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Bufadienolides are digitalis-like aglycones mainly found in skin secretions of toads. Among their biological properties, the mechanisms of antiproliferative action on tumor cells remain unclear for many compounds, including against leukemia cells. Herein, it was evaluated the mechanisms involved in the antiproliferative and genotoxic actions of hellebrigenin on tumor cell lines and in silico capacity to inhibit the human topoisomerase IIa enzyme. Firstly, its cytotoxic action was investigated by colorimetric assays in human tumor and peripheral blood mononuclear cells (PBMC). Next, biochemical and morphological studies were detailed by light microscopy (trypan blue dye exclusion), immunocytochemistry (BrdU uptake), flow cytometry and DNA/chromosomal damages (Cometa and aberrations). Finally, computational modelling was used to search for topoisomerase inhibition. Hellebrigenin reduced proliferation, BrdU incorporation, viability, and membrane integrity of HL-60 leukemia cells. Additionally, it increased G2/M arrest, internucleosomal DNA fragmentation, mitochondrial depolarization, and phosphatidylserine externalization in a concentration-dependent manner. In contrast to doxorubicin, hellebrigenin did not cause DNA strand breaks in HL-60 cell line and lymphocytes, and it interacts with ATPase domain residues of human topoisomerase IIa, generating a complex of hydrophobic and van der Waals interactions and hydrogen bonds. So, hellebrigenin presented potent anti-leukemic activity at concentrations as low as 0.06 µM, a value comparable to the clinical anticancer agent doxorubicin, and caused biochemical changes suggestive of apoptosis without genotoxic/clastogenic-related action, but it probably triggers catalytic inhibition of topoisomerase II. These findings also emphasize toad steroid toxins as promising lead antineoplasic compounds with relatively low cytotoxic action on human normal cells.
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Antineoplásicos , Bufanolídeos , Leucemia , Humanos , Leucócitos Mononucleares , Bromodesoxiuridina/farmacologia , Dano ao DNA , Antineoplásicos/farmacologia , Bufanolídeos/química , Células HL-60 , Apoptose , DNA/farmacologia , Doxorrubicina/farmacologiaRESUMO
OBJETIVO: Descrever a trajetória de desenvolvimento dos curativos biológicos oriundos de pele de tilápia (Oreochromis niloticus) em glicerol e liofilizada para uso em cirurgias externas e, posteriormente, uma matriz proteica acelular (scaffold) para uso interno. RESULTADOS: A pele de tilapia no glicerol e liofilizada foi aplicada com sucesso em mais de 550 pacientes queimados. A pele de tilápia liofilizada obteve sucesso no tratamento de 53 mulheres em vaginoplastias, em 160 pacientes na redesignação sexual e na preparação do leito da ferida na autoenxertia em 15 portadores da Síndrome de Apert. O scaffold está sendo empregado na oftalmologia na medicina veterinária na reconstrução de córnea em 420 cães, nas duroplastias na neurocirurgia nos testes em animais, e em estudos para uso cirúrgico em 10 especialidades médicas. CONCLUSÕES: O curativo de pele de tilápia supera desafios do tratamento de queimados do Brasil. É barato, biossustentável, efetivo e reduz a dor do paciente, propiciando melhores resultados com potencial redução de custos, contribuindo para a qualidade de vida dos pacientes. O sucesso da pesquisa confirma a pele de tilápia como um novo biomaterial de grande potencial em medicina regenerativa.
OBJECTIVE: To describe the development trajectory of biological dressings made from tilapia (Oreochromis niloticus) skin in glycerol and freeze-dried for use in external surgeries and, subsequently, an acellular protein matrix (scaffold) for internal use. RESULTS: Tilapia skin in glycerol and freeze-dried was successfully applied to more than 550 burn patients. Freeze-dried tilapia skin was successful in the treatment of 53 women undergoing vaginoplasty, in 160 patients in sexual reassignment and in preparing the wound bed in self-grafting in 15 patients with Apert Syndrome. The scaffold is being used in ophthalmology, veterinary medicine in corneal reconstruction in 420 dogs, in duraplasty in neurosurgery in animal tests, and in studies for surgical use in 10 medical specialties. CONCLUSIONS: The tilapia skin dressing overcomes challenges in treating burns in Brazil. It is cheap, biosustainable, effective and reduces patient pain, providing better results with potential cost reduction, contributing to patients' quality of life. The success of the research confirms tilapia skin as a new biomaterial with great potential in regenerative medicine.
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OBJETIVO: Produzir um scaffold baseado em matriz extracelular (SMEC) biocompatível, atóxico e estéril, para tratamento de queimaduras e feridas. Explorou-se a utilização da pele de tilápia como alternativa, ressaltando suas propriedades semelhantes à pele humana e sua aplicação bem-sucedida em diferentes áreas médicas. MÉTODO: Descreve o processo de preparação dos SMEC de pele de tilápia, incluindo etapas de desengorduramento, descontaminação, descelularização e irradiação por raios gama a 25kGy para esterilização. São realizados testes laboratoriais para avaliar a toxicidade celular in vitro pelo método do MTT, análises histológicas com coloração de hematoxilina-eosina, análises microbiológicas e de quantificação de DNA. RESULTADOS: Destacam que os SMEC produzidos foram descelularizados de maneira eficaz, preservando a matriz extracelular e mostrando-se não citotóxicos. Além disso, a análise microbiológica evidenciou a esterilidade dos materiais após a irradiação, comprovando sua adequação para aplicação clínica. A quantificação de DNA revelou a efetividade da descelularização, reduzindo significativamente o conteúdo de DNA original do tecido. CONCLUSÕES: Foi possível o desenvolvimento de uma matriz oriunda da pele de tilápia, sendo ela não citotóxica, estéril, portadora de morfologia adequada para aplicação clínica e acelular. Assim, contribuindo para inovação da ciência brasileira.
