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1.
World J Urol ; 35(6): 913-919, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-27734132

RESUMO

PURPOSE: To evaluate stool habits and associated quality of life (QoL) in a matched pair analysis of patients who underwent continent cutaneous diversion using the ileocecal segment [Mainz pouch I (MzPI)] with an intussuscepted ileal nipple as efferent segment with those receiving an ileal conduit (IC) after radical cystectomy. METHODS: We identified 250 patients who underwent radical cystectomy and urinary diversion (UD) with either MzPI with an ileal nipple or IC in our database. A detailed history of stool habits using the modified Wexner score was obtained, and questions addressing general lifestyle, comparison of symptom differences before and after surgery considering bowel function as well as bowel-associated QoL were assessed. RESULTS: Forty-five age- and sex-matched pairs could be compared. Overall, stool incontinence (p = 0.481) and the Wexner score (p = 0.464) revealed no differences between both groups. However, patients with MzPI as compared to those with IC had significant higher rates of stool frequency (53 vs 31 %), softer stool consistencies (60 vs 13 %), diarrhea (62 vs 20 %) and a lower rate of constipation (4 vs 22 %). Patients with MzPI had a trend toward lower bowel-associated QoL compared with patients with IC. Similarly, the MzPI group reported a significantly impaired overall postoperative QoL (51 %) compared to the IC group (29 %) (p = 0.024). CONCLUSIONS: Patients following UD by MzPI have an increased stool frequency and softer stool consistency. However, there is no difference between both groups in terms of de novo stool incontinence. Change in bowel habits should be part of preoperative informed consent in any kind of UD. Careful patient selection is of paramount importance.


Assuntos
Qualidade de Vida , Neoplasias da Bexiga Urinária/cirurgia , Derivação Urinária/métodos , Derivação Urinária/psicologia , Coletores de Urina , Adulto , Idoso , Estudos de Casos e Controles , Constipação Intestinal/epidemiologia , Constipação Intestinal/fisiopatologia , Cistectomia/efeitos adversos , Cistectomia/métodos , Incontinência Fecal/epidemiologia , Incontinência Fecal/fisiopatologia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Medição de Risco , Inquéritos e Questionários , Resultado do Tratamento , Neoplasias da Bexiga Urinária/patologia
2.
Antimicrob Agents Chemother ; 57(7): 2996-3002, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23587954

RESUMO

The use of cardiopulmonary bypass (CPB) during cardiac surgery causes regional ventilation-perfusion mismatch, contributing to regional disturbances in antibiotic penetration into lung tissue. Ventilation-perfusion mismatch is associated with postoperative pneumonia, a frequent and devastating complication after cardiac surgery. In this prospective clinical animal study, we performed in vivo microdialysis to determine the effect of CPB on regional penetration of levofloxacin (LVX) into lung tissue. Six pigs underwent surgery with CPB (CPB group), and another six pigs underwent surgery without CPB (off-pump coronary artery bypass grafting; OPCAB group). LVX (750 mg) was administered intravenously to all pigs immediately after surgery. For regional measurements of LVX in pulmonary concentrations, microdialysis probes were inserted in both lungs of each pig. Pigs were placed in the right lateral position. Time versus concentration profiles of unbound LVX were measured in the upper and lower lung tissue and plasma in all pigs. In all pigs, maximum concentrations (Cmax) of LVX were significantly lower in the upper lung than in the lower lung (OPCAB, P = 0.035; CPB, P < 0.001). Median Cmax of LVX showed a significant difference in the upper versus lower lung in the CPB group (P < 0.05). No significant difference was found in the median Cmax of LVX in the upper and the lower lung in the OPCAB group (P = 0.32). Our data indicate that CPB affects perioperative regional antibiotic penetration into lung tissue. Common clinical antibiotic dosing schemes should be reevaluated in patients undergoing coronary artery bypass grafting with CPB.


