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1.
Radiat Oncol ; 17(1): 67, 2022 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-35379264

RESUMO

PURPOSE/OBJECTIVE(S): To report results from our phase II study of stereotactic body radiotherapy (SBRT) delivering 36 Gy in 4 fractions for patients with localized prostate cancer. MATERIALS/METHODS: We enrolled 55 patients treated with SBRT delivering 36 Gy in 4 fractions between 2015 to 2018. All patients were categorized as low-risk (n = 4), intermediate-risk (n = 31) or high-risk (n = 20) according to National Comprehensive Cancer Network criteria. Median age was 73 years (range 54-86 years). Two-thirds of patients (n = 37) had received androgen-deprivation therapy for 3-46 months (median, 31 months). Median duration of follow-up was 36 months (range 1-54 months). We used Radiation Therapy Oncology Group and National Cancer Institute-Common Toxicity Criteria version 4 for toxicity assessments. Quality of life (QOL) outcomes were also evaluated using the Expanded Prostate Cancer Index Composite (EPIC). RESULTS: Protocol treatments were completed for all patients. Six patients experienced biochemical failures. Among these six patients, three patients experienced clinical failure. One patient showed bone metastasis before biochemical failure. One patient died of gastric cancer. The 3-year biochemical control rate was 89.8%. Acute grade 2 genitourinary (GU) and gastrointestinal (GI) toxicities were observed in 5 patients (9%) and 6 patients (11%), respectively. No grade 3 or higher acute toxicities were observed. Late grade 2 GU and GI toxicities were observed in 7 patients (13%) and 4 patients (7%), respectively. Late grade 3 GU and GI toxicities were observed in 1 patient (1.8%) each. EPIC scores decreased slightly during the acute phase and recovered within 3 months after treatment. CONCLUSION: Our phase II study showed that SBRT delivering 36 Gy in 4 fractions was safe and effective with favorable QOL outcomes, although this regimen showed slightly more severe toxicities compared to current standards.


Assuntos
Neoplasias da Próstata , Radiocirurgia , Idoso , Idoso de 80 Anos ou mais , Antagonistas de Androgênios , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias da Próstata/radioterapia , Neoplasias da Próstata/cirurgia , Qualidade de Vida , Radiocirurgia/efeitos adversos , Radiocirurgia/métodos , Sistema Urogenital
2.
Stud Health Technol Inform ; 264: 1745-1746, 2019 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-31438323

RESUMO

Albumin level is q significant indicator of patient nutritional status. However, Point of Care Testing (POCT) devices and telemedicine system that nurses can operate easily in-home medical care is not developed. The aim of this work is the development of a POCT device for Albumin level and application to a telemedicine support system. The operability of our system was simple and easy for the nurse or patient. We believe our method is useful for Nutrition Support Team activities in-home medical care.


Assuntos
Serviços de Assistência Domiciliar , Enfermagem Domiciliar , Terapia Nutricional , Telemedicina , Albuminas , Humanos
3.
Osteoporos Int ; 28(8): 2367-2376, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-28409215

RESUMO

Once a localized reaction (beaking) was detected, discontinuation of bisphosphonates (BPs) and switching to vitamin D supplementation or teriparatide therapy effectively improved its shape. When the localized reaction was high, of the pointed type, and/or accompanied by prodromal pain, the risks of complete and incomplete atypical femoral fracture increased and consideration of prophylactic fixation for such patients was required. INTRODUCTION: Femoral localized reaction (localized periosteal thickening of the lateral cortex, beaking) is reported to precede atypical femoral fractures (AFFs) and to develop in 8-10% of patients with autoimmune diseases taking BPs and glucocorticoids. The aims of the present study were to retrospectively investigate the shapes of localized reaction to consider how to manage the condition. METHODS: Twenty femora of 12 patients with autoimmune diseases who were on BPs and glucocorticoids exhibited femoral localized reaction. The heights of localized reaction were measured and the shapes classified as pointed, arched, and other. Localized reaction changes were divided into three categories: deterioration, no change, and improvement. A severe form of localized reaction was defined; this was associated with prodromal pain, de novo complete AFF, or incomplete AFF with a fracture line at the localized reaction. RESULTS: The mean height of localized reaction was 2.3 ± 0.8 mm (range, 1.0-3.7 mm) and the pointed type was 35%. Localized reaction was significantly higher (3.3 ± 0.8 vs. 2.1 ± 0.7 mm; p = 0.003) and the pointed type more common (78 vs. 27%; p = 0.035) in those with the severe form of localized reaction. Seven patients with localized reactions discontinued BPs just after localized reaction was detected, but five continued on BPs for 2 years. Localized reaction deterioration was more common in patients who continued than discontinued BPs (100 vs. 29%; p = 0.027). After 2 years, all patients had discontinued BPs and localized reaction did not deteriorate further in any patient. CONCLUSIONS: Once a localized reaction was detected, discontinuation of BPs and switching to vitamin D supplementation or teriparatide therapy effectively improved it. When the localized reaction was high, of the pointed type, and/or accompanied by prodromal pain, the risks of complete and incomplete AFF increased and consideration of prophylactic fixation for such patients was required.


