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1.
Int J Biol Macromol ; 239: 124350, 2023 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-37028631

RESUMO

It is commonly known that agricultural pest and disease management is achieved through the use of agricultural chemicals and other synthetic compounds, which can contaminate water, soil, and food. Using agrochemicals indiscriminately has negative effects on the environment and poor food quality. In contrast, the world's population is increasing rapidly, and arable land is diminishing daily. Traditional agricultural methods must be replaced by nanotechnology-based treatments that efficiently address both the demands of the present and the needs of the future. As a promising contributor to sustainable agriculture and food production worldwide, nanotechnology has been applied through innovative and resourceful tools. Recent advances in nanomaterial engineering have increased agricultural and food sector production and protected crops using nanoparticles (1000 nm). Agrochemicals, nutrients, and genes can now be distributed to plants in a precise and tailored manner through nanoencapsulation (nanofertilizers, nanopesticides, and genes). Despite the advancement of technology in agriculture, some areas remain unexplored. The various agricultural domains must therefore be updated in priority order. The development of long-lasting and efficient nanoparticle materials will be key to the development of future eco-friendly and nanoparticle-based technologies. We thoroughly covered the many types of nanoscale agro-materials and gave an overview of biological techniques in nano-enabled tactics that can effectively reduce plant biotic and abiotic challenges while potentially boosting plant nutritional values.


Assuntos
Agricultura , Nanotecnologia , Nanotecnologia/métodos , Agricultura/métodos , Agroquímicos , Produtos Agrícolas , Substâncias Macromoleculares , Carboidratos
2.
Bratisl Lek Listy ; 122(2): 111-115, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33502878

RESUMO

OBJECTIVES: We aimed to evaluate the effects of leptin and nitro-L-arginine methyl ester hydrochloride (L-NAME) on testicular damage and expression of nitric oxide synthase (NOS) types (neuronal, endothelial and inducible NOS) in streptozotocin (STZ) -induced diabetic and non-diabetic rats. METHODS: Testicular damage was evaluated histologically and expression of NOSs was evaluated immunohistochemically in testis. Plasma leptin level and blood glucose level were assessed. RESULTS: Blood glucose levels increased in all diabetic groups. L-NAME reduced it, but leptin had no effect. Three types NOS expression were shown in germ cells immunohistochemically. Increased eNOS and iNOS expression and decreased nNOS expression was detected in diabetic group. Testicular damage was observed in diabetic groups. Leptin ameliorated the damage by reducing iNOS expression and L-NAME partially prevented injury by supressing excessive NO production in diabetic rats. CONCLUSIONS: It can be suggested that leptin and L-NAME partially prevents testicular damage by ameliorating histopathological changes by stimulating and /or supressing three types of NOS expression in diabetic rats. Leptin exhibited its effects by reducing iNOS expression in diabetic rats. This is the first report demonstrating the relationship between leptin and nitric oxide in testicular tissue in STZ-induced diabetic rats (Fig. 3, Ref. 33).


Assuntos
Diabetes Mellitus Experimental , Animais , Inibidores Enzimáticos , Leptina , Masculino , NG-Nitroarginina Metil Éster/farmacologia , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Óxido Nítrico Sintase Tipo III , Ratos , Ratos Sprague-Dawley
3.
Pol J Vet Sci ; 23(3): 349-357, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33006866

RESUMO

Nitric oxide (NO) is known to be a neuromodulator with dual proconvulsive and anticonvul- sive action. Valeriana officinalis (VAL) was previously believed to be antiepileptic, but is today known as a sedative and sleep regulator. Seizures may be associated with abnormal electrocardio- graphic changes and cardiac dysfunction arising from epilepsy may be related with neuronal nitric oxide (nNO). This study was aimed to investigate the effects of the neuronal nitric oxide synthase (nNOS) inhibitor 7-Nitroindazole (7-NI) and VAL on seizure behaviours and electrocar- diographic parameters in the pentylentetrazole (PTZ)-kindled seizure model. Wistar rats were randomised into saline control, PTZ-kindled, 7-NI, VAL and VAL+PTZ, 7-NI+PTZ and VAL+7-NI+PTZ groups. Latency, stage, frequency of seizures, blood pressure (BP), heart rate (HR) and corrected QT (QTc) values were evaluated. Frequency and stage of seizures, BP and HR increased, while seizure latency decreased and QTc was prolonged in the PTZ-kindled group. 7-NI and VAL had no effects on BP and HR variables under normal conditions, but ameliorated the seizure stage and frequency of seizures. 7-NI treatment also resulted in a reduction of the increased BP and prolonged QTc values observed in PTZ-kindled rats. Considering these results, QTc prolongation may be used as a predictor for recurrent seizures. 7-NI and VAL exhibited different effects on seizures and ECG variables. 7-NI shows potential as an anticonvulsant drug agent in epileptic patients with cardiac dysfunctions and those additional studies including in-vivo experiments are essential.


Assuntos
Pressão Sanguínea/efeitos dos fármacos , Eletrocardiografia/efeitos dos fármacos , Indazóis/farmacologia , Pentilenotetrazol/toxicidade , Extratos Vegetais/farmacologia , Valeriana/química , Animais , Anticonvulsivantes/química , Anticonvulsivantes/farmacologia , Convulsivantes/toxicidade , Masculino , Extratos Vegetais/química , Distribuição Aleatória , Ratos
4.
Braz. j. biol ; 80(3): 484-496, July-Sept. 2020. graf
Artigo em Inglês | LILACS | ID: biblio-1132402

RESUMO

Abstract The main objective of current study was to investigate the chemopreventive and chemotherapeutic activity of Artemisia vulgaris extract on diethylnitrosoamine induced hepatocarcinogenesis in Balb C mice. Diethylnitrosoamine (DEN: 0.9%) was prepared to induce hepatocarcinoma in Balb C mice. The extract Artemisia vulgaris (AV) was prepared by maceration technique. Mice were classified into four groups as follows: Group 1 a control group (N=7) received saline solution (3.5 μl/mg), group 2 (N=14) received diethylnitrosoamine (3.5 μl/mg) intraperitoneally once in a week for eight consecutive weeks, group 3 (N=7) received only plant extract (AV: 150 mg/kg (Body weight) once in a week, while group 4 (N=7) was given in combination of diethylnitrosoamine (3.5 μl/mg) and plant extract (AV: 150 mg/kg (body weight). After eight weeks of DEN administration, mice of group 2 were divided into two subgroups containing seven mice each; subgroup 1 was sacrificed while subgroup 2 was treated with plant extract only (150 mg/kg (body weight)) once in a week for eight consecutive weeks. The DEN injected mice significant decline in levels of albumin with concomitant significant elevations such as aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, alpha feto protein, gamma glutamyl transferase, 5 nucleotidase, glucose-6-phosphate dehydrogenase and bilirubin. The administration of A. vulgaris significantly decreased the DEN induced hepatotoxicity. Present study revealed the potential anti-cancerous nature of Artemisia vulgaris, both in case of chemopreventive and post-treatment of A. vulgaris. Further studies are needed to explore the mechanism of prevention and therapy.


