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1.
Br J Anaesth ; 119(6): 1161-1168, 2017 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-29029049

RESUMO

Background: Intraoperative use of a high-dose remifentanil may induce postoperative hyperalgesia. Low-dose naloxone can selectively reverse some adverse effects of opioids without compromising analgesia. We thus hypothesized that the intraoperative use of a high-dose remifentanil combined with a low-dose naloxone infusion reduces postoperative hyperalgesia compared with the use of remifentanil alone. Methods: Patients undergoing elective thyroid surgery were randomly assigned into one of three groups, depending on the intraoperative effect-site concentration of remifentanil, with or without a continuous infusion of naloxone: 4 ng ml-1 remifentanil with 0.05 µg kg-1 h-1 naloxone in the high-remifentanil with naloxone group, and 4 or 1 ng ml-1 remifentanil with a placebo in the high- or low-remifentanil groups, respectively. We measured the pain thresholds (primary outcome) to mechanical stimuli using von Frey filaments and incidence of hyperalgesia on the peri-incisional area 24 h after surgery. We also measured pain intensity, analgesic consumptions and adverse events up to 48 h after surgery. Results: The pain threshold presented as von Frey numbers [median (interquartile range)] was significantly lower in the high-remifentanil group (n=31) than in the high-remifentanil with naloxone (n=30) and the low-remifentanil (n=30) groups [3.63 (3.22-3.84) vs 3.84 (3.76-4.00) vs 3.80 (3.69-4.08), P=0.011]. The incidence of hyperalgesia was also higher in the high-remifentanil group than in the other groups [21/31 vs 10/30 vs 9/30, P=0.005]. Postoperative pain intensity, analgesic consumptions and adverse events were similar between groups. Conclusions: The intraoperative use of low-dose naloxone combined with high-dose remifentanil reduced postoperative hyperalgesia but not pain. Clinical trial registration: NCT02856087.


Assuntos
Analgésicos Opioides/efeitos adversos , Hiperalgesia/induzido quimicamente , Cuidados Intraoperatórios/métodos , Naloxona/uso terapêutico , Dor Pós-Operatória/induzido quimicamente , Remifentanil/efeitos adversos , Adulto , Idoso , Método Duplo-Cego , Feminino , Humanos , Hiperalgesia/prevenção & controle , Masculino , Pessoa de Meia-Idade , Antagonistas de Entorpecentes/uso terapêutico , Medição da Dor , Dor Pós-Operatória/prevenção & controle , Estudos Prospectivos , Adulto Jovem
2.
Anaesthesia ; 72(10): 1196-1205, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28891056

RESUMO

We studied the predictive performance of the Minto pharmacokinetic model during cardiopulmonary bypass in patients undergoing cardiac surgery. Patients received remifentanil target-controlled infusion using the Minto model during total intravenous anaesthesia with propofol. From 56 patients, 275 arterial blood samples were drawn before, during and after bypass to determine the plasma concentration of remifentanil, and the predicted concentrations were recorded at each time. For pooled data, the median prediction error and median absolute prediction error were 21.3% and 21.8%, respectively, and 22.1% and 22.3% during bypass. Both were 148.4% during hypothermic circulatory arrest and measured concentrations were more than three times greater than predicted (26.9 (17.0) vs. 7.1 (1.6) ng.ml-1 ). The Minto model showed considerable bias but overall acceptable precision during bypass. The target concentration of remifentanil should be reduced when using the Minto model during hypothermic circulatory arrest.


Assuntos
Analgésicos Opioides/administração & dosagem , Ponte Cardiopulmonar , Modelos Biológicos , Remifentanil/administração & dosagem , Adulto , Idoso , Analgésicos Opioides/sangue , Anestésicos Intravenosos/administração & dosagem , Método Duplo-Cego , Esquema de Medicação , Sistemas de Liberação de Medicamentos/métodos , Feminino , Humanos , Infusões Intravenosas , Masculino , Pessoa de Meia-Idade , Monitorização Intraoperatória/métodos , Propofol/administração & dosagem , Remifentanil/sangue
3.
J Endocrinol Invest ; 40(10): 1069-1076, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28391584

