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INTRODUCTION: The aim of this study is to share preliminary experiences and outcomes with a novel custom-made fenestrated TREO® Abdominal Stent-Graft System to treat juxtarenal and pararenal abdominal aortic aneurysms (AAAs). METHODS: Juxtarenal and pararenal AAA patients treated with the custom-made fenestrated TREO® Abdominal Stent-Graft System were included from 4 high-volume European academic medical centers from June 2021 to September 2023. Technical success and 30-day/in-hospital mortality and complications were analyzed. Technical success was defined as successful endovascular implantation of the stent graft with preservation of antegrade flow to the target vessels, and absence of type 1 or 2 endoleak (EL) at the first postoperative computed tomography angiography (CTA). RESULTS: Forty-two consecutive patients were included. The majority of the devices were constructed with 2 (N=4; 9.5%), 3 (N=9; 21.4%), or 4 (N=27; 64%) fenestrations. In 1 case, the device was constructed with a single fenestration (2.4%) and 1 device contained 5 fenestrations (2.4%); 17% had previous AAA repair. Target vessel cannulation with placement of a bridging stent was successful in all but 1 vessel (99, 3%). One aneurysm-related death occurred in the direct postoperative period and 2 limb occlusions necessitated reintervention during admission. In the median follow-up period of 101 (2-620) days, 3 more patients died due to non-aneurysm-related causes. Technical success was achieved in 90% of the cases. Nineteen ELs were seen on the first postoperative CT scan: 1 type 1b EL (N=1; 2%), 15 type 2 ELs (N=15; 36%), and 3 type 3 ELs (N=3%). Eleven patients received more than 1 CT scan during a median follow-up of 361 days (82-620): 3 type 2 ELs resolved and 1 type 3 EL was treated in this period. In the follow-up, 1 patient had a coagulation disorder that caused occlusions of the branches. CONCLUSION: The results of the first experiences using the custom-made fenestrated TREO® Abdominal Stent-Graft System in Europe are promising. There was a low short-term mortality and morbidity rate in these patients of which 17% had previous AAA repair. Mid-term and long-term follow-up data are needed to evaluate endograft durability and performance. CLINICAL IMPACT: This study shows the first experiences and short-term results of a novel low-profile custom-made device: the custom-made fenestrated TREO® Abdominal Stent-Graft System. Showing these results and experiences can help the physicians in clinical decision-making for their patients.
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BACKGROUND: The incidence of peripheral arterial occlusions in Asian populations is likely to increase exponentially in the present and future decades due to the adapted Western lifestyle in metropolitan Asian life, extended life expectancies, and high rates of smoking. The literature on thrombolytic treatment of peripheral arterial occlusions in Asian populations is limited. Therefore, we evaluated the thrombolysis results in a real-world contemporary Asian cohort of patients with peripheral arterial occlusions. METHODS: Retrospective review of all electronic patient records of patients who underwent thrombolytic therapy for peripheral arterial occlusions between July 2011 and July 2016 was conducted. Outcomes were angiographic patency, clinical success, bleeding complications, amputation rates, and mortality rates. RESULTS: In total, 82 patients (median age 66 years, range 34-95) underwent catheter-directed thrombolysis. Median treatment duration was 26 hr (3-209). Angiographic patency and clinical success rates were 64% and 66%, respectively. Bleeding complications occurred in 12% of patients of which 6% were major. Amputation-free rates were 81%, 67%, and 63% for 30 days, 6 months, and 1 year, respectively. In-hospital mortality was 6%. CONCLUSIONS: This study demonstrates that thrombolytic treatment of peripheral arterial occlusions in an Asian patient cohort yields comparable treatment success rates to Western cohorts; however, higher rates of bleeding complications are hazardous and remain a detrimental drawback of this treatment.
