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1.
Food Chem ; 438: 137863, 2024 Apr 16.
Article in English | MEDLINE | ID: mdl-37980871

ABSTRACT

Unripe tomatoes are among the main waste produced during tomato cultivation and processing. In this study, unripe tomatoes from seven different Italian cultivars have been investigated to evaluate their nutraceutical potential. Phytochemical investigation allowed shedding light on the identification of seventy-five bioactive compounds. The highest amount of polyphenolic and glycoalkaloids along with the high level of antioxidant activities was found in the Datterini tomatoes variety. The peculiarity of this variety is the high chlorogenic acid content, being ten times higher compared to the other cultivars examined. Moreover, the total α-tomatine amount has been found substantially higher (34.699 ± 1.101 mg/g dry weight) with respect to the other tomato varieties analyzed. Furthermore, the cultivars metabolomic profiles were investigated with the PCA approach. Based on Datterini cultivar's metabolomic profile, its waste-recovery could represent a good option for further added value products in pharmaceutical and nutraceutical areas with a high α-tomatine content.


Subject(s)
Antioxidants , Solanum lycopersicum , Antioxidants/chemistry , Chlorogenic Acid , Phytochemicals , Plant Extracts/chemistry
2.
Cad. Saúde Pública (Online) ; 38(7): e00272421, 2022. tab, graf
Article in English | LILACS | ID: biblio-1384278

ABSTRACT

The Brazilian government shares the responsibility of financing public health among federal, state, and municipal levels. Health expenditures are thus uneven across the country and cannot contribute equally to health outcomes across disease categories. This study aims to identify how the health expenditures of municipalities affect the mortality rate in the state of Paraná by causa mortis. We considered years of life lost for each municipality, the chapters of the International Classification of Diseases (10th revision), and the elasticity of this measure in relation to public health expenditure. Considering the possibility of endogeneity, this study follows the instrumental variable approach in a panel of generalized method of moments - instrumental variable (GMM-IV) with fixed effects. Our results show that a 1% increase in health expenditure could decrease the average number of years lost specifically for some causes from 0.176% to 1.56% at the municipal level. These findings could elucidate policy perspective within state finance.


O financiamento da saúde pública é uma responsabilidade compartilhada entre as três esferas governamentais brasileiras, i.e., a federal, estadual e municipal. Logo, gastos divergem pelo território e não se poderia esperar que contribuíssem de forma homogênea para os desfechos de saúde em todos os tipos de doença. Este artigo busca identificar como gastos municipais afetam a taxa de mortalidade no Estado do Paraná dado sua causa mortis. Consideramos anos de vida perdidos para cada município, os capítulos da Classificação Internacional de Doenças (10ª revisão) e estimamos a elasticidade dessa medida em relação aos gastos públicos em saúde. Considerando uma possível endogeneidade, este artigo segue a abordagem variável instrumental em um painel de método generalizado de momentos (GMM-IV) com efeitos fixos. Nossos resultados mostram que um aumento de 1% nos gastos municipais com saúde pode diminuir o número médio de anos perdidos entre 0,176% e 1,56% para algumas causas especificas de mortalidade. Nosso estudo pode lançar alguma luz sobre a perspectiva política das finanças dos estados.


La financiación de la salud pública es una responsabilidad compartida entre las tres esferas del gobierno brasileño, a nivel federal, estatal y municipal. En este sentido, los gastos son desiguales en el territorio, y no se puede esperar que contribuyan de forma homogénea a los resultados de salud en las distintas categorías de enfermedades. La función de este trabajo es identificar cómo los gastos de los municipios afectan a la tasa de mortalidad en el Estado de Paraná, por causa mortis. Se consideraron los años de vida perdidos para cada municipio, los capítulos de la Clasificación Internacional de Enfermedades (10ª revisión), y se estimó la elasticidad de esta medida en relación con el gasto sanitario público. Teniendo en cuenta la posibilidad de endogeneidad, este trabajo sigue el enfoque de variables instrumentales en un panel de los método generalizado de momentos (GMM-IV) con efectos fijos. Nuestros resultados muestran que un aumento del 1% en el gasto sanitario puede disminuir el número medio de años perdidos específicamente por algunas causas del 0,176% al 1,56%, a nivel municipal. Esto puede arrojar algo de luz sobre la perspectiva política dentro de las finanzas de los estados.


Subject(s)
Humans , Health Expenditures , Financing, Government , Brazil , Cities , Government
3.
Porto Alegre; s.n; 2021. s.p
Monography in Portuguese | Coleciona SUS | ID: biblio-1254421