RESUMO

BACKGROUND: Although sodium glucose cotransporter 2 (SGLT2) inhibitors have many beneficial effects for type 2 diabetes, including decreased cardiovascular death, recent reports that they increased glucagon through SGLT2 inhibition raised some concern. Troglitazone, Peroxisome proliferator-activated receptor γ (PPAR-γ) agonist, was reported to increase SGLT2 in renal proximal tubule cells, but its role on pancreatic alpha cells have not been reported. We investigated the effect of troglitazone on SGLT2 expression in alpha cells and subsequent glucagon regulation in hyperglycemia. METHODS: An Alpha TC1-6 cell line was cultured in control (5 mM) or hyperglycemia (HG, 15 mM) for 72 h. We applied troglitazone with or without PPARγ antagonist (GW9662 10 µM). To investigate the involvement of PI3K/Akt pathway, we applied troglitazone with or without Wortmanin. We measured sodium glucose transporter 2 (SGLT2) and glucagon (GCG) mRNA and protein expression. PPAR gamma, PI3K and Akt protein were also measured. RESULTS: Exposure of alpha TC cells to HG for 72 h increased glucagon mRNA and protein expression. HG decreased SGLT2 mRNA and protein expression. Troglitazone significantly reversed HG-induced reduction of SGLT2 expression and increase of glucagon secretion. PPARγ antagonist (GW9662 10 µM) decreased the expression of SGLT2 and increased glucagon as HG did. Hyperglycemia increased PI3K and pAkt expression in alpha cells. Wortmanin (PI3K inhibitor, 1 µM) reversed HG-induced SGLT2 decrease and glucagon increase. Troglitazone treatment decreased PI3K and pAkt expression in HG. CONCLUSION: In conclusion, PPARγ agonist, troglitazone improved glucose transport SGLT2 dysfunction and subsequent glucagon dysregulation in alpha cell under hyperglycemia. Those effects were through the involvement of PI3K/pAkt signaling pathway. This study may add one more reason for the ideal combination of PPARγ agonist and SGLT2 inhibitor in clinical practice.


Assuntos
Cromanos/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Células Secretoras de Glucagon/metabolismo , Glucagon/metabolismo , Hiperglicemia/fisiopatologia , PPAR gama/agonistas , Transportador 2 de Glucose-Sódio/metabolismo , Tiazolidinedionas/farmacologia , Animais , Células Cultivadas , Células Secretoras de Glucagon/efeitos dos fármacos , Células Secretoras de Glucagon/patologia , Glucose/farmacologia , Hipoglicemiantes/farmacologia , Camundongos , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais , Troglitazona
4.
Rev Sci Instrum ; 88(1): 013106, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28147670

RESUMO

A synchrotron radiation beamline in the photon energy range of 18-240 eV and an electron spectroscopy end station have been constructed at the 3 GeV Diamond Light Source storage ring. The instrument features a variable polarisation undulator, a high resolution monochromator, a re-focussing system to form a beam spot of 50 × 50 µm2, and an end station for angle-resolved photoelectron spectroscopy (ARPES) including a 6-degrees-of-freedom cryogenic sample manipulator. The beamline design and its performance allow for a highly productive and precise use of the ARPES technique at an energy resolution of 10-15 meV for fast k-space mapping studies with a photon flux up to 2 ⋅ 1013 ph/s and well below 3 meV for high resolution spectra.

5.
Anaesthesia ; 72(2): 204-213, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27666136

RESUMO

The infusion of fluids to patients may affect tissue microcirculation and the endothelial glycocalyx. However, the effects of hydroxyethyl starch and crystalloid on endothelial glycocalyx degradation and microvascular reactivity have not been evaluated in detail. We hypothesised that hydroxyethyl starch may cause less endothelial glycocalyx degradation and better microvascular reactivity than that caused by crystalloid. We randomly allocated 120 patients undergoing off-pump coronary artery bypass graft surgery to receive up to 20 ml.kg-1 of either hydroxyethyl starch 670/0.75 or crystalloid for intra-operative fluid resuscitation. Crystalloid was then infused to meet ongoing fluid requirements. During the peri-operative period, vascular occlusion tests were performed to assess microvascular reactivity, and serum syndecan-1 was measured as an index of endothelial glycocalyx degradation. The median (IQR [range]) fluid infused during surgery was significantly less in the hydroxyethyl starch group than the crystalloid group; 2800 (2150-3550 [1400-7300]) vs. 3925 (3100-4725 [1900-6700]) ml, respectively, p < 0.001. Vascular occlusion test parameters, including tissue oxygen saturation, occlusion and recovery slope did not differ significantly between the groups. Peri-operative changes in syndecan-1 were not significantly different between the groups. We conclude that, in patients undergoing off-pump coronary artery bypass graft surgery, compared with crystalloid, the use of hydroxyethyl starch 670/0.75 did not result in significant differences in microvascular reactivity or endothelial glycocalyx degradation.


