Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 35
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Issues Ment Health Nurs ; 42(9): 862-869, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33739236

RESUMO

Academic educators in universities are well positioned to detect early signs and symptoms of unexplained behaviour change in students that could be the beginning of mental health issues. The purpose of this research was to explore the attitudes, beliefs, knowledge and practices of university academics in Japan towards health science students with psychological/mental health issues. This study used a qualitative descriptive design. Three focus groups using a semi-structured interview guide were conducted with 15 academics teaching health science students. Data were collected between March to October 2019. Themes revealed three areas of interest: 1) Reflection on mental health issues in Japan with sub-themes "family issues"; "society expectations and changes", and "stigma"; 2) Reflection on students' mental health issues with sub-themes "student behaviors", "staff involvement", "barriers encountered"; and, 3) Potential supports with sub-themes "university assistance", "communication and connection", and "interventions and prevention." The findings provide insight and can benefit student populations across diverse cultural university settings. Further research to investigate academic staff support with early recognition of mental ill-health and ability to provide information and advice to students is warranted. Recommendations include mental health education for academics and for students to encourage healthy university campuses and well-being within the community.


Assuntos
Saúde Mental , Universidades , Grupos Focais , Humanos , Japão , Estudantes
2.
Nat Commun ; 9(1): 3948, 2018 09 26.
Artigo em Inglês | MEDLINE | ID: mdl-30258055

RESUMO

A charge excitation in a two-dimensional Mott insulator is strongly coupled with the surrounding spins, which is observed as magnetic-polaron formations of doped carriers and a magnon sideband in the Mott-gap transition spectrum. However, the dynamics related to the spin sector are difficult to measure. Here, we show that pump-probe reflection spectroscopy with seven-femtosecond laser pulses can detect the optically induced spin dynamics in Nd2CuO4, a typical cuprate Mott insulator. The bleaching signal at the Mott-gap transition is enhanced at ~18 fs. This time constant is attributable to the spin-relaxation time during magnetic-polaron formation, which is characterized by the exchange interaction. More importantly, ultrafast coherent oscillations appear in the time evolution of the reflectivity changes, and their frequencies (1400-2700 cm-1) are equal to the probe energy measured from the Mott-gap transition peak. These oscillations can be interpreted as the interference between charge excitations with two magnons originating from charge-spin coupling.

3.
Nat Mater ; 16(11): 1100-1105, 2017 11.
Artigo em Inglês | MEDLINE | ID: mdl-28825731

RESUMO

The transition of a Mott insulator to metal, the Mott transition, can occur via carrier doping by elemental substitution, and by photoirradiation, as observed in transition-metal compounds and in organic materials. Here, we show that the application of a strong electric field can induce a Mott transition by a new pathway, namely through impulsive dielectric breakdown. Irradiation of a terahertz electric-field pulse on an ET-based compound, κ-(ET) 2Cu[N(CN) 2]Br (ET:bis(ethylenedithio)tetrathiafulvalene), collapses the original Mott gap of ∼30 meV with a ∼0.1 ps time constant after doublon-holon pair productions by quantum tunnelling processes, as indicated by the nonlinear increase of Drude-like low-energy spectral weights. Additionally, we demonstrate metallization using this method is faster than that by a femtosecond laser-pulse irradiation and that the transition dynamics are more electronic and coherent. Thus, strong terahertz-pulse irradiation is an effective approach to achieve a purely electronic Mott transition, enhancing the understanding of its quantum nature.

4.
Phys Rev Lett ; 116(7): 076402, 2016 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-26943548

RESUMO

To control the efficiency of photoinduced charge-order melting in perovskite manganites, we performed femtosecond pump-probe spectroscopy using double-pulse excitation on Pr_{0.6}Ca_{0.4}MnO_{3}. The results revealed that the transfer of the spectral weight from the near-infrared to infrared region by the second pump pulse is considerably enhanced by the first pump pulse and that the suppression of crystal anisotropy, that is, the decrease of long-range lattice deformations due to the charge order by the first pump pulse is a key factor to enhance the charge-order melting. This double-pulse excitation method can be applied to various photoinduced transitions in complex materials with electronic and structural instabilities.