Resumo O objetivo principal do presente estudo foi investigar as atividades quimiopreventiva e quimioterápica do extrato de Artemisia vulgaris em hepatocarcinogênese induzida por dietilnitrosoamina (DEN) em camundongos Balb C. Dietilnitrosoamina (DEN: 0,9%) foi preparada para induzir hepatocarcinoma em camundongos da linhagem Balb C. O extrato de A. vulgaris (AV) foi preparado pela técnica de maceração. Os camundongos foram classificados em quatro grupos conforme os seguintes: grupo 1, grupo controle (N=7) recebeu solução salina (3,5 µl/mg); grupo 2 (N=14) recebeu dietilnitrosoamina (3,5 µl/mg) por via intraperitoneal uma vez por semana durante oito semanas consecutivas; grupo 3 (N=7) recebeu apenas o extrato vegetal (AV: 150 mg/kg (peso corporal) uma vez por semana; enquanto no grupo 4 (N=7) foi administrado uma combinação de dietilnitrosoamina (3,5 μl/mg) com extrato vegetal (AV: 150 mg/kg (peso corporal). Após oito semanas de administração de DEN, os camundongos do grupo 2 foram divididos em dois subgrupos, contendo sete camundongos cada um; no subgrupo 1, os animais foram sacrificados, enquanto no subgrupo 2, os animais foram tratados apenas com extrato vegetal (150 mg/kg (peso corporal)) uma vez por semana durante oito semanas consecutivas. Os camundongos nos quais foram injetados DEN apresentaram declínio significativo nos níveis de albumina, mas elevações significativas concomitantes de: aspartato aminotransferase, alanina aminotransferase, lactato desidrogenase, alfa-fetoproteína, gama-glutamiltransferase, 5' nucleotidase, glicose-6-fosfato desidrogenase e bilirrubina. A administração de A. vulgaris diminuiu significativamente a hepatotoxicidade induzida pelo DEN. O presente estudo apresentou a potencialidade anticancerosa da A. vulgaris, tanto nos casos de quimioprevenção quanto no pós-tratamento da A. vulgaris. Mais estudos são necessários para explorar o mecanismo de prevenção e a terapia.


Assuntos
Animais , Coelhos , Carcinoma Hepatocelular , Artemisia , Neoplasias Hepáticas , Extratos Vegetais , Dietilnitrosamina , Carcinogênese , Camundongos Endogâmicos BALB C
5.
Braz. j. biol ; 80(3): 489-496, July-Sept. 2020. graf
Artigo em Inglês | LILACS, VETINDEX | ID: biblio-1468409

RESUMO

The main objective of current study was to investigate the chemopreventive and chemotherapeutic activity of Artemisia vulgaris extract on diethylnitrosoamine induced hepatocarcinogenesis in Balb C mice. Diethylnitrosoamine (DEN: 0.9%) was prepared to induce hepatocarcinoma in Balb C mice. The extract Artemisia vulgaris (AV) was prepared by maceration technique. Mice were classified into four groups as follows: Group 1 a control group (N=7) received saline solution (3.5 l/mg), group 2 (N=14) received diethylnitrosoamine (3.5 l/mg) intraperitoneally once in a week for eight consecutive weeks, group 3 (N=7) received only plant extract (AV: 150 mg/kg (Body weight) once in a week, while group 4 (N=7) was given in combination of diethylnitrosoamine (3.5 l/mg) and plant extract (AV: 150 mg/kg (body weight). After eight weeks of DEN administration, mice of group 2 were divided into two subgroups containing seven mice each; subgroup 1 was sacrificed while subgroup 2 was treated with plant extract only (150 mg/kg (body weight)) once in a week for eight consecutive weeks. The DEN injected mice significant decline in levels of albumin with concomitant significant elevations such as aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, alpha feto protein, gamma glutamyl transferase, 5 nucleotidase, glucose-6-phosphate dehydrogenase and bilirubin. The administration of A. vulgaris significantly decreased the DEN induced hepatotoxicity. Present study revealed the potential anti-cancerous nature of Artemisia vulgaris, both in case of chemopreventive and post-treatment of A. vulgaris. Further studies are needed to explore the mechanism of prevention and therapy.


O objetivo principal do presente estudo foi investigar as atividades quimiopreventiva e quimioterápica do extrato de Artemisia vulgaris em hepatocarcinogênese induzida por dietilnitrosoamina (DEN) em camundongos Balb C. Dietilnitrosoamina (DEN: 0,9%) foi preparada para induzir hepatocarcinoma em camundongos da linhagem Balb C. O extrato de A. vulgaris (AV) foi preparado pela técnica de maceração. Os camundongos foram classificados em quatro grupos conforme os seguintes: grupo 1, grupo controle (N=7) recebeu solução salina (3,5 µl/mg); grupo 2 (N=14) recebeu dietilnitrosoamina (3,5 µl/mg) por via intraperitoneal uma vez por semana durante oito semanas consecutivas; grupo 3 (N=7) recebeu apenas o extrato vegetal (AV: 150 mg/kg (peso corporal) uma vez por semana; enquanto no grupo 4 (N=7) foi administrado uma combinação de dietilnitrosoamina (3,5 l/mg) com extrato vegetal (AV: 150 mg/kg (peso corporal). Após oito semanas de administração de DEN, os camundongos do grupo 2 foram divididos em dois subgrupos, contendo sete camundongos cada um; no subgrupo 1, os animais foram sacrificados, enquanto no subgrupo 2, os animais foram tratados apenas com extrato vegetal (150 mg/kg (peso corporal)) uma vez por semana durante oito semanas consecutivas. Os camundongos nos quais foram injetados DEN apresentaram declínio significativo nos níveis de albumina, mas elevações significativas concomitantes de: aspartato aminotransferase, alanina aminotransferase, lactato desidrogenase, alfa-fetoproteína, gama-glutamiltransferase, 5 nucleotidase, glicose-6-fosfato desidrogenase e bilirrubina. A administração de A. vulgaris diminuiu significativamente a hepatotoxicidade induzida pelo DEN. O presente estudo apresentou a potencialidade anticancerosa da A. vulgaris, tanto nos casos de quimioprevenção quanto no pós-tratamento da A. vulgaris. Mais estudos são necessários para explorar o mecanismo de prevenção e a terapia.


