EFFECT OF PROBIOTIC ORAL ADMINISTRATION ON SKIN WOUND HEALING IN RATS.

BACKGROUND: Manipulating intestinal microbiota with probiotics might stimulate skin response. Understanding all stages of the healing process, as well as the gut-skin-healing response can improve the skin healing process. AIM: To evaluate the effect of perioperative oral administration of probiotics on the healing of skin wounds in rats. METHODS: Seventy-two Wistar male adult rats were weighed and divided into two groups with 36 each, one control group (supplemented with oral maltodextrin 250 mg/day) and one probiotic group (supplemented with Lactobacillus paracasei LPC-37, Bifidobacterium lactis HN0019, Lactobacillus rhamnosus HN001, Lactobacillus acidophilus NCFM® at a dose of 250 mg/day), both given orally daily for 15 days. The two groups were subsequently divided into three subgroups according to the moment of euthanasia: in the 3rd, 7th and 10th postoperative days. RESULTS: There were no significant changes in weight in both groups. Wound contraction was faster in probiotic group when compared to the controls, resulting in smaller wound area in the 7th postoperative day. As for histological aspects, the overall H&E score was lower in the probiotic group. The probiotic group showed increased fibrosis from 3rd to the 7th postoperative day. The type I collagen production was higher in the probiotic group at the 10th postoperative day, and the type III collagen increased in the 7th. CONCLUSION: The perioperative use of orally administrated probiotic was associated with a faster reduction of the wound area in rats probably by reducing the inflammatory phase, accelerating the fibrosis process and the deposition of collagen.

Animal models in metabolic syndrome. / Modelos animais na síndrome metabólica.

Knowledge about animal models for metabolic study is the basis of research in this area. This work aims to review the main animal models used in the study of obesity and metabolic syndrome. For this, we performed a search in the Pubmed database using the terms "animal models", "obesity", "metabolic syndrome" and "bariatric surgery". Several species of animals can be used for the study of metabolic disorders. However, rodents are the most commonly used, both as monogenic models and as diet-induced obesity (DIO) ones. Monogenic animals are the best choice if only one aspect is being evaluated. DIO animals tend to better demonstrate the interaction between disease, environment and genetics. However, they are still not fully effective in providing understanding of all disease mechanisms.

O conhecimento sobre modelos animais para estudo metabólico representa a base da pesquisa nessa área. Este trabalho tem por objetivo revisar os principais modelos animais a serem utilizados no estudo da obesidade e da síndrome metabólica. Para isso, pesquisa no banco de dados Pubmed foi realizada usando as palavras-chave "animal models", "obesity", "metabolic syndrome", e "bariatric surgery". Várias espécies de animais podem ser usadas para o estudo de distúrbios metabólicos, no entanto, os roedores, tanto modelos monogênicos quanto modelos de obesidade induzida por dieta (DIO), são os animais mais utilizados nessa área. Animais monogênicos são a melhor escolha se apenas um aspecto estiver sendo avaliado. Animais DIO tendem a demonstrar melhor a interação entre doença, ambiente e gene. No entanto, eles ainda não são totalmente eficazes para a compreensão de todos os mecanismos dessa doença.

ANIMAL MODELS FOR COLORECTAL CANCER.

INTRODUCTION: Colorectal cancer is a very frequent sort of neoplasm among the population, with a high mortality rate. It develops from an association of genetic and environmental factors, and it is related to multiple cell signaling pathways. Cell cultures and animal models are used in research to reproduce the process of disease development in humans. Of the existing animal models, the most commonly used are animals with tumors induced by chemical agents and genetically modified animals. OBJECTIVE: To present and synthesize the main animal models of colorectal carcinogenesis used in the research, comparing its advantages and disadvantages. METHOD: This literature review was performed through the search for scientific articles over the last 18 years in PubMed and Science Direct databases, by using keywords such as "animal models", "colorectal carcinogenesis" and "tumor induction". RESULTS: 1,2-dimethylhydrazine and azoxymethane are carcinogenic agents with high specificity for the small and large intestine regions. Therefore, the two substances are widely used. Concerning the genetically modified animal models, there is a larger number of studies concerning mutations of the APC, p53 and K-ras genes. Animals with the APC gene mutation develop colorectal neoplasms, whereas animals with p53 and K-ras genes mutations are able to potentiate the effects of the APC gene mutation as well as the chemical inducers. CONCLUSION: Each animal model has advantages and disadvantages, and some are individually efficient as to the induction of carcinogenesis, and in other cases the association of two forms of induction is the best way to obtain representative results of carcinogenesis in humans.

