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2.
J Neonatal Perinatal Med ; 13(1): 55-61, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31609703

RESUMO

BACKGROUND: Developmental changes in the hypothalamus-pituitary-adrenal (HPA) axis during infancy have been reported in term infants, but those in preterm infants have yet to be elucidated. If developmental changes in the HPA axis of preterm infants are modulated by any factors, it may affect their future health. Few studies have examined the lasting consequences of antenatal glucocorticoids on the development of the HPA axis. METHODS: We measured pre- and post-palivizumab vaccination salivary cortisol values in two conforming periods of three-months intervals during infancy, and compared cortisol values and the response of cortisol secretion between groups with and without antenatal glucocorticoid (AG) therapy. RESULTS: Although the strength of the response of cortisol secretion to palivizumab fell age-dependently (until late infancy) in the Non-AG group, the opposite pattern was exhibited in the AG group. The changes of the delta cortisol values between the 2 groups were significant. CONCLUSIONS: This study suggests that the HPA axis of preterm infants whose mothers receive AG therapy may be upregulated during infancy, possibly leading to long lasting health problems.


Assuntos
Glucocorticoides/uso terapêutico , Hidrocortisona/metabolismo , Sistema Hipotálamo-Hipofisário/metabolismo , Injeções Intramusculares , Sistema Hipófise-Suprarrenal/metabolismo , Estresse Fisiológico/fisiologia , Antivirais/administração & dosagem , Estudos de Casos e Controles , Feminino , Humanos , Sistema Hipotálamo-Hipofisário/crescimento & desenvolvimento , Lactente , Recém-Nascido Prematuro , Masculino , Palivizumab/administração & dosagem , Sistema Hipófise-Suprarrenal/crescimento & desenvolvimento , Cuidado Pré-Natal , Infecções por Vírus Respiratório Sincicial/prevenção & controle , Saliva/química
3.
AJNR Am J Neuroradiol ; 40(6): 1037-1042, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31122915

RESUMO

BACKGROUND AND PURPOSE: Reliable preoperative facial nerve mapping may help avoid or minimize facial nerve injury during parotid tumor resection. The purpose of this study was to investigate the diagnostic performance of the 3D double-echo steady-state with water excitation sequence in localizing parotid gland tumors through direct visualization of the intraparotid facial nerve in comparison with indirect methods of estimating the facial nerve location. MATERIALS AND METHODS: We retrospectively reviewed 91 parotid gland tumors in 90 patients who underwent surgical resection and preoperative MR imaging, including the 3D double-echo steady-state with water excitation sequence. The tumor locations were categorized as deep or superficial on the basis of direct and 3 indirect methods: the facial nerve line, retromandibular vein, and Utrecht line. Surgical localization was considered the criterion standard. The diagnostic performance for localizing deep lobe lesions using direct and indirect methods was calculated and compared using the McNemar test. RESULTS: Surgical localization confirmed 75 superficial lesions and 16 deep lesions. The interobserver variability of the 3D double-echo steady-state with water excitation sequence was excellent (κ = 0.870). The diagnostic accuracy, sensitivity, specificity, positive predictive value, and negative predictive value for localizing deep lobe lesions using the 3D double-echo steady-state with water excitation method were 97.8%, 87.5%, 100%, 100%, and 97.4%, respectively. These findings were significantly higher than the facial nerve line in sensitivity, the retromandibular vein in sensitivity, and the Utrecht line in accuracy and specificity (P < .05). Overall, the direct method was the most accurate, sensitive, and specific in localizing parotid gland tumors. CONCLUSIONS: We can achieve higher diagnostic performance in localizing parotid gland tumors by directly visualizing the intraparotid facial nerve using the 3D double-echo steady-state with water excitation sequence compared with indirect methods.


Assuntos
Nervo Facial/diagnóstico por imagem , Imageamento Tridimensional/métodos , Imageamento por Ressonância Magnética/métodos , Neuroimagem/métodos , Neoplasias Parotídeas/diagnóstico por imagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Glândula Parótida/diagnóstico por imagem , Estudos Retrospectivos , Sensibilidade e Especificidade , Água
4.
Transplant Proc ; 50(10): 3496-3500, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30577227