Assuntos
Antibacterianos/farmacocinética , Ponte Cardiopulmonar , Levofloxacino/farmacocinética , Pulmão/metabolismo , Animais , Antibacterianos/análise , Feminino , Levofloxacino/análise , Pulmão/irrigação sanguínea , Pulmão/efeitos dos fármacos , Masculino , Microdiálise , Suínos
3.
Br J Anaesth ; 109(5): 790-6, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-22831890

RESUMO

BACKGROUND: Arterial catheterization is painful and is associated with patient stress and anxiety. Analgesia is usually provided by subcutaneous injection of local anaesthetic. An alternative is topical anaesthesia, such as Rapydan which is a novel topical anaesthetic patch containing 70 mg each of lidocaine and tetracaine. We therefore tested the hypothesis that Rapydan patch analgesia is non-inferior to subcutaneous local anaesthetic. METHODS: Ninety patients undergoing elective major cardiac surgery were included in this prospective, double-blind clinical trial. Patients were randomly assigned to receive either a lidocaine/tetracaine patch, followed by subcutaneous injection 0.5 ml of normal saline solution, or placebo patch with subsequent subcutaneous injection of 0.5 ml of lidocaine 1%. Pain during arterial catheterization using 100-mm-long visual analogue scale (VAS) was the primary outcome. Other outcomes were pain during anaesthetic/saline injection and plasma tetracaine concentrations. RESULTS: VAS pain scores during arterial puncture were comparable in both groups and Rapydan was non-inferior to subcutaneous lidocaine. Pain scores at the time of subcutaneous injection were significantly lower (better) in patients assigned to the lidocaine/tetracaine patch than to lidocaine (P=0.001). Plasma tetracaine concentrations never exceeded the detection limit of 25 ng ml(-1) at any time in any patient. CONCLUSIONS: Both the lidocaine/tetracaine patch and subcutaneous injection of lidocaine provided comparable pain control during arterial catheter insertion. Subcutaneous lidocaine caused discomfort during injection, whereas the lidocaine/tetracaine patch required placement 20 min before the procedure. Given adequate time, the patch provided better overall analgesia by obviating the need for subcutaneous infiltration.


Assuntos
Anestésicos Locais/administração & dosagem , Cateterismo Venoso Central/efeitos adversos , Lidocaína/administração & dosagem , Dor/prevenção & controle , Tetracaína/administração & dosagem , Adesivo Transdérmico , Administração Cutânea , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anestesia Local/métodos , Método Duplo-Cego , Combinação de Medicamentos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Dor/etiologia , Estudos Prospectivos , Adulto Jovem
4.
Science ; 288(5469): 1193-8, 2000 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-10817986

RESUMO

During late 1999/early 2000, the solid state imaging experiment on the Galileo spacecraft returned more than 100 high-resolution (5 to 500 meters per pixel) images of volcanically active Io. We observed an active lava lake, an active curtain of lava, active lava flows, calderas, mountains, plateaus, and plains. Several of the sulfur dioxide-rich plumes are erupting from distal flows, rather than from the source of silicate lava (caldera or fissure, often with red pyroclastic deposits). Most of the active flows in equatorial regions are being emplaced slowly beneath insulated crust, but rapidly emplaced channelized flows are also found at all latitudes. There is no evidence for high-viscosity lava, but some bright flows may consist of sulfur rather than mafic silicates. The mountains, plateaus, and calderas are strongly influenced by tectonics and gravitational collapse. Sapping channels and scarps suggest that many portions of the upper approximately 1 kilometer are rich in volatiles.


