RESUMO
Palmitic acid esters of hydroxy stearic acids (PAHSAs) are bioactive lipids with antiinflammatory and antidiabetic effects. PAHSAs reduce ambient glycemia and improve glucose tolerance and insulin sensitivity in insulin-resistant aged chow- and high-fat diet-fed (HFD-fed) mice. Here, we aimed to determine the mechanisms by which PAHSAs improve insulin sensitivity. Both acute and chronic PAHSA treatment enhanced the action of insulin to suppress endogenous glucose production (EGP) in chow- and HFD-fed mice. Moreover, chronic PAHSA treatment augmented insulin-stimulated glucose uptake in glycolytic muscle and heart in HFD-fed mice. The mechanisms by which PAHSAs enhanced hepatic insulin sensitivity included direct and indirect actions involving intertissue communication between adipose tissue and liver. PAHSAs inhibited lipolysis directly in WAT explants and enhanced the action of insulin to suppress lipolysis during the clamp in vivo. Preventing the reduction of free fatty acids during the clamp with Intralipid infusion reduced PAHSAs' effects on EGP in HFD-fed mice but not in chow-fed mice. Direct hepatic actions of PAHSAs may also be important, as PAHSAs inhibited basal and glucagon-stimulated EGP directly in isolated hepatocytes through a cAMP-dependent pathway involving Gαi protein-coupled receptors. Thus, this study advances our understanding of PAHSA biology and the physiologic mechanisms by which PAHSAs exert beneficial metabolic effects.
Assuntos
Resistência à Insulina/fisiologia , Fígado/efeitos dos fármacos , Fígado/metabolismo , Estearatos/farmacologia , Tecido Adiposo Branco/efeitos dos fármacos , Tecido Adiposo Branco/metabolismo , Animais , AMP Cíclico/metabolismo , Dieta Hiperlipídica/efeitos adversos , Glucagon/farmacologia , Técnicas In Vitro , Lipólise/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Modelos Biológicos , Receptores Acoplados a Proteínas G/metabolismo , Transdução de Sinais/efeitos dos fármacos , Estearatos/administração & dosagemRESUMO
A novel hyaluronic acid modified transfersome was prepared to deliver drugs to lymphatics through the transdermal route. Doxorubicin loaded HA-GMS-T was able to efficiently penetrate into the deep skin tissue, leading to enhanced absorption by lymphatics. Most importantly, hyaluronic acid effectively improved the uptake of drug loaded nanocarriers by tumor cells.
Assuntos
Antibióticos Antineoplásicos/administração & dosagem , Doxorrubicina/administração & dosagem , Ácido Hialurônico/administração & dosagem , Nanopartículas/administração & dosagem , Neoplasias/metabolismo , Absorção Cutânea , Administração Cutânea , Animais , Antibióticos Antineoplásicos/química , Antibióticos Antineoplásicos/farmacocinética , Linhagem Celular , Doxorrubicina/química , Doxorrubicina/farmacocinética , Glicerol/administração & dosagem , Glicerol/análogos & derivados , Glicerol/química , Ácido Hialurônico/química , Lipossomos , Fígado/metabolismo , Sistema Linfático/metabolismo , Células MCF-7 , Camundongos , Nanopartículas/química , Neoplasias/tratamento farmacológico , Ratos Wistar , Pele/metabolismo , Estearatos/administração & dosagem , Estearatos/químicaRESUMO
Multidrug resistance (MDR) and drug toxicity are two major factors responsible for the failure of cancer chemotherapy. Herein the efficacy and safety of combination therapy using doxorubicin (Dox, D)-mitomycin C (MMC, M) co-loaded stealth polymer-lipid hybrid nanoparticles (DMsPLNs) were evaluated in sensitive and MDR human mammary tumor xenografts. DMsPLN demonstrated enhanced efficacy compared to liposomal Dox (PLD) with up to a 3-fold increase in animal life span, a 10-20% tumor cure rate, undetectable normal tissue toxicity and decreased tumor angiogenesis. These results suggest DMsPLN have potential as an effective treatment of breast cancer.