RESUMO

BACKGROUND: Despite reported associations between intrapulmonary vascular shunting (IPVS) and morbidity and mortality in pediatric liver transplantation (LT), there are no guidelines for screening. OBJECTIVE: To investigate IPVS before and after pediatric LT. METHODS: Retrospective records review of all pediatric LT (n = 370) from 2005 to 2015 at a single institute in Japan. All children with cirrhosis and clinical suspicion of IPVS without cardiac or pulmonary conditions were included. 99mTechnetium labelled macroaggregated albumin (99mTcMAA) scans were performed before and after LT. The severity of IPVS was graded using shunt ratios. RESULTS: Twenty-four children fulfilled inclusion criteria and underwent Tc99MAA scans. All revealed mild (<20%) to moderate (20%-40%) grades of IPVS. Following LT, the mean shunt ratio regressed from 20.69 ± 6.26% to 15.1 ± 3.4% (P = .06). The median (range) follow-up was 17 (4-85) months. Mortality was zero. The incidence of portal vein thrombosis (4.2%) biliary strictures (12.5%) and graft loss (4.1%) in the study group was not statistically significant compared to the remainder of the 370 transplants (3.2%, 9.4% and 3%, respectively). Sub-group analysis revealed hepatopulmonary syndrome (HPS) in 2 out of 24 children. The mean shunt ratios before and after LT were 39.2 ± 0.77% and 16.2 ± 8.5%, respectively (P = .08). There was 1 complication (intra-abdominal abscess). CONCLUSIONS: HPS is less likely in mild to moderate IPVS. LT may achieve comparable results when performed in the presence of mild to moderate IPVS.


Assuntos
Transplante de Fígado , Pulmão/irrigação sanguínea , Pulmão/diagnóstico por imagem , Criança , Pré-Escolar , Feminino , Síndrome Hepatopulmonar/etiologia , Humanos , Lactente , Japão , Transplante de Fígado/efeitos adversos , Pulmão/patologia , Masculino , Imagem de Perfusão/métodos , Estudos Retrospectivos , Resultado do Tratamento
5.
Climacteric ; 21(6): 601-606, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30296854

RESUMO

OBJECTIVE: Royal jelly (RJ) has been used for medical and nutritional purposes, and previous studies have indicated that it may have estrogenic activity. The present study investigated the effects of RJ on bone metabolism in ovariectomized (OVX) rats. METHODS: Rats (12 weeks old) were randomly divided into four groups, namely Baseline, Sham, OVX, and OVX + RJ groups. Rats in the Baseline group were killed immediately, whereas rats in the OVX and OVX + RJ groups underwent bilateral ovariectomy and those in the Sham group underwent sham operation. RJ was administered to rats in the OVX + RJ group daily for 12 weeks. At the end of the 12-week period, bone mass, bone histomorphometry, and bone mechanics were analyzed. RESULTS: Femur bone mineral density (BMD) was significantly lower in the OVX group than in the Sham group, and this decrease in BMD was not ameliorated by RJ administration. However, femur stiffness, as evaluated by a three-point bending test, was significantly higher in the OVX + RJ group than in the OVX group. CONCLUSION: The findings of the present study suggest that RJ does not prevent bone loss, but does improve bone strength in OVX rats.


Assuntos
Peso Corporal , Densidade Óssea/efeitos dos fármacos , Doenças Ósseas Metabólicas/tratamento farmacológico , Ácidos Graxos/farmacologia , Animais , Fenômenos Biomecânicos , Doenças Ósseas Metabólicas/fisiopatologia , Densitometria , Feminino , Fêmur/fisiopatologia , Tamanho do Órgão , Ovariectomia , Distribuição Aleatória , Ratos , Útero/anatomia & histologia
6.
Res Vet Sci ; 115: 34-42, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28152385

RESUMO

The objective of this study was to characterize the propofol-fentanyl interaction in Beagles for four pharmacodynamic endpoints: apnea, response to mechanical ventilation, endotracheal tube, and tetanic stimulation. After anesthesia was induced with varying combinations of propofol and fentanyl, the pharmacodynamic endpoints were assessed in intubated dogs (n=6) using the cross-over design. Effective concentrations of propofol plasma concentration (Cp) and fentanyl Cp were assessed using additive, reduced Greco, Minto, and hierarchical interaction models. The interaction was best described as synergistic by the hierarchical model. A 1ng/mL fentanyl Cp reduced the effective propofol Cp to half or less of that without fentanyl for all endpoints. An additional increment of fentanyl Cp to 5ng/mL or higher hardly reduced effective propofol Cp for all endpoints except response to tetanic stimulation. Additionally, the effective propofol Cp in 50% dogs for response to tetanic stimulation (15% increase of heart rate) was lower than that for the other endpoints at fentanyl Cp >7ng/mL. Peripheral oxygen saturation decreased below 90% after extubation in five treatments in which fentanyl Cps were ≥5ng/mL. Propofol and fentanyl interacted synergistically. To avoid patient-ventilator dyssynchrony and hypoxemia after extubation, fentanyl Cp at 1-5ng/mL may be appropriate in intubated dogs. When a dog responds to mechanical ventilation or endotracheal tube at a high fentanyl Cp >5ng/mL under propofol anesthesia even if the dog tolerate to tetanic stimulation, it may be necessary to increase propofol Cp to eliminate the responses because an additional fentanyl may be little impact.