OBJECTIVE: To produce a biocompatible, non-toxic, and sterile scaffold based on extracellular matrix (ECM) for the treatment of burns and wounds. The utilization of tilapia skin was explored as an alternative, highlighting its similar properties to human skin and its successful application in different medical areas. METHODS: The process of preparing tilapia skin-derived ECM scaffolds is described, including steps of degreasing, decontamination, decellularization, and gamma ray irradiation at 25kGy for sterilization. Laboratory tests were conducted to assess in vitro cellular toxicity using the MTT method, histological analyses with hematoxylin-eosin staining, microbiological analyses, and DNA quantification. RESULTS: It is emphasized that the produced ECM scaffolds were effectively decellularized, preserving the extracellular matrix and demonstrating non-cytotoxicity. Furthermore, microbiological analysis evidenced the sterility of the materials after irradiation, confirming their suitability for clinical application. DNA quantification revealed the effectiveness of decellularization, significantly reducing the original DNA content of the tissue. CONCLUSIONS: The development of a tilapia skin-derived matrix was achieved, which is non-cytotoxic, sterile, possesses suitable morphology for clinical application, and is acellular. Thus, contributing to the innovation of Brazilian science.
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BACKGROUND: Penile cancer is one of the most aggressive male tumors. Although it is preventable, the main etiologic causes are lifestyle behaviors and viral infection, such as human papillomavirus (HPV). Long-term epigenetic changes due to environmental factors change cell fate and promote carcinogenesis, being an important marker of prognosis. We evaluated epidemiological aspects of penile squamous cell carcinoma (SCC) and the prevalence of HPV infection using high-risk HPV (hrHPV) and p16INK4A expression of 224 participants. Global DNA methylation was evaluated through 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC). RESULTS: The incidence of HPV was 53.2% for hrHPV and 22.32% for p16INK4a. hrHPV was not related to systemic or lymph node metastasis and locoregional recurrence, nor influenced the survival rate. P16INK4a seems to be a protective factor for death, which does not affect metastasis or tumor recurrence. Lymph node and systemic metastases and locoregional recurrence increase the risk of death. An increased 5mC mark was observed in penile SCC regardless of HPV infection. However, there is a reduction of the 5hmC mark for p16INK4a + (P = 0.024). Increased 5mC/5hmC ratio (> 1) was observed in 94.2% of penile SCC, irrespective of HPV infection. Despite the increase in 5mC, it seems not to affect the survival rate (HR = 1.06; 95% CI 0.33-3.38). CONCLUSIONS: P16INK4a seems to be a good prognosis marker for penile SCC and the increase in 5mC, an epigenetic mark of genomic stability, may support tumor progression leading to poor prognosis.
Assuntos
Alphapapillomavirus , Carcinoma de Células Escamosas , Infecções por Papillomavirus , Neoplasias Penianas , Masculino , Humanos , Neoplasias Penianas/genética , Neoplasias Penianas/epidemiologia , Neoplasias Penianas/patologia , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/genética , Infecções por Papillomavirus/epidemiologia , Inibidor p16 de Quinase Dependente de Ciclina/genética , Prognóstico , 5-Metilcitosina , Metilação de DNA , Recidiva Local de Neoplasia/genética , Papillomaviridae/genética , Carcinoma de Células Escamosas/metabolismo , Alphapapillomavirus/genética , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Epigênese Genética , DNA ViralRESUMO
Maternal separation (MS) is a risk factor for major depressive disorder. Both cancer and depression seem to share a common biological link. Here, we evaluated the progression of melanoma and the underlying mechanisms related to this progression, namely cell proliferation and apoptosis, in adult female mice exposed to MS. Female C57BL/6 mice were exposed to MS for 60 min/day during the first 2 postnatal weeks (here called MS mice) or left undisturbed (here called non-MS mice). Melanoma cells were inoculated subcutaneously into the axillary region of adult animals, and tumor progression was evaluated for 25 days. Adult MS mice presented depressive-like behavior and working memory deficits. MS accelerated murine melanoma growth by mechanisms related to decreased apoptosis and increased cell proliferation rate, such as increased expression of IL-6 and mTOR. MS stimulated eukaryotic elongation factor 2 expression and increased the number of circulating monocytes and DNA damage in peripheral blood leukocytes, an effect associated with oxidative DNA damage. In conclusion, MS accelerated the progression of murine melanoma by mechanisms related to tumor proliferation and apoptosis, revealing a relationship between adverse childhood experiences and cancer progression, particularly melanoma.