Assuntos
Meio Ambiente Extraterreno , Júpiter , Voo Espacial , Erupções Vulcânicas , Fenômenos Geológicos , Geologia , Aumento da Imagem , Espectrofotometria Infravermelho
5.
J Physiol Pharmacol ; 69(3)2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30279307

RESUMO

Turmeric is a yellowish orange spice, widely used in Asian cuisine and obtained from the rhizome of Curcuma longa. It is a mixture of three curcuminoids namely, curcumin, demethoxycurcumin and bisdemethoxycurcumin. Turmeric has been used as a medicinal substance since ancient times for respiratory and gastrointestinal problems. The aim of the present study was to investigate which curcuminoid contributes to the observed pharmacological activities, all three curcuminoids, the major curcumin metabolite tetrahydrocurcumin, and the non-enzymatic curcumin hydrolysis products ferulic acid, feruloyl methane and vanillin were analyzed for spasmolytic, inotropic and chronotropic activity. Furthermore, their uptake in respective tissue samples was also investigated and correlated with activity. Spasmolytic activity was determined in guinea pig ileum, aorta and pulmonary artery. Inotropic and chronotropic activity was determined on guinea pig papillary muscles and right atrium respectively, while tissue uptake was quantified by using high-performance liquid chromatography (HPLC). All the curcuminoids exhibited significant spasmolytic activity with highest EC50 values for bisdemethoxycurcumin (5.8 ± 0.6 µM) followed by curcumin (12.9 ± 0.7 µM), demethoxycurcumin (16.8 ± 3 µM) and tetrahydrocurcumin (22.9 ± 1.5 µM). While only demethoxycurcumin was able to significantly relax the pulmonary artery with EC50 value of 15.78 ± 0.85 µM. All three curcuminoids showed mild negative chronotropic effects in the isolated right atrium; tetrahydrocurcumin demonstrated no activity. Curcumin and bisdemethoxycurcumin also showed mild positive inotropic effect whereas demethoxycurcumin and tetrahydrocurcumin exhibited weak negative inotropic one. Interestingly, ferulic acid, feruloyl methane and vanillin demonstrated no pharmacologicical activity at all in the various isolated organs. All three curcuminoids and tetrahydrocurcumin showed high uptake into the various tissues where concentrations correlated with pharmacological activity. The results indicate pronounced differences in the in vitro pharmacological activities of curcumin, demethoxycurcumin, bisdemethoxycurcumin and tetrahydrocurcumin which have to be considered in humans after per-oral intake of turmeric powder.


Assuntos
Cardiotônicos/farmacologia , Curcumina/análogos & derivados , Curcumina/farmacologia , Parassimpatolíticos/farmacologia , Vasodilatadores/farmacologia , Animais , Aorta/efeitos dos fármacos , Aorta/fisiologia , Função Atrial/efeitos dos fármacos , Curcuma , Feminino , Cobaias , Átrios do Coração/efeitos dos fármacos , Frequência Cardíaca/efeitos dos fármacos , Íleo/efeitos dos fármacos , Íleo/fisiologia , Técnicas In Vitro , Masculino , Músculos Papilares/efeitos dos fármacos , Músculos Papilares/fisiologia , Artéria Pulmonar/efeitos dos fármacos , Artéria Pulmonar/fisiologia
6.
J Phys Chem B ; 111(29): 8572-81, 2007 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-17461569

RESUMO

In this work, the lateral mobility of polyelectrolyte multilayers was investigated by means of the fluorescence recovery after photobleaching (FRAP) technique, with special attention to the effect of relevant parameters during and after preparation. Different polyelectrolytes with respect to charge density, stiffness, and hydrophilicity were compared. From the experimental results emerged that the density of charged sites along the polymer is the most important parameter controlling the formation of polymer complexes. At higher charge density, more complexes are formed, and the diffusion coefficient decreases. It was observed that the intrinsic backbone stiffness reduces the interpenetration of polyelectrolyte layers and the formation of complexes promoting the lateral mobility. In addition, the lateral mobility increases with increasing ionic strength and with decreasing hydration shell of the added anion in the polyelectrolyte solution. The effect of heating or annealing in electrolyte solution after preparation was also investigated along with the embedding of the probing layer at controlled distances to the multilayer surface.