Assuntos
Doenças Autoimunes/tratamento farmacológico , Conservadores da Densidade Óssea/efeitos adversos , Difosfonatos/efeitos adversos , Fraturas do Fêmur/induzido quimicamente , Glucocorticoides/efeitos adversos , Adulto , Idoso , Biomarcadores/metabolismo , Conservadores da Densidade Óssea/administração & dosagem , Conservadores da Densidade Óssea/uso terapêutico , Osso e Ossos/metabolismo , Difosfonatos/administração & dosagem , Difosfonatos/uso terapêutico , Esquema de Medicação , Feminino , Fraturas do Fêmur/diagnóstico por imagem , Fraturas do Fêmur/patologia , Fraturas de Estresse/induzido quimicamente , Fraturas de Estresse/diagnóstico por imagem , Fraturas de Estresse/patologia , Glucocorticoides/administração & dosagem , Glucocorticoides/uso terapêutico , Humanos , Pessoa de Meia-Idade , Radiografia , Estudos Retrospectivos
4.
J Anim Sci ; 93(8): 4048-57, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26440184

RESUMO

The aim of the study was to clarify 1) the distribution of 6 α-tocopherol (α-Toc)-associated gene expressions in 20 major tissues, including metabolic, reproductive, endocrine, immune, and digestive and absorptive tissues, in relation to α-Toc status and 2) the change in expression patterns of the genes induced when α-Toc was orally administered to Japanese Black (JB) calves. This study examined weaned male JB calves ( = 10), of which 5 calves were orally administered α-Toc for 2 wk (30 IU·kg BW·d; TOC group). The others did not receive the α-Toc supplement and were the control (CONT) group. The 20 tissues and venous blood (serum) were sampled on the final day. In both groups, the mean mRNA expression levels for α-Toc transfer protein, afamin (AFM), ATP-binding cassette transporter A1, and tocopherol-associated protein were greatest in the liver ( < 0.05), whereas scavenger receptor class B, Type I (SR-BI) mRNA was greatest in the adrenal gland ( < 0.05). The gene for cytochrome P450 family 4, subfamily F, polypeptide 2 was most highly expressed in the liver, testes, and adrenal gland. The α-Toc content was greatest ( < 0.05) in the testes of the 20 sampled tissues in the CONT group. However, the levels in the testes and jejunum were similar and greater ( < 0.05) than the levels in the other 18 tissues in the TOC group. The mean increase in α-Toc levels after oral α-Toc administration (mean α-Toc content for the TOC group divided by the CONT group content) were greater ( < 0.05) in the jejunum (40.7-fold) and duodenum and liver (26.3- and 23.1-fold) than in the serum (7.8-fold). In the liver, α-Toc administration significantly increased ( < 0.05) the AFM and SR-BI mRNA expression levels. The results show that the liver may play an important role in the regulation of α-Toc disposition, but other peripheral tissues that accumulate large amounts of α-Toc could moderate the local α-Toc status and functions, as inferred from the high expressions of the α-Toc-associated genes in JB calves.


Assuntos
Transportadores de Cassetes de Ligação de ATP/metabolismo , Bovinos/fisiologia , Suplementos Nutricionais , Regulação da Expressão Gênica/efeitos dos fármacos , alfa-Tocoferol/administração & dosagem , Animais , Fígado/metabolismo , Masculino , Reprodução/efeitos dos fármacos , alfa-Tocoferol/metabolismo
5.
Caries Res ; 45(1): 56-63, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21311187

RESUMO

BACKGROUND: Oenothera biennis (evening primrose) seed extract (OBSE) is known to contain polyphenols, which may possess antioxidant activities. Polyphenols extracted from several plants are reported to exhibit cariostatic activities by inhibiting mutans streptococcus growth and glucosyltransferase activities. The purpose of the present study was to examine the inhibitory effects of OBSE on the development of dental caries, both in vitro and in vivo. METHODS: OBSE was investigated for its inhibitory effects on cellular aggregation, hydrophobicity, sucrose-dependent adherence and insoluble glucan synthesis. Furthermore, biofilm formation was examined in the presence of OBSE, using confocal microscopic imaging. An animal experiment was also performed to examine the in vivo effects. RESULTS: OBSE induced a strong aggregation of Streptococcus mutans MT8148 cells, while cell surface hydrophobicity was decreased by approximately 90% at a concentration of 0.25 mg/ml. The sucrose-dependent adherence of the MT8148 cells was also reduced by addition of OBSE, with a reduction rate of 73% seen at a concentration of 1.00 mg/ml. Additionally, confocal microscopic observations revealed the biofilm development phase to be remarkably changed in the presence of OBSE. Furthermore, insoluble glucan synthesis was significantly reduced when OBSE was present at concentrations greater than 0.03 mg/ml. In an animal experiment, the caries scores in rats given OBSE (0.05 mg/ml in drinking water) were significantly lower than those in rats given water without OBSE. CONCLUSION: Our results indicate that OBSE has inhibitory activity on dental caries.


