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1.
J Dairy Sci ; 102(2): 1033-1043, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30594386

RESUMO

The protocooperation between Streptococcus thermophilus and Lactobacillus delbrueckii ssp. bulgaricus relies on metabolite exchanges that accelerate acidification during yogurt fermentation. Conflicting results have been obtained in terms of the effect of the Strep. thermophilus urease and the NH3 and CO2 that it generates on the rate of acidification in yogurt fermentation. It is difficult to perform a systematic study of the effects of urease on protocooperation because it is necessary to distinguish among the direct, indirect, and strain-specific effects resulting from the combination of the strains of both species. To evaluate the direct effects of urease on protocooperation, we generated 3 urease-deficient mutants (ΔureC) of fast- and slow-acidifying Strep. thermophilus strains and observed the effects of NH3 or CO2 supplementation on acidification by the ΔureC strains. Further, we examined 5 combinations of 3 urease-deficient ΔureC strains with 2 CO2-responsive or CO2-unresponsive strains of L. bulgaricus. Urease deficiency induced a shortage of ammonia nitrogen and CO2 for the fast- and slow-acidifying Strep. thermophilus and for the CO2-responsive L. bulgaricus, respectively. Notably, the shortage of ammonia nitrogen had more severe effects than that of CO2 on yogurt fermentation, even if coculture with L. bulgaricus masked the effect of urease deficiency. Our work established (1) that urease deficiency inhibits the fermentative acceleration of protocooperation regardless of the Strep. thermophilus and L. bulgaricus strain combinations, and (2) that urease is an essential factor for effective yogurt acidification.


Assuntos
Fermentação , Lactobacillus delbrueckii/enzimologia , Streptococcus thermophilus/enzimologia , Urease/metabolismo , Iogurte , Animais , Lactobacillus delbrueckii/genética , Lactobacillus delbrueckii/metabolismo , Mutação , Streptococcus thermophilus/genética , Streptococcus thermophilus/metabolismo , Urease/deficiência , Urease/genética
2.
Appl Microbiol Biotechnol ; 98(15): 6633-40, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24723292

RESUMO

Carotenoids are a class of naturally occurring pigment, carrying out important biological functions in photosynthesis and involved in environmental responses including nutrition in organisms. Saproxanthin and myxol, which have monocyclic carotenoids with a γ-carotene skeleton, have been reported to show a stronger antioxidant activity than those with ß-carotene and zeaxanthin. In this research, a yellow-orange bacterium of strain 11shimoA1 (JCM19538) was isolated from a seaweed collected at Nabeta Bay (Shizuoka, Japan). The 16S rRNA gene sequence of strain 11shimoA1 revealed more than 99.99 % similarity with those of Jejuia pallidilutea strains in the family Flavobacteriaceae. Strain 11shimoA1 synthesized two types of carotenoids. One of them was (3R, 3'R)-zeaxanthin with dicyclic structure and another was identified as (3R, 2'S)-2'-isopentenylsaproxanthin, a novel monocyclic carotenoid with pentenyl residue at C-2' position of saproxanthin, using FAB-MS, (1)H NMR, and CD analyses. Culturing strain 11shimoA1 in an alkaline medium at pH 9.2 resulted in a markedly increased in production of 2'-isopentenylsaproxanthin per dry cell weight, but a decreased in zeaxanthin production as compared to their respective production levels in medium with pH 7.0. These carotenoids are likely to play some roles in the adaptation of the bacterium to the environmental conditions.


Assuntos
Álcalis/metabolismo , Carotenoides/biossíntese , Flavobacteriaceae/isolamento & purificação , Flavobacteriaceae/metabolismo , Alga Marinha/microbiologia , Carotenoides/química , Flavobacteriaceae/classificação , Flavobacteriaceae/genética , Japão , Estrutura Molecular , Zeaxantinas/biossíntese
3.
Neuroscience ; 218: 295-304, 2012 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-22609937

RESUMO

Prostaglandin (PG) F(2α) is one of the major prostanoids biosynthesized by cyclooxygenases (COXs) from arachidonic acid. Although it has been reported that there is a selective surge in PGF(2α) production in the hippocampus during kainic acid (KA)-induced seizure activity, the precise intra-hippocampal distribution of PGF(2α) has not been elucidated due to the paucity of effective histological techniques for detecting PGs in tissues. We investigated the tissue distribution of PGF(2α) in the rat hippocampus 30 min after KA injection by developing fixation and immunohistological-staining methods. To detect PGF(2α) directly on histological sections, we used systemic perfusion fixation with water-soluble carbodiimide fixative, followed by immersion of the brains in Zamboni's fixative. We then performed immunofluorescence staining with anti-PGF(2α) antibody, with negative control experiments used to confirm the staining specificity. Definitive immunolabeling for PGF(2α) was evident most markedly in pyramidal cells of the hippocampal cornu Ammonis (CA) 3 sector and neurons of the hilus in KA-treated rats. Immunolabeling for PGF(2α) was also evident in granule cells of the dentate gyrus. Double immunfluorescence staining revealed that PGF(2α)-immunopositive neurons expressed cytosolic phospholipases A(2), COX-2, and FP receptor. These results suggest that the major source of PGF(2α) production immediately after KA injection was neurons of the hippocampal CA3 sector, hilus and dentate gyrus. These neurons exert PGF(2α)-mediated functions via FP receptors in an autocrine/paracrine manner and may play pathophysiological roles in the acute phase (30 min) of excitotoxicity.