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias da Mama/tratamento farmacológico , Lipídeos/administração & dosagem , Nanopartículas/administração & dosagem , Animais , Protocolos de Quimioterapia Combinada Antineoplásica/química , Linhagem Celular Tumoral , Doxorrubicina/administração & dosagem , Doxorrubicina/química , Combinação de Medicamentos , Resistência a Múltiplos Medicamentos , Resistencia a Medicamentos Antineoplásicos , Feminino , Humanos , Lipídeos/química , Camundongos , Camundongos Nus , Mitomicina/administração & dosagem , Mitomicina/química , Nanopartículas/química , Polietilenoglicóis/administração & dosagem , Polietilenoglicóis/química , Distribuição Aleatória , Estearatos/administração & dosagem , Estearatos/química , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
A rational development of an efficient siRNA delivery system is important for streamlining the RNAi-based drug development process. However, a huge gap frequently exists between in vitro and in vivo activity, which is the rate-limiting step for developing versatile nanoparticles. We report herein on a remarkable non-linearity in pharmacokinetics (PK), but not pharmacodynamics (PD) using octaarginine (R8) modified lipid nanoparticles in mice. A quantitative study of siRNA molecules between cultured cells and mouse liver revealed a high correlation between intracellular siRNA molecules and their RNAi activities, indicating that there was no significant difference in the efficiency in PD. In contrast, a remarkable difference was observed in the non-linearity in PK. Quantitative analysis of the time profile for siRNA showed that the percentage of siRNA accumulation in mice was severely decreased with decreasing input dose compared to in vitro data. These unexpected data reveal an important clue to bridging the gap between in vitro and in vivo activity.
Assuntos
Nanopartículas/administração & dosagem , Oligopeptídeos/administração & dosagem , RNA Interferente Pequeno/administração & dosagem , Estearatos/administração & dosagem , Animais , Linhagem Celular Tumoral , Feminino , Inativação Gênica , Fígado/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Oligopeptídeos/farmacocinética , Fosfatidiletanolaminas/administração & dosagem , Fosfatidiletanolaminas/farmacocinética , RNA Interferente Pequeno/farmacocinética , Estearatos/farmacocinéticaRESUMO
Gemcitabine is a deoxycytidine analog used in the treatment of various solid tumors. However, tumors often develop resistances over time, which becomes a major issue for most gemcitabine-related chemotherapies. In the present study, a previously reported stearoyl gemcitabine nanoparticle formulation (GemC18-NPs) was evaluated for its ability to overcome gemcitabine resistance. In the wild type CCRF-CEM human leukemia cells, the IC(50) value of GemC18-NPs was 9.5-fold greater than that of gemcitabine hydrochloride (HCl). However, in the CCRF-CEM-AraC-8C cells that are deficient in the human equilibrative nucleoside transporter-1, the IC(50) of GemC18-NPs was only 3.4-fold greater than that in the parent CCRF-CEM cells, whereas the IC(50) of gemcitabine HCl was 471-fold greater than that in the parent CCRF-CEM cells. The GemC18-NPs were also more cytotoxic than gemcitabine HCl in the deoxycytidine kinase deficient (CCRF-CEM/dCK(-/-)) tumor cells. Similar to gemcitabine HCl, GemC18-NPs induced apoptosis through caspase activation. Another gemcitabine-resistant tumor cell line, TC-1-GR, was developed in our laboratory. In the TC-1-GR cells, the IC(50) of GemC18-NPs was only 5% of that of gemcitabine HCl. Importantly, GemC18-NPs effectively controlled the growth of gemcitabine resistant TC-1-GR tumors in mice, whereas the molar equivalent dose of gemcitabine HCl did not show any activity against the growth of the TC-1-GR tumors. Proteomics analysis revealed that the TC-1-GR cells over-expressed ribonucleotide reductase M1, which was likely the cause of the acquired gemcitabine resistance in the TC-1-GR cells. To our best knowledge, this represents the first report demonstrating that a nanoparticle formulation of gemcitabine overcomes gemcitabine resistance related to ribonucleotide reductase M1 over-expression.