A novel percutaneous magnetically guided gastrostomy technique without endoscopy or imaging guidance: a feasibility study in a porcine model.

BACKGROUND: In order to simplify a percutaneous gastrostomy procedure and avoid the need of endoscopy or imaging methods, a novel percutaneous magnetically guided gastrostomy (PMG) technique was conceived. The aim of the present study is to evaluate the feasibility of a novel PMG technique with no endoscopy or any imaging guidance in a porcine model. METHODS: Fourteen crossbred domestic pigs were used for prototype development (cadaveric experiments) and proof-of concept, survival study. The magnetic device was conceived using commercially available rare-earth neodymium-based magnets. The experimental design consisted of developing an internal magnetic gastric tube prototype to be orally inserted and coupled to an external magnet placed on the skin, which facilitated stomach and abdominal wall apposition for blind percutaneous gastrostomy tube placement. Then, a gastrostomy tube was percutaneously and blindly placed. RESULTS: Twelve procedures were undertaken in animal cadavers and two in live models. The technique chosen consisted of using a magnetic gastric tube prototype using six 1 × 1-cm-ring magnets attached to its end. This device enabled successful magnetic coupling with a large (5 cm in diameter) magnet disc placed on the skin. For gastric tube placement, a direct trocar insertion allowed easier and safer placement of a gastric tube as compared to a needle-guide-wire dilation (Seldinger-based) technique. Gastropexy was added to avoid early gastric tube displacement. This novel PMG technique was feasible in a live model experiment. CONCLUSIONS: A novel magnetically guided percutaneous gastrostomy tube insertion technique without the use of endoscopy or image-guidance was successful in a porcine model. A non-inferiority experimental controlled study comparing this technique to percutaneous endoscopic gastrostomy is needed to confirm its efficacy and safety.

Prolonged use of alendronate alters the biology of cranial repair in estrogen-deficient rats' associated simultaneous immunohistochemical expression of TGF-ß1+, α-ER+, and BMPR1B.

OBJECTIVES: TGF-ß1 is a cytokine that may induce both osteoneogenesis through Runx-2 or fibrosis via the transcription of α-smooth muscle actin (α-SMA). Because it has been previously known that alendronate increases the level of TGF-ß1 and that under the usual condition of bone metabolism the estrogen may prevent the fibrotic effect of TGF-ß1, the aim of this study was to evaluate if alendronate alters the cellular differentiation process post calvarial surgery in estrogen-deficient specimens. MATERIALS AND METHODS: A transosseous defect that was 5 mm in diameter was created on the calvarium of each of 32 female rats with previous ovarian-salpingo-oophorectomy. All defects were treated with autografts, and 16 rats received the administration of 1 mg/kg of alendronate three times a week until euthanasia on the 15th and 60th day post surgery. Histomorphometric and immunohistochemical analyses of the expression of TGF-ß1, estrogen receptor alpha nuclear (α-ER), α-SMA, BMPR1B, and Runx-2 were performed, and ELISA was used to measure the level of estrogen. RESULTS: All animals demonstrated low levels of estrogen post ovarian-salpingo-oophorectomy. The histological results demonstrated larger bone matrix deposition in specimens treated with alendronate on the 15th day post surgery. The result was associated with a higher co-expression of TGF-ß1, BMPR1B, and Runx-2 when compared with the control group. In addition, on the 60th day post surgery, the increase of bone matrix deposition from 15th to 60th day was discrete in specimens treated with alendronate compared with the control group. This result coincided with the intense simultaneous expression of TGF-ß1, α-ER, and α-SMA, whereas the expression of BMPR1B and Runx-2 decreased. CONCLUSION: The prolonged administration of alendronate altered the cranial repair in ovarian-salpingo-oophorectomized specimens due to the simultaneous occurrence of low estrogen and the presence of TGF-ß1+/α-ER+ inducing the presence of α-SMA+, whereas BMPR1B and Runx-2 were suppressed. CLINICAL RELEVANCE: The prolonged administration of alendronate alters osteoneogenesis and induces an unusual microenvironment in the bone that seems to imitate the physiological tissue damage that culminates in the loss of the functional layer of endometrium.