Assuntos
Região CA3 Hipocampal/metabolismo , Dinoprosta/biossíntese , Convulsões/metabolismo , Animais , Região CA3 Hipocampal/efeitos dos fármacos , Convulsivantes/toxicidade , Ensaio de Imunoadsorção Enzimática , Imunofluorescência , Imuno-Histoquímica , Ácido Caínico/toxicidade , Masculino , Ratos , Ratos Wistar , Receptores de Prostaglandina/biossíntese , Convulsões/induzido quimicamente , Coloração e Rotulagem/métodos
4.
Br J Pharmacol ; 166(3): 1183-91, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22242910

RESUMO

BACKGROUNDS AND PURPOSE: Lactic acidosis is a fatal adverse effect of metformin, but the risk factor remains unclear. Multidrug and toxin extrusion 1 (MATE1) is expressed in the luminal membrane of the kidney and liver. MATE1 was revealed to be responsible for the tubular and biliary secretion of metformin. Therefore, some MATE polymorphisms, that cause it to function abnormally, are hypothesized to induce lactic acidosis. The purpose of this study is to clarify the association between MATE dysfunction and metformin-induced lactic acidosis. EXPERIMENTAL APPROACH: Blood lactate, pH and bicarbonate ion (HCO(3) (-) ) levels were evaluated during continuous administration of 3 mg·mL(-1) metformin in drinking water using Mate1 knockout (-/-), heterozygous (+/-) and wild-type (+/+) mice. To determine the tissue accumulation of metformin, mice were given 400 mg·kg(-1) metformin orally. Furthermore, blood lactate data were obtained from diabetic patients given metformin. KEY RESULTS: Seven days after metformin administration in drinking water, significantly higher blood lactate, lower pH and HCO(3) (-) levels were observed in Mate1(-/-) mice, but not in Mate1(+/-) mice. The blood lactate levels were not affected in patients with the heterozygous MATE variant (MATE1-L125F, MATE1-G64D, MATE2-K-G211V). Sixty minutes after metformin administration (400 mg·kg(-1) , p.o.) the hepatic concentration of metformin was markedly higher in Mate1(-/-) mice than in Mate1(+/+) mice. CONCLUSION AND IMPLICATIONS: MATE1 dysfunction caused a marked elevation in the metformin concentration in the liver and led to lactic acidosis, suggesting that the homozygous MATE1 variant could be one of the risk factors for metformin-induced lactic acidosis.


Assuntos
Acidose Láctica/induzido quimicamente , Hipoglicemiantes/efeitos adversos , Metformina/efeitos adversos , Proteínas de Transporte de Cátions Orgânicos/genética , Acidose Láctica/sangue , Acidose Láctica/metabolismo , Animais , Diabetes Mellitus/sangue , Diabetes Mellitus/tratamento farmacológico , Relação Dose-Resposta a Droga , Células HEK293 , Homozigoto , Humanos , Hipoglicemiantes/sangue , Hipoglicemiantes/farmacocinética , Hipoglicemiantes/uso terapêutico , Rim/efeitos dos fármacos , Rim/metabolismo , Testes de Função Renal , Ácido Láctico/sangue , Fígado/efeitos dos fármacos , Fígado/metabolismo , Testes de Função Hepática , Metformina/sangue , Metformina/farmacocinética , Metformina/uso terapêutico , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Especificidade da Espécie , Transfecção
5.
Neuropathol Appl Neurobiol ; 38(6): 559-71, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22013984

RESUMO

AIMS: Multiple system atrophy (MSA) is pathologically characterized by the formation of α-synuclein-containing glial cytoplasmic inclusions (GCIs) in oligodendrocytes. However, the mechanisms of GCI formation are not fully understood. Cellular machinery for the formation of aggresomes has been linked to the biogenesis of the Lewy body, a characteristic α-synuclein-containing inclusion of Parkinson's disease and dementia with Lewy bodies. Here, we examined whether GCIs contain the components of aggresomes by immunohistochemistry. METHODS: Sections from five patients with MSA were stained immunohistochemically with antibodies against aggresome-related proteins and analysed in comparison with sections from five patients with no neurological disease. We evaluated the presence or absence of aggresome-related proteins in GCIs by double immunofluorescence and immunoelectron microscopy. RESULTS: GCIs were clearly immunolabelled with antibodies against aggresome-related proteins, such as γ-tubulin, histone deacetylase 6 (HDAC6) and 20S proteasome subunits. Neuronal cytoplasmic inclusions (NCIs) were also immunopositive for these aggresome-related proteins. Double immunofluorescence staining and quantitative analysis demonstrated that the majority of GCIs contained these proteins, as well as other aggresome-related proteins, such as Hsp70, Hsp90 and 62-kDa protein/sequestosome 1 (p62/SQSTM1). Immunoelectron microscopy demonstrated immunoreactivities for γ-tubulin and HDAC6 along the fibrils comprising GCIs. CONCLUSIONS: Our results indicate that GCIs, and probably NCIs, share at least some characteristics with aggresomes in terms of their protein components. Therefore, GCIs and NCIs may be another manifestation of aggresome-related inclusion bodies observed in neurodegenerative diseases.