ABSTRACT

Sendo a Atenção Básica a porta de entrada no Sistema Único de Saúde do Brasil e a coordenadora do cuidado em rede, esta pesquisa foi feita acerca do perfil dos imigrantes e refugiados pertencentes ao território adstrito a uma unidade de atenção primária do Serviço de Saúde Comunitária do Grupo Hospitalar Conceição (GHC), em Porto Alegre - RS, por meio de um estudo descritivo transversal. Trouxe dados quantitativos do sistema de informações eletrônicas do GHC e relatos de experiência de atendimentos a essa população. O acesso foi classificado em três categorias: usuários que não acessaram a unidade, que acessaram o serviço multiprofissional e que acessaram o serviço de odontologia. Dos 29 imigrantes cadastrados na unidade, oito não foram atendidos na Atenção Básica. A maioria são homens com idades entre 30 e 51 anos. O país de maior emigração é o Senegal. As razões pela procura, tanto de saúde geral, quanto de saúde bucal,são em sua maioria relacionadas a questões agudas, com dores musculares, problemas digestivos e dores de origem orofaciais e odontogênicas. Apesar das barreiras previstas e relatadas em experiências de atendimento, pode-se inferir o estabelecimento do vínculo, embora com dificuldades, pois algumas consultas são por rotina, manutenção, acompanhamento, retorno, e finalização de tratamentos realizados na atenção secundária. Conclui-se que as atuais políticas públicas no país poderiam ser suficientes para abranger a população imigrante e refugiada. A Estratégia da Saúde da Família pode ser uma maneira muito eficiente de conhecer, vincular e assistir essa população. A saúde geral e bucal ainda são vistas de maneira sintomática, tratando apenas a dor. Novas maneiras de educação em saúde devem ser exploradas, associando a formação profissional à comunicação com a população. Políticas públicas de acesso para essa população devem ser estabelecidas a fim de aprimorar o cuidado.(AU)


Subject(s)
Humans , Male , Female , Primary Health Care , Refugees , Unified Health System , Public Health , Emigrants and Immigrants
4.
Food Chem ; 276: 1-8, 2019 Mar 15.
Article in English | MEDLINE | ID: mdl-30409571

ABSTRACT

Edible berries are good sources of several phytochemicals. However, the native folate levels in berries are not well known. The structure of native folates contains polyglutamyl chains, which reportedly jeopardize the bioavailability of native folates; further γ-glutamyl hydrolase (GGH) can deglutamylate polyglutamyl chains. In this study we use a validated ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method to determine the distribution of polyglutamyl 5-methyltetrahydrofolate (5-CH3THF-Glun), folate vitamers, and total folates in different berries and to monitor changes in their concentration during processing of berries into juice. The pre-boiling treatment was optimized during extraction to stabilize the native polyglutamyl folates profile and facilitate folate extraction, which can replace the traditional di-enzyme treatment process. Additionally, the efficiency of commercially available human recombinant GGH was tested and it was found that a 10 µg GGH/mL extract at a pH of 6 could completely deconjugate polyglutamyl folates into monoglutamyl folates when incubated for 30 min. Pure human recombinant GGH with a higher catalytic efficiency and stable enzymatic properties was better than traditional folate conjugase for this purpose. From experimental analysis, it could be inferred that strawberries and blackberries contained the highest amount of total folates (93-118 µg/100 g), while the total folate contents in blueberries were the lowest. Most of the investigated berries are good to excellent folate sources. This study is the first time that 5-CH3THF-Glun and distribution of folate vitamers in various berries are quantitated. Further, this is the first study to show the application of recombinant pure GGH for the deconjugation of polyglutamyl folates for folate vitamers and total folates analysis.


Subject(s)
Food Analysis/methods , Fruit and Vegetable Juices/analysis , Fruit/chemistry , Tandem Mass Spectrometry , Tetrahydrofolates/analysis , Chromatography, High Pressure Liquid , Humans
5.
Food Chem ; 249: 104-110, 2018 May 30.
Article in English | MEDLINE | ID: mdl-29407912

ABSTRACT

This investigation aims to evaluate the effects of high hydrostatic pressure (HHP) applied prior to germination on functionality and quality of wholegrain-germinated brown rice (GBR). Wholegrain brown rice (WBR) were firstly stressed by HHP treatments (50-350 MPa/20 min), and then incubated at 37 °C to obtain GBR grains after a 2-day soaking period. Gama-aminobutyric acid contents significantly depended on the pressure applied, showing 25% increment in 50 MPa-stressed grains compared to the control. HHP shock led to significantly improved in vitro starch digestibility, which was related to the transformation of crystalline starch granules into amorphous form as consistently revealed by scanning electron microscope imaging and Fourier-transform infrared spectroscopy. HHP-pretreated samples achieved markedly enhanced storability by influencing kinetic curves of lipid hydrolysis and oxidation. These results suggested that metabolic response to HHP during germination could significantly improve functional and quality characteristics of WBR products.


Subject(s)
Oryza/chemistry , Seeds/growth & development , Germination , Hydrostatic Pressure , Oryza/growth & development , Oryza/metabolism , Quality Control , Seeds/chemistry , Seeds/metabolism , Starch/chemistry , Starch/metabolism , Whole Grains/chemistry , Whole Grains/growth & development , Whole Grains/metabolism
6.
J Pharmacol Toxicol Methods ; 88(Pt 1): 56-63, 2017 Nov.
Article in English | MEDLINE | ID: mdl-28712933

