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1.
Biometals ; 2020 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-32681432

RESUMO

Vibrio vulnificus, a pathogenic bacterium that causes serious infections in humans, requires iron for growth. Clinical isolate, V. vulnificus M2799, secretes a catecholate siderophore, namely, vulnibactin, to capture iron (III) from the environment. Growth experiments using a deletion mutant indicated that VuuB, a member of the FAD-containing siderophore-interacting protein family, plays a crucial role in Fe3+-vulnibactin reduction. IutB, a member of the ferric-siderophore reductase family, stands a substitute for VuuB in its absence. It remained unclear why V. vulnificus M2799 has two proteins with relevant functions. Here we biochemically characterized VuuB and IutB using purified recombinant proteins. Purified VuuB, a flavoprotein, catalyzed the reduction of Fe3+-nitrilotriacetic acid as its electron acceptor, in the presence of NADH as its electron donor and FAD as its cofactor. IutB catalyzed the reduction of Fe3+-nitrilotriacetic acid, in the presence of NADH, NADPH, or reduced glutathione as its electron donor. The optimal pH values and temperatures of VuuB and IutB were 7.0 and 37 °C, and 8.5 and 45 °C, respectively. On analyzing their ferric-chelate reductase activities, both VuuB and IutB were found to catalyze the reduction of Fe3+-aerobactin, Fe3+-vibriobactin, and Fe3+-vulnibactin. When the biologically relevant substrate, Fe3+-vulnibactin, was used, the levels of ferric-chelate reductase activities were similar between VuuB and IutB. Finally, the mRNA levels were quantified by qRT-PCR in M2799 cells cultivated under low-iron conditions. The number of vuuB mRNA was 8.5 times greater than that of iutB. The expression ratio correlated with the growth of their mutants in the presence of vulnibactin.

2.
FEBS Lett ; 2020 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-32282060

RESUMO

Neurofibrillary tangles formed by abnormally aggregated tau protein are a histopathological feature of tauopathies. A tau aggregation inhibitor is a potential therapeutic agent for tauopathies. In this study, we prepared a monoclonal antibody for tau, monoclonal antibody to tau protein (Tau2r3), using as epitope the 272 GGKVQIINKKLD283 peptide in the microtubule-binding domain of tau, the key region mediating tau aggregation. We show that Tau2r3 clearly inhibits tau aggregation. To analyze the inhibition mechanism of Tau2r3, we solved the crystal structure of the Fab domain of Tau2r3 (Fab2r3) in complex with the VQIINK peptide. In the Fab2r3-VQIINK structure, the second and sixth polar residues and the fourth hydrophobic residue of VQIINK are crucial for binding to Fab2r3. The structural data for the Fab2r3-VQIINK complex could contribute to the design of new tau aggregation inhibitors.

3.
Dose Response ; 17(2): 1559325819842733, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31040760

RESUMO

We investigated the effects of continuous low-dose radiation on proliferation, clonogenicity, radiosensitivity, and repair of DNA double-strand breaks (DSBs) in human salivary gland (HSG) tumor cells. Human salivary gland cells were cultured on acrylic boards above very-low-dose (4.3 µSv/h) or low-dose (27 µSv/h) radiation-emitting sheets or without sheets. Total cell numbers and plating efficiencies were compared among the 3 groups every 1 or 2 weeks until 6 weeks after starting culture. At 2, 4, and 6 weeks, surviving fractions of HSG cells after irradiation at 2 to 8 Gy cultured on the very-low-dose or low-dose sheets were compared to those of the control. At 4 weeks, HSG cells irradiated at 2 Gy were assessed for phosphorylated histone (γH2AX) foci formation, and DSBs were evaluated. No significant differences were observed in total cell number or plating efficiencies with or without low-dose-emitting sheets. The surviving fractions after irradiation of the very-low-dose group at 2 to 6 weeks and those of the low-dose group at 2 to 4 weeks were higher than those of the control (P < .01). Thus, a radioadaptive response was clearly demonstrated. From the γH2AX foci quantification, the adaptive responses were considered to be associated with the efficient repair of DSB, especially slow repair, in this cell line.

