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1.
Gan To Kagaku Ryoho ; 50(1): 59-64, 2023 Jan.
Artigo em Japonês | MEDLINE | ID: mdl-36759989

RESUMO

A variety of immune-related adverse events(irAEs)occur during the use of immune checkpoint inhibitors, and delayed detection may make it difficult to continue treatment. To detect irAEs as early as possible, we have been administering an irAEs self-reported interview system(ISRIS)to all outpatients using a tablet device. We conducted a retrospective study of outpatients who received pembrolizumab, nivolumab, atezolizumab, ipilimumab, and durvalumab and utilized the ISRIS from June 2019 to May 2020. The survey items were the primary disease, initial symptoms of irAEs, and detected irAEs. The total number of patients was 140, and the total number of interviews was 1,095. Overall, 42 irAEs occurred. The ISRIS is useful for detecting subjective skin disorders. However, its detection rate of myocarditis and thyroid, hepatic, and renal dysfunction was low, and there is room for improvement. We are currently developing an ISRIS application that maintains sensitivity and increases specificity to allow for early detection of irAEs at home.


Assuntos
Nivolumabe , Humanos , Autorrelato , Estudos Retrospectivos , Nivolumabe/efeitos adversos , Ipilimumab
2.
J Cutan Pathol ; 48(3): 451-454, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33300158

RESUMO

Acantholytic dyskeratotic acanthoma is a rare variant of epidermal acanthoma. It has a flat, plaque-like structure and is characterized microscopically by acantholysis and dyskeratosis. Eccrine syringofibroadenomatous hyperplasia is benign and likely reactive. It has recently been considered as a hyperplastic process affecting the eccrine ducts rather than the neoplasm because of its pathological heterogeneity and wide clinical associations. In this article, we present the case of 97-year-old Japanese women with a 10-mm wide, painful acantholytic dyskeratotic acanthoma accompanied by syringofibroadenomatous hyperplasia in the right femoral region. Although syringofibroadenomatous hyperplasia is known to occur as a reactive process with various dermatoses and cutaneous tumors, to date, there have been no reports of cases of acantholytic dyskeratotic acanthoma accompanying syringofibroadenomatous hyperplasia. Moreover, this case also includes the unusual finding of an increase in the mature sebocytes in the area of the syringofibroadenomatous hyperplasia.


Assuntos
Acantólise/patologia , Acantoma/diagnóstico , Epiderme/patologia , Poroma/diagnóstico , Neoplasias Cutâneas/patologia , Neoplasias das Glândulas Sudoríparas/patologia , Acantólise/diagnóstico , Acantoma/cirurgia , Acantoma/ultraestrutura , Idoso de 80 Anos ou mais , Povo Asiático/etnologia , Proliferação de Células , Diagnóstico Diferencial , Feminino , Humanos , Hiperplasia/diagnóstico , Hiperplasia/patologia , Pessoa de Meia-Idade , Dor/diagnóstico , Dor/etiologia , Poroma/patologia , Pele/patologia
3.
Biochim Biophys Acta Mol Cell Biol Lipids ; 1862(6): 615-622, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28336329

RESUMO

We previously demonstrated that the aromatic moiety of Tyr143 within the intracellular loop 2 (ICL2) region of the prostaglandin EP2 receptor plays a crucial role in Gs coupling. Here we investigated whether the ICL2 of the EP2 receptor directly binds to Gαs and whether an aromatic moiety affects this interaction. In Chinese hamster ovary cells, mutations of Tyr143 reduced the ability of the EP2 receptor to interact with G proteins as demonstrated by GTPγS sensitivity, as well as the ability of agonist-induced cAMP formation, with the rank order of Phe>Tyr (wild-type)=Trp>Leu>Ala (=0). We found that the wild-type ICL2 peptide (i2Y) and its mutant with Phe at Tyr143 (i2F) inhibited receptor-G protein complex formation of wild-type EP2 in membranes, whereas the Ala-substituted mutant (i2A) did not. Specific interactions between these peptides and the Gαs protein were detected by surface plasmon resonance, but Gαs showed different association rates, with a rank order of i2F>i2Y≫i2A, with similar dissociation rates. Moreover, i2F and i2Y, but not i2A activated membrane adenylyl cyclase. These results indicate that the ICL2 region of the EP2 receptor is its potential interaction site with Gαs, and that the aromatic side chain moiety at position 143 is a determinant for the accessibility of the ICL2 to the Gαs protein.


