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1.
Biol Pharm Bull ; 47(3): 713-722, 2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38432946

RESUMO

Diabetic retinopathy (DR) can cause visual impairment and blindness, and the increasing global prevalence of diabetes underscores the need for effective therapies to prevent and treat DR. Therefore, this study aimed to evaluate the protective effect of pemafibrate treatment against DR, using a Spontaneously Diabetic Torii (SDT) fatty rat model of obese type 2 diabetes. SDT fatty rats were fed either a diet supplemented with pemafibrate (0.3 mg/kg/d) for 16 weeks, starting at 8 weeks of age (Pf SDT fatty: study group), or normal chow (SDT fatty: controls). Normal chow was provided to Sprague-Dawley (SD) rats (SD: normal controls). Electroretinography (ERG) was performed at 8 and 24 weeks of age to evaluate the retinal neural function. After sacrifice, retinal thickness, number of retinal folds, and choroidal thickness were evaluated, and immunostaining was performed for aquaporin-4 (AQP4). No significant differences were noted in food consumption, body weight, or blood glucose level after pemafibrate administration. Triglyceride levels were reduced, and high-density lipoprotein cholesterol levels were increased. Extension of oscillatory potential (OP)1 and OP3 waves on ERG was suppressed in the Pf SDT fatty group. Retinal thickness at 1500 microns from the optic disc improved in the Pf SDT fatty group. No significant improvements were noted in choroidal thickness or number of retinal folds. Quantitative analyses showed that AQP4-positive regions in the retinas were significantly larger in the Pf SDT fatty group than in the SDT fatty group. The findings suggest that pemafibrate treatment can exert protective effects against DR.


Assuntos
Benzoxazóis , Butiratos , Diabetes Mellitus Tipo 2 , Retinopatia Diabética , Ratos , Animais , Retinopatia Diabética/tratamento farmacológico , Retinopatia Diabética/prevenção & controle , Ratos Sprague-Dawley , Modelos Animais de Doenças
2.
Vet Med (Praha) ; 69(2): 42-51, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38550620

RESUMO

Heart rate variability analyses using Poincaré plots can be useful for evaluating the autonomic nervous system function. However, the interpretation of the quantitative indicators of Poincaré plots remains controversial. Thus, few studies have verified the effectiveness of the quantitative indicators in veterinary medicine. This study aimed to verify the reliability of Poincaré plot indicators using pharmacological models in dogs. Four healthy beagles were used in this study. Each dog was treated with propranolol, atropine, and propranolol-atropine to block the sympathetic, parasympathetic, and sympathetic-parasympathetic functions, respectively. The quantitative indicators of the Poincaré plots were calculated based on data from 300 electrocardiogram beats collected before and after the administration of each drug and statistically analysed. The quantitative indicators of the Poincaré plots, such as the standard deviation perpendicular to the major axis (SD1), standard deviation along the major axis (SD2), and SD1 × SD2, significantly decreased after the drug administration in both the parasympathetic and sympathetic-parasympathetic blockade models. However, no significant differences were observed in SD1/SD2 between the groups. The Poincaré plots reflected the changes in the autonomic nervous system of dogs. In dogs, SD1, SD2, and SD1 × SD2 can detect a state in which parasympathetic nerve activity is suppressed.

3.
Pharmacology ; 108(5): 444-450, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37531935

RESUMO

INTRODUCTION: The incidence of acute kidney injury (AKI) caused by vancomycin hydrochloride (VCM) was reported to be 5-43%. VCM-induced AKI was reported to be more likely to occur 4-17 days after initiating VCM treatment; however, it may occur earlier. The aim of this study was therefore to investigate risk factors for the development of AKI within two (AKI2days) and seven (AKI7days) days of VCM administration. METHODS: This was a single-center, retrospective study including patients who underwent VCM therapy between April 1, 2013, and December 31, 2019. AKI was evaluated based on the Kidney Disease: Improving Global Outcomes criteria. RESULTS: In total, 287 patients were enrolled. The incidence of VCM-induced AKI within 7 days was 10.8% (31/286 cases), and the incidence of AKI within 2 days was 5.9% (15/252 cases). Serum VCM trough concentrations and tazobactam-piperacillin (TZP) were shown to be a risk factor for VCM-induced AKI. The serum VCM trough concentration was 12.67 µg/mL within the 48 h threshold (AKI2days) and 19.03 µg/mL within the 7-day threshold (AKI7days). CONCLUSION: Our study demonstrated that high serum VCM trough concentrations and the combination of VCM and TZP were independent risk factors for VCM-induced AKI. Avoiding the concomitant use of TZP, or thorough monitoring of renal function with the concomitant use of TZP, may be helpful in reducing the occurrence of AKI. Furthermore, monitoring serum VCM trough concentrations within 2 days may effectively reduce the incidence of AKI.


Assuntos
Injúria Renal Aguda , Vancomicina , Humanos , Vancomicina/efeitos adversos , Antibacterianos/efeitos adversos , Estudos Retrospectivos , Combinação Piperacilina e Tazobactam/efeitos adversos , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/epidemiologia , Fatores de Risco , Quimioterapia Combinada
4.
Matern Child Health J ; 27(5): 933-943, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36752905

RESUMO

OBJECTIVES: We aimed to clarify the accuracy of pregnant women's knowledge and understanding regarding infectious disease screening in early pregnancy and clarify the roles that should be played by health care providers in promoting the health of pregnant women and their children. METHODS: A cross-sectional questionnaire survey was conducted in 25 hospitals across Japan from May 2018 to September 2019. We compared the agreement rates regarding screening results for hepatitis B virus (HBV), hepatitis C virus (HCV), syphilis, human T-cell leukemia virus-1 (HTLV-1), and cervical cytology in the medical records and understanding of their results by pregnant women. We then investigated whether participants had knowledge regarding the risk of mother-to child transmission in these diseases and factors associated with their knowledge. RESULTS: We enrolled 2,838 respondents in this study. The rates of agreement for HBV and cervical cancer screening related to human papillomavirus infection were "substantial," those for syphilis was "moderate," and those for HCV and HTLV-1 were "fair," according to the Kappa coefficient. The rate of knowledge regarding mother-to-child transmission of syphilis was highest (37.0%); this rate for the other items was approximately 30%. Increased knowledge was associated with higher educational level and higher annual income. CONCLUSIONS FOR PRACTICE: Pregnant women in Japan had generally good levels of understanding regarding their results in early-pregnancy infectious disease screening. However, they had insufficient knowledge regarding mother-to-child transmission of these diseases. Health care providers should raise awareness in infectious disease prevention among pregnant women and the general public, providing appropriate measures and implementing effective perinatal checkups and follow-ups for infectious diseases.


Assuntos
Hepatite B , Hepatite C , Transmissão Vertical de Doenças Infecciosas , Complicações Infecciosas na Gravidez , Sífilis , Gestantes , Humanos , Feminino , Transmissão Vertical de Doenças Infecciosas/prevenção & controle , Complicações Infecciosas na Gravidez/diagnóstico , Complicações Infecciosas na Gravidez/prevenção & controle , Gravidez , Adulto , Estudos Transversais , Japão/epidemiologia , Conhecimentos, Atitudes e Prática em Saúde , Vírus da Hepatite B , Hepacivirus , Programas de Rastreamento
5.
J Phys Ther Sci ; 35(4): 306-310, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37020828

RESUMO

[Purpose] Fall risk is immanent in humans because they are bipedal. Bipedalism has transited from quadrupedalism in both evolutional and developmental contexts. Past studies have measured the peak vertical ground force of forelimbs and hindlimbs in quadrupedalism; and revealed that load dominancy shifted from forelimbs to hindlimbs during evolution. The dominance of hindlimb peak vertical ground force allows forelimb freedom and is considered important for locomotor evolution toward bipedalism. With this consideration, we hypothesize that hindlimb peak vertical ground force is dominant in human adults when they designedly crawl in a quadrupedal manner. [Participants and Methods] Six healthy human adults crawled on their hands and knees over a pressure platform. We calculated the peak vertical ground force of their hands and knees by integrating the pressure of the contact area of each limb. [Results] The mean knee peak vertical ground force at 0.694 (per body weight) was significantly higher than that of the hand at 0.372 (per body weight). The mean hand/knee peak vertical ground force ratio was 0.536; therefore, it was -0.624 on the natural logarithmic scale. [Conclusions] Our findings on human adults are compatible with existing considerations on locomotor evolution toward bipedalism. Our findings contribute to the comprehensive understanding of human locomotion.

6.
J Phys Ther Sci ; 35(9): 613-618, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37670762

RESUMO

[Purpose] Plantar pain is associated with the prevalence of low back pain. Therefore, it is reasonable to assume that some kind of physical change should be occurring in the trunk due to plantar pain. However, the physical effect of plantar pain on the trunk remains unknown. We evaluated the effect of plantar pain on trunk posture during gait. [Participants and Methods] Ten healthy volunteers participated in the present study. Participants walked under two conditions: without pain and with pain. In the with pain condition, we set pain-inducing devices to the right foot to induce plantar pain during stance phase. By using 3D motion analysis system, the angles of the head, thorax, and pelvis segments, as well as the neck, trunk, bilateral hip, bilateral knee, and bilateral ankle joints, were measured. We analyzed the angle data throughout the gait cycle by using one-dimensional statistical parametric mapping. [Results] The anterior trunk tilt was observed in the right stance phase. [Conclusion] The anterior trunk tilt observed in the with pain condition may be a burden on the trunk. Our results presented one of the possible reasons for increased prevalence of low back pain in the plantar pain patients.

7.
Gynecol Oncol ; 165(2): 293-301, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35221133

RESUMO

OBJECTIVES: We investigated whether surgical skill and procedure were related to oncological outcomes in cervical cancer patients who underwent Laparoscopic Radical Hysterectomy (LRH). METHODS: We previously assessed data of LRH from 251 patients with FIGO stage (2009) IA2, IB1and IIA1 cervical cancer collected for JGOG 1081s study. 1) The JGOG 1081s cohort study was re-examined to refine the surgical details and extend the follow-up period as chart review. 2) Unedited videos for recurrent cases and matched non-recurrent control cases were newly compared by experts for various surgical skills and surgical procedures using the modified Objective Structured Assessment of Technical Skills (OSATS) tool, without awareness of the recurrence status as video review. RESULTS: After a median follow-up of 46 months, tumors had recurred in 31 of the 251 patients. The five-year Recurrence-Free Survival rate was 86.9% (81.8-90.6) and five-year Overall Survival rate was 93.7% (87.5-96.8). Multivariate analysis from chart reviews found that an experience with LRH of less than 20 cases per institution was an independent prognostic factor for recurrence (Hazard Ratio (HR) 2.49, 95%CI 1.12-5.53, p = 0.025). For the surgical video review, we compared 23 videos of recurrent cases with 23 background-matched non-recurrent controls. Lower modified OSATS scores from the video review were consistently trended to have a higher risk of recurrence. CONCLUSIONS: Our new study has found that LRH surgical experience and skill trended to have better oncological outcomes.


Assuntos
Laparoscopia , Neoplasias do Colo do Útero , Estudos de Coortes , Feminino , Humanos , Histerectomia , Japão , Neoplasias do Colo do Útero/cirurgia
8.
Biosci Biotechnol Biochem ; 86(6): 755-762, 2022 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-35333283

RESUMO

Isoamyl alcohol (i-AmOH) is produced from α-ketoisocaproate in the l-leucine biosynthetic pathway in yeast and controlled by the negative feedback regulation of α-isopropylmalate synthase (IPMS), which senses the accumulation of l-leucine. It is known that i-AmOH production increases when mutations in the regulatory domain reduce the susceptibility to feedback inhibition. However, the impact of mutations in this domain on the IPMS activity has not been examined. In this study, we obtained 5 IPMS mutants, encoding the LEU4 gene, N515D/S520P/S542F/A551D/A551V, that are tolerant to 5,5,5-trifluoro-dl-leucine. All mutant proteins were purified and examined for both IPMS activity and negative feedback activity by in vitro experiments. The results showed that not only the negative-feedback regulation by l-leucine was almost lost in all mutants, but also the IPMS activity was greatly decreased and the difference in IPMS activity among Leu4 mutants in the presence of l-leucine was significantly correlated with i-AmOH production.


Assuntos
2-Isopropilmalato Sintase , Proteínas de Saccharomyces cerevisiae , 2-Isopropilmalato Sintase/genética , 2-Isopropilmalato Sintase/metabolismo , Retroalimentação , Leucina/genética , Leucina/metabolismo , Mutação , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Proteínas de Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/metabolismo
9.
Xenobiotica ; 51(2): 155-166, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33146575

RESUMO

Nabumetone (NAB) is a non-steroidal anti-inflammatory drug used clinically, and its biotransformation includes the major active metabolite 6-methoxy-2-naphthylacetic acid (6-MNA). One of the key intermediates between NAB and 6-MNA may be 3-hydroxy nabumetone (3-OH-NAB). The aim of the present study was to investigate the role of flavin-containing monooxygenase (FMO) isoform 5 in the formation of 6-MNA from 3-OH-NAB. To elucidate the biotransformation of 3-OH-NAB to 6-MNA, an authentic standard of 3-OH-NAB was synthesised and used as a substrate in an incubation with human liver samples or recombinant enzymes. The formation of 3-OH-NAB was observed after the incubation of NAB with various cytochrome P450 (CYP) isoforms. However, 6-MNA itself was rarely detected from NAB and 3-OH-NAB. Further experiments revealed a 6-MNA peak derived from 3-OH-NAB in human hepatocytes. 6-MNA was also detected in the extract obtained from 3-OH-NAB by a combined incubation of recombinant human FMO5 and human liver S9. We herein demonstrated that the reaction involves carbon-carbon cleavage catalyzed by the Baeyer-Villiger oxidation (BVO) of a carbonyl compound, the BVO substrate, such as a ketol, by FMO5. Further in vitro inhibition experiments showed that multiple non-CYP enzymes are involved in the formation of 6-MNA from 3-OH-NAB.


Assuntos
Anti-Inflamatórios não Esteroides/metabolismo , Nabumetona/metabolismo , Ácidos Naftalenoacéticos/metabolismo , Biotransformação , Sistema Enzimático do Citocromo P-450/metabolismo , Humanos , Microssomos Hepáticos/metabolismo , Oxirredução , Oxigenases
10.
J Vasc Interv Radiol ; 31(6): 1000-1004, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32376172

RESUMO

Transhepatic placement of a metallic biliary stent for internal drainage of persistent liver abscesses was performed in 9 patients (males; median age, 65 years; range, 57-82 years) with refractory liver abscess. The median follow-up period was 2.8 months (range, 0.4-50.3 months). Technical success was achieved in all cases without any major complications. Clinical success, defined as the removal of the drainage tube without recurrent symptoms of infection, was achieved in 8 cases. Median duration until removal of the drainage tube from stent placement was 7 days (range, 0-36).


Assuntos
Ductos Biliares , Drenagem/instrumentação , Abscesso Hepático/terapia , Stents , Idoso , Idoso de 80 Anos ou mais , Ductos Biliares/diagnóstico por imagem , Remoção de Dispositivo , Drenagem/efeitos adversos , Estudos de Viabilidade , Feminino , Humanos , Abscesso Hepático/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Desenho de Prótese , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento
11.
Xenobiotica ; 50(7): 783-792, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31855101

RESUMO

The pathway for the transformation of the prodrug nabumetone, 4-(6-methoxynaphthalen-2-yl)butan-2-one, to the active metabolite 6-methoxy-2-naphthylacetic acid (6-MNA), a potent cyclooxygenase-2 inhibitor, has not yet been clarified in humans.To confirm the activation pathway, authentic standards of the nabumetone intermediates, 2-(6-methoxynaphthalen-2-yl)ethyl acetate (6-MNEA), 2-(6-methoxynaphthalen-2-yl)ethan-1-ol (6-MNE-ol) and 2-(6-methoxynaphthalen-2-yl)acetaldehyde (6-MN-CHO) were synthesized. High performance liquid-chromatography and gas chromatography-mass spectrometry on nabumetone oxidation revealed the generation of three metabolites.The formation of 6-MNA after a 60-min incubation of nabumetone was detected and 6-MNE-ol, an alcohol-related intermediate, was also generated by in cryopreserved hepatocytes. However, 6-MNA was below detection limit, but 4-(6-methoxynaphthalen-2-yl)butan-2-ol (MNBO) and 4-(6-hydroxynaphthalen-2-yl)butan-2-one (M3) peak were found in both the microsomes and S9 extracts with any cofactors.Nabumetone has recently been proposed as a typical substrate of flavin-containing monooxygenase isoform 5 (FMO5) and was shown to be efficiently oxidized in vitro to 6-MNEA. 6-MNA was detected in the extract obtained from a combined incubation of recombinant FMO5 and S9 fractions.The specificity of FMO5 towards catalyzing this Baeyer-Villiger oxidation (BVO) was demonstrated by the inhibition of the BVO substrate, 4-methoxyphenylacetone. Further in vitro inhibition studies demonstrated that multiple non-cytochrome P450 enzymes are involved in the formation of 6-MNA.


Assuntos
Anti-Inflamatórios não Esteroides/metabolismo , Sistema Enzimático do Citocromo P-450/metabolismo , Nabumetona/metabolismo , Ácidos Naftalenoacéticos/metabolismo , Humanos , Redes e Vias Metabólicas , Microssomos Hepáticos/metabolismo , Pró-Fármacos
12.
Int J Clin Oncol ; 24(9): 1129-1136, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31069549

RESUMO

OBJECTIVE: To examine the necessity and sufficiency of different types of hysterectomy for the surgical treatment of endometrial cancer. METHODS: This was a multicenter collaborative study conducted by 11 institutions. Among patients with stage I-III endometrial cancer who underwent surgery as the initial treatment (only chemotherapy was provided if adjuvant therapy was needed) from 2001 to 2012, we retrospectively examined the type of hysterectomy, clinicopathological factors, recurrence rate over a maximum period of 5 years, and the site of recurrence. The local recurrence rate was examined by univariate and multivariate analyses. RESULTS: Among 1335 patients, 982 (73.6%) underwent simple hysterectomy (SH) and 353 (26.4%) underwent modified radical hysterectomy (mRH) and were observed for a mean duration of 51.8 months. No significant difference was observed in the rate of local recurrence between the SH and mRH groups (p = 0.928). In multivariate analysis, clinicopathological factors independently associated with localized recurrence included postmenopausal status [hazard ratio (HR) 5.036, 95% confidence interval (CI) 1.506-16.841, p = 0.009], with stages II (HR 3.337, 95% CI 1.701-6.547, p < 0.001) and III (HR 2.445, 95% CI 1.280-4.668, p = 0.007), vs stage I and histological type 2 (HR 1.610, 95% CI 0.938-2.762, p = 0.001). CONCLUSIONS: For endometrial cancer patients requiring surgery, the selection of a more extensive type of hysterectomy did not reduce the rate of local recurrence. Therefore, there is little significance in performing mRH in such cases.


Assuntos
Neoplasias do Endométrio/patologia , Neoplasias do Endométrio/cirurgia , Histerectomia/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Quimioterapia Adjuvante , Neoplasias do Endométrio/tratamento farmacológico , Neoplasias do Endométrio/mortalidade , Feminino , Humanos , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/patologia , Estudos Retrospectivos , Resultado do Tratamento
13.
BMC Ophthalmol ; 19(1): 111, 2019 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-31096954

RESUMO

INTRODUCTION: To report a case of unilateral peripheral cone dysfunction syndrome and evaluate the associated clinicopathological changes using swept-source optical coherence tomography (SS-OCT). CASE PRESENTATION: A 39-year-old Japanese woman reported a visual field defect of 2-years duration in the right eye. The patient underwent visual field testing, full-field electroretinography (ff-ERG), SS-OCT, and a routine ophthalmologic examination. The best-corrected visual acuity was 20/20 bilaterally. The funduscopy examination was normal bilaterally. Visual field testing showed a relative paracentral scotoma in the right eye. SS-OCT scans showed an unclear interdigitation zone (IZ) throughout the posterior pole except for the foveal zone in the right eye. SS-OCT macular analysis showed thinning of the ganglion cell layer (GCL) and inner plexiform layer (IPL) corresponding to the region of the IZ defect. ff-ERG showed almost normal flash ERGs and normal rod responses bilaterally. The cone response and flicker ERG response were decreased markedly only in the right eye. CONCLUSION: To the best of our knowledge, this is the first case report of unilateral peripheral cone dysfunction syndrome in which SS-OCT showed pathological changes in the GCL and IPL. The OCT findings corresponded well to the ERG changes and visual field abnormality. Because foveolar cone photoreceptor cells are connected in a one-to-one correspondence to retinal ganglion cells without connection to the horizontal cells or amacrine cells, the GCL and IPL were not present in the fovea. Based on this analysis, we speculated that the primary lesion of peripheral cone dysfunction syndrome is not in the cone photoreceptor cells but in the horizontal cells and/or amacrine cells. The clinicopathological changes in the ganglion cells and cone photoreceptor cells might be the subsequent pathologies in the horizontal cells in peripheral cone dysfunction syndrome.


Assuntos
Células Fotorreceptoras Retinianas Cones/patologia , Distrofias Retinianas/fisiopatologia , Células Ganglionares da Retina/patologia , Tomografia de Coerência Óptica , Adulto , Eletrorretinografia , Feminino , Humanos
14.
Chem Pharm Bull (Tokyo) ; 67(1): 75-78, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30606953

RESUMO

The absolute configuration of (+)-4-(6-methoxy-2-naphthyl)butan-2-ol ((+)-MNBO), a nabumetone metabolite, was determined using 1-fluoroindan-1-carboxylic acid (FICA). Both enantiomers of the FICA methyl esters were derivatized to diastereomeric esters of (+)-MNBO by an ester exchange reaction. The results of 1H- and 19F-NMR spectroscopy of the diastereomeric FICA esters of (+)-MNBO confirmed the absolute configuration of (+)-MNBO was (S).


Assuntos
Butanos/química , Ácidos Carboxílicos/química , Nabumetona/metabolismo , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Nabumetona/química , Estereoisomerismo
15.
J Am Chem Soc ; 140(22): 6754-6757, 2018 06 06.
Artigo em Inglês | MEDLINE | ID: mdl-29781615

RESUMO

We report a superconducting transition in a LaO epitaxial thin film with the superconducting transition onset temperature ( Tc) at around 5 K. This Tc is higher than those of other lanthanum monochalcogenides and opposite to their chemical trend: Tc = 0.84, 1.02, and 1.48 K for LaX (X = S, Se, Te), respectively. The carrier control resulted in a dome-shaped Tc as a function of electron carrier density. In addition, the Tc was significantly sensitive to epitaxial strain in spite of the highly symmetric crystal structure. This rock-salt superconducting LaO could be a building block to design novel superlattice superconductors.

16.
Gynecol Oncol ; 149(3): 513-519, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29661497

RESUMO

OBJECTIVE: This multicenter phase II Japanese Gynecologic Oncology Group study (JGOG1067) was designed to evaluate the efficacy and safety of postoperative chemotherapy in patients with node-positive cervical cancer. METHODS: Patients with stage IB-IIA squamous cervical cancer who underwent radical hysterectomy and were confirmed to have pelvic lymph node metastasis were eligible for this study. The patients postoperatively received irinotecan (CPT-11; 60mg/m2 intravenously on days 1 and 8) and nedaplatin (NDP; 80mg/m2 intravenously on day 1). Chemotherapy administration commenced within 6weeks after surgery and was repeated every 28days for up to 5cycles. The primary endpoint of this study was the 2-year recurrence-free survival (RFS) rate. The secondary endpoints were the 5-year overall survival (OS) rate, 5-year RFS rate, and adverse events such as complications of chemotherapy and lower-limb edema. RESULTS: Sixty-two patients were analyzed according to our protocol, among whom 55 (88.7%) completed 5cycles of scheduled treatment. The median follow-up period was 66.1months (range, 16.8-96.6months). The 2-year and 5-year RFS rates were 87.1% (95% confidence interval [CI]: 75.9-99.3) and 77.2% (95% CI: 64.5-85.8), respectively. Fourteen patients (22.5%) experienced recurrence during the follow-up period, 8 of whom died of the disease. The 5-year OS rate in this study was 86.5% (95% CI: 74.8-93.0). Only 9.7% of the patients experienced lymphedema in their legs. CONCLUSION: Postoperative chemotherapy without radiotherapy was found to be very effective in high-risk patients with node-positive cervical cancer.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias do Colo do Útero/tratamento farmacológico , Neoplasias do Colo do Útero/cirurgia , Adulto , Idoso , Camptotecina/administração & dosagem , Camptotecina/análogos & derivados , Quimioterapia Adjuvante , Intervalo Livre de Doença , Feminino , Humanos , Irinotecano , Metástase Linfática , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Compostos Organoplatínicos/administração & dosagem , Neoplasias do Colo do Útero/patologia
17.
Inorg Chem ; 57(17): 10587-10590, 2018 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-30125094

RESUMO

Recently, superconductivity was induced by expanding interlayer distance between Bi square nets in anti-ThCr2Si2-type Y2O2Bi through incorporation of excess oxygen with increased nominal amount of oxygen. However, such oxygen incorporation was applicable to only Y2O2Bi among R2O2Bi ( R = rare earth metal), probably due to a larger amount of oxygen incorporation for Y2O2Bi. In this study, the interlayer distance in Er2O2Bi was increased by cosintering with CaO, which served as an oxidant, indicating that excess oxygen was incorporated in Er2O2Bi. As a result, superconductivity was induced in Er2O2Bi at 2.2 K.

18.
J Vasc Interv Radiol ; 28(1): 50-59.e5, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27321887

RESUMO

PURPOSE: To evaluate risk factors predicting death and complications of primary therapy for hepatic and gastric duodenal artery pseudoaneurysms following endovascular treatment (EVT) after pancreaticoduodenectomy (PD). MATERIALS AND METHODS: Between April 2004 and December 2014, 28 patients (mean age, 64.7 y) with post-PD hemorrhage underwent EVT. Prevention of hepatic artery blockage via stents or side-holed catheter grafts was stratified in cases without a replaced hepatic artery. Mortality and major hepatic complications following EVT were evaluated according to age; sex; surgery-EVT interval; presence of portal vein stenosis, shock, and coagulopathy at EVT onset; and post-EVT angiographic findings. RESULTS: All hemorrhages were successfully treated with microcoils (n = 17; 61%), covered stents (n = 1; 3%), bare stent-assisted coil embolization (n = 5; 18%), or catheter grafts with coil embolization (n = 5; 18%). Hepatic arterial flow was observed after EVT in 18 patients (64%). Mortality and major hepatic complication rates were 28.6% and 32.1%, respectively. Hemorrhagic shock and coagulopathy at EVT onset (n = 8 each; odds ratio [OR], 27; 95% confidence interval [CI], 3.1-235.7; P < .01) were significantly associated with mortality. Coagulopathy at EVT onset (adjusted OR [aOR], 48.1; 95% CI, 3.2-2,931), portal vein stenosis (n = 16; aOR, 16.9; 95% CI, 1.3-721.9), and no visualization of hepatopetal flow through the hepatic arteries (n = 10; aOR, 29.5; 95% CI, 2.1-1,477) were significantly associated with major hepatic complications. CONCLUSIONS: EVT should be performed as soon as possible before the development of shock or coagulopathy. Hepatic arterial flow visualization decreases major hepatic complications.