Assuntos
Ponte de Artéria Coronária sem Circulação Extracorpórea , Soluções Cristaloides/farmacologia , Endotélio Vascular/efeitos dos fármacos , Hidratação , Glicocálix/metabolismo , Derivados de Hidroxietil Amido/farmacologia , Microcirculação/efeitos dos fármacos , Idoso , Endotélio Vascular/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Sindecana-1/sangue
6.
Oncogene ; 35(34): 4540-8, 2016 08 25.
Artigo em Inglês | MEDLINE | ID: mdl-26804173

RESUMO

Epithelial ovarian cancer (EOC) invasion and metastasis are complex phenomena that result from the coordinated action of many metastatic regulators and must be overcome to improve clinical outcomes for patients with these cancers. The identification of novel therapeutic targets is critical because of the limited success of current treatment regimens, particularly in advanced-stage ovarian cancers. In this study, we found that tetraspanin 8 (TSPAN8) is overexpressed in about 52% (14/27) of EOC tissues and correlates with poor survival. Using small interfering RNA-mediated TSPAN8 knockdown and a competition assay with purified TSPAN8 large extracellular loop (TSPAN8-LEL) protein, we identified TSPAN8-LEL as a key regulator of EOC cell invasion. Furthermore, monotherapy with TSPAN8-blocking antibody we developed shows that antibody-based modulation of TSPAN8-LEL can significantly reduce the incidence of EOC metastasis without severe toxicity in vivo. Finally, we demonstrated that the TSPAN8-blocking antibody promotes the internalization and concomitant downregulation of cell surface TSPAN8. Collectively, our data suggest TSPAN8 as a potential novel therapeutic target in EOCs and antibody targeting of TSPAN8 as an effective strategy for inhibiting invasion and metastasis of TSPAN8-expressing EOCs.


Assuntos
Neoplasias Epiteliais e Glandulares/patologia , Neoplasias Ovarianas/patologia , Tetraspaninas/antagonistas & inibidores , Anticorpos/farmacologia , Anticorpos/uso terapêutico , Carcinoma Epitelial do Ovário , Feminino , Humanos , Imunoglobulina G/farmacologia , Invasividade Neoplásica , Metástase Neoplásica , Neoplasias Epiteliais e Glandulares/tratamento farmacológico , Neoplasias Ovarianas/tratamento farmacológico , Tetraspaninas/análise
7.
Br J Anaesth ; 117(4): 497-503, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28077538

RESUMO

BACKGROUND: We evaluated the effect of magnesium sulphate on increased pain in 44 patients undergoing staged bilateral total knee arthroplasty (TKA). METHODS: The magnesium group (n=22) and the control group (n=22) received magnesium sulphate and isotonic saline, respectively, throughout the surgery. Postoperative pain (visual analogue scale, VAS) at rest and the amounts of patient-controlled analgesia (PCA, fentanyl) and rescue analgesia (ketoprofen) administered during the first 48 h were compared between the two groups and within each group between the first and second TKA. RESULTS: The VAS scores were significantly higher in the control group than in the magnesium group not only after the first TKA [29 (11) vs 19 (9) at 24 h and 33 (8) vs 24 (10) at 48 h; P=0.001] but also after the second TKA [44 (17) vs 20 (10) at 24 h and 43 (14) vs 25 (10) at 48 h; P<0.001]. In the control group, VAS scores were significantly higher for the second than for the first operated knee [44 (17) vs 29 (11) at 24 h and 43 (14) vs 33 (8) at 48 h; P<0.001 and P=0.006, respectively]. In the magnesium group, there were no significant differences in VAS scores between the first and second TKA. Magnesium significantly reduced the amounts of rescue analgesics and fentanyl administered over the first 48 h postoperatively. CONCLUSIONS: Magnesium sulphate administration significantly reduced postoperative pain and minimized the difference in pain intensity between the first and second operations. CLINICAL TRIAL REGISTRATION: KCT0001361.