Animal models for colorectal cancer / Modelos animais de carcinogênese colorretal

ABSTRACT Introduction: Colorectal cancer is a very frequent sort of neoplasm among the population, with a high mortality rate. It develops from an association of genetic and environmental factors, and it is related to multiple cell signaling pathways. Cell cultures and animal models are used in research to reproduce the process of disease development in humans. Of the existing animal models, the most commonly used are animals with tumors induced by chemical agents and genetically modified animals. Objective: To present and synthesize the main animal models of colorectal carcinogenesis used in the research, comparing its advantages and disadvantages. Method: This literature review was performed through the search for scientific articles over the last 18 years in PubMed and Science Direct databases, by using keywords such as "animal models", "colorectal carcinogenesis" and "tumor induction". Results: 1,2-dimethylhydrazine and azoxymethane are carcinogenic agents with high specificity for the small and large intestine regions. Therefore, the two substances are widely used. Concerning the genetically modified animal models, there is a larger number of studies concerning mutations of the APC, p53 and K-ras genes. Animals with the APC gene mutation develop colorectal neoplasms, whereas animals with p53 and K-ras genes mutations are able to potentiate the effects of the APC gene mutation as well as the chemical inducers. Conclusion: Each animal model has advantages and disadvantages, and some are individually efficient as to the induction of carcinogenesis, and in other cases the association of two forms of induction is the best way to obtain representative results of carcinogenesis in humans.

RESUMO Introdução: O câncer de cólon e reto é bastante frequente na população e com elevado índice de mortalidade. Ele se desenvolve a partir da associação de fatores genéticos e ambientais e está relacionado a múltiplas vias de sinalização celular. Para o estudo da doença são utilizados cultivos celulares e modelos animais, que sejam capazes de reproduzir o processo de desenvolvimento da doença em humanos. Dos modelos existentes, os mais comumente utilizados são os animais induzidos ao desenvolvimento tumoral por agentes químicos e os animais geneticamente modificados. Objetivo: Apresentar e sintetizar os principais modelos animais de carcinogênese colorretal utilizados na pesquisa, comparando suas vantagens e desvantagens. Método: Para o desenvolvimento dessa revisão foi realizada uma busca por artigos científicos dos últimos 18 anos nas bases de dados PubMed e Science Direct, utilizando como palavras-chave "modelos animais", "carcinogênese colorretal" e "indução tumoral". Resultado: O 1,2 dimetilhidrazina e o azoximetano são agentes carcinógenos com alta especificidade para o intestino delgado e grosso. Por isso, as duas substâncias são amplamente utilizadas. Dos modelos animais geneticamente modificados observa-se maior quantidade de estudos referentes às mutações dos genes APC, p53eK-ras. Os animais com mutação do gene APC desenvolvem neoplasias colorretais, enquanto que animais com mutações dos genes p53 e K-ras são capazes de potencializar os efeitos da mutação do gene APC, bem como dos indutores químicos. Conclusão: Cada modelo animal apresenta vantagens e desvantagens, sendo que alguns são individualmente eficientes na indução da carcinogênese, e em outros casos a associação de duas formas de indução é a melhor maneira de se obter resultados representativos da carcinogênese em humanos.

