Beneficial effects of coconut oil (Cocos nucifera) on hematobiochemicl and histopathological markers in CCL4-intoxicated rabbits / Efeitos benéficos do óleo de coco (Cocos nucifera) em marcadores hematobioquímicos e histopatológicos em coelhos intoxicados com CCL4

The study was designed to investigate the effect of Coconut Oil on the levels of some liver and hematological parameters in carbon tetrachloride intoxicated rabbits. Also the antioxidant capacity of Coconut Oil for various concentrations was assessed on the basis of percent scavenging of (DPPH) free radical. Experimental animals were divided into five groups, eight rabbits in each group. These were: group A (Normal control), group B (Toxic control), group C (Standard control), group D (Treated with Coconut Oil 50 mL/kg body weight after CCl4 intoxication), group E (Treated with Coconut Oil 200 mL/kg body weight after CCl4 intoxication). The effects observed were compared with a standard hepatoprotective drug silymarine (50 mL/kg body weight). The Coconut Oil (200 mL/kg body weight) significantly (P<0.05) reduced the elevated serum levels of alanine transaminase (ALT), aspartate transaminase (AST) and alkaline phosphatase (ALP) when compared to a toxic control rabbits. The results of extract treated rabbits were similar to silymarine administered rabbits group. Treatment with Coconut Oil root and silymarine caused no significant changes in RBC, Platelets, (Hb), (MCH) concentration and (HCT) values. However, significant (P<0.05) increase was observed in the total WBC count. The present study suggested that Coconut Oil can be used as an herbal alternative (need further exploration i.e to detect its bioactive compound and its efficacy) for hepatoprotective activit.

O estudo foi desenhado para investigar o efeito do óleo de coco nos níveis de alguns parâmetros hepáticos e hematológicos em coelhos intoxicados com tetracloreto de carbono. Também a capacidade antioxidante do óleo de coco para várias concentrações foi avaliada com base na porcentagem de eliminação de radicais livres (DPPH). Os animais experimentais foram divididos em cinco grupos, oito coelhos em cada grupo. Estes foram: grupo A (controle normal), grupo B (controle tóxico), grupo C (controle padrão), grupo D (tratado com óleo de coco 50 mL/kg de peso corporal após intoxicação por CCl4), grupo E (tratado com óleo de coco 200 mL/kg de peso corporal após intoxicação por CCl4). Os efeitos observados foram comparados com um fármaco hepatoprotetor padrão silimarina (50 mL/kg de peso corporal). O óleo de coco (200 mL/kg de peso corporal) reduziu significativamente (P<0,05) os níveis séricos elevados de alanina transaminase (ALT), aspartato transaminase (AST) e fosfatase alcalina (ALP), quando comparado a um coelho controle tóxico. Os resultados dos coelhos tratados com extrato foram semelhantes aos do grupo de coelhos administrados com silimarina. O tratamento com raiz de óleo de coco e silimarina não causou alterações significativas nos valores de RBC, Plaquetas, (Hb), (MCH) e (HCT). No entanto, observou-se aumento significativo (P<0,05) na contagem total de leucócitos. O presente estudo sugeriu que o óleo de coco pode ser usado como uma alternativa fitoterápica (precisa de mais exploração, ou seja, para detectar seu composto bioativo e sua eficácia) para atividade hepatoprotetora.

Beneficial effects of coconut oil (Cocos nucifera) on hematobiochemicl and histopathological markers in CCL4-intoxicated rabbits

Abstract The study was designed to investigate the effect of Coconut Oil on the levels of some liver and hematological parameters in carbon tetrachloride intoxicated rabbits. Also the antioxidant capacity of Coconut Oil for various concentrations was assessed on the basis of percent scavenging of (DPPH) free radical. Experimental animals were divided into five groups, eight rabbits in each group. These were: group A (Normal control), group B (Toxic control), group C (Standard control), group D (Treated with Coconut Oil 50 mL/kg body weight after CCl4 intoxication), group E (Treated with Coconut Oil 200 mL/kg body weight after CCl4 intoxication). The effects observed were compared with a standard hepatoprotective drug silymarine (50 mL/kg body weight). The Coconut Oil (200 mL/kg body weight) significantly (P 0.05) reduced the elevated serum levels of alanine transaminase (ALT), aspartate transaminase (AST) and alkaline phosphatase (ALP) when compared to a toxic control rabbits. The results of extract treated rabbits were similar to silymarine administered rabbits group. Treatment with Coconut Oil root and silymarine caused no significant changes in RBC, Platelets, (Hb), (MCH) concentration and (HCT) values. However, significant (P 0.05) increase was observed in the total WBC count. The present study suggested that Coconut Oil can be used as an herbal alternative (need further exploration i.e to detect its bioactive compound and its efficacy) for hepatoprotective activity.

Resumo O estudo foi desenhado para investigar o efeito do óleo de coco nos níveis de alguns parâmetros hepáticos e hematológicos em coelhos intoxicados com tetracloreto de carbono. Também a capacidade antioxidante do óleo de coco para várias concentrações foi avaliada com base na porcentagem de eliminação de radicais livres (DPPH). Os animais experimentais foram divididos em cinco grupos, oito coelhos em cada grupo. Estes foram: grupo A (controle normal), grupo B (controle tóxico), grupo C (controle padrão), grupo D (tratado com óleo de coco 50 mL/kg de peso corporal após intoxicação por CCl4), grupo E (tratado com óleo de coco 200 mL/kg de peso corporal após intoxicação por CCl4). Os efeitos observados foram comparados com um fármaco hepatoprotetor padrão silimarina (50 mL/kg de peso corporal). O óleo de coco (200 mL/kg de peso corporal) reduziu significativamente (P 0,05) os níveis séricos elevados de alanina transaminase (ALT), aspartato transaminase (AST) e fosfatase alcalina (ALP), quando comparado a um coelho controle tóxico. Os resultados dos coelhos tratados com extrato foram semelhantes aos do grupo de coelhos administrados com silimarina. O tratamento com raiz de óleo de coco e silimarina não causou alterações significativas nos valores de RBC, Plaquetas, (Hb), (MCH) e (HCT). No entanto, observou-se aumento significativo (P 0,05) na contagem total de leucócitos. O presente estudo sugeriu que o óleo de coco pode ser usado como uma alternativa fitoterápica (precisa de mais exploração, ou seja, para detectar seu composto bioativo e sua eficácia) para atividade hepatoprotetora.