7.
J Phys Chem B ; 111(29): 8649-54, 2007 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-17608514

RESUMO

The flocculation behaviors of three series of polycations with narrow molecular weight distributions carrying hydrophobic substituents on their backbones [poly(N-vinylbenzyl-N,N,N-trimethylammonium chloride), poly(N-vinylbenzyl-N,N-dimethyl-N-butylammonium chloride), and poly(N-vinylbenzylpyridinium chloride)] were investigated in dispersions of monodisperse polystyrene latexes and kaolin. Apparently, the charge density of the polycations decreases with increasing substituent hydrophobicity and increasing molecular weight of the polyelectrolytes. The necessary amount of flocculant for phase separation in dispersions with high substrate surface charge densities increases with increasing hydrophobicity of the polyelectrolyte. Nevertheless, the introduction of hydrophobic functionalities is beneficial, resulting in a substantial broadening of the range between the minimum and maximum amounts of flocculant necessary for efficient flocculation (flocculation window). An increase in ionic strength supports this effect. When the substrate has a low charge density, the hydrophobic interactions play a much more significant role in the flocculation process. Here, the minimum efficient doses remained the same for all three polyelectrolytes investigated, but the width of the flocculation window increased as the polycation hydrophobicity and the molecular weight increased. The necessary amount of flocculant increased with an increase in particle size at constant solid content of the dispersion, as well as with a decreasing number of particles at a constant particle size.

8.
Nucleosides Nucleotides Nucleic Acids ; 25(9-11): 1013-7, 2006.
Artigo em Inglês | MEDLINE | ID: mdl-17065056

RESUMO

Resveratrol (3,4',5-trihydroxystilbene, RV) exerts remarkable cytostatic and cytotoxic effects against a multitude of human cancer cell lines. Since the introduction of additional hydroxyl groups was supposed to increase the biological activity of RV, we have synthesized a number of polyhydroxylated stilbene analogues as potential antitumor agents. In this study, the activity of 3,3',4,4',5,5'-hexahydroxystilbene (M8) was investigated in HL-60 human promyelocytic leukemia cells. Employing a growth inhibition assay, incubation with M8 and RV resulted in IC50 values of 6.25 and 12 microM, respectively. Using a specific Hoechst/propidium iodide double staining method, we found that M8 was able to induce apoptosis in concentrations significantly lower than those of RV. In addition, M8 arrested cells in the S phase and totally depleted cells in the G2-M phase of the cell cycle (143% and 0% of control after treatment with 12.5 microM M8, respectively). We therefore believe that this promising agent deserves further preclinical and in vivo testing.


Assuntos
Antineoplásicos/farmacologia , Ensaios de Seleção de Medicamentos Antitumorais , Leucemia Promielocítica Aguda/tratamento farmacológico , Pirogalol/análogos & derivados , Estilbenos/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bisbenzimidazol/farmacologia , Ciclo Celular/efeitos dos fármacos , Citarabina/administração & dosagem , Relação Dose-Resposta a Droga , Sinergismo Farmacológico , Corantes Fluorescentes/farmacologia , Células HL-60 , Humanos , Concentração Inibidora 50 , Propídio/farmacologia , Pirogalol/farmacologia
9.
Nucleosides Nucleotides Nucleic Acids ; 25(9-11): 1019-24, 2006.
Artigo em Inglês | MEDLINE | ID: mdl-17065057

RESUMO

Resveratrol (RV), a naturally occurring stilbene derivative, is a potent free radical scavenger causing a number of biochemical and antineoplastic effects. It was shown to induce differentiation and apoptosis in leukemia cells and was also identified as an inhibitor of ribonucleotide reductase (RR), a key enzyme of DNA synthesis. In this study, we report about the biochemical effects of RV in HL-60 human promyelocytic leukemia cells. RV effectively inhibited in situ RR activity. Furthermore, incubation of HL-60 cells with RV significantly decreased intracellular dCTP, dTTP, dATP and dGTP concentrations. In growth inhibition and clonogenic assays, RV acted synergistically with both Ara-C and tiazofurin in HL-60 cells. We conclude that RV could become a viable candidate as one compound in the combination chemotherapy of leukemia and therefore deserves further in vitro and in vivo testing.