4.
Phys Med Biol ; 64(6): 06NT01, 2019 03 08.
Artigo em Inglês | MEDLINE | ID: mdl-30695772

RESUMO

MR-only simulations provide pseudo-CT images which are segmented into 5 kinds of tissues from DIXON-based images. However, it is difficult to register pseudo-CT images to cone-beam CT (CBCT) images collected for image-guided radiation therapy (IGRT), because of the lack of contrasts among tissues. We validated gaps of IGRT between pseudo-CT or planning CT and CBCT for patients without implanted markers. We also propose calcification-assisted registration for MR-only simulation. We conducted retrospective analyses to verify the registration accuracy in 15 patients who underwent volumetric modulated arc therapy (VMAT) for prostate cancer. They underwent planning CT and pseudo-CT. Pseudo-CT images after deformable image registration (DIR) to planning CT images were rendered automatic pelvic bone matching to CBCT images. Patient positions on the pseudo-CT images after DIR were shifted on the basis of tissues around the prostate. We compared registration gaps between the images of planning CT and pseudo-CT with DIR, assuming that the tissue-based matching between the planning CT and CBCT was the gold standard. To the pseudo-CT images with DIR, calcifications detected on planning CT were added. We validated IGRT accuracy for a calcification-assisted registration. The absolute registration errors of the pseudo-CT, in comparison with the planning CT, were 0.34 ± 0.50 (lateral), 1.3 ± 1.3 (longitudinal), and 1.1 ± 1.0 mm (vertical). The absolute registration errors of the pseudo-CT with calcification contouring, in comparison with the planning CT, were 0.41 ± 1.0 (lateral), 0.87 ± 0.92 (longitudinal), and 0.74 ± 0.64 mm (vertical). Reduced absolute registration errors were observed in the proposed approach in the longitudinal (P < 0.01) and vertical (P < 0.01) dimensions when using calcification-assisted registration. The tissue-based registration using the MR-only simulation was not sufficient for use in patients with prostate cancer without implanted markers. The calcification-assisted registration might help to improve IGRT accuracy using MRI alone.


Assuntos
Calcinose/diagnóstico , Tomografia Computadorizada de Feixe Cônico/métodos , Marcadores Fiduciais , Neoplasias da Próstata/radioterapia , Planejamento da Radioterapia Assistida por Computador/métodos , Radioterapia Guiada por Imagem/métodos , Radioterapia de Intensidade Modulada/métodos , Idoso , Calcinose/diagnóstico por imagem , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias da Próstata/diagnóstico por imagem , Estudos Retrospectivos
5.
J Inorg Biochem ; 192: 82-86, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30612029

RESUMO

We synthesized and characterized 15 new derivatives of the highly anticancer-active platinum(II) complex [{cis-Pt(NH3)2}2(µ-OH)(µ-tetrazolato-N2,N3)]2+ (5-H-Y) by making substitutions at tetrazole C5. We then evaluated the comprehensive structure-cytotoxicity relationships of a total of 23 derivatives in two murine lymphocytic leukaemia cell lines, sensitive and resistant to cisplatin. We also report the in vivo antitumor efficacy of three ester derivatives, two of which exhibited much higher efficacy than oxaliplatin against mouse homografted Colon-26 colorectal tumor.


Assuntos
Neoplasias Colorretais , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Compostos Organoplatínicos , Tetrazóis , Animais , Antineoplásicos/síntese química , Antineoplásicos/química , Antineoplásicos/farmacocinética , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Cisplatino/química , Cisplatino/farmacocinética , Cisplatino/farmacologia , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , Camundongos , Camundongos Endogâmicos BALB C , Compostos Organoplatínicos/síntese química , Compostos Organoplatínicos/química , Compostos Organoplatínicos/farmacocinética , Compostos Organoplatínicos/farmacologia , Oxaliplatina/química , Oxaliplatina/farmacocinética , Oxaliplatina/farmacologia , Relação Estrutura-Atividade , Tetrazóis/química , Tetrazóis/farmacocinética , Tetrazóis/farmacologia
6.
Chempluschem ; 84(11): 1647, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31943871