ABSTRACT

INTRODUCTION: Unanticipated effects on the central nervous system are a concern during new drug development. A larval zebrafish locomotor assay can reveal seizure liability of experimental molecules before testing in mammals. Relative absorption of compounds by larvae is lacking in prior reports of such assays; having those data may be valuable for interpreting seizure liability assay performance. METHODS: Twenty-eight reference drugs were tested at multiple dose levels in fish water and analyzed by a blinded investigator. Responses of larval zebrafish were quantified during a 30min dosing period. Predictive metrics were calculated by comparing fish activity to mammalian seizure liability for each drug. Drug level analysis was performed to calculate concentrations in dose solutions and larvae. Fifteen drug candidates with neuronal targets, some having preclinical convulsion findings in mammals, were tested similarly. RESULTS: The assay has good predictive value of established mammalian responses for reference drugs. Analysis of drug absorption by larval fish revealed a positive correlation between hyperactive behavior and pro-convulsive drug absorption. False negative results were associated with significantly lower compound absorption compared to true negative, or true positive results. The predictive value for preclinical toxicology findings was inferior to that suggested by reference drugs. DISCUSSION: Disproportionately low exposures in larvae giving false negative results demonstrate that drug exposure analysis can help interpret results. Due to the rigorous testing commonly performed in preclinical toxicology, predicting convulsions in those studies may be more difficult than predicting effects from marketed drugs.


Subject(s)
Absorption, Physiological , Biological Assay/methods , Drug Evaluation, Preclinical/methods , Seizures/chemically induced , Zebrafish/physiology , Animals , Biological Assay/instrumentation , Dose-Response Relationship, Drug , Drug Evaluation, Preclinical/instrumentation , False Negative Reactions , Larva/drug effects , Maximum Tolerated Dose , Models, Animal , Neurons/drug effects , Predictive Value of Tests
7.
Phytomedicine ; 23(12): 1475-1483, 2016 Nov 15.
Article in English | MEDLINE | ID: mdl-27765368

ABSTRACT

BACKGROUND: Hepatic steatosis (HS) is the early stage of nonalcoholic fatty liver disease which is caused by impaired hepatic lipid homeostasis. Cyclocarya paliurus, an herbal tea consumed in China, has been demonstrated to ameliorate abnormal lipid metabolism for the treatment of metabolic diseases. PURPOSE: We aimed to investigate the regulative effect of chloroform extract from Cyclocarya paliurus (ChE) on treatment of HS, as well as key factors involved in hepatic lipid metabolism. STUDY DESIGN: Sprague Dawley rats were fed with high-fat diet (HFD) for 6 weeks to induce HS and treated with or without ChE by gavage for 4 weeks. METHODS: The body weight, relative liver weight and liver fat content were measured. Serum and liver total cholesterol, triglyceride and non-esterified fatty acids, as well as hepatic malonaldehyde levels were accessed by biochemical methods. Serum and liver TNF-α levels were quantified by ELISA kit. Histologic analysis and 1H-MRS study were performed to evaluate HS level. RT-PCR and Western blot were also applied to observe the expression changes of key factors involved in hepatic lipid intake, synthesis, utilization and export. RESULTS: ChE significantly decreased the rats' body weight, serum lipid and TNF-α level. ChE also reduced their relative liver weight, liver fat content, hepatic oxidative products and TNF-α level. Hepatic steatosis in HFD-fed rats was effectively regressed after 2-weeks administration of ChE. Moreover, ChE treatment remarkably reduced HFD-induced high expression level of fatty acid synthesis genes (including sterol-regulatory element-binding protein 1, acetyl-CoA carboxylase 1 and fatty acid synthase). However, it had no effect on mRNA expression of some genes involved in lipid uptake, ß-oxidation and lipid outflow. CONCLUSION: ChE exerted a promising regression effect on HS due to a reduced level of serum non-esterified fatty acids which might lead to a decrease in the amount of lipid taken in by the liver, as well as owing to the inhibition of hepatic lipid de novo synthesis to reduce liver lipid production.


Subject(s)
Diet, High-Fat , Juglandaceae , Lipogenesis/drug effects , Liver/drug effects , Non-alcoholic Fatty Liver Disease/drug therapy , Acetyl-CoA Carboxylase/metabolism , Animals , China , Cholesterol/blood , Fatty Acid Synthases/metabolism , Fatty Acids, Nonesterified/metabolism , Lipids/blood , Liver/metabolism , Liver/pathology , Male , Non-alcoholic Fatty Liver Disease/etiology , Non-alcoholic Fatty Liver Disease/pathology , Rats, Sprague-Dawley , Sterol Regulatory Element Binding Protein 1/metabolism , Triglycerides/blood , Tumor Necrosis Factor-alpha/metabolism
8.
J Control Release ; 241: 57-67, 2016 11 10.
Article in English | MEDLINE | ID: mdl-27620073

ABSTRACT

Parasite proteins exported to the surface of Plasmodium falciparum-parasitized red blood cells (pRBCs) have a major role in severe malaria clinical manifestation, where pRBC cytoadhesion and rosetting processes have been strongly linked with microvascular sequestration while avoiding both spleen filtration and immune surveillance. The parasite-derived and pRBC surface-exposed PfEMP1 protein has been identified as one of the responsible elements for rosetting and, therefore, considered as a promising vaccine candidate for the generation of rosette-disrupting antibodies against severe malaria. However, the potential role of anti-rosetting antibodies as targeting molecules for the functionalization of antimalarial drug-loaded nanovectors has never been studied. Our manuscript presents a proof-of-concept study where the activity of an immunoliposomal vehicle with a dual performance capable of specifically recognizing and disrupting rosettes while simultaneously eliminating those pRBCs forming them has been assayed in vitro. A polyclonal antibody against the NTS-DBL1α N-terminal domain of a rosetting PfEMP1 variant has been selected as targeting molecule and lumefantrine as the antimalarial payload. After 30min incubation with 2µM encapsulated drug, a 70% growth inhibition for all parasitic forms in culture (IC50: 414nM) and a reduction in ca. 60% of those pRBCs with a rosetting phenotype (IC50: 747nM) were achieved. This immunoliposomal approach represents an innovative combination therapy for the improvement of severe malaria therapeutics having a broader spectrum of activity than either anti-rosetting antibodies or free drugs on their own.