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Cateterismo Periférico , Fibrinolíticos/administração & dosagem , Isquemia/tratamento farmacológico , Doença Arterial Periférica/tratamento farmacológico , Terapia Trombolítica/métodos , Doença Aguda , Adulto , Idoso , Idoso de 80 Anos ou mais , Amputação Cirúrgica , Povo Asiático , Cateterismo Periférico/efeitos adversos , Registros Eletrônicos de Saúde , Feminino , Fibrinolíticos/efeitos adversos , Hemorragia/induzido quimicamente , Hemorragia/etnologia , Mortalidade Hospitalar , Humanos , Isquemia/diagnóstico por imagem , Isquemia/etnologia , Isquemia/fisiopatologia , Masculino , Pessoa de Meia-Idade , Doença Arterial Periférica/diagnóstico por imagem , Doença Arterial Periférica/etnologia , Doença Arterial Periférica/fisiopatologia , Estudos Retrospectivos , Fatores de Risco , Taiwan/epidemiologia , Terapia Trombolítica/efeitos adversos , Fatores de Tempo , Resultado do Tratamento , Grau de Desobstrução VascularRESUMO
OBJECTIVES: Extensive reactive oxygen and nitrogen species (also reactive species) production is a mechanism involved in abdominal aortic aneurysm (AAA) development. White blood cells (WBCs) are a known source of reactive species. Their production may be decreased by statins, thereby reducing the AAA growth rate. Reactive species production in circulating WBCs of AAA patients and the effect of statins on their production was investigated. METHODS: This observational study investigated reactive species production in vivo and ex vivo in circulating WBCs of AAA patients, using venous blood from patients prior to elective AAA repair (n = 34; 18 statin users) and from healthy volunteers (n = 10). Reactive species production was quantified in circulating WBCs using immunofluorescence microscopy: nitrotyrosine (footprint of peroxynitrite, a potent reactive nitrogen species) in snap frozen blood smears; mitochondrial superoxide and cytoplasmic hydrogen peroxide (both reactive oxygen species) by live cell imaging. Neutrophils, lymphocytes, and monocytes were examined individually. RESULTS: In AAA patients using statins, the median nitrotyrosine level in neutrophils was 646 (range 422-2059), in lymphocytes 125 (range 74-343), and in monocytes 586 (range 291-663). Median levels in AAA patients not using statins were for neutrophils 928 (range 552-2095, p = .03), lymphocytes 156 (101-273, NS), and for monocytes 536 (range 535-1635, NS). The statin dose tended to correlate negatively with nitrotyrosine in neutrophils (Rs -0.32, p = .06). The median levels in controls were lower for neutrophils 466 (range 340-820, p < .01) and for monocytes 191 (range 102-386, p = .03), but similar for lymphocytes 99 (range 82-246) when compared to the AAA patients. There were no differences in mitochondrial superoxide and cytoplasmic hydrogen peroxide between statin and non-statin users within AAA patients. CONCLUSIONS: It was found that the peroxynitrite footprint in circulating neutrophils and monocytes of AAA patients is higher than in controls. AAA patients treated with statins had a lower peroxynitrite footprint in neutrophils than non-statin users.
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Aneurisma da Aorta Abdominal/tratamento farmacológico , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Neutrófilos/efeitos dos fármacos , Ácido Peroxinitroso/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Aneurisma da Aorta Abdominal/sangue , Aneurisma da Aorta Abdominal/diagnóstico , Biomarcadores/sangue , Estudos de Casos e Controles , Feminino , Humanos , Peróxido de Hidrogênio/sangue , Linfócitos/efeitos dos fármacos , Linfócitos/metabolismo , Masculino , Pessoa de Meia-Idade , Monócitos/efeitos dos fármacos , Monócitos/metabolismo , Neutrófilos/metabolismo , Tirosina/análogos & derivados , Tirosina/sangueRESUMO
In plants, the oxidative cleavage of carotenoid substrates produces volatile apocarotenoids, including α-ionone, ß-ionone, and dihydro-ß-ionone, compounds that are important in herbivore-plant communication. For example, ß-ionone is part of an induced defense in canola, Brassica napus, and is released following wounding by herbivores. The objectives of the research were to evaluate whether these volatile compounds would: 1) be released in higher quantities from plants through the over-expression of the carotenoid cleavage dioxygenase1 (CCD1) gene and 2) cause herbivores to be repelled or attracted to over-expressing plants relative to the wild-type. In vivo dynamic headspace collection of volatiles coupled with gas chromatography-mass spectrometry was used to determine volatile organic compounds (VOC) in the headspace of the Arabidopsis thaliana ecotype Columbia-0 (L.) over-expressing the AtCCD1 gene. The analytical method allowed the detection of ß-ionone in the Arabidopsis headspace where emission rates ranged between 2 and 5-fold higher compared to the wild type, thus corroborating the in vivo enhancement of gene expression. A two chamber choice test between wild type and AtCCD1 plants revealed that crucifer flea beetle Phyllotreta cruciferae (Goeze) adults were repelled by the AtCCD1 plants with the highest transcription and ß-ionone levels. α-Ionone and dihydro-ß-ionone were not found in the headspace analysis, but solutions of the three compounds were tested in the concentration range of ß-ionone found in the Arabidopsis headspace (0.05 to 0.5 ng/µl) in order to assess their biological activity with crucifer flea beetle, two spotted spider mite Tetranychus urticae (Koch), and silverleaf whiteflies Bemisia tabaci (Gennadius). Choice bioassays demonstrated that ß-ionone has a strong repellent effect toward both the flea beetle and the spider mite, and significant oviposition deterrence to whiteflies. In contrast, dihydro-ß-ionone had attractant properties, especially to the crucifer flea beetle, while α-ionone did not show any significant activity. These findings demonstrate how regulating genes of the carotenoid pathway can increase herbivore deterrent volatiles, a novel tool for insect pest management.