Assuntos
Dor Aguda/tratamento farmacológico , Artroplastia do Joelho , Sulfato de Magnésio/uso terapêutico , Dor Pós-Operatória/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Escala Visual Analógica
8.
Clin Pharmacol Ther ; 98(1): 96-106, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25786663

RESUMO

We retrospectively investigated whether palonosetron administered during the induction of general anesthesia is associated with an increased risk of perioperative cardiovascular complications in a single tertiary center cohort consisting of 4,517 palonosetron-exposed patients and 4,517 propensity score-matched patients without palonosetron exposure. The primary endpoint was a composite of perioperative cardiovascular complications, including intraoperative cardiac arrhythmia, intraoperative cardiac death, and myocardial injury within the first postoperative week, and there was no significant difference between the groups (odds ratio [OR] = 1.04; 95% confidence interval [CI] = 0.92-1.19). As secondary endpoints, intraoperative cardioversion, cardiac compression, use of cardiovascular drugs, postoperative hospital stay, and in-hospital mortality showed no differences between the groups. However, the palonosetron group showed decreased intraoperative hypotension (OR = 0.88; 95% CI = 0.79-0.97) and length of postoperative intensive care unit (ICU) stay (4.26 ± 9.86 vs. 6.14 ± 16.75; P = 0.026). Palonosetron did not increase the rate of perioperative cardiovascular complications, and can therefore be used safely during anesthetic induction.


Assuntos
Anestesia Geral , Antieméticos/efeitos adversos , Sistema Cardiovascular/efeitos dos fármacos , Isoquinolinas/efeitos adversos , Quinuclidinas/efeitos adversos , Antagonistas do Receptor 5-HT3 de Serotonina/efeitos adversos , Adulto , Idoso , Arritmias Cardíacas/induzido quimicamente , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/induzido quimicamente , Palonossetrom , Período Perioperatório , Estudos Retrospectivos
10.
Phys Rev Lett ; 113(17): 177601, 2014 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-25379937

RESUMO

We report on the formation of a two-dimensional electron gas (2DEG) at the bare surface of (111) oriented SrTiO3. Angle resolved photoemission experiments reveal highly itinerant carriers with a sixfold symmetric Fermi surface and strongly anisotropic effective masses. The electronic structure of the 2DEG is in good agreement with self-consistent tight-binding supercell calculations that incorporate a confinement potential due to surface band bending. We further demonstrate that alternate exposure of the surface to ultraviolet light and atomic oxygen allows tuning of the carrier density and the complete suppression of the 2DEG.

12.
Arch Biochem Biophys ; 563: 79-93, 2014 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-24997364

RESUMO

To study the effect of melanogenesis on HIF-1α expression and attendant pathways, we used stable human and hamster melanoma cell lines in which the amelanotic vs. melanotic phenotypes are dependent upon the concentration of melanogenesis precursors in the culture media. The induction of melanin pigmentation led to significant up-regulation of HIF-1α, but not HIF-2α, protein in melanized cells for both lines. Similar upregulation of nuclear HIF-1α was observed in excisions of advanced melanotic vs. amelanotic melanomas. In cultured cells, melanogenesis also significantly stimulated expression of classical HIF-1-dependent target genes involved in angiogenesis and cellular metabolism, including glucose metabolism and stimulation of activity of key enzymes in the glycolytic pathway. Several other stress related genes containing putative HRE consensus sites were also upregulated by melanogenesis, concurrently with modulation of expression of HIF-1-independent genes encoding for steroidogenic enzymes, cytokines and growth factors. Immunohistochemical studies using a large panel of pigmented lesions revealed that higher levels of HIF-1α and GLUT-1 were detected in advanced melanomas in comparison to melanocytic nevi or thin melanomas localized to the skin. However, the effects on overall or disease free survival in melanoma patients were modest or absent for GLUT-1 or for HIF-1α, respectively. In conclusion, induction of the melanogenic pathway leads to robust upregulation of HIF-1-dependent and independent pathways in cultured melanoma cells, suggesting a key role for melanogenesis in regulation of cellular metabolism.