Subject(s)
Antibodies, Protozoan/immunology , Antigens, Protozoan/immunology , Antimalarials/administration & dosage , Erythrocytes/parasitology , Plasmodium falciparum/drug effects , Protozoan Proteins/immunology , Rosette Formation , Antimalarials/pharmacology , Cells, Cultured , Humans , Liposomes , Plasmodium falciparum/immunology
9.
Fitoterapia ; 113: 35-43, 2016 Sep.
Article in English | MEDLINE | ID: mdl-27373875

ABSTRACT

Ajuga chamaepitys (L.) Schreb, well-known as Camaepitium or Ground Pine, is an annual herb typical of the Mediterranean area accounting several uses in the traditional medicine. In this work we have, analyzed the plant iridoid fraction together with the essential oil composition and study of the plant indumentum. Finally, we assayed the polar extracts and essential oil obtained from the aerial parts for antioxidant activity and cytotoxicity on tumor cells. The analysis of the monoterpene glycosides allowed us to isolate from roots and aerial parts and to structurally elucidate by NMR and MS the following compounds: ajugoside (1), reptoside (2), 8-O-acetylharpagide (3), harpagide (4), 5-O-ß-d-glucopyranosyl-harpagide (5), asperulosidic acid (6), deacetyl asperulosidic acid (7) and 5-O-ß-d-glucopyranosyl-8-O-acetylharpagide (8), among which 5 and 8 were two new natural products. Chemotaxomic relevance of these constituents was discussed. The chemical analysis of A. chamaepitys essential oil by GC-FID and GC-MS showed ethyl linoleate (13.7%), germacrene D (13.4%), kaurene (8.4%), ß-pinene (6.8%), and (E)-phytol (5.3%) as the major volatile components. The micromorphological and histochemical study showed that iridoids and essential oil are mainly produced in the type III capitates and peltate trichomes of leaves and flowers. Biological evaluations of A. chamaepitys polar extracts and essential oil showed that the former were more potent as radical scavengers than the latter. MTT assay revealed that essential oil and ethanolic extracts were moderately cytotoxic on tumor cells with IC50 of 36.88 and 59.24µg/mL on MDA-MB 231 cell line, respectively, and IC50 of 60.48 and 64.12µg/mL on HCT116, respectively.


Subject(s)
Ajuga/chemistry , Iridoid Glycosides/chemistry , Oils, Volatile/chemistry , Plant Oils/chemistry , Pyrans/chemistry , Antineoplastic Agents, Phytogenic/chemistry , Antineoplastic Agents, Phytogenic/isolation & purification , Cell Line, Tumor , Free Radical Scavengers/chemistry , Free Radical Scavengers/isolation & purification , Humans , Iridoid Glycosides/isolation & purification , Plant Extracts/chemistry , Pyrans/isolation & purification , Trichomes/chemistry , Volatile Organic Compounds/chemistry , Volatile Organic Compounds/isolation & purification
10.
Fitoterapia ; 113: 69-73, 2016 Sep.
Article in English | MEDLINE | ID: mdl-27425447

ABSTRACT

Three new triterpenoids, triregelolides A, B (1, 2), and triregeloic acid (3), were isolated from the stems of Tripterygium regelii along with twenty known triterpene analogues (4-23). The structures of three new compounds were identified by analyzing their NMR spectroscopic and HRESIMS data. Compounds 4, 7, 8, 10, 13, 14, 17, 21-23 were isolated from T. regelii for the first time. Compounds 3, 5, 6, 8, 9, 10, 14 and 16 showed inhibitory effects on the proliferation of human breast cancer cells MCF-7 by 24.1%, 69.6%, 72.8%, 21.6%, 23.1%, 43.3%, 25.5% and 23.5% (p<0.05) at a concentration of 10µM, respectively.


Subject(s)
Plant Stems/chemistry , Tripterygium/chemistry , Triterpenes/chemistry , Antineoplastic Agents, Phytogenic/chemistry , Antineoplastic Agents, Phytogenic/isolation & purification , Cell Line, Tumor , Humans , Molecular Structure , Plant Extracts/chemistry , Triterpenes/isolation & purification
11.
Eur J Pharm Sci ; 85: 123-31, 2016 Mar 31.
Article in English | MEDLINE | ID: mdl-26883760