Assuntos
Artemisia/efeitos dos fármacos , Artemisia/química , Camundongos , Carcinogênese , Dietilnitrosamina , Preparações Farmacêuticas
6.
J Appl Lab Med ; 5(4): 704-715, 2020 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-32603436

RESUMO

BACKGROUND: Total calcium is a less accurate test in predicting ionized calcium (Ca2+) in patients suspected of calcium metabolic disease. Nevertheless, total calcium continues to be used as routine measurement instead of adjusted Ca2+ (at pH 7.4). In the current study we evaluate a new multichannel instrument, the ISE Module E1200 for adjusted Ca2+ (at pH 7.4), containing three different ion-selective electrode (ISE) units. METHODS: Serum from 1350 patients was compared to the ABL835 flex and KoneLab. Total calcium was also evaluated on the Dimension Vista 1500 system. Correlations between instruments were assessed by Deming regression and degree of agreement by Cohen's kappa (κ). RESULTS: Analytical imprecisions for the three ISE units for adjusted Ca2+ (at pH 7.4) was between 0.36% and 2.52%, and for pH between 0.32% and 3.24%. Results were comparable for each ISE unit (r = 0.797-0.917; all P < 0.0001) and in high-throughput settings (r = 0.871; P < 0.0001). The degree of agreement between instruments was moderate to good (κ = 0.52-0.77). In contrast, there was a very poor agreement (κ = -0.14) for total calcium with discrepancy in 53.4% of the samples. CONCLUSIONS: The new ISE Module E1200 is comparable with the ABL835 flex and KoneLab 30i and therefore may be used for routine analysis of serum adjusted Ca2+ (at pH 7.4). The measured adjusted Ca2+ (at pH 7.4) was less comparable with very poor agreement to total calcium measured on the Dimension Vista 1500 system.


Assuntos
Análise Química do Sangue/instrumentação , Distúrbios do Metabolismo do Cálcio/diagnóstico , Cálcio/sangue , Ensaios de Triagem em Larga Escala/instrumentação , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Cálcio/metabolismo , Distúrbios do Metabolismo do Cálcio/sangue , Distúrbios do Metabolismo do Cálcio/metabolismo , Cátions Bivalentes/sangue , Criança , Pré-Escolar , Feminino , Humanos , Concentração de Íons de Hidrogênio , Eletrodos Seletivos de Íons , Masculino , Pessoa de Meia-Idade , Adulto Jovem
7.
Int J Lab Hematol ; 42(3): 256-262, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32039560

RESUMO

BACKGROUND: White blood cell (WBC) counts are used to monitor bone marrow function and to screen for infections. The HemoCue WBC DIFF Point-Of-Care (POC) instrument classifies WBCs through cell image recognition. To evaluate its suitability for monitoring cancer patients, we examined its performance in samples from patient with leukopenia and in samples containing nRBC. METHODS: Sysmex samples with WBCs 0.05-3.40 × 109 /L were examined on the HemoCue WBC DIFF, and the correlations between the instruments were assessed by Deming regression for total WBC, neutrophils, and lymphocytes. The theoretical CV% (CVt), calculated from number of cells counted by the HemoCue WBC DIFF, was used to determine the statistical error of the WBC counts. The interference of nRBC was also evaluated. RESULTS: The counting variation was primarily the source of statistical error in the lower counts with an imprecision between 3.8-9.2% for total WBC (0.56-2.29 ×109 /L), 8.7-14.3% for neutrophils (0.36-1.33 ×109 /L) and 9.8-15.1% for lymphocytes (0.35-0.89 ×109 /L). The correlation coefficient was between 0.658 and 0.986-poorest for lymphocytes. The total WBC count on the HemoCue WBC DIFF was significantly increased in nRBC samples due to lymphocyte count overestimation, and not by other WBCs. CONCLUSIONS: The HemoCue WBC DIFF provided reliable and accurate counts of total WBC, neutrophil, and lymphocyte in leukopenic samples. Until POC instruments that can perform an accurate complete blood count are available, the HemoCue WBC DIFF can be used to assist physicians in making decisions in situations of postchemotherapy leukopenia and neutropenia.


Assuntos
Leucopenia/sangue , Neoplasias/sangue , Testes Imediatos , Adulto , Humanos , Contagem de Leucócitos/instrumentação , Masculino
8.
Braz J Biol ; 80(3): 484-496, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31691741

RESUMO

The main objective of current study was to investigate the chemopreventive and chemotherapeutic activity of Artemisia vulgaris extract on diethylnitrosoamine induced hepatocarcinogenesis in Balb C mice. Diethylnitrosoamine (DEN: 0.9%) was prepared to induce hepatocarcinoma in Balb C mice. The extract Artemisia vulgaris (AV) was prepared by maceration technique. Mice were classified into four groups as follows: Group 1 a control group (N=7) received saline solution (3.5 µl/mg), group 2 (N=14) received diethylnitrosoamine (3.5 µl/mg) intraperitoneally once in a week for eight consecutive weeks, group 3 (N=7) received only plant extract (AV: 150 mg/kg (Body weight) once in a week, while group 4 (N=7) was given in combination of diethylnitrosoamine (3.5 µl/mg) and plant extract (AV: 150 mg/kg (body weight). After eight weeks of DEN administration, mice of group 2 were divided into two subgroups containing seven mice each; subgroup 1 was sacrificed while subgroup 2 was treated with plant extract only (150 mg/kg (body weight)) once in a week for eight consecutive weeks. The DEN injected mice significant decline in levels of albumin with concomitant significant elevations such as aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, alpha feto protein, gamma glutamyl transferase, 5 nucleotidase, glucose-6-phosphate dehydrogenase and bilirubin. The administration of A. vulgaris significantly decreased the DEN induced hepatotoxicity. Present study revealed the potential anti-cancerous nature of Artemisia vulgaris, both in case of chemopreventive and post-treatment of A. vulgaris. Further studies are needed to explore the mechanism of prevention and therapy.