RESUMO

Invited for this month's cover are Takahiro Tsuchiya and Yasuhiro Mazaki, and their colleague Yuka Katsuoka, from Kitasato University, Japan, along with collaborators from Bruker Japan (Kenji Yoza) and Rigaku Corporation (Hiroyasu Sato). The cover picture shows the twisted structure of 2,2'-di(pyridin-4-yl)-1,1'-biazulenes, which form a 3:3 cyclic complex with PdCl2 . The rotation of the bonds at the 1,1'-positions of the azulene subunits was padlocked by the complexation. Read the full text of the article at 10.1002/cplu.201900262.

7.
Chempluschem ; 84(11): 1659-1667, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31943874

RESUMO

2,2'-Diaryl-1,1'-biazulenes were synthesized and electronic communication between the azulene subunits was suggested based on redox measurements. The linkage of azulene at the 1-position also appeared to increase the HOMO levels. In addition, cyclic voltammetry measurements of 2-arylazulenes showed a return peak associated with the oxidation, which was not observed for azulene. The stabilization of the single-electron oxidant may be due to the SOMO-HOMO energy inversion phenomenon. X-ray crystallography of the azulene dimers revealed that this species possessed a syn-type structure in which both aryl groups in the 2-positions formed π-stacks. The twisted structure was indicated to be in the (R)- or (S)-configuration for all molecules in the unit cell. Spontaneous resolution was also shown. Furthermore, from the solid circular dichroism (CD) spectral measurements, the relationship between the absolute configuration of the molecules and the CD spectra was determined. A racemization rotational barrier of ca. 27 kcal mol-1 was calculated. Moreover, the pyridylazulene dimer cyclized upon reaction with PdCl2 to form a 3 : 3 complex, in which the biazulene units cyclized to give ratios between the (R)- and (S)-forms of either 2 : 1 or 1 : 2.

8.
Chempluschem ; 84(6): 655-664, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31944016

RESUMO

Rhodium dinuclear complexes (1-3) with azulene moieties as equatorial ligands were obtained by reacting Rh2 (OAc)4 with guaiazulene-2-carboxylic acid, azulene-2-carboxylic acid, and azulene-1-carboxylic acid, respectively. The molecular structures in their crystalline states were determined by X-ray diffraction to be 1 ⋅ (H2 O)2 , 1 ⋅ (MeCN)2 , 2 ⋅ (MeCN)2 , and 3 ⋅ (DMF)2 , which were coordinated with the crystallization solvent at the axial positions. Among these, the crystal packing of 1 ⋅ (H2 O)2 , 1 ⋅ (MeCN)2 , and 3 ⋅ (DMF)2 revealed the formation of one-dimensional stacked chains nearly along the axial direction and of two-dimensional stacked sheets along the equatorial direction. In addition, it was found that 1 ⋅ (H2 O)2 contained cavities that could adsorb CO2 , thereby inducing structural changes. Furthermore, redox measurements revealed the stepwise one-electron redox behaviors of these complexes, indicating the intramolecular interactions between the azulene units. In addition, transient absorption measurements suggested the presence of an ultrafast intersystem crossing caused by the heavy-atom effect of rhodium, and an extended lifetime of the triplet state due to the energy migration among the azulene ligands.