5.
Sci Rep ; 6: 20571, 2016 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-26864779

RESUMO

In electronic-type ferroelectrics, where dipole moments produced by the variations of electron configurations are aligned, the polarization is expected to be rapidly controlled by electric fields. Such a feature can be used for high-speed electric-switching and memory devices. Electronic-type ferroelectrics include charge degrees of freedom, so that they are sometimes conductive, complicating dielectric measurements. This makes difficult the exploration of electronic-type ferroelectrics and the understanding of their ferroelectric nature. Here, we show unambiguous evidence for electronic ferroelectricity in the charge-order (CO) phase of a prototypical ET-based molecular compound, α-(ET)2I3 (ET:bis(ethylenedithio)tetrathiafulvalene), using a terahertz pulse as an external electric field. Terahertz-pump second-harmonic-generation(SHG)-probe and optical-reflectivity-probe spectroscopy reveal that the ferroelectric polarization originates from intermolecular charge transfers and is inclined 27° from the horizontal CO stripe. These features are qualitatively reproduced by the density-functional-theory calculation. After sub-picosecond polarization modulation by terahertz fields, prominent oscillations appear in the reflectivity but not in the SHG-probe results, suggesting that the CO is coupled with molecular displacements, while the ferroelectricity is electronic in nature. The results presented here demonstrate that terahertz-pump optical-probe spectroscopy is a powerful tool not only for rapidly controlling polarizations, but also for clarifying the mechanisms of ferroelectricity.

6.
Phys Rev Lett ; 109(9): 097403, 2012 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-23002882

RESUMO

The relaxation dynamics of an exciton in rubrene was investigated by femtosecond absorption spectroscopy. Exciton relaxation to a self-trapped state occurs via the coherent oscillation with 78 cm(-1) due to a coupled mode of molecular deformations with phenyl-side-group motions and molecular displacements. From the temperature dependence of the decay time of excitons, the energy necessary for an exciton to escape from a self-trapped state is evaluated to be ~35 meV (~400 K). As a result, a self-trapped exciton is stable at low temperatures. At room temperature, excitons can escape from a self-trapped state and, subsequently, they are dissociated to charged species. The exciton dissociation mechanism is discussed on the basis of the results.

7.
Food Addit Contam ; 20(3): 215-20, 2003 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-12623644

RESUMO

Acrylamide concentrations in processed foods (63 samples covering 31 product types) from Japan were analysed by LC-MS/MS and GC-MS methods. The limit of detection and limit of quantification of acrylamide were 0.2 ng x ml(-1) (6 fmol) and 0.8 ng x ml(-1) (22 fmol), respectively, by LC-MS/MS, and those of 2,3-dibromopropionamide derived from acrylamide were 12 ng x ml(-1) (52 fmol) and 40 ng x ml(-1) (170 fmol), respectively, by GC-MS. Repeatability given as RSD was <5 and <15% for the LC-MS/MS and GC-MS methods, respectively. High correlation (r(2) - 0.946) was observed between values obtained by the two methods. Most potato crisps and whole potato-based fried snacks showed acrylamide concentrations >1000 microg x kg(-1). The concentrations in non-whole potato-based snacks, rice crackers processed by grilling or frying, and candied sweet potatoes were lower compared with those in the potato crisps and the whole potato-based fried snacks. One of the whole potato-based fried snacks, however, showed low acrylamide concentration (<50 microg x kg(-1)) suggesting the formation of acrylamide is strongly influenced by processing conditions. Acrylamide concentrations in instant precooked noodles and won-tons were <100 microg x kg(-1) with only one exception. Roasted barley grains for 'Mugi-cha' tea contained 200-600 microg x kg(-1) acrylamide.