Assuntos
Encéfalo/metabolismo , Corpos de Inclusão/metabolismo , Atrofia de Múltiplos Sistemas/metabolismo , Neuroglia/metabolismo , Idoso , Idoso de 80 Anos ou mais , Encéfalo/patologia , Feminino , Desacetilase 6 de Histona , Histona Desacetilases/metabolismo , Humanos , Corpos de Inclusão/patologia , Corpos de Lewy/metabolismo , Corpos de Lewy/patologia , Masculino , Pessoa de Meia-Idade , Atrofia de Múltiplos Sistemas/patologia , Neuroglia/patologia , Neurônios/metabolismo , Neurônios/patologia , Complexo de Endopeptidases do Proteassoma/metabolismo , Tubulina (Proteína)/metabolismo
6.
Endoscopy ; 43(3): 184-9, 2011 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21234854

RESUMO

BACKGROUND AND STUDY AIMS: Growing evidence suggests that esophageal stricture frequently develops after endoscopic mucosal resection (EMR) or endoscopic submucosal dissection (ESD) in early esophageal cancer patients, with an incidence proportional to the greater extent of mucosal defects resulting from improved EMR/ESD techniques. There seems to be a potential risk of perforation during bougienage in such patients. PATIENTS AND METHODS: 648 stricture dilations for 78 lesions in 76 patients were consecutively included. The outcomes after combined use of Maloney and Savary wire-guided bougienage for esophageal strictures after EMR/ESD were analyzed in a single-institute retrospective case series study. The perforation rate was determined and risk factors for perforation were identified. RESULTS: Patients underwent a median of 5.0 dilation procedures performed over a median 3.0 months for post-EMR/ESD strictures. Initial dilation was done a median 14 days following endoscopic resection. Perforations developed in seven patients (7/648 dilation procedures, 1.1%), all in the lower esophagus, and bleeding occurred in one patient (0.1% dilations). Two independent risk factors for development of perforation during dilation therapy for post-EMR/ESD stricture were identified: multiple dilations (odds ratio [OR] 1.2; P=0.012), and lower site of stricture (OR 12.8; P=0.043). Dysphagia was ameliorated by the dilations, and no patient required surgery. CONCLUSIONS: A specific emerging risk of perforation in dilation therapy for post-EMR/ESD strictures was identified. Carefully planned treatment is necessary in patients with severe post-EMR/ESD strictures especially strictures requiring multiple dilations or located in the lower esophagus.


Assuntos
Carcinoma de Células Escamosas/cirurgia , Dilatação/efeitos adversos , Neoplasias Esofágicas/cirurgia , Perfuração Esofágica/epidemiologia , Perfuração Esofágica/etiologia , Estenose Esofágica/terapia , Esofagoscopia/efeitos adversos , Esôfago/cirurgia , Mucosa/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Dilatação/instrumentação , Estenose Esofágica/etiologia , Esôfago/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Mucosa/patologia , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento
7.
Diabetologia ; 53(7): 1472-81, 2010 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-20349346

RESUMO

AIMS/HYPOTHESIS: Metformin, the major target of which is liver, is commonly used to treat type 2 diabetes. Although metformin activates AMP-activated protein kinase (AMPK) in hepatocytes, the mechanism of activation is still not well known. To investigate AMPK activation by metformin in liver, we examined the role of reactive nitrogen species (RNS) in suppression of hepatic gluconeogenesis. METHODS: To determine RNS, we performed fluorescence examination and immunocytochemical staining in mouse hepatocytes. Since metformin is a mild mitochondrial complex I inhibitor, we compared its effects on suppression of gluconeogenesis, AMPK activation and generation of the RNS peroxynitrite (ONOO(-)) with those of rotenone, a representative complex I inhibitor. To determine whether endogenous nitric oxide production is required for ONOO(-) generation and metformin action, we used mice lacking endothelial nitric oxide synthase (eNOS). RESULTS: Metformin and rotenone significantly decreased gluconeogenesis and increased phosphorylation of AMPK in wild-type mouse hepatocytes. However, unlike rotenone, metformin did not increase the AMP/ATP ratio. It did, however, increase ONOO(-) generation, whereas rotenone did not. Exposure of eNOS-deficient hepatocytes to metformin did not suppress gluconeogenesis, activate AMPK or increase ONOO(-) generation. Furthermore, metformin lowered fasting blood glucose levels in wild-type diabetic mice, but not in eNOS-deficient diabetic mice. CONCLUSIONS/INTERPRETATION: Activation of AMPK by metformin is dependent on ONOO(-). For metformin action in liver, intra-hepatocellular eNOS is required.