Assuntos
Analgésicos Opioides/farmacologia , Apneia/induzido quimicamente , Fentanila/farmacologia , Hipnóticos e Sedativos/farmacologia , Intubação Intratraqueal/veterinária , Propofol/farmacologia , Respiração Artificial/veterinária , Anestésicos Intravenosos/farmacologia , Animais , Cães , Feminino , Masculino , Modelos Biológicos
7.
Climacteric ; 19(6): 568-573, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27736245

RESUMO

OBJECTIVE: Royal jelly (RJ) from honeybees (Apis mellifera) has estrogenic activity. Estrogen deficiency after menopause leads to a high risk of memory impairment and depression as well as metabolic syndrome and osteoporosis. We here investigated the effect of RJ on memory impairment and depression-like behaviors in ovariectomized (OVX) rats. METHODS: OVX rats were administered with RJ for 82 days. Hippocampus-dependent spatial memory and depression-like behaviors were assessed by the Morris water maze test and the forced swimming test, respectively. The weights of body, brain and uterus and the contents of protein and myelin galactolipids including galactosylceramide and sulfatide were measured. RESULTS: Memory impairment and depression-like behaviors in OVX rats were recovered to the levels of sham-operated rats by RJ administration. Increased body weight and decreased uterine weight in OVX rats were recovered to the levels of sham-operated rats by 17ß-estradiol (E2) administration but not by RJ administration. In contrast, brain weight was slightly increased by RJ administration but not by E2 administration. The contents of protein and myelin galactolipids were higher in the brains of RJ-administered OVX rats than in the brains of E2-administered OVX rats. CONCLUSION: The results suggest that RJ has a beneficial effect on neurological symptoms of a menopausal disorder.


Assuntos
Depressão/tratamento farmacológico , Ácidos Graxos/uso terapêutico , Transtornos da Memória/tratamento farmacológico , Pós-Menopausa/fisiologia , Animais , Comportamento Animal/efeitos dos fármacos , Química Encefálica/efeitos dos fármacos , Estradiol/farmacologia , Ácidos Graxos/administração & dosagem , Feminino , Galactolipídeos/análise , Aprendizagem em Labirinto/efeitos dos fármacos , Bainha de Mielina/química , Proteínas do Tecido Nervoso/análise , Tamanho do Órgão/efeitos dos fármacos , Ovariectomia , Ratos , Ratos Wistar , Natação , Útero/efeitos dos fármacos
8.
Pediatr Transplant ; 20(7): 981-986, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27534385

RESUMO

LT for PFIC type 1 is often complicated by postoperative diarrhea and recurrent graft steatosis. A 26-month-old female child with cholestatic jaundice, pruritus, diarrhea, and growth retardation revealed total bilirubin 9.1 mg/dL, gamma-glutamyl transpeptidase 64 IU/L, and TBA 295.8 µmol/L. Genetic analysis confirmed ATP8B1 defects. A LT (segment 2, 3 graft) from the heterozygous father was performed. Biliary diversion was performed by a 35-cm jejunum conduit between the graft hepatic duct and the mid-transverse colon. Stools became pigmented immediately. Follow-up at 138 days revealed resolution of jaundice and pruritus and soft-to-hard stools (6-8 daily). Radioisotope hepato-biliary scintigraphy (days 26, 68, and 139) confirmed unobstructed bile drainage into the colon (t1/2 34, 27, and 19 minutes, respectively). Contrast meal follow-through at day 62 confirmed the absence of any colo-jejuno-hepatic reflux. At 140 days, contrast follow-through via the biliary stent revealed patent jejuno-colonic anastomosis and satisfactory transit. Graft biopsy at LT, 138 days, and 9 months follow-up revealed comparable grades of macrovesicular steatosis (<20%). TIBD during LT may be a clinically effective stoma-free biliary diversion and may prevent recurrent graft steatosis following LT for PFIC type 1.