Assuntos
Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Melaninas/biossíntese , Melanoma/metabolismo , Neoplasias Cutâneas/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Linhagem Celular Tumoral , Cricetinae , Progressão da Doença , Feminino , Transportador de Glucose Tipo 1/metabolismo , Glicólise , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Masculino , Melanócitos/metabolismo , Melanoma/etiologia , Melanoma/genética , Melanoma Amelanótico/etiologia , Melanoma Amelanótico/genética , Melanoma Amelanótico/metabolismo , Pessoa de Meia-Idade , Modelos Biológicos , Transdução de Sinais , Neoplasias Cutâneas/etiologia , Neoplasias Cutâneas/genética , Regulação para Cima , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/metabolismo , Adulto Jovem
13.
Br J Anaesth ; 113(3): 391-401, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24829443

RESUMO

BACKGROUND: Inflammation plays a key role in the pathogenesis of vascular occlusive diseases, such as myocardial infarction and stroke. Additionally, these conditions are predicted by C-reactive protein (CRP), a general inflammation marker. We hypothesized that the inflammation induced by surgery itself augments vascular occlusive disease. We retrospectively evaluated the relationship between postoperative CRP elevation and postoperative major adverse cardiovascular and cerebral events (MACCE) in patients undergoing off-pump coronary artery bypass surgery (OPCAB). METHODS: The electronic medical records of 1046 patients who underwent OPCAB were reviewed retrospectively. The relationship between postoperative serum CRP and long-term postoperative MACCE (median follow-up 28 months) was investigated. RESULTS: Patients were divided into quartiles according to maximum postoperative CRP levels (<18, 18-22, 22-27, ≥27 mg dl(-1)). The adjusted hazard ratios (HRs) were 2.15, 2.45, and 2.81, respectively (P=0.004), compared with the lowest quartile (<18 mg dl(-1)). In the multivariate analysis, the postoperative CRP quartile (HR 2.81; P=0.004), postoperative non-use of statins (HR 1.86; P=0.003), and postoperative maximum troponin I (HR 1.02; P<0.001) independently predicted postoperative MACCE, while preoperative CRP did not (P=0.203). Several parameters were correlated with postoperative maximum CRP level: body temperature (P=0.001) and heart rate (P<0.001) at the end of surgery; intraoperative last lactate (P<0.001) and base excess (P<0.001); and red blood cell transfusion (P=0.019). CONCLUSIONS: Postoperative CRP elevation was associated with long-term postoperative MACCE in OPCAB patients. This was mitigated by postoperative statin medication. Furthermore, postoperative CRP elevation was associated with intraoperative parameters reflecting hypoperfusion and inflammation.


Assuntos
Proteína C-Reativa/metabolismo , Doenças Cardiovasculares/sangue , Transtornos Cerebrovasculares/sangue , Ponte de Artéria Coronária sem Circulação Extracorpórea/efeitos adversos , Complicações Pós-Operatórias/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Proteína C-Reativa/análise , Doenças Cardiovasculares/etiologia , Transtornos Cerebrovasculares/etiologia , Feminino , Seguimentos , Humanos , Inflamação/sangue , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/etiologia , Período Pós-Operatório , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Resultado do Tratamento
14.
Exp Clin Endocrinol Diabetes ; 122(4): 240-5, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24623499