Modelos animais na síndrome metabólica / Animal models in metabolic syndrome

RESUMO O conhecimento sobre modelos animais para estudo metabólico representa a base da pesquisa nessa área. Este trabalho tem por objetivo revisar os principais modelos animais a serem utilizados no estudo da obesidade e da síndrome metabólica. Para isso, pesquisa no banco de dados Pubmed foi realizada usando as palavras-chave "animal models", "obesity", "metabolic syndrome", e "bariatric surgery". Várias espécies de animais podem ser usadas para o estudo de distúrbios metabólicos, no entanto, os roedores, tanto modelos monogênicos quanto modelos de obesidade induzida por dieta (DIO), são os animais mais utilizados nessa área. Animais monogênicos são a melhor escolha se apenas um aspecto estiver sendo avaliado. Animais DIO tendem a demonstrar melhor a interação entre doença, ambiente e gene. No entanto, eles ainda não são totalmente eficazes para a compreensão de todos os mecanismos dessa doença.

ABSTRACT Knowledge about animal models for metabolic study is the basis of research in this area. This work aims to review the main animal models used in the study of obesity and metabolic syndrome. For this, we performed a search in the Pubmed database using the terms "animal models", "obesity", "metabolic syndrome" and "bariatric surgery". Several species of animals can be used for the study of metabolic disorders. However, rodents are the most commonly used, both as monogenic models and as diet-induced obesity (DIO) ones. Monogenic animals are the best choice if only one aspect is being evaluated. DIO animals tend to better demonstrate the interaction between disease, environment and genetics. However, they are still not fully effective in providing understanding of all disease mechanisms.

The role of the sleeve gastrectomy and the management of type 2 diabetes / O papel da gastrectomia vertical no controle do diabete melito tipo 2

ABSTRACT Background : Currently, bariatric surgery has promoted weight loss and improved glycemic control in obese patients through different techniques, including vertical sleeve gastrectomy. Aim : Present and update the different vertical sleeve gastrectomy ways of action, both in the treatment of obesity and diabetes, approaching its potential effect on gastrointestinal physiology, as well as the benefits achieved by this manipulation. Methods : Pubmed database search was used crossing the headings: obesity, type 2 diabetes and sleeve gastrectomy. Results : Published data have shown that short-term weight loss tends to be higher in patients undergoing vertical sleeve gastrectomy compared to Roux-en-Y gastric bypass. In relation to glycemic control, the procedure demonstrated remission of diabetes in up to 60% after one year of surgery. After three years, however, differences in remission rate between surgical and clinical group was not observed, questioning the durability of the technical in a long-term. Conclusion : Despite showing good results, both in the weight loss and co-morbidities, conflicting results reinforce the need for more studies to prove the efficiency of the vertical sleeve gastrectomy as well as to understand its action about the molecular mechanisms involved in the disease.

RESUMO Racional : Nos últimos anos a cirurgia bariátrica vem promovendo a perda de peso e melhora do controle glicêmico em pacientes obesos por meio de diversas técnicas, entre elas a gastrectomia vertical. Objetivo : Apresentar e atualizar as diferentes formas da ação da gastrectomia vertical, tanto no tratamento da obesidade quanto no diabete, abordando seu potencial efeito na fisiologia gastrointestinal, assim como os benefícios obtidos por meio desta manipulação. Método : Foi realizada revisão de literatura utilizando artigos selecionados na base de dados Pubmed, por meio dos descritores: obesity, type 2 diabetes e sleeve gastrectomy. Resultados : Dados publicados demonstraram que a perda de peso em curto prazo tende a ser maior nos pacientes submetidos à gastrectomia vertical quando comparada ao desvio gástrico em Y-de-Roux. Em relação ao controle glicêmico, a técnica apresentou remissão da taxa de diabete em até 60% após um ano. Após três anos, entretanto, diferença na taxa de remissão entre o grupo cirúrgico e clínico não foram evidenciadas, questionando a durabilidade da técnica em longo prazo. Conclusão : Apesar de apresentar bons resultados no tratamento da obesidade e co-morbidades, resultados conflitantes reforçam a necessidade de mais estudos para demonstrar a eficiência da gastrectomia vertical, assim como para compreender sua ação sobre os mecanismos moleculares envolvidos na doença.