9.
Microb Pathog ; 117: 100-108, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29432914

RESUMO

Vibrio vulnificus, the causative agent of serious, often fatal, infections in humans, requires iron for its pathogenesis. As such, it obtains iron via both vulnibactin and heme-mediated iron-uptake systems. In this study, we identified the heme acquisition system in V. vulnificus M2799. The nucleotide sequences of the genes encoding heme receptors HupA and HvtA and the ATP-binding cassette (ABC) transport system proteins HupB, HupC, and HupD were determined, and then used in the construction of deletion mutants developed from a Δics strain, which could not synthesize vulnibactin. Growth experiments using these mutants indicated that HupA and HvtA are major and minor heme receptors, respectively. The expressions of two proteins were analyzed by the quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR). Furthermore, complementation analyses confirmed that the HupBCD proteins are the only ABC transport system shared by both the HupA and HvtA receptors. This is the first genetic evidence that the HupBCD proteins are essential for heme acquisition by V. vulnificus. Further investigation showed that hupA, hvtA, and hupBCD are regulated by Fur. The qRT-PCR analysis of the heme receptor genes revealed that HupR, a LysR-family positive transcriptional activator, upregulates the expression of hupA, but not hvtA. In addition, ptrB was co-transcribed with hvtA, and PtrB had no influence on growth in low-iron CM9 medium supplemented with hemin, hemoglobin, or cytochrome C.


Assuntos
Proteínas da Membrana Bacteriana Externa/metabolismo , Proteínas de Bactérias/metabolismo , Proteínas de Transporte/metabolismo , Ferro/metabolismo , Fatores de Transcrição/metabolismo , Vibrio vulnificus/metabolismo , Transportadores de Cassetes de Ligação de ATP/genética , Transportadores de Cassetes de Ligação de ATP/metabolismo , Amidas/metabolismo , Proteínas da Membrana Bacteriana Externa/genética , Proteínas de Bactérias/genética , Sequência de Bases , Proteínas de Transporte/genética , Grupo dos Citocromos b/genética , Citocromos c/metabolismo , DNA Bacteriano , Perfilação da Expressão Gênica , Regulação Bacteriana da Expressão Gênica , Genes Bacterianos/genética , Hemina/metabolismo , Hemoglobinas/metabolismo , Humanos , Hidrogenase/genética , Transferases Intramoleculares/metabolismo , Metaloendopeptidases/metabolismo , Oxazóis/metabolismo , Proteínas Periplásmicas de Ligação/genética , Proteínas Periplásmicas de Ligação/metabolismo , Proteínas Repressoras/genética , Proteínas Repressoras/metabolismo , Análise de Sequência , Deleção de Sequência , Fatores de Transcrição/genética , Transcrição Genética , Vibrio vulnificus/genética , Vibrio vulnificus/crescimento & desenvolvimento
10.
Obes Surg ; 28(6): 1643-1652, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29235014

RESUMO

BACKGROUND: The increasing incidence of non-alcoholic steatohepatitis (NASH) has resulted in it becoming a common cause of liver-related mortality; however, no efficient treatment has been established. It has been reported that bariatric surgery improves metabolic comorbidities, such as diabetes mellitus and NASH. Although the mechanism is unclear, it is thought that the changes in bile acid (BA) signaling via its nuclear receptor, farnesoid X receptor (FXR), produce various metabolic effects. We sought to investigate the effects and mechanisms of bariatric surgery on NASH improvement. METHODS: Male Sprague-Dawley rats were fed by a high-fat and high-fructose diet, which results in obesity, insulin resistance, and NASH. Rats underwent duodenal-jejunal bypass (DJB), which is a main component of bariatric procedures. The liver pathological findings and the expression level of mRNA of FXR were investigated. The plasma BA level was measured in peripheral and portal vein blood. RESULTS: DJB suppressed weight gain, improved insulin resistance, and ameliorated NASH mainly in a point of inflammation. The plasma BA level along with the expression of FXR and its target transcriptional factor, small heterodimer partner (SHP), in the liver were elevated. CONCLUSIONS: DJB has a direct effect on NASH improvement, and there is a possibility that an anti-inflammatory effect is functioning as a part of the mechanism. The increase of plasma bile acid level followed by the stimulation of FXR signaling may contribute to this phenomenon.