Assuntos
Acrilamida/análise , Carcinógenos/análise , Contaminação de Alimentos/análise , Análise de Alimentos/métodos , Manipulação de Alimentos , Cromatografia Gasosa-Espectrometria de Massas/métodos , Japão , Reprodutibilidade dos Testes
9.
Biosci Biotechnol Biochem ; 64(1): 1-8, 2000 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-10705441

RESUMO

D-Aminoacylase from Alcaligenes xylosoxydans subsp. xylosoxydans A-6 (Alcaligenes A-6) was strongly inactivated by diethylpyrocarbonate (DEPC). An H67N mutant was barely active, with a kcat/Km 6.3 x 10(4) times lower than that of the recombinant wild-type enzyme, while the H67I mutant lost detectable activity. The H67N mutant had almost constant Km, but greatly decreased kcat. These results suggested that His67 is essential to the catalytic event. Both H69N and H69I mutants were overproduced in the insoluble fraction. The kcat/Km of H250N mutant was reduced by a factor of 2.5 x 10(4)-fold as compared with the wild-type enzyme. No significant difference between H251N mutant and wild-type enzymes in the Km and kcat was found. The Zn content of H250N mutant was nearly half of that of wild-type enzyme. These results suggest that the His250 residue might be essential to catalysis via Zn binding.


Assuntos
Alcaligenes/enzimologia , Amidoidrolases/metabolismo , Histidina/metabolismo , Alcaligenes/efeitos dos fármacos , Amidoidrolases/genética , Catálise , Dicroísmo Circular , Cobalto/farmacologia , Dietil Pirocarbonato/farmacologia , Histidina/genética , Cinética , Mutagênese Sítio-Dirigida , Conformação Proteica , Relação Estrutura-Atividade , Zinco/farmacologia
10.
Biol Reprod ; 61(6): 1480-6, 1999 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-10569992

RESUMO

We have investigated the possible role of theca and granulosa cell interaction in the control of the hormone-producing activity and growth of granulosa and theca cells during bovine ovarian follicular development, using a coculture system in which granulosa and theca cells were grown on opposite sides of a collagen membrane. When follicular cells were isolated from small follicles (3-5 mm), theca cells reduced estradiol, progesterone, and inhibin production by granulosa cells to 14 +/- 5%, 64 +/- 6%, and 27 +/- 4%, respectively, of the production by granulosa cells cultured alone. On the other hand, when the cells were isolated from large follicles (15-18 mm), theca cells increased these levels to 253 +/- 34%, 156 +/- 24%, and 287 +/- 45%, respectively. Theca cells did not affect the growth of granulosa cells. Androstenedione production by theca cells was augmented by granulosa cells to 861 +/- 190% (in small follicles) and 1298 +/- 414% (in large follicles), respectively. The growth of theca cells was also augmented by granulosa cells (small follicle, 210 +/- 43%, and large follicle, 194 +/- 24%, respectively). These results indicate that theca cells secrete factor(s) inhibiting the differentiation of immature while promoting that of matured granulosa cells; they also suggest that granulosa cells secrete factor(s) promoting both the differentiation and growth of theca cells throughout the follicular maturation process.


Assuntos
Bovinos/fisiologia , Divisão Celular , Células da Granulosa/fisiologia , Hormônios/biossíntese , Folículo Ovariano/fisiologia , Células Tecais/fisiologia , Androstenodiona/biossíntese , Animais , Células Cultivadas , Técnicas de Cocultura , Estradiol/biossíntese , Feminino , Inibinas/biossíntese , Progesterona/biossíntese
11.
Jpn J Clin Oncol ; 29(2): 74-7, 1999 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-10089947