Assuntos
Colestase Intra-Hepática/cirurgia , Transplante de Fígado , Adenosina Trifosfatases/genética , Bile , Ductos Biliares/fisiopatologia , Ductos Biliares/cirurgia , Pré-Escolar , Diarreia/etiologia , Fígado Gorduroso/etiologia , Feminino , Heterozigoto , Humanos , Icterícia/etiologia , Jejuno/cirurgia , Complicações Pós-Operatórias , Prurido/etiologia , Resultado do Tratamento
9.
AJNR Am J Neuroradiol ; 36(7): 1333-7, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25836724

RESUMO

BACKGROUND AND PURPOSE: Although visualization of the extracranial branches of the cranial nerves has improved with advances in MR imaging, only limited studies have assessed the detection of extracranial branches of the mandibular nerve (V3). We investigated the detectability of the branches of V3 on a 3D double-echo steady-state with water excitation sequence. MATERIALS AND METHODS: We retrospectively evaluated the detectability of the 6 branches of the V3, the masseteric, buccal, auriculotemporal, lingual, inferior alveolar, and mylohyoid nerves, by using a 5-point scale (4, excellent; 3, good; 2, fair; 1, poor; and 0, none) in 86 consecutive patients who underwent MR imaging with the 3D double-echo steady-state with water excitation sequence. Weighted κ analysis was used to calculate interobserver variability among the 3 readers. RESULTS: The detection of the lingual and inferior alveolar nerves was the most successful, with excellent average scores of 3.80 and 3.99, respectively. The detection of the masseteric, the buccal, and the auriculotemporal nerves was good, with average scores of 3.31, 2.67, and 3.11, respectively. The mylohyoid nerve was difficult to detect with poor average scores of 0.62. All nerves had excellent interobserver variability across the 3 readers (average weighted κ value, 0.95-1.00). CONCLUSIONS: The 3D double-echo steady-state with water excitation sequence demonstrated excellent visualization of the extracranial branches of V3 in most patients. The 3D double-echo steady-state with water excitation sequence has the potential for diagnosing V3 pathologies and preoperatively identifying peripheral cranial nerves to prevent surgical complications.


Assuntos
Imageamento Tridimensional/métodos , Imageamento por Ressonância Magnética/métodos , Nervo Trigêmeo/anatomia & histologia , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
10.
Transplant Proc ; 46(4): 1095-8, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24815137

RESUMO

BACKGROUND: Use of grafts from donors after cardiac death (DCD) would greatly contribute to the expansion of the donor organ pool. However, this requires the development of novel preservation methods to recover the organ from changes due to warm ischemia time (WIT). METHODS: Porcine livers were perfused with a newly developed machine perfusion (MP) system. The livers were perfused with modified University of Wisconsin solution (UW) - gluconate. All grafts were procured after acute hemorrhagic shock with the ventilator off. For group 1 (n = 6), grafts were procured after WIT of 60 minutes and preserved by hypothermic MP (HMP) for 3 hours. For group 2 (n = 5), grafts were preserved with 2 hours of simple cold storage (SCS) and HMP for 2 hours. For group 3 (n = 6), grafts were preserved with 2 hours of SCS and rewarming up to 25°C by MP for 2 hours (RMP). The preserved liver grafts were transplanted orthotopically. RESULTS: The alanine aminotransferase level in perfusate in RMP during perfusion preservation was maintained at less than that of HMP. The levels of aspartate aminotransferase and lactate dehydrogenase in the 2 hours after reperfusion were significantly lower in group 3. Histologically, the necrosis of hepatocytes was less severe in group 3. The survival rate in group 3 was 2/4, but 0/4 in the other group. CONCLUSION: RMP is expected to facilitate the recovery of the DCD liver grafts.


Assuntos
Parada Cardíaca , Transplante de Fígado/métodos , Fígado/cirurgia , Preservação de Órgãos/métodos , Perfusão/métodos , Traumatismo por Reperfusão/prevenção & controle , Reaquecimento/métodos , Coleta de Tecidos e Órgãos/métodos , Adenosina/farmacologia , Alanina Transaminase/metabolismo , Alopurinol/farmacologia , Animais , Aspartato Aminotransferases/metabolismo , Biomarcadores/metabolismo , Isquemia Fria , Modelos Animais de Doenças , Feminino , Glutationa/farmacologia , Sobrevivência de Enxerto , Hepatectomia , Insulina/farmacologia , L-Lactato Desidrogenase/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Transplante de Fígado/efeitos adversos , Necrose , Preservação de Órgãos/efeitos adversos , Soluções para Preservação de Órgãos/farmacologia , Perfusão/efeitos adversos , Rafinose/farmacologia , Traumatismo por Reperfusão/etiologia , Traumatismo por Reperfusão/patologia , Reaquecimento/efeitos adversos , Sus scrofa , Fatores de Tempo , Coleta de Tecidos e Órgãos/efeitos adversos , Isquemia Quente
11.
Transplant Proc ; 46(5): 1371-6, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24836837