Assuntos
Cromograninas/metabolismo , Subunidades alfa Gs de Proteínas de Ligação ao GTP/metabolismo , Receptores de Prostaglandina E Subtipo EP2/metabolismo , Substituição de Aminoácidos , Animais , Cromograninas/química , Cromograninas/genética , Cricetinae , Subunidades alfa Gs de Proteínas de Ligação ao GTP/química , Subunidades alfa Gs de Proteínas de Ligação ao GTP/genética , Humanos , Mutação de Sentido Incorreto , Domínios Proteicos , Estrutura Secundária de Proteína , Receptores de Prostaglandina E Subtipo EP2/química , Receptores de Prostaglandina E Subtipo EP2/genética
4.
Surg Today ; 46(3): 326-34, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25940758

RESUMO

PURPOSE: In most general thoracic operations performed via standard posterolateral thoracotomy, such as for descending aortic aneurysms and lung cancer, the latissimus dorsi (LD) muscle is divided. However, division of the LD can hamper reconstructive surgery because the initial operation creates unstable blood flow to the divided LD. We conducted this study to assess blood flow in a divided distal LD muscle flap using intraoperative indocyanine green-fluorescence angiography (ICG-FA) with the Hyper Eye Medical System(®) (Mizuho Medical Co., Ltd., Tokyo, Japan). METHODS: The subjects were 11 patients who underwent posterolateral thoracotomy with reconstructive surgery using a divided distal LD and other peripheral muscle flaps. Intraoperative ICG-FA was conducted to assess blood flow to the LD. RESULTS: Intraoperative ICG-FA revealed that at least two intercostal perforators from the sixth to the tenth intercostal spaces were preserved as feeding vessels to the divided distal LD. There were no major complications associated with inadequate blood flow to the muscle flaps. CONCLUSION: Intraoperative ICG-FA proved extremely useful for assessing altered blood flow of the divided LD and for selecting preserved intercostal perforators.


Assuntos
Aorta Torácica/cirurgia , Aneurisma Aórtico/cirurgia , Neoplasias Pulmonares/cirurgia , Procedimentos de Cirurgia Plástica/métodos , Músculos Superficiais do Dorso/irrigação sanguínea , Retalhos Cirúrgicos/fisiologia , Toracotomia/métodos , Idoso , Idoso de 80 Anos ou mais , Feminino , Angiofluoresceinografia , Humanos , Verde de Indocianina , Período Intraoperatório , Masculino , Pessoa de Meia-Idade , Pneumonectomia/métodos , Fluxo Sanguíneo Regional , Resultado do Tratamento
5.
Metab Brain Dis ; 30(3): 813-9, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25575695

RESUMO

It remains unclear whether prolonged febrile seizures (pFS) in childhood facilitate mesial temporal lobe epilepsy (MTLE) in adulthood. Interleukin (IL)-1ß is associated with seizures in children and immature animal models. Here, we use a rat model of pFS to study the effects of IL-1ß on adult epileptogenesis, hippocampal damage, and cognition. We produced prolonged hyperthermia-induced seizures on postnatal days (P) 10-11 and administered IL-1ß or saline intranasally immediately after the seizures. Motor and cognitive functions were assessed at P85 using rotarod and passive avoidance tests. Electroencephalogram recordings were conducted at P90 and P120. Hippocampal CA1 and CA3 neurons and gliosis were quantified at the end of the experiment. Spontaneous seizure incidence was significantly greater in rats that had received IL-1ß than in those that had received saline or those without hyperthermia-induced seizures (p < 0.05). Seizure frequency did not differ significantly between the three groups and no motor deficits were observed. Passive avoidance learning was impaired in rats that received IL-1ß compared with controls (p < 0.05), but was not different from that in rats that received saline. Hippocampal cell numbers and gliosis did not differ between the three groups. These results indicate that neuronal loss and gliosis are not prerequisites for the epileptogenic process that follows pFS. Our results suggest that infantile pFS combined with IL-1ß overproduction can enhance adulthood epileptogenesis, and might contribute to the development of MTLE.


Assuntos
Epilepsia do Lobo Temporal/induzido quimicamente , Epilepsia do Lobo Temporal/metabolismo , Interleucina-1beta/administração & dosagem , Interleucina-1beta/toxicidade , Convulsões Febris/metabolismo , Fatores Etários , Animais , Animais Recém-Nascidos , Epilepsia do Lobo Temporal/etiologia , Feminino , Humanos , Masculino , Ratos , Ratos Endogâmicos Lew , Convulsões Febris/complicações
6.
Biochem Pharmacol ; 227: 116454, 2024 09.
Artigo em Inglês | MEDLINE | ID: mdl-39069137

RESUMO

Given the significance of the intrauterine lipid environment in glucose metabolic homeostasis in offspring, the present study was undertaken to investigate the feasibility and efficacy of pemafibrate, a triglyceride-lowering peroxisome proliferator-activated agent, for maternal high-fat diet (HFD) intake-induced glucose metabolic dysfunction in offspring. A mouse model of HFD-induced gestational obesity was employed, and pemafibrate was orally administered from day 10 of gestation until delivery. The influences of maternal pemafibrate treatment on biological processes and toxicity were evaluated in both newborns and 12-week-old offspring. The findings of a dose-dependent decrease of ß cell islet mass and of impairment of glucose tolerance and insulin sensitivity in offspring suggest that maternal pemafibrate intervention can prevent maternal HFD-intake-induced diabetes in offspring. Of particular interest in the prevention of future glucose metabolic dysfunction in offspring, low-dose maternal pemafibrate treatment (0.02 mg/kg/day) had sufficient efficacy and appeared to be safe in offspring. Therefore, pemafibrate may be a potential agent for the prevention of maternal high-fat exposure-induced diabetes in offspring. Abbreviations: CD, control diet; DEG, differentially expressed genes; GTT, glucose tolerance test; HFD, high-fat diet; ITT, insulin tolerance test; MC, 0.5w/v% methyl cellulose 400 solution; PPAR, triglyceride-lowering peroxisome proliferator-activated receptor; RNA-seq, RNA sequencing; TC, total cholesterol; TG, triglycerides.


Assuntos
Benzoxazóis , Butiratos , Dieta Hiperlipídica , Animais , Feminino , Dieta Hiperlipídica/efeitos adversos , Gravidez , Butiratos/farmacologia , Camundongos , Benzoxazóis/farmacologia , Benzoxazóis/administração & dosagem , Efeitos Tardios da Exposição Pré-Natal/prevenção & controle , Efeitos Tardios da Exposição Pré-Natal/metabolismo , Masculino , Estudos de Viabilidade , Glicemia/efeitos dos fármacos , Glicemia/metabolismo , Camundongos Endogâmicos C57BL , Resistência à Insulina/fisiologia , Animais Recém-Nascidos
7.
J Nutr Biochem ; 124: 109508, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-37898392

RESUMO

With the aim of offsetting immune dysfunction preceded by sarcopenia, the feasibility and efficiency of nutritional leucine supplementation were evaluated using a murine denervation-induced sarcopenia model. Sciatic nerve axotomy caused significant loss of skeletal muscle of the hind limbs and accelerated mitochondrial stress along with suppressed ATP production in spleen-derived T cells. Dietary leucine intake not only ameliorated muscle mass anabolism in a sarcopenic state, but also restored mitochondrial respiratory function, as indicated by elevated levels of basal respiration, maximal respiration, spare respiratory capacity, and ATP production, in T cells, which in turn led to downregulated expression of mTOR and downstream signals, as indicated by the findings of comprehensive transcriptome analysis. Consequentially, this finally resulted in amelioration of the sarcopenia-induced relative Th1/Th17-dominant proinflammatory microenvironment. These results highlight the importance of leucine-promoted metabolic cues in directing T cell fate in a sarcopenic microenvironment. The present study provides insights that particularly help rationalize the design and optimization of leucine supplementation for chronic sarcopenic patients with autoimmune diseases.


Assuntos
Sarcopenia , Humanos , Camundongos , Animais , Sarcopenia/metabolismo , Leucina/farmacologia , Leucina/metabolismo , Músculo Esquelético/metabolismo , Suplementos Nutricionais , Respiração , Denervação , Trifosfato de Adenosina/metabolismo
8.
Life Sci ; 334: 122214, 2023 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-37907153

RESUMO

AIMS: The activity and interactions of cellular subpopulations in the adipose tissue microenvironment are critical for the coordination of local and systemic adaptation during pregnancy. With a particular interest in parametrial adipose tissue (PmAT), single-cell RNA-sequencing (scRNA-seq) was utilized to unveil the gestative cellular composition and functional shift. MATERIALS AND METHODS: To identify cell-type-enriched transcriptome profiles, a total of 18,074 cells in adipose tissue were studied. The cell populations were cataloged, and signaling crosstalk between adipocytes and other composition factions via soluble and membrane-bound factors were evaluated. KEY FINDINGS: A marked decline of pregnancy adipocytes and relative elevation of non-adipocyte fractions were observed. A subpopulation of adipocytes, Adipo_5, with unique properties in the response to estrogen and the embryonic processes involved in pregnancy, was defined. Interactome analysis revealed the potential contribution of PmAT to the establishment of maternal-fetal immune tolerance. During gestation, adipocytes shut down outgoing signaling, resulting in deterioration of the resistin-related incoming signaling network in B cells, which would therefore benefit tissue-specific maternal-fetal tolerance. Furthermore, a subpopulation of adipocytes, Aipo_2, was also considered to take part in a paradigm shift in the process of pregnancy-induced chemical stiffness-triggered vesicular remodeling via the THBS signaling pathway network. SIGNIFICANCE: These data-derived findings will encourage investigation into the role of pregnant PmTA in pregnancy-related immunological, hypertensive and metabolic disorders, with the ultimate goal of establishing preventive strategies to mitigate these pregnancy-related health challenges. This translational aspect of our work holds significant promise for improving maternal and fetal well-being.


Assuntos
Tecido Adiposo , Transcriptoma , Gravidez , Feminino , Camundongos , Animais , Tecido Adiposo/metabolismo , Adipócitos/metabolismo , Perfilação da Expressão Gênica , Comunicação Celular
9.
Geriatr Gerontol Int ; 23(4): 263-269, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36855031

RESUMO

Frailty attracts research as it represents a significant target for intervention to extend the healthy life span. An unanswered question in this field is the time point during the life-course at which an individual becomes predisposed to frailty. Here, we propose that frailty has a fetal origin and should be regarded as part of the spectrum of the developmental origins of health and disease. The developmental origins of health and disease theory originated from findings linking the fetal environment to lifestyle-related disorders such as hypertension and diabetes. Coincidentally, a recent trend in frailty research also centers on vascular dysfunction and metabolic alterations as the causality of lifestyle-related disorders such as sarcopenia and dementia. Here, we explore the relationship between fetal programming, frailty-related disorders (sarcopenia and dementia), and other age-related diseases mainly based on reports on intrauterine growth restriction. We propose a "total" life-course approach to combat frailty. With this viewpoint, not only physicians and gerontologists but also obstetricians and pediatricians should team up to overcome age-related diseases in the elderly. Geriatr Gerontol Int 2023; 23: 263-269.


Assuntos
Demência , Diabetes Mellitus , Fragilidade , Sarcopenia , Humanos , Idoso , Estilo de Vida , Idoso Fragilizado
10.
Front Oncol ; 13: 1082441, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36969081

RESUMO

Introduction: The incidence of endometrial cancer (EC) has been increasing worldwide. However, because there are limited chemotherapeutic options for the treatment of EC, the prognosis of advanced-stage EC is poor. Methods: Gene expression profile datasets for EC cases registered in The Cancer Genome Atlas (TCGA) was reanalyzed. Highly expressed genes in advanced-stage EC (110 cases) compared with early-stage EC (255 cases) were extracted and Gene Ontology (GO) enrichment analysis was performed. Among the enriched genes, Kaplan-Meier (KM) plotter analysis was performed. Candidate genes expression was analyzed in HEC50B cells and Ishikawa cells by RT-qPCR. In HEC50B cells, LIM homeobox1 (LIM1) was knocked down (KD) and cell proliferation, migration, and invasion ability of the cells were evaluated. Xenografts were generated using LIM1-KD cells and tumor growth was evaluated. Ingenuity Pathway Analysis (IPA) of RNA-seq data using LIM-KD cells was performed. Expression of phospho-CREB and CREB-related proteins were evaluated in LIM1-KD cells by western blotting and in xenograft tissue by immunofluorescent staining. Two different CREB inhibitors were treated in HEC50B and cell proliferation was evaluated by MTT assay. Results: Reanalysis of TCGA followed by GO enrichment analysis revealed that homeobox genes were highly expressed in advanced-stage EC. Among the identified genes, KM plotter analysis showed that high LIM1 expression was associated with a significantly poorer prognosis in EC. Additionally, LIM1 expression was significantly higher in high-grade EC cell lines, HEC50B cells than Ishikawa cells. Knockdown of LIM1 showed reduced cell proliferation, migration and invasion in HEC50B cells. Xenograft experiments revealed that tumor growth was significantly suppressed in LIM1-KD cells. IPA of RNA-seq data using LIM-KD cells predicted that the mRNA expression of CREB signaling-related genes was suppressed. Indeed, phosphorylation of CREB was decreased in LIM1-KD cells and LIM1-KD cells derived tumors. HEC50B cells treated by CREB inhibitors showed suppression of cell proliferation. Conclusion and discussion: Collectively, these results suggested that high LIM1 expression contributed to tumor growth via CREB signaling in EC. Inhibition of LIM1 or its downstream molecules would be new therapeutic strategies for EC.

11.
Nucleic Acids Res ; 38(10): 3489-501, 2010 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-20156995

RESUMO

Many well-characterized examples of antisense RNAs from prokaryotic systems involve hybridization of the looped regions of stem-loop RNAs, presumably due to the high thermodynamic stability of the resulting loop-loop and loop-linear interactions. In this study, the identification of RNA stem-loops that inhibit U1A protein binding to the hpII RNA through RNA-RNA interactions was attempted using a bacterial reporter system based on phage lambda N-mediated antitermination. As a result, loop sequences possessing 7-8 base complementarity to the 5' region of the boxA element important for functional antitermination complex formation, but not the U1 hpII loop, were identified. In vitro and in vivo mutational analysis strongly suggested that the selected loop sequences were binding to the boxA region, and that the structure of the antisense stem-loop was important for optimal inhibitory activity. Next, in an attempt to demonstrate the ability to inhibit the interaction between the U1A protein and the hpII RNA, the rational design of an RNA stem-loop that inhibits U1A-binding to a modified hpII was carried out. Moderate inhibitory activity was observed, showing that it is possible to design and select antisense RNA stem-loops that disrupt various types of RNA-protein interactions.


Assuntos
RNA Antissenso/química , RNA Nuclear Pequeno/química , Ribonucleoproteína Nuclear Pequena U1/química , Bactérias/genética , Genes Reporter , Mutação , Conformação de Ácido Nucleico , RNA Nuclear Pequeno/metabolismo , Sequências Reguladoras de Ácido Ribonucleico , Ribonucleoproteína Nuclear Pequena U1/metabolismo , Proteínas Virais Reguladoras e Acessórias/metabolismo
12.
J Plast Reconstr Aesthet Surg ; 74(1): 108-115, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32586757

RESUMO

BACKGROUND: Although the free jejunal graft is commonly used for reconstruction after resection of a tumor of the pharynx or cervical esophagus, adequate monitoring for detecting graft failure is not available. We employed near-infrared spectroscopy to measure regional oxygen saturation (rSO2) in the graft. METHODS: In 25 consecutive cases who underwent reconstructive surgery using a free jejunal graft, the feasibility of postoperative rSO2 monitoring was examined along with the changes in rSO2 values following vascular clamping or reperfusion. RESULTS: No operative mortality occurred, and except for one case of subcutaneous hematoma that necessitated evacuation surgery, no complications related to surgery or graft failure occurred. Postoperative rSO2 monitoring was feasible for >50 hours in most cases. It mostly remained >55% with a stable hemoglobin index (HbI) which reflects tissue hemoglobin density. A marked increase in the HbI was noted in a patient with hematoma. Intraoperatively, the rSO2 of intact jejunal tissue was >60% in every case but dropped within a few minutes after arterial clamping because of decreased oxygenated hemoglobin concentration. With venous clamping, the HbI was elevated while the rSO2 remained unchanged or was slightly decreased. Upon graft reperfusion, the rSO2 rapidly recovered in all 18 cases because of the recovery of oxygenated hemoglobin concentrations. CONCLUSIONS: The near-infrared spectroscopic assessment sensitively and accurately reflected the condition of the jejunal graft. It appears to be a promising postoperative method for monitoring graft perfusion. An rSO2 value of 55% appears to be an adequate criterion for ischemia.


Assuntos
Autoenxertos/diagnóstico por imagem , Retalhos de Tecido Biológico/fisiologia , Isquemia/diagnóstico por imagem , Jejuno/transplante , Espectroscopia de Luz Próxima ao Infravermelho , Adulto , Idoso , Idoso de 80 Anos ou mais , Autoenxertos/irrigação sanguínea , Autoenxertos/metabolismo , Constrição , Esofagoplastia , Esôfago/cirurgia , Feminino , Sobrevivência de Enxerto , Hemoglobinas/metabolismo , Humanos , Isquemia/metabolismo , Jejuno/metabolismo , Masculino , Pessoa de Meia-Idade , Monitorização Fisiológica/métodos , Oxigênio/metabolismo , Período Pós-Operatório , Reperfusão
13.
Biomolecules ; 11(6)2021 05 31.
Artigo em Inglês | MEDLINE | ID: mdl-34072941

RESUMO

Preeclampsia (PE) is a serious disease that can be fatal for the mother and fetus. The two-stage theory has been proposed as its cause, with the first stage comprising poor placentation associated with the failure of fertilized egg implantation. Successful implantation and placentation require maternal immunotolerance of the fertilized egg as a semi-allograft and appropriate extravillous trophoblast (EVT) invasion of the decidua and myometrium. The disturbance of EVT invasion during implantation in PE results in impaired spiral artery remodeling. PE is thought to be caused by hypoxia during remodeling failure-derived poor placentation, which results in chronic inflammation. High-mobility group protein A (HMGA) is involved in the growth and invasion of cancer cells and likely in the growth and invasion of trophoblasts. Its mechanism of action is associated with immunotolerance. Thus, HMGA is thought to play a pivotal role in successful pregnancy, and its dysfunction may be related to the pathogenesis of PE. The evaluation of HMGA function and its changes in PE might confirm that it is a reliable biomarker of PE and provide prospects for PE treatment through the induction of EVT proliferation and invasion during the implantation.


Assuntos
Proliferação de Células , Decídua/metabolismo , Proteína HMGA1a/metabolismo , Pré-Eclâmpsia/metabolismo , Trofoblastos/metabolismo , Animais , Decídua/patologia , Feminino , Humanos , Pré-Eclâmpsia/patologia , Gravidez , Trofoblastos/patologia
14.
Biochem Biophys Res Commun ; 389(4): 678-82, 2009 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-19769944

RESUMO

We previously demonstrated that prostaglandin EP3 receptor augments EP2-elicited cAMP formation in COS-7 cells in a G(i/o)-insensitive manner. The purpose of our current study was to identify the signaling pathways involved in EP3-induced augmentation of receptor-stimulated cAMP formation. The enhancing effect of EP3 receptor was irrespective of the C-terminal structure of the EP3 isoform. This EP3 action was abolished by treatment with inhibitors for phospholipase C and intracellular Ca(2+)-related signaling molecules such as U73122, staurosporine, 2-APB and SK&F 96365. Indeed, an EP3 agonist stimulated IP(3) formation and intracellular Ca(2+) mobilization, which was blocked by U73122, but not by pertussis toxin. The enhancing effect by EP3 on cAMP formation was mimicked by both a Ca(2+) ionophore and the activation of a typical G(q)-coupled receptor. Moreover, EP3 was exclusively localized to the raft fraction in COS-7 cells and EP3-elicited augmentation of cAMP formation was abolished by cholesterol depletion and introduction of a dominant negative caveolin-1 mutant. These results suggest that EP3 elicits adenylyl cyclase superactivation via G(q)/phospholipase C activation and intracellular Ca(2+) mobilization in a lipid raft microdomain-dependent manner.


Assuntos
Adenilil Ciclases/biossíntese , Cálcio/metabolismo , Subunidades alfa Gq-G11 de Proteínas de Ligação ao GTP/metabolismo , Microdomínios da Membrana/metabolismo , Receptores de Prostaglandina E/metabolismo , Fosfolipases Tipo C/metabolismo , Animais , Compostos de Boro/farmacologia , Células COS , Caveolina 1/metabolismo , Chlorocebus aethiops , Ativação Enzimática , Estrenos/farmacologia , Humanos , Imidazóis/farmacologia , Ionóforos/farmacologia , Pirrolidinonas/farmacologia , Receptores de Prostaglandina E/antagonistas & inibidores , Receptores de Prostaglandina E Subtipo EP2 , Estaurosporina/farmacologia , Fosfolipases Tipo C/antagonistas & inibidores
15.
Acta Neurochir Suppl ; 102: 385-8, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-19388351

RESUMO

BACKGROUND: L-type amino acid transporter 1 (LAT1) is proposed to be a major nutrient transporter at the blood brain barrier. LAT1 requires the heavy chain of 4F2 cell surface antigen (4F2hc) for functional expression. METHODS: We investigated the expression of this heterodimeric transporter after traumatic spinal cord injury in rat by using immunohistochemical and western blot analyses. FINDINGS: LAT1 immunoreactivities were up-regulated in the capillary endothelia in close to the injury epicenter 24 hours after injury. It reached a peak at 48 hours after injury, and thereafter decreased. 4F2hc was abundant and unchanged all through the time course after SCI. Western blot analysis under reductive and non-reductive conditions showed that LAT1 and 4F2hc were conjugated as a heterodimeric transporter and the functional regulation was dependent on the light chain, LAT1. CONCLUSIONS: We suggest that LAT1 may be transiently upregulated as part of the tissue-repair process after traumatic contusion injury in the spinal cord.


Assuntos
Sistema L de Transporte de Aminoácidos/metabolismo , Traumatismos da Medula Espinal/metabolismo , Regulação para Cima/fisiologia , Análise de Variância , Animais , Modelos Animais de Doenças , Feminino , Cadeia Pesada da Proteína-1 Reguladora de Fusão/metabolismo , Ratos , Ratos Sprague-Dawley , Medula Espinal/metabolismo , Traumatismos da Medula Espinal/patologia , Traumatismos da Medula Espinal/fisiopatologia , Fatores de Tempo
16.
Surg Case Rep ; 4(1): 83, 2018 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-30066205

RESUMO

BACKGROUND: The demand for breast reconstruction after mastectomy is rising. The use of deep inferior epigastric perforator (DIEP) flap in autologous reconstruction is a popular approach. There were some reports about abdominal complications after breast reconstruction. However, there was no report about spontaneous rupture of abdominal wall. CASE PRESENTATION: A 46-year-old female patient was diagnosed with left breast cancer. Left mastectomy with sentinel lymph node biopsy was performed, and the breast was reconstructed using DIEP flap simultaneously. She suffered heavy abdominal pain and vomiting at postoperative day 4. Computed tomography showed bowel herniation into the subcutaneous tissue caused by left abdominal wall rupture. The abdominal wall was sutured and repaired using mesh by emergency surgery. CONCLUSIONS: To the best of our knowledge, this is the first case about spontaneous rupture of abdominal wall after breast reconstruction using DIEP flap to be reported in the English literature. DIEP flap on breast reconstructive surgery may cause spontaneous rupture of abdominal wall.

17.
J Cancer ; 8(8): 1371-1377, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28638451

RESUMO

Purpose The therapeutic benefit of a three-drug combination of antiemetics has not been established in moderately emetogenic chemotherapy (MEC). The aim of this study was to compare the antiemetic effectiveness and cost-saving of palonosetron plus dexamethasone (control group) with aprepitant, granisetron, and dexamethasone (study group) in cancer patients who received MEC. Methods We switched the standard antiemetic treatment from the control group to the study group in gastrointestinal cancer patients who received MEC after October 2015. The antiemetics in both groups were modified using salvage antiemetic therapy at the clinicians' discretion, according to the severity of chemotherapy-induced nausea and vomiting. We retrospectively reviewed the electronic medical records from patients, before and after switching groups, from between April 2014 and March 2016. Results We evaluated 443 treatment courses in 83 patients. The proportion of courses that included salvage antiemetic therapy in the control group and the study group was 34.8 % (116/333) and 8.2 % (9/110), respectively, and was statistically significant (p < 0.001). The mean integrated costs of antiemetics per course in the control group and the study group were 193 ± 55 USD and 143 ± 38 USD, respectively. Multivariate logistic regression analysis revealed that the study group was significantly associated with a reduced risk of requiring salvage antiemetic therapy (p = 0.038). Conclusions These results suggest that the antiemetic effectiveness and cost-saving of a three-drug combination of aprepitant, generic granisetron, and dexamethasone was superior to a two-drug combination of palonosetron plus dexamethasone in gastrointestinal cancer patients who received MEC.

18.
PLoS One ; 12(2): e0171066, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28158216

RESUMO

PURPOSE: As the major toxicity induced by pemetrexed plus carboplatin is severe hematologic toxicities, the aim of this study was to determine the risk factors for severe hematologic toxicities in lung cancer patients. METHODS: We retrospectively investigated data from lung cancer patients who had received pemetrexed plus carboplatin, with or without bevacizumab. This observational study was carried out at Ehime University Hospital using electronic medical records dating from July 2009 to March 2015. Severe hematologic toxicities were defined as grade 3 or 4, according to the Common Terminology Criteria for Adverse Events, version 4.0. RESULTS: Forty-two patients were included in the study. The incidence of grade 3 or 4 hematologic toxicities during the first cycle of chemotherapy and during all cycles was 19.0% and 16.1%, respectively. Multivariate time-depend generalized estimating equations logistic regression analysis revealed that regular use of non-steroidal anti-inflammatory drugs (NSAIDs) was significantly associated with an increased risk of severe hematologic toxicities during all cycles (adjusted odds ratio (OR): 8.32, 95% confidence interval (CI): 1.27-54.38; p = 0.03), whereas creatinine clearance of <45 mL/min was not significantly associated with an increased risk of severe hematologic toxicities during all cycles (adjusted OR: 0.91, 95% CI: 0.25-3.34; p = 0.88). CONCLUSIONS: The results suggest that severe hematologic toxicities in patients receiving carboplatin-based pemetrexed may be significantly induced by the inhibition of renal tubular pemetrexed secretion through drug-drug interactions between NSAIDs and pemetrexed rather than through glomerular filtration of pemetrexed, even with moderate to sufficient renal function.


Assuntos
Anti-Inflamatórios não Esteroides/efeitos adversos , Carboplatina/uso terapêutico , Doenças Hematológicas/induzido quimicamente , Neoplasias Pulmonares/tratamento farmacológico , Pemetrexede/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Anemia/sangue , Anemia/induzido quimicamente , Anemia/patologia , Feminino , Doenças Hematológicas/sangue , Doenças Hematológicas/patologia , Humanos , Leucopenia/sangue , Leucopenia/induzido quimicamente , Leucopenia/patologia , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Neutropenia/sangue , Neutropenia/induzido quimicamente , Neutropenia/patologia , Estudos Retrospectivos , Trombocitopenia/sangue , Trombocitopenia/induzido quimicamente , Trombocitopenia/patologia , Resultado do Tratamento
19.
Brain Res ; 1069(1): 54-62, 2006 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-16386718

RESUMO

The purpose of this study was to identify mechanisms that mediate the impairment of spatial memory induced by 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), a 5-HT1A/5-HT7 receptor agonist, in the eight-arm radial maze in rats. WAY-100635 and NAN-190, 5-HT1A receptor antagonists, reversed the impairment of spatial memory induced by systemic injection of 8-OH-DPAT (1 mg/kg, i.p.). On the other hand, the alpha1-adrenoceptor antagonist prazosin and a selective 5-HT7 receptor antagonist SB269970 had no effect on 8-OH-DPAT-induced impairment of spatial memory. Bilateral microinjection of 8-OH-DPAT (4 microg/side) impaired spatial memory when injected into the dorsal hippocampus (DH). Contrastingly, spatial memory was unaffected by microinjections of 8-OH-DPAT into the other six areas examined: ventral hippocampus (VH), central amygdaloid nucleus (ACE), lateral hypothalamus (LH), nucleus accumbens (NAc), and dorsal (DR) and median (MR) raphe nucleus. Furthermore, NAN-190 significantly reversed the impairment of spatial memory induced by intra-DH injection of 8-OH-DPAT. These findings suggest that 5-HT1A receptors in the DH play an important role in the mechanisms underlying the 8-OH-DPAT-induced impairment of spatial memory in rats.


Assuntos
Hipocampo/fisiopatologia , Transtornos da Memória/fisiopatologia , Receptor 5-HT1A de Serotonina/fisiologia , 8-Hidroxi-2-(di-n-propilamino)tetralina , Antagonistas Adrenérgicos alfa/farmacologia , Análise de Variância , Animais , Comportamento Animal , Relação Dose-Resposta a Droga , Vias de Administração de Medicamentos , Interações Medicamentosas , Hipocampo/efeitos dos fármacos , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Transtornos da Memória/induzido quimicamente , Transtornos da Memória/patologia , Microinjeções/métodos , Fenóis/farmacologia , Piperazinas/farmacologia , Prazosina/farmacologia , Piridinas/farmacologia , Ratos , Ratos Wistar , Antagonistas da Serotonina/farmacologia , Sulfonamidas/farmacologia
20.
J Pharm Policy Pract ; 9: 35, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27795831

RESUMO

BACKGROUND: High oral bioavailability of antimicrobial agents can result in the replacement of intravenous (IV) therapy with oral therapy when a patient meets defined clinical criteria. However, few studies have evaluated the effects of switching antibiotic administration route in Japan, especially for linezolid. This study evaluated an IV-to-oral antibiotic switching program for linezolid treatment at a university hospital in Japan. METHODS: In a retrospective cohort study of 73 patients, we assessed the efficacy and safety of IV-to-oral linezolid therapy (n = 21 patients) compared with IV therapy alone (n = 52 patients). RESULTS: Duration of linezolid treatment, changes in C-reactive protein or platelet count from baseline, re-administration of anti-methicillin-resistant Staphylococcus aureus agent within 90 days of discharge, and mortality within 28 days of discharge were not significantly different between the two groups. CONCLUSIONS: An IV-to-oral switching program could reduce the duration of IV linezolid therapy without worsening clinical outcomes in Japanese patients receiving linezolid therapy.

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