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Avaliação do Impacto na Saúde , Imunidade , Privação Materna , Melanoma/imunologia , Melanoma/patologia , Animais , Apoptose , Comportamento Animal , Biomarcadores , Proliferação de Células , Dano ao DNA , Modelos Animais de Doenças , Progressão da Doença , Suscetibilidade a Doenças , Feminino , Contagem de Leucócitos , Melanoma/metabolismo , Melanoma Experimental , Camundongos , Neuroimunomodulação , Fatores Sexuais , Estresse FisiológicoRESUMO
Background: Wounds are disruptions of the normal continuity of anatomic structures, generally due to local trauma. Theyare extremely prevalent in animals, especially horses, and a common reason for seeking veterinary attention. Their management aims to restore the function and integrity of the affected area in the shortest possible time and cost, while providingsatisfactory cosmetic results. This task becomes challenging when working with horses, considering the contact betweenwounds and contaminated environment is common. Thus, the present study aims to report the case of a traumatic equinewound treated with Nile Tilapia Fish Skin (NTFS).Case: A male 27-year-old horse previously castrated, with no defined breed (NDB), and weighing 400 kg presented a 6.0 x5.5 cm superficial wound in the distal left anterior limb (LAL) due to skin laceration. The animal belonged to the cavalry ofthe Military Police of Ceará, a public institution in Fortaleza, Brazil. Although in excellent general health, with no previouscomorbidities or restriction of movement, the animal was removed from its role in equine-assisted therapy (EAT) until completewound healing, aiming adequate evaluation of the novel biomaterial via lower influence of external factors. After informedconsent from the owner was obtained, Nile Tilapia Fish Skin was applied to the lesion. The Ethics Committee on the use ofanimals of the Drug Research and Development Center of the Federal University of Ceará, Fortaleza, Brazil, approved the studyprotocol. Compliance with regulations on the ethical treatment of animals was performed. Nile Tilapia Fish Skin applicationfollowed a protocol similar to that established in human clinical studies. Initially, the horse was submitted to wound cleaningwith tap water and 2% chlorhexidine gluconate, with no requirement of pre-treatment surgical...(AU)
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Animais , Transplante de Pele/veterinária , Cavalos/cirurgia , Ferimentos e Lesões/cirurgia , Ferimentos e Lesões/veterinária , Ciclídeos , Técnicas de Fechamento de Ferimentos/veterináriaRESUMO
Background: Wounds are disruptions of the normal continuity of anatomic structures, generally due to local trauma. Theyare extremely prevalent in animals, especially horses, and a common reason for seeking veterinary attention. Their management aims to restore the function and integrity of the affected area in the shortest possible time and cost, while providingsatisfactory cosmetic results. This task becomes challenging when working with horses, considering the contact betweenwounds and contaminated environment is common. Thus, the present study aims to report the case of a traumatic equinewound treated with Nile Tilapia Fish Skin (NTFS).Case: A male 27-year-old horse previously castrated, with no defined breed (NDB), and weighing 400 kg presented a 6.0 x5.5 cm superficial wound in the distal left anterior limb (LAL) due to skin laceration. The animal belonged to the cavalry ofthe Military Police of Ceará, a public institution in Fortaleza, Brazil. Although in excellent general health, with no previouscomorbidities or restriction of movement, the animal was removed from its role in equine-assisted therapy (EAT) until completewound healing, aiming adequate evaluation of the novel biomaterial via lower influence of external factors. After informedconsent from the owner was obtained, Nile Tilapia Fish Skin was applied to the lesion. The Ethics Committee on the use ofanimals of the Drug Research and Development Center of the Federal University of Ceará, Fortaleza, Brazil, approved the studyprotocol. Compliance with regulations on the ethical treatment of animals was performed. Nile Tilapia Fish Skin applicationfollowed a protocol similar to that established in human clinical studies. Initially, the horse was submitted to wound cleaningwith tap water and 2% chlorhexidine gluconate, with no requirement of pre-treatment surgical...
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Animais , Cavalos/cirurgia , Ferimentos e Lesões/cirurgia , Ferimentos e Lesões/veterinária , Transplante de Pele/veterinária , Ciclídeos , Técnicas de Fechamento de Ferimentos/veterináriaRESUMO
Mayer-Rokitansky-Küster-Hauser syndrome is the second most common cause of primary amenorrhea, trailing only to gonadal dysgenesis. Neovaginoplasty is an appropriate treatment option for patients who have failed dilation therapy. Several biomaterials have been used in this procedure, including peritoneum, amnion, skin grafts, and myocutaneous flaps. Nile Tilapia Fish Skin has noninfectious microbiota, morphologic structure comparable to human skin, and high in vivo bioresorption. In addition, it showed good outcomes when used as a xenograft for burn treatment. Thus, we suggest it as a new biologic graft for vaginal agenesis management. In this descriptive study, neovaginoplasty using Nile Tilapia Fish Skin offered 3 patients an anatomic and functional neovagina via a simple method with potential long-term effectiveness. When postsurgical dilation was performed correctly, a vaginal length greater than 6 cm was maintained at 180 days follow-up. Histologic and immunohistochemical analyses revealed the presence of stratified squamous epithelium with high expression of cytokeratins and fibroblast growth factor, matching the characteristics of normal adult vaginal tissue. We believe that further studies will show Nile Tilapia Fish Skin to be a relevant option in the therapeutic arsenal of Mayer-Rokitansky-Küster-Hauser syndrome.
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Transtornos 46, XX do Desenvolvimento Sexual/cirurgia , Ciclídeos , Anormalidades Congênitas/cirurgia , Ductos Paramesonéfricos/anormalidades , Procedimentos de Cirurgia Plástica/métodos , Transplante de Pele/métodos , Vagina/anormalidades , Administração Intravaginal , Adolescente , Adulto , Animais , Produtos Biológicos/uso terapêutico , Brasil , Dilatação/métodos , Feminino , Humanos , Ductos Paramesonéfricos/cirurgia , Procedimentos de Cirurgia Plástica/efeitos adversos , Transplante de Pele/efeitos adversos , Retalhos Cirúrgicos , Transplante Heterólogo/efeitos adversos , Transplante Heterólogo/métodos , Transplante Heterotópico/efeitos adversos , Transplante Heterotópico/métodos , Resultado do Tratamento , Vagina/cirurgia , Adulto JovemRESUMO
This study aims to evaluate the efficacy of Nile tilapia skin as a xenograft for the treatment of partial-thickness burn wounds in children. This is an open-label, monocentric, randomized phase II pilot study conducted in Fortaleza, Brazil. The study population consisted of 30 children between the ages of 2 and 12 years with superficial "partial-thickness" burns admitted less than 72 hours from the thermal injury. In the test group, the tilapia skin was applied. In the control group, a thin layer of silver sulfadiazine cream 1% was applied. Tilapia skin showed good adherence to the wound bed, reducing the number of dressing changes required, the amount of anesthetics used, and providing benefits for the patients and also for healthcare professionals, by reducing the overall work load. The number of days to complete burn wound healing, the total amount of analgesics required throughout the treatment, burn improvement on the day of dressing removal, and pain throughout the treatment were similar to the conventional treatment with silver sulfadiazine. Thus, tilapia skin can be considered an effective and low-cost extra resource in the therapeutic arsenal of pediatric superficial partial thickness burns.