Assuntos
Citarabina/administração & dosagem , Sinergismo Farmacológico , Leucemia Promielocítica Aguda/tratamento farmacológico , Ribavirina/análogos & derivados , Estilbenos/administração & dosagem , Antimetabólitos Antineoplásicos/administração & dosagem , Antineoplásicos Fitogênicos/administração & dosagem , Apoptose , Proliferação de Células/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Sequestradores de Radicais Livres , Radicais Livres , Células HL-60 , Humanos , Resveratrol , Ribavirina/administração & dosagem
10.
Eur J Cancer ; 40(7): 998-1005, 2004 May.
Artigo em Inglês | MEDLINE | ID: mdl-15093574

RESUMO

To study the role of radiotherapy and tamoxifen after breast-conserving surgery (BCS) in patients with a favourable prognosis, a clinical trial was initiated by the German Breast Cancer Study Group. Between 1991 and 1998, 361 patients (pT1pN0M0, aged 45-75 years, receptor positive, grade I-II) were randomised to radiotherapy (yes/no) and tamoxifen for 2 years (yes/no) in a 2x2 factorial design; the exclusion of seven centres (14 patients) left 347 patients in the analysis. After a median follow-up of 5.9 years, 77 events concerning event-free survival have been observed. Since a strong interactive effect between radiotherapy and tamoxifen has been established, the results are presented in terms of the treatment effects for all four treatment groups separately. Mainly due to the presence of local recurrences, the event rate was about three times higher in the group with BCS only than in the other three groups. No difference could be established between the four treatment groups for distant disease-free survival rates. It is concluded that even in patients with a favourable prognosis, the avoidance of radiotherapy and tamoxifen after BCS increases the rate of local recurrences substantially.


Assuntos
Antineoplásicos Hormonais/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/radioterapia , Tamoxifeno/uso terapêutico , Idoso , Neoplasias da Mama/cirurgia , Terapia Combinada , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Mastectomia Segmentar/métodos , Pessoa de Meia-Idade , Resultado do Tratamento
11.
Eur J Cancer ; 35(1): 47-53, 1999 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-10211087

RESUMO

An established biochemical index for monitoring therapy in patients with metastatic breast cancer was tested prospectively in a multicentre study. The index uses two serum tumour markers--carcinoembryonic antigen (CEA) and carbohydrate antigen 15-3 (CA15-3) along with erythrocyte sedimentation rate (ESR). 67 patients treated by either endocrine or chemotherapy had CA15-3, CEA and ESR measured at diagnosis of metastases and sequentially during therapy. Two markers, CA15-3 and CEA, were measured on a further 16 patients giving a total of 83 patients who were assessable for CA15-3 and CEA. Of the patients with CA15-3, CEA and ESR measured at diagnosis of metastases 84% (56/67) had elevation of 1 or more markers. During therapy the number with elevated marker(s) rose to 96% (64/67). Changes in the markers were in line with and often pre-dated therapeutic outcome as assessed by the International Union Against Cancer (UICC) criteria both for remission and progression. Patients without elevation of markers on diagnosis subsequently showed a rise in the marker(s) at or before documented disease progression by UICC. The 3 women in whom markers were at no time significantly elevated remain in remission. The results using CA15-3 and CEA were similar but 12% less patients were assessable. CA15-3 and CEA (with and without ESR) provide an objective method to guide therapy in patients with metastatic breast cancer.