THE IMPACT OF THE USE OF SYMBIOTICS IN THE PROGRESSION OF NONALCOHOLIC FATTY LIVER DISEASE IN A RAT MODEL.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is characterized by accumulation of intrahepatic lipid. The use of live microorganisms promotes beneficial effects; however, the use of symbiotic and its role in NAFLD is not yet fully understood. AIM: Verify if the symbiotic administration influences the occurrence and progression of NAFLD in rats, after induction of hepatic steatosis by high calorie diet. METHOD: Forty-five rats were divided into four groups: G1 (control); G2 (control+symbiotic); G3 (high calorie+symbiotic) and G4 (high calorie), and euthanized after 60 days of diet. Liver disease was evaluated by biochemical analysis, IL6 measurement and histological assessment. RESULTS: Symbiotic had influence neither on weight gain, nor on coefficient dietary intake in G3 and G4. G2 had the greatest weight gain, while G1 had the highest coefficient dietary intake between groups. G1 showed higher expression of aspartate aminotransferase than those from G2 (150±35 mg/dl, and 75±5 mg/dl) while G4 showed higher expression of the enzyme compared to G3 (141±9.7 mg/dl to 78±4 mg/dl). Liver histology showed different stages of NAFLD between groups. G4 animals showed increased serum interleukin-6 when compared to G3 (240.58±53.68 mg/dl and 104.0±15.31 mg/dl). CONCLUSION: Symbiotic can reduce hepatic aminotransferases and interleukin-6 expression. However, the histology showed that the symbiotic was not able to prevent the severity of NAFLD in rats.

The impact of the use of symbiotics in the progression of nonalcoholic fatty liver disease in a rat model / Impacto do uso de simbiótico na doença hepática gordurosa não alcoólica em modelo de ratos

ABSTRACT Background: Non-alcoholic fatty liver disease (NAFLD) is characterized by accumulation of intrahepatic lipid. The use of live microorganisms promotes beneficial effects; however, the use of symbiotic and its role in NAFLD is not yet fully understood. Aim: Verify if the symbiotic administration influences the occurrence and progression of NAFLD in rats, after induction of hepatic steatosis by high calorie diet. Method: Forty-five rats were divided into four groups: G1 (control); G2 (control+symbiotic); G3 (high calorie+symbiotic) and G4 (high calorie), and euthanized after 60 days of diet. Liver disease was evaluated by biochemical analysis, IL6 measurement and histological assessment. Results: Symbiotic had influence neither on weight gain, nor on coefficient dietary intake in G3 and G4. G2 had the greatest weight gain, while G1 had the highest coefficient dietary intake between groups. G1 showed higher expression of aspartate aminotransferase than those from G2 (150±35 mg/dl, and 75±5 mg/dl) while G4 showed higher expression of the enzyme compared to G3 (141±9.7 mg/dl to 78±4 mg/dl). Liver histology showed different stages of NAFLD between groups. G4 animals showed increased serum interleukin-6 when compared to G3 (240.58±53.68 mg/dl and 104.0±15.31 mg/dl). Conclusion: Symbiotic can reduce hepatic aminotransferases and interleukin-6 expression. However, the histology showed that the symbiotic was not able to prevent the severity of NAFLD in rats.