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Queimaduras/cirurgia , Transplante de Pele/métodos , Tilápia , Animais , Brasil , Criança , Pré-Escolar , Feminino , Xenoenxertos , Humanos , Lactente , Masculino , Projetos Piloto , Sulfadiazina de Prata/uso terapêutico , CicatrizaçãoRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Extracts, essential oils and molecules from Casearia sylvestris have popularly shown pharmacological actions against chronic diseases, as anxiety, inflammation, cancer and dyslipidemia. In the context of antitumoral therapy, we investigated in vitro, ex vivo and in vivo toxicological changes induced by a Fraction with Casearins (FC) and its component Casearin X isolated from C. sylvestris on animal and vegetal cells, and upon invertebrates and mammals. MATERIAL AND METHODS: Cytotoxicity was carried out using normal lines and absorbance and flow cytometry techniques, Artemia salina nauplii, Danio rerio embryos and meristematic cells from Allium cepa roots. Acute and 30 days-mice analysis were done by behavioral, hematological and histological investigations and DNA/chromosomal damages detected by alkaline Cometa and micronucleus assays. RESULTS: FC was cytotoxic against lung and fibroblasts cells and caused DNA breaks, loss of integrity and mitochondrial depolarization on ex vivo human leukocytes. It revealed 24 h-LC50 values of 48.8 and 36.7⯵g/mL on A. salina nauplii and D. rerio embryos, reduced mitotic index of A. cepa roots, leading to cell cycle arrest at metaphase and anaphase and micronuclei. FC showed i.p. and oral LD50 values of 80.9 and 267.1â¯mg/kg body weight. Subacute i.p. injections induced loss of weight, swelling of hepatocytes and tubules, tubular and glomerular hemorrhage, microvesicular steatosis, lung inflammatory infiltration, augment of GPT, decrease of albumin, alkaline phosphatase, glucose, erythrocytes, and lymphocytes, and neutrophilia (pâ¯>â¯0.05). FC-treated animals at 10â¯mg/kg/day i.p. caused micronuclei in bone marrow and DNA strand breaks in peripheral leukocytes. CONCLUSIONS: This research postulated suggestive side effects after use of FC-related drugs, demonstrating FC as antiproliferative and genotoxic on mammal and meristematic cells, including human leukocytes, teratogenicity upon zebrafish embryos, myelosuppression, clastogenicity, and morphological and biochemical markers indicating liver as main target for FC-induced systemic toxicity.
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Antineoplásicos Fitogênicos/toxicidade , Casearia , Diterpenos Clerodânicos/toxicidade , Animais , Brasil , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Cricetulus , Embrião não Mamífero/efeitos dos fármacos , Feminino , Fibroblastos/efeitos dos fármacos , Humanos , Leucócitos Mononucleares/efeitos dos fármacos , Medicina Tradicional , Meristema/citologia , Camundongos , Cebolas , Testes de Toxicidade , Peixe-ZebraRESUMO
Introduction: Experimental animal models represent a key tool used to elucidate the mechanisms of action and toxicity of anticancer drugs. Objective: The purpose was to establish a correlation of neoplastic growth with the combinatorial therapeutic application of sodium alendronate (ALD) and methotrexate (MTX), and to evaluate the gastrointestinal toxicity of these drugs, in the rat Walker 256 carcinosarcoma inoculation model. Methods: Female rats were selected and randomly distributed into 5 groups (n=10): negative control (NC), positive control (PC), MTX-treated group, ALD-treated group, and MTX-ALD-treated group (MTX/ALD). Tumor cells were inoculated as a suspension of 1x106cells/mL into the alveolar cavities produced by exodontia procedures. The following parameters were evaluated: body weight, tumor volume and percentage of tumor inhibition, and gastrointestinal toxicity. Results: The body weight variation was statistically significant between NC animals and PC animals, and between NC animals and ALD-treated group (p<0.01). Tumor volume variation was statistically significant between PC animals, MTX-treated group and MTX/ALD-co-treated group (p<0.05). Analysis of gastric toxicity of MTX-treated group reveled slight reduction of chief (Ch) and parietal (Pr) cellular populations; ALD-treated group exhibited gastric mucosa without histological alterations of Ch cells but intense reduction of Pr cellular population; and MTX/ALD-co-treated group presented reduction of Ch and Pr cellular populations. Conclusions: ALD does not elicit significant antitumor effects on Walker 256 carcinosarcoma cells and decreases antitumor effects of MTX due to toxicity on the gastric epithelium, which is intensified with MTX association.