Caracterización de los sistemas productores de conejos en el municipio Ciego de Ávila, Cuba / Characterization of rabbit production systems in the Ciego de Ávila municipality, Cuba

Resumen La crianza de conejos contribuye a la obtención de proteína animal, así como de ingresos por la venta de dicha especie. La descripción y caracterización de los sistemas de producción de estos animales arrojan información valiosa para el diseño de planes de intervención y mejoras. El objetivo del presente trabajo fue determinar las principales variables que influyen en la heterogeneidad de los sistemas productores de conejos en el municipio Ciego de Ávila, Cuba. La muestra estuvo formada por 49 fincas. Se obtuvo la información cuantitativa de indicadores productivos, reproductivos y sociales, a través de un análisis de factores, usando componentes principales (CP). Se calcularon las puntuaciones factoriales de cada caso, en cada CP, y los estadísticos descriptivos de los indicadores medidos. En las condiciones del territorio estudiado, la eficiencia estuvo determinada por 6 CP que explicaron el 77.6 % de la varianza: 1) tamaño del rebaño y áreas de forrajes; 2) comportamiento reproductivo; 3) edad del productor y manejo reproductivo; 4) mortalidad; 5) edad al destete y sacrificio y 6) número de montas para gestar las conejas. La caracterización a partir del uso de CP, y el índice factorial de cada caso de estudio en cada CP, sirve de base para interpretar la gran heterogeneidad existente en los indicadores estudiados, así como su similitud, y contribuye a definir relaciones y comportamientos en la caracterización de fincas cunícolas en esta región, lo que permitirá implementar planes de mejora productiva.

Abstract The breeding of rabbits contributes to obtaining animal protein and generating income from the sale of this species. The description and characterization of the production systems of these animals provide valuable information for the design of intervention and improvement plans. The aim of this study was to determine the main variables that influence the heterogeneity of the rabbit production systems in the Ciego de Ávila municipality, Cuba. The sample consisted of 49 farms. Quantitative data on productive, reproductive and social indicators were obtained through factor analysis using principal components (PC). The factor scores of each case were calculated, in each PC, and descriptive statistics of the indicators measured. In the conditions of the studied territory, the efficiency was determined by 6 PC that explained 77.6 % of the variance: 1) size of the herd and forage areas; 2) reproductive behavior; 3) age of the producer and reproductive management; 4) mortality; 5) age at weaning and age at slaughter and 6) number of mounts to gestate the breeders. The characterization from the use of PC, and the factor index for each case study in each PC, serve as the basis for interpreting the great existing heterogeneity in the indicators studied, as well as their similarity. It also contributes to defining relationships and behaviors in the characterization of rabbit farms in this region, which will allow the implementation of productive improvement plans.

Does Anzer Propolis Have a Protective Effect on Rabbit Spinal Cord Ischemia/Reperfusion Injury?*

Abstract Introduction: In this study, Anzer propolis, which can only be obtained from the Eastern Black Sea region in Turkey, is studied for its effect on spinal cord ischemia/reperfusion injury. Methods: A total of 12 healthy male New Zealand White rabbits with an average weight of 3.0 to 3.5 kg were separated into two blind and randomized groups: the ischemia/reperfusion group (n=6) and the treatment group (n=6). Each rabbit in the treatment group was given a dose of 100 mg/kg of ethanol-dissolved Anzer propolis orally 1 hour before surgery. Blood samples were examined at the 0th hour and postoperatively at the 24th and 48th hours. Tissue samples were taken at the 48th hour during the sacrification. Results: There was a statistically significant difference between the two groups in terms of postoperative Tarlov scoring (P=0.012). There was a difference between the two groups in terms of the blood levels of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) at the 48th hour, myeloperoxidase (MPO) at the 24th and 48th hours, ischemia-modified albumin (IMA) at the 24th hour, and intercellular adhesion molecule-1 (ICAM-1) and total oxidant status (TOS) at the 48th hour (P<0.005). There was also a difference between the two groups in terms of apoptotic index data obtained with the terminal deoxynucleotidyl transferase (TdT)‐mediated dUTP nick‐end labelling (TUNEL) method in the histopathological examination (P=0.001). In the transmission electron microscopic (TEM) analysis, while ischemia/reperfusion group generally had axon-myelin separation, axoplasmic dissolution and myelin separation, the propolis treatment group had normal myelin sequencing. Discussion: In our study, after biochemical, histopathological, ultrastructural and neurological functional examination, it was demonstrated that Anzer propolis has sufficient neuroprotective effect on spinal cord ischemia/reperfusion injury in rabbits.

Preclinical evaluation of 89Zr labeled Daratumumab for imaging diagnosis of multiple myeloma / 中华核医学与分子影像杂志

Objective:To prepare 89Zr labeled Daratumumab and evaluate its feasibility in the imaging diagnosis of multiple myeloma (MM). Methods:According to the principle of 89Y (p, n) 89Zr nuclear reaction, 89Zr was produced by cyclotron solid target system (30 μA, 1.5 h) and automatic purification module. The radionuclide purity, half-life and impurity metal ion concentration were detected. Desferrioxamine (DFO) was coupled with Daratumumab and then chelated with 89Zr to prepare 89Zr-DFO-Daratumumab. The quality control analyses of three consecutive batches were carried out. Pharmacokinetic evaluation and 89Zr-DFO-Daratumumab microPET/CT imaging were performed in normal rabbits and orthotopic myeloma mouse models, respectively. The SUV in situ myeloma and that in normal bone were compared by independent-sample t test. Results:About 560 MBq of 89Zr was obtained, and there were only two characteristic energy peaks of 89Zr (909 keV and 511 keV) by γ spectrometer. The half-life of 89Zr was 78.2 h, and the content of metal impurities was small. 89Zr-DFO-Daratumumab was prepared with pH of 7.2, radiochemical purity of more than 99%, good stability in vitro, and sterility and endotoxin tests were passed. Pharmacokinetic studies in rabbits showed that 89Zr-DFO-Daratumumab was gradually distributed from blood to liver, spleen, kidney and bone joints over time and metabolism. The results of microPET/CT imaging in orthotopic myeloma mouse models showed that the SUVs of 89Zr-DFO-daratumumab in situ myeloma were significantly higher than those in normal bone (2 h: 0.22±0.02 vs 0.06±0.00; 1 d: 0.38±0.01 vs 0.08±0.00; t values: 8.89, 21.90, both P=0.001). Conclusion:89Zr and 89Zr-DFO-daratumumab are successfully prepared, and relevant quality control and biological evaluation in vivo and in vitro are completed, which verify the feasibility of 89Zr-DFO-Daratumumab in the imaging diagnosis of MM, thus laying a foundation for clinical transformation.