Assuntos
Artemisia , Carcinoma Hepatocelular , Neoplasias Hepáticas , Animais , Carcinogênese , Dietilnitrosamina , Camundongos , Camundongos Endogâmicos BALB C , Extratos Vegetais
9.
Braz. j. biol ; 79(4): 629-638, Nov. 2019. tab, graf
Artigo em Inglês | LILACS | ID: biblio-1001489

RESUMO

Abstract Background Hepatocellular carcinoma is the most frequent primary malignancy of liver and accounts for as many as one million deaths worldwide in a year. Objectives The aim of the present study was to evaluate the anti-cancerous efficiency of Bergenia ciliata rhizome against diethylnitrosoamine induced hepatocarcinogenesis in Balb C mice. Methods One percent diethylnitrosoamine was prepared by using 99 ml of normal saline NaCl (0.9 percent) solution to which was added 1 ml of concentrated diethylnitrosoamine (DEN) solution (0.01 μg/μl). Extract of Bergenia ciliata was prepared by maceration technique. Mice were classified into four groups as follows: Group 1 a control group (N=7) received saline solution (3.5 μl/mg), group 2 (N=14) received diethylnitrosoamine (3.5 μl/mg) intraperitoneally once in a week for eight consecutive weeks, group 3 (N=7) received plant extract (150 mg/kg (Body weight)) once in a week, while group 4 (N=7) was given combination of diethylnitrosoamine (3.5 μl/mg) and plant extract (150 mg/kg (Body weight)). After eight weeks of DEN induction group 2 mice were divided into two subgroups containing seven mice each, subgroup 1 was sacrificed while subgroup 2 was treated with plant extract (150 mg/kg (Body weight)) once in a week for eight consecutive weeks. Results The model of DEN injected hepatocellular carcinomic (HCC) mice elicited significant decline in levels of albumin with concomitant significant elevations in tumor markers aspartate aminotransferase, alanine aminotransferase (ALT), lactate dehydrogenase (LDH), alpha feto protein (AFP), gamma glutamyl transferase (Y-GT), 5 nucleotidase (5NT), glucose-6-phosphate dehydrogenase (G6PDH) and bilirubin. The intraperitoneal administration of B. ciliata as a protective agent, produced significant increase in albumin levels with significant decrease in the levels of tumor markers aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), alpha feto protein (AFP), gamma glutamyl transferase (Y-GT), 5 nucleotidase (5NT), glucose-6-phosphate dehydrogenase (G6PDH) and bilirubin. Conclusion Bergenia ciliata has potent antioxidant activity, radical scavenging capacity and anticancerous properties. Bergenia ciliata extracts may provide a basis for development of anti-cancerous drug.


Resumo Antecedentes O carcinoma hepatocelular é a neoplasia primária mais frequente do fígado e é responsável por até um milhão de mortes em todo o mundo em um ano. Objetivos O objetivo do presente estudo foi avaliar a eficiência anticancerígena do rizoma de Bergenia ciliata contra a hepatocarcinogênese induzida por dietilnitrosoamina em camundongos balb c. Métodos Um por cento de dietilnitrosoamina foi preparado usando 99 ml de solução salina normal (0,9 por cento) à qual foi adicionado 1 ml de solução concentrada de dietilnitrosoamina (DEN) (0,01 μg / μl). O extrato de Bergenia ciliata foi preparado pela técnica de maceração. Os ratos foram classificados em quatro grupos: Grupo 1 grupo controle (N = 7) recebeu solução salina (3,5 mL / mg), grupo 2 (N = 14) recebeu dietilnitrosoamina (3,5 mL / mg) por via intraperitoneal uma vez por semana para oito semanas consecutivas, o grupo 3 (N = 7) recebeu extrato vegetal (150 mg / kg (peso corporal)) uma vez por semana, enquanto o grupo 4 (N = 7) recebeu combinação de dietilnitrosoamina (3,5 μl / mg) e extrato (150 mg / kg (peso corporal). Após oito semanas do grupo de indução DEN 2 ratos foram divididos em dois subgrupos contendo sete ratos cada, subgrupo 1 foi sacrificado enquanto subgrupo 2 foi tratado com extrato vegetal (150 mg / kg)) uma vez por semana durante oito semanas consecutivas. Resultados O modelo de camundongos hepatocelulares carcinômicos (CHC) injetados com DEN provocou declínio significativo nos níveis de albumina com elevações significativas concomitantes nos marcadores tumorais: aspartato aminotransferase, alanina aminotransferase (ALT), lactato desidrogenase (LDH), proteína alfa feto (AFP), gama glutamiltransferase (Y-GT), 5 nucleotidase (5NT), glicose-6-fosfato ehidrogenase (G6PDH) e bilirrubina. A administração intraperitoneal de B. ciliata como agente protetor produziu um aumento significativo nos níveis de albumina com uma diminuição significativa nos níveis dos marcadores tumorais: aspartato aminotransferase, alanina aminotransferase (ALT), lactato desidrogenase (LDH), proteína alfa feto (AFP), gama glutamiltransferase (Y-GT), 5 nucleotidase (5NT), glicose-6-fosfato desidrogenase (G6PDH) e bilirrubina. Conclusão Bergenia ciliata possui atividade antioxidante potente, capacidade de eliminação de radicais livres e propriedades anticancerígenas. Extratos de Bergenia ciliata podem fornecer uma base para o desenvolvimento de drogas anti-cancerígenas.


Assuntos
Animais , Masculino , Ratos , Carcinoma Hepatocelular/induzido quimicamente , Carcinoma Hepatocelular/patologia , Dietilnitrosamina/farmacologia , Neoplasias Hepáticas/induzido quimicamente , Neoplasias Hepáticas/patologia , Neoplasias Experimentais/induzido quimicamente , Extratos Vegetais/farmacologia , Saxifragaceae , Alquilantes/farmacologia , Camundongos Endogâmicos BALB C
10.
Braz J Biol ; 79(4): 629-638, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31017181