RESUMO

BACKGROUND: The long-term survival of 200 patients with gastric cancer who underwent radical gastrectomy was analyzed with respect to the number and anatomical extent of lymph node metastasis. All of the patients received intra-lymph node injection of fine activated carbon particle solution (CH40) during surgery. METHODS: The average number of resected lymph nodes increased in line with the anatomical level of lymph node dissection; 32.5 per patient in D1, 42.3 in D2, 3 and 66.3 in D4. The percentage of blackened lymph nodes without metastasis (42.4%) was slightly higher than that of lymph nodes containing metastasis (37.2%), but the difference was not statistically significant. Of the 200 patients, 61 (30.5%) had microscopic evidence of metastatic lymph node involvement. Twenty-two patients had between one and three metastatic lymph nodes, 19 had between four and nine and 20 patients had more than nine. The 5-year survival rate was 93.1% in patients without lymph node metastasis, 71.9% in patients with 1-8 metastatic nodes, 36.1% in patients with 4-9 nodes and 19.2% in patients with > 9 nodes. RESULTS: The 5-year survival rate according to the anatomical extent of metastatic lymph nodes was 93.1% in n0, 63.1% in n1, 37.9% in n2, 27.8% in n3 and 0% in n4. The number of metastatic lymph nodes and also their anatomical extent were identified as independent prognostic factors for survival by multivariate analysis. CONCLUSION: The number and anatomical extent of metastatic lymph nodes have similar impacts on prognosis in gastric cancer.


Assuntos
Excisão de Linfonodo , Linfonodos/patologia , Metástase Linfática/patologia , Neoplasias Gástricas/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carbono/administração & dosagem , Feminino , Gastrectomia , Humanos , Injeções , Masculino , Pessoa de Meia-Idade , Prognóstico , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/cirurgia , Taxa de Sobrevida
12.
Cancer Lett ; 122(1-2): 195-9, 1998 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-9464510

RESUMO

In order to determine the effects of intermittent hormonal manipulation on the promotion stage of rat prostate carcinogenesis, testosterone and/or estrogen were administered to F344 rats for 40 weeks after 20-weeks treatment with the prostate carcinogen, 3,2'-dimethyl-4-aminobiphenyl. For this purpose testosterone propionate (TP) and diethylstilbestrol (DES) were introduced into silastic tubes, 2- and 0.5-cm long, respectively, and implanted into the subcutis for seven repeated cycles of 30 days treatment and 10 days withdrawal. Intermittent administration of TP resulted in suppression of ventral prostate adenocarcinoma development and slight but non-significant increases in the incidences of invasive carcinomas of the lateral prostate and seminal vesicles. Intermittent administration of DES completely suppressed tumorigenesis in all sites and the combination of TP and DES generally inhibited prostate tumor development. Thus, under the present experimental conditions, no strong enhancing effects of cyclic hormonal manipulation were observed on rat prostate carcinogenesis. Indeed, the opposite appeared to be the case.


Assuntos
Compostos de Aminobifenil/toxicidade , Carcinógenos/toxicidade , Dietilestilbestrol/toxicidade , Neoplasias da Próstata/induzido quimicamente , Testosterona/toxicidade , Animais , DNA/biossíntese , Masculino , Ratos , Ratos Endogâmicos F344
13.
World J Surg ; 21(1): 109-15, 1997 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-8943187

RESUMO

To determine the indications for limited colon cancer surgery in each location, we reviewed the arterial branching patterns and lymph node metastases along the course of specific vascular trunks in 344 colon cancer patients who had undergone preoperative angiography and colectomy with lymph node dissection. Our conclusions are follows: Because the ileocecal artery always arises from the superior mesenteric artery and lymph node metastases of cecum cancer were limited to nodes along the ileocolic artery, cecum cancer can be cured by ileocecal resection. The right colic artery has various origins, and ascending colon cancer shows various patterns of lymph node metastases. Therefore a right hemicolectomy should be performed for ascending colon cancer. The middle colic artery forks into right and left branches, and each branch has different branching variations. If the right colic and middle colic arteries have a common trunk, a right hemicolectomy should be performed for transverse colon cancer on the right side. If the left branch of the middle colic artery has an independent replaced origin, lymph node dissection should be modified according to the variant origin. If the left colic artery and the first sigmoidal artery have a common trunk, the lymph nodes along the common trunk should be removed for sigmoid colon cancer and for descending colon cancer. Of the patients with sigmoid colon cancer, 6.3% also had lymph node metastases along the superior rectal artery. Given that the lymph nodes along the superior rectal artery are skeletonized, sigmoid colon cancer can be also cured by partial sigmoidectomy.