Assuntos
Desoxicitidina/análogos & derivados , Farmacorresistência Bacteriana/efeitos dos fármacos , Regulação Enzimológica da Expressão Gênica , Nanopartículas/administração & dosagem , Estearatos/administração & dosagem , Proteínas Supressoras de Tumor/biossíntese , Animais , Linhagem Celular Tumoral , Química Farmacêutica , Desoxicitidina/administração & dosagem , Desoxicitidina/química , Relação Dose-Resposta a Droga , Farmacorresistência Bacteriana/fisiologia , Feminino , Humanos , Camundongos , Camundongos Nus , Nanopartículas/química , Distribuição Aleatória , Ribonucleosídeo Difosfato Redutase , Estearatos/química , GencitabinaRESUMO
Intrathecal delivery of gene therapeutics is a route of administration that overcomes several of the limitations that plague current immunosuppressive treatments for autoimmune diseases of the central nervous system (CNS). Here we report intrathecal delivery of small amounts (3 µg) of plasmid DNA that codes for an immunomodulatory fusion protein, OX40-TRAIL, composed of OX40, a tumor necrosis factor receptor, and tumor necrosis factor related apoptosis inducing ligand (TRAIL). This DNA was delivered in a formulated nucleic acid-lipid complex (lipoplexes) with an asymmetric two-chain cationic lipid myristoyl (14:0) and lauroyl (12:1) rosenthal inhibitor-substituted compound (MLRI) formed from the tetraalkylammonium glycerol-based compound N-(1-(2,3-dioleoyloxy)-propyl-N-1-(2-hydroxy)ethyl)-N,N-dimethyl ammonium iodide. Delivery and expression in the CNS of OX40-TRAIL in the mouse prior to onset of experimental autoimmune encephalomyelitis (EAE), an animal model for multiple sclerosis, decreased the severity of clinical disease. We believe this preclinical demonstration of rapid, widespread, and biologically therapeutic nonviral gene delivery to the CNS is important in further development of clinical lipid-based therapeutics for CNS disorders.
Assuntos
DNA/química , Encefalomielite Autoimune Experimental/terapia , Técnicas de Transferência de Genes , Terapia Genética , Lipídeos/química , Animais , Sistema Nervoso Central/metabolismo , Cisterna Magna , DNA/administração & dosagem , Encefalomielite Autoimune Experimental/metabolismo , Encefalomielite Autoimune Experimental/patologia , Feminino , Expressão Gênica , Genes Reporter , Injeções Espinhais , Lauratos/química , Lipídeos/administração & dosagem , Camundongos , Camundongos Endogâmicos C57BL , Esclerose Múltipla/metabolismo , Esclerose Múltipla/terapia , Miristatos/química , Plasmídeos/administração & dosagem , Plasmídeos/química , Receptores OX40/genética , Receptores OX40/metabolismo , Proteínas Recombinantes de Fusão/metabolismo , Estearatos/administração & dosagem , Estearatos/química , Ligante Indutor de Apoptose Relacionado a TNF/genética , Ligante Indutor de Apoptose Relacionado a TNF/metabolismoRESUMO
Objetivo: avaliar os resultados perinatais do uso profilático de estearato de eritromicina nas pacientesinternadas na unidade de gestação alto risco da Maternidade Carmela Dutra (MCD), FlorianópolisSC, com diagnóstico de ruptura prematura pré-termo de membranas (RPM). Métodos: estudo descritivo com análise de todas as pacientes internadas com o diagnóstico de RPM e com idade gestacional entre 20 semanas e 33 semanas e cinco dias. Foram excluídas da pesquisa gestantes com históriade hipersensibilidade à eritromicina, com sinais clínicos e/ou laboratoriais de corioamnionite, que estavam emtrabalho de parto ou que faziam uso de antibióticos no momento da internação. A amostra obtida entre 1º de abril de 2007 e 15 de maio de 2008 foi de 22 pacientes. Resultados e conclusões: o tempo médio de latência foi de 12 dias. Não houve casos confirmados decorioamnionite. Uma (4,54%) gestante desenvolveu quadro de endometrite puerperal. Não houve óbitos maternos. Dois (9,09%) recém-nascidos desenvolveram sepse. A taxa de óbito neonatal foi de 13,63%. Apesarda nossa pequena casuística, o uso de eritromicina nas pacientes com RPM parece estar associado a umadiminuição na taxa de corioamnionite.