Effect of application of fibrin glue on vocal fold healing after surgical manipulation in rabbits / Efeito da aplicação de cola de fibrina na cicatrização de pregas vocais após manipulação cirúrgica em coelhos

Abstract Introduction A challenge in phonosurgery is achieving good vocal quality with minimal vocal fold fibrosis. Fibrin glue can be applied to minimize fibrosis; however, its use in the larynx is based primarily on clinical experience, particularly in extensive lesions. Objective The objective of this study was to evaluate the effect of application of fibrin glue on collagen concentration at the late phase of the healing process after detaching a pedicled flap of the vocal fold cover in rabbits. Methods In this prospective animal study, twelve adult male rabbits underwent laryngeal microsurgery, in which an incision was made along the entire length of both vocal folds, followed by extensive mucosal detachment and section of the incision ends. Fibrin glue was applied in the left vocal fold, and the mucosa was repositioned. In the right vocal fold, the mucosa was repositioned without treatment with fibrin glue. After 3-months, the rabbits were euthanized. Histological analyses were performed, and the data collected were subjected to statistical analysis. Results Vocal folds treated with fibrin glue presented higher collagen concentration in Masson trichrome staining and significantly higher (p< 0.05) collagen concentration in picrosirius red staining compared to control vocal folds. Conclusion Treatment with fibrin glue led to greater vocal fold fibrogenesis in the present study. Nonetheless, further studies are necessary to determine the prophylactic effect of sealants in laryngeal surgeries that require extensive detachment of the vocal fold cover.

Resumo Introdução Um desafio na fonocirurgia é conseguir uma boa qualidade vocal com o mínimo de fibrose das pregas vocais. A cola de fibrina pode ser aplicada para minimizar a fibrose; porém, seu uso na laringe é baseado principalmente na experiência clínica, particularmente em lesões extensas. Objetivo Avaliar o efeito da aplicação da cola de fibrina na concentração de colágeno na fase tardia do processo de cicatrização, após o descolamento do retalho pediculado da cobertura da prega vocal em coelhos. Método Neste estudo prospectivo com animais, 12 coelhos adultos machos foram submetidos à microcirurgia de laringe, na qual uma incisão foi feita em toda a extensão de ambas as pregas vocais, seguida de extenso descolamento da mucosa e secção das extremidades da incisão. A cola de fibrina foi aplicada na prega vocal esquerda e a mucosa foi reposicionada. Na prega vocal direita, a mucosa foi reposicionada sem tratamento com cola de fibrina. Após três meses, os coelhos foram sacrificados. Análises histológicas foram feitas e os dados coletados foram submetidos à análise estatística. Resultados As pregas vocais tratadas com cola de fibrina apresentaram maior concentração de colágeno na coloração tricrômica de Masson e concentração significativamente maior de colágeno (p < 0,05) na coloração com picrosirius red comparadas às pregas vocais controle. Conclusão O tratamento com cola de fibrina resultou em maior fibrogênese das pregas vocais no presente estudo. Contudo, novos estudos são necessários para determinar o efeito profilático dos selantes em cirurgias de laringe que requerem extenso descolamento da cobertura das pregas vocais.

Alendronato de sódio tópico associado ao osso bovino liofilizado no reparo ósseo / Topical alendronate associated with lyophilized bovine bone in bone repair

Introdução: O osso bovino inorgânico é o enxerto mais utilizado na Odontologia, tendo como desvantagem longo tempo de integração ao leito receptor. Os bifosfonatos têm sido utilizados para modular a quantidade e a qualidade do osso regenerado e diminuir o tempo de integração do enxerto. Objetivo: Avaliar o efeito do bifosfonato alendronato de sódio (ALN) 0,5%, associado ou não ao osso bovino inorgânico, na reparação de defeitos ósseos. Material e método: Dois defeitos ósseos foram confeccionados na calvária de 12 coelhos, sendo a cavidade esquerda/experimental preenchida com: GI = osso bovino inorgânico (Bio-Oss®); GII = Bio-Oss® + ALN 0,5%; GIII = ALN 0,5%; e a cavidade direita por coágulo sanguíneo (controle). Os animais foram mortos aos 60 dias pós-operatórios. Por meio de análise histomorfométrica calculou-se o percentual de osso neoformado e remanescente do biomaterial em relação à área total do defeito. Resultado: Osso neoformado: GI = 38,16 ± 15,44%; GII = 55,77 ± 16,75%; GII I = 60,28 ± 11,45%. Controle = 45,11 ± 11,09%. Remanescente do enxerto: GI = 7,02 ± 5,36% e GII = 16,59 ± 9,56%. Não houve diferença quanto ao percentual de osso neoformado entre os grupos (ANOVA p = 0,15512; teste de Tukey F = 2,089). O percentual de remanescente do enxerto também foi estatisticamente semelhante entre os grupos GI e GII (teste de Tukey F = 5,019). Conclusão: O uso tópico da solução de ALN 0,5% isoladamente ou associado ao osso bovino liofilizado não alterou o percentual de neoformação óssea nem a degradação dos grânulos do enxerto.