Assuntos
Colo/irrigação sanguínea , Neoplasias do Colo/cirurgia , Artérias/anatomia & histologia , Feminino , Humanos , Linfonodos/anatomia & histologia , Metástase Linfática , Masculino , Pessoa de Meia-Idade
14.
Cancer Lett ; 112(1): 33-45, 1997 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-9029167

RESUMO

The carcinogenic and metastatic processes are thought to consist of a sequence of steps, and animal models featuring highly metastatic lesions are clearly necessary to allow analysis of the whole process of transformation from preneoplastic changes to high grade metastatic tumors, and to access effectiveness of therapeutic treatments of advanced cancers in vivo. The purpose of the present study was to establish a model and to screen for reported genetic alterations in induced lesions. In the present study, it was confirmed that lung metastasis of hepatocellular carcinomas (HCCs) induced in male F344 rats by N-nitrosomorpholine (NNM), given in the drinking water at a dose of 120 ppm for 24 weeks, was significantly enhanced by additional carcinogenic pretreatments and that a single i.p. injection of 100 mg/kg body weight N-diethylnitrosamine (DEN) alone was sufficient for that purpose. Molecular biological analyses of the induced lesions revealed point mutations in the p53 gene in 60.9% of HCCs, and elevated expression of mRNAs for p53, c-myc, c-fos, TGF-alpha, TGF-beta1, alpha-fetoprotein, GST-P, and GGT, and decreased mRNA expression of EGF and EGFR in HCCs when compared to controls. No obvious association of gene alterations with metastatic potential of primary tumors was found except for an increase in the incidence of p53 mutations. Since the process of metastasis is thought to be sequential and selective, further comparative analysis of metastatic and primary lesions should clarify the mechanisms involved in the multi-step process of metastasis.


Assuntos
Carcinoma Hepatocelular/genética , Genes p53/efeitos dos fármacos , Neoplasias Hepáticas Experimentais/genética , Mutação , Animais , Carcinógenos , Carcinoma Hepatocelular/induzido quimicamente , Carcinoma Hepatocelular/secundário , Genes p53/genética , Neoplasias Hepáticas Experimentais/induzido quimicamente , Neoplasias Hepáticas Experimentais/patologia , Neoplasias Pulmonares/secundário , Masculino , Nitrosaminas , Oncogenes/efeitos dos fármacos , Oncogenes/genética , RNA Mensageiro/metabolismo , Ratos , Ratos Endogâmicos F344
15.
Jpn J Cancer Res ; 87(11): 1116-20, 1996 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-9045939

RESUMO

The dose-dependence of 2-amino-l-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) induction of mammary carcinomas was investigated in female Sprague-Dawley (SD) rats given PhIP in the diet for 48 weeks at concentrations of 0, 25, 100 and 200 ppm in experiment 1, and 0, 12.5, 50 in experiment 2. Yields of ductular lesions, including intraductal papillomas and carcinomas, as well as papillo-tubular and solid-tubular carcinomas, showed dependence on the dose, with the respective total incidences being 0, 4.8, 25, 72.2 and 0, 10 and 35%. There was thus no apparent carcinogen exposure threshold. The present results confirmed the carcinogenicity demonstrated in a previous study using F344 rats and revealed the SD rat strain to be more susceptible.


Assuntos
Adenocarcinoma/induzido quimicamente , Carcinógenos/toxicidade , Imidazóis/toxicidade , Neoplasias Mamárias Experimentais/induzido quimicamente , Papiloma Intraductal/induzido quimicamente , Adenocarcinoma/patologia , Animais , Peso Corporal/efeitos dos fármacos , Divisão Celular/fisiologia , Relação Dose-Resposta a Droga , Feminino , Glândulas Mamárias Animais/citologia , Glândulas Mamárias Animais/efeitos dos fármacos , Neoplasias Mamárias Experimentais/patologia , Papiloma Intraductal/patologia , Ratos , Ratos Sprague-Dawley , Sensibilidade e Especificidade
17.
Biosci Biotechnol Biochem ; 60(4): 650-3, 1996 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-8829533