RESUMO

There are few reports about the quality of life (QOL) and morbidities of pediatric living donor liver transplantation (LDLT) donors. We evaluated the potential morbidities and identified the predictive factors regarding the QOL of living donors after pediatric LDLT. This cross-sectional study was a single-center analysis of 100 donors for pediatric LDLT. The severity of morbidities was assessed with the Clavien classification, the QOL was investigated with the short form-36 (SF-36), and the decision-making process regarding donation was analyzed with questionnaires. The median follow-up period was 3.8 years (range, 2.2-6.0 years). A total of 13% of the donors developed postoperative complications of Clavien grades I (7%), II (3%), and IIIA (3%). There was no grade IV morbidity or mortality. Eighty-one donors responded to the questionnaire and SF-36. The analysis of the questionnaires revealed that the donors had difficulty in the decision-making process, and suggested that it may be necessary to administer multistep informed consent. We identified unique predictive risk factors for lower SF-36 scores in the donors, which were the time to donation (more than 4 weeks) and the predonation self-oriented perception. The donors who have risk factors require enhanced pre- and post-donation psychological care.


Assuntos
Transplante de Fígado , Doadores Vivos , Qualidade de Vida , Adulto , Criança , Estudos Transversais , Humanos , Resultado do Tratamento
12.
Acta Paediatr ; 103(6): e262-7, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24528278

RESUMO

AIM: Physical growth in neurologically healthy preterm infants affects motor development. This study investigated the separate relationships between muscle and fat in infancy and later motor development and physical growth. METHODS: Muscle thickness and subcutaneous fat thickness of the anterior thigh were measured using ultrasound images obtained from neurologically healthy preterm infants at birth, 3, 6, 12 and 18 months' corrected age. We also obtained the Pediatric Evaluation of Disability Inventory and Alberta Infant Motor Scale scores at 18 months' corrected age to assess motor ability and motor delay. RESULTS: Thirty preterm infants completed the study protocol. There was a significant positive correlation between motor ability and increments in subcutaneous fat thickness during the first 3 and 6 months' corrected age (r = 0.48 and 0.40, p < 0.05, respectively), but not between motor ability and muscle thickness growth in any of the periods. A secondary, logistic regression analysis showed that increments in subcutaneous fat thickness during the first 3 months were a protective factor for motor delay. CONCLUSION: Subcutaneous fat accumulation in early infancy is more strongly associated with motor development and delay than muscle growth.


Assuntos
Desenvolvimento Infantil , Transtornos das Habilidades Motoras , Destreza Motora/fisiologia , Músculo Esquelético/crescimento & desenvolvimento , Gordura Subcutânea/crescimento & desenvolvimento , Análise de Variância , Previsões , Humanos , Lactente , Recém-Nascido , Recém-Nascido Prematuro , Japão , Modelos Logísticos , Músculo Esquelético/diagnóstico por imagem , Músculo Esquelético/fisiologia , Estatísticas não Paramétricas , Gordura Subcutânea/diagnóstico por imagem , Gordura Subcutânea/fisiologia , Ultrassonografia , Aumento de Peso
13.
Climacteric ; 17(4): 492-9, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24502200

RESUMO

OBJECTIVE: Postmenopausal bone loss and the possible progression to osteoporosis are a major health concern. Mushrooms have been recognized as functional foods. Pleurotus eryngii extract has been reported to have estrogenic activity, suggesting that its consumption may mitigate postmenopausal bone loss. The aim of the present study was to determine the effect of supplementation with an ethanol extract of P. eryngii on bone metabolism in a postmenopausal osteoporosis rat model. METHODS: Female 12-week-old Wistar rats were subjected to either sham operation or bilateral ovariectomy. The ovariectomized rats were then subdivided into two groups: one fed the extract and the other not. Twelve weeks after surgery, indices of bone mass, bone histomorphometry, and bone mechanics were measured. RESULTS: The right femur bone mineral content and density of the ovariectomized group were significantly lower than in the Sham group, and extract supplementation did not have any significant effect on these differences. Furthermore, ovariectomy significantly increased measures of mineralizing surface and bone formation rates; again, extract supplementation again had no significant effect. CONCLUSION: Our findings suggest that the ethanol extract of P. eryngii does not alter bone metabolism in ovariectomized rats, suggesting that consumption of P. eryngii may not be beneficial in slowing bone loss after menopause.