Objective: The purposes of this study were to evaluate perinatal results of the prophylactic use of erythromycin to patients admitted in the high-riskgestation unit at Carmela Dutra Maternity Hospital, Florianópolis SC with preterm premature rupture ofmembranes (PROM). Methods: We performed a descriptive analysis ofall patients with PROM and gestational age between 20 weeks and 33 weeks plus 5 days. Patients with erythromycin allergy, with chorioamnionitis signs orwomen who already being prescribed antibiotics were excluded from this study. Enrolment was from April 1,2007, until May 15, 2008. Twenty-two women had been followed up in this study. Results and Conclusions: The medium latency period was 12 days. There was not confirmed chorioamnionitis case. The occurrence of endometritis was 4,54%. There was not maternal death. The occurrence of neonatal sepsis was 9,09% and theoccurrence of neonatal deaths was 13,63%. Despite our small casuistry, the prophylactic use of erythromycinseems to reduce the chorioamnionitis rate.
Assuntos
Humanos , Feminino , Gravidez , Recém-Nascido , Antibioticoprofilaxia , Eritromicina , Ruptura Prematura de Membranas Fetais , Gravidez de Alto Risco , Estearatos , Antibioticoprofilaxia/estatística & dados numéricos , Antibioticoprofilaxia/métodos , Antibioticoprofilaxia/mortalidade , Antibioticoprofilaxia , Eritromicina/metabolismo , Eritromicina , Eritromicina/uso terapêutico , Estearatos/administração & dosagem , Estearatos , Estearatos/farmacocinética , Estearatos/uso terapêutico , Gravidez de Alto Risco/fisiologia , Gravidez de Alto Risco/metabolismo , Ruptura Prematura de Membranas Fetais/diagnóstico , Ruptura Prematura de Membranas Fetais/mortalidade , Ruptura Prematura de Membranas Fetais/prevenção & controleRESUMO
BACKGROUND: Gemcitabine is a deoxycytidine analogue that exhibits antitumoral activity against adenocarcinomas of the colon, lung and pancreas. After intravenous injection, gemcitabine is rapidly converted to the inactive metabolite 2'-deoxy-2',2'-difluorouridine by cytidine deaminase. MATERIALS AND METHODS: To improve the pharmacokinetic behavior and the antitumor activity of the drug, the gemcitabine prodrug, 4-(N)-stearoylgemcitabine (C18gem) was incorporated in liposomes and both the pharmacokinetic and the in vivo activity of this formulation intravenously or peritumorally administered in nude female CR1:Nu/Nu(CD-1)BR mice grafted with HT-29 and KB 396p cells were studied. RESULTS: The C18gem-liposomes showed both higher plasma half life and tumor regression than control and gemcitabine. CONCLUSION: The incorporation of C18gem-prodrug in liposomes increased the plasma half life of the drug resulting in increased accumulation in the tumor cells and a higher level of antitumoral efficacy. The results obtained with different tumors sensitive to gemcitabine support the efficacy of this proposed drug delivery system.