RESUMO

N-Acyl-D-glutamate amidohydrolase (D-AGase) from Pseudomonas sp. 5f-1 was inactivated by diethyl pyrocarbonate (DEP). The chemical modification by DEP showed a difference spectrum at 246 nm due to the N-carbethoxyhistidine residue. Removal of the carbethoxy group from inactivated enzyme with hydroxylamine restored enzyme activity. The inactivation by DEp proceeded with pseudo-first-order kinetics, and was protected in the presence of the substrate N-acetyl-D-glutamate (Glu), or the competitive inhibitor sodium alpha-ketoglutarate (alpha-KGA). These results suggest the presence of an essential histidine residue at or near of the active site of the enzyme.


Assuntos
Amidoidrolases/química , Dietil Pirocarbonato/farmacologia , Inibidores Enzimáticos/farmacologia , Histidina/química , Pseudomonas/enzimologia , Amidoidrolases/antagonistas & inibidores , Sítios de Ligação , Ácidos Carboxílicos/farmacologia , Catálise , Concentração de Íons de Hidrogênio
18.
J Toxicol Sci ; 19 Suppl 2: 145-53, 1994 Oct.
Artigo em Japonês | MEDLINE | ID: mdl-7830284

RESUMO

Tazobactam (TAZ) is a newly developed beta-lactamase inhibitor. Tazobactam/Piperacillin (TAZ/PIPC) is a formulation consisting of TAZ and PIPC in a ratio of 1:4. Singe-dose toxicity studies in TAZ/PIPC and TAZ were carried out using mice and rats of both sexes and male dogs. The results were as follows. 1. A common clinical sign in mice and rats administered TAZ/PIPC or TAZ by all routes was soft stool. Other signs in mice and rats included a decrease in spontaneous motor activity and/or a decreased respiratory rate for the intraperitoneal (i.p.), subcutaneous (s.c.) or intravenous (i.v.) route. The animals administered by the i.v. route showed tremor for mice and clonic convulsion for rats before death. Hyperemia, hemorrhage or edema of the lung, and hemorrhage of the digestive tract were observed in these animals at necropsy. An enlargement of the spleen was seen in some of the surviving animals treated with TAZ/PIPC. 2. In dogs, TAZ/PIPC caused vomiting, and TAZ caused vomiting, respiratory abnormality, soft stool and diarrhea by the intravenous (i.v.) administration. 3. TAZ/PIPC or TAZ caused clinical signs such as the loss of hair at the injection site for the s.c. route, and necrosis of the tail for the i.v. route in mice and rats, also caused limping of the injected anterior limb in dogs. Necrosis and hemorrhage at the injection site, and peritonitis by the i.p. injection were observed at necropsy. These findings were due to the irritation of TAZ/PIPC or TAZ.(ABSTRACT TRUNCATED AT 250 WORDS)


Assuntos
Quimioterapia Combinada/toxicidade , Ácido Penicilânico/análogos & derivados , Piperacilina/toxicidade , Animais , Cães , Feminino , Dose Letal Mediana , Masculino , Camundongos , Camundongos Endogâmicos ICR , Ácido Penicilânico/toxicidade , Ratos , Ratos Sprague-Dawley , Respiração/efeitos dos fármacos , Tazobactam , Inibidores de beta-Lactamases
19.
J Toxicol Sci ; 19 Suppl 2: 155-76, 1994 Oct.
Artigo em Japonês | MEDLINE | ID: mdl-7830285