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Besouros/fisiologia , Hemípteros/fisiologia , Herbivoria , Ácaros/fisiologia , Norisoprenoides/fisiologia , Animais , Cromatografia Gasosa-Espectrometria de Massas , VolatilizaçãoRESUMO
OBJECTIVE: To evaluate the efficacy and bleeding complications associated with a low-dose thrombolysis protocol for thromboembolic lower extremity arterial occlusions. DESIGN: A retrospective cohort study. MATERIALS AND METHODS: A retrospective analysis was performed using data from all consecutive patients who underwent catheter-directed, intra-arterial thrombolysis for thromboembolic lower extremity arterial occlusions between January 2004 and May 2013. All patients were treated on a standard surgical ward. Endpoints were incidence of bleeding complications, duration of thrombolysis, angiographic patency rate, 30-day mortality rate, and amputation-free rate at 6 months. RESULTS: Of the 171 cases analyzed, 129 cases underwent low-dose thrombolysis and 42 underwent high-dose thrombolysis. No major bleeding complications occurred in the low-dose group versus 5% in the high-dose group (p = .01). The median duration of thrombolysis was 67 hours (4-304 hours) in the low-dose and 49 hours (2-171 hours) in the high-dose group (p = .027). Angiographic patency was restored in 67% of the cases in the low-dose group versus 79% of the high-dose group (p = .17). The 30-day mortality rates were 1% in the low-dose versus 5% in the high-dose group (p = .09). However, this higher mortality rate was not related to bleeding complications. Major amputation-free rates at 6 months were 81% in the low-dose group and 88% in the high-dose group (p = .22). CONCLUSIONS: Based on this data series, low-dose thrombolysis for thromboembolic lower extremity arterial occlusions is as effective as high-dose thrombolysis; however, the risk of major bleeding complications is substantially lower when using low-dose thrombolysis.
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Arteriopatias Oclusivas/tratamento farmacológico , Fibrinolíticos/administração & dosagem , Extremidade Inferior/irrigação sanguínea , Complicações Pós-Operatórias , Terapia Trombolítica , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Feminino , Fibrinolíticos/uso terapêutico , Oclusão de Enxerto Vascular/prevenção & controle , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/prevenção & controle , Estudos Retrospectivos , Terapia Trombolítica/efeitos adversosRESUMO
BACKGROUND: To evaluate the feasibility of robot-assisted thoracoscopic T2-T5 ramicotomy. METHODS: In 5 pigs, a robot-assisted thoracoscopic T2-T5 ramicotomy was performed, followed by T2-T5 sympathectomy 10 min later. Ramicotomy and sympathectomy times, and core (esophageal) and surface (left front foot) temperatures, were monitored and recorded. RESULTS: The procedure was successfully completed in all 5 animals. In all cases, the sympathetic chain remained intact. No major hemorrhage occurred. The mean operating time for T2-T5 ramicotomy from incision until transsection of the last efferent ramus was 34 min (32-40). After completion of the ramicotomy, a total T2-T5 sympathectomy was performed, with a mean duration of 7 min (4-12). Mean core temperature before the operation was 37.6°C (36.7-38.0). Mean surface temperature before the operation was 34.2°C (33.3-35.5). Ten minutes after completion of the ramicotomy, temperatures stabilized. Mean postramicotomy core temperature was 37.4°C (36.3-38) and mean postramicotomy surface temperature was 35.4°C (33.9-37). Mean postsympathectomy temperatures were: core 37.3°C (36.1-38) and surface 35.8°C (33.8-37.1). CONCLUSION: Robot-assisted thoracoscopic T2-T5 ramicotomy is feasible and effective in a porcine model.