RESUMO

BACKGROUND: Hepatocellular carcinoma is the most frequent primary malignancy of liver and accounts for as many as one million deaths worldwide in a year. OBJECTIVES: The aim of the present study was to evaluate the anti-cancerous efficiency of Bergenia ciliata rhizome against diethylnitrosoamine induced hepatocarcinogenesis in Balb C mice. METHODS: One percent diethylnitrosoamine was prepared by using 99 ml of normal saline NaCl (0.9 percent) solution to which was added 1 ml of concentrated diethylnitrosoamine (DEN) solution (0.01 µg/µl). Extract of Bergenia ciliata was prepared by maceration technique. Mice were classified into four groups as follows: Group 1 a control group (N=7) received saline solution (3.5 µl/mg), group 2 (N=14) received diethylnitrosoamine (3.5 µl/mg) intraperitoneally once in a week for eight consecutive weeks, group 3 (N=7) received plant extract (150 mg/kg (Body weight)) once in a week, while group 4 (N=7) was given combination of diethylnitrosoamine (3.5 µl/mg) and plant extract (150 mg/kg (Body weight)). After eight weeks of DEN induction group 2 mice were divided into two subgroups containing seven mice each, subgroup 1 was sacrificed while subgroup 2 was treated with plant extract (150 mg/kg (Body weight)) once in a week for eight consecutive weeks. RESULTS: The model of DEN injected hepatocellular carcinomic (HCC) mice elicited significant decline in levels of albumin with concomitant significant elevations in tumor markers aspartate aminotransferase, alanine aminotransferase (ALT), lactate dehydrogenase (LDH), alpha feto protein (AFP), gamma glutamyl transferase (Y-GT), 5 nucleotidase (5NT), glucose-6-phosphate dehydrogenase (G6PDH) and bilirubin. The intraperitoneal administration of B. ciliata as a protective agent, produced significant increase in albumin levels with significant decrease in the levels of tumor markers aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), alpha feto protein (AFP), gamma glutamyl transferase (Y-GT), 5 nucleotidase (5NT), glucose-6-phosphate dehydrogenase (G6PDH) and bilirubin. CONCLUSION: Bergenia ciliata has potent antioxidant activity, radical scavenging capacity and anticancerous properties. Bergenia ciliata extracts may provide a basis for development of anti-cancerous drug.


Assuntos
Carcinoma Hepatocelular , Dietilnitrosamina/farmacologia , Neoplasias Hepáticas , Neoplasias Experimentais/induzido quimicamente , Extratos Vegetais/farmacologia , Saxifragaceae , Alquilantes/farmacologia , Animais , Carcinoma Hepatocelular/induzido quimicamente , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/induzido quimicamente , Neoplasias Hepáticas/patologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C
11.
Transl Psychiatry ; 7(1): e996, 2017 01 10.
Artigo em Inglês | MEDLINE | ID: mdl-28072413

RESUMO

Repeated withdrawal from alcohol is clinically associated with progressive cognitive impairment. Microglial activation occurring during pre-clinical models of alcohol withdrawal is associated with learning deficits. We investigated whether there was microglial activation in recently detoxified alcohol-dependent patients (ADP), using [11C]PBR28 positron emission tomography (PET), selective for the 18kDa translocator protein (TSPO) highly expressed in activated microglia and astrocytes. We investigated the relationship between microglial activation and cognitive performance. Twenty healthy control (HC) subjects (45±13; M:F 14:6) and nine ADP (45±6, M:F 9:0) were evaluated. Dynamic PET data were acquired for 90 min following an injection of 331±15 MBq [11C]PBR28. Regional volumes of distribution (VT) for regions of interest (ROIs) identified a priori were estimated using a two-tissue compartmental model with metabolite-corrected arterial plasma input function. ADP had an ~20% lower [11C]PBR28 VT, in the hippocampus (F(1,24) 5.694; P=0.025), but no difference in VT in other ROIs. Hippocampal [11C]PBR28 VT was positively correlated with verbal memory performance in a combined group of HC and ADP (r=0.720, P<0.001), an effect seen in HC alone (r=0.738; P=0.001) but not in ADP. We did not find evidence for increased microglial activation in ADP, as seen pre-clinically. Instead, our findings suggest lower glial density or an altered activation state with lower TSPO expression. The correlation between verbal memory and [11C]PBR28 VT, raises the possibility that abnormalities of glial function may contribute to cognitive impairment in ADP.


Assuntos
Alcoolismo/metabolismo , Hipocampo/metabolismo , Microglia/metabolismo , Receptores de GABA/metabolismo , Acetamidas , Alcoolismo/diagnóstico por imagem , Astrócitos/metabolismo , Radioisótopos de Carbono , Estudos de Casos e Controles , Contaminação de Medicamentos , Feminino , Hipocampo/diagnóstico por imagem , Humanos , Masculino , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons , Piridinas , Compostos Radiofarmacêuticos
12.
Artigo em Inglês | LILACS-Express | LILACS, VETINDEX | ID: biblio-1467254

RESUMO

Abstract Background Hepatocellular carcinoma is the most frequent primary malignancy of liver and accounts for as many as one million deaths worldwide in a year. Objectives The aim of the present study was to evaluate the anti-cancerous efficiency of Bergenia ciliata rhizome against diethylnitrosoamine induced hepatocarcinogenesis in Balb C mice. Methods One percent diethylnitrosoamine was prepared by using 99 ml of normal saline NaCl (0.9 percent) solution to which was added 1 ml of concentrated diethylnitrosoamine (DEN) solution (0.01 g/l). Extract of Bergenia ciliata was prepared by maceration technique. Mice were classified into four groups as follows: Group 1 a control group (N=7) received saline solution (3.5 l/mg), group 2 (N=14) received diethylnitrosoamine (3.5 l/mg) intraperitoneally once in a week for eight consecutive weeks, group 3 (N=7) received plant extract (150 mg/kg (Body weight)) once in a week, while group 4 (N=7) was given combination of diethylnitrosoamine (3.5 l/mg) and plant extract (150 mg/kg (Body weight)). After eight weeks of DEN induction group 2 mice were divided into two subgroups containing seven mice each, subgroup 1 was sacrificed while subgroup 2 was treated with plant extract (150 mg/kg (Body weight)) once in a week for eight consecutive weeks. Results The model of DEN injected hepatocellular carcinomic (HCC) mice elicited significant decline in levels of albumin with concomitant significant elevations in tumor markers aspartate aminotransferase, alanine aminotransferase (ALT), lactate dehydrogenase (LDH), alpha feto protein (AFP), gamma glutamyl transferase (Y-GT), 5 nucleotidase (5NT), glucose-6-phosphate dehydrogenase (G6PDH) and bilirubin. The intraperitoneal administration of B. ciliata as a protective agent, produced significant increase in albumin levels with significant decrease in the levels of tumor markers aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), alpha feto protein (AFP), gamma glutamyl transferase (Y-GT), 5 nucleotidase (5NT), glucose-6-phosphate dehydrogenase (G6PDH) and bilirubin. Conclusion Bergenia ciliata has potent antioxidant activity, radical scavenging capacity and anticancerous properties. Bergenia ciliata extracts may provide a basis for development of anti-cancerous drug.


