute (5 mg/kg) or 14-day repeated (1 mg/kg/day) dosing was mediated by the serotonergic system (5-HT(1A) receptors). Acute treatment with the EO showed no activity in the forced swim test, which is sensitive to antidepressants. A neurochemical evaluation showed no alterations in neurotransmitter levels in the cortex, the striatum, the pons, and the hypothalamus. Furthermore, no locomotor impairment or signs of toxicity or biochemical changes, except a reduction in cholesterol levels, were observed after treatment with the EO. CONCLUSION: This work contributes to a better understanding of the biological activity of C. aurantium EO by characterizing the mechanism of action underlying its anxiolytic-like activity.

Cholesterol reduction and lack of genotoxic or toxic effects in mice after repeated 21-day oral intake of lemongrass (Cymbopogon citratus) essential oil.

Cymbopogon citratus (lemongrass) is currently used in traditional folk medicine. Although this species presents widespread use, there are no scientific data on its efficacy or safety after repeated treatments. Therefore, this work investigated the toxicity and genotoxicity of this lemongrass's essential oil (EO) in male Swiss mice. The single LD(50) based on a 24h acute oral toxicity study was found to be around 3500 mg/kg. In a repeated-dose 21-day oral toxicity study, mice were randomly assigned to two control groups, saline- or Tween 80 0.01%-treated groups, or one of the three experimental groups receiving lemongrass EO (1, 10 or 100mg/kg). No significant changes in gross pathology, body weight, absolute or relative organ weights, histology (brain, heart, kidneys, liver, lungs, stomach, spleen and urinary bladder), urinalysis or clinical biochemistry were observed in EO-treated mice relative to the control groups. Additionally, blood cholesterol was reduced after EO-treatment at the highest dose tested. Similarly, data from the comet assay in peripheral blood cells showed no genotoxic effect from the EO. In conclusion, our findings verified the safety of lemongrass intake at the doses used in folk medicine and indicated the beneficial effect of reducing the blood cholesterol level.

Influência da suplementação de vitamina E na profilaxia e tratamento da broncopneumonia moderada e grave em bezerros / Influence of vitamin E on prophylaxis and treatment of moderate and severe bronchopneumonia in calves

Estudou-se a broncopneumonia de ocorrência natural em bezerros e a influência da administração de acetato de DL-α-tocoferol na profilaxia e tratamento desta enfermidade. Foram avaliados 60 bezerros machos, com idade máxima de 10 dias, divididos em dois grupos experimentais: GSV (grupo sem vitamina) e GCV (grupo com vitamina). A suplementação com dose única de 4.500 UI de acetato de DL-α-tocoferol por via intramuscular (IM) foi precedida por exame físico, perfil hematológico, determinação de proteínas séricas, globulinas, gamaglutamiltransferase e citologia do lavado traqueobrônquico (D0) para verificar a sanidade e homogeinização dos grupos. Os bezerros foram mantidos em bezerreiro e distribuídos aleatoriamente, 2 a 2 em baias individuais de 2,40m², onde permaneceram até o 21º dia (D0 ao D21). Foram avaliados por exame físico diário e, na presença de sinais clínicos indicativos de broncopneumonia (DX), retirados do bezerreiro, avaliados por hemograma e citologia do lavado traqueobrônquico, e tratados com enrofloxacina (5mg/kg, IM). Durante o tratamento, o exame físico foi realizado diariamente, e o hemograma e a citologia do lavado traqueobrônquico repetidos uma semana após seu término (DY). Nos bezerros sadios foram repetidos hemograma e citologia do lavado traqueobrônquico, no último dia (D21) do experimento. Não houve diferença significativa quanto às variáveis gamaglutamiltrasfrase (p=0,09), proteínas séricas (p=0,27) e globulinas (p=0,10) e a idade dos bezerros (p=0,15) entre os grupos. Os bezerros do grupo GSV e GCV levaram em média 11 e 12 dias para adoecerem, respectivamente. Contudo, não houve diferença estatística significativa entre os grupos (p=0,68). Em 34 bezerros (56,66 por cento) foi diagnosticado broncopneumonia, sendo que 17 destes bezerros (50 por cento) pertenciam ao grupo GCV e 17 (50 por cento) ao grupo GSV. Com relação aos sinais clínicos, não houve diferença significativa entre os grupos em nenhum dos momentos estudados. Dos 34 bezerros que adoeceram 73,52 por cento morreram pela doença, sendo 64,7 por cento do GCV e 82,35 por cento do GSV. A citologia do lavado traqueobrônquico não apresentou diferença significativa entre os grupos em nenhum dos momentos estudados (D0, DX, DY e D21). A suplementação com vitamina E não teve influência na profilaxia e no tratamento de broncopneumonia de bezerros.

The natural occurrence of bronchopneumonia in calves and the effect of DL-α-tocopherol in the prophylaxis and treatment of this disease is studied. We evaluated 60 male calves, aged up to 10 days, divided into two groups: GSV (group without vitamin) and GCV (group with vitamin). Supplementation with a single dose of 4,500 IU of DL-α-tocopherol administered intramuscularly (IM) was preceded by clinical examination, complete blood count (CBC), determination of serum proteins, globulins, gamaglutamyltransferase and tracheobronchial lavage cytology (D0) to check sanity and homogenization of the groups. The animals were kept two by two in individual 2.40 m² stalls, where they remained until day 21 (D0 to D21). The animals were examined daily and, in the presence of clinical signs of bronchopneumonia (DX), taken from stalls, evaluated by CBC and tracheobronchial lavage cytology, and treated with enrofloxacin (5 mg/kg, IM). During the treatment, clinical examination was performed daily by the CBC and tracheobronchial lavage cytology repeated one week after the end of treatment (DY). In healthy animals, CBC and tracheobronchial lavage cytology were repeated on the last day of the experiment (D21). No significant difference for the blood variables gamaglutamiltrasfrase (p=0.09), serum protein (p=0.27) and globulin (p=0.10) and the age of animals (p=0.15) were observed in both of groups. Animals in group GSV and GCV took an average of 11 and 12 days for get sick, respectively. However, no statistical difference between was observed in both groups (p=0.68). In 34 (56.66 percent) animals were diagnosed bronchopneumonia, and 17 of these calves (50 percent) belonged to group GCV and 17 (50 percent) to group GSV. With respect to clinical signs, there was no significant difference between groups in any of the times studied. Out of 34 animals which were affected, 73.52 percent died of the disease, 64.7 percent were from GCV group and 82.35 percent were from GSV group. Cytology of tracheobronchial lavage showed no difference between groups in any of the times studied (D0, DX, DY and D21). We conclude that supplementation with vitamin E had no influence in the prophylaxis and Treatment of bronchopneumonia in calves.