Assuntos
Ácidos e Sais Biliares/sangue , Duodeno/cirurgia , Derivação Gástrica , Jejuno/cirurgia , Hepatopatia Gordurosa não Alcoólica/fisiopatologia , Animais , Modelos Animais de Doenças , Masculino , Ratos , Ratos Sprague-Dawley
11.
Dose Response ; 15(4): 1559325817735252, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29051717

RESUMO

To investigate the influence of low-dose-rate irradiation on the growth of silkworms, Bombyx mori, eggs of silkworms were randomly divided into 2 groups and were grown on either low-dose-radiation-emitting sheets or control sheets. On the radiation-emitting sheets, the dose rate was measured as 66.0 (4.3) µSv/h (mean [standard deviation]) by a Geiger-Müller counter for α, ß, and γ rays and 3.8 (0.3) µSv/h by a survey meter for γ rays. The silkworms became larger when bred on the radiation-emitting sheets, and their body weight was about 25% to 37% heavier on day 42 to 49 after starting the experiment. Continuous low-dose-rate irradiation promoted the growth of silkworms. It should be further investigated whether this phenomenon could be utilized by the silk industry.

12.
Cancer Sci ; 108(9): 1787-1792, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28627761

RESUMO

Despite insufficient laboratory data, radiotherapy after intratumoral injection of hydrogen peroxide (H2 O2 ) is increasingly being used clinically for radioresistant tumors. Especially, this treatment might become an alternative definitive treatment for early and advanced breast cancer in patients who refuse any type of surgery. The purpose of this study was to investigate the biological effects and appropriate combination methods of irradiation and H2 O2 in vivo. SCCVII tumor cells transplanted into the legs of C3H/HeN mice were used. Chronological changes of intratumoral distribution of oxygen bubbles after injection of H2 O2 were investigated using computed tomography. The effects of H2 O2 alone and in combination with single or five-fraction irradiation were investigated using a growth delay assay. The optimal timing of H2 O2 injection was investigated. Immunostaining of tumors was performed using the hypoxia marker pimonidazole. Oxygen bubbles decreased gradually and almost disappeared after 24 h. Administration of H2 O2 produced 2-3 days' tumor growth delay. Tumor regrowth was slowed further when H2 O2 was injected before irradiation. The group irradiated immediately after H2 O2 injection showed the longest tumor growth delay. Dose-modifying factors were 1.7-2.0 when combined with single irradiation and 1.3-1.5 with fractionated irradiation. Pimonidazole staining was weaker in tumors injected with H2 O2 . H2 O2 injection alone had modest antitumor effects. Greater tumor growth delays were demonstrated by combining irradiation and H2 O2 injection. The results of the present study could serve as a basis for evaluating results of various clinical studies on this treatment.


Assuntos
Carcinoma de Células Escamosas/terapia , Peróxido de Hidrogênio/administração & dosagem , Radiossensibilizantes/administração & dosagem , Animais , Carcinoma de Células Escamosas/patologia , Avaliação Pré-Clínica de Medicamentos , Feminino , Injeções Intralesionais , Camundongos Endogâmicos C3H , Transplante de Neoplasias , Tolerância a Radiação , Carga Tumoral
13.
Biometals ; 30(2): 203-216, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-28150143

RESUMO

Vibrio vulnificus, an opportunistic pathogen that causes a serious, often fatal, infection in humans, requires iron for its growth. This bacterium utilizes iron from the environment via the vulnibactin-mediated iron uptake system. The mechanisms of vulnibactin biosynthesis, vulnibactin export, and ferric-vulnibactin uptake systems have been reported, whereas the ferric-vulnibactin reduction mechanism in the cell remains unclear. The results of our previous study showed that VuuB, a member of the flavin adenine dinucleotide-containing siderophore-interacting protein family, is a ferric-vulnibactin reductase, but there are other reductases that can complement for the defective vuuB. The aim of this study was to identify these proteins that can complement the loss of function of VuuB. We constructed mutants of genes encoding putative reductases in V. vulnificus M2799, and analyzed their growth under low-iron conditions. Complementation analyses confirmed that IutB, which functions as a ferric-aerobactin reductase, participates in ferric-vulnibactin reduction in the absence of VuuB. This is the first genetic evidence that ferric-vulnibactin is reduced by a member of the ferric-siderophore reductase protein family. In the aerobactin-utilization system, IutB plays a major role in ferric-aerobactin reduction in V. vulnificus M2799, and VuuB and DesB can compensate for the defect of IutB. Furthermore, the expression of iutB and desB was found to be regulated by iron and a ferric uptake regulator.