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Robótica , Simpatectomia/métodos , Toracoscopia/métodos , Animais , Temperatura Corporal , Feminino , Modelos Animais , SuínosRESUMO
INTRODUCTION: Follicle stimulating hormone (FSH) is identified to play a role in postmenopausal disease and hypothesized to affect abdominal aortic aneurysm (AAA) onset/progression in postmenopausal women. We aimed to detect FSHR gene expression in AAA tissue and cell types involved in AAA formation. METHODS: FSH stimulation of human umbilical cord endothelial cells (HUVECs), smooth muscle cells (HUCs) and PMA-differentiated macrophages to assess gene expression of FSHR and various markers. Human macrophages activated with various stimuli were assessed for FSHR gene expression. AAA dataset, AAA tissue samples and AAA-derived smooth muscle cells (SMC) obtained from elderly female donors were assessed for FSHR gene expression. AAA-SMCs were stimulated with FSH to assess its effect on gene expression. Lastly, oxidized low-density-lipoprotein (ox-LDL) uptake and abundance of cell surface protein markers were assessed by flow cytometry after FSH stimulation of human monocytes. RESULTS: FSH stimulation showed similar levels of gene expression in HUVECs and HUCs. Only ACTA2 was downregulated in HUCs. In PMA-differentiated macrophages, gene expression of inflammation markers was unchanged after FSH stimulation. FSHR gene expression was found to be low in the AAA datasets. Female AAA-SMCs show occasional FSHR gene expression at a very low level, yet stimulation with FSH did not affect gene expression of SMC- or inflammation markers. FSH stimulation did not impact ox-LDL uptake or alter cell surface protein expression in monocytes. While FSHR gene expression was detected in human testis tissue, it was below quantification level in all other investigated cell types, even upon activation of macrophages with various stimuli. CONCLUSION: Despite previous reports, we did not detect FSHR gene expression in various extragonadal cell types, except in occasional female AAA-SMCs. No clear effect on cell activation was observed upon FSH stimulation in any cell type. Our data suggest that a direct effect of FSH in AAA-related extragonadal cells is unlikely to influence AAA.
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Aneurisma da Aorta Abdominal , Receptores do FSH , Humanos , Feminino , Masculino , Idoso , Receptores do FSH/genética , Células Endoteliais/metabolismo , Testículo/metabolismo , Hormônio Foliculoestimulante/farmacologia , Hormônio Foliculoestimulante/metabolismo , Hormônio Foliculoestimulante Humano , Aneurisma da Aorta Abdominal/genéticaRESUMO
INTRODUCTION: Thoracic endovascular aortic repair (TEVAR) is the treatment of choice for blunt thoracic aortic injury (BTAI) and has proven to be a good alternative to open surgery. TEVAR requires less operation time, has fewer complications, can be used for relatively unstable patients, and is associated with a significantly lower mortality rate. Moreover, long term follow up data demonstrate low re-intervention rates and stentgraft failure. REPORT: The case of a 21 year old man who sustained severe trauma, including a traumatic pseudoaneurysm of the descending thoracic aorta distal to the left subclavian artery in 2016, is presented. The patient was treated by TEVAR. Two years later, he presented with progressive paraplegia due to stentgraft occlusion occurring four days after a new high velocity motor vehicle accident. An axillofemoral bypass was performed to assure blood flow to the lower body. Two days later the stentgraft was removed via left thoracotomy and replaced by a Dacron graft. Gross examination showed severe thrombus formation at the proximal edge, and a thrombotic occlusion in the middle and distal third of the stent. After three months of hospitalisation the patient was discharged to a rehabilitation clinic with partial recovery of his paraplegia. As of June 2020, the patient was able to walk without assistance and his paraplegia improved with only loss of sensation of his lower legs. CONCLUSION: A serious thrombotic complication two years after TEVAR is described. Although TEVAR is the currently preferred treatment for BTAI, more research is needed to examine the mechanisms behind this thrombotic complication and to elucidate whether TEVAR is definitive treatment or a "bridge to further surgery". Smaller diameter stentgrafts, anticoagulation, regular (lifelong) follow up imaging, and prophylactic surgical conversion in (selected) patients might help to prevent this serious complication.
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OBJECTIVES: Surgical treatment of JAAs (juxtarenal aortic aneurysms) requires suprarenal aortic cross-clamping, causing temporary renal artery occlusion. We implemented a standardized protocol of hypothermic renal perfusion for all elective JAA operations. DESIGN: Retrospective study. MATERIALS AND METHODS: Over a period of 6 years, 23 consecutive patients received a 300ml bolus followed by an infusion (20ml/minute) of cold (4 degrees C) saline to each kidney during suprarenal aortic clamping. We assessed outcome in terms of rise in serum creatinine, new onset of dialysis and mortality. RESULTS: None of the patients suffered from postoperative acute renal failure and in-hospital mortality was zero. Five patients did not show any rise in serum creatinine level, whereas in the others rises were <25% in comparison with the admission level, except for one patient (38%). Postoperative rise in serum creatinine level was not related to renal ischemia time (Spearman rank correlation=0.24, p=0.27), preoperative renal function, total aortic clamping time or renal re-implantation. There were no renal complications at 6 months. CONCLUSIONS: Our results suggest that a standardized strategy to apply renal hypothermia during the ischemic period of elective JAA surgery may reduce postoperative renal failure.