Resumo Antecedentes O carcinoma hepatocelular é a neoplasia primária mais frequente do fígado e é responsável por até um milhão de mortes em todo o mundo em um ano. Objetivos O objetivo do presente estudo foi avaliar a eficiência anticancerígena do rizoma de Bergenia ciliata contra a hepatocarcinogênese induzida por dietilnitrosoamina em camundongos balb c. Métodos Um por cento de dietilnitrosoamina foi preparado usando 99 ml de solução salina normal (0,9 por cento) à qual foi adicionado 1 ml de solução concentrada de dietilnitrosoamina (DEN) (0,01 g / l). O extrato de Bergenia ciliata foi preparado pela técnica de maceração. Os ratos foram classificados em quatro grupos: Grupo 1 grupo controle (N = 7) recebeu solução salina (3,5 mL / mg), grupo 2 (N = 14) recebeu dietilnitrosoamina (3,5 mL / mg) por via intraperitoneal uma vez por semana para oito semanas consecutivas, o grupo 3 (N = 7) recebeu extrato vegetal (150 mg / kg (peso corporal)) uma vez por semana, enquanto o grupo 4 (N = 7) recebeu combinação de dietilnitrosoamina (3,5 l / mg) e extrato (150 mg / kg (peso corporal). Após oito semanas do grupo de indução DEN 2 ratos foram divididos em dois subgrupos contendo sete ratos cada, subgrupo 1 foi sacrificado enquanto subgrupo 2 foi tratado com extrato vegetal (150 mg / kg)) uma vez por semana durante oito semanas consecutivas. Resultados O modelo de camundongos hepatocelulares carcinômicos (CHC) injetados com DEN provocou declínio significativo nos níveis de albumina com elevações significativas concomitantes nos marcadores tumorais: aspartato aminotransferase, alanina aminotransferase (ALT), lactato desidrogenase (LDH), proteína alfa feto (AFP), gama glutamiltransferase (Y-GT), 5 nucleotidase (5NT), glicose-6-fosfato ehidrogenase (G6PDH) e bilirrubina. A administração intraperitoneal de B. ciliata como agente protetor produziu um aumento significativo nos níveis de albumina com uma diminuição significativa nos níveis dos marcadores tumorais: aspartato aminotransferase, alanina aminotransferase (ALT), lactato desidrogenase (LDH), proteína alfa feto (AFP), gama glutamiltransferase (Y-GT), 5 nucleotidase (5NT), glicose-6-fosfato desidrogenase (G6PDH) e bilirrubina. Conclusão Bergenia ciliata possui atividade antioxidante potente, capacidade de eliminação de radicais livres e propriedades anticancerígenas. Extratos de Bergenia ciliata podem fornecer uma base para o desenvolvimento de drogas anti-cancerígenas.

13.
Artigo em Inglês | LILACS-Express | LILACS, VETINDEX | ID: biblio-1467346

RESUMO

Abstract The main objective of current study was to investigate the chemopreventive and chemotherapeutic activity of Artemisia vulgaris extract on diethylnitrosoamine induced hepatocarcinogenesis in Balb C mice. Diethylnitrosoamine (DEN: 0.9%) was prepared to induce hepatocarcinoma in Balb C mice. The extract Artemisia vulgaris (AV) was prepared by maceration technique. Mice were classified into four groups as follows: Group 1 a control group (N=7) received saline solution (3.5 l/mg), group 2 (N=14) received diethylnitrosoamine (3.5 l/mg) intraperitoneally once in a week for eight consecutive weeks, group 3 (N=7) received only plant extract (AV: 150 mg/kg (Body weight) once in a week, while group 4 (N=7) was given in combination of diethylnitrosoamine (3.5 l/mg) and plant extract (AV: 150 mg/kg (body weight). After eight weeks of DEN administration, mice of group 2 were divided into two subgroups containing seven mice each; subgroup 1 was sacrificed while subgroup 2 was treated with plant extract only (150 mg/kg (body weight)) once in a week for eight consecutive weeks. The DEN injected mice significant decline in levels of albumin with concomitant significant elevations such as aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, alpha feto protein, gamma glutamyl transferase, 5 nucleotidase, glucose-6-phosphate dehydrogenase and bilirubin. The administration of A. vulgaris significantly decreased the DEN induced hepatotoxicity. Present study revealed the potential anti-cancerous nature of Artemisia vulgaris, both in case of chemopreventive and post-treatment of A. vulgaris. Further studies are needed to explore the mechanism of prevention and therapy.


Resumo O objetivo principal do presente estudo foi investigar as atividades quimiopreventiva e quimioterápica do extrato de Artemisia vulgaris em hepatocarcinogênese induzida por dietilnitrosoamina (DEN) em camundongos Balb C. Dietilnitrosoamina (DEN: 0,9%) foi preparada para induzir hepatocarcinoma em camundongos da linhagem Balb C. O extrato de A. vulgaris (AV) foi preparado pela técnica de maceração. Os camundongos foram classificados em quatro grupos conforme os seguintes: grupo 1, grupo controle (N=7) recebeu solução salina (3,5 µl/mg); grupo 2 (N=14) recebeu dietilnitrosoamina (3,5 µl/mg) por via intraperitoneal uma vez por semana durante oito semanas consecutivas; grupo 3 (N=7) recebeu apenas o extrato vegetal (AV: 150 mg/kg (peso corporal) uma vez por semana; enquanto no grupo 4 (N=7) foi administrado uma combinação de dietilnitrosoamina (3,5 l/mg) com extrato vegetal (AV: 150 mg/kg (peso corporal). Após oito semanas de administração de DEN, os camundongos do grupo 2 foram divididos em dois subgrupos, contendo sete camundongos cada um; no subgrupo 1, os animais foram sacrificados, enquanto no subgrupo 2, os animais foram tratados apenas com extrato vegetal (150 mg/kg (peso corporal)) uma vez por semana durante oito semanas consecutivas. Os camundongos nos quais foram injetados DEN apresentaram declínio significativo nos níveis de albumina, mas elevações significativas concomitantes de: aspartato aminotransferase, alanina aminotransferase, lactato desidrogenase, alfa-fetoproteína, gama-glutamiltransferase, 5 nucleotidase, glicose-6-fosfato desidrogenase e bilirrubina. A administração de A. vulgaris diminuiu significativamente a hepatotoxicidade induzida pelo DEN. O presente estudo apresentou a potencialidade anticancerosa da A. vulgaris, tanto nos casos de quimioprevenção quanto no pós-tratamento da A. vulgaris. Mais estudos são necessários para explorar o mecanismo de prevenção e a terapia.

14.
Biotech Histochem ; 91(8): 493-500, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27849392

RESUMO

We investigated the effects of Nigella sativa on apoptosis and gamma-aminobutyric acid (GABAA) receptor density in cerebral cortical and hippocampal neurons in a pentylenetetrazol (PTZ)-induced kindling model in rats. The PTZ kindling model was produced by injecting PTZ in subconvulsive doses to rats on days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22 and 24 of the study into animals of PTZ treated (PTZ) and PTZ + N. sativa treated (PTZ + NS) groups. Clonic and tonic seizures were induced by injecting a convulsive dose of PTZ on day 26 of the study. Rats in the PTZ + NS group were treated also with a 10 mg/kg methanolic extract of N. sativa 2 h before each PTZ injection. Rats in the control group were treated with 4 ml/kg saline. The number of neurons that expressed GABAA receptors in the hippocampus and cerebral cortex of rats in the PTZ and PTZ + NS groups increased significantly. There was no significant difference in the number of GABAA receptors between the PTZ and PTZ + NS groups. GABAA receptor density of the neurons in the cerebral cortex, but not hippocampus, was increased in PTZ group compared to controls. We observed a significant increase in the number of apoptotic neurons in the cerebral cortex of rats of both the PTZ and PTZ + NS groups compared to controls. We observed a significant decrease in the number of the apoptotic neurons in the cerebral cortex of rats in the PTZ + NS group compared to the PTZ group. N. sativa treatment ameliorated the PTZ induced neurodegeneration in the cerebral cortex as reflected by neuronal apoptosis and neuronal GABAA receptor frequency.


Assuntos
Apoptose/fisiologia , Hipocampo/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Nigella sativa/metabolismo , Pentilenotetrazol/toxicidade , Receptores de GABA-A/metabolismo , Animais , Hipocampo/metabolismo , Excitação Neurológica , Masculino , Neurônios/metabolismo , Ratos Wistar , Ácido gama-Aminobutírico/metabolismo
15.
Monaldi Arch Chest Dis ; 77(1): 8-18, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22662640

RESUMO

AIM: The aim of our study was to assess the role of non-invasive methods in assessing airway inflammation and structural changes in asthma and COPD. METHODS: The study was conducted on patients attending outpatient and inpatient department of TB and Chest Diseases and Department of Pathology at our hospital from January 2006 to August 2007. 50 asthmatic and 46 COPD patients were selected. A detailed history and clinical examination, routine laboratory investigations, pulmonary function testing, Chest X-ray PA and lateral view, HRCT Thorax, biochemical and cellular analysis of sputum was carried out in all cases. Quality control and procedures of pulmomary function test were performed according to the European Respiratory Society guidelines. RESULTS: Bronchial wall thickening, bronchiectasis and air trapping correlated well with disease severity in asthmatics while all abnormal HRCT finding correlate well with disease severity in COPD patients. The levels of MMP-9 and TIMP-1 increased significantly with increasing disease severity in both asthmatic and COPD groups. The MMP-9/TIMP-1 ratio decreased with increasing disease severity in both groups. The major source of MMP-9 in human lungs is macrophages, neutrophils and eosinophils. Macrophages and neutrophils were also the source of TIMP-1. CONCLUSION: Asthma and COPD are characterised by an imbalance between MMP-9 and TIMP-1. COPD patients showed a higher prevalence of HRCT findings which correlate with their lower MMP-1/TIMP-1 ratio than asthmatics supporting fact that the destruction and fibrosis of alveolar walls are more prominent in COPD. MMP-9/TIMP-1 ratio is associated with magnitude of HRCT findings in asthma and COPD and suggests that level of these markers reflect the extent of structural changes of airway.


Assuntos
Asma/diagnóstico , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Feminino , Humanos , Masculino , Metaloproteinase 9 da Matriz/análise , Escarro/química , Inibidor Tecidual de Metaloproteinase-1/análise , Tomografia Computadorizada por Raios X
16.
Phytother Res ; 20(1): 66-70, 2006 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-16397846

RESUMO

Crataegus (hawthorn) has long been used as a folk medicine all around the world. Most of the studies with Crataegus species focus on effects on heart failure and cardiovascular disease. The pharmacological effects of Crataegus have been attributed mainly to the content of flavonoids, procyanidin, aromatic acid and cardiotonic amines. The present study investigated the blood pressure and the structure of the coronary arterial wall of L-NAME-induced hypertensive rats given an aqueous leaf extract of C. tanacetifolia (100 mg/kg), for 4 weeks via gavage. It was observed that C. tanacetifolia, especially the hyperoside fraction, prevented L-NAME-induced hypertension in rats and had beneficial effects on the cardiovascular system.


Assuntos
Pressão Sanguínea/efeitos dos fármacos , Vasos Coronários/efeitos dos fármacos , Hipertensão/prevenção & controle , Extratos Vegetais/uso terapêutico , Quercetina/análogos & derivados , Animais , Vasos Coronários/citologia , Crataegus/química , Inibidores Enzimáticos/toxicidade , Hipertensão/induzido quimicamente , Rim/enzimologia , Lipídeos/sangue , Masculino , Miocárdio/citologia , Miócitos de Músculo Liso/citologia , NG-Nitroarginina Metil Éster/toxicidade , Óxido Nítrico Sintase/análise , Óxido Nítrico Sintase/antagonistas & inibidores , Extratos Vegetais/farmacologia , Folhas de Planta/química , Quercetina/isolamento & purificação , Quercetina/farmacologia , Ratos
17.
João Pessoa; s.n; 2004. 175 p. ilus.
Tese em Português | Index Psicologia - Teses | ID: pte-29103

RESUMO

Este estudo tem como objetivo analisar a produção de subjetividades das trabalhadoras (professoras, diretoras, merendeiras, técnicas e diretoras adjuntas) que participam do 'Programa de Formação em Saúde, Gênero e trabalho em Escolas Públicas' realizado no município de João Pessoa - PB. Este Programa foi estruturado a partir de um dispositivo metodológico denominado 'Comunidade Ampliada de Pesquisa' (Oddone et al.,1986), que possibilita a produção de conhecimento a partir da articulação entre o pólo da experiência dos/as trabalhadores/as e o pólo dos conceitos científicos. O Programa tem como objetivo geral intervir na problemática das condições de saúde e trabalho nas escolas públicas do ensino fundamental, através de ciclos de formação de trabalhadores/as para sua auto-defesa e do desenvolvimento de uma metodologia de monitoramento das condições de saúde e trabalho, sob a perspectiva das relações de gênero. Como aportes teóricos principais que fundamentam nosso estudo recorremos ao Modelo Operário de Produção de Conhecimento sobre saúde-trabalho e a 'Comunidade Ampliada de Pesquisa (Oddone et al.,1986). Também atravessa nossas análises a noção de Produção de Subjetividades formulada por Guattari (1986), a partir da qual este autor pensa como a subjetividade é modelada, fabricada e consumida na sociedade atual. Como instrumentos metodológicos foram utilizados a observação participante e entrevistas individuais de caráter semi-estruturado. Participaram da pesquisa as quinze trabalhadoras que integram o Programa desde o seu primeiro ciclo, que se iniciou em outubro de 2001. Verificamos que no decorrer do processo de formação essas trabalhadoras sinalizavam para um embate de forças fazendo movimentos diferenciados que oscilavam entre a naturalização/desnaturalização, manutenção/desmanchamento dos modos de perceber, sentir e agir em relação às questões de gênero, saúde e trabalho na escola. Nessa perspectiva, alguns focos de resistências aos processos de trabalho instituídos nas escolas foram agenciados, proliferando o desejo de inventar novas estratégias principalmente em defesa da saúde e da afirmação da vida no trabalho...(AU)