RESUMO Racional: A doença hepática gordurosa não alcoólica (DHGNA) é caracterizada por acúmulo de lipídios intra-hepáticos. O uso de microrganismos vivos promove diversos efeitos benéficos; porém, a utilização de simbióticos e sua atuação na DHGNA ainda não está totalmente esclarecida. Objetivo: Verificar se a administração de simbióticos influencia na ocorrência e na progressão da DHGNA em ratos, após a indução de esteatose hepática por dieta hipercalórica. Método: Quarenta e cinco ratos Wistar foram divididos em quatro grupos: G1 (controle); G2 (controle+simbiótico); G3 (hipercalórica+ simbiótico) e G4 (hipercalórica), e eutanasiados após 60 dias de dieta. Coleta de sangue foi realizada para obtenção de análises bioquímicas e dosagem de IL6, e de tecido para análise histológica do fígado. Resultados: O simbiótico não influenciou no ganho de peso e no coeficiente de consumo alimentar nos grupos G3 e G4. Já G2 obteve maior ganho de peso, enquanto G1 apresentou o maior coeficiente de consumo alimentar entre os grupos. G1 apresentou maior expressão de aspartato aminotransferase em relação ao G2 (150±35 mg/dl e 75±5 mg/dl), enquanto G4 teve maior expressão desta enzima em relação ao G3 (141±9,7 mg/dl e 78±4 mg/dl,). A análise histológica hepática mostrou diferentes estágios de evolução da DHGNA entre os grupos. Animais do G4 apresentaram aumento sérico de interleucina-6 quando comparados a G3 (240,58±53,68 mg/dl, e 104,0±15,31 mg/dl). Conclusão: Os simbióticos reduziram aminotransferases hepáticas e a expressão de interleucina-6. No entanto, a histopatologia demonstrou que o simbiótico não foi capaz de prevenir a severidade da DHGNA em ratos.

Use of Low-Dose Alendronate Improves Cranial Bone Repair and Is Associated With an Increase of Osteocalcin: An Experimental Study.

PURPOSE: The objective of the present study was to evaluate cranial bone repair and remodeling after systemic application of alendronate (ALN), using histologic analysis, histometric analysis, and immunohistochemistry (osteocalcin). MATERIALS AND METHODS: Female rabbits (n = 28) were randomly divided into 2 groups: control (C) and ALN treated (A). Group A received 3 systemic intraperitoneal injections of ALN weekly for 4 weeks, at a dose of 0.2 mg/kg. Group C received intraperitoneal injections of physiologic saline for the same period. After 4 weeks, all the rabbits underwent surgery to create 2 noncritical defects on the calvaria (5 mm in diameter). The groups were divided into 2 subgroups for sacrificing, at 15 and 60 postoperative days. After death, the analyses were performed. The data were also analyzed statistically. RESULTS: Histologic analysis of group C revealed healing in the dense connective tissue and trabecular bone, and the presence of compact bone with osteoblastic activity was noted in both 15- and 60-day subgroups. In group A, at 15 days, the presence of conjunctive tissue with osteoblastic activity and intense, compact, newly formed bone was observed. At 60 days, the created bone defect in group A showed a large amount of neoformed compact bone with a surface of dense modeled connective tissue and the presence of adipocytes and trabecular bone. The histometric analysis confirmed that a statistically significant difference was present between groups C and A when comparing the measured bone area and the area of connective tissue. Group A presented with a statistically significant larger amount of bone area in the 60-day subgroup than in the 15-day subgroup. The immunohistochemical analysis showed stronger immunostaining for osteocalcin in group A. CONCLUSIONS: Within the limits of the present study, our results have shown that the systemic application of ALN, at a dose of 0.2 mg/kg, increased the repair and remodeling of cranial bone.

THE ROLE OF THE SLEEVE GASTRECTOMY AND THE MANAGEMENT OF TYPE 2 DIABETES.

BACKGROUND: Currently, bariatric surgery has promoted weight loss and improved glycemic control in obese patients through different techniques, including vertical sleeve gastrectomy. AIM: Present and update the different vertical sleeve gastrectomy ways of action, both in the treatment of obesity and diabetes, approaching its potential effect on gastrointestinal physiology, as well as the benefits achieved by this manipulation. METHODS: Pubmed database search was used crossing the headings: obesity, type 2 diabetes and sleeve gastrectomy. RESULTS: Published data have shown that short-term weight loss tends to be higher in patients undergoing vertical sleeve gastrectomy compared to Roux-en-Y gastric bypass. In relation to glycemic control, the procedure demonstrated remission of diabetes in up to 60% after one year of surgery. After three years, however, differences in remission rate between surgical and clinical group was not observed, questioning the durability of the technical in a long-term. CONCLUSION: Despite showing good results, both in the weight loss and co-morbidities, conflicting results reinforce the need for more studies to prove the efficiency of the vertical sleeve gastrectomy as well as to understand its action about the molecular mechanisms involved in the disease.