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Aneurisma da Aorta Abdominal/cirurgia , Implante de Prótese Vascular/métodos , Hipotermia Induzida , Artéria Renal , Adulto , Idoso , Idoso de 80 Anos ou mais , Implante de Prótese Vascular/efeitos adversos , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Insuficiência Renal/etiologia , Insuficiência Renal/prevenção & controle , Estudos Retrospectivos , StentsRESUMO
A total of 22 genes have been identified in the carcinoembryonic antigen (CEA) gene family. The protein products of this family are highly homologous and include CEA, biliary glycoprotein, nonspecific cross-reacting antigen 50/90 (NCA 50/90), NCA 95, and pregnancy-specific beta-glycoprotein. We used a monoclonal antibody with high affinity to develop a specific enzyme-linked immunosorbent assay (ELISA) method for NCA 50/90 in serum and plasma. Our calibrators were based on affinity-purified recombinant protein from a baculovirus expression system. No significant reactivity with purified CEA, recombinant NCA 95, or recombinant biliary glycoprotein was found by Western blot analysis or in the ELISA method. Only 1 of 15 sera from pregnant women (chorionic gonadotropin > 1000 ng/ml) was positive in the NCA 50/90 ELISA, suggesting that this method does not detect pregnancy-specific glycoprotein. A cutoff value of 18 ng/ml was established based on the 95% value of serum and plasma from 147 healthy volunteers. Only 3 of 31 serum and plasma samples from patients with clinically inactive breast cancer were elevated above the cutoff value, but 44% of 136 samples from patients with clinically active breast cancer were positive. NCA 50/90 measurements were elevated in 7 of 25 patients with active breast cancer whose CEA and CA 15-3 values were below cutoff, and NCA 50/90 values do not correlate with CEA in breast cancer. In addition, we found sensitivities of 70, 39, and 42% for lung cancer, colon cancer, and leukemia, respectively. The sensitivity for non-small cell lung cancer was 85%, however, compared to 50% for small cell lung cancer. Serum from leukemia patients showed an overall sensitivity of 43%, but 71% (10 of 14) sera from patients with chronic myelogenous leukemia were positive compared to, for example, chronic lymphocytic leukemia where 0 of 7 sera had NCA 50/90 values above the cutoff. These studies suggest that NCA 50/90 may have clinical utility in the management of patients with a variety of cancers.
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Antígenos de Diferenciação Mielomonocítica/sangue , Antígenos de Neoplasias/sangue , Neoplasias da Mama/sangue , Moléculas de Adesão Celular , Neoplasias do Colo/sangue , Neoplasias Pulmonares/sangue , Glicoproteínas de Membrana/sangue , Animais , Anticorpos Monoclonais/metabolismo , Afinidade de Anticorpos , Especificidade de Anticorpos , Antígenos de Neoplasias/análise , Antígenos de Superfície/sangue , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/sangue , Western Blotting , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Cinética , Glicoproteínas de Membrana/análise , Camundongos , Camundongos Endogâmicos BALB C , Valores de ReferênciaRESUMO
Latex reagents for HCG obtained from commercially available pregnancy test kits were adapted for use on Instrumentation Laboratory's Multistat III Plus centrifugal analyzer. The clearance rate of an agglutinating reaction mixture can be measured by absorbance over a time period of 15 min. The automated system has a sensitivity of less than 5 mIU HCG/ml in buffer or urine with a range of up to 100 mIU HCG/ml. Statistical analyses on urine samples indicated CVs of between 7.6% and 10.7% for within-run precision and between 6.8% and 10.8% for between-run precision. The correlation between the centrifugal latex agglutination method and two commercially available RIAs was found to be about 87%.
