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Abstract Background It is justified by the high population's morbidity and mortality rate, as well as the increasing present use of nanoparticles in this pathological context. Objectives To describe the main nanotechnology breakthroughs in the field of cardiovascular disease (CVD) and disseminate pertinent information in the literature. Methods This is a systematic review conducted between September and October 2021. The review was carried out through basic nature, following the initial script for the selective reading of articles in chronological order to collect relevant and consistent data related to the theme. Results It is evidenced the main advances of nanotechnology in the field of CVDs, namely, acute coronary syndromes (ACSs), heart failure (HF), and systemic arterial hypertension (SAH). Conclusion The importance of further and deeper studies in this area is emphasized, in order to make the already approved treatments feasible, so they can reach all publics at a low cost.
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The expression of the inositol 1,4,5-trisphosphate receptor type 3 (ITRP3) in hepatocytes is a common event in the pathogenesis of hepatocellular carcinoma (HCC), regardless of the type of underlying liver disease. However, it is not known whether ITPR3 expression in hepatocytes is involved in tumor maintenance. The aim of the present study was to determine whether there is an association between ITPR3 expression and clinical and morphological parameters using HCC samples obtained from liver explants from patients (n=53) with different etiologies of underlying chronic liver disease (CLD). ITPR3 expression, mitosis and apoptosis were analyzed in human liver samples by immunohistochemistry. Clinical and event-free survival data were combined to assess the relationship between ITPR3 and liver cancer growth in patients. RNA sequencing analysis was performed to identify apoptotic genes altered by ITPR3 expression in a liver tumor cell line. ITPR3 was highly expressed in HCC tumor cells relative to adjacent CLD tissue and healthy livers. There was an inverse correlation between ITPR3 expression and mitotic and apoptotic indices in HCC, suggesting that ITPR3 contributed to the maintenance of HCC by promoting resistance to apoptosis. This was confirmed by the upregulation of CTSB, CHOP and GADD45, genes involved in the apoptotic pathway in HCC. The expression of ITPR3 in the liver may be a promising prognostic marker of HCC.
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Introduction: This study assessed the knowledge and satisfaction of a nursing staff regarding peripherally inserted central catheter (PICC) care before and after a combined training strategy consisting of a video and hands-on practice.Methods: A cross-sectional and prospective study with data collection held at a public university hospital from March 2018 to May 2018 and in March 2019. Participants answered a pre-test about PICC lines, watched a video on PICC care and maintenance, attended hands-on sessions, and answered a post-test.Results: A total of 520 professionals participated in the study, of which 87.4% were from the nursing staff. The pre-test was answered by 211 individuals and the post-test questions were answered by 203 people. The satisfaction research showed 97% of satisfied respondents.Conclusions: Our results indicate that a change from the traditional training model to an active educational approach reached more participants, representing an innovative pedagogical tool in the training of critical and reflexive professionals.
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Recursos Audiovisuais , Ensino/educação , Cateterismo Periférico/enfermagem , Cuidados de Enfermagem/métodos , Capacitação de Recursos Humanos em Saúde , Dispositivos de Acesso VascularRESUMO
Objetivo: compreender as principais complicações ocasionadas pelo vírus SARS-CoV-2 no sistema cardíaco do público idoso. Métodos: trata-se de uma revisão sistemática da literatura de abordagem qualitativa e característica descritivo-exploratória realizada no ano de 2020. Resultados: as complicações cardíacas mais prevalentes na população idosa foram miocardite, arritmias, insuficiência cardíaca, infarto agudo, choque cardiogênico, lesão miocárdica aguda e parada cardiorrespiratória. O principal biomarcador cardíaco foi a troponina, apresentando elevação superior ao percentil 99°, evidenciando a necessidade de tratamento em Unidade de Terapia Intensiva. Considerações Finais: o aparecimento desse vírus causou grande prejuízo no campo da saúde, especialmente a população idosa, que apresenta risco elevado de óbito ao contrair essa doença. Destarte, é de extrema importância se ater a mensuração da troponina sérica no público alvo e realizar monitorização longitudinal, utilizando para tal a telecardiologia, uma vez que diminuem as chances de contaminação entre infectado e profissional de saúde