Introdução: Modelos experimentais em animais representam um instrumento fundamental para elucidar os mecanismos de ação e toxicidade de drogas anticâncer. Objetivo: estabelecer uma correlação do crescimento neoplásico com a aplicação terapêutica combinatória de alendronato de sódio (ALD) e metotrexato (MTX), e avaliar a toxicidade gastrointestinal dessas drogas, no modelo de inoculação de carcinossarcoma de Walker 256 em ratos. Métodos: Ratas fêmeas foram selecionadas e distribuídas aleatoriamente em 5 grupos (n = 10): controle negativo (NC), controle positivo (PC), grupo tratado com MTX, grupo tratado com ALD e grupo tratado com MTX-ALD (MTX/ALD). As células tumorais foram inoculadas como uma suspensão de 1x106 células/mL nas cavidades alveolares produzidas por procedimentos de exodontia. Os seguintes parâmetros foram avaliados: peso corporal, volume tumoral e porcentagem de inibição tumoral e toxicidade gastrointestinal. Resultados: A variação do peso corporal foi estatisticamente significante entre animais NC e animais PC, e entre animais NC e grupo tratado com ALD (p <0,01). A variação do volume tumoral foi estatisticamente significativa entre animais PC, grupo tratado com MTX e grupo tratado com MTX / ALD (p <0,05). A análise da toxicidade gástrica do grupo tratado com MTX revelou uma ligeira redução das populações celulares principais (Ch) e parietais (Pr); o grupo tratado com ALD exibiu mucosa gástrica sem alterações histológicas de células Ch mas intensa redução da população celular Pr; e o grupo tratado com MTX / ALD apresentou redução das populações celulares Ch e Pr. Conclusões: O ALD não provoca efeitos antitumorais significativos nas células do carcinossarcoma Walker 256 e diminui os efeitos antitumorais do MTX devido à toxicidade no epitélio gástrico, que é intensificada com a associação MTX.
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Carcinoma 256 de Walker , Mucosa Gástrica , Metotrexato , AlendronatoRESUMO
PURPOSE: To evaluate the contribution of ursodeoxycholic acid (UDCA) in the first 12 months after Roux-en-Y gastric bypass in the prevention of gallstone formation. METHODS: A community-based clinical trial was conducted. A total of 137 patients were included in the study; 69 were treated with UDCA, starting 30 days after the surgery, at a dose of 150 mg twice daily (300 mg/day) over a period of 5 consecutive months (GROUP A), and 68 were control patients (GROUP B). The patients were followed-up, and ultrasonography was performed to determine the presence of gallstones at various times during follow-up. Demographic, anthropometric and comorbid indicators were obtained. The data were subjected to normality tests and evaluated using appropriate tests. RESULTS: Patients did not differ in their baseline characteristics. Of the 69 patients who used UDCA, only one patient developed cholelithiasis (1%), whereas 18 controls (26%) formed gallstones (OR = 24.4, p <0.001). Also, other factors were found not to influence the formation of calculi, such as pre-operative or postoperative hepatic steatosis or diabetes (p = 0.759, 0.468, 0.956). CONCLUSION: The results demonstrated that patients who did not use UDCA showed a 24.4-fold greater probability of developing cholelithiasis.
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Colagogos e Coleréticos/uso terapêutico , Cálculos Biliares/prevenção & controle , Derivação Gástrica/efeitos adversos , Obesidade Mórbida/cirurgia , Complicações Pós-Operatórias/prevenção & controle , Ácido Ursodesoxicólico/uso terapêutico , Adulto , Antropometria , Comorbidade , Feminino , Cálculos Biliares/tratamento farmacológico , Cálculos Biliares/etiologia , Humanos , Masculino , Complicações Pós-Operatórias/tratamento farmacológico , Complicações Pós-Operatórias/etiologia , Período Pós-Operatório , Estudos Prospectivos , Estômago/cirurgiaRESUMO
Purpose:To evaluate the contribution of ursodeoxycholic acid (UDCA) in the first 12 months after Roux-en-Y gastric bypass in the prevention of gallstone formation.Methods:A community-based clinical trial was conducted. A total of 137 patients were included in the study; 69 were treated with UDCA, starting 30 days after the surgery, at a dose of 150 mg twice daily (300 mg/day) over a period of 5 consecutive months (GROUP A), and 68 were control patients (GROUP B). The patients were followed-up, and ultrasonography was performed to determine the presence of gallstones at various times during follow-up. Demographic, anthropometric and comorbid indicators were obtained. The data were subjected to normality tests and evaluated using appropriate tests.Results:Patients did not differ in their baseline characteristics. Of the 69 patients who used UDCA, only one patient developed cholelithiasis (1%), whereas 18 controls (26%) formed gallstones (OR = 24.4, p <0.001). Also, other factors were found not to influence the formation of calculi, such as pre-operative or postoperative hepatic steatosis or diabetes (p = 0.759, 0.468, 0.956).Conclusion:The results demonstrated that patients who did not use UDCA showed a 24.4-fold greater probability of developing cholelithiasis.(AU)
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Abstract Purpose: To evaluate the contribution of ursodeoxycholic acid (UDCA) in the first 12 months after Roux-en-Y gastric bypass in the prevention of gallstone formation. Methods: A community-based clinical trial was conducted. A total of 137 patients were included in the study; 69 were treated with UDCA, starting 30 days after the surgery, at a dose of 150 mg twice daily (300 mg/day) over a period of 5 consecutive months (GROUP A), and 68 were control patients (GROUP B). The patients were followed-up, and ultrasonography was performed to determine the presence of gallstones at various times during follow-up. Demographic, anthropometric and comorbid indicators were obtained. The data were subjected to normality tests and evaluated using appropriate tests. Results: Patients did not differ in their baseline characteristics. Of the 69 patients who used UDCA, only one patient developed cholelithiasis (1%), whereas 18 controls (26%) formed gallstones (OR = 24.4, p <0.001). Also, other factors were found not to influence the formation of calculi, such as pre-operative or postoperative hepatic steatosis or diabetes (p = 0.759, 0.468, 0.956). Conclusion: The results demonstrated that patients who did not use UDCA showed a 24.4-fold greater probability of developing cholelithiasis.