RESUMO

BACKGROUND: 3,5,3'-Triiodothyronine (T3) has a stimulatory effect on cellular growth via thyroid hormone receptors (TRs) in several cell lines. TR expression in the pancreas suggests that pancreatic beta cell proliferation might be induced by T3. The purpose of this study was to demonstrate that T3 induces pancreatic beta cell proliferation through the mitogen activated protein kinase/extracellular regulated kinase (MAPK/ERK) pathway. METHODS: INS-1 cells were plated as a monolayer at densities of 4×104, cultured in RPMI 1,640 with 10% fetal bovine serum with 2-mercaptoethanol, respectively, in 6-well multiplates. After 48 h, they were exposed to 10-7 M T3 or to vehicle alone. Viable cells were harvested after 24, 48, and 72 h of continuous exposure. Cell proliferation and TRα1 and TRß1 expression were analyzed by flow-assisted cell sorting analysis, Ki-67 staining, and Western blotting. The p38 MAPK, ERK, and Akt pathways were analyzed by Western blotting. Beta cell function was evaluated by assaying insulin secretion. RESULTS: T3 enhanced INS-1 cell proliferation at a dose of 10-7 M in a time-dependent manner via the MAPK/ERK pathway and promoted insulin secretion. CONCLUSIONS: Our results demonstrate that MAPK/ERK pathway plays an important role in the T3 induced pancreatic beta cell proliferation.


Assuntos
Células Secretoras de Insulina/efeitos dos fármacos , Insulina/metabolismo , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Receptores dos Hormônios Tireóideos/metabolismo , Tri-Iodotironina/farmacologia , Animais , Western Blotting , Bromodesoxiuridina/química , Linhagem Celular , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Citometria de Fluxo , Indóis/química , Secreção de Insulina , Células Secretoras de Insulina/citologia , Células Secretoras de Insulina/enzimologia , Células Secretoras de Insulina/metabolismo , Antígeno Ki-67/química , Ratos
15.
J Hand Surg Eur Vol ; 39(3): 258-61, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23468080

RESUMO

Osteophyte excision is a mainstay of treatment for mucous cyst combined with Heberden's node in a distal interphalangeal joint or in an interphalangeal joint of the thumb. The aim of this study was to evaluate the results of osteophyte excision without cyst excision for the treatment of a mucous cyst combined with Heberden's node. The medical records of 37 patients (42 cases) with a mucous cyst with Heberden's node were retrospectively reviewed. Thirty-eight of 40 cases with available pre-operative simple radiographs showed evidence of joint arthrosis. A T-shaped skin incision of the joint capsule between the extensor tendon and lateral collateral ligament was used. Osteophyte excision without cyst excision was performed. All cysts, except one, regressed without recurrence or a skin complication after osteophyte excision, but eight cases showed post-operative pain and loss of range of motion. Osteophyte excision without cyst excision may be a good treatment choice for mucous cyst of the finger.


Assuntos
Dedos/cirurgia , Cistos Glanglionares/cirurgia , Osteófito/cirurgia , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
16.
Int Angiol ; 31(6): 501-16, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23222928

RESUMO

Venous thromboembolism (VTE) prophylaxis is under-utilized in Asia because of the misconception that its incidence is lower in Asians as compared to the Caucasians. The available data on VTE in Asia is limited due to the lack of well-designed multicenter randomized controlled trials as well as non-standardized research designs, making data comparison difficult. Emerging data indicates that the VTE incidence is not low in Asia, and is comparable to that reported in the Western literature in some instances. There is also a trend towards increasing incidence of VTE, as demonstrated by a number of hospital-based studies in Asia. This could be attributed to lifestyle changes, ageing population, increasing awareness of VTE and wider availability of Duplex ultrasound. The risk of VTE in hospitalized patients remain the same in Asians and Caucasians, even though there may be factors that are inherent to patients in Asia that influence the slight variation in incidence. The utilization rate of VTE prophylaxis remains suboptimal in Asia. The Asian Venous Thrombosis Forum (AVTF) comprises participants from various countries such as China, Hong Kong, India, Indonesia, Korea, Malaysia, Philippines, Singapore, Taiwan, Thailand and experts from Australia and Europe. The forum evaluated the available data on VTE from the Asian region and formulated guidelines tailored to meet the needs of the region. We recommend that serious considerations are given to VTE prophylaxis especially in the at-risk group and a formal hospital policy be established to facilitate the implementation. On admission to the hospital, we recommend assessing the patients for both VTE and bleeding risk. We recommend mechanical prophylaxis for patients at increased risk of bleeding and utilizing it as an adjunctive measure in combination with pharmacological prophylaxis in patients with high risk of VTE. For patients undergoing general or gynecological surgery and with moderate risk for VTE, we recommend prophylaxis with one of the following: low dose unfractionated heparin (LDUH), low molecular weight heparin (LMWH), fondaparinux or intermittent pneumatic compression (IPC). For the same group of patients at high risk of VTE, we recommend pharmacological or combination of pharmacological and mechanical prophylaxis. For patients undergoing major orthopedic surgeries like total hip replacement, total knee replacement and proximal hip fracture surgery, we recommend using one of the following: LMWH, fondaparinux, rivaroxaban, apixaban, edoxaban, dabigatran, warfarin or aspirin with IPC. For patients admitted to the hospital with acute medical illness and has moderate risk of VTE, we recommend prophylaxis with LDUH, LMWH or Fondaparinux. For the same group at high risk of VTE, we recommend combination of pharmacological and mechanical prophylaxis.