Assuntos
Amidas/metabolismo , Proteínas de Bactérias/metabolismo , Regulação Bacteriana da Expressão Gênica , Ferro/metabolismo , Oxazóis/metabolismo , Oxirredutases/metabolismo , Sideróforos/metabolismo , Vibrio vulnificus/metabolismo , Amidas/química , Sequência de Aminoácidos , Proteínas de Bactérias/genética , Clonagem Molecular , Desferroxamina/química , Desferroxamina/metabolismo , Escherichia coli/genética , Escherichia coli/metabolismo , Teste de Complementação Genética , Vetores Genéticos/química , Vetores Genéticos/metabolismo , Ácidos Hidroxâmicos/química , Ácidos Hidroxâmicos/metabolismo , Mutação , Oxazóis/química , Oxirredução , Oxirredutases/genética , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Alinhamento de Sequência , Homologia de Sequência de Aminoácidos , Sideróforos/química , Vibrio vulnificus/genética
14.
Gan To Kagaku Ryoho ; 44(12): 1068-1070, 2017 Nov.
Artigo em Japonês | MEDLINE | ID: mdl-29394536

RESUMO

A 40-year-old man was referred to our hospital because of severe anemia and small intestinal tumor revealed by computed tomography. The enteroscopy exam showed the intraluminal penetration of the tumor, which was considered as a cause of anemia. Although emergency operation was performed laparoscopically, intraoperative findings indicated tumor invasion into peritoneum, and we converted from laparoscopic surgery to open surgery that included concomitant peritoneum resection. Histopathological findings showed spindle-shaped tumor cells with severe atypia. Immunohistochemical study showed tumor cells to be positive for aSMA, but negative for c-kit and CD34, then we diagnosed the tumor as leiomyosarcoma of the ileum. Since leiomyosarcoma of the small intestine is a rare entity, we have reported with literature consideration.


Assuntos
Hemorragia Gastrointestinal/etiologia , Neoplasias Intestinais/patologia , Perfuração Intestinal/etiologia , Intestino Delgado/patologia , Leiomiossarcoma , Adulto , Hemorragia Gastrointestinal/cirurgia , Humanos , Neoplasias Intestinais/complicações , Neoplasias Intestinais/cirurgia , Perfuração Intestinal/cirurgia , Intestino Delgado/cirurgia , Leiomiossarcoma/complicações , Leiomiossarcoma/cirurgia , Masculino , Resultado do Tratamento
15.
Gan To Kagaku Ryoho ; 44(12): 2009-2010, 2017 Nov.
Artigo em Japonês | MEDLINE | ID: mdl-29394850

RESUMO

Chemoradiotherapy(CRT)has been recognized as a standard treatment for locoregional squamous cell carcinoma of the anal canal in Western countries. However, surgery had historically been considered as a standard treatment and there are only a few reports on CRT for anal canal cancer in Japan. In this study, we analyzed medical records of 5 anal canal cancer patients treated with CRT in our hospital between 2005 and 2015. Patients' characteristics were as follows: median age, 70 years (range 42-80 years); male/female, 1/4; and clinical Stage I / III a/ III b, 3/1/1. The regimens of chemotherapy were MMC plus 5-FU in 4 patients and CDDP in 1 patient. The median follow-up period was 30 months(range, 6 to 100 months). After CRT, 4 patients achieved complete response. The other patient with partial response underwent salvage surgery. All patients were alive without recurrence. In conclusion, our retrospective study showed that CRT is considered to be a standard treat- ment for anal canal cancer.