Assuntos
Densidade Óssea/efeitos dos fármacos , Remodelação Óssea/efeitos dos fármacos , Misturas Complexas/administração & dosagem , Fêmur , Osteoporose Pós-Menopausa , Ovariectomia/efeitos adversos , Pleurotus , Administração Oral , Animais , Modelos Animais de Doenças , Feminino , Fêmur/efeitos dos fármacos , Fêmur/metabolismo , Humanos , Osteoporose Pós-Menopausa/diagnóstico , Osteoporose Pós-Menopausa/tratamento farmacológico , Osteoporose Pós-Menopausa/etiologia , Ratos , Ratos Wistar , Resultado do Tratamento
14.
Transplant Proc ; 45(5): 1684-9, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23769024

RESUMO

BACKGROUND: Utilization of grafts from donors after cardiac death (DCD) greatly expands the organ pool. However, implementation of such a strategy requires the development of novel preservation methods to achieve recovery from changes owing to warm ischemia. METHODS: To assess potential methods, porcine livers harvested after 60 minutes of warm ischemic time (WIT) were perfused and preserved under the following conditions: Group 1 (n = 3), 2-hour simple cold storage and 2-hour machine perfusion (MP) at 8°C; group 2 (n = 3), 2 hours at 25°C and MP at 25°C and group 3 (n = 3), 2-hour simple cold storage and gradual rewarming to 25°C by MP. The preserved liver grafts were transplanted orthotopically into recipients. RESULTS: The aspartate aminotransferase (AST), lactate dehydrogenase (LDH), and hyaluronic acid (HA) levels in recipient blood at 2 hours after reperfusion were significantly lower among group 3: AST, 789 ± 258.8, 1203 ± 217.0, and 421 ± 55.8 IU/L; LDH, 1417 ± 671.2, 2132 ± 483.9, and 634 ± 263.9 IU/L; and HA, 1660 ± 556.5, 1463 ± 332.3, and 575 ± 239.0 ng/mL for groups 1, 2 and 3, respectively. Histologically, necrosis and swelling of hepatocytes were less severe among group 3 than groups 1 and 2. Group 3 animals showed better vital responses and started spontaneous breathing within 2 hours after reperfusion; 1 recipient survived for >24 hours, although all animals in groups 1 and 2 died within 2 to 3 hours after reperfusion. CONCLUSION: Rewarming by MP preservation may facilitate recovery and resuscitation of DCD liver grafts.


Assuntos
Transplante de Fígado , Perfusão , Cuidados Pós-Operatórios , Animais , Aspartato Aminotransferases/sangue , Feminino , Ácido Hialurônico/sangue , L-Lactato Desidrogenase/sangue , Suínos , Temperatura
15.
Curr Med Chem ; 20(9): 1091-102, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23317163

RESUMO

Recently, genomics and proteomics have been utilized as advanced tools for investigation of cellular signaling pathways and molecular interactions, and elucidated promiscuous networks composed of numerous interactions among pathways. However, some of these interactions are considered to be simply contributing to background 'noise' and others are as 'crosstalk' biologically-relevant to cellular physiology, leading to synergy effects more than additive responses in an entire organism. Effort is now required to determine which interactions truly contribute to final physiological output. A receptor is the prime example of connectors among the networks. It functions, not simply as a signaling gateway, but also as an active trader by forming inter-receptor dimers. Furthermore, various receptors can modulate the function of the other receptors by input to common intracellular signaling pathways, establishing functional crosstalk among networks. Our findings by combined analyses of gene polymorphisms of two separate genes present evidences that such is the case with human body in a clinical setting: 1) an integrated effect of epidermal growth factor receptor (EGFR) and protease activated receptor-1 (PAR-1) on susceptibility to airway hyperresponsiveness (AHR), and 2) a crosstalk effect between muscarinic acetylcholine receptor (mAChRs) and ß(2) adrenoceptor (ß(2)AR) on bronchodilatory response to anticholinergic agents in patients with COPD. These results indicate that these interactions are unlikely to be 'noise' but functionally-relevant 'crosstalk' in a human body. This review attempts to highlight the clinically-relevant 'crosstalk' paradigm in a human body which provides us a novel insight necessary to investigate pathophysiology in common multifactorial diseases and to develop new drugs.