Assuntos
Anticoagulantes/uso terapêutico , Fibrinolíticos/uso terapêutico , Serviços Preventivos de Saúde/normas , Tromboembolia Venosa/prevenção & controle , Anticoagulantes/efeitos adversos , Ásia/epidemiologia , Povo Asiático , Terapia Combinada , Fibrinolíticos/efeitos adversos , Hemorragia/induzido quimicamente , Hospitalização , Humanos , Incidência , Padrões de Prática Médica/normas , Medição de Risco , Fatores de Risco , Procedimentos Cirúrgicos Operatórios/efeitos adversos , Resultado do Tratamento , Tromboembolia Venosa/diagnóstico , Tromboembolia Venosa/etnologia
17.
Pharmazie ; 67(9): 789-91, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23016452

RESUMO

The purpose of this study was to evaluate the plasma-protein binding of docetaxel in two different formulations, Taxotere and SID530, a new docetaxel formulation with hydroxypropyl-beta-cyclodextrin (HP-beta-CD), in human plasma in vitro, using equilibrium dialysis. Unbound docetaxel concentration in the human plasma was determined by LC-MS/MS analysis. SID530 showed a plasma-protein binding profile comparable to that of Taxotere in the clinically relevant concentration range of docetaxel. In both formulations, the unbound fraction of docetaxel increased in a concentration-dependent biphasic manner. The resulting data indicate that the excipient used in SID530, HP-beta-CD, generates similar effects as polysorbate 80 of Taxotere in terms of plasma-protein binding of docetaxel.


Assuntos
Antineoplásicos Fitogênicos/sangue , Taxoides/sangue , 2-Hidroxipropil-beta-Ciclodextrina , Antineoplásicos Fitogênicos/administração & dosagem , Proteínas Sanguíneas/metabolismo , Química Farmacêutica , Cromatografia Líquida de Alta Pressão , Diálise , Docetaxel , Humanos , Indicadores e Reagentes , Espectrometria de Massas , Pós , Ligação Proteica , Reprodutibilidade dos Testes , Taxoides/administração & dosagem , Equivalência Terapêutica , beta-Ciclodextrinas
18.
Arzneimittelforschung ; 62(6): 280-4, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22508174

RESUMO

SID530 is a new parenteral formulation of docetaxel containing hydroxypropyl-beta-cyclodextrin (HP-ß-CD). In this study, a comparative pharmacokinetic study of 2 docetaxel parenteral solutions, SID530 and Taxotere, was carried out. In a crossover experimental design, 6 male cynomolgus monkeys received each formulation by intravenous infusion of a single dose. The concentration of docetaxel in whole blood and plasma was determined using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The 2 formulations showed similar pharmacokinetic parameters in both whole blood and plasma, and displayed comparable values for maximum serum concentration (Cmax), time to peak concentration (Tmax), and area under the concentration-time curve (AUC). The 90% confidence intervals for the ratios of Cmax and AUC values for SID530 to Taxotere were within the acceptable range of 0.80-1.20 in both plasma and whole blood. These findings indicate that SID530 and Taxotere are comparable in terms of their distribution in the blood and their plasma profile; consequently, these drugs are bioequivalent in the monkey.