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Humanos , Masculino , Feminino , Adulto , Complicações Pós-Operatórias/prevenção & controle , Ácido Ursodesoxicólico/uso terapêutico , Obesidade Mórbida/cirurgia , Colagogos e Coleréticos/uso terapêutico , Derivação Gástrica/efeitos adversos , Cálculos Biliares/prevenção & controle , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/tratamento farmacológico , Período Pós-Operatório , Estômago/cirurgia , Cálculos Biliares/etiologia , Cálculos Biliares/tratamento farmacológico , Comorbidade , Antropometria , Estudos ProspectivosRESUMO
Cell cycle control genes are frequently mutated in cancer cells, which usually display higher rates of proliferation than normal cells. Dysregulated mitosis leads to genomic instability, which contributes to tumor progression and aggressiveness. Many drugs that disrupt mitosis have been studied because they induce cell cycle arrest and tumor cell death. These antitumor compounds are referred to as antimitotics. Vinca alkaloids and taxanes are natural products that target microtubules and inhibit mitosis, and their derivatives are among the most commonly used drugs in cancer therapy worldwide. However, severe adverse effects such as neuropathies are frequently observed during treatment with microtubule-targeting agents. Many efforts have been directed at developing improved antimitotics with increased specificity and decreased likelihood of inducing side effects. These new drugs generally target specific components of mitotic regulation that are mainly or exclusively expressed during cell division, such as kinases, motor proteins and multiprotein complexes. Such small molecules are now in preclinical studies and clinical trials, and many are products or derivatives from natural sources. In this review, we focused on the most promising targets for the development of antimitotics and discussed the advantages and disadvantages of these targets. We also highlighted the novel natural antimitotic agents under investigation by our research group, including combretastatins, withanolides and pterocarpans, which show the potential to circumvent the main issues in antimitotic therapy.
Assuntos
Antimitóticos/química , Antineoplásicos/química , Produtos Biológicos/química , Desenvolvimento de Medicamentos/métodos , Antimitóticos/farmacologia , Antineoplásicos/farmacologia , Produtos Biológicos/farmacologia , Humanos , Mitose/efeitos dos fármacos , Neoplasias/tratamento farmacológico , Neoplasias/patologiaRESUMO
O objetivo do estudo foi estabelecer valores de referências dos principais parâmetros bioquímicos de ratos Wistar (fêmeas e machos) provenientes do Biotério Central da Universidade Federal do Ceará. Pesquisa aprovada sob o protocolo n° 62/2017. O experimento foi realizado no período de setembro de 2017 a janeiro de 2018, realizado no Biotério do Núcleo de Pesquisa e Desenvolvimento de Medicamentos, na Universidade Federal do Ceará. Foram utilizados ratos Wistar (200 a 250g) de ambos os gêneros, em que se coletou 3 mL de sangue a partir da aorta abdominal (rato Wistar). Após o procedimento os animais foram eutanasiados por aprofundamento do plano anestésico. A análise foi através da estatística descritiva. Os resultados deste trabalho visam estabelecer valores de homeostasia normal. Valores encontrados nos animais do biotério da UFC, para creatinina (0,33mg/dL), colesterol total (62,95mg/dL), bilirrubinas totais e frações (0,14mg/dL), e albumina (4,68g/dL). Os triglicerídeos (60,35mg/dL), TGP (54,95U/I) e TGO (104,35U/I) estão com valores inferiores em relação a outros estudos. Os ratos da linhagem Wistar machos apresentaram os valores dos eletrólitos. Na (136,35mEq/I), K (5,07mEq/I), Cl (100,84mEq/I), Ca (9,9235mEq/I). O magnésio apresentou uma média 2,44 mg/dL, não foi possível correlacionar com outros estudos. As ratas Wistar, apresentaram valores dos eletrólitos semelhantes aos dos machos, sendo o Na (136,33 mEq/I), K (4,62 mEq/I), Cl (99,49 mEq/I), Ca (9,70 mEq/I), Mg (2,27). Os resultados apresentados neste trabalho caracterizam alguns parâmetros relevantes para avaliação de condições clínicas dos ratos Wistar.
The objective of the study was to establish reference values of the main biochemical parameters of Wistar rats (females and males) from the Central Biotério of the Federal University of Ceará. Research approved under protocol no. 62/2017. The experiment was carried out from September 2017 to January 2018, at the Biotério do Centro de Pesquisa e Desenvolvimento de Medicamentos at the Federal University of Ceará. Wistar rats (200 to 250g) of both genders were used. 3 ml of blood was collected from the abdominal aorta (Wistar rat). After the procedure the animals were euthanized by deepening the anesthetic plane. The analysis was through descriptive statistics. The results of this work aim to establish values of normal homeostasis. The values found in the animals of the UFC, for creatinine (0.33mg/dL), total cholesterol (62.95mg/dL), total bilirubin and fractions (0.14mg/dL), albumin (4.68g/dL). Triglycerides (60.35mg/dL), TGP (54,95U/I) and TGO (104,35U/I) are lower than in other studies. Male Wistar rats presented values of the electrolytes Na (136.35mEq/I), K (5.07mEq/I), Cl (100.84mEq/I), Ca (9.9235mEq/I). Magnesium presented a mean of 2.44 mg/dL, it was not possible to correlate with other studies. The Wistar rats presented electrolyte values similar to those of males, with Na (136.33 mEq/I), K (4.62 mEq/I), Cl (99.49 mEq/I), Ca (9.70 mEq/I), Mg (2.27). The results presented in this work characterize some relevant parameters for the evaluation of clinical conditions of Wistar rats.