Assuntos
Falso Aneurisma/terapia , Aneurisma Roto/terapia , Embolização Terapêutica , Procedimentos Endovasculares , Artéria Hepática/lesões , Pancreaticoduodenectomia/efeitos adversos , Hemorragia Pós-Operatória/terapia , Lesões do Sistema Vascular/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Falso Aneurisma/diagnóstico por imagem , Falso Aneurisma/etiologia , Falso Aneurisma/mortalidade , Aneurisma Roto/diagnóstico por imagem , Aneurisma Roto/etiologia , Aneurisma Roto/mortalidade , Angiografia por Tomografia Computadorizada , Embolização Terapêutica/efeitos adversos , Embolização Terapêutica/instrumentação , Embolização Terapêutica/mortalidade , Procedimentos Endovasculares/efeitos adversos , Procedimentos Endovasculares/instrumentação , Procedimentos Endovasculares/mortalidade , Feminino , Artéria Hepática/diagnóstico por imagem , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Pancreaticoduodenectomia/mortalidade , Hemorragia Pós-Operatória/diagnóstico por imagem , Hemorragia Pós-Operatória/etiologia , Hemorragia Pós-Operatória/mortalidade , Estudos Retrospectivos , Fatores de Risco , Stents , Fatores de Tempo , Resultado do Tratamento , Lesões do Sistema Vascular/diagnóstico por imagem , Lesões do Sistema Vascular/etiologia , Lesões do Sistema Vascular/mortalidade
19.
Chem Pharm Bull (Tokyo) ; 65(7): 674-677, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28674341

RESUMO

The suitability of apparatuses for the quality control of indomethacin (IND, 50 mg) compounded suppositories was evaluated and the effects of the type of suppository base on release profiles was investigated. The release characteristics of hydrophilic and lipophilic suppositories containing IND were compared using four types of dissolution methods: basket (RB), paddle (PD), dialysis tubing (DT) and flow-through cell (FTC). The release process was evaluated using the following model independent parameters: the mean dissolution time (MDT), cumulative percent of drug released (Q) at the end of the sampling time, and dissolution efficiency (DE). The fastest and most reproducible release profiles were observed for a hydrophilic base (macrogols), which resulted in more than 90% of the drug being released in 30 min using PD, RB and FTC. After 90 min, 90% of the total amount of the drug was released from a mixture of hydrophilic bases with a lipophilic base (macrogols and hard fat) in compendial dissolution methods and the mixture base was the second fastest only to the hydrophilic base. The slowest release profiles in each method were observed for the lipophilic base (hard fat). Poor drug release from any type of suppository base was noted using DT. Based on the results of the present study, FTC may be regarded as an adequate technique allowing sufficient discriminating power for the quality control of IND compounded suppositories.


Assuntos
Anti-Inflamatórios/química , Liberação Controlada de Fármacos , Indometacina/química , Supositórios , Interações Hidrofóbicas e Hidrofílicas , Técnicas In Vitro , Solubilidade
20.
J Am Chem Soc ; 138(35): 11085-8, 2016 09 07.
Artigo em Inglês | MEDLINE | ID: mdl-27541176

RESUMO

Discovery of layered superconductors such as cuprates and iron-based compounds has unveiled new science and compounds. In these superconductors, quasi-two-dimensional layers including transition metal cations play principal role in the superconductivity via carrier doping by means of aliovalent-ion substitution. Here, we report on a two-dimensional superconductivity at 2 K in ThCr2Si2-type layered oxide Y2O2Bi possessing conducting monatomic Bi(2-) square net, possibly associated with an exotic superconductivity. The superconductivity emerges only in excessively oxygen-incorporated Y2O2Bi with expanded inter-net distance, in stark contrast to nonsuperconducting pristine Y2O2Bi reported previously. This result suggests that the element incorporation into hidden interstitial site could be an alternative approach to conventional substitution and intercalation methods for search of novel superconductors.

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