Objective: to understand the main complications of SARS-CoV-2 in the elderly cardiac system. Methods: systematic literature review conducted in 2020. Results: the most prevalent cardiac complications in the elderly population were myocarditis, arrhythmias, heart failure, acute infarction, cardiogenic shock, acute myocardial injury and cardiorespiratory arrest. The main cardiac biomarker was troponin, showing an elevation above the 99th percentile, evidencing the need for treatment in the Intensive Care Unit. Final Considerations: the appearance of this virus has caused great damage in the health field, especially the elderly population, who is at high risk of death when contracting this disease. Therefore, it is important to stick to the measurement of serum troponin in the target audience and perform longitudinal monitoring, using telecardiology for this purpose, since they reduce the chances of contamination between infected and health professionals
Objetivo: comprender las principales complicaciones del SARS-CoV-2 en el sistema cardíaco anciano. Métodos: revisión sistemática de la literatura realizada en 2020. Resultados: las complicaciones cardíacas más prevalentes en la población anciana fueron miocarditis, arritmias, insuficiencia cardíaca, infarto agudo, shock cardiogénico, lesión miocárdica aguda y parada cardiorrespiratoria. El principal biomarcador cardíaco fue la troponina, mostrando una elevación por encima del percentil 99, evidenciando la necesidad de tratamiento en la Unidad de Cuidados Intensivos. Consideraciones finales: la aparición de este virus ha provocado un gran daño en el campo de la salud, especialmente en la población anciana, que se encuentra en alto riesgo de muerte al contraer esta enfermedad. Por tanto, es importante ceñirse a la medición de troponina sérica en el público objetivo y realizar un seguimiento longitudinal, utilizando para ello la telecardiología, ya que reducen las posibilidades de contaminación entre los infectados y los profesionales sanitarios
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Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Troponina , Saúde do Idoso , COVID-19/complicações , Cardiopatias/etiologia , Equipe de Assistência ao Paciente , Choque Cardiogênico , Telecardiologia , Parada Cardíaca , Insuficiência Cardíaca , Unidades de Terapia Intensiva , MiocarditeRESUMO
The liver is a complex organ that performs several functions to maintain homeostasis. These functions are modulated by calcium, a second messenger that regulates several intracellular events. In hepatocytes and cholangiocytes, which are the epithelial cell types in the liver, inositol 1,4,5-trisphosphate (InsP3) receptors (ITPR) are the only intracellular calcium release channels. Three isoforms of the ITPR have been described, named type 1, type 2 and type 3. These ITPR isoforms are differentially expressed in liver cells where they regulate distinct physiological functions. Changes in the expression level of these receptors correlate with several liver diseases and hepatic dysfunctions. In this review, we highlight how the expression level, modulation, and localization of ITPR isoforms in hepatocytes and cholangiocytes play a role in hepatic homeostasis and liver pathology.
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Ductos Biliares Intra-Hepáticos/metabolismo , Sinalização do Cálcio , Receptores de Inositol 1,4,5-Trifosfato/metabolismo , Hepatopatias/patologia , Fígado/metabolismo , Animais , Ductos Biliares Intra-Hepáticos/citologia , Cálcio/metabolismo , Modelos Animais de Doenças , Hepatócitos/metabolismo , Humanos , Fígado/citologia , Fígado/patologia , Isoformas de Proteínas/metabolismoRESUMO
Alcoholic liver disease (ALD) is a highly prevalent spectrum of pathologies caused by alcohol overconsumption. Morbidity and mortality related to ALD are increasing worldwide, thereby demanding strategies for early diagnosis and detection of ALD predisposition. A potential candidate as a marker for ALD susceptibility is the transcription factor nuclear factor erythroid-related factor 2 (Nrf2), codified by the nuclear factor erythroid 2-related factor 2 gene (NFE2L2). Nrf2 regulates expression of proteins that protect against oxidative stress and inflammation caused by alcohol overconsumption. Here, we assessed genetic variants of NFE2L2 for association with ALD. Specimens from patients diagnosed with cirrhosis caused by ALD were genotyped for three NFE2L2 single nucleotide polymorphisms (SNP) (SNPs: rs35652124, rs4893819, and rs6721961). Hematoxylin & eosin and immunohistochemistry were performed to determine the inflammatory score and Nrf2 expression, respectively. SNPs rs4893819 and rs6721961 were not specifically associated with ALD, but analysis of SNP rs35652124 suggested that this polymorphism predisposes to ALD. Furthermore, SNP rs35652124 was associated with a lower level of Nrf2 expression. Moreover, liver samples from ALD patients with this polymorphism displayed more severe inflammatory activity. Together, these findings provide evidence that the SNP rs35652124 variation in the Nrf2-encoding gene NFE2L2 is a potential genetic marker for susceptibility to ALD.