Assuntos
Animais , Ratos , Análise Química do Sangue/veterinária , Fenômenos Bioquímicos , Ratos Wistar/sangue , Coleta de Amostras Sanguíneas/veterinária , Valores de ReferênciaRESUMO
O objetivo do estudo foi estabelecer valores de referências dos principais parâmetros bioquímicos de ratos Wistar (fêmeas e machos) provenientes do Biotério Central da Universidade Federal do Ceará. Pesquisa aprovada sob o protocolo n° 62/2017. O experimento foi realizado no período de setembro de 2017 a janeiro de 2018, realizado no Biotério do Núcleo de Pesquisa e Desenvolvimento de Medicamentos, na Universidade Federal do Ceará. Foram utilizados ratos Wistar (200 a 250g) de ambos os gêneros, em que se coletou 3 mL de sangue a partir da aorta abdominal (rato Wistar). Após o procedimento os animais foram eutanasiados por aprofundamento do plano anestésico. A análise foi através da estatística descritiva. Os resultados deste trabalho visam estabelecer valores de homeostasia normal. Valores encontrados nos animais do biotério da UFC, para creatinina (0,33mg/dL), colesterol total (62,95mg/dL), bilirrubinas totais e frações (0,14mg/dL), e albumina (4,68g/dL). Os triglicerídeos (60,35mg/dL), TGP (54,95U/I) e TGO (104,35U/I) estão com valores inferiores em relação a outros estudos. Os ratos da linhagem Wistar machos apresentaram os valores dos eletrólitos. Na (136,35mEq/I), K (5,07mEq/I), Cl (100,84mEq/I), Ca (9,9235mEq/I). O magnésio apresentou uma média 2,44 mg/dL, não foi possível correlacionar com outros estudos. As ratas Wistar, apresentaram valores dos eletrólitos semelhantes aos dos machos, sendo o Na (136,33 mEq/I), K (4,62 mEq/I), Cl (99,49 mEq/I), Ca (9,70 mEq/I), Mg (2,27). Os resultados apresentados neste trabalho caracterizam alguns parâmetros relevantes para avaliação de condições clínicas dos ratos Wistar.(AU)
The objective of the study was to establish reference values of the main biochemical parameters of Wistar rats (females and males) from the Central Biotério of the Federal University of Ceará. Research approved under protocol no. 62/2017. The experiment was carried out from September 2017 to January 2018, at the Biotério do Centro de Pesquisa e Desenvolvimento de Medicamentos at the Federal University of Ceará. Wistar rats (200 to 250g) of both genders were used. 3 ml of blood was collected from the abdominal aorta (Wistar rat). After the procedure the animals were euthanized by deepening the anesthetic plane. The analysis was through descriptive statistics. The results of this work aim to establish values of normal homeostasis. The values found in the animals of the UFC, for creatinine (0.33mg/dL), total cholesterol (62.95mg/dL), total bilirubin and fractions (0.14mg/dL), albumin (4.68g/dL). Triglycerides (60.35mg/dL), TGP (54,95U/I) and TGO (104,35U/I) are lower than in other studies. Male Wistar rats presented values of the electrolytes Na (136.35mEq/I), K (5.07mEq/I), Cl (100.84mEq/I), Ca (9.9235mEq/I). Magnesium presented a mean of 2.44 mg/dL, it was not possible to correlate with other studies. The Wistar rats presented electrolyte values similar to those of males, with Na (136.33 mEq/I), K (4.62 mEq/I), Cl (99.49 mEq/I), Ca (9.70 mEq/I), Mg (2.27). The results presented in this work characterize some relevant parameters for the evaluation of clinical conditions of Wistar rats.(AU)
Assuntos
Animais , Ratos , Ratos Wistar/sangue , Fenômenos Bioquímicos , Análise Química do Sangue/veterinária , Coleta de Amostras Sanguíneas/veterinária , Valores de ReferênciaRESUMO
Cell cycle control genes are frequently mutated in cancer cells, which usually display higher rates of proliferation than normal cells. Dysregulated mitosis leads to genomic instability, which contributes to tumor progression and aggressiveness. Many drugs that disrupt mitosis have been studied because they induce cell cycle arrest and tumor cell death. These antitumor compounds are referred to as antimitotics. Vinca alkaloids and taxanes are natural products that target microtubules and inhibit mitosis, and their derivatives are among the most commonly used drugs in cancer therapy worldwide. However, severe adverse effects such as neuropathies are frequently observed during treatment with microtubule-targeting agents. Many efforts have been directed at developing improved antimitotics with increased specificity and decreased likelihood of inducing side effects. These new drugs generally target specific components of mitotic regulation that are mainly or exclusively expressed during cell division, such as kinases, motor proteins and multiprotein complexes. Such small molecules are now in preclinical studies and clinical trials, and many are products or derivatives from natural sources. In this review, we focused on the most promising targets for the development of antimitotics and discussed the advantages and disadvantages of these targets. We also highlighted the novel natural antimitotic agents under investigation by our research group, including combretastatins, withanolides and pterocarpans, which show the potential to circumvent the main issues in antimitotic therapy.