Assuntos
Glicemia/efeitos dos fármacos , Gluconeogênese/efeitos dos fármacos , Hepatócitos/efeitos dos fármacos , Hepatócitos/metabolismo , Hipoglicemiantes/farmacologia , Metformina/farmacologia , Espécies Reativas de Nitrogênio/metabolismo , Animais , Células Cultivadas , Immunoblotting , Imuno-Histoquímica , Masculino , Camundongos , Camundongos Endogâmicos C57BL
8.
Xenobiotica ; 40(2): 119-28, 2010 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-20082576

RESUMO

Carboxylesterase 1A1 (CES1A1) efficiently catalyses the hydrolysis of a substrate containing ester, amide, or thioester bonds. It is expressed at a high level in the human liver, but at a low level in the human kidney. In this study, we found the cause of this tissue-specific expression of the CES1A1 gene using 5-aza-2'-deoxycytidine (5-aza-dC) and bisulfite sequencing. Treatment of HEK293 cells, human embryonic kidney cells not expressing the CES1A1 gene, with 5-aza-dC caused dramatic expression of the CES1A1 gene. Bisulfite sequencing revealed that the region around the transcription start site (TSS) of the CES1A1 gene was almost entirely methylated in HEK293 cells, whereas the region was almost entirely unmethylated in HepG2 cells, human hepatoma cells. The hypomethylated DNA molecules for the region were observed in HEK293 cells treated with 5-aza-dC. In the genome obtained from the kidney, the region downstream of the TSS was methylated compared with that obtained from the liver. From these findings, it can be concluded that DNA methylation is involved in CES1A1 gene expression and that the difference between CES1A1 gene expression in the human kidney and that in the human liver may arise from the difference in DNA methylation levels in the region around the TSS.


Assuntos
Carboxilesterase/metabolismo , Metilação de DNA , Rim/metabolismo , Fígado/metabolismo , Azacitidina/análogos & derivados , Sequência de Bases , Linhagem Celular , Decitabina , Expressão Gênica , Humanos , Hidrólise , Dados de Sequência Molecular , Nitrofenóis , RNA Mensageiro/metabolismo , Ativação Transcricional
9.
J Food Sci Technol ; 47(1): 94-9, 2010 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23572608

RESUMO

Free radicals and singlet oxygen are responsible for oxidative stress related diseases and many natural compounds are known to have antioxidant properties. In this study, extracts from brown and red seaweeds of Indian origin were evaluated for their ability to scavenge different radicals and quench singlet oxygen. The crude extract in methanol and its fractions in different solvents were evaluated for their activity. The methanol extract and its fractions from brown seaweed exhibited higher 2,2'-azinobis(3-ethylbenzothizoline-6-sulfonic acid) radical scavenging activity with more than 90% scavenging in butanol and ethyl acetate fractions and correlated with polyphenol content. There was a significant difference (p≤0.001) in hydroxyl radical scavenging activity between different fractions of the same seaweed. Among the crude extracts, extract from Gracilaria corticata showed the highest (14.0%) activity. Crude extract from brown seaweeds showed higher peroxyl radical scavenging activity compared to red seaweeds. In fractions from brown seaweed extracts, highest activity was observed in ethyl acetate fraction (>88%) followed by hexane fraction (>40 %). Ethyl acetate fraction from crude extract showed higher inhibitory activity against hemoglobin induced linoleic acid oxidation. Singlet oxygen quenching activity of the crude extract from brown seaweed was lower (<13%) compared to red seaweeds (16.4-20.5%).

10.
Arch Environ Contam Toxicol ; 58(4): 1065-73, 2010 May.
Artigo em Inglês | MEDLINE | ID: mdl-19937321

RESUMO

Neurotoxicity is one of the major effects of tributyltin (TBT). The effects on the next generation of F(1) rats exposed to TBT via the placenta and their dams' milk may be stronger than those on adults. Pregnant Wister rats were exposed to TBT at 0 and 125 ppm in their food. Half of the female F(1) rats in both groups were exposed to TBT at 125 ppm in their food from 9 to 15 weeks of age. Female F(1) rats were divided into the following groups: the control-control (CC) group, with no exposure; the TBT-control (TC) group, exposed to TBT via the placenta and their dams' milk; the control-TBT (CT) group, exposed to TBT via their food from 9 to 15 weeks of age; and the TBT-TBT (TT) group, exposed to TBT via the placenta, their dams' milk, and their food (n = 10/group). After administration, an open-field test and prepulse inhibition (PPI) test were performed at 15 weeks of age. The mean body weights of the TC and TT groups were significantly lower than that of the CC group from 9 to 15 weeks of age. The mean relative thymus weight of the TC and TT groups was significantly lower than that of the CC group. In the open-field test, a marked decrease in the total locomotion distance was observed in the TT group. The mean values in the TT and TC groups were significantly lower than that in the CC group. For the locomotion distance between 15 and 20 min, the mean values in the CT, TC, and TT groups were significantly lower than that in the CC group. The mean locomotor distance between 25 and 30 min in the TT group was significantly lower than that in the CC and TC groups. The mean values of instances of wall rearing in the TC, CT, and TT groups were significantly lower than that in the CC group. The mean value of face washing or body washing in the TT group was significantly lower than that in the CT group. There were no significant differences in indexes of the PPI test. Exposure to TBT via the placenta and their dams' milk inhibited the development of F(1) rats, which continued after weaning. Inhibition of the rats' activity induced by exposure to TBT via the placenta and their dams' milk and/or via their food was suggested. The effects were most evident in the TT group.