Assuntos
Antimetabólitos Antineoplásicos/administração & dosagem , Desoxicitidina/análogos & derivados , Pró-Fármacos/administração & dosagem , Pró-Fármacos/farmacocinética , Animais , Antimetabólitos Antineoplásicos/farmacocinética , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/metabolismo , Desoxicitidina/administração & dosagem , Desoxicitidina/farmacocinética , Feminino , Células HT29 , Humanos , Lipossomos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Neoplasias Nasofaríngeas/tratamento farmacológico , Neoplasias Nasofaríngeas/metabolismo , Estearatos/administração & dosagem , Estearatos/farmacocinética , Ensaios Antitumorais Modelo de Xenoenxerto , GencitabinaRESUMO
BACKGROUND: We used a novel lipopolymeric gene delivery system, TeplexDNA, to transfect myocardium with plasmid vascular endothelial growth factor-165 (pVEGF) and evaluated the ability of pVEGF to preserve left ventricular function and structure after coronary ligation in a rabbit model. METHODS: New Zealand white rabbits underwent circumflex coronary ligation after direct intramyocardial injection of either Terplex alone or Terplex + 50 microg pVEGF-165. Serial echocardiography and histologic studies were performed (n = 12/group). Mortality did not differ between groups. The data is reported as the mean +/- standard deviation. RESULTS: Over the 21 days following coronary ligation, pVEGF-165-treated animals demonstrated significant improvement in fractional shortening (20-25%, p = 0.02), long axis two-dimensional ejection fraction (42-51%, p=0.02) and short axis m-mode ejection fraction (46-54%, p = 0.02). No significant improvements were noted in the control group. VEGF-treated animals had a 50% increase in peri-infarct vessel density and a trend towards a smaller infarct size (20% vs. 29%, p = 0.10). In animals receiving pVEGF-165, the diastolic ventricular area increased from 1.87 +/- 0.24 cm2 prior to ligation to 2.19 +/- 0.23 cm2 at 21 days following ligation, compared to an increase from 1.84 +/- 0.38 to 2.54 +/- 0.55 cm2 over the same period in control animals (p = 0.03). Similarly, the systolic ventricular area in VEGF-165 animals increased from 1.06 +/- 0.26 cm2 prior to ligation to 1.50 +/- 0.29 cm2 at 21 days following ligation, compared to an increase from 1.16 +/- 0.30 to 1.86 +/- 0.43 cm2 over the same period in the control animals (p = 0.04). CONCLUSION: TerplexDNA mediated delivery of plasmid VEGF administered at the time of coronary occlusion improves left ventricular function and reduces left ventricular dilation following myocardial infarction.
Assuntos
DNA/genética , Terapia Genética/métodos , Ventrículos do Coração/efeitos dos fármacos , Infarto do Miocárdio/terapia , Fator A de Crescimento do Endotélio Vascular/genética , Fatores de Crescimento do Endotélio Vascular/genética , Fatores de Crescimento do Endotélio Vascular/farmacocinética , Animais , Doença das Coronárias/complicações , Doença das Coronárias/tratamento farmacológico , Doença das Coronárias/fisiopatologia , Vasos Coronários/lesões , Vasos Coronários/fisiopatologia , DNA/administração & dosagem , DNA/farmacocinética , Avaliação Pré-Clínica de Medicamentos , Ecocardiografia , Vetores Genéticos/administração & dosagem , Vetores Genéticos/farmacocinética , Ventrículos do Coração/anatomia & histologia , Lipídeos/administração & dosagem , Lipídeos/química , Lipídeos/farmacocinética , Lipoproteínas LDL/administração & dosagem , Lipoproteínas LDL/genética , Lipoproteínas LDL/farmacocinética , Infarto do Miocárdio/mortalidade , Infarto do Miocárdio/fisiopatologia , Plasmídeos/administração & dosagem , Plasmídeos/genética , Plasmídeos/farmacocinética , Polilisina/administração & dosagem , Polilisina/genética , Polilisina/farmacocinética , Polímeros/administração & dosagem , Polímeros/química , Polímeros/farmacocinética , Coelhos , Estearatos/administração & dosagem , Estearatos/farmacocinética , Volume Sistólico/efeitos dos fármacos , Volume Sistólico/fisiologia , Fatores de Tempo , Fator A de Crescimento do Endotélio Vascular/administração & dosagem , Fator A de Crescimento do Endotélio Vascular/farmacocinética , Fatores de Crescimento do Endotélio Vascular/administração & dosagem , Função Ventricular , Função Ventricular Esquerda/efeitos dos fármacos , Função Ventricular Esquerda/fisiologiaRESUMO