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Gonadotropina Coriônica/análise , Testes de Fixação do Látex/métodos , Anticorpos/análise , Centrifugação , Gonadotropina Coriônica/imunologia , Feminino , Humanos , Concentração de Íons de Hidrogênio , Cinética , Nefelometria e Turbidimetria/métodos , Tamanho da Partícula , Radioimunoensaio/métodos , TemperaturaRESUMO
A sandwich capture ELISA technique is presented for detection of recombinant proteins sharing a common affinity domain or reagents such as antibodies that bind to these proteins. An activated carrier protein (BSA) is modified with reduced glutathione (GT), forming an affinity capture reagent for glutathione-S-transferase (GST) and recombinant fusion proteins bearing the GST moiety. GT-BSA is immobilized on microtiter plates, and a sandwich is formed consisting of the recombinant fusion protein, reactive antibodies, and detection antibodies. An example is given that demonstrates that this format yields equivalent results to a conventional ELISA test with a panel of newly diagnosed diabetic sera reacting with an islet cell autoantigen.
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Ensaio de Imunoadsorção Enzimática/métodos , Glutationa Transferase/análise , Proteínas Recombinantes de Fusão/análise , Cromatografia de Afinidade , Clonagem Molecular/métodos , Humanos , Ilhotas PancreáticasRESUMO
The activation of stress-activated protein (SAP) kinase may lead to an induction of apoptosis that is responsible for part of the cardiomyocyte death in reperfusion injury. The objective of the present study was to investigate the mechanism by which magnesium tanshinoate B (MTB), a bioactive compound isolated from Danshen, prevents apoptosis in cardiomyocytes in the ischemic/reperfused heart. Isolated adult rat hearts were perfused by the Langendorff mode with medium containing MTB prior to the induction of normothermic global ischemia. At the end of the 30-min ischemic period, the heart was reperfused with the same medium with or without MTB for an additional 20 min. In the MTB-treated ischemic/reperfused heart, the number of apoptotic nuclei was reduced by 2.5-fold in comparison to that in untreated ischemic/reperfused controls [23 +/- 4 vs 57 +/- 7 (mean +/- SD) TUNEL-positive cells, respectively, N = 3-4, P < 0.001]. SAP kinase activity was elevated 1.7-fold in ischemic/reperfused rat hearts [35.6 +/- 3.8 vs 21.2 +/- 3.3 (control) (mean +/- SEM) relative densitometric units, N = 4-6, P < 0.05]. Treatment with MTB abolished this elevation in SAP kinase activity (25.0 +/- 5.2 relative densitometric units), which was also decreased by 40% in the nucleus. When the heart was subjected to ischemia alone, there was no significant change in SAP kinase activity in the presence or absence of MTB. MTB did not appear to affect the p38 mitogen-activated protein kinase activity in this model system. In conclusion, MTB was shown to have cardioprotective activity against apoptosis, probably through the inhibition of SAP kinase activity.
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Apoptose , Magnésio/farmacologia , Proteínas Quinases Ativadas por Mitógeno/antagonistas & inibidores , Isquemia Miocárdica/enzimologia , Fenantrolinas/farmacologia , Substâncias Protetoras/farmacologia , Animais , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Núcleo Celular/metabolismo , Coração/efeitos dos fármacos , Técnicas In Vitro , Magnésio/uso terapêutico , Masculino , Proteína Quinase 8 Ativada por Mitógeno , Proteínas Quinases Ativadas por Mitógeno/efeitos dos fármacos , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Isquemia Miocárdica/patologia , Isquemia Miocárdica/prevenção & controle , Reperfusão Miocárdica , Miocárdio/enzimologia , Fenantrolinas/uso terapêutico , Substâncias Protetoras/uso terapêutico , Ratos , Ratos Sprague-Dawley , Estatística como Assunto , Frações Subcelulares , Proteínas Quinases p38 Ativadas por MitógenoRESUMO
OBJECTIVES: Prostate-specific antigen (PSA) is the most useful of all tumor markers. Although the sensitivity is impressive, low specificity results in a lack of cancer detection in a significant proportion of patients undergoing prostate biopsy. Several recent studies have addressed the need for improved specificity. Of all these approaches, the free/total PSA ratio appears to be the most promising. Given that most circulating PSA is complexed to alpha1-antichymotrypsin, and that this moiety represents a greater proportion of the total PSA in those men with carcinoma, we set out to determine whether complexed PSA would improve specificity in the detection of men with prostate cancer. METHODS: Archival sera were obtained from 300 men, 75 of whom had biopsy-proved prostate cancer. All sera had been previously stored at -70 degrees C for variable periods. An investigative assay for complexed PSA (Bayer) was used. The Tandem-R free and total PSA assays (Hybritech) were used according to the manufacturer's recommendations. RESULTS: Among all patients, specificities for the total PSA, free/total PSA, and complexed PSA alone were 21.8%, 15.6%, and 26.7%, respectively, at cutoffs yielding 95% sensitivity. Similar equivalence or superior performance, in terms of specificity relative to the free/total PSA ratio, was seen at other sensitivity thresholds and other total PSA ranges. CONCLUSIONS: Complexed PSA alone performs better than total PSA or the free/total PSA ratio and obviates the need for a second analyte determination. We believe this marker may offer significant enhancement in PSA testing with significant economic advantages.