Assuntos
Asma/metabolismo , Descoberta de Drogas/métodos , Receptores ErbB/metabolismo , Doença Pulmonar Obstrutiva Crônica/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Transdução de Sinais/efeitos dos fármacos , Animais , Asma/tratamento farmacológico , Asma/patologia , Brônquios/efeitos dos fármacos , Brônquios/metabolismo , Brônquios/patologia , Biologia Computacional/métodos , Humanos , Modelos Moleculares , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Doença Pulmonar Obstrutiva Crônica/patologia , Receptor PAR-1/metabolismo , Receptores Adrenérgicos beta/metabolismo , Receptores Muscarínicos/metabolismo
16.
J Vet Pharmacol Ther ; 36(2): 169-73, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22568878

RESUMO

Propofol is a short-acting intravenous anesthetic used for induction/maintenance anesthesia. The objective of this study was to assess a population pharmacokinetic (PPK) model for Japanese macaques during a step-down infusion of propofol. Five male Japanese macaques were immobilized with ketamine (10 mg/kg) and atropine (0.02 mg/kg). A bolus dose of propofol (5 mg/kg) was administrated intravenously (360 mg/kg/h) followed by step-down infusion at 40 mg/kg/h for 10 min, 20 mg/kg/h for 10 min, and then 15 mg/kg/h for 100 min. Venous blood samples were repeatedly collected following the administration. The plasma concentration of propofol (Cp) was measured by high-speed LC-FL. PPK analyses were performed using NONMEM VII. Median absolute prediction error and median prediction error (MDPE), the indices of prediction inaccuracy and bias, respectively, were calculated, and PE - individual MDPE vs. time was depicted to show the variability of prediction errors. In addition, we developed another population pharmacokinetic model using previous and current datasets. The previous PK model achieved stable prediction of propofol Cp throughout the study period, although it underestimates Cp. The step-down infusion regimen described in this study would be feasible in macaques during noninvasive procedures.


Assuntos
Anestésicos Intravenosos/farmacocinética , Macaca/sangue , Propofol/farmacocinética , Anestésicos Intravenosos/sangue , Animais , Injeções Intravenosas , Masculino , Modelos Biológicos , Propofol/sangue
17.
J Viral Hepat ; 19(9): 615-22, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22863265

RESUMO

Pegylated interferon (PEG-IFN)/ribavirin combination therapy is the standard-of-care (SOC) treatment for chronic hepatitis C patients infected with hepatitis C virus (HCV) genotype 1b and high viral load. The addition of fluvastatin to SOC treatment has been suggested to be effective for better outcome in retrospective pilot analyses. We investigated whether the combination of fluvastatin with PEG-IFN/ribavirin could actually improve sustained viral response (SVR) in patients with HCV genotype 1b and high viral load. A randomized, open-labeled, controlled study was conducted between July 2008 and December 2009 in 101 chronic hepatitis C patients allocated to PEG-IFN/ribavirin combination therapy with or without fluvastatin. SVR rates were calculated in groups, stratifying host and viral factors. We also analyzed predictive factors for SVR among patients on fluvastatin with multivariate regression analysis. Rapid and early virological, and end of treatment response rates in the fluvastatin group were not significantly different from those in the non-fluvastatin group. Notwithstanding, SVR rate was significantly higher in the fluvastatin group than in the non-fluvastatin group (63.0%vs 41.7%, P = 0.0422). Comparison of the two groups stratifying demographic data and HCV characteristics showed significantly higher SVR rates to more than 80% in males, more than two mutations in the interferon sensitivity determining region (ISDR), and a history of relapse among the fluvastatin group than the non-fluvastatin group. Being male and major genotype IL28B single nucleotide polymorphisms (SNPs) were independent predictive factors for SVR among patients on fluvastatin with multivariate analysis. Fluvastatin-combined with PEG-IFN/ribavirin therapy significantly improves SVR rates in patients with HCV genotype 1b and high viral load. Male and major genotype IL28B SNPs were independent predictors for SVR among patients on fluvastatin combination therapy.


Assuntos
Antivirais/administração & dosagem , Ácidos Graxos Monoinsaturados/administração & dosagem , Hepatite C Crônica/tratamento farmacológico , Indóis/administração & dosagem , Interferons/administração & dosagem , Ribavirina/administração & dosagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticolesterolemiantes/administração & dosagem , Quimioterapia Combinada/métodos , Feminino , Fluvastatina , Genótipo , Hepacivirus/classificação , Hepacivirus/isolamento & purificação , Humanos , Interleucinas/genética , Masculino , Pessoa de Meia-Idade , Fatores Sexuais , Resultado do Tratamento , Carga Viral
18.
Transplant Proc ; 44(4): 946-7, 2012 May.
Artigo em Inglês | MEDLINE | ID: mdl-22564592