Assuntos
Cariostáticos/uso terapêutico , Cárie Dentária/tratamento farmacológico , Oenothera biennis , Fitoterapia , Extratos Vegetais/uso terapêutico , Streptococcus mutans/efeitos dos fármacos , Animais , Aderência Bacteriana/efeitos dos fármacos , Biofilmes/efeitos dos fármacos , Cariostáticos/farmacologia , Cárie Dentária/microbiologia , Glucanos/metabolismo , Glucosiltransferases/antagonistas & inibidores , Interações Hidrofóbicas e Hidrofílicas/efeitos dos fármacos , Masculino , Extratos Vegetais/farmacologia , Ratos , Ratos Sprague-Dawley , Sementes
6.
Physiol Res ; 55(2): 157-164, 2006.
Artigo em Inglês | MEDLINE | ID: mdl-15910170

RESUMO

The aim of this study was to investigate the effects of rooibos tea as a natural source of a wide scale of antioxidants on the prevention and treatment of oxidative stress in streptozotocin-induced diabetic rats. Expected significant changes of biochemical parameters characteristic for experimental diabetic state were found in plasma and tissues eight weeks after single dose streptozotocin application. Administration of aqueous and alkaline extracts of rooibos tea (or N-acetyl-L-cysteine for comparison) to diabetic rats did not affect markers of the diabetic status (glucose, glycated hemoglobin and fructosamine). Besides the parameters characterizing hepatotoxic effect of streptozotocin, rooibos tea significantly lowered advanced glycation end-products (AGEs) and malondialdehyde (MDA) in the plasma and in different tissues of diabetic rats, particularly MDA concentration in the lens. From these results we can conclude that antioxidant compounds in rooibos tea partially prevent oxidative stress and they are effective in both hydrophobic and hydrophilic biological systems. Therefore, rooibos tea as a commonly used beverage can be recommended as an excellent adjuvant support for the prevention and therapy of diabetic vascular complications, particularly for protecting ocular membrane systems against their peroxidation by reactive oxygen species.


Assuntos
Aspalathus , Diabetes Mellitus Experimental/tratamento farmacológico , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/farmacologia , Acetilcisteína/farmacologia , Animais , Concentração de Íons de Hidrogênio , Masculino , Extratos Vegetais/química , Extratos Vegetais/uso terapêutico , Ratos , Ratos Wistar
7.
Physiol Res ; 53(5): 515-21, 2004.
Artigo em Inglês | MEDLINE | ID: mdl-15479130

RESUMO

The effect of rooibos tea (Aspalathus linearis) on liver antioxidant status and oxidative stress was investigated in rat model of carbon tetrachloride-induced liver damage. Synthetic antioxidant N-acetyl-L-cysteine (NAC) was used for comparison. Administration of carbon tetrachloride (CCl4) for 10 weeks decreased liver concentrations of reduced and oxidized forms of coenzyme Q9 (CoQ9H2 and CoQ9), reduced -tocopherol content and simultaneously increased the formation of malondialdehyde (MDA) as indicator of lipid peroxidation. Rooibos tea and NAC administered to CCl4-damaged rats restored liver concentrations of CoQ9H2 and alpha-tocopherol and inhibited the formation of MDA, all to the values comparable with healthy animals. Rooibos tea did not counteract the decrease in CoQ9, whereas NAC was able to do it. Improved regeneration of coenzyme Q9 redox state and inhibition of oxidative stress in CCl4-damaged livers may explain the beneficial effect of antioxidant therapy. Therefore, the consumption of rooibos tea as a rich source of natural antioxidants could be recommended as a market available, safe and effective hepatoprotector in patients with liver diseases.


Assuntos
Antioxidantes/uso terapêutico , Aspalathus/metabolismo , Bebidas , Falência Hepática Aguda/tratamento farmacológico , Falência Hepática Aguda/metabolismo , Regeneração Hepática/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Ubiquinona/metabolismo , Acetilcisteína/administração & dosagem , Animais , Tetracloreto de Carbono , Masculino , Oxirredução/efeitos dos fármacos , Fitoterapia/métodos , Extratos Vegetais/administração & dosagem , Ratos , Ratos Wistar , Resultado do Tratamento
8.
Xenobiotica ; 32(5): 399-409, 2002 May.
Artigo em Inglês | MEDLINE | ID: mdl-12065062

RESUMO

1. The disposition of SM-11355, an anticancer platinum complex for hepatocellular carcinoma, was investigated in dog by measuring platinum (Pt) and radioactivity levels following intrahepatic arterial administration of (14)C-SM-11355 suspended in Lipiodol, an oily lymphographic agent. Plasma and excretion profiles were monitored in six animals, with tissue distribution studied after 1 day, 4 and 13 weeks (n = 2/time point). 2. SM-11355 was released very slowly into the systemic circulation from Lipiodol, resulting in very low levels of Pt compounds in plasma, urine, faeces and organs. Plasma levels of Pt and radioactivity declined with apparent half-lives of 5-7 weeks. Excretion continued even at 3 months after the administration with proportions excreted for Pt and radioactivity up to 30-60% in urine and 8-10% in faeces. 3. The Pt and radioactivity in the liver accounted for 80-100% of the dose at 1 day and for 20-50% at 13 weeks after the administration, predominately as intact SM-11355. The concentrations were highest in the left lobe of the liver, the administration site, but levels in the remainder of the liver were also markedly higher than those in plasma and other tissues. 4. The results strongly support the concept that SM-11355 targets the liver with highly selectivity and sustained release of Pt compounds.


Assuntos
Antineoplásicos/farmacocinética , Compostos Organoplatínicos/farmacocinética , Animais , Antineoplásicos/administração & dosagem , Radioisótopos de Carbono , Cães , Artéria Hepática , Infusões Intra-Arteriais , Óleo Iodado/administração & dosagem , Fígado/metabolismo , Masculino , Compostos Organoplatínicos/administração & dosagem , Platina/sangue , Platina/farmacocinética , Distribuição Tecidual
9.
Neuroscience ; 109(4): 677-85, 2002.
Artigo em Inglês | MEDLINE | ID: mdl-11927150

RESUMO

Cortical pyramidal neurons are considered to be less excitable in the immature cortex than in adults. Our previous report revealed that a negative feedback regulation of membrane excitability is highly correlated with a novel form of calcium release from inositol-1,4,5-trisphosphate (IP(3))-sensitive calcium stores (IP(3)-assisted calcium-induced calcium release) in neocortical pyramidal neurons under muscarinic cholinergic activation. As a step to understand the ground for the low membrane excitability in immature tissue, we examined development of IP(3)-assisted calcium-induced calcium release. In visual cortex neurons from 'juvenile' rats (2-3 weeks of age), an enhancement of spike-frequency adaptation occurred at high spike-frequencies (16-22 Hz), whereas the reduction was observed at low frequencies (6-10 Hz). IP(3)-assisted calcium-induced calcium release occurred at the higher frequencies only. In 'early' postnatal tissue (1 week of age), by contrast, at neither high nor low frequencies did this form of calcium release occur, and muscarinic cholinergic activation always induced a reduction of spike-frequency adaptation at any spike-frequencies. The mechanism for the failure of induction of IP(3)-assisted calcium-induced calcium release in 'early' postnatal tissue was investigated. Both an ample supply of calcium influx, elicited by higher frequency spike trains, and a supplementary injection of IP(3) through whole-cell pipets, combined together or applied alone, failed to enable IP(3)-assisted calcium-induced calcium release in 'early' postnatal tissue. Muscarinic cholinergic activation alone induced a conventional IP(3)-induced calcium release similar to that observed in neurons from 'juvenile' tissue. Together, it is most likely that functional IP(3)Rs and calcium channels are already present and functional, but are not yet adequately assembled to allow IP(3)-assisted calcium-induced calcium release in cortical pyramidal neurons from rats of 1 week old.


Assuntos
Canais de Cálcio/metabolismo , Cálcio/metabolismo , Diferenciação Celular/fisiologia , Neurônios/metabolismo , Receptores Citoplasmáticos e Nucleares/metabolismo , Córtex Visual/crescimento & desenvolvimento , Córtex Visual/metabolismo , Potenciais de Ação/efeitos dos fármacos , Potenciais de Ação/fisiologia , Animais , Animais Recém-Nascidos , Canais de Cálcio/efeitos dos fármacos , Sinalização do Cálcio/efeitos dos fármacos , Sinalização do Cálcio/fisiologia , Carbacol/farmacologia , Inositol 1,4,5-Trifosfato/metabolismo , Receptores de Inositol 1,4,5-Trifosfato , Agonistas Muscarínicos/farmacologia , Neurônios/efeitos dos fármacos , Ratos , Ratos Wistar , Receptores Citoplasmáticos e Nucleares/efeitos dos fármacos , Córtex Visual/efeitos dos fármacos
10.
Exp Biol Med (Maywood) ; 226(8): 758-65, 2001 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-11520942

RESUMO

The effects of mushroom fibers on serum cholesterol and hepatic low-density lipoprotein (LDL) receptor mRNA in rats were investigated. Rats were fed a cholesterol-free diet with 50 g/kg cellulose powder (CP), 50 g/kg maitake (Grifola frondosa) fiber (MAF), 50 g/kg shiitake (Lentinus edodes) fiber (SF), or 50 g/kg enokitake (Flammulina velutipes) fiber (EF) for 4 weeks. There were no significant differences in the body weight, food intake, liver weight, cecum weight, and cecum pH among the groups. Cecal acetic acid, butyric acid, and total short-chain fatty acid (SCFA) concentrations in the SF and EF groups were significantly higher than those in the other groups. The serum total cholesterol concentration in the CP group was significantly higher than that in the MAF and EF groups. The very LDL (VLDL) + intermediate-density lipoprotein (IDL) + LDL-cholesterol concentration in the CP group was significantly higher than that in the MAF, SF, and EF groups, whereas the high-density lipoprotein (HDL)-cholesterol concentration in the EF group was significantly lower than that in the other groups at the end of the 4-week feeding period. The hepatic LDL receptor mRNA level in the EF group was significantly higher than that in the CP group. The fecal cholesterol excretion in the MAF, SF, and EF groups was significantly higher than that in the CP group. The results of this study demonstrate that MAF and EF lowered the serum total cholesterol level by enhancement of fecal cholesterol excretion, and in particular, by enhancement of hepatic LDL receptor mRNA in EF group.


Assuntos
Agaricales/química , Colesterol/metabolismo , Fibras na Dieta/uso terapêutico , Hipercolesterolemia/tratamento farmacológico , Lentinula/química , Extratos Vegetais/uso terapêutico , Cogumelos Shiitake/uso terapêutico , Ácido Acético/metabolismo , Animais , Southern Blotting , Peso Corporal/efeitos dos fármacos , Butiratos/metabolismo , Ceco/metabolismo , Colesterol 7-alfa-Hidroxilase/metabolismo , Ácidos Graxos Voláteis/metabolismo , Concentração de Íons de Hidrogênio , Hidroximetilglutaril-CoA Redutases/metabolismo , Fígado/enzimologia , Masculino , Tamanho do Órgão/efeitos dos fármacos , RNA/metabolismo , RNA Mensageiro/metabolismo , Ratos , Ratos Endogâmicos F344 , Receptores de LDL/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fatores de Tempo
11.
Urology ; 58(1): 125-8, 2001 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-11445503

RESUMO

OBJECTIVES: To present a case of fluoroquinolone treatment failure in urinary tract infection caused by Pseudomonas aeruginosa, accompanied by in vivo selection of the post-treatment isolate that showed decreased susceptibilities to fluoroquinolones, and to report fluoroquinolone resistance mechanisms in the post-treatment isolate. METHODS: A patient with urinary tract infection was treated with a suboptimal dose of a fluorinated quinolone, gatifloxacin. P. aeruginosa strains were isolated before and after fluoroquinolone treatment. The pretreatment and post-treatment isolates were examined for relatedness by arbitrarily primed polymerase chain reaction. For these isolates, the minimum inhibitory concentration of antimicrobial agents was determined and mutations in the target genes (gyrA and parC) and regulatory genes (mexR and nfxB) for drug efflux pumps were analyzed. RESULTS: Failure of fluoroquinolone treatment of urinary tract infection was observed. The post-treatment isolate, which was assumed to be isogenic to the pretreatment isolate, exhibited fourfold to 16-fold increases in the MIC of fluoroquinolones. In this isolate, a new mutation, not observed in the pretreatment isolate, was found only in the gyrA gene, resulting in an amino acid change of aspartic acid to asparagine in codon 87 of GyrA. CONCLUSIONS: The P. aeruginosa isolate that was initially susceptible to fluoroquinolones showed decreased susceptibility to fluoroquinolones after treatment with a suboptimal dose of one fluoroquinolone. In the post-treatment isolate, the alteration of GyrA would be responsible for the decreased susceptibility to fluoroquinolones. We should be aware that inappropriate use of fluoroquinolones could select such a strain harboring a quinolone resistance-associated alteration of DNA gyrase.


Assuntos
Anti-Infecciosos/administração & dosagem , Pseudomonas aeruginosa/classificação , Pseudomonas aeruginosa/efeitos dos fármacos , Infecções Urinárias/tratamento farmacológico , Infecções Urinárias/microbiologia , Idoso , DNA Bacteriano/análise , Resistência Microbiana a Medicamentos , Fluoroquinolonas , Humanos , Masculino , Testes de Sensibilidade Microbiana , Mutação , Pseudomonas aeruginosa/genética , Especificidade da Espécie , Falha de Tratamento
12.
Bioorg Med Chem ; 9(6): 1571-8, 2001 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-11408176

RESUMO

A new class of 1 beta-methylcarbapenems bearing a doubly quaternarized 1,4-diazabicyclooctane (DABCO) substituted dithiocarbamate moiety at the C-2 side chain was prepared, and the biological profiles of the compounds, including in vitro and in vivo anti-MRSA activity and DHP-I susceptibility, were evaluated to identify a carbapenem derivative that was superior to BO-3482 (1). As a result, we discovered a 1 beta-methyl-2-[4-(4-carbamoylmethyl-1,4-diazabicyclo[2,2,2]octanediium-1-yl)methyl-1,2,3,6-tetrahydropyridinylthiocarbonylthio]carbapenem, 14a showing greater than 2-fold better anti-MRSA activity in a mouse infection model and 3-fold better DHP-I susceptibility as compared with BO-3482 (1).


Assuntos
Compostos Aza/química , Compostos Aza/farmacologia , Carbapenêmicos/química , Carbapenêmicos/farmacologia , Resistência a Meticilina , Piridinas/química , Piridinas/farmacologia , Staphylococcus aureus/efeitos dos fármacos , Animais , Compostos Aza/metabolismo , Proteínas Sanguíneas/metabolismo , Carbapenêmicos/metabolismo , Dipeptidases/metabolismo , Avaliação Pré-Clínica de Medicamentos , Masculino , Camundongos , Camundongos Endogâmicos ICR , Testes de Sensibilidade Microbiana , Piridinas/metabolismo , Ratos , Ratos Sprague-Dawley , Infecções Estafilocócicas/tratamento farmacológico , Staphylococcus aureus/fisiologia , Relação Estrutura-Atividade
13.
Lipids ; 36(3): 261-6, 2001 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-11337981

RESUMO

Hypocholesterolemic effects in older animals after long-term feeding are unknown. Therefore, aged rats (24 wk of age) fed a conventional diet were shifted to diets containing 10% perilla oil [PEO; oleic acid + linoleic acid + alpha-linolenic acid; n-6/n-3, 0.3; polyunsaturated fatty acid/saturated fatty acid (P/S), 9.6], borage oil [oleic acid + linoleic acid + alpha-linolenic acid; n-6/n-3, 15.1; P/S, 5.3], evening primrose oil (EPO; linoleic acid + gamma-linolenic acid; P/S, 10.5), mixed oil (MIO; oleic acid + linoleic acid + gamma-linolenic acid + alpha-linolenic acid; n-6/n-3, 1.7; P/S, 6.7), or palm oil (PLO; palmitic acid + oleic acid + linoleic acid; n-6/n-3, 25.3; P/S, 0.2) with 0.5% cholesterol for 15 wk in this experiment. There were no significant differences in the food intake and body weight gain among the groups. The liver weight in the PEO (n-6/n-3, 0.3) group was significantly higher than those of other groups in aged rats. The serum total cholesterol and very low density lipoprotein (VLDL) + intermediate density lipoprotein (IDL) + low density lipoprotein (LDL)-cholesterol concentrations of the PLO (25.3) group were consistently higher than those in the other groups. The serum high density lipoprotein cholesterol concentrations of the PEO (0.3) and EPO groups were significantly lower than in the other groups at the end of the 15-wk feeding period. The liver cholesterol concentration of the PLO (25.3) group was significantly higher than those of other groups. There were no significant differences in the hepatic LDL receptor mRNA level among the groups. Hepatic apolipoprotein (apo) B mRNA levels were not affected by the experimental conditions. The fecal neutral steroid excretion of the PLO (25.3) group tended to be low compared to the other groups. The results of this study demonstrate that both n-6 fatty acid and n-3 fatty acids such as gamma-linolenic acid and alpha-linolenic acid inhibit the increase of serum total cholesterol and VLDL + IDL + LDL-cholesterol concentrations of aged rats in the presence of excess cholesterol in the diet compared with dietary saturated fatty acid.


Assuntos
Colesterol na Dieta/administração & dosagem , Colesterol/sangue , Gorduras Insaturadas na Dieta/farmacologia , Ácidos Graxos Ômega-3/farmacologia , Ácidos Graxos Insaturados/farmacologia , Envelhecimento , Animais , Apolipoproteínas B/genética , Colesterol/análise , Ácidos Graxos Ômega-3/administração & dosagem , Ácidos Graxos Ômega-6 , Ácidos Graxos Insaturados/administração & dosagem , Fezes/química , Ácido Linoleico/administração & dosagem , Lipídeos/análise , Lipoproteínas/sangue , Fígado/anatomia & histologia , Fígado/química , Masculino , Ácido Oleico/administração & dosagem , Tamanho do Órgão , RNA Mensageiro/análise , Ratos , Ratos Endogâmicos F344 , Receptores de LDL/genética , Ácido alfa-Linolênico/administração & dosagem , Ácido gama-Linolênico/administração & dosagem
14.
EMBO J ; 20(6): 1310-9, 2001 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-11250897

RESUMO

Nuclear targeting of adenovirus is mediated by the microtubule-dependent, minus-end-directed motor complex dynein/dynactin, in competition with plus- end-directed motility. We demonstrate that adenovirus transiently activates two distinct signaling pathways to enhance nuclear targeting. The first pathway activates integrins and cAMP-dependent protein kinase A (PKA). The second pathway activates the p38/MAP kinase and the downstream MAPKAP kinase 2 (MK2), dependent on the p38/MAPK kinase MKK6, but independent of integrins and PKA. Motility measurements in PKA-inhibited, p38-inhibited or MK2-lacking (MK2(-/-)) cells indicate that PKA and p38 stimulated both the frequency and velocity of minus-end-directed viral motility without affecting the perinuclear localization of transferrin-containing endosomal vesicles. p38 also suppressed lateral viral motilities and MK2 boosted the frequency of minus-end-directed virus transport. Nuclear targeting of adenovirus was rescued in MK2(-/-) cells by overexpression of hsp27, an MK2 target that enhances actin metabolism. Our results demonstrate that complementary activities of PKA, p38 and MK2 tip the transport balance of adenovirus towards the nucleus and thus enhance infection.


Assuntos
Adenovírus Humanos/crescimento & desenvolvimento , Núcleo Celular/virologia , Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , Proteínas de Choque Térmico , Microtúbulos/metabolismo , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Animais , Transporte Biológico , Proteínas Quinases Dependentes de Cálcio-Calmodulina/metabolismo , Células , Ativação Enzimática , Proteínas de Choque Térmico HSP27 , Células HeLa , Humanos , Integrinas/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular , MAP Quinase Quinase 6 , Camundongos , Chaperonas Moleculares , Movimento , Proteínas de Neoplasias/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Transdução de Sinais , Proteínas Quinases p38 Ativadas por Mitógeno
15.
Lipids ; 36(2): 129-34, 2001 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-11269692

RESUMO

The effects of resistant starches of beans on serum cholesterol and hepatic low density lipoprotein (LDL) receptor mRNA in rats were investigated. Rats were fed a cholesterol-free diet with 150 g/kg corn starch (CS), 150 g/kg adzuki (Vigna angularis) starch (AS), 150 g/kg kintoki (Phaseolus vulgaris, variety) starch (KS), or 150 g/kg tebou (P. vulgaris, variety) starch (TS) for 4 wk. There were no significant differences in body weight among groups through the experimental period. The liver weight in the CS group was 1.1-1.2 times higher than that in the AS, KS, and TS groups. The cecum weight in the TS was 1.4 times higher than that in the CS group, and the cecal pH in the CS group was significantly higher than in the other groups. The serum total cholesterol, very low density lipoprotein + intermediate density lipoprotein + LDL-cholesterol and high density lipoprotein (HDL)-cholesterol concentrations in the bean starch groups were significantly lower than those in the CS group through the feeding period. The total cholesterol/HDL-cholesterol ratio in the bean starch groups was also significantly lower than that in the CS group at the end of the 4-wk feeding period. The hepatic cholesterol concentration in the TS group was significantly higher than in the CS group at the end of the 4-wk feeding period. The relative quantity of hepatic apo B mRNA in the AS group was 1.2 times higher than that in the CS group, and the hepatic LDL receptor mRNA levels in the AS and TS groups were 1.8-2.0 times higher than that in the CS group. The results of this study demonstrate that AS, KS, and TS lowered the serum total cholesterol level by enhancing the hepatic LDL receptor mRNA level.


Assuntos
Fabaceae , Lipídeos/sangue , Fígado/metabolismo , Plantas Medicinais , Receptores de LDL/genética , Amido/farmacologia , Animais , Apolipoproteínas B/efeitos dos fármacos , Apolipoproteínas B/genética , Apolipoproteínas B/metabolismo , Ceco/química , Ceco/efeitos dos fármacos , Ceco/metabolismo , Fezes , Fígado/efeitos dos fármacos , Fígado/crescimento & desenvolvimento , Masculino , Tamanho do Órgão/efeitos dos fármacos , Ratos , Ratos Endogâmicos F344 , Receptores de LDL/efeitos dos fármacos , Receptores de LDL/metabolismo
16.
Nihon Shokakibyo Gakkai Zasshi ; 98(2): 151-6, 2001 Feb.
Artigo em Japonês | MEDLINE | ID: mdl-11235189

RESUMO

The efficacy and safety of mesalamine enema were examined in 20 patients with steroid-resistant or dependent, distal ulcerative colitis. Rectal bleeding disappeared in 3 (18%). 8 (50%) of 16 patients within 2 weeks and 4 weeks after the start of mesalamine enema treatment, respectively. Mean clinical activity index (CAI) score after the treatment was significantly reduced (8.1-->3.6, p < 0.001). Furthermore, Mean doses of oral corticosteroid after the treatment (7.3 mg) were also significantly lower than those before the treatment (12.8 mg) (p < 0.01). Four patients dropped out. Three patients could not retain the enemas because of abdominal discomfort and one patient had fever and rash. There were no significant differences in age, gender, disease duration, disease type, and mean doses of oral corticosteroid before the treatment between the response group (n = 8) and the non-response group (n = 8). However, clinical and endoscopic activities before mesalamine enema treatment in the non-response group (CAI 9.8, Matts score 8.0) were higher than those in the response group (CAI 6.4, Matts score 5.5). These results suggest that mesalamine enema is useful for mildly to moderately active distal ulcerative colitis by improving clinical symptoms and reducing corticosteroid.


Assuntos
Anti-Inflamatórios/administração & dosagem , Colite Ulcerativa/tratamento farmacológico , Enema , Mesalamina , Prednisolona/administração & dosagem , Adolescente , Corticosteroides/administração & dosagem , Adulto , Colite Ulcerativa/diagnóstico , Resistência a Medicamentos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
18.
Kyobu Geka ; 53(8 Suppl): 715-7, 2000 Jul.
Artigo em Japonês | MEDLINE | ID: mdl-10935394

RESUMO

We report a case of 59-year-old man of descending necrotizing mediastinitis (DNM) secondary to peritonsillar abscess. A 59-year-old man with diabetes mellitus was admitted to a local hospital because of cervical swelling related to a peritonsillar abscess. Despite administration of antibiotics, swelling of the neck, dysphagia and dyspnea deteriorated. Therefore he was urgently undergone a tracheotomy and transferred to our hospital by an ambulance. The surgery consisted with neck and anterior mediastinal drainage through neck and cervical collar incision. Culture of drainage fluid showed clostridium difficile. On postoperative day 5, we started hyperbaric oxygen therapy (HBOT). After lavage and HBOT, the patient improved by degrees, and discharged on postoperative day 82. DNM is a rare but serious complication of otopharyngeal and deep neck infection that spreads down to the mediastinum through the cervical-facial planes. Its mortality rate remains high even with aggressive surgical drainage and appropriate antibiotics. Our patient was successfully treated with urgent surgical drainage, antibiotics and HBOT. HBOT might be of great value as an adjunctive management to control this fatal infection.


Assuntos
Drenagem/métodos , Oxigenoterapia Hiperbárica , Mediastinite/terapia , Antibacterianos , Terapia Combinada , Quimioterapia Combinada/uso terapêutico , Humanos , Masculino , Mediastinite/patologia , Pessoa de Meia-Idade , Necrose , Resultado do Tratamento
19.
Gen Physiol Biophys ; 19(4): 365-71, 2000 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-11409839

RESUMO

The antihemolytic activity of Rooibos and black tea on Japanese quail erythrocytes was studied. Peroxide and hypotonic hemolysis of the red blood cells of quails, either fed with Rooibos tea supplemented food or fed without tea, was performed. Long-term consumption of Rooibos tea did not change the erythrocyte fragility to either peroxide or hypotonia induced hemolysis. However, Rooibos and black teas decreased peroxide induced hemolysis of erythrocytes incubated with each of them, but not hemolysis induced by hypotonic NaCl solution. Stronger inhibition of hemolysis has been obtained when a boiled water extract of Rooibos tea was used for the inhibition. The degree of inhibition was comparable with the effect of ascorbic acid.


Assuntos
Membrana Eritrocítica/fisiologia , Eritrócitos/fisiologia , Hemólise/efeitos dos fármacos , Extratos Vegetais/farmacologia , Rosales , Chá , Animais , Coturnix , Dieta , Membrana Eritrocítica/efeitos dos fármacos , Eritrócitos/efeitos dos fármacos , Feminino , Peróxido de Hidrogênio/sangue , Masculino
20.
Antiviral Res ; 44(2): 113-22, 1999 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-10669261

RESUMO

A polysaccharide extracted from the leaf of Rhizophora apiculata (RAP) was assessed in cell culture systems, for its activity against human and simian immunodeficiency viruses. RAP inhibited HIV-1 or HIV-2 or SIV strains in various cell cultures and assay systems. It blocked the expression of HIV-1 antigen in MT-4 cells and abolished the production of HIV-1 p24 antigen in peripheral blood mononuclear cells (PBMC); the 50% effective concentration (EC50) of RAP in HIV-1 infected MT-4 cells and in PBMC was 10.7 and 25.9 microg/ml, respectively. RAP (100 microg/ml) completely blocked the binding of HIV-1 virions to MT-4 cells. RAP also reduced the production of viral mRNA when added before virus adsorption. RAP inhibited syncytium formation in cocultures of MOLT-4 cells and MOLT-4/HIV-1(IIIB) cells. RAP did not prolong activated partial thromboplastin time (APTT) up to 500 microg/ml. These properties may be advantageous should RAP be considered for further development.


Assuntos
Fármacos Anti-HIV/farmacologia , HIV-1/efeitos dos fármacos , HIV-2/efeitos dos fármacos , Rosales/química , Vírus da Imunodeficiência Símia/efeitos dos fármacos , Fármacos Anti-HIV/isolamento & purificação , Anticoagulantes/isolamento & purificação , Anticoagulantes/farmacologia , Células Cultivadas , Efeito Citopatogênico Viral/efeitos dos fármacos , Células Gigantes/efeitos dos fármacos , Células Gigantes/virologia , HIV-1/crescimento & desenvolvimento , HIV-2/crescimento & desenvolvimento , Humanos , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Polissacarídeos/isolamento & purificação , Polissacarídeos/farmacologia , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Vírus da Imunodeficiência Símia/crescimento & desenvolvimento
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