A new DNA delivery vector (the terplex system) based on a balanced hydrophobicity and net surface charge between stearyl-poly(L-lysine), low density lipoprotein (LDL), and genetic material (i.e. plasmid DNA or antisense oligonucleotide) was developed. The pSV-beta-gal plasmid in terplex system showed a 2-5-fold increase in beta-galactosidase expression on murine smooth muscle cells (A7R5) compared to Lipofectin. Delivery of unmodified c-myb antisense oligonucleotide to A7R5 cells was also facilitated significantly by the terplex system, requiring as little as 5.4 nM of antisense oligonucleotide to achieve a 50% antiproliferative effect. Similar antiproliferative effect was observed when the c-myb antisense/terplex formulation was tested on CCD-32 Lu human lung fibroblasts. Characterization of the physical properties of the terplex system was performed using various techniques. Plasmid DNA was condensed by addition of stearyl-PLL and LDL, resulting in the terplex system of about 100 nm in diameter as shown by atomic force microscopy. A strong hydrophobic interaction between stearyl-poly(L-lysine) and LDL was registered by 1H-NMR spectrometry, showing a significant decrease in the epsilon-methylene signal of poly(L-lysine) backbone when stearyl-poly(L-lysine) was mixed with LDL; however, this phenomenon was not observed with unmodified poly(L-lysine). Agarose gel electrophoresis revealed that electrophoretic mobility of the terplex system decreased with increasing amounts of stearyl-poly(L-lysine), indicating that the surface charge of the terplex system became more positive by addition of stearyl-poly(L-lysine). Zeta-potential measurement showed that the terplex system exerted a slightly positive charge (+2 mV) at a 1:1:1 weight ratio of plasmid DNA:LDL:stearyl-poly(L-lysine). The obtained results will be utilized in the design of more efficient and safer DNA delivery vectors for in vivo gene therapy.
Assuntos
DNA/administração & dosagem , Vetores Genéticos , Lipoproteínas LDL/administração & dosagem , Oligonucleotídeos Antissenso/administração & dosagem , Polilisina/administração & dosagem , Estearatos/administração & dosagem , Animais , Sequência de Bases , Linhagem Celular , Eletroforese em Gel de Ágar , Humanos , Lipoproteínas LDL/química , Camundongos , Microscopia de Força Atômica , Oligonucleotídeos Antissenso/química , Plasmídeos , Polilisina/química , Proteínas Proto-Oncogênicas/genética , Proteínas Proto-Oncogênicas c-myb , Eletricidade Estática , Estearatos/química , Transativadores/genéticaRESUMO
We prospectively studied the effect of a foam composite containing glycerin, propylene glycol, polyol, stearine, stearate and silicone oil, which is known to form a temporary barrier layer when applied to epithelial surface, on adhesion prevention in rats. The small intestine abrasion model was used for creation of adhesions. Sixty male Sabra rats of a mean weight of 295 +/- 23 g were randomly assigned into four groups: group 1 (n = 20) underwent laparotomy and abrasion; group 2 (n = 20) underwent laparotomy, abrasion and intraperitoneal instillation of the foam composite; group 3 (n = 10) underwent laparotomy with abrasion and a second laparotomy with adhesiolysis 2 weeks later; and group 4 (n = 10), was treated in the same way as group 3 but during the second laparotomy the foam composite was instilled intraperitoneally. All animals were relaparotomized 2 weeks (groups 1 and 2) and 4 weeks (groups 3 and 4) after the initial laparotomy for adhesion scoring performed by a blinded independent investigator using the standard 0-3 adhesion grading score. Representative specimens of small intestine and liver from animals in groups 2 and 4 were analyzed. A significantly lower mean adhesion score was noted in group 2 (1.15 +/- 0.3) compared with that of group 1 (2.65 +/- 0.1) or group 3 (2.60 +/- 0.1) (P < 0.01). Group 4 had a significantly lower score (1.4 +/- 0.3) than group 3 or group 1 (P < 0.05). There was no significant difference in the mean adhesion score between groups 1 and 3. Histological examination revealed no evidence of residual foam composite or adverse reaction to its use in the intestine and liver. The foam composite tested may reduce the severity of intestinal adhesions after laparotomy and may also reduce the severity of recurrent adhesions after adhesiolysis. Intraperitoneal use of this composite is safe in rats. The exact mechanism of action is unclear but may be related to the formation of a temporary microlayer that coats the injured surface of the intestine and facilitates healing without adhesion formation. Further investigation is needed to evaluate its full potential.