ABSTRACT

Tilianin is attracting considerable attention because of its antihypertensive, anti-atherogenic and anticonvulsive efficacy. However, tilianin has poor oral bioavailability. Thus, to improve the oral bioavailability of tilianin, composite phospholipid liposomes were adopted in this work as a novel nanoformulation. The aim was to develop and formulate tilianin composite phospholipid liposomes (TCPLs) through ethanol injection and to apply the response surface-central composite design to optimize the tilianin composite phospholipid liposome formulation. The independent variables were the amount of phospholipids (X1), amount of cholesterol (X2) and weight ratio of phospholipid to drug (X3); the depended variables were particle size (Y1) and encapsulation efficiency (EE) (Y2) of TCPLs. Results indicated that the optimum preparation conditions were as follows: phospholipid amount, 500 mg, cholesterol amount, 50mg and phospholipid/drug ratio, 25. These variables were also the major contributing variables for particle size (101.4 ± 6.1 nm), higher EE (90.28% ± 1.36%), zeta potential (-18.3 ± 2.6 mV) and PDI (0.122 ± 0.027). Subsequently, differential scanning calorimetry techniques were used to investigate the molecular interaction in TCPLs, and the in vitro drug release of tilianin and TCPLs was investigated by the second method of dissolution in the Chinese Pharmacopoeia (Edition 2015). Furthermore, pharmacokinetics in Sprague Dawley rats was evaluated using a rat jugular vein intubation tube. Results demonstrated that the Cmax of TCPLs became 5.7 times higher than that of tilianin solution and that the area under the curve of TCPLs became about 4.6-fold higher than that of tilianin solution. Overall, our results suggested that the prepared tilianin composite phospholipid liposome formulations could be used to improve the bioavailability of tilianin after oral administration.


Subject(s)
Flavonoids/chemistry , Flavonoids/pharmacokinetics , Glycosides/chemistry , Glycosides/pharmacokinetics , Liposomes/chemistry , Liposomes/pharmacokinetics , Phospholipids/chemistry , Phospholipids/pharmacokinetics , Administration, Oral , Animals , Area Under Curve , Biological Availability , Calorimetry, Differential Scanning/methods , Chemistry, Pharmaceutical/methods , Cholesterol/metabolism , Drug Liberation , Male , Particle Size , Rats , Rats, Sprague-Dawley
12.
Life Sci ; 147: 46-58, 2016 Feb 15.
Article in English | MEDLINE | ID: mdl-26796578

ABSTRACT

Osteoporosis is a systemic metabolic bone disease characterized by a reduction in bone mass, bone quality, and microarchitectural deterioration. An imbalance in bone remodeling that is caused by more osteoclast-mediated bone resorption than osteoblast-mediated bone formation results in such pathologic bone disorder. Traditional Chinese medicines (TCM) have long been used to prevent and treat osteoporosis and have received extensive attentions and researches at home and abroad, because they have fewer adverse reactions and are more suitable for long-term use compared with chemically synthesized medicines. Here, we put the emphasis on osteoblasts, summarized the detailed research progress on the active compounds derived from TCM with potential anti-osteoporosis effects and their molecular mechanisms on promoting osteoblast-mediated bone formation. It could be concluded that TCM with kidney-tonifying, spleen-tonifying, and stasis-removing effects all have the potential effects on treating osteoporosis. The active ingredients derived from TCM that possess effects on promoting osteoblasts proliferation and differentiation include flavonoids, glycosides, coumarins, terpenoids (sesquiterpenoids, monoterpenoids, diterpenoids), phenolic acids, phenols and others (tetrameric stilbene, anthraquinones, diarylheptanoids). And it was confirmed that the bone formation effect induced by the above natural products was regulated by the expressions of bone specific matrix proteins (ALP, BSP, OCN, OPN, COL I), transcription factor (Runx2, Cbfa1, Osx), signal pathways (MAPK, BMP), local factors (ROS, NO), OPG/RANKL system of osteoblasts and estrogen-like biological activities. All the studies provided theoretical basis for clinical application, as well as new drug research and development on treating osteoporosis.


Subject(s)
Biological Products/therapeutic use , Osteoblasts/metabolism , Osteogenesis/drug effects , Osteoporosis/drug therapy , Animals , Biological Products/pharmacology , Cell Differentiation/drug effects , Cell Proliferation/drug effects , Humans , Medicine, Chinese Traditional , Osteoblasts/drug effects , Osteoporosis/physiopathology
13.
J Control Release ; 220(Pt A): 5-17, 2015 Dec 28.
Article in English | MEDLINE | ID: mdl-26439663

ABSTRACT

Antibody-drug conjugates (ADCs), combining monoclonal antibody with high cytotoxicity chemotherapeutic drug (warhead), have been successfully applied for clinical cancer therapy. Linker technology to select and design linker connecting warhead with antibody, is critical to the success of therapeutic ADCs. In this study, three kinds of linkers were designed to connect SN-38, the bioactive metabolite of the anticancer drug irinotecan (CPT-11), which is 100-1000 times more potent than CPT-11, with the anti-HER2 antibody trastuzumab to prepare three different ADC conjugates (T-SN38 A, B and C). Meanwhile, we compared the anti-ovarian cancer effect of these three T-SN38 conjugates with trastuzumab in vitro and in vivo. Our in vitro results showed that T-SN38 A, B and C (drug-to-antibody ratio, DAR=3.7, 3.2, 3.4) were 2 to 3 times as cytotoxic as SN-38, and the IC50 for these three conjugates on SKOV-3 cell line at 72 h were 5.2 ± 0.3, 4.4 ± 0.7, and 5.1 ± 0.4 nM respectively. In our in vivo studies, T-SN38 conjugates had well targeting ability for tumor tissue and all three of them had much higher anti-ovarian cancer potency than trastuzumab. Among of them, T-SN38 B, which coupled SN-38 with trastuzumab by a carbonate bond, has the best anti-ovarian cancer potency. In conclusion, the novel HER2-targeting ADCs T-SN38 have great potential for HER2-positive ovarian cancer. Moreover, the SN-38-Linkers designed in this study can also be used to connect with other antibodies for the therapy of other cancers.