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Predisposição Genética para Doença , Cirrose Hepática Alcoólica/genética , Fator 2 Relacionado a NF-E2/genética , Polimorfismo de Nucleotídeo Único , Regiões Promotoras Genéticas , Adulto , Estudos de Casos e Controles , Etanol/farmacologia , Feminino , Expressão Gênica , Hepacivirus/crescimento & desenvolvimento , Hepacivirus/patogenicidade , Hepatite C/patologia , Hepatite C/virologia , Humanos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Cirrose Hepática Alcoólica/metabolismo , Cirrose Hepática Alcoólica/patologia , Cirrose Hepática Alcoólica/cirurgia , Transplante de Fígado , Masculino , Pessoa de Meia-Idade , Estresse OxidativoRESUMO
Background: Rheumatic carditis is a challenge for treatment and secondary prophylaxis, due to severe valve sequelae. Objective: To evaluate the cases of rheumatic carditis in patients under 18 years old treated with corticosteroids.Methods: An observational, longitudinal and retrospective study was carried out on the profile of patients, in the period of 2000-2015. We selected those who received corticosteroid therapy at immunosuppressive doses, for the treatment of carditis and were aged 5 to 18 years. Data were extracted from medical records. Calculations of: averages, standard deviations, medians and interquartile ranges, ratios and 95% confidence intervals were obtained. Chi-square and Wilcoxon tests were applied for comparisons. The level of significance was 5%. Results: Of the 93 cases, 93.53% developed moderate or severe carditis. Mitral regurgitation was detected in 100% of the sample. Pulse therapy was administered in 11.83%. Surgery was performed in 23.69% of patients: mitral, aortic and/or tricuspid valve repair or replacement. The evolution of the cases was favorable in 70.96%. There was a good response among those who received only clinical treatment and those who belonged to the surgical group. The comparison of the initial and posterior valve lesions to the corticoid use was statistically significant (p < 0.001). A difference between the ejection fraction medians was observed (p = 0.048). Hospitalization was required twice or more for 45.16% of the patients. The mortality rate was 5.38%.Conclusions: The patients showed significant clinical improvement. The treatment was effective, reducing trivalvular impairment
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Humanos , Masculino , Feminino , Criança , Adolescente , Febre Reumática/terapia , Corticosteroides/uso terapêutico , Hospitais Públicos , Miocardite/complicações , Miocardite/fisiopatologia , Valva Aórtica , Penicilinas/uso terapêutico , Próteses e Implantes , Atenção Terciária à Saúde/métodos , Prednisona/administração & dosagem , Interpretação Estatística de Dados , Resultado do Tratamento , Estudo Observacional , Antibacterianos/administração & dosagem , Valva Mitral , Insuficiência da Valva MitralRESUMO
Previous studies showed that P1G10, a proteolytic fraction from Vasconcellea cundinamarcensis latex, reduced the tumor mass in animals bearing melanoma, increased in vitro DNA fragmentation and decreased cell adhesion. Here, we present some molecular and cellular events related to the antimetastatic effect induced by the CMS-2 fraction derived from P1G10 in metastatic melanoma B16-F10 and melanocyte Melan-a. Using difference gel electrophoresis and mass spectrometry, we identified four proteins overexpressed in tumor cells, all of them related to proliferation, survival, migration and cell invasion, that had their expression normalized upon treatment with CMS-2: nucleophosmin 1, heat shock protein 65, calcyclin binding protein and eukaryotic translation initiation factor 4H. In addition, some antioxidant and glycolytic enzymes show increased expression after exposure to CMS-2, along with an induction of melanogenesis (differentiation marker). The down regulation of cofilin 1, a protein involved in cell motility, may explain the inhibition of cell migration and dendritic-like outgrowth in B16-F10 and Melan-a, observed after CMS-2 treatment. Taken together, it is argued that CMS-2 modulates the expression of proteins related to metastatic development, driving the cell to a more differentiated-like state. These effects support the CMS-2 antimetastatic activity and place this fraction in the category of anticancer agent.
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Antineoplásicos Fitogênicos/farmacologia , Caricaceae/enzimologia , Cisteína Proteases/farmacologia , Melanoma/tratamento farmacológico , Metástase Neoplásica/tratamento farmacológico , Proteínas de Plantas/farmacologia , Animais , Diferenciação Celular/efeitos dos fármacos , Linhagem Celular , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Cisteína Proteases/uso terapêutico , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Melanoma/patologia , Camundongos , Metástase Neoplásica/patologia , NucleofosminaRESUMO
OBJETIVOS: Observar a aquisição de habilidades em cirurgia videolaparoscópica em um grupo de residentes de cirurgia geral após o treinamento em simulador de alta fidelidade. MÉTODOS: Série de casos com abordagem qualitativa, descritiva e aplicada. Os participantes foram residentes de cirurgia geral que já haviam cursado o módulo de técnicas cirúrgicas e realizado o treinamento em um simulador de videolaparoscopia de alta fidelidade. A coleta de dados foi realizada por meio de um questionário semiestruturado aplicado aos residentes após o treinamento e de entrevistas com os preceptores cirurgiões, gravadas entre um ano e um ano e meio após o treinamento, quando os residentes já estavam realizando o procedimento em pacientes reais. RESULTADOS: De acordo com os critérios de inclusão, foram analisadas as respostas de sete residentes de cirurgia geral. Após o treinamento em simulador os residentes relataram adquirir habilidades em procedimentos videolaparoscópicos. Dois dos residentes entrevistados mencionaram que tiveram dificuldades na execução das tarefas devido à alta sensibilidade exigida pelo simulador em alguns procedimentos. A metodologia dos "seis passos", utilizada durante o treinamento no simulador, foi bem aceita pelos residentes. Foi apontada a importância da presença de um tutor durante o uso do simulador. Os preceptores de cirurgia videolaparoscópica relataram que as habilidades adquiridas pelos residentes após o treinamento no simulador de alta fidelidade foram transferidas para o mesmo procedimento em pacientes reais. CONCLUSÕES: O presente estudo permite concluir que, de acordo com a percepção técnica e críticas dos residentes e dos preceptores do programa de residência médica em cirurgia geral, o treinamento padronizado utilizando o simulador de cirurgia videolaparoscópica de alta fidelidade mostrou-se eficiente para aquisição de habilidades por esse grupo de residentes, inclusive em posteriores procedimentos cirúrgicos em pacientes reais.
AIMS: To observe the acquisition of skills in videolaparoscopic surgery in a group of residents of general surgery, after training in a high fidelity simulator. METHODS: Case series with a qualitative, descriptive and applied approach. The participants were residents of general surgery who had already completed the surgical techniques module and accomplished the training in a high-fidelity simulator of videolaparoscopy. Data were collected through a semi-structured questionnaire applied to the residents after the training and interviews with the preceptors surgeons, recorded between one year and a year and a half after the training, when the residents were already performing the procedure in real patients. RESULTS: According to the inclusion criteria, the responses of seven general surgery residents were analyzed. After simulator training, they reported to have acquired skills in videolaparoscopic procedures. Two among the interviewed residents mentioned that they have had difficulties in performing the tasks due to the high sensitivity required by the simulator in some procedures. The "Six-Steps" methodology used during simulator training was well accepted by the residents. The importance of the presence of a tutor during the use of the simulator was pointed out. The videolaparoscopic surgery preceptors reported that skills acquired by the residents after training in the high-fidelity simulator were transferred to the same procedure in real patients. CONCLUSIONS: The present study allows to conclude that, according to the technical perception and criticals of residents and preceptors of the medical residency program in general surgery, the standardized training using the high-fidelity videolaparoscopic surgery simulator has proved to be effective for skills acquisition by this group of residents, including future surgical procedures in real patients.
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Laparoscopia , Treinamento por Simulação , Cirurgia Vídeoassistida , Educação Médica , Internato e ResidênciaRESUMO
ABSTRACT In spite of advances in colorectal cancer treatments, approximately 1.4 million new global cases are estimated for 2015. In this sense, Brazilian plant diversity offers a multiplicity of essential oils as prospective novel anticancer compounds. This study aimed to evaluate the antiproliferative effect of the essential oils from four Lippia species in CT26.WT colon tumor cells, as a measurement of cell cycle phase distribution and microRNA expression. CT26.WT showed cell cycle arrest at G2/M phase after treatment with 100 µg/ml of Lippia alba (Mill.) N.E.Br. ex Britton & P. Wilson, Lippia sidoides Cham., and Lippia lacunosa Mart. & Schauer, Verbenaceae, essential oils and, at the same concentration, Lippia rotundifolia Cham. essential oil caused an augment of G0/G1 phase. The miRNA expression profiling shows change of expression in key oncogenic miRNAs genes after treatment. Our findings suggest growth inhibition mechanisms for all four essential oils on CT26.WT cells involving direct or indirect interference on cell cycle arrest and/or oncogenic miRNAs expression.
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Abstract Prior studies demonstrate that a proteinase fraction from Vasconcellea cundinamarcensis V.M. Badillo, Caricaceae, exhibits wound healing activity in gastric and cutaneous models and antitumoral/antimetastatic effects. Here, we present the toxicity, pharmacokinetics and biodistribution data for this proteinase fraction following a single dose into Swiss mice by i.v., s.c. or p.o. routes. The i.v. and s.c. toxicity assays demonstrate that proteinase fraction at ≤20 mg/kg is non-lethal after single injection, while parental administration (p.o.) of ≤300 mg/kg does not cause death. Based on p.o. acute toxicity dose using Organisation for Economic Cooperation and Development protocols, proteinase fraction ranks as Class IV “harmful” substance. Proteinase fraction shows high uptake determined as Kp (distribution tissue/blood) in organs linked to metabolism and excretion. Also, high bioavailability (≈100%) was observed by s.c. administration. The blood contents following i.v. dose fits into a pharmacokinetic bi-compartmental model, consisting of high removal constants – kel 0.22 h−1 and kd 2.32 h−1and a half-life – t½ = 3.13 h. The Ames test of proteinase fraction (0.01–1%) demonstrates absence of mutagenic activity. Likewise, genotoxic evaluation of proteinase fraction (5 or 10 mg/kg, i.p.) shows no influence in micronuclei frequency. In conclusion, the acute doses for proteinase fraction lack mutagenic and genotoxic activity, clearing the way for clinical assays.
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The proteolytic enzymes from V. cundinamarcensis latex, (P1G10), display healing activity in animal models following various types of lesions. P1G10 or the purified isoforms act as mitogens on fibroblast and epithelial cells by stimulating angiogenesis and wound healing in gastric and cutaneous ulcers models. Based on evidence that plant proteinases act as antitumorals, we verified this effect on a murine melanoma model. The antitumoral effect analyzed mice survival and tumor development after subcutaneous administration of P1G10 into C57BL/6J mice bearing B16F1 low metastatic melanoma. Possible factors involved in the antitumoral action were assessed, i.e., cytotoxicity, cell adhesion and apoptosis in vitro, haemoglobin (Hb), vascular endothelial growth factor (VEGF), tumor growth factor-ß (TGF-ß), tumor necrosis factor-α (TNF-α) content and N-acetyl-glucosaminidase (NAG) activity. We observed that P1G10 inhibited angiogenesis measured by the decline of Hb and VEGF within the tumor, and TGF-ß displayed a non-significant increase and TNF-α showed a minor non-significant reduction. On the other hand, there was an increase in NAG activity. In treated B16F1 cells, apoptosis was induced along with decreased cell binding to extracellular matrix components (ECM) and anchorage, without impairing viability.
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Inibidores da Angiogênese/administração & dosagem , Antineoplásicos Fitogênicos/administração & dosagem , Carica/enzimologia , Melanoma Experimental/tratamento farmacológico , Peptídeo Hidrolases/administração & dosagem , Neoplasias Cutâneas/tratamento farmacológico , Inibidores da Angiogênese/farmacologia , Animais , Antineoplásicos Fitogênicos/farmacologia , Apoptose , Adesão Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Masculino , Melanoma Experimental/metabolismo , Melanoma Experimental/patologia , Camundongos , Peptídeo Hidrolases/farmacologia , Proteínas de Plantas/administração & dosagem , Proteínas de Plantas/farmacologia , Neoplasias Cutâneas/metabolismo , Neoplasias Cutâneas/patologia , Fator de Crescimento Transformador beta/metabolismo , Resultado do Tratamento , Fator de Necrose Tumoral alfa/metabolismoRESUMO
OBJECTIVES: The aim of this study was to extend our knowledge about the mechanism involved in the gastroprotective effect of P1G10, a proteolytic fraction rich in cysteine proteinases from Vasconcellea cundinamarcensis (syn. Carica candamarcensis) latex, which demonstrated gastric healing and protection activities in rats. METHODS: Wistar rats were submitted to gastric lesions by indomethacin and treated with P1G10 (10 mg/kg). Free thiol groups and prostaglandin E2 content were measured in gastric mucosal and gastrin levels in blood samples. To evaluate the participation of nitric oxide (NO) or proteolytic activity of P1G10 on its gastroprotective effect, animals were treated with an inhibitor of NO production (L-NAME) or the fraction inhibited by iodoacetamide, respectively. Gastric secretion study (acidity and pepsin activity) was also performed. KEY FINDINGS: P1G10 (10 mg/kg) inhibited the occurrence of gastric lesions by indomethacin, restored the free thiol groups content on gastric mucosa and increased moderately prostaglandin E2 levels (34%). Furthermore, the treatment decreased the gastrin levels (95%), suggesting a possible modulation of secretory activity. This effect was accordant with attenuation of gastric acidity (42%) and pepsin activity (69%) seen in animals subjected to pyloric ligation. The inhibition of NO production or the proteolytic activity of P1G10 does not affect the gastroprotective effect. CONCLUSIONS: These results can explain the gastroprotective activity of P1G10 and serve a basis for further studies of this active principle.
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Carica , Cisteína Proteases/farmacologia , Dinoprostona/metabolismo , Ácido Gástrico/metabolismo , Extratos Vegetais/farmacologia , Compostos de Sulfidrila/metabolismo , Animais , Feminino , Ácido Gástrico/química , Ácido Gástrico/fisiologia , Mucosa Gástrica , Gastrinas/biossíntese , Gastrinas/sangue , Indometacina/farmacologia , NG-Nitroarginina Metil Éster/farmacologia , Óxido Nítrico/antagonistas & inibidores , Ratos , Ratos WistarRESUMO
Angiotensin-(1-7) has been described as a new potential therapeutic tool for the treatment and prevention of metabolic disorders by regulating several pathways in visceral white adipose tissue (vWAT). The aim of this study was to access the proteins differentially regulated by Ang-(1-7) using proteomic analysis of visceral adipose tissue. Male mice were divided into three groups and fed for 60 days, with each group receiving one of the following diets: standard diet+HPßCD (ST), high fat diet+HPßCD (HFD) and high fat diet+Ang-(1-7)/HPßCD (HFD+Ang-(1-7)). Body weight, fat weight and food intake were measured. At the end of treatment, Ang-(1-7) induced a decrease in body and fat weight. Differential proteomic analysis using two-dimensional electrophoresis (2-DE) combined with mass spectrometry were performed. Results of protein mapping of mesenteric adipose tissue using 2-DE revealed the presence of about 450 spots in each gel (n=3/treatment) with great reproducibility (>70%). Image analysis and further statistical analysis allowed the detection and identification of eight proteins whose expression was modulated in response to HFD when compared to ST. Among these, two proteins showed a sensitive response to Ang-(1-7) treatment (eno1 and aldehyde dehydrogenase). In addition, three proteins were expressed statistically different between HFD+Ang-(1-7) and HFD groups, and four proteins were modulated compared to standard diet. In conclusion, comparative proteomic analysis of a mice model of diet-induced obesity allowed us to outline possible pathways involved in the response to Ang-(1-7), suggesting that Ang-(1-7) may be a useful tool for the treatment of metabolic disorders.
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Tecido Adiposo Branco/efeitos dos fármacos , Tecido Adiposo Branco/metabolismo , Angiotensina I/administração & dosagem , Angiotensina I/farmacologia , Dieta Hiperlipídica/efeitos adversos , Obesidade/tratamento farmacológico , Fragmentos de Peptídeos/administração & dosagem , Fragmentos de Peptídeos/farmacologia , Proteoma/análise , Administração Oral , Animais , Eletroforese em Gel Bidimensional , Masculino , Espectrometria de Massas , Camundongos , Camundongos Endogâmicos , Obesidade/induzido quimicamente , Obesidade/metabolismo , Proteoma/metabolismo , Proteômica , Aumento de Peso/efeitos dos fármacosRESUMO
Os répteis possuem um sistema porta-renal, o qual pode desviar parte do sangue proveniente das porções caudais do corpo aos rins antes que a mesma atinja a circulação sistêmica. Em vista disto, vem sendo aconselhada a administração de medicamentos injetáveis nos membros torácicos, para que se evite a filtração imediata pelo parênquima renal, causando redução do efeito esperado. O objetivo do presente estudo foi comparar aspectos qualitativos e quantitativos da associação de cetamina (30 mg/kg) e xilazina (1 mg/kg), injetada no membro torácico ou pélvico, em jacarés-do-papo-amarelo (Caiman latirostris) juvenis. Oito animais machos com peso médio (±DP) de 1,3 (±0,3) kg e, aproximadamente, dois anos de idade foram anestesiados em duas ocasiões distintas com intervalo de sete dias. Em cada ocasião, os animais receberam, de forma aleatória, a associação anestésica por via intramuscular em membro torácico (tratamento MT) ou pélvico (tratamento MP). Foram avaliados os intervalos de tempo entre a administração do tratamento e a perda do reflexo de endireitamento (período de indução), entre a perda e o retorno desse reflexo (duração do efeito clínico importante) e entre o retorno do reflexo de endireitamento e os primeiros movimentos de deambulação (duração do efeito residual), as frequências cardíaca e respiratória e as temperaturas ambiental e cloacal. Os escores de sedação/anestesia foram avaliados através de uma escala com variação de 0 (alerta/consciente) a 10 (anestesia profunda/sobredosagem). No tratamento MP, dois animais não apresentaram perda de reflexo de endireitamento. Considerando somente aqueles que apresentaram a perda desse reflexo, o tempo de indução (21±9 e 17±5 minutos) e a duração do efeito clínico importante (35±19 e 43±21 minutos) e residual (28±31 e 12±11 minutos) foram similares entre os tratamentos MT e MP (média±desvio padrão)...
Reptiles possess a renal portal system which can divert part of the blood from the caudal portions of the body to the kidney before it reaches the systemic circulation. In view of this, it has been recommended the administration of injectable medications in the forelimbs, in order to avoid immediate glomerular filtration, which might result in a reduction of the expected effect. The aim of this study was to compare qualitative and quantitative aspects of the pharmacological restraint provided by the combination of ketamine (30mg/kg) and xylazine (1mg/kg), injected into the forelimb or hindlimb, in broad-snouted caiman juveniles (Caiman latirostris). Eight male animals, with a mean weight (±SD) of 1.3 (±0.3) kg, and aged about 2 years old, were anesthetized on two separate occasions with an interval of 7 days. On each occasion, the animals were randomly assigned to receive the anesthetic combination intramuscularly into the forelimb (FL treatment) or hindlimb (HL treatment). The time intervals between administration of treatment and loss of the righting reflex (induction time), between the loss and return of this reflex (duration of important clinical effect), and between the return of the righting reflex and first movements of ambulation (duration of residual effect) were measured as well as heart and respiratory rates and cloacal and environmental temperatures. Sedation/anesthesia scores were evaluated using a scale ranging from 0 (alert/conscious) to 10 (deep anesthesia/overdose). In the HL treatment, loss of righting reflex was not observed in two animals. Considering only those animals whose loss of righting reflex was observed, the induction time (21±9 and 17±5 minutes), the duration of important clinical effect (35±19 and 43±21 minutes), and the duration of residual effect (28±31 and 12±11 minutes) were similar between the FL and HL treatments, respectively (mean±SD). Sedation/anesthesia scores were significantly higher than at baseline...
Assuntos
Animais , Anestésicos Dissociativos/efeitos adversos , Jacarés e Crocodilos/metabolismo , Ketamina/administração & dosagem , Membro Anterior , Pelve , Xilazina/administração & dosagem , Circulação Renal , Sedação Profunda/veterináriaRESUMO
Os répteis possuem um sistema porta-renal, o qual pode desviar parte do sangue proveniente das porções caudais do corpo aos rins antes que a mesma atinja a circulação sistêmica. Em vista disto, vem sendo aconselhada a administração de medicamentos injetáveis nos membros torácicos, para que se evite a filtração imediata pelo parênquima renal, causando redução do efeito esperado. O objetivo do presente estudo foi comparar aspectos qualitativos e quantitativos da associação de cetamina (30 mg/kg) e xilazina (1 mg/kg), injetada no membro torácico ou pélvico, em jacarés-do-papo-amarelo (Caiman latirostris) juvenis. Oito animais machos com peso médio (±DP) de 1,3 (±0,3) kg e, aproximadamente, dois anos de idade foram anestesiados em duas ocasiões distintas com intervalo de sete dias. Em cada ocasião, os animais receberam, de forma aleatória, a associação anestésica por via intramuscular em membro torácico (tratamento MT) ou pélvico (tratamento MP). Foram avaliados os intervalos de tempo entre a administração do tratamento e a perda do reflexo de endireitamento (período de indução), entre a perda e o retorno desse reflexo (duração do efeito clínico importante) e entre o retorno do reflexo de endireitamento e os primeiros movimentos de deambulação (duração do efeito residual), as frequências cardíaca e respiratória e as temperaturas ambiental e cloacal. Os escores de sedação/anestesia foram avaliados através de uma escala com variação de 0 (alerta/consciente) a 10 (anestesia profunda/sobredosagem). No tratamento MP, dois animais não apresentaram perda de reflexo de endireitamento. Considerando somente aqueles que apresentaram a perda desse reflexo, o tempo de indução (21±9 e 17±5 minutos) e a duração do efeito clínico importante (35±19 e 43±21 minutos) e residual (28±31 e 12±11 minutos) foram similares entre os tratamentos MT e MP (média±desvio padrão). O escore de sedação foi significativamente maior que o basal de 20 a 50 minutos nos dois tratamentos e, aos 30 minutos (pico de efeito), o escore mediano (interquartil) foi 3,5(2,3-4,0) no tratamento MT e 3,0(2,0-4,0) no tratamento MP. Assim como nos escores de sedação, diferenças entre tratamentos nas variáveis fisiológicas não foram observadas. Em ambos os tratamentos, o reflexo de retirada de membro ao pinçamento digital não foi abolido. A administração da associação de xilazina e cetamina em membro pélvico ou torácico de jacarés-do-papo-amarelo juvenis promove efeitos similares, sugerindo que a influência do sistema porta-renal não é clinicamente relevante. Nas doses empregadas, tal protocolo não promove anestesia cirúrgica e a imobilidade/contenção farmacológica é imprevisível e de curta duração.(AU)
Reptiles possess a renal portal system which can divert part of the blood from the caudal portions of the body to the kidney before it reaches the systemic circulation. In view of this, it has been recommended the administration of injectable medications in the forelimbs, in order to avoid immediate glomerular filtration, which might result in a reduction of the expected effect. The aim of this study was to compare qualitative and quantitative aspects of the pharmacological restraint provided by the combination of ketamine (30mg/kg) and xylazine (1mg/kg), injected into the forelimb or hindlimb, in broad-snouted caiman juveniles (Caiman latirostris). Eight male animals, with a mean weight (±SD) of 1.3 (±0.3) kg, and aged about 2 years old, were anesthetized on two separate occasions with an interval of 7 days. On each occasion, the animals were randomly assigned to receive the anesthetic combination intramuscularly into the forelimb (FL treatment) or hindlimb (HL treatment). The time intervals between administration of treatment and loss of the righting reflex (induction time), between the loss and return of this reflex (duration of important clinical effect), and between the return of the righting reflex and first movements of ambulation (duration of residual effect) were measured as well as heart and respiratory rates and cloacal and environmental temperatures. Sedation/anesthesia scores were evaluated using a scale ranging from 0 (alert/conscious) to 10 (deep anesthesia/overdose). In the HL treatment, loss of righting reflex was not observed in two animals. Considering only those animals whose loss of righting reflex was observed, the induction time (21±9 and 17±5 minutes), the duration of important clinical effect (35±19 and 43±21 minutes), and the duration of residual effect (28±31 and 12±11 minutes) were similar between the FL and HL treatments, respectively (mean±SD). Sedation/anesthesia scores were significantly higher than at baseline from 20 to 50 minutes in both treatments and, at 30 minutes (peak sedative effect), the median score (interquartile range) was 3.5(2.3-4.0) in the FL treatment and 3.0(2.0-4.0) in the HL treatment. Differences between treatments in physiological variables were not observed. In both treatments, withdrawal reflex in response to digital clamping was not absent at any timepoint. The administration of xylazine-ketamine combination in the forelimb or hindlimb of broad-snouted caiman juveniles provides similar effects, suggesting that the influence of the renal portal system is not clinically relevant. At the doses used, such combination does not induce surgical anesthesia and the immobility/pharmacological restraint is unpredictable and of short duration.(AU)