RESUMO

Tazobactam (TAZ) is a newly developed beta-lactamase inhibitor. Tazobactam/Piperacillin (TAZ/PIPC) is a formulation consisting of TAZ and PIPC in a ratio of 1:4. A six-month intraperitoneal repeated dose toxicity study of TAZ/PIPC and TAZ including a one-month recovery period were carried out using male and female rats. The doses were 200, 400 and 800 mg/kg/day for TAZ/PIPC, and 40, 80 and 160 mg/kg/day for TAZ. The results were as follows. 1. No test article-related deaths occurred during the study period. No effect on clinical finding of survival rats was evident. 2. There was no dose-related increases of food consumption in both the males and females given TAZ/PIPC and PIPC. Slight reductions in body weight gain occurred in males given 800 mg/kg/day of TAZ/PIPC. 3. Decreases in erythrocyte, hemoglobin and hematocrit, and increases in reticulocytes were seen only at study termination in the group given 800 mg/kg/day of TAZ/PIPC. Increases in reticulocytes were seen only at study termination in the females given 80 or 160 mg/kg/day of TAZ. 4. A decrease in triglyceride levels was observed in the males given 800 mg/kg/day of TAZ/PIPC or 160 mg/kg/day of TAZ. 5. The ophthalmoscopic examination or urinalysis show no test article-related changes. 6. Enlarged ceca in all groups of animals given TAZ/PIPC and in the females given 160 mg/kg/day of TAZ were observed. 7. An increase of relative organ weight in liver was noted in the males and females given 800 mg/kg/day of TAZ/PIPC, in the males given 80 or 160 mg/kg/day of TAZ and in the females given 160 mg/kg/day of TAZ. 8. In the hepatocytes, accumulation of PAS-positive materials which was identified histochemically and ultrastructurally as glycogen, was present in the males given 800 mg/kg/day of TAZ/PIPC and in the males given 80 or 160 mg/kg/day of TAZ. 9. After a one-month recovery period, the changes of liver had generally disappeared, suggesting that they were reversible. 10. From the histopathological changes of liver, the no-toxic dose level in both the males and females was 400 mg/kg/day and 40 mg/kg/day for TAZ/PIPC and TAZ, respectively.


Assuntos
Quimioterapia Combinada/toxicidade , Ácido Penicilânico/análogos & derivados , Piperacilina/toxicidade , Animais , Feminino , Glicogênio/metabolismo , Injeções Intraperitoneais , Masculino , Tamanho do Órgão/efeitos dos fármacos , Ácido Penicilânico/toxicidade , Ratos , Ratos Sprague-Dawley , Tazobactam , Inibidores de beta-Lactamases
20.
J Toxicol Sci ; 19 Suppl 2: 177-97, 1994 Oct.
Artigo em Japonês | MEDLINE | ID: mdl-7830286

RESUMO

Tazobactam (TAZ) is a newly developed beta-lactamase inhibitor. Tazobactam/Piperacillin (TAZ/PIPC) is a formulation consisting of TAZ and PIPC in a ratio of 1:4. A six-month intravenous repeated dose toxicity study of TAZ/PIPC and TAZ including a one-month recovery period were carried out using male and female dogs. The doses were 200, 400 and 800 mg/kg/day for TAZ/PIPC, and 40, 80 and 160 mg/kg/day for TAZ. The results were as follows. 1. No test article-related deaths occurred during the study period. No effects on clinical findings, body weight and food consumption were evident. 2. No test article-related changes were noted in hematological, serum biochemical and urinalysis evaluations, and opthalmological and electrocardiographic examinations. 3. There were no test article-related changes in macroscopic findings or organ weight. 4. The histopathological examination revealed deposition of marked PAS-positive aggregates in liver cells of dogs given 400 mg/kg/day or more of TAZ/PIPC and 80 mg/kg/day or more of TAZ. Electron micrographs of hepatocytes revealed glycogen granules to be accumulated in the cytoplasm, and an increase of smooth endoplasmic reticulum. 5. After a one-month recovery period, the histopathological changes had generally disappeared, suggesting that they were reversible. 6. From the histopathological changes of liver, the no-toxic dose levels for TAZ/PIPC and TAZ were 200 mg/kg/day and 40 mg/kg/day, respectively.


Assuntos
Quimioterapia Combinada/toxicidade , Ácido Penicilânico/análogos & derivados , Piperacilina/toxicidade , Animais , Cães , Feminino , Injeções Intravenosas , Masculino , Ácido Penicilânico/toxicidade , Tazobactam , Inibidores de beta-Lactamases
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA