Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 33
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
2.
Front Oncol ; 11: 681997, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33996612

RESUMO

Currently, only a few reports exist on the cytokine release syndrome (CRS) as one of the severe immune-related adverse events (irAEs) induced by immune checkpoint inhibitors (ICIs). Notably, it is very rare that grade 4 CRS related to ICI therapy overlaps with the drug-induced hypersensitivity syndrome (DiHS). A 46-year old woman with metastatic kidney cancer had grade 3 interstitial pneumonitis induced by four cycles of combination therapy of anti-programmed death-1 and anti-cytotoxic T lymphocyte-4 antibodies after right cytoreductive nephrectomy. Prophylactic administration of trimethoprim/sulfamethoxazole (TMP/SMX) was started concomitantly with prednisolone therapy to treat the interstitial pneumonitis. She developed hypotensive shock when reducing the dosage of prednisolone, and required intubation and ventilation using vasopressors at the intensive care unit. She subsequently exhibited prominent leukocytosis and an increased level of C-reactive protein, suggesting markedly increased cytokine levels. Interestingly, facial edema and erythema increased in association with pyrexia, leukocytosis, liver dysfunction, and renal failure, suggesting that she developed DiHS. She received hemodialysis three times, a plasma exchange, and anti-interleukin-6 therapy to treat severe renal dysfunction, a thrombotic thrombocytopenic purpura-suspected condition, and possible grade 4 CRS, respectively. Although these therapies did not elicit sufficient effects, high-dose administration of intravenous immunoglobulin was successful. With steroid mini-pulse therapy and the subsequent administration of prednisolone, she recovered successfully. To the best of our knowledge, this is the first report that ICIs and TMP/SMX can induce hypotensive shock accompanied with CRS and DiHS during immunosuppressive therapy for an irAE. Importantly, the prophylactic administration of TMP/SMX should be performed cautiously to avoid severe drug reactions such as CRS or DiHS.

3.
J Cardiol ; 76(2): 177-183, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32199753

RESUMO

BACKGROUND: Although recent attention to palliative care for patients with cardiovascular diseases has been increasing, there are no specific recommendations on detailed palliative care practices. We proceed on a discussion of the appropriateness and applicability of potential quality indicators for acute cardiovascular diseases according to our previous systematic review. METHODS: We created a multidisciplinary panel of 20 team members and 7 external validation clinicians composed of clinical cardiologists, a nutritionist, a physiotherapist, a clinical psychologist, a critical and emergent care specialist, a catheterization specialist, a primary care specialist, a palliative care specialist, and nurses. After crafting potential indicators, we performed a Delphi rating, ranging from "1 = minimum" to "9 = maximum". The criterion for the adoption of candidate indicators was set at a total mean score of seven or more. Finally, we subcategorized these indicators into several domains by using exploratory factor analysis. RESULTS: Sixteen of the panel members (80%) were men (age, 49.5 ± 13.7 years old). Among the initial 32 indicators, consensus was initially reached on total 23 indicators (71.8%), which were then summarized into 21 measures by selecting relatively feasible time variations. The major domains were "symptom palliation" and "supporting the decision-making process". Factor analysis could not find optimal model. Narratively-developed seven sub-categories included "presence of palliative care team", "patient-family relationship", "multidisciplinary team approach", "policy of approaching patients", "symptom screening and management", "presence of ethical review board", "collecting and providing information for decision-maker", and "determination of treatment strategy and the sharing of the care team's decision". CONCLUSION: In this study we developed 21 quality indicators, which were categorized into 2 major domains and 7 sub-categories. These indicators might be useful for many healthcare providers in the initiation and enhancement of palliative care practices for acute cardiovascular diseases in Japan.


Assuntos
Doenças Cardiovasculares/terapia , Cuidados Paliativos/normas , Indicadores de Qualidade em Assistência à Saúde , Adulto , Consenso , Técnica Delfos , Feminino , Humanos , Japão , Masculino , Pessoa de Meia-Idade
4.
Chem Commun (Camb) ; 55(52): 7566-7567, 2019 07 04.
Artigo em Inglês | MEDLINE | ID: mdl-31190033

RESUMO

Correction for 'Enzyme-mediated dual-targeted-assembly realizes a synergistic anticancer effect' by Dingze Mang et al., Chem. Commun., 2019, 55, 6126-6129.

5.
Chem Commun (Camb) ; 55(43): 6126-6129, 2019 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-31070616

RESUMO

We designed and synthesized homochiral-peptide-based boron diketonate complexes. Co-administration of the two stereoisomers in cancer cells led to molecular assembly targeting both the plasma membrane and the lysosomes mediated via membrane-bonded enzymes. The dual-targeted-assembly generates a synergistic anticancer effect with amplified cancer spheroid toxicity and enhanced inhibition efficacy on cancer cell migration.


Assuntos
Antineoplásicos/farmacologia , Neoplasias/patologia , Linhagem Celular Tumoral , Sinergismo Farmacológico , Humanos , Estereoisomerismo
6.
Development ; 145(20)2018 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-30322969

RESUMO

In vertebrate lens, lens epithelial cells cover the anterior half of the lens fiber core. Lens epithelial cells proliferate, move posteriorly and start to differentiate into lens fiber cells at the lens equator. Although FGF signaling promotes this equatorial commencement of lens fiber differentiation, the underlying mechanism is not fully understood. Here, we show that lens epithelial cells abnormally enter lens fiber differentiation without passing through the equator in zebrafish vps45 mutants. VPS45 belongs to the Sec1/Munc18-like protein family and promotes endosome trafficking, which differentially modulates signal transduction. Ectopic lens fiber differentiation in vps45 mutants does not depend on FGF, but is mediated through activation of TGFß signaling and inhibition of canonical Wnt signaling. Thus, VPS45 normally suppresses lens fiber differentiation in the anterior region of lens epithelium by modulating TGFß and canonical Wnt signaling pathways. These data indicate a novel role of endosome trafficking to ensure equator-dependent commencement of lens fiber differentiation.


Assuntos
Diferenciação Celular , Endocitose , Cristalino/citologia , Cristalino/metabolismo , Proteínas de Transporte Vesicular/metabolismo , Proteínas de Peixe-Zebra/metabolismo , Peixe-Zebra/metabolismo , Animais , Epitélio/metabolismo , Fatores de Crescimento de Fibroblastos/metabolismo , Integrina beta1/metabolismo , Mutação/genética , Fenótipo , Transporte Proteico , Fator de Crescimento Transformador beta/metabolismo , Proteínas de Transporte Vesicular/genética , Via de Sinalização Wnt , Proteínas de Peixe-Zebra/genética
7.
Chem Commun (Camb) ; 53(44): 6033-6036, 2017 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-28524186

RESUMO

The precision and efficacy of photodynamic therapy (PDT) is essential for the treatment of brain tumors because the cancer cells are within or adjacent to the delicate nervous system. Taurine is an abundant amino acid in the brain that serves the central nervous system (CNS). A taurine-modified polypyridyl Ru-complex was shown to have optimized intracellular affinity in cancer cells through accumulation in lysosomes. Symmetrical modification of this Ru-complex by multiple taurine molecules enhanced the efficiency of molecular emission with boosted generation of reactive oxygen species. These characteristic features make the taurine-modified Ru-complex a potentially effective photosensitizer for PDT of target cancer cells, with outstanding efficacy in cancerous brain cells.


Assuntos
Antineoplásicos/farmacologia , Neoplasias Encefálicas/tratamento farmacológico , Fotoquimioterapia , Fármacos Fotossensibilizantes/farmacologia , Rutênio/farmacologia , Taurina/farmacologia , Animais , Antineoplásicos/síntese química , Antineoplásicos/química , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patologia , Morte Celular/efeitos dos fármacos , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Conformação Molecular , Células PC12 , Fármacos Fotossensibilizantes/síntese química , Fármacos Fotossensibilizantes/química , Ratos , Espécies Reativas de Oxigênio/metabolismo , Rutênio/química , Taurina/química
8.
Development ; 144(4): 708-719, 2017 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-28196805

RESUMO

In vertebrates, lens epithelial cells cover the anterior half of the lens fiber core. During development, lens epithelial cells proliferate, move posteriorly and differentiate into lens fiber cells after passing through the equator. To elucidate the mechanisms underlying lens epithelial cell movement, we conducted time-lapse imaging of zebrafish lens epithelium. Lens epithelial cells do not intermingle but maintain their relative positions during development. Cell division induces epithelial rearrangement, which subsequently promotes cell movement towards the equator. These data suggest that cell division is the major driving force for cell movement. In zebrafish, E-cadherin is expressed in lens epithelium, whereas N-cadherin is required for lens fiber growth. E-cadherin reduced lens epithelial cell movement, whereas N-cadherin enhanced it. Laser ablation experiments revealed that lens epithelium is governed by pulling tension, which is modulated by these cadherins. Thus, cell division and cadherin-mediated adhesion regulate lens epithelial cell movement via modulation of epithelial tension.


Assuntos
Caderinas/metabolismo , Células Epiteliais/citologia , Cristalino/embriologia , Proteínas de Peixe-Zebra/metabolismo , Animais , Animais Geneticamente Modificados , Divisão Celular , Linhagem da Célula , Movimento Celular , Proteínas de Fluorescência Verde/metabolismo , Cristalino/citologia , Oligonucleotídeos Antissenso/metabolismo , Peixe-Zebra
9.
Acute Med Surg ; 3(4): 419-423, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-29123827

RESUMO

Case: A 19-year-old man had nausea, diarrhea, and general malaise the day before requesting emergency transport to his former primary physician. The patient became restless and had tonic seizures after admission. The patient was transferred to our hospital as there had been no improvement in his level of consciousness. On arrival, cranial computed tomography showed generalized swelling, and blood ammonia concentration was ≥500 µg/dL. After admission, seizures recurred continually despite careful monitoring and increased doses of sedatives and antiseizure drugs. Dilated pupils and a flat electroencephalogram were evident on day 4 of admission, and the patient died on day 11. Ornithine transcarbamylase deficiency was diagnosed at postmortem based on fractionation of blood and urine amino acids and orotic acid. Outcome: Urea cycle disorders need to be treated urgently to prevent irreversible neurological damage when accompanied by hyperammonemia. Conclusion: In cases of hyperammonemia, early dialysis should be considered to reduce the ammonia level.

10.
Resuscitation ; 96: 135-41, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26291387

RESUMO

AIM: This study investigated the value of regional cerebral oxygen saturation (rSO2) monitoring upon arrival at the hospital for predicting post-cardiac arrest intervention outcomes. METHODS: We enrolled 1195 patients with out-of-hospital cardiac arrest of presumed cardiac cause from the Japan-Prediction of Neurological Outcomes in Patients Post-cardiac Arrest Registry. The primary endpoint was a good neurologic outcome (cerebral performance categories 1 or 2 [CPC1/2]) 90 days post-event. RESULTS: A total of 68 patients (6%) had good neurologic outcomes. We found a mean rSO2 of 21%±13%. A receiver operating characteristic curve analysis indicated an optimal rSO2 cut-off of ≥40% for good neurologic outcomes (area under the curve 0.92, sensitivity 0.81, specificity 0.96). Good neurologic outcomes were observed in 53% (55/103) and 1% (13/1092) of patients with high (≥40%) and low (<40%) rSO2, respectively. Even without return of spontaneous circulation (ROSC) upon arrival at the hospital, 30% (9/30) of patients with high rSO2 had good neurologic outcomes. Furthermore, 16 patients demonstrating ROSC upon arrival at the hospital and low rSO2 had poor neurologic outcomes. Multivariate analyses indicated that high rSO2 was independently associated with good neurologic outcomes (odds ratio=14.07, P<0.001). Patients with high rSO2 showed favourable neurologic prognoses if they had undergone therapeutic hypothermia or coronary angiography (CPC1/2, 69% [54/78]). However, 24% (25/103) of those with high rSO2 did not undergo these procedures and exhibited unfavourable neurologic prognoses (CPC1/2, 4% [1/25]). CONCLUSION: rSO2 is a good indicator of 90-day neurologic outcomes for post-cardiac arrest intervention patients.


Assuntos
Encéfalo/metabolismo , Reanimação Cardiopulmonar/métodos , Circulação Cerebrovascular/fisiologia , Cardiopatias/complicações , Parada Cardíaca Extra-Hospitalar/terapia , Consumo de Oxigênio/fisiologia , Oxigênio/metabolismo , Idoso , Encéfalo/fisiopatologia , Feminino , Seguimentos , Cardiopatias/metabolismo , Humanos , Japão/epidemiologia , Masculino , Parada Cardíaca Extra-Hospitalar/complicações , Parada Cardíaca Extra-Hospitalar/mortalidade , Oximetria , Prognóstico , Estudos Prospectivos , Espectroscopia de Luz Próxima ao Infravermelho/métodos , Taxa de Sobrevida
12.
Am J Emerg Med ; 32(12): 1485-9, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25440233

RESUMO

BACKGROUND: The prevalence of anisakiasis is rare in the United States and Europe compared with that in Japan, with few reports of its presentation in the emergency department (ED). This study describes the clinical, hematologic, computed tomographic (CT) characteristics, and treatment in gastric and small intestinal anisakiasis patients in the ED. METHODS: We retrospectively reviewed the data of 83 consecutive anisakiasis presentations in our ED between 2003 and 2012. Gastric anisakiasis was endoscopically diagnosed with the Anisakis polypide. Small intestinal anisakiasis was diagnosed based on both hematologic (Anisakis antibody) and CT findings. RESULTS: Of the 83 cases, 39 had gastric anisakiasis and 44 had small intestinal anisakiasis based on our diagnostic criteria. Although all patients had abdominal pain, the gastric anisakiasis group developed symptoms significantly earlier (peaking within 6 hours) than the small intestinal anisakiasis group (peaking within 48 hours), and fewer patients with gastric anisakiasis needed admission therapy (5% vs 57%, P<.01). All patients in the gastric and 40 (91%) in the small intestinal anisakiasis group had a history of raw seafood ingestion. Computed tomographic findings revealed edematous wall thickening in all patients, and ascites and phlegmon of the mesenteric fat were more frequently observed in the small intestinal anisakiasis group. CONCLUSIONS: In the ED, early and accurate diagnosis of anisakiasis is important to treat and explain to the patient, and diagnosis can be facilitated by a history of raw seafood ingestion, evaluation of the time-to-symptom development, and classic CT findings.


Assuntos
Anisaquíase/diagnóstico , Adulto , Animais , Anisaquíase/diagnóstico por imagem , Anisaquíase/patologia , Anisaquíase/terapia , Anisakis , Serviço Hospitalar de Emergência/estatística & dados numéricos , Feminino , Gastroscopia , Humanos , Enteropatias Parasitárias/diagnóstico , Enteropatias Parasitárias/diagnóstico por imagem , Masculino , Estudos Retrospectivos , Alimentos Marinhos/efeitos adversos , Alimentos Marinhos/parasitologia , Gastropatias/diagnóstico , Gastropatias/diagnóstico por imagem , Gastropatias/parasitologia , Tóquio/epidemiologia , Tomografia Computadorizada por Raios X
13.
Biol Open ; 3(10): 982-94, 2014 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-25260917

RESUMO

Cell proliferation is a key regulator of tissue morphogenesis. We examined cell proliferation and cell division in zebrafish lens epithelium by visualizing cell-cycle phases and nuclear positions, using fluorescent-labeled geminin and histone proteins. Proliferation was low in the anterior region of lens epithelium and higher in the marginal zone anterior to the equator, suggesting that the proliferation zone, called the germinative zone, is formed in zebrafish lens. Interestingly, cell-division orientation was biased longitudinally in the anterior region, shifted from longitudinal to circumferential along the anterior-posterior axis of lens sphere, and was biased circumferentially in the peripheral region. These data suggest that cell-division orientation is spatially regulated in zebrafish lens epithelium. The Hertwig rule indicates that cells tend to divide along their long axes. Orientation of long axes and cell division were biased similarly in zebrafish lens epithelium, suggesting that cell geometry correlates with cell-division orientation. A cell adhesion molecule, E-cadherin, is expressed in lens epithelium. In a zebrafish e-cadherin mutant, the long axes and cell-division orientation were shifted more longitudinally. These data suggest that E-cadherin is required for the spatial pattern of cell geometry and cell-division orientation in zebrafish lens epithelium.

14.
Springerplus ; 3: 371, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25089254

RESUMO

BACKGROUND: Hypocapnia induced following the accidental intravenous infusion of a local anesthetic can mitigate anesthetic toxicity, but the effects of hypocapnia induced prior to local anesthetic infusion are unknown. In this study, we examined the effects of prior hypocapnia on bupivacaine-induced cardiotoxicity in rats. METHODS: Eighteen Sprague-Dawley rats were randomly divided into two groups: one receiving sevoflurane with normal ventilation (Control Group) and the other receiving sevoflurane with hyperventilation to induce hypocapnia (Hypocapnia Group). After 30 min, both groups received continuous intravenous infusions of 0.25% bupivacaine at 2 mg · kg(-1) · min(-1). The time taken to reach 25% and 50% reductions in heart rate (HR; HR-25%, HR-50%) and mean arterial pressure (MAP; MAP-25%, MAP-50%) from the start of bupivacaine infusion were recorded. The difference between HR-25% and MAP-25% was calculated. The times of the first ventricular premature beat (VPB) and final systole were also recorded. RESULTS: In the Hypocapnia Group, HR-50%, MAP-25%, and MAP-50% were prolonged compared with the Control Group (P < 0.001). Furthermore, the interval between HR-25% and MAP-25% and the times between the first VPB and final systole were prolonged in the Hypocapnia Group (P < 0.001). CONCLUSION: In rats under sevoflurane anesthesia, prior hypocapnia delayed the onset of bupivacaine-induced cardiotoxicity. Prior hypocapnia should be avoided during continuous bupivacaine nerve block under general anesthesia, because it may delay the detection of cardiotoxicity.

15.
Dev Growth Differ ; 56(5): 387-401, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24720470

RESUMO

The vertebrate lens is a transparent, spheroidal tissue, located in the anterior region of the eye that focuses visual images on the retina. During development, surface ectoderm associated with the neural retina invaginates to form the lens vesicle. Cells in the posterior half of the lens vesicle differentiate into primary lens fiber cells, which form the lens fiber core, while cells in the anterior half maintain a proliferative state as a monolayer lens epithelium. After formation of the primary fiber core, lens epithelial cells start to differentiate into lens fiber cells at the interface between the lens epithelium and the primary lens fiber core, which is called the equator. Differentiating lens fiber cells elongate and cover the old lens fiber core, resulting in growth of the lens during development. Thus, lens fiber differentiation is spatially regulated and the equator functions as a platform that regulates the switch from cell proliferation to cell differentiation. Since the 1970s, the mechanism underlying lens fiber cell differentiation has been intensively studied, and several regulatory factors that regulate lens fiber cell differentiation have been identified. In this review, we focus on the lens equator, where these regulatory factors crosstalk and cooperate to regulate lens fiber differentiation. Normally, lens epithelial cells must pass through the equator to start lens fiber differentiation. However, there are reports that when the lens epithelium structure is collapsed, lens fiber cell differentiation occurs without passing the equator. We also discuss a possible mechanism that represses lens fiber cell differentiation in lens epithelium.


Assuntos
Cristalino/citologia , Vertebrados/embriologia , Animais , Diferenciação Celular , Proliferação de Células , Epitélio/metabolismo , Humanos , Vertebrados/metabolismo
16.
Resuscitation ; 85(6): 778-84, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24606889

RESUMO

AIM: To investigate the association between regional brain oxygen saturation (rSO2) at hospital arrival and neurological outcomes at 90 days in patients with out-of-hospital cardiac arrest (OHCA). METHODS: The Japan-Prediction of neurological Outcomes in patients post cardiac arrest (J-POP) registry is a prospective, multicenter, cohort study to test whether rSO2 predicts neurological outcomes after OHCA. We measured rSO2 in OHCA patients immediately after hospital arrival using a near-infrared spectrometer placed on the forehead with non-blinded fashion. The primary endpoint was "neurological outcomes" at 90 days after OHCA. RESULTS: EMS providers are not permitted to terminate CPR in the field in Japan, and so most patients with OHCA who are treated by EMS personnel are transported to emergency hospitals. Among 1017 OHCA patients, 672 patients including 52 comatose patients with pulses detectable (8%) and 620 cardiac arrest patients (92%) at hospital arrival were enrolled prospectively and consecutively. Twenty-nine patients with good neurological outcome had a significantly higher value of rSO2 at hospital arrival than 643 patients with poor neurological outcome (mean [±SD] 55.6±20.8% vs. 19.7±11.0%, p<0.001). Receiver operating curve analysis indicated an optimal rSO2 cutoff point of >42% for predicting good neurological outcome, with sensitivity 0.79 (95% confidence interval [CI], 0.60-0.92), specificity 0.95 (95% CI, 0.93-0.96), positive predictive value, 0.41 (95% CI, 0.28-0.55), negative predictive value, 0.99 (95% CI, 0.98-1.00), and area under the curve 0.90 (95% CI, 0.88-0.92). CONCLUSION: The rSO2 at hospital arrival can predict good neurological outcome at 90 days after OHCA.


Assuntos
Encefalopatias/diagnóstico , Encefalopatias/metabolismo , Encéfalo/metabolismo , Parada Cardíaca Extra-Hospitalar/metabolismo , Oxigênio/metabolismo , Espectroscopia de Luz Próxima ao Infravermelho , Idoso , Encefalopatias/etiologia , Técnicas de Diagnóstico Neurológico , Feminino , Humanos , Masculino , Parada Cardíaca Extra-Hospitalar/complicações , Valor Preditivo dos Testes , Prognóstico , Estudos Prospectivos
17.
Microarrays (Basel) ; 3(4): 226-44, 2014 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-27600346

RESUMO

Pufferfish accumulate tetrodotoxin (TTX) mainly in the liver and ovary. This study aims at investigating the effect of TTX accumulation in the liver of cultured specimens of torafugu Takifugu rubripes on the hepatic gene expression by microarray analysis on Day 5 after the intramuscular administration of 0.25 mg TTX/kg body weight into the caudal muscle. TTX was detected in the liver, skin and ovary in the TTX-administered individuals. The total amount of TTX accumulated in the body was 67 ± 8% of the administered dose on Day 5. Compared with the buffer-administered control group, a total of 59 genes were significantly upregulated more than two-fold in the TTX-administered group, including those encoding chymotrypsin-like elastase family member 2A, transmembrane protein 168 and Rho GTP-activating protein 29. In contrast, a total of 427 genes were downregulated by TTX administration, including those encoding elongation factor G2, R-spondin-3, nuclear receptor activator 2 and fatty acyl-CoA hydrolase precursor. In conclusion, our results demonstrate that the intramuscular administration of TTX changes the expression of hepatic genes involved in various signaling pathways.

18.
Dev Cell ; 25(4): 374-87, 2013 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-23725763

RESUMO

Intracellular vesicular transport is important for photoreceptor function and maintenance. However, the mechanism underlying photoreceptor degeneration in response to vesicular transport defects is unknown. Here, we report that photoreceptors undergo apoptosis in a zebrafish ß-soluble N-ethylmaleimide-sensitive factor attachment protein (ß-SNAP) mutant. ß-SNAP cooperates with N-ethylmaleimide-sensitive factor to recycle the SNAP receptor (SNARE), a key component of the membrane fusion machinery, by disassembling the cis-SNARE complex generated in the vesicular fusion process. We found that photoreceptor apoptosis in the ß-SNAP mutant was dependent on the BH3-only protein BNip1. BNip1 functions as a component of the syntaxin-18 SNARE complex and regulates retrograde transport from the Golgi to the endoplasmic reticulum. Failure to disassemble the syntaxin-18 cis-SNARE complex caused BNip1-dependent apoptosis. These data suggest that the syntaxin-18 cis-SNARE complex functions as an alarm factor that monitors vesicular fusion competence and that BNip1 transforms vesicular fusion defects into photoreceptor apoptosis.


Assuntos
Apoptose , Fusão de Membrana , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Células Fotorreceptoras Retinianas Cones/patologia , Proteínas de Ligação a Fator Solúvel Sensível a N-Etilmaleimida/metabolismo , Animais , Retículo Endoplasmático/metabolismo , Complexo de Golgi/metabolismo , Complexos Multiproteicos/genética , Complexos Multiproteicos/metabolismo , Mutação , Mapeamento de Interação de Proteínas , Estrutura Terciária de Proteína , Transporte Proteico , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Qa-SNARE/genética , Proteínas Qa-SNARE/metabolismo , Células Fotorreceptoras Retinianas Cones/metabolismo , Neurônios Retinianos/metabolismo , Neurônios Retinianos/patologia , Proteínas de Ligação a Fator Solúvel Sensível a N-Etilmaleimida/genética , Peixe-Zebra/genética , Peixe-Zebra/metabolismo
19.
Shock ; 39(6): 527-32, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23680771