Assuntos
Comportamento Animal/efeitos dos fármacos , Poluentes Ambientais/toxicidade , Exposição Materna/efeitos adversos , Atividade Motora/efeitos dos fármacos , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Compostos de Trialquitina/toxicidade , Animais , Peso Corporal/efeitos dos fármacos , Feminino , Tamanho do Órgão/efeitos dos fármacos , Gravidez , Efeitos Tardios da Exposição Pré-Natal/fisiopatologia , Efeitos Tardios da Exposição Pré-Natal/psicologia , Ratos , Ratos Wistar
11.
Qual Saf Health Care ; 18(4): 278-82, 2009 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-19651931

RESUMO

BACKGROUND: At the University of Missouri School of Medicine (MUSOM), "commitment to improving quality and safety in healthcare" is one of eight key characteristics set as goals for our graduates. As educators, we have modelled our commitment to continuous improvement in the educational experiences through the creation of a method to monitor and analyse patient encounters in the third year of medical school. This educational improvement project allowed course directors to (1) confirm adequate clinical exposure, (2) obtain prompt information on student experiences, (3) adjust individual student rotations to meet requirements and (4) ascertain the range of clinical experiences available to students. DISCUSSION: Data illustrate high levels of use and satisfaction with the educational innovation. We are in our second year using the new Patient Log (PLOG) process and are now considering expanding the use of PLOG into the fourth year of medical school.


Assuntos
Educação de Pós-Graduação em Medicina/organização & administração , Garantia da Qualidade dos Cuidados de Saúde/organização & administração , Competência Clínica , Continuidade da Assistência ao Paciente/organização & administração , Humanos , Relações Interprofissionais , Modelos Educacionais , Inovação Organizacional , Equipe de Assistência ao Paciente/organização & administração , Gestão da Segurança/organização & administração
12.
J Food Sci ; 73(8): H201-6, 2008 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-19019116

RESUMO

Trans and conjugated fatty acids may exhibit either beneficial or detrimental bioactive effects depending on their metabolic properties. This study was conducted to elucidate if isomerization and conjugation of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) demonstrate more favorable bioactivity on lipid metabolism compared to unmodified EPA and DHA. The effects of dietary intake of trans and conjugated forms of EPA and DHA on lipid metabolism were evaluated in animal trials and compared to a control group fed soybean oil. None of the experimental diets showed significant differences from the control in terms of body weight; however, the white adipose tissue weight of rodents fed trans DHA, conjugated EPA (CEPA), and conjugated DHA (CDHA) was significantly lower than the control. Triacylglycerol levels in plasma were significantly decreased in groups fed trans DHA (17.2 mg/dL) and CDHA (31.9 mg/dL) relative to the control (51.3 mg/dL). The total cholesterol concentrations were significantly lower than the control (68.0 mg/dL) in all experimental groups (47.3 to 53.7 mg/dL) except CEPA (58.3 mg/dL). Fatty acid compositions of lipids extracted from rodent livers were influenced by the dietary fatty acid profiles, with all groups showing higher concentrations of stearic acid and lower levels of linoleic acid compared to the control. Rodents fed trans DHA did not have detectable levels of these fatty acid isomers in their livers, suggesting either quick metabolism or a difficulty with bio-absorption.


Assuntos
Gordura Abdominal/anatomia & histologia , Ácidos Graxos Ômega-3/administração & dosagem , Ácidos Graxos trans/administração & dosagem , Animais , Colesterol/sangue , Dieta , Ácidos Docosa-Hexaenoicos/administração & dosagem , Ácidos Docosa-Hexaenoicos/química , Ácido Eicosapentaenoico/administração & dosagem , Ácido Eicosapentaenoico/química , Ácidos Graxos/análise , Isomerismo , Lipídeos/sangue , Lipídeos/química , Fígado/química , Masculino , Tamanho do Órgão , Ratos , Ratos Wistar , Triglicerídeos/sangue
13.
Neuropathol Appl Neurobiol ; 34(1): 33-51, 2008 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-17973906