Assuntos
Enteropatias/prevenção & controle , Aderências Teciduais/prevenção & controle , Animais , Modelos Animais de Doenças , Glicerol/administração & dosagem , Injeções Intraperitoneais , Enteropatias/etiologia , Intestino Delgado , Laparotomia/efeitos adversos , Lubrificação , Masculino , Polímeros/administração & dosagem , Propilenoglicol/administração & dosagem , Estudos Prospectivos , Ratos , Óleos de Silicone/administração & dosagem , Estearatos/administração & dosagem , Aderências Teciduais/etiologiaRESUMO
Male Sprague-Dawley rats were fed semipurified diets containing 12% fat and 0.4% cholesterol for 4 wk. The fats were palm oil, a high-stearate fat and canola oil; each of the latter two fat sources was substituted for palm oil in 4% (w/w) increments (i.e, 4, 8 and 12%) thus yielding 3 stearate-containing, 3 canola-containing, and a 12% palm oil diet. Stearate-fed animals exhibited significantly decreased food efficiency ratios, plasma total cholesterol, and liver cholesterol whereas the substitution of canola for palm oil did not consistently alter these parameters. Liver fatty acids generally reflected the composition of the dietary fat sources with the exception of significantly higher arachidonate observed in the stearate-fed rats.
Assuntos
Gorduras na Dieta/farmacologia , Ácidos Graxos Monoinsaturados/farmacologia , Lipídeos/análise , Fígado/metabolismo , Estearatos/farmacologia , Animais , Peso Corporal/efeitos dos fármacos , Colesterol/análise , Colesterol/sangue , Gorduras na Dieta/administração & dosagem , Gorduras na Dieta/metabolismo , Ingestão de Alimentos/efeitos dos fármacos , Ácidos Graxos Monoinsaturados/administração & dosagem , Lipídeos/sangue , Masculino , Óleo de Palmeira , Óleos de Plantas/administração & dosagem , Óleos de Plantas/farmacologia , Óleo de Brassica napus , Ratos , Ratos Sprague-Dawley , Estearatos/administração & dosagem , Triglicerídeos/sangueRESUMO
The medical and nursing literature suggests a wide variety of pharmacological and nonpharmacological approaches to treatment of acute radiation skin damages (erythema, dry and moist desquamation, ulceration), but no specific and standardized therapy. The incidence of radiodermatitis has decreased with mega-voltage instruments, but it can nevertheless influence the therapeutic program and impair quality of life of patients. A study has been conducted to evaluate the tolerability and effectiveness of a nonpharmacological remedy, a mixture of hydrophobic (stearic acid) and hydrophilic (propylene glycol, glycerol, and polyunsaturated alcohols) components in a foam emulsion for the treatment of acute skin injuries following radiotherapy. Thirty-eight of 42 initial patients were evaluable: we observed a complete response in 22 (57.9%), improvement in 14 (36.8%), and failure in only two (5.3%).