Assuntos
Animais , Jacarés e Crocodilos/metabolismo , Anestésicos Dissociativos/efeitos adversos , Ketamina/administração & dosagem , Xilazina/administração & dosagem , Membro Anterior , Pelve , Circulação Renal , Sedação Profunda/veterináriaRESUMO
Several Lippia species have been used in folk medicine mainly for gastrointestinal and respiratory diseases. Their biological properties have been partially associated to the terpenoids found in their essential oils. According to the World Health Organization, cancer is the leading cause of death worldwide and is described as a complex group of diseases with several hallmarks. One of its acceptable defining features is the cell proliferation beyond their boundaries forming the tumors. Importantly, some drugs currently available were discovered by the investigation of plant secondary metabolites. Thus, this study aimed to evaluate in vitro cytotoxic effect of the essential oils extracted from five Lippia species against tumor cell lines. The results indicated that mouse colon carcinoma CT26.WT cell line viability was significantly reduced showing an IC50 of 19.05, 30.20 and 36.30 µg/ml when treated with the essential oils of L. sidoides, L. salviifolia and L. rotundifolia, respectively. Human lung carcinoma A549 cell line also had a compromised viability to the action of L. alba carvone chemotype essential oil. The tested essential oils did not compromise viability of the normal cell line CHO. These finds suggest that the studied Lippia essential oils might be good candidates for further in-depth studies.
RESUMO
Liposome encapsulation of platinum (Pt) drugs has emerged as a promising strategy to overcome their toxicity and cellular Pt resistance. The aim of the present work was to examine the impact of liposome encapsulation of a novel antitumor lipophilic Pt complex, dichloro-(N-dodecyl)-propanediamine-platinum(II) complex (DDPP), on its pharmacological profile as an antitumor agent. Biological assays included acute toxicity and histopathological evaluations, pharmacokinetics, and growth inhibition of B16-F1 tumor cells in C57Bl/6 mice. Comparison was made with cisplatin and free DDPP dissolved in castor oil. DDPP encapsulated in pegylated liposomes showed reduced acute toxicity in mice following intraperitoneal administration, compared with the free complex. Free DDPP at 5 mg Pt/kg induced histopathological alterations in the liver, in contrast to liposomal DDPP and cisplatin. Interestingly, the marked loss of body weight following the treatment of mice with cisplatin was not observed after liposomal DDPP at the same Pt dose. Liposomal DDPP was found to inhibit tumor growth significantly, when administered at 5 mg Pt/kg/day for 3 days, similar to cisplatin, but in contrast to the free complex. Pharmacokinetic studies after intraperitoneal and intravenous administrations at 5 mg Pt/kg indicated greater and more prolonged Pt levels in the plasma, liver, spleen, and kidneys from liposomal DDPP, compared with free DDPP or cisplatin. The tumor concentration of Pt increased after liposomal DDPP over the 24-h period, whereas it decreased after cisplatin. In conclusion, the encapsulation of DDPP in pegylated liposomes reduced the drug toxicity and enhanced its antitumoral activity in mice, as a result of improved drug pharmacokinetics.
Assuntos
Antineoplásicos/administração & dosagem , Lipossomos/administração & dosagem , Compostos Organoplatínicos/administração & dosagem , Animais , Antineoplásicos/química , Antineoplásicos/farmacocinética , Linhagem Celular Tumoral , Cisplatino/farmacocinética , Cisplatino/farmacologia , Portadores de Fármacos/administração & dosagem , Portadores de Fármacos/química , Injeções Intraperitoneais , Lipossomos/química , Masculino , Melanoma Experimental/tratamento farmacológico , Melanoma Experimental/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Neoplasias/tratamento farmacológico , Compostos Organoplatínicos/química , Compostos Organoplatínicos/farmacocinética , Polietilenoglicóis/administração & dosagem , Polietilenoglicóis/química , Distribuição TecidualRESUMO
Previous studies demonstrated that proteinases from latex of C. candamarcensis act as mitogens on fibroblast and epithelial cells and a subsequent report showed their protective, angiogenic and wound healing effects on gastric ulcers. In this study, we present evidence of skin healing activity by the group of proteinases known as P1G10. By using a hairless mouse model, we compared the healing effect following topical application of various concentrations of P1G10. The data confirm that healing actions take place between 0.1 and 1%, without adverse local irritation or systemic toxicological action after a prolonged period of use. The wound healing effect is unaltered when P1G10 is previously inhibited with iodoacetamide. The low permeation of the hydrosoluble formulation Polawax(®) supports the maintenance of the drug at the site of application. These results extend the healing properties of these groups of enzymes in situations of dermatological trauma and open the way to future clinical applications.