18.
Clin Cancer Res ; 4(3): 545-57, 1998 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-9533521

RESUMO

Analogues of camptothecins are specific inhibitors of eukaryotic DNA topoisomerase I (topo I) that lead to DNA damage and, eventually, cellular cytotoxicity. Camptothecin analogues bind to this target enzyme in the course of its normal function and stabilize the DNA-enzyme adduct to form a "cleavable complex." Preclinical experiments using Western blot analyses have shown cleavable complex formation to be the key intermediate step in topo I inhibition. In this series of experiments, it was our goal to convert this laboratory technique into a useful clinical assay, allowing measurement of the target enzyme and detection of the key intermediate in clinical specimens taken from patients being treated with the topo I inhibitor topotecan. Because available antibodies were not sufficiently sensitive at the start of this project, we identified a highly specific human SCL-70 antibody from a patient with scleroderma, which allowed quantitative determination of topo I copy number in HeLa and HT-29 cell lines. Additional refinements of the Western blot technique were accomplished to improve signal:noise ratio. In surgical tumor specimens, we found the median topo I level to be 30.1 x 10(5) copies/cell for gastric adenocarcinomas, compared to 18.4 x 10(5) copies/cell for normal gastric mucosae in the same samples. For lung adenocarcinoma, the median protein level was 21.5 x 10(5) copies/cell, compared with the normal tissue counterpart protein level of 12.7 x 10(5) copies/cell. The median tumor:normal ratios from paired samples of these tumor types were 1.51 and 1.84, respectively. As part of a Phase II study evaluating the efficacy of topotecan (1.5-2.0 mg/m2 daily for 5 days) in upper gastrointestinal malignancies, we obtained tumor and normal mucosa biopsies in 11 patients with gastric or esophageal cancer, 30 min after administration on day 4 or 5. Three patients with gastric adenocarcinoma had stable disease as their best response, with the remainder of patients progressing. Improvement in Western blotting methodology allowed the quantitation of topo I levels in these gastric and esophageal cancer biopsies, which could be augmented by brief heating to release complexed topo I. We were also able to directly visualize high molecular weight topo I-containing bands, which were shown to be cleavable complexes by heat reversal, with restoration of the topo I Mr 100,000 band. Using this heat reversal technique, we determined the presence of cleavable complex in a total of 7 of 11 patient biopsy samples (5 tumors and 2 normal mucosae). In patients treated with topotecan on this dose and schedule, we determined that a median of 73% of the total tumor topo I was involved in cleavable complex (range, 18.3-91%). The intensity of the Mr 100,000 topo I band in biopsy specimens of patients receiving topotecan represented "free" or noncomplexed topo I. The median copy number for the residual, noncomplexed topo I (n = 11) was 7.36 x 10(5) copies/cell, significantly less than the median of 30.1 x 10(5) copies/cell for random tumor specimens from patients with gastric adenocarcinomas (P < 0.001). Pharmacodynamic analysis demonstrated a negative correlation between the noncomplexed topo I copy number and topotecan area under the curve (Spearman rank test: r(s) = -0.81, P = 0.003). Nonlinear regression analyses of these data were best fit with an inhibitory maximum effect model, yielding parameter estimates for Emax and EC50 of 29.3 x 10(5) copies/cell (coefficient of variation = 22%) and 43.1 ng x h/ml (coefficient of variation = 27%), respectively. Through a series of careful modifications and refinements, we have improved the Western blot assay for topo I for use in clinical monitoring. We have demonstrated the ability to directly visualize cleavable complex in patients being treated with topo I inhibitor therapy and have directly quantitated free topo I, as well as the key topo I intermediate (cleavable complex), in biopsy specimens obtained from pat


Assuntos
Antineoplásicos/uso terapêutico , DNA Topoisomerases Tipo I/metabolismo , Neoplasias Gastrointestinais/tratamento farmacológico , Neoplasias Gastrointestinais/enzimologia , Topotecan/uso terapêutico , Adenoma de Células das Ilhotas Pancreáticas/enzimologia , Antineoplásicos/sangue , Autoanticorpos/sangue , Autoantígenos/imunologia , Biomarcadores/sangue , Biópsia , Neoplasias da Mama/enzimologia , Linhagem Celular , Neoplasias do Endométrio/enzimologia , Neoplasias Esofágicas/enzimologia , Feminino , Neoplasias Gastrointestinais/patologia , Células HeLa , Humanos , Neoplasias Pulmonares/enzimologia , Proteínas Nucleares/imunologia , Neoplasias Ovarianas/enzimologia , Neoplasias Pancreáticas/enzimologia , Escleroderma Sistêmico/sangue , Escleroderma Sistêmico/imunologia , Neoplasias Gástricas/enzimologia , Inibidores da Topoisomerase I , Topotecan/sangue , Células Tumorais Cultivadas
19.
Intensive Care Med ; 22(9): 995-6, 1996 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-8905441

RESUMO

Ingestion of 3,4-methylene dioxymethamphetamine (MDMA), commonly known as "Ecstasy", can produce toxicity that is characterised by hyperthermia, coagulopathy, rhabdomyolysis and renal failure. We report a fatality associated with MDMA ingestion and briefly review the current literature on MDMA-induced hyperthermia.


Assuntos
Injúria Renal Aguda/induzido quimicamente , Transtornos da Coagulação Sanguínea/induzido quimicamente , Febre/induzido quimicamente , Alucinógenos/intoxicação , N-Metil-3,4-Metilenodioxianfetamina/intoxicação , Rabdomiólise/induzido quimicamente , Adolescente , Dantroleno/uso terapêutico , Evolução Fatal , Febre/tratamento farmacológico , Humanos , Masculino , Relaxantes Musculares Centrais/uso terapêutico
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