Assuntos
Neoplasias do Ânus/terapia , Carcinoma de Células Escamosas/terapia , Quimiorradioterapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias do Ânus/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico
16.
Surgery ; 159(5): 1360-71, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26767308

RESUMO

BACKGROUND AND AIMS: Roux-en-Y gastric bypass improves glucose metabolism in clinical practice, and duodenal-jejunal bypass (DJB), an experimental bypass procedure, also improves metabolism in animals. However, the mechanism remains controversial; especially, the role of the biliopancreatic limb (BP-limb) remains unclear. Our aim was to examine the importance of the function of the BP-limb after DJB using a novel operative model. METHODS: Otsuka Long-Evans Tokushima Fatty rats with diabetes were divided into the following groups: DJB with a short alimentary limb (A-limb) and long BP-limb (B-DJB group), DJB with jejunectomy (J-DJB group) in which the entire length of the jejunum used for the BP-limb of the B-DJB group was excised; and a sham operation group. Glucose tolerance, plasma bile acid levels, and the gut microbiota were assessed postoperatively. RESULTS: Glucose tolerance was improved and weight gain was suppressed after surgery in the B-DJB group. In contrast, these effects were cancelled in the J-DJB group. The plasma levels of bile acids in the B-DJB group were greater than those in other groups. The analysis of gut microbiota showed distinct differences between the B-DJB and other groups; especially, the relative abundance of genus Bifidobacterium was much higher in the B-DJB group. CONCLUSION: The BP-limb played an important role in the control of weight gain, glucose tolerance, and increased plasma bile acid levels after DJB in this rat model of type 2 diabetes mellitus. Plasma bile acids and gut microbiota may be involved in these processes.


Assuntos
Cirurgia Bariátrica/métodos , Sistema Biliar/metabolismo , Diabetes Mellitus Tipo 2/cirurgia , Duodeno/cirurgia , Jejuno/cirurgia , Pâncreas/metabolismo , Perda de Peso/fisiologia , Anastomose Cirúrgica , Animais , Ácidos e Sais Biliares/sangue , Biomarcadores/sangue , Diabetes Mellitus Tipo 2/metabolismo , Microbioma Gastrointestinal , Teste de Tolerância a Glucose , Masculino , Distribuição Aleatória , Ratos , Ratos Endogâmicos OLETF
17.
Acta Crystallogr F Struct Biol Commun ; 71(Pt 8): 1078-82, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26249703

RESUMO

Vibrio vulnificus is a halophilic marine microorganism which causes gastroenteritis and primary septicaemia in humans. An important factor that determines the survival of V. vulnificus in the human body is its ability to acquire iron. VatD is a periplasmic siderophore-binding protein from V. vulnificus M2799. The current study reports the expression, purification and crystallization of VatD. Crystals of both apo VatD and a VatD-desferrioxamine B-Fe(3+) (VatD-FOB) complex were obtained. The crystal of apo VatD belonged to space group P6422, while the crystal of the VatD-FOB complex belonged to space group P21. The difference in the two crystal forms could be caused by the binding of FOB to VatD.


Assuntos
Proteínas de Bactérias/química , Periplasma/química , Proteínas Periplásmicas de Ligação/química , Proteínas Recombinantes de Fusão/química , Vibrio vulnificus/química , Sequência de Aminoácidos , Proteínas de Bactérias/genética , Clonagem Molecular , Cristalização , Cristalografia por Raios X , Desferroxamina/química , Escherichia coli/genética , Escherichia coli/metabolismo , Expressão Gênica , Ferro/química , Dados de Sequência Molecular , Periplasma/metabolismo , Proteínas Periplásmicas de Ligação/genética , Ligação Proteica , Proteínas Recombinantes de Fusão/genética , Alinhamento de Sequência , Sideróforos/química , Vibrio vulnificus/metabolismo
18.
Microb Pathog ; 75: 59-67, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25205089