Assuntos
Antineoplásicos Fitogênicos/farmacocinética , Excipientes , Taxoides/farmacocinética , beta-Ciclodextrinas/farmacocinética , 2-Hidroxipropil-beta-Ciclodextrina , Animais , Antineoplásicos Fitogênicos/administração & dosagem , Antineoplásicos Fitogênicos/sangue , Área Sob a Curva , Calibragem , Química Farmacêutica , Docetaxel , Macaca fascicularis , Masculino , Padrões de Referência , Espectrometria de Massas em Tandem , Taxoides/administração & dosagem , Taxoides/sangue , Equivalência Terapêutica , beta-Ciclodextrinas/administração & dosagem , beta-Ciclodextrinas/sangue
19.
Br J Cancer ; 105(12): 1874-84, 2011 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-22095230

RESUMO

BACKGROUND: Melanoma is highly resistant to current modalities of therapy, with the extent of pigmentation playing an important role in therapeutic resistance. Nuclear factor-κB (NF-κB) is constitutively activated in melanoma and can serve as a molecular target for cancer therapy and steroid/secosteroid action. METHODS: Cultured melanoma cells were used for mechanistic studies on NF-κB activity, utilising immunofluorescence, western blotting, EMSA, ELISA, gene reporter, and estimated DNA synthesis assays. Formalin-fixed, paraffin-embedded specimens from melanoma patients were used for immunocytochemical analysis of NF-κB activity in situ. RESULTS: Novel 20-hydroxyvitamin (20(OH)D(3)) and classical 1α,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3)) secosteroids inhibited melanoma cell proliferation. Active forms of vitamin D were found to inhibit NF-κB activity in nonpigmented cells, while having no effect on pigmented cells. Treatment of nonpigmented cells with vitamin D3 derivatives inhibited NF-κB DNA binding and NF-κB-dependent reporter assays, as well as inhibited the nuclear translocation of the p65 NF-κB subunit and its accumulation in the cytoplasm. Moreover, analysis of biopsies of melanoma patients showed that nonpigmented and slightly pigmented melanomas displayed higher nuclear NF-κB p65 expression than highly pigmented melanomas. CONCLUSION: Classical 1,25(OH)(2)D(3) and novel 20(OH)D(3) hydroxyderivatives of vitamin D3 can target NF-κB and regulate melanoma progression in nonpigmented melanoma cells. Melanin pigmentation is associated with the resistance of melanomas to 20(OH)D(3) and 1,25(OH)(2)D(3) treatment.


Assuntos
Colecalciferol/farmacologia , Melanoma/metabolismo , NF-kappa B/metabolismo , Divisão Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Humanos , Melanoma/patologia
20.
J Bone Joint Surg Br ; 93(3): 337-44, 2011 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21357955

RESUMO

We aimed to document the pre-operative expectations in Korean patients undergoing total knee replacement using an established survey form and to determine whether expectations were influenced by sociodemographic factors or pre-operative functional status. Expectations regarding 17 items in the Knee Replacement Expectation Survey form were investigated in 454 patients scheduled for total knee replacement. The levels and distribution patterns of summated expectation and of five expectation categories (relief from pain, baseline activity, high flexion activity, social activity and psychological well-being) constructed from the 17 items were assessed. Univariate analyses and multivariate logistic regression were performed to examine the associations of expectations with the sociodemographic factors and the functional status. The top three expectations were relief from pain, restoration of walking ability, and psychological well-being. Of the five expectation categories, relief from pain was ranked the highest, followed by psychological well-being, restoration of baseline activity, ability to perform high flexion activities and ability to participate in social activities. An age of < 65 years, being employed, a high Western Ontario and McMaster Universities osteoarthritis index function score and a low Short-form 36 social score were found to be significantly associated with higher overall expectations.


Assuntos
Artroplastia do Joelho/psicologia , Atitude Frente a Saúde , Atividades Cotidianas , Idoso , Idoso de 80 Anos ou mais , Análise de Variância , Artroplastia do Joelho/reabilitação , Feminino , Humanos , Articulação do Joelho/fisiopatologia , Coreia (Geográfico) , Masculino , Pessoa de Meia-Idade , Osteoartrite do Joelho/complicações , Osteoartrite do Joelho/reabilitação , Osteoartrite do Joelho/cirurgia , Dor/etiologia , Dor/cirurgia , Satisfação do Paciente , Estudos Prospectivos , Psicometria , Recuperação de Função Fisiológica , Análise de Regressão , Resultado do Tratamento
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