RESUMO

INTRODUCTION: Grafts from donation after cardiac death (DCD) will greatly contribute to the expand the donor pool. However, these grafts may require the development of the preservation methods because of primary nonfunction and severe ischemic bile duct injury. METHODS: Porcine livers were perfused with a newly developed machine perfusion (MP) system. Each system for the portal vein or the hepatic artery had a roller pump, a flow meter, and a pressure sensor. The livers were perfused with University of Wisconsin (UW)-gluconate at 4°C-6°C for 3 hours after 2 hours simple cold storage (CS). The portal vein flow rate was 0.5 mL/min/g liver (pressure, 10 mm Hg) and the hepatic artery flow rate was 0.2 mL/min/g liver (pressure, 30 mm Hg). Orthotopic liver transplantation was performed in pigs comparing Group 1 (n = 4) procured after acute hemorrhagic shock preserved by MP, Group 2 (n = 3) procured after warm ischemia time (WIT) of 30 minutes with CS preservation, and Group 3 (n = 4) procured with 30 minutes of WIT and MP preservation. RESULTS: Collected effluent aspartate aminotransferase (AST) and lactate dehydrogenase (LDH) levels in the perfusion solution and serum AST and LDH were significantly lower in Group 1. AST and LDH results were lower in Group 3 than Group 2. Survival rates in Groups 1 and 3 were 3/4, but 0/3 in Group 2. CONCLUSION: MP preservation was a useful promising preservation mode for DCD liver grafts.


Assuntos
Gluconatos/administração & dosagem , Artéria Hepática/cirurgia , Transplante de Fígado , Fígado/cirurgia , Soluções para Preservação de Órgãos/administração & dosagem , Preservação de Órgãos/métodos , Perfusão/métodos , Veia Porta/cirurgia , Adenosina/administração & dosagem , Alopurinol/administração & dosagem , Animais , Aspartato Aminotransferases/metabolismo , Temperatura Baixa , Desenho de Equipamento , Glutationa/administração & dosagem , Insulina/administração & dosagem , L-Lactato Desidrogenase/metabolismo , Fígado/irrigação sanguínea , Fígado/enzimologia , Preservação de Órgãos/instrumentação , Perfusão/instrumentação , Rafinose/administração & dosagem , Suínos , Fatores de Tempo , Isquemia Quente/efeitos adversos
19.
Transplant Proc ; 43(5): 2093-6, 2011 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21693334

RESUMO

Treatment of Budd-Chiari syndrome consists of medical management, surgical shunt, transjugular intrahepatic portosystemic shunt (TIPS), and liver transplantation. Liver transplantation is indicated only when other treatments have failed. A 36-year-old Japanese man underwent living-donor liver transplantation after radiologic intervention procedures. Because of the position of the TIPS stent and the damaged vascular lesion of Budd-Chiari syndrome, a supradiaphragmatic approach was employed to achieve a safe total hepatectomy. Moreover, after resection of damaged portion of the inferior vena cava (IVC), an artificial vascular graft was utilized to fill the IVC gap. The postoperative course was uneventful; no serious complications were experienced within 2 years after liver transplantation. This supradiaphragmatic IVC approach and IVC reconstruction technique emphasized the option of surgical techniques to decrease the operative risk during liver transplantation for Budd-Chiari syndrome.


Assuntos
Síndrome de Budd-Chiari/cirurgia , Transplante de Fígado , Doadores Vivos , Adulto , Síndrome de Budd-Chiari/diagnóstico por imagem , Humanos , Masculino , Derivação Portossistêmica Transjugular Intra-Hepática , Tomografia Computadorizada por Raios X
20.
J Clin Pathol ; 63(4): 362-4, 2010 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-20354209

RESUMO

Sialadenoma papilliferum (SP) is a benign non-invasive lesion with slow and limited growth. This report describes an unusual SP that enlarged rapidly and presented as an extensive intraoral tumour highly suspicious for verrucous carcinoma. Radiographic resorption of the underlying bone was evident in the mandible. This type of destructive growth does not conform to any previously reported SP. Histological features were also atypical: surface verrucous hyperplasia and deeper florid cystic-duct adenoma. Overall, the SP is likely to be considered a borderline lesion with malignant potential. Four published cases of malignancy associated with SP showed completely different clinical and pathological settings, further obfuscating the concept of malignant SP.


Assuntos
Adenoma/diagnóstico , Neoplasias Mandibulares/diagnóstico , Papiloma/diagnóstico , Idoso , Processo Alveolar , Carcinoma Verrucoso/diagnóstico , Diagnóstico Diferencial , Humanos , Masculino , Tomografia Computadorizada por Raios X
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