Introduction: Inorganic bovine bone is the most used graft in dentistry, with the disadvantage of long integration time into the receptor bed. Bisphosphonates have been used to modulate the quantity and quality of regenerated bone and decrease graft integration time. Objective: To evaluate the effect of alendronate sodium bisphosphonate (ALN) 0.5%, associated or not with Inorganic bovine bone, in the repair of bone defects. Material and method Two bone defects were made in the calvaria of 12 rabbits, and the left/experimental cavity was filled with: GI = Inorganic bovine bone (Bio-Oss®); GII = Bio-Oss® + 0.5% ALN; GIII = 0.5% ALN; and the right cavity/blood clot control. The animals were killed at 60 days after surgery. Through histomorphometric analysis, the percentage of newly formed bone and remnant biomaterial relative to the total area of the defect was calculated. Result: Neoformed bone: GI = 38.16 ± 15.44%, GII = 55.77 ± 16.75%; GIII= 60.28 ± 11.45%; Control=45,11 ± 11,09%. Graft remnant: GI = 7.02 ± 5.36% and GII = 16.59 ± 9.56%. There was no difference in the percentage of newly formed bone between the groups (ANOVA p = 0.15512; Tukey's test F = 2.089). The percentage of graft remnant was also statistically similar between groups GI and GII (Tukey's test F = 5019). Conclusion: Topical use of 0.5% ALN solution alone or associated with lyophilized bovine bone did not change the percentage of bone neoformation, nor the degradation of graft granules.

The round ligament in developmental hip dysplasia: are its mechanical and histological properties preserved? / O ligamento redondo na displasia do desenvolvimento do quadril: suas propriedades mecânicas e histológicas são preservadas?

ABSTRACT Introduction During open surgical dislocated hip reduction, several anatomical structures, such as the round ligament, are approached. However, there is controversy over both the possibility of preserving the ligament and its functional importance. Materials and Methods This experimental study used skeletally immature rabbits as a model for congenital hip dislocation. Thirty-six rabbits comprised the sample that was submitted to the round ligament analysis. The sample was stratified for analysis (biomechanics, zymography, histology, and immunohistochemistry). Statistical analysis compared the unstable side to the control side of each rabbit. Results Biomechanical assays showed that the mean maximal strength of the round ligament on the unstable side was similar to that of the control side (p = 0.594), which was also the case with maximum deformation (p = 0.328). Histologically, there was a statistically significant increase in cellularity on the unstable side (p <0.001). Additionally, there was significantly greater collagen occupancy on the control side (p <0.001). Zymography revealed no significant difference in the amount of active metalloproteinase 2 (MMP-2) (p = 0.068). Conclusions Although histological analysis found evidence of significant changes in the RL in unstable hips, there were no significant differences in zymography, and no changes were observed in biomechanical tests. Evidence Level V; Experimental study.

RESUMO Introdução Durante a redução cirúrgica aberta de luxação de quadril, várias estruturas anatômicas são abordadas, entre elas, o ligamento redondo. No entanto, há controvérsias quanto à possibilidade de preservação desse ligamento, bem como sua importância funcional. Materiais e Métodos Este estudo experimental usou coelhos esqueleticamente imaturos como modelo de luxação congênita do quadril. Trinta e seis coelhos compuseram a amostra que foi submetida à análise do ligamento redondo. A amostra foi estratificada para análise (biomecânica, zimografia, histologia e imuno-histoquímica). A análise estatística comparou o lado instável com o lado controle de cada coelho. Resultados Os ensaios biomecânicos mostraram que a força máxima média do ligamento redondo no lado instável era semelhante ao lado controle (p = 0,594), o que também ocorreu com a deformação máxima (p = 0,328). Em termos histológicos, houve um aumento estatisticamente significante da celularidade no lado instável (p < 0,001). Além disso, houve maior ocupação de colágeno no lado controle (p < 0,001). A zimografia não mostrou diferença significativa da quantidade de metaloproteinase 2 ativa (MMP-2) (p = 0,068). Conclusões Embora a análise histológica tenha encontrado evidências de alterações significativas do LR nos quadris instáveis, não houve diferenças significativas na zimografia e não foram observadas alterações nos testes biomecânicos. Nível de evidência V; Estudo experimental.

Effect of local gene therapy on expression of Wnt3a and β-catenin in callus of distraction gap during mandibular distraction osteogenesis in rabbits / 中华医学美学美容杂志

Objective:To investigate the effect of electroporation-mediated local gene therapy on the expression of Wnt3a and β-catenin in callus of distraction gap during mandibular distraction osteogenesis of rabbits.Methods:The experiments were conducted in the laboratory of the Affiliated Friendship Plastic Surgery Hospital of Nanjing Medical University from September 2019 to December 2019. Forty eight New-Zealand rabbits were randomly divided into control group (group A), gene therapy group (group B) and normal saline group (group C), with 16 rabbits in each group. After bilateral mandible osteotomy and distractors were implanted, the distractors were activated at a speed of 0.8 mm/d on 4th day, postoperatively, and lasted for 7 days, followed by consolidation period. Group A distracted only, group B was subject to local injection of recombinant plasmid pIRES-hBMP2-hVEGF165 in the distraction gap and electroporation stimulation at the beginning of activation distractors; and group C local injection of the same dose of normal saline in the distraction gap and electroporation stimulation at the beginning of activation distractors. Four animals in each group were sacrificed on the day at the end of distraction, 7th, 14th, 28th days of consolidation period, respectively. The callus in the distraction gap was taken for immunohistochemical staining and RT-PCR to detect the expression of Wnt3a and β-catenin, and image analysis was performed. SPSS 22.0 statistical software was used for data analysis.Results:Immunohistochemical staining showed that Wnt3a and β-catenin were mainly located in the cytoplasm and nuclei of fibroblasts, chondrocytes and osteoblasts in callus tissue. Immunohistochemistry and RT-PCR showed that the expression of Wnt3a and β-catenin reached a peak at the end of distraction. With the disappearance of distraction tension, the expression of Wnt3a and β-catenin gradually decreased. After gene therapy intervention, the expression of Wnt3a and β-catenin was significantly increased, and the expression of Wnt3a and β-catenin in group B was the highest at each time point, with statistically significant difference compared with groups A and C ( F=96.3, P<0.01). Conclusions:Gene therapy promotes the expression of Wnt3a and β-catenin in the callus of distraction gap, regulating the balance of the bone reconstruction system and thus promoting the formation of new bone in the distraction gap.

Propagation and phenotypic analysis of mutant rabbits with MSTN homozygous mutation / 生物工程学报

Myostatin gene (MSTN) encodes a negative regulator for controlling skeletal muscle growth in animals. In this study, MSTN-/- homozygous mutants with "double muscle" phenotypic traits and stable inheritance were bred on the basis of MSTN gene editing rabbits, with the aim to establish a method for breeding homozygous progeny from primary MSTN biallelic mutant rabbits. MSTN-/- primary mutant rabbits were generated by CRISPR/Cas9 gene editing technology. The primary mutant rabbits were mated with wild type rabbits to produce F1 rabbits, whereas the F2 generation homozygous rabbits were bred by half-sibling mating or backcrossing with F1 generation rabbits of the same mutant strain. Sequence analysis of PCR products and its T vector cloning were used to screen homozygous rabbits. The MSTN mutant rabbits with 14-19 week-old were weighed and the difference of gluteus maximus tissue sections and muscle fiber cross-sectional area were calculated and analyzed. Five primary rabbits with MSTN gene mutation were obtained, among which three were used for homozygous breeding. A total of 15 homozygous rabbits (5 types of mutants) were obtained (M2-a: 3; M2-b: 2; M3-a: 2; M7-a: 6; M7-b: 2). The body weight of MSTN-/- homozygous mutant rabbits aged 14-19 weeks were significantly higher than that of MSTN+/+ wild-type rabbits of the same age ((2 718±120) g vs. (1 969±53) g, P < 0.01, a 38.0% increase). The mean cross sections of gluteus maximus muscle fiber in homozygous mutant rabbits were not only significantly higher than that of wild type rabbits ((3 512.2±439.2) μm2 vs. (1 274.8±327.3) μm2, P < 0.01), but also significantly higher than that of MSTN+/- hemizygous rabbits ((3 512.2±439.2) μm2 vs. (2 610.4±604.4) μm2, P < 0.05). In summary, five homozygous mutants rabbits of MSTN-/- gene were successfully bred, which showed a clear lean phenotype. The results showed that the primary breeds were non-chimeric mutant rabbits, and the mutant traits could be inherited from the offspring. MSTN-/- homozygous mutant rabbits of F2 generation could be obtained from F1 hemizygous rabbits by inbreeding or backcrossing. The progenies of the primary biallelic mutant rabbits were separated into two single-allelic mutants, both of which showed a "double-muscle" phenotype. Thus, this study has made progress in breeding high-quality livestock breeds with gene editing technology.

O coelho é a saúva: a proposta brasileira e o uso do vírus do mixoma (MYXV) contra a praga de coelhos na Austrália, 1896-1952 / Rabbits and leaf-cutting ants: the Brazilian plan to use the myxoma virus (MYXV) against rabbit plagues in Australia, 1896-1952

Resumo O artigo analisa a singularidade dos processos históricos, científicos e políticos que vão da descoberta da doença que passou a ser conhecida como mixomatose infecciosa, causada pelo vírus do mixoma (MYXV), à sua aplicação no controle de uma praga de coelhos na Austrália. A narrativa segue especialmente as pesquisas de Henrique de Beaurepaire Aragão, pesquisador do Instituto Oswaldo Cruz, e posteriormente os esforços da cientista Jean Macnamara para promover pesquisas e implementar o MYXV na Austrália. Foram consultadas notas de pesquisa de cientistas, documentos oficiais que registraram o desenvolvimento dos experimentos, bem como periódicos. Nesse processo, foi considerado o desenvolvimento histórico do campo de estudos da virologia e controle biológico.

Abstract This article analyzes the singularity of historical, scientific, and political processes from the discovery of the disease caused by the myxoma virus (MYXV) that came to be known as infectious myxomatosis to the application of this virus against a plague of rabbits in Australia. This narrative focuses on research by Henrique de Beaurepaire Aragão, a researcher at the Oswaldo Cruz Institute, and later efforts by the scientist Jean Macnamara to promote studies and implement MYXV in Australia. The scientists' research notes were consulted, along with official documents recording the experiments and periodicals. In this process, the historical development of virology and biological controls as a field of study was also considered.

Location and Vascular Classification of 188 parathyroid glands in New Zealand White Rabbits / [Localização e Classificação Vascular de 188 glândulas paratireoidianas em coelhos brancos da Nova Zelândia]

The function and protection of the parathyroid glands are increasingly popular research topics. New Zealand white rabbits are the most commonly used animal model of parathyroid ischemia. However, information on the vasculature of their parathyroid glands is limited. We used 94 healthy New Zealand white rabbits, 3-4 months of age and 2-3kg in weight, for exploration of the parathyroid glands, which were stained using hematoxylin and eosin (HE) after removal. The following types were classified according to the relationship between the position of the inferior parathyroid gland and the thyroid: Type A, Close Type, Type B, and Distant Type. There were 188 cases, 4 where the inferior parathyroid glands were located near the dorsal side of thyroid (2.13%), 8 where the inferior parathyroid glands were located superior to the upper pole of the thyroid (4.26%), 20 where the inferior parathyroid glands were located parallel to the thyroid (10.64%), and 155 cases where the inferior parathyroid glands were located inferior to the lower pole of thyroid (82.45%). Identifying the location and classifying the vasculature of the parathyroid glands in New Zealand white rabbits will provide an anatomical model to assist in future research.(AU)

A função e proteção das glândulas paratireoidianas é um tópico de pesquisa cada vez mais popular. Coelhos brancos da Nova Zelândia são o modelo animal mais comumente usada para isquemia da paratireóide. Porém, informação sobre a vasculatura de suas glândulas paratireóides é limitada. Foram usados 94 coelhos brancos da Nova Zelândia saudáveis, com 3-4 meses de idade, 2-3kg de peso, para exploração das glândulas paratireóides, que foram coradas com hematoxilina e eosina (HE) após a remoção. Os seguintes tipos foram classificados de acordo com a relação entre a posição da glândula paratireoidiana inferior e a tireoide: Tipo A, Tipo Próximo, Tipo B e Tipo Distante. Houve 188 casos, 4 em que as glândulas paratireoidianas inferiores estavam localizadas próximas ao lado dorsal da tireoide (2.13%), 8 onde as glândulas paratireoidianas inferiores estavam localizadas superiores ao polo superior da tireoide (4.26%), 20 onde as glândulas paratireoidianas inferiores estavam localizadas paralelo à tireoide (10.64%) e 155 casos em que as glândulas paratireoidianas inferiores estavam localizadas inferiores ao polo inferior da tireoide (82.45%). A identificação da localização e a classificação da vasculatura das glândulas paratireóides em coelhos brancos da Nova Zelândia fornecerão um modelo anatômico para auxiliar em pesquisas futuras.(AU)