RESUMO

Vibrio vulnificus, an opportunistic marine bacterium that causes a serious, often fatal, infection in humans, requires iron for its pathogenesis. This bacterium exports vulnibactin for iron acquisition from the environment. The mechanisms of vulnibactin biosynthesis and ferric-vulnibactin uptake systems have recently been reported, while the vulnibactin export system has not been reported. Mutant growth under low-iron concentration conditions and a bioassay of the culture supernatant indicate that the VV1_0612 protein plays a crucial role in the vulnibactin secretion as a component of the resistance-nodulation-division (RND)-type efflux system in V. vulnificus M2799. To identify which RND protein(s) together with VV1_0612 TolC constituted the RND efflux system for vulnibactin secretion, deletion mutants of 11 RND protein-encoding genes were constructed. The growth inhibition of a multiple mutant (Δ11) of the RND protein-encoding genes was observed 6 h after the beginning of the culture. Furthermore, ΔVV1_1681 exhibited a growth curve that was similar to that of Δ11, while the multiple mutant except ΔVV1_1681 showed the same growth as the wild-type strain. These results indicate that the VV1_1681 protein is involved in the vulnibactin export system of V. vulnificus M2799. This is the first genetic evidence that vulnibactin is secreted through the RND-type efflux systems in V. vulnificus.


Assuntos
Amidas/metabolismo , Proteínas de Membrana Transportadoras/metabolismo , Oxazóis/metabolismo , Vibrio vulnificus/metabolismo , Meios de Cultura/química , Análise Mutacional de DNA , DNA Bacteriano/química , DNA Bacteriano/genética , Deleção de Genes , Proteínas de Membrana Transportadoras/genética , Dados de Sequência Molecular , Análise de Sequência de DNA , Vibrio vulnificus/genética , Vibrio vulnificus/crescimento & desenvolvimento
19.
Gan To Kagaku Ryoho ; 41(12): 2279-81, 2014 Nov.
Artigo em Japonês | MEDLINE | ID: mdl-25731495

RESUMO

We report 2 cases of resectable advanced gastric cancer who achieved pathological complete response by preoperative chemotherapy with S-1 plus weekly low-dose cisplatin (CDDP). S-1 (80 mg/m²)was administered consecutively for 21 days followed by 14 days' rest, with CDDP (25mg/m²) injected on days 1, 8, and 21. Case 1: A man in his 70s diagnosed with cStage III gastric cancer with lymph node metastases received 2 courses of preoperative chemotherapy with S-1 plus weekly low-dose CDDP followed by total gastrectomy with D2 lymph node dissection. Case 2: A man in his 60s diagnosed with cStage III gastric cancer with lymph node metastases received 4 courses of preoperative chemotherapy with S-1 plus weekly low-dose CDDP followed by total gastrectomy with D2 lymph-node dissection. In both cases, postoperative pathological examination revealed no cancer cells in the resected stomach and lymph nodes. The therapeutic effect of preoperative chemotherapy was assessed as Grade 3. With this regimen, we accomplished preoperative chemotherapy successfully without inpatient care. This regimen can be a promising option as preoperative chemotherapy for advanced gastric cancer.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Gástricas/patologia , Idoso , Cisplatino/administração & dosagem , Combinação de Medicamentos , Gastrectomia , Humanos , Metástase Linfática , Masculino , Terapia Neoadjuvante , Invasividade Neoplásica , Ácido Oxônico/administração & dosagem , Indução de Remissão , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/cirurgia , Tegafur/administração & dosagem
20.
Nihon Rinsho ; 71(10): 1733-7, 2013 Oct.
Artigo em Japonês | MEDLINE | ID: mdl-24261200

RESUMO

In Japan, the elderly patients generally account for high percentages of both inpatients and outpatients. As aging of the population accelerates, it will become increasingly important to properly detect, assess and intervene for psychiatric symptoms of the elderly patients to establish differential diagnoses. Thus, we must assess all existing psychiatric symptoms by keeping in mind the brain/physical conditions and social circumstances of the elderly patients and considering not just their complaints but also objective information from other organizations/services. In doing so, particular emphasis should be placed on assessing consciousness. Decreased alertness should not be dismissed as "old age". Medical professionals and caregivers must carefully assess psychiatric symptoms in the elderly patients while respecting their self-esteem.


Assuntos
Transtornos Mentais/diagnóstico , Idoso , Doença de Alzheimer/diagnóstico , Diagnóstico Diferencial , Feminino , Humanos , Doença por Corpos de Lewy/diagnóstico , Masculino , Neoplasias Gástricas/diagnóstico
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