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Antígeno Prostático Específico/sangue , Neoplasias da Próstata/sangue , Neoplasias da Próstata/diagnóstico , Idoso , Idoso de 80 Anos ou mais , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Sensibilidade e Especificidade , Fatores de TempoRESUMO
Clomiphene citrate (CC) was given to 24 men with idiopathic oligospermia at a daily dose of 25 mg (10 subjects) or 50 mg (14 subjects). Sperm concentration increased slightly after CC treatment in both groups. Sperm motility and morphology remained unchanged. Spermatozoal fertilizing capacity as assessed by the zona-free hamster ova penetration test showed no significant change throughout the treatment period. Two pregnancies occurred in the partners of the subjects treated with 50 mg CC/day, but none occurred in the other group. We conclude that oral administration of CC does not improve fertilizing capacity of sperm as measured by the zona-free hamster ova penetration test in idiopathic oligospermia.
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Clomifeno/uso terapêutico , Oligospermia/tratamento farmacológico , Motilidade dos Espermatozoides/efeitos dos fármacos , Interações Espermatozoide-Óvulo/efeitos dos fármacos , Adulto , Animais , Cricetinae , Feminino , Humanos , Masculino , Oligospermia/fisiopatologia , Contagem de Espermatozoides , Fatores de TempoRESUMO
Forty-six subfertile men with idiopathic oligospermia were randomly assigned to 6 months of treatment with a placebo, clomiphene citrate (25 or 50 mg/day), mesterolone (100 mg/day), or pentoxifylline (1200 mg/day) or 4 months of testosterone enanthate treatment (100 or 250 mg on alternate weeks). Treatment with the placebo, mesterolone, pentoxifylline, and testosterone rebound therapy did not result in a significant increase in the mean sperm concentration or pregnancy in the partners. Clomiphene citrate at both dosages significantly increased the mean sperm concentration without improving sperm motility or morphology during the 6-month treatment period. Pregnancy rates of 36.4% and 22.2% were observed in partners of men receiving clomiphene citrate 25 mg/day and 50 mg/day, respectively. This study also illustrates the difficulties in identifying suitable patients for and assessing the efficacy of different treatment regimens.
Assuntos
Clomifeno/uso terapêutico , Di-Hidrotestosterona/análogos & derivados , Mesterolona/uso terapêutico , Oligospermia/tratamento farmacológico , Pentoxifilina/uso terapêutico , Testosterona/uso terapêutico , Teobromina/análogos & derivados , Adulto , Hormônio Foliculoestimulante/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Oligospermia/patologia , Placebos , Testículo/patologiaRESUMO
PURPOSE: The normal human cornea flattens peripherally. The amount of flattening, or asphericity, has traditionally been calculated from multiple keratometric measurements. We devised a mathematical technique for determining asphericity from computed corneal topography. We then determined whether asphericity affects the refractive outcome of radial keratotomy. METHODS: One eye each of 41 patients who underwent four- or eight-incision radial keratotomy and preoperative computed corneal topography was identified retrospectively and analyzed. The asphericity, P, of each cornea was calculated by fitting Baker's equation (y2 = 2r0x-Px2) to each meridian of the topographic map. For each patient, we calculated the difference between the refractive outcome in diopters for radial keratotomy and the prediction of a quadratic least-squares best-fit model involving optical zone size and age. RESULTS: Aspericity could be calculated from the topographic maps in all 41 patients and ranged from 0.33 to 1.28, with mean +/- S.D. of 0.82 +/- 0.21. Aphericity varied among the meridians of a cornea, with an average standard deviation among meridians of 0.17. No statistical correlation was found between calculated asphericity and refractive outcome. CONCLUSIONS: Corneal asphericity can be calculated from corneal topographic maps. Asphericity is not constant in the different meridians of a normal cornea. Corneal asphericity is not useful in predicting the refractive outcome of radial keratotomy.