The action of subconjunctival cyclophosphamide in rabbits / Ação da ciclofosfamida subconjuntival em coelhos

ABSTRACT Objective: To observe clinically, in rabbits, the side effects of topical injection of subconjunctival cyclophosphamide, studying its role as an antifibrotic drug. Methods: Prospective study in 20 albino rabbits of New Zealand race. All rabbits were treated with cyclophosphamide, 10mg/ml in a volume of 0.3 ml, in the left eye through subconjunctival injection. They were evaluated for 1, 7, 30, and 60 days after the procedure. All the animals were examined for the detection of ocular reactions such as necrosis, hyperemia, chemosis, secretion, opacity, and iritis. Other side effects as changes in the behavior, in the feed, and the water consumption were also evaluated. Results: It was observed that from the 20 rabbits studied, three rabbits (15%) showed side effects only at the 24 hours analysis. One rabbit (5%) presented hyperemia, one rabbit (5%) had hyperemia associated with iritis, and one rabbit (5%) presented hyperemia associated with secretion. These reactions were not observed at 1, 7, 30, and 60 days. Conclusion: Cyclophosphamide subconjunctival injection induces minor side effects on the conjunctiva of rabbits such as hyperemia, associated with iritis and secretion.

RESUMO Objetivo: Observar clinicamente os efeitos colaterais de injeção subconjuntival de ciclofosfamida, pensando em sua ação como um agente antifibrótico. Métodos: Estudo prospectivo realizado com 20 coelhos albinos da raça Nova Zelândia. Todos os coelhos foram submetidos a 0,3 ml de injeção subconjuntival de ciclofosfamida 10mg/ml no olho esquerdo e foram avaliados de acordo com os efeitos locais no primeiro dia após a injeção, 7, 30 e 60 dias. Foram examinados para detecção de reações oculares como necrose, hiperemia, quemose, secreção, opacidade corneana, irite além de alterações comportamentais e variação no consumo de água e alimentação. Resultados: Dos 20 coelhos estudados, apenas 3 apresentaram reações oculares e somente na leitura de 24 horas. Um coelho (5%) apresentou hiperemia, 1 coelho (5%) apresentou hiperemia associada a presença de irite e 1 coelho (5%) apresentou hiperemia associada a presença de secreção. As reações não foram mais observadas durante os exames de 7, 30 e 60 dias. Conclusão: A ciclofosfamida subconjuntival causou poucos efeitos colaterais na conjuntiva dos coelhos. Os únicos efeitos encontrados foram hiperemia, irite e secreção.

Experimental comparative study of arterial implants made of silicone reinforced with polyester fabric and expanded polytetrafluoroethylene (PTFE) in rabbits aorta / Estudo experimental comparativo de implantes arteriais em silicone com reforço de poliéster e politetrafluoretileno expandido (PTFE) em aorta de coelhos

ABSTRACT Objectives: the aim of this study was to compare the outcomes of a new silicone vascular prostheses with PTFE vascular prostheses, on a rabbit experimental model. Methods: forty rabbits underwent infra-renal aorta replacement with 4 mm diameter prostheses, twenty animals with PDMS and twenty animals with PTFE (control group). Retrograde aortic angiography was performed to assess patency. Histological graft samples were examined by electron microscopy to evaluate prostheses endothelialization. Results: patency rates were 100% for both grafts after 30 days; after 60 days, patency rate for PDMS was 92.3% (±7.4), and 73,8% (±13.1) at 90 days. PTFE grafts had patency rates of 87.5% (±11.7) at 60 and 90 days. No statistically significant difference was found in between groups for patency rates (p=0.62). Postoperative complications (death, paraplegia) rates (p=0.526) and aortic clamping times (p=0.299) were comparable in both groups. No statistically significant difference for stenosis was found on angiographical analysis between groups (p=0.650). Electron microscopy revealed limited anastomotic endothelial ingrowth in both prostheses. Conclusion: in this experimental model, PDMS and PTFE vascular prostheses had comparable outcomes and PDMS prosthesis could be used as a vascular graft.

RESUMO Objetivo: analisar novo tubo de silicone como material para prótese vascular e compará-lo a prótese de PTFE, em modelo experimental com coelhos. Métodos: quarenta coelhos foram submetidos a interposição, na aorta infrarrenal, de próteses de 4mm de diâmetro, sendo 20 animais com PDMS e 20 com PTFE (grupo controle). Foi realizada arteriografia retrógrada da aorta para avaliar a patência das próteses. Para avaliar a endotelização das próteses foi realizada microscopia eletrônica de maneira amostral pareada. Resultados: a patência em 30 dias foi de 100% para as duas próteses. Aos 60 dias, a taxa de patência do PDMS foi de 92,3% (± 7,4), e de 73,8% (±13,1) em 90 dias; as próteses de PTFE tiveram taxas de patência de 87,5% (± 11,7) aos 60 e 90 dias. Não foi observada diferença significativa entre as taxas de patência dos grupos (p=0,62). Não foi observada diferença entre os grupos quanto à evolução com complicações pós-operatórias (p=0,526) e quanto ao tempo de clampeamento da aorta (p=0,299). Não houve diferença significativa entre os grupos quanto ao grau de estenose das próteses (p=0,650) à avaliação angiográfica. A microscopia eletrônica mostrou crescimento endotelial limitado às regiões próximas às anastomoses nos dois tipos de próteses. Conclusões: o PDMS mostrou-se passível de utilização como prótese vascular, com resultados comparáveis aos do PTFE no modelo utilizado.

Hemostatic evaluation of rabbits envenomed with Bothrops alternatus treated with anti-bothropic serum, desmopressin and tranexamin acid / Avaliação hemostática de coelhos envenenados com Bothrops alternatus e tratados com soro antibotrópico, desmopressina e ácido tranexâmico

In Brazil, snakes from the Bothrops genus are responsible for thousands of accidents, and their venoms are mainly composed of proteolytic enzymes. Although the antibothropic serum produced by the Brazilian Institutes is remarkably efficient, more studies are necessary, especially in veterinary medicine. The venom contain enzymes and non-enzymatic proteins that interfere with hemostasis leading to hemorrhage or even thrombosis. Possible treatment associations with known bothropic antivenom were the reason for the development of the present study. The aim of this study was to evaluate hemostasis alterations caused by Bothrops alternatus venom in rabbits followed by treatments with anti-bothropic serum, tranexamic acid and desmopressin. Twenty New Zealand rabbits were distributed into five groups (n=4) that were experimentally envenomed with 150mcg/kg of B. alternatus venom via intramuscular injection and treated as follow: Group 1 (G1) was the positive control and received venom and PBS/BSA; Group 2 (G2) was treated with tranexamic acid; Group 3 (G3) with desmopressin; Group 4 (G4) with tranexamic acid and anti-bothropic serum; and Group 5 (G5) with anti-bothropic serum and desmopressin. Blood samples were collected before venom administration, and one, four, eight and 12 hours after, for Partial activated partial thromboplastin time, Prothrombin Time, Thrombin Time and fibrinogen evaluation. Thrombin generation (TG) test was carried out with a pool of samples from final times (8 and 12h). At the end of 12h, all animals were euthanized and necropsy was conducted. Samples from muscle tissue, heart, lungs and kidney were analyzed. Classic coagulation tests showed no significant differences amongst groups and times. However, TG indicated that the venom causes a hypocoagulability state, which was not reversed by proposed treatments. Histology showed muscle inflammation, hemorrhage and necrosis, as well as hemorrhage in other tissues with no differences amongst groups. B. alternatus envenomation causes hypocoagulability detected by TG assay, but not through classical coagulation tests. The use of tranexamic acid and desmopressin for hemostasis stabilization after inoculation of the venom did not show advantage in coagulation restoration.(AU)

No Brasil, as serpentes do gênero Bothrops são responsáveis por milhares de acidentes, e seus venenos são compostos principalmente de enzimas proteolíticas. Embora o soro antiofídico produzido pelos institutos brasileiros seja notavelmente eficiente, mais estudos são necessários, especialmente na medicina veterinária. O veneno contem enzimas e proteínas não-enzimáticas que interferem com a hemostasia levando a hemorragias ou trombose. A associação de outros tratamentos ao soro antibotrópico foi a razão para o desenvolvimento do presente estudo. O objetivo deste estudo foi avaliar as alterações da hemostasia causadas pelo veneno de Bothrops alternatus em coelhos, após tratamento com soro antibotrópico, ácido tranexâmico e desmopressina. Vinte coelhos da Nova Zelândia foram distribuídos em cinco grupos (n = 4) que foram submetidos a experimentos com 150mcg/kg de veneno de B. alternatus por injeção intramuscular. O Grupo 1 (G1) foi o controle positivo e recebeu veneno e PBS / BSA, enquanto o Grupo 2 (G2) foi tratado com ácido tranexâmico, o Grupo 3 (G3) com desmopressina, o Grupo 4 (G4) com ácido tranexâmico e soro antibotrópico, e o Grupo 5 (G5) com soro antibotrópico e desmopressina. As amostras de sangue foram coletadas antes da administração do veneno, e uma, quatro, oito e 12 horas após os tratamentos para realização de tempo de tromboplastina parcial ativada parcial (TTPa), tempo de protrombina (TP), tempo de trombina (TT) e mensuração de fibrinogênio. Para o ensaio de geração de trombina (TG) foi realizado com um pool de amostras nos tempos finais (8 e 12h). Ao final das 12h, todos os animais foram sacrificados e a necropsia foi realizada. Amostras de tecido muscular, coração, pulmões e rins foram analisadas. Os testes TTPa, TP, TT e fibrinogênio não mostraram diferenças significativas entre os grupos e os tempos. No entanto, o TG indicou que o veneno causa um estado de hipocoagulabilidade, que não foi revertido pelos tratamentos propostos. Na histologia, foram observadas inflamação muscular, hemorragia e necrose, além de hemorragia em outros tecidos, sem diferenças entre os grupos. O envenenamento por B. alternatus causa hipocoagulabilidade detectada mais precocemente pelo teste de geração de trombina. O uso de ácido tranexâmico e desmopressina para estabilização da hemostasia após a inoculação do veneno não mostrou vantagem na restauração da coagulação.(AU)

Platelet-concentrated and platelet poor-plasma promote different pattern on immunohistochemical expression of TGF-β1, however they impairs the osteoneogensis in calvarial defects treated with autograft due suppression of osteocalcin

ABSTRACT Purpose Herein we evaluated the effects of platelet concentrate (PC) and platelet-poor plasma (PPP) on bone repair using noncritical defects in the calvaria of rabbits and compared them to the presence of TGF-β1 and osteocalcin on reparative sites. Methods Five noncritical defects of 8.7 mm in diameter were created on the calvaria of 15 animals. Each defect was treated differently, using autograft (ABG), ABG associated with PC (ABG + PC), ABG with PPP (ABG + PPP), isolated PPP, and blood clot (control). The animals were submitted to euthanasia on the second, fourth and sixth week post-surgery. Results The defects that received ABG+PC or PPP demonstrated lower bone formation when compared to specimens that received ABG in the same period. These results coincided to significant higher immunopositivity for TGF-β1 for specimens that received PC, and lower presence of cytokine in the group PPP. However, either higher or lower presence of TGF-β1 were also correlated to lower presence of osteocalcin. Likewise, these results were similar to findings in specimens treated only with PPP when compared to control. Conclusions PC and PPP were not effective when applied in association with ABG. Similarly, isolated use of PPP was not beneficial in optimizing the bone repair.

Cervical ventral slot in rabbits (Oryctolagus cuniculus). Piezosurgery versus conventional technique

ABSTRACT Purpose To investigate the applicability of piezosurgery for cervical ventral slot (CVS), comparing it with the conventional technique of using high-speed burs for bone wear. Methods Thirty rabbits (Oryctolagus cuniculus) were divided into two treatment groups (T1 and T2) corresponding to CVS between C3-C4. In T1, the surgery was performed with piezoelectric apparatus, and in T2 with high-speed burs. The evaluated parameters were: duration of each stage of surgery, temperature variations during CVS, visibility of the surgical field, intra and postoperative complications, and anesthetic monitoring. At 14, 28, and 56 postoperative days, five animals from each treatment group were submitted for histopathological study of the surgical site. Results Compared with T2, T1 had more precise bone cut, and better visibility of the operative field, although it required longer total surgical time (p = 0.02) and triggered a greater number of intraoperative complications (p < 0.01), microscopic lesions in the spinal cord (p < 0.05), and transient neurological deficits in the postoperatively (p < 0.05). Conclusions It is necessary to perform surgical planning and have several tips of the piezoelectric instrument available for the safe use of the piezoelectric device in neurosurgery.