RESUMO

In this study, we aimed to compare the effects of low- and high-quality cardiopulmonary resuscitation (CPR) on cardioprotection by induced hypothermia (IH) at 34 °C and examine whether extracellular signal-regulated kinase or endothelial nitric oxide synthase mediates this cardioprotection. Left ventricle infarct sizes were evaluated in six groups of rat hearts (n = 6) following Langendorff perfusion and triphenyltetrazolium chloride staining. Controls underwent 30 min of global ischemia at 37 °C, followed by 10 min of simulated low- or high-quality CPR reperfusion and 90 min of reperfusion at 75 mmHg. The IH groups underwent IH at 34 °C during reperfusion. The U0126 group received U0126 (60 µM)-an extracellular signal-regulated kinase inhibitor-during reperfusion at 34 °C. The L-NIO (N-(1-iminoethyl)-L-ornithine dihydrochloride) group received L-NIO (2 µM)-an endothelial nitric oxide synthase inhibitor-5 min before global ischemia at 37 °C to the end of reperfusion at 34 °C. Infarct size did not significantly differ between the control and IH groups receiving low-quality CPR. However, IH with high-quality CPR reduced the infarct size from 47.2% ± 10.2% to 26.0% ± 9.4% (P = 0.005). U0126 reversed the IH-induced cardioprotection (45.9% ± 9.4%, P = 0.010), whereas L-NIO had no significant effect. Cardiopulmonary resuscitation quality affects IH-induced cardioprotection. Extracellular signal-regulated kinase may mediate IH-induced cardioprotection.


Assuntos
Reanimação Cardiopulmonar/métodos , Hipotermia Induzida/métodos , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Animais , Butadienos/farmacologia , Modelos Animais de Doenças , Inibidores Enzimáticos/farmacologia , MAP Quinases Reguladas por Sinal Extracelular/antagonistas & inibidores , MAP Quinases Reguladas por Sinal Extracelular/fisiologia , Hemodinâmica/efeitos dos fármacos , Hemodinâmica/fisiologia , Técnicas In Vitro , Masculino , Infarto do Miocárdio/patologia , Infarto do Miocárdio/fisiopatologia , Infarto do Miocárdio/prevenção & controle , Traumatismo por Reperfusão Miocárdica/patologia , Traumatismo por Reperfusão Miocárdica/fisiopatologia , Óxido Nítrico Sintase Tipo III/antagonistas & inibidores , Óxido Nítrico Sintase Tipo III/fisiologia , Nitrilas/farmacologia , Ornitina/análogos & derivados , Ornitina/farmacologia , Ratos , Ratos Sprague-Dawley
20.
Am J Emerg Med ; 31(7): 1118-20, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23688571

RESUMO

OBJECTIVE: We aimed to generate equation to predict arterial lactate (a-Lac) using venous lactate (v-Lac) and other lab data. METHODS: A prospective cross-sectional study was conducted on emergency patients in the emergency department for 6 months at a general hospital in Tokyo, Japan. We collected arterial and venous gas analysis data. Patients were eligible for entry into the study if an arterial blood gas analysis was required for appropriate diagnostic care by the treating physician. Univariate linear regression analysis was conducted to generate an equation to calculate a-Lac incorporating only v-Lac. A multivariate forward stepwise logistic regression model (p-value of 0.05 for entry, 0.1 for removal) was used to generate an equation including v-Lac and other potentially relevant variables. Bland-Altman plot was drawn and the two equations were compared for model fitting using R-squares. RESULTS: Seventy-two arterial samples from 72 participants (61% male; mean age, 58.2 years) were included in the study. An initial regression equation was derived from univariate linear regression analysis:"(a-Lac) = -0.259 + (v-Lac) × 0.996". Subsequent multivariate forward stepwise logistic regression analysis, incorporating v-Lac and Po2, generated the following equation:"(a-Lac) = -0.469+(venous Po2) × 0.005 + (v-Lac) × 0.997". Calculated R-squares by single and multiple regression were 0.94 and 0.96, respectively. CONCLUSION: v-Lac estimates showed a high correlation with arterial values and our data provide two clinically useful equations to calculate a-Lac from v-Lac data. Considering clinical flexibility, "Lac = -0.259 + v-Lac × 0.996" might be more useful while avoiding a time-consuming and invasive procedure.


Assuntos
Gasometria/métodos , Técnicas de Apoio para a Decisão , Serviço Hospitalar de Emergência , Ácido Láctico/sangue , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Artérias , Biomarcadores/sangue , Estudos Transversais , Feminino , Humanos , Modelos Lineares , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Estudos Prospectivos , Veias , Adulto Jovem
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...