RESUMO

AIMS: Neurodegenerative diseases are characterized by ubiquitinated inclusions in selective brain regions. Here we investigated whether the dysfunction of the ubiquitin proteasome system might be involved in the pathogenesis and regional selectivity of neuronal ubiquitinated inclusions using the SAMP10 strain of mouse, an inbred model of age-related cerebral degeneration. METHODS: By comparing SAMP10 mice at various ages with SAMR1 and C57BL mice as normal brain ageing controls, we studied morphological features and distribution of inclusions. We measured tissue proteasome activity in different brain regions of mice at various ages by fluorogenic substrate assays. We induced inclusions in cultured neurones by inhibiting the proteasome and analysed changes in the dendritic morphology. RESULTS: Inclusions were formed in association with lipofuscin in neuronal perikarya and occurred most frequently in the limbic-related forebrain structures. There were sparse inclusion-bearing neurones in the non-limbic forebrain. In aged SAMR1 and C57BL, there were far fewer inclusions in the limbic-related forebrain than in aged SAMP10. The proteasome activity in the limbic-related forebrain decreased much more rapidly and remarkably upon ageing (26% activity was detected in 17-month-old compared with 3-month-old mice) in SAMP10 than in SAMR1. The proteasome activity in the non-limbic forebrain did not change significantly with advancing age in either SAMP10 or SAMR1. Proteasomal inhibition enhanced the formation of ubiquitinated inclusions in cultured neurones. Neurones bearing inclusions had shortened neurites. CONCLUSIONS: We propose that the regional selectivity of proteasomal impairment is causally related to the selectivity of inclusion formation and associated dendritic degeneration in neurones of ageing SAMP10 mice.


Assuntos
Envelhecimento , Corpos de Inclusão/ultraestrutura , Sistema Límbico/fisiopatologia , Degeneração Neural/fisiopatologia , Neurônios/ultraestrutura , Complexo de Endopeptidases do Proteassoma/metabolismo , Envelhecimento/patologia , Envelhecimento/fisiologia , Animais , Córtex Cerebral/fisiopatologia , Córtex Cerebral/ultraestrutura , Modelos Animais de Doenças , Imuno-Histoquímica , Sistema Límbico/ultraestrutura , Camundongos , Camundongos Endogâmicos , Microscopia Imunoeletrônica , Degeneração Neural/patologia , Neurônios/metabolismo , Ubiquitinação
14.
J Food Sci ; 72(5): C231-4, 2007 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-17995707

RESUMO

Dietary effects of herring roe lipids (HR-L) and proteins (HR-P) on plasma lipids and abdominal fat pad weight were determined. The main lipid class of HR-L was phospholipids (74%) and the main fatty acids were palmitic acid (16:0, 25.8%), DHA (22:6n-3, 21.6%), EPA (20:5n-3, 14.4%), and oleic acid (18:1n-9, 13.2%). A little increase in total cholesterol level was observed in plasma lipids of mouse fed with HR-L, although HR-L contained 9% cholesterol. This would be due to the lowering effect of EPA and DHA contained in HR-L on plasma cholesterol. Replacement of a part of dietary protein (5%) to HR-P reduced abdominal fat pad weight, but not significantly. On the other hand, combination of HR-P and HR-L significantly reduced the fat pad weight of the mouse as compared with the control. A significant effect of HR-P + HR-L was also observed in the reducing plasma lipid levels.


Assuntos
Gordura Abdominal/efeitos dos fármacos , Colesterol/sangue , Gorduras Insaturadas na Dieta/farmacologia , Proteínas Alimentares/farmacologia , Lipídeos/sangue , Gordura Abdominal/metabolismo , Análise de Variância , Animais , Composição Corporal , Peso Corporal , Gorduras Insaturadas na Dieta/administração & dosagem , Ácidos Docosa-Hexaenoicos/administração & dosagem , Ácidos Docosa-Hexaenoicos/farmacologia , Ácido Eicosapentaenoico/administração & dosagem , Ácido Eicosapentaenoico/farmacologia , Fígado/efeitos dos fármacos , Fígado/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos ICR , Tamanho do Órgão , Ácido Palmítico/administração & dosagem , Ácido Palmítico/farmacologia , Fosfolipídeos/administração & dosagem , Fosfolipídeos/farmacologia , Distribuição Aleatória
15.
Chemotherapy ; 52(5): 220-5, 2006.
Artigo em Inglês | MEDLINE | ID: mdl-16899971

RESUMO

BACKGROUND: We have previously reported that troglitazone, a synthetic ligand for peroxisome proliferator-activated receptor gamma (PPARgamma), and bitter gourd seed oil rich in 9cis,11trans,13trans-conjugated linolenic acid (9c,11t,13t-CLN) prevent colon carcinogenesis. To evaluate the chemotherapeutic effect and potency of these compounds on colon cancer cells, we investigated their antiproliferative and apoptosis-inducing effects using different human colon cancer cell lines. METHODS: The antiproliferative and apoptosis-inducing effects of troglitazone and 9c,11t,13t-CLN were evaluated and compared using HT-29, DLD-1 and Caco-2 cells at different stages of enterocytic differentiation. RESULTS: Troglitazone and 9c,11t,13t-CLN decreased cell viability and induced apoptosis in three colon cancer cell lines. The susceptibility of HT-29, which expresses PPARgamma at high levels, to troglitazone and 9c,11t,13t-CLN was higher than that of Caco-2 cells with low levels of PPARgamma. CONCLUSION: Troglitazone and 9c,11t,13t-CLN exhibited more effective chemotherapeutic effects on HT-29 cells than on Caco-2 cells.


Assuntos
Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Cromanos/farmacologia , Neoplasias do Colo/patologia , Ácidos Linolênicos/farmacologia , Tiazolidinedionas/farmacologia , Western Blotting , Células CACO-2 , Diferenciação Celular , Neoplasias do Colo/metabolismo , Células HT29 , Humanos , PPAR gama/genética , PPAR gama/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Troglitazona , Ácido alfa-Linolênico
16.
Neuroscience ; 141(2): 917-927, 2006 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-16716527

RESUMO

Leukotriene B4 is a potent lipid mediator, which has been identified as a potent proinflammatory and immunomodulatory compound. Although there has been robust evidence indicating that leukotriene B4 is synthesized in the normal brain, detailed distribution and its functions in the nervous system have been unclear. To obtain insight into the possible neural function of leukotriene B4, we examined the immunohistochemical distribution of leukotriene A4 hydrolase, an enzyme catalyzing the final and committed step in leukotriene B4 biosynthesis, in the mouse nervous system. Immunoreactivity for leukotriene A4 hydrolase showed widespread distribution with preference to the sensory-associated structures; i.e. neurons in the olfactory epithelium and vomeronasal organ, olfactory glomeruli, possibly amacrine cells, neurons in the ganglion cell layer and three bands in the inner plexiform layer of the retina, axons in the optic nerve and tract up to the superior colliculus, inner and outer hair cells and the spiral ganglion cells in the cochlea, vestibulocochlear nerve bundle, spinal trigeminal tract, and lamina II of the spinal cord. Double immunofluorescence staining demonstrated that most of the leukotriene A4-hydrolase-immunopositive neurons coexpressed calretinin, a calcium-binding protein in neurons. The ubiquitous distribution of leukotriene A4 hydrolase was in sharp contrast with the distribution of leukotriene C4 synthase [Shimada A, Satoh M, Chiba Y, Saitoh Y, Kawamura N, Keino H, Hosokawa M, Shimizu T (2005) Highly selective localization of leukotriene C4 synthase in hypothalamic and extrahypothalamic vasopressin systems of mouse brain. Neuroscience 131:683-689] which was confined to the hypothalamic and extrahypothalamic vasopressinergic neurons. These results suggest that leukotriene B4 may exert some neuromodulatory function mainly in the sensory nervous system, in concert with calretinin.


Assuntos
Epóxido Hidrolases/metabolismo , Sistema Nervoso/metabolismo , Proteína G de Ligação ao Cálcio S100/metabolismo , Animais , Calbindina 2 , Imuno-Histoquímica/métodos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Sistema Nervoso/citologia , Sistema Nervoso/enzimologia
17.
Int J Immunogenet ; 33(2): 117-22, 2006 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-16611256

RESUMO

We examined the genetic status of human leucocyte antigens (HLA), human platelet alloantigens (HPA) and neutrophil-specific antigens (NA) in patients with type 2 diabetes mellitus and diabetic arteriosclerosis obliterans (ASO). To our knowledge, the present study is the first report showing the relationship among three genetic factors in type 2 diabetes mellitus and ASO patients. HLA typing was performed by the polymerase chain reaction (PCR)-restriction fragment length polymorphism method. HPA-typing and NA-typing were by a PCR-sequence-specific primer method. The incidence of HLA-DRB1*1501 was found to be significant in type 2 diabetes and non-diabetic, particularly ASO-positive patients, compared to control subjects. There were no differences in NA1/NA2 between the control and diabetic or non-diabetic ASO groups. However, the frequency of NA2/NA2 in ASO-positive diabetes and non-diabetic ASO patients was significantly higher than controls. The a/b genotype of HPA-5a/5b was significantly lower in type 2 diabetes and non-diabetic ASO-positive patients than in controls. These findings suggest that genetic studies of HLA, NA and HPA could be useful to understand the pathogenesis of type 2 diabetes and ASO.


Assuntos
Antígenos de Plaquetas Humanas/genética , Arteriosclerose Obliterante/genética , Arteriosclerose Obliterante/imunologia , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/imunologia , Antígenos HLA-DR/genética , Neutrófilos/imunologia , Neutrófilos/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Arteriosclerose Obliterante/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Feminino , Cadeias HLA-DRB1 , Teste de Histocompatibilidade , Humanos , Masculino , Pessoa de Meia-Idade
18.
Br J Cancer ; 94(6): 854-62, 2006 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-16508635

RESUMO

Weakly tumorigenic and nonmetastatic QR-32 cells derived from a fibrosarcoma in C57BL6 mouse are converted to malignant cells once they have grown after being coimplanted with a gelatine sponge which induces inflammation. We administered a newly developed peroral superoxide dismutase (SOD), oxykine, and as control vehicle, gliadin and saline, starting 2 days before the coimplantation and continued daily throughout the experiment. In the oxykine group, tumour incidence was lower (41%) than in the gliadin or saline group (83 and 79%, respectively). The inhibitory effect of oxykine was lost when an individual component of oxykine was administered, that is, SOD alone and gliadin alone. The effect was also abolished when administered by intraperitoneal route. When perfused in situ with nitroblue tetrazolium, an indicator of superoxide formation, the tumour masses from gliadin and saline groups displayed intense formazan deposition, whereas, those from oxykine group had less deposition. Enzymatic activity of SOD was also increased in oxykine group. Arising tumour cells in gliadin and saline groups acquired metastatic phenotype, but those in oxykine group showed reduced metastatic ability. These results suggested that the orally active SOD derivative prevented tumour progression promoted by inflammation, which is thought to be through scavenging inflammatory cell-derived superoxide anion.


Assuntos
Fibrossarcoma/imunologia , Fibrossarcoma/patologia , Inflamação , Metástase Neoplásica/imunologia , Superóxido Dismutase/metabolismo , Administração Oral , Animais , Progressão da Doença , Feminino , Camundongos , Camundongos Endogâmicos C57BL , Superóxido Dismutase/administração & dosagem
19.
Rozhl Chir ; 85(1): 9-13, 2006 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-16541634

RESUMO

AIM OF THE STUDY: A gastric tube is commonly used in thoracic esophageal reconstruction. When a gastric tube is not available, pedicled jejunum transfer and colonic interposition are alternative methods. Oral end of the reconstructed esophagus occasionally has poor blood flow and may result in partial necrosis of the oral segment. We performed additional microvascular blood flow augmentation, the "supercharge" technique, to improve a blood flow circulation in the oral segment of the reconstructed esophagus. METHODS: A series of 86 esophageal reconstructions with microvascular blood flow augmentation using the "supercharge" technique were performed. Reconstructive methods included a gastric tube in five patients, a gastric tube combined with a free jejunual graft in one, an elongated gastric tube in eight, a pedicled colonic interposition in 22, and a pedicled jejunum in 50. Recipient vessels were used in neck or chest region. RESULTS: The color and blood flow of the transferred intestine appeared greatly improved after microvascular blood flow augmentation. Thrombosis was noticed in three patients during the surgery, and all thrombosies were salvaged by re-anastomosis. There were only three patients with partial graft necrosis of oral segment, two patients with anastomotic leakage, one anastomotic stricture. CONCLUSIONS: Augmentation of microvascular blood flow by this "supercharge" technique can be expected to reduce the risk of leakage and partial necrosis of the transferred intestine. This technique contributes to the successful reconstruction of esophageal defect.


Assuntos
Esofagoplastia/métodos , Esôfago/irrigação sanguínea , Faringe/cirurgia , Procedimentos Cirúrgicos Vasculares/métodos , Adulto , Idoso , Feminino , Humanos , Jejuno/transplante , Masculino , Microcirculação , Microcirurgia , Pessoa de Meia-Idade , Estômago/transplante , Retalhos Cirúrgicos
20.
Neuropathol Appl Neurobiol ; 32(1): 1-14, 2006 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-16409548

RESUMO

The SAMP10 mouse is a model of accelerated ageing in which senescence is characterized by age-related atrophy of the cerebral cortex and limbic structures, poor learning and memory task performance with depressive behaviour and cholinergic and dopaminergic alterations. Here we studied age-related changes in the dendritic arbors and spine density of pyramidal cells in the medial prefrontal cortex of SAMP10 mice using a quantitative Golgi method. Dendrites of prefrontal neurones gradually retracted with ageing towards the soma with the relative preservation of overall complexity. Apical dendrites were much more severely affected than basal dendrites. The combined length of the apical dendrites and spine density were decreased by 45% and 55%, respectively, in mice at 12 months, compared with mice at 3 months of age. Immunohistochemical and immunoblot analyses indicated that expression of microtubule-associated protein (MAP) 2, a marker of dendrites, decreased in an age-related manner not only in the anterior cortex but also in the posterior cortex and olfactory structures in SAMP10 mice. Decreased expression of MAP2 mRNA caused the decrease in MAP2 protein expression. These results suggest that retraction of apical, but not of basal dendrites, with a loss of spines in prefrontal neurones, appears to be responsible for poor learning and memory performance in aged SAMP10 mice. It is also suggested that age-related dendritic retraction occurs in a wide area including the entire cerebral cortex and olfactory structures.


Assuntos
Envelhecimento , Dendritos/patologia , Degeneração Neural/patologia , Córtex Pré-Frontal/patologia , Animais , Western Blotting , Imuno-Histoquímica , Camundongos , RNA Mensageiro/análise , Reação em Cadeia da Polimerase Via Transcriptase Reversa
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