Assuntos
Córnea/anatomia & histologia , Córnea/cirurgia , Ceratotomia Radial , Procedimentos Cirúrgicos Refrativos , Adulto , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Masculino , Pessoa de Meia-Idade , Erros de Refração/fisiopatologia , Estudos Retrospectivos , Resultado do Tratamento , Acuidade VisualRESUMO
Danshen, a Chinese herbal medicine has been widely used for the treatment of cardiovascular diseases. Magnesium tanshinoate B (MTB) is an active compound purified from Danshen. The objective of this study was to investigate the effect of MTB on the susceptibility of low density lipoproteins (LDL) to oxidative modification as well as on the accumulation of lipids in THP-1 derived macrophages. Aliquots of LDL were incubated with copper sulfate in the absence or presence of MTB. The degrees of oxidative modification of LDL were assessed by examining the relative gel electrophoretic mobility, by measuring the amount of thiobarbituric acid reactive substances (TBARS), and by continuous monitoring of the formation of conjugated dienes upon the increase in absorbency at 234 nm. MTB at concentrations of 1-10 microM significantly inhibited oxidative modification of LDL. Such inhibitory effect resulted in a decrease in the uptake of LDL by THP-1 derived macrophages. Taken together, these results clearly demonstrate that MTB inhibits oxidative modification of LDL and hence prevents the uptake of LDL by cultured macrophages. Such effect may be therapeutically relevant in protecting cells from lipid peroxidation in vascular disorders.
Assuntos
Antioxidantes/farmacologia , Medicamentos de Ervas Chinesas/farmacologia , Lipoproteínas LDL/metabolismo , Magnésio/farmacologia , Fenantrolinas/farmacologia , Adulto , Linhagem Celular , Sulfato de Cobre/farmacologia , Humanos , Metabolismo dos Lipídeos , Lipoproteínas LDL/farmacocinética , Macrófagos/metabolismo , Masculino , Monócitos/efeitos dos fármacos , Oxirredução/efeitos dos fármacos , Acetato de Tetradecanoilforbol/farmacologiaRESUMO
A method of combining capillary electrophoresis (CE) using a surfactant-modified capillary with matrix-assisted laser desorption ionization (MALDI) mass spectrometry (MS) is described for protein analysis. The CE-MALDI-MS coupling is based on CE fraction collection of nanoliter volume samples in less than 5 microl of dilute acid. This offline coupling does not require any special instrumentation and can be readily performed with commercial instruments. Protein adsorption during CE separation is prevented by coating the capillary with the surfactant didodecyldimethylammonium bromide. This surfactant binds strongly with the capillary wall, hence it does not desorb significantly to interfere with subsequent MALDI-MS analysis. It is shown that the use of a dilute acid for CE fraction collection is advantageous in lowering the detection limit of MALDI-MS compared to using an electrophoretic buffer. The detection limit for proteins such as cytochrome c is 23 fmol injected for CE, or 1.2 fmol spotted for MALDI-MS. This sensitivity is comparable to alternative CE-MALDI-MS coupling techniques using direct CE sample deposition on the MALDI target. In addition, the fraction collection approach has the advantage of allowing multiple reactions to be carried out on the fractioned sample. These reactions are very important in protein identification and structure analysis.
Assuntos
Grupo dos Citocromos c/análise , Eletroforese Capilar/instrumentação , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/métodos , Tensoativos/química , Reprodutibilidade dos Testes , Sensibilidade e EspecificidadeRESUMO
UNLABELLED: The clinical utility of automated serum HER-2/neu measurements in breast cancer run on the Bayer random analyzer Immuno 1 was analyzed in several steps: [a] The reference interval was determined for 242 normal healthy pre- and postmenopausal females. [b] The clinical specificity of serum HER-2/neu to separate healthy controls from 210 patients with non-malignant breast--and non-breast diseases was calculated. [c] The clinical sensitivity of cross-sectional serum HER-2/neu values for 204 patients (pts) with stage I-IV breast cancer was established. [d] Specimens from 103 stage IV breast cancer pts were tested for their parallel between serial serum HER-2/neu results and disease course. RESULTS: [a] The value of 13.03 ng/ml exceeded 95% of the results from the healthy female population. Based on the mean +2 standard deviations value of 14.7 ng/dl, the upper limit of normal was established at 15 ng/ml. [b] The specificity for benign breast diseases and other benign non-breast diseases was 98.0% and 94.6%, respectively. [c] The correlation of increased serum HER-2/neu levels and stage of breast cancer revealed the best sensitivity of 40% for stage IV disease. [4] Thirty-eight (36.9%) of 103 stage IV patients had initial HER-2/neu values > 15 ng/ml, 33 of whom showed longitudinal HER-2/neu concentrations which paralleled the clinical course of the disease giving a sensitivity of 86.8%.