Subject(s)
Camptothecin/analogs & derivatives , Immunoconjugates/therapeutic use , Ovarian Neoplasms/drug therapy , Trastuzumab/administration & dosage , Animals , Camptothecin/administration & dosage , Camptothecin/metabolism , Cell Line, Tumor , Female , Humans , Irinotecan , Mice , Mice, Inbred BALB C , Ovarian Neoplasms/chemistry , Ovarian Neoplasms/pathology , Receptor, ErbB-2/analysis , Trastuzumab/metabolism , Xenograft Model Antitumor Assays
14.
Int J Pharm ; 493(1-2): 271-84, 2015 Sep 30.
Article in English | MEDLINE | ID: mdl-26222745

ABSTRACT

Topical glucocorticosteroids were incorporated into nanocarrier-based formulations, to overcome side effects of conventional formulations and to achieve maximum skin deposition. Nanoparticulate carriers have the potential to prolong the anti-inflammatory effect and provide higher local concentration of drugs, offering a better solution for treating dermatological conditions and improving patient compliance. Nanoparticles were formulated with poly-ϵ-caprolactone as the polymeric core along with stearic acid as the fatty acid, for incorporation of betamethasone-21-acetate. Oleic acid was applied as the coating fatty acid. Improvement of the drug efficacy, and reduction in drug degradation with time in the encapsulated form was examined, while administering it locally through controlled release. Nanoparticles were spherical with mean size of 300 nm and negatively charged surface. Encapsulation efficiency was 90%. Physicochemical stability in aqueous media of the empty and loaded nanoparticles was evaluated for six months. Drug degradation was reduced compared to free drug, after encapsulation into nanoparticles, avoiding the potency decline and promoting a controlled drug release over one month. Fourier transform infrared spectroscopy and thermal analysis confirmed drug entrapment, while cytotoxicity studies performed in vitro on human keratinocytes, Saccharomyces cerevisiae models and Artemia salina, showed a dose-response relationship for nanoparticles and free drug. In all models, drug loaded nanoparticles had a greater inhibitory effect. Nanoparticles increased drug permeation into lipid membranes in vitro. Preliminary safety and permeation studies conducted on rats, showed betamethasone-21-acetate in serum after 48 h application of a gel containing nanoparticles. No skin reactions were observed. In conclusion, the developed nanoparticles may be applied as topical treatment, after encapsulation of betamethasone-21-acetate, as nanoparticles promote prolonged drug release, increase drug stability in aqueous media, reducing drug degradation, and increase drug permeability through lipid membranes.


Subject(s)
Anti-Inflammatory Agents , Betamethasone , Drug Carriers , Nanoparticles , Acrylic Resins/chemistry , Administration, Cutaneous , Animals , Anti-Inflammatory Agents/administration & dosage , Anti-Inflammatory Agents/blood , Anti-Inflammatory Agents/chemistry , Anti-Inflammatory Agents/pharmacokinetics , Artemia/drug effects , Betamethasone/administration & dosage , Betamethasone/blood , Betamethasone/chemistry , Betamethasone/pharmacokinetics , Cell Line , Cell Survival/drug effects , Drug Carriers/administration & dosage , Drug Carriers/chemistry , Drug Carriers/pharmacokinetics , Drug Liberation , Drug Stability , Humans , Keratinocytes/drug effects , Male , Nanoparticles/administration & dosage , Nanoparticles/chemistry , Oleic Acid/chemistry , Poloxamer/chemistry , Rats, Wistar , Saccharomyces cerevisiae/drug effects , Saccharomyces cerevisiae/growth & development , Skin Absorption
15.
Food Res Int ; 78: 201-208, 2015 Dec.
Article in English | MEDLINE | ID: mdl-28433283

ABSTRACT

This study seeks to clarify and determine the fundamental properties of N-terminal domain of high molecular weight glutenin subunits (HMW-GS) 1Dx5 (1Dx5-N). 1Dx5-N was expressed in E. coli and its solubility was measured by spectrophotometry. Effects of edible salts (NaCl, Na2CO3), disulfide bond reductant dithiothreitol (DTT) and hydrophobic interactions of denaturant sodium dodecyl sulfonate (SDS) on 1Dx5-N polymer were investigated by native polyacrylamide gelelectrophoresis (PAGE), nonreducing/reducing SDS-PAGE, intrinsic fluorescence, size exclusion chromatography (SEC), dynamic light scattering (DLS) and circular dichroism (CD). Results showed that 1Dx5-N formed a soluble aggregate in aqueous solutions by native-PAGE, clarifying the role of N-terminal of HMW-GS in the insolubility of the whole subunits. Meanwhile, the hydrophobic interaction was more potent in promoting the aggregation of 1Dx5-N in aqueous solutions from the results of SEC, DLS and CD. Edible salts, NaCl and Na2CO3, could improve the polymer formation of 1Dx5-N through disulfide bonds. Moreover, Na2CO3 at high concentrations (>200mM) greatly favored polymer formation by disulfide bonds, and it induced other types of cross-links between amino acids in 1Dx5-N according to nonreducing/reducing SDS-PAGE and fluorescence spectrum. Moreover, the formation of covalent bonds was reinforced by hydrophobic interactions between 1Dx5-N. Therefore, these results provide much novel information on the N-terminal domain of HMW-GS to facilitate the understanding of its functional properties in wheat flour.