Integration of heterologous bone matrix associated with polymethylmethacrylate in induced tibial bone defects. An experimental study in rabbits

ABSTRACT Purpose To analyze and compare the reactions at the interface between the composite, composed of fragmented heterologous mineralized bone matrix (MOMHF) and polymethylmethacrylate (PMMA), and the rabbit's tibias, through macroscopic evaluation and scanning electron microscopy (SEM) in different periods. Methods In this study, 12 New Zealand adult rabbits were used (E1: n = 3, E2: n = 3, E3: n = 3 and E4: n = 3). They had the right tibial defects filled with composite and were evaluated immediately after surgery and at 30, 60, 90, and 120 days. Results The composites were incorporated and integrated into the recipient beds in 100% of the cases, defined by the MOMHF osseointegration and the PMMA fibrointegration, with no sign of infection, migration, or rejection. Conclusions The behavior of the composites in the recipient beds demonstrates that these biomaterials have the potential to be used in bone defect repairs, offering, thus, better quality of life to the orthopedic patient.

Effect of low-level laser therapy on the membrane induced by the Masquelet technique at an orthotopic site in rabbits

ABSTRACT Purpose: To evaluate the low-level laser therapy (LLLT) on the membrane induced by the Masquelet technique in rabbits. Methods: Twelve Norfolk rabbits at approximately 3 months of age were used. A 1-cm segmental defect was induced in both radii, which were filled with polymethylmethacrylate cylinder. LLLT was used postoperatively in the bone defect of one of the forelimbs every 48 hours for 15 days. Six rabbits were euthanatized on third and sixth postoperative weeks. Results: In both forelimbs, radiographs showed new bone growth from radius cut ends on the third postoperative week and more advanced stage on the sixth postoperative week. Ultrasound showed induced membrane one week after the surgery. Histologically, there were no significant differences in the semi-quantitative score of inflammation intensity, total number of blood vessels, bone metaplasia, and collagen. The average thicknesses were 2,050.17 and 1,451.96 μm for control membranes and 2,724.26 and 2,081.03 μm for irradiated membranes, respectively, on third and sixth postoperative weeks. Vascular endothelial growth factor A (VEGF-A) and platelet derived growth factor (PDGF) expression were present in the induced membranes of control and irradiated forelimbs, but there was no significant difference. Conclusions: Based on assessment methods, it was not possible to demonstrate the effect of LLLT on the induced membrane.

Avaliação do reparo ósseo com Bio-Oss® associado ao raloxifeno em levantamento de seio maxilar de coelhos / Evaluation of bone repair with Bio-Oss® associated with raloxifene in rabbit maxillary sinus lifting

O objetivo deste estudo foi analisar o potencial do Bio-oss® otimizado pelo processamento ultrassônico e associação com o raloxifeno no reparo ósseo em aumento de seio maxilar de coelhos. A associação dos materiais pesquisados foi realizada pelo processamento ultrassônico com 80% de Bio-oss e 20% de Raloxifeno. Para tanto, 8 coelhos (Oryctolagus cunilicus), machos, 6 meses de idade foram submetidos ao levantamento de membrana do seio maxilar bilateralmente, em seguida os seios maxilares foram preenchidos pelos biomateriais, de acordo com o grupo experimetal, sendo 4 animais (8 seios) por grupo: grupo 1 (BS) foi realizada a aplicação do Bio-oss submetido ao processamento ultrassônico sem raloxifeno, nos dois seios. O grupo 2 (BR) foi realizada a aplicação do Bio-oss com processamento ultrassônico juntamente ao raloxifeno, nos dois seios. Foi realizada eutanásia de 2 animais de cada grupo após 2 semanas da enxertia, para análise histométrica de osso neoformado, tecido conjuntivo e material remanescente, e para as reações de imunoistoquímica através do anticorpo primário contra Runx2. Já com 6 semanas, os outros 2 animais de cada grupo foram submetidos a eutanásia para avaliação de parâmetros histométricos (HE) e imunohistoquímicos para OCN, OPG, RANKK-L e TRAP. Os resultados obtidos mostraram superioridade para o grupo BS, que apresentou mais organização tecidual no período de 14 dias, além de maior quantidade de tecido ósseo neoformado aos 14 e 42 dias (p< 0,05). A avaliação imunoistoquímica revelou similaridade entre os escores para ambos os grupos, independente do tempo e proteína analisada. Conclui-se que a adição do raloxifeno, pelo processamento ultrassônico, aumentou reduzindo a quantidade de osso neoformado(AU)

The aim of this study was to analyze the potential of Bio-oss® optimized by the ultrasonic process and association with raloxifene in bone repair in rabbit maxillary sinus augmentation. The association of the researched materials was carried out by the ultrasonic process with 80% Bio-oss and 20% Raloxifene. Eight male rabbits (Oryctolagus cunilicus), six-months of age were subjected to a bilateral maxillary sinus lifting and, they were filled with biomaterials according to two groups, with four animals (eight maxillary sinus) per group: group 1 (BS) Biooss was subjected to ultrasonic process without raloxifene in both sinuses. Group 2 (BR) performed the application of the Bio-osssubjected to ultrasonic process together with raloxifene in both sinuses. The euthanasia of two animals for each group was performed two weeks after grafting, for histometric analysis of newly formed bone, connective tissue, and remaining material, and for immunohistochemical reactions using the primary antibody against Runx2. At 6 weeks, the other two animals for each group were euthanized to evaluate histomorphometric (HE), and immunohistochemical parameters for OCN, OPG, RANK -L, and TRAP. The results obtained showed superiority for the BS group, which presented more tissue organization in the period of 14 days, in addition to a greater amount of new bone tissue at 14-, and 42- days (P< 0.05). The immunohistochemical evaluation revealed a similarity between the scores for both groups, regardless of the time and protein analyzed. It is concluded that the addition of raloxifene, through the ultrasonic process, increases the inflammatory process in the initial period, reducing bone repair(AU)