Assuntos
Humanos , Produtos Biológicos/química , Antimitóticos/química , Desenvolvimento de Medicamentos/métodos , Antineoplásicos/química , Produtos Biológicos/farmacologia , Antimitóticos/farmacologia , Mitose/efeitos dos fármacos , Neoplasias/patologia , Neoplasias/tratamento farmacológico , Antineoplásicos/farmacologiaRESUMO
OBJETIVO: Caracterizar a pele de tilápia do Nilo, uma possível fonte de biomaterial para enxertia, a partir de suas características físicas (resistência à tração), histomorfológicas e da tipificação da composição do colágeno. MÉTODOS: Amostras de pele de tilápia do Nilo foram utilizadas e, para os testes de tração (utilizando a máquina de ensaios universais Instron®), as peles foram submetidas à imersão em soluções de glicerol em crescente concentração. Parte das amostras foi fixada em formol neutro a 10%, processada e corada com o uso da hematoxilina e da eosina, para confecção de lâminas e posterior análise histológica e histoquímica. Todas as etapas foram reproduzidas também em pele humana, doada de cirurgias plásticas, para efeito comparativo. RESULTADOS: A morfologia da pele da tilápia mostrou-se semelhante à da pele humana, com derme profunda formada por espessas fibras colágenas organizadas, em disposição paralela/horizontal e transversal/vertical. A pele de tilápia também apresentou maior composição por colágeno tipo I em relação à pele humana (p=0,015). Nos testes de tração, a carga média suportada pela pele de tilápia foi de 43,9±26,2 N, enquanto a extensão à traçao teve valores médios de 4,4±1,045 cm CONCLUSAO: A pele de tilápia possui características microscópicas semelhantes à estrutura morfológica da pele humana e elevada resistência e extensão à tração em quebra, o que suporta sua possível aplicação como biomaterial. A derme desta pele é composta por feixes organizados de fibras de colágeno denso, predominantemente do tipo I, o que traz considerável importância para seu uso clínico.
OBJECTIVE: To characterize the Nile tilapia skin, a possible source of biomaterial for grafting, from their physical (tensile strength) and histomorphological characteristics, and from collagen classification. METHODS: Samples of Nile tilapia skin were used and, for microtensile tests (by Instron® universal testing machine), were subjected to immersion in glycerol solutions of increasing concentration. Part of the samples was fixed in neutral formalin 10%, processed and prepared using routine staining with hematoxylin and eosin into tissue slides, for further histological and histochemical analysis. All steps were also played in human skin, donated by plastic surgeries, for comparative effects. RESULTS: The morphology of Nile tilapia skin presented similarities with human skin, showing the deep dermis formed by thick organized collagen fibers, on parallel/horizontal and transversal/vertical arrangement. The tilapia skin also presented a larger composition of type I collagen, compared with human skin (p=0.015). On traction tests, the load average supported by tilapia skin was 43.9±26.2 N, while the traction extensile had mean values of 4.44±1.045cm. CONCLUSION: The tilapia skin has microscopic characteristics, similar to the morphological structure of human skin, and high resistance and tensile extension at break, which supports its possible application as biomaterial. The dermis of this skin is composed by organized bundles of dense collagen fibers, predominantly type I ones, which brings considerable importance for its clinical use.
RESUMO
PURPOSE: To develop a model to evaluate the effects of focal pulsed ultrasound (US) waves as a source of heat for treatment of murine subcutaneous implanted Walker tumor. METHODS: An experimental, controlled, comparative study was conducted. Twenty male Wistar rats (160-300 g) randomized in 2 equal groups (G-1: Control and G-2: Hyperthermia) were inoculated with Walker-256 carcinosarcoma tumor. After 5 days G-2 rats were submitted to 45ºC hyperthermia. Heat was delivered directly to the tumor by an ultrasound (US) equipment (3 MHz frequency, 1,5W/cm³). Tumor temperature reached 45º C in 3 minutes and was maintained at this level for 5 minutes. Tumor volume was measured on days 5, 8, 11, 14 e 17 post inoculation in both groups. Unpaired t-test was used for comparison. P<0.05 was considered significant. RESULTS: Tumor volume was significantly greater in day 5 and decreased in days 11, 14 and 17 in treated rats. Rats treated with hyperthermia survived longer than control animals. On the 29th day following tumor inoculation, 40 percent of control rats and 77.78 percent of hyperthermia-treated rats remained alive. CONCLUSION: The proposed model is quite simple and may be used in less sophisticated laboratory settings for studying the effects of focal hyperthermia in the treatment of malignant implanted tumours or in survival studies.(AU)
OBJETIVO: Desenvolver um modelo para avaliar os efeitos do ultra-som focal pulsado como fonte de calor para o tratamento de tumores de Walker subcutâneos implantados em ratos. MÉTODOS: Um estudo experimental, controlado, comparativo foi realizado. Vinte ratos Wistar machos (160-300 g) divididos em dois grupos (G-1: Controle e G-2: hipertermia) foram inoculados com tumor de Walker carcinossarcoma-256. Após cinco dias os ratos do grupo G-2 ratos foram submetidos a hipertermia (45ºC). O calor foi aplicado diretamente no tumor por um equipamento de ultrassonografia (3 MHz, 1,5 W/cm³). A temperatura no tumor atingiu 45ºC em 3 minutos e foi mantida nesse nível por 5 minutos. O volume do tumor foi medido nos dias 5, 8, 11, 14 e 17 após a inoculação, em ambos os grupos. Teste t não pareado foi utilizado para comparação. P <0,05 foi considerado significante. RESULTADOS: O volume do tumor foi significativamente maior no 5º dia e diminuiu nos dias 11, 14 e 17 nos ratos tratados. Animais submetidos à hipertermia sobreviveram mais tempo que os animais do grupo controle. Vinte nove dias após a inoculação do tumor, 40 por cento dos ratos do grupo controle e 77,78 por cento dos ratos tratados com hipertermia permaneceram vivos. CONCLUSÃO: O modelo proposto é bastante simples e pode ser utilizado em laboratórios menos sofisticados para estudar os efeitos da hipertermia focal no tratamento dos tumores malignos implantados ou em estudos de sobrevida.(AU)