16.
Psicol. reflex. crit ; 25(3): 422-434, 2012. tab
Article in Portuguese | LILACS | ID: lil-653613

ABSTRACT

Trata de um estudo de correlação entre as variáveis da técnica de Rorschach (Sistema Klopfer) e os grupos de sinais e sintomas da CID-10 para a esquizofrenia. Participaram desse estudo 80 pacientes com o diagnóstico de esquizofrenia pela CID-10, com recidiva da doença, internados em hospitais psiquiátricos de Goiânia. Observou-se que, dentre os 8 grupos de sinais e sintomas da CID-10 para esquizofrenia, 7 grupos tiveram correlações com variáveis distintas do Rorschach. Tais dados sugerem que, embora exista uma relação entre as variáveis dos dois instrumentos, estas variáveis não se sobrepõem substancialmente. Entende-se que são importantes as pesquisas que indiquem padrões de inter-relação entre diferentes modelos de avaliação de distúrbios psíquicos, a fim de que se possam apontar pontos de convergência e divergência entre os mesmos, avançando desse modo em questões conceituais.


This is a correlational study between the variables of the Rorschach technique (Klopfer System) and groups of signals and symptoms of ICD-10 for schizophrenia. Eighty patients diagnosed with schizophrenia by the ICD-10, with disease recidivation, who were hospitalized in a psychiatric service in the city of Goiânia participated in the study. We observed that among the 8 groups of signals and symptoms of ICD10 for schizophrenia, 7 groups had correlations with distinct variable of Rorschach. These data suggest that while there is a relationship between the variables of the two instruments, such variables do not overlap substantially. It is understood that researches are important to indicate patterns of interrelationship between different models for evaluation of mental disorders so that they can point out similarities and differences between them, thereby advancing the conceptual issues.


Subject(s)
Humans , Male , Female , Young Adult , Middle Aged , Schizophrenia/diagnosis , International Classification of Diseases , Rorschach Test
17.
Psicol. reflex. crit ; 25(3): 422-434, 2012. tab
Article in Portuguese | Index Psychology - journals | ID: psi-57663

ABSTRACT

Trata de um estudo de correlação entre as variáveis da técnica de Rorschach (Sistema Klopfer) e os grupos de sinais e sintomas da CID-10 para a esquizofrenia. Participaram desse estudo 80 pacientes com o diagnóstico de esquizofrenia pela CID-10, com recidiva da doença, internados em hospitais psiquiátricos de Goiânia. Observou-se que, dentre os 8 grupos de sinais e sintomas da CID-10 para esquizofrenia, 7 grupos tiveram correlações com variáveis distintas do Rorschach. Tais dados sugerem que, embora exista uma relação entre as variáveis dos dois instrumentos, estas variáveis não se sobrepõem substancialmente. Entende-se que são importantes as pesquisas que indiquem padrões de inter-relação entre diferentes modelos de avaliação de distúrbios psíquicos, a fim de que se possam apontar pontos de convergência e divergência entre os mesmos, avançando desse modo em questões conceituais.(AU)


This is a correlational study between the variables of the Rorschach technique (Klopfer System) and groups of signals and symptoms of ICD-10 for schizophrenia. Eighty patients diagnosed with schizophrenia by the ICD-10, with disease recidivation, who were hospitalized in a psychiatric service in the city of Goiânia participated in the study. We observed that among the 8 groups of signals and symptoms of ICD10 for schizophrenia, 7 groups had correlations with distinct variable of Rorschach. These data suggest that while there is a relationship between the variables of the two instruments, such variables do not overlap substantially. It is understood that researches are important to indicate patterns of interrelationship between different models for evaluation of mental disorders so that they can point out similarities and differences between them, thereby advancing the conceptual issues.(AU)


Subject(s)
Humans , Male , Female , Young Adult , Adult , Middle Aged , Schizophrenia/diagnosis , International Classification of Diseases , Rorschach Test
18.
Psicol. pesq ; 5(1): 61-67, ago. 2011.
Article in Portuguese | LILACS | ID: lil-603566

ABSTRACT

Este artigo descreve as principais dificuldades e limitações para diagnosticar transtornos alimentares na infância sob os critérios do DSM-IV e CID-10. São revistos todos os critérios de cada tipo de transtorno e paralelamente à sua indicação são apontados os principais pontos frágeis e de críticas. Em seguida, é feita uma explanação acerca dos transtornos subclínicos que, apesar de serem de difícil detecção, também prescindem de um diagnóstico precoce. Ao final, se apresenta um sistema de classificação ainda pouco difundido no Brasil: GOS, que é uma sistematização dos tipos de transtornos alimentares infantis e seus sintomas, baseada em achados de investigações. Deste modo, o propósito é de trazer novas possibilidades para discutir o refinamento do diagnóstico infantil.


This article summarizes the main limitations and difficulties of classification of eating problems and disorders in childhood based on DSM-IV and ICD-10's criteria. Each eating disorder's criterion is revised and problems with current classification schemes are identified and discussed. Subclinical eating disorders are recognized as another finding that makes an early diagnostic even hard. As the current classifications have their weak points, a new classification system is presented: GOS. It is an alternative system, built on scientific researches conducted in this age, that meets children's specific eating disorders and its symptoms. Thus, the purpose is to bring a range of possible discussions to refine the classification strategies for eating disorders in children and adolescents.


Subject(s)
Humans , Male , Female , Child , Diagnostic and Statistical Manual of Mental Disorders , Feeding and Eating Disorders of Childhood , International Classification of Diseases
19.
Cad. saúde colet., (Rio J.) ; 18(1)jan.-mar. 2010.
Article in Portuguese | LILACS-Express | LILACS | ID: lil-621260

ABSTRACT

Este trabalho apresenta a Família de Classificações Internacionais da Organização Mundial da Saúde, conjunto de produtos que podem ser usados de forma integrada para comparar informações de saúde. Organizada segundo critérios internacionais, é composta por classificações de referência, derivadas e as classificações relacionadas. A Classificação Internacional de Doenças, em sua décima revisão, é uma das classificações de referência. Adotada internacionalmenteem 1893, é o instrumento para a elaboração das estatísticas de saúde, utilizada por mais de cem países. Outra classificação de referência é a Classificação Internacional de Funcionalidade,Incapacidade e Saúde. Esta permite conhecer aspectos relacionados à funcionalidade e às situações de vida das pessoas que experimentam qualquer incapacidade, transitória ou permanente. Entre as classificações derivadas encontram-se as adaptações para especialidades,como a CID-O-3, para oncologia ou a adaptação para transtornos mentais. No grupo das classificações relacionadas, estão classificações como a de Atenção Primária (CIAP) ou a Classificação Internacional de Ajudas Técnicas da norma ISO 9999. No momento em que se planejaa próxima revisão da CID, primeira com a possibilidade de ampla colaboração dos usuários, entender sua inserção e os contextos em que se fazem as mudanças é fundamental para a área de informações de saúde.


This paper aimed to present the World Health Organization Family of International Classifications, a suite of classification products that may be used integrated to compare health information. This family is organized following international criteria that include reference, derived and relatedclassifications. The International Classification of Diseases, now in the 10th revision, is one of the references classifications. It was internationally adopted in 1893 and has been used for health statistics by more than a hundred countries. Another reference classification is theInternational Classification of Functioning, Disability and Health. This is a tool which includes aspects of functioning as well as situations related to life to be applied in people with temporarily or permanent disability. Among the derived classifications there are the specialty-based adaptations, as the ICD-O-3 for Oncology or the one for mental disorders. In the group ofrelated classifications it is included the International Classification for Primary Care (ICPC) and the ISO 9999 Technical Aids for Persons with disability, among others. To understand the role of this suite of products, as a consequence of the changes in many areas, facing the challenge ofa new ICD revision, is fundamental for the area of health informatics.

20.
Rev. latinoam. psicopatol. fundam ; 12(2): 285-302, jun. 2009.
Article in Portuguese | LILACS, Index Psychology - journals | ID: lil-522911

ABSTRACT

A psicopatia é descrita como personalidade antissocial pelos manuais nosográficos contemporâneos: CID-10 e DSM-IV-TR. Contrastando tais nosografias entre si quanto aos critérios diagnósticos propostos para a psicopatia, assinalam-se as consequências de sua operacionalização, promovida, sobretudo, pelo DSM. Dentre elas, destacam-se: (1) a degradação do diagnóstico ao mero levantamento protocolar; (2) a acentuação da correlação histórica entre psicopatia e delinquência.


La psicopatía es descrita como la personalidad antisocial por los manuales nosográficos contemporáneos: CIE-10 y DSM-IV-TR. Contrastando tales nosografías entre sí, con relación a los criterios de diagnósticos propuestos para la psicopatía, se observan las consecuencias de su operacionalización, particularmente las derivadas del DSM. Entre ellas, se destaca: (1) la degradación del diagnóstico a una mera lista protocolar; (2) la acentuación de la relación histórica entre la psicopatía y la delincuencia.


La psychopathie est décrite comme personnalité antisociale par les manuels nosographiques contemporains, comme le CIM-10 et le DSM-IV-TR. La comparaison de ces nosographies entre elles par rapport à leurs critères de diagnostique de la psychopathie permet d'obtenir les conséquences opérationnelles, surtout en ce qui concerne le DSM, parmi lesquelles on retiendra spécialement: (1) la dégradation du diagnostique au simple classement protocolaire; (2) l´accentuation du rapport historique entre la psychopathie et la délinquance.


Psychopathy is described in two contemporary nosographic handbooks (ICD-10 and DSM-IV-TR0) as the condition of having an anti-social personality. This article contrasts these nosographies in terms of the diagnostic criteria used for psychopathy. The consequences of this use, especially that presented by the DSM, are discussed, such as (1) the degradation of diagnoses to the mere filling out of forms; (2) emphasis on the historical correlation between psychopathy and delinquency.


Subject(s)
International Classification of Diseases , Diagnostic and Statistical Manual of Mental Disorders , Antisocial Personality Disorder
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