Assuntos
Antígenos Glicosídicos Associados a Tumores/sangue , Neoplasias da Mama/diagnóstico , Antígeno Carcinoembrionário/sangue , Sedimentação Sanguínea , Neoplasias da Mama/sangue , Progressão da Doença , Feminino , Humanos , Metástase Neoplásica , Estudos Prospectivos , Indução de Remissão
12.
Atherosclerosis ; 49(1): 99-108, 1983 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-6316995

RESUMO

Fifteen healthy volunteers were put on a mackerel and herring diet, consisting of a prescribed daily isocaloric regimen in a cross-over design, for 2 weeks. Eicosapentaenoic acid (EPA - C20:5, n-3) was predominantly incorporated into cholesterol esters, whereas docosahexaenoic acid (C22:6, n-3) appeared more in serum triglycerides, indicating that the function of the latter may be different from that of EPA. After mackerel ingestion, serum triglycerides, total cholesterol and lecithin cholesterol acyl transferase (LCAT) activity were significantly decreased, returning to basal levels 3 months later. Low density lipoprotein (LDL) cholesterol, high density lipoprotein (HDL) cholesterol and postheparin lipolytic activity (PHLA) remained unchanged at the end of the mackerel diet. Generally, after the herring diet the differences were minor, only LCAT activity being significantly decreased. A markedly lower systolic and diastolic blood pressure at the end of the mackerel period could be observed. After herring diet a slight diminution of blood pressure was not significant. Accordingly, plasma noradrenaline was only significantly decreased at the end of the mackerel period. Dopamine-beta-hydroxylase (DBH) activity in serum had no differences before, during and after the study. From the data presented it can be said that a mackerel diet exerts a beneficial influence on cardiovascular risk.


Assuntos
Pressão Sanguínea , Dieta , Peixes , Lipídeos/sangue , Adulto , Animais , Ésteres do Colesterol/sangue , Ácido Eicosapentaenoico , Ácidos Graxos Insaturados/sangue , Feminino , Conservação de Alimentos , Humanos , Lipoproteínas HDL/sangue , Lipoproteínas LDL/sangue , Masculino , Triglicerídeos/sangue
13.
J Cancer Res Clin Oncol ; 127(8): 495-501, 2001 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-11501749

RESUMO

PURPOSE: In this study the effect of continuous stimulation of gonadotropins on sex cord stromal tumors in the rat was examined. METHODS: Sex cord stromal tumors were induced by transplantation of ovaries under the splenic capsule of ovariectomized rats. Beginning 180 days after transplantation, these tumors were taken out and cut into several pieces, which were then retransplanted (by isotransplantation) under the splenic capsule of 80 either intact or ovariectomized rats. RESULTS: Most of the tumor grafts grew up to a median size of 0.7 cm in ovariectomized rats. However, some of the tumors recovered from recipient rats that were retransplanted with donor tumors differed significantly from the others. Characterized by a high mitotic rate, nuclear atypia, size (up to 3.8 cm) as well as growth in intact animals, these tumors were defined as malignant. They could be kept in culture and always led to the development of metastases after retransplantation into other rats. CONCLUSION: Benign sex cord stromal tumors can show malignant growth after transplantation. This study for the first time demonstrates that gonadotropins are involved in the induction of ovarian malignancies.


Assuntos
Gonadotropinas/metabolismo , Neoplasias Ovarianas/patologia , Ovário/transplante , Tumores do Estroma Gonadal e dos Cordões Sexuais/patologia , Animais , Transformação Celular Neoplásica , Progressão da Doença , Estradiol/sangue , Feminino , Hormônio Foliculoestimulante/sangue , Hormônio Luteinizante/sangue , Neoplasias Ovarianas/metabolismo , Ovariectomia , Ratos , Tumores do Estroma Gonadal e dos Cordões Sexuais/metabolismo , Fatores de Tempo , Transplante Autólogo , Transplante Isogênico
14.
J Hum Hypertens ; 4(3): 227-33, 1990 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-1972963

RESUMO

Forty-four male in-patients with mild essential hypertension were randomly allocated to three groups and put on diets supplemented with 60 ml/day of olive (n = 15), sunflowerseed (n = 15) or linseed oils (n = 14), respectively, for two weeks within a blind study. In the group receiving sunflowerseed oil an increase of linoleic acid in serum lipids could be observed, whereas arachidonic and eicosapentaenoic acids appeared unchanged in serum triglycerides and even significantly lower in cholesterol esters. The subjects ingesting the linseed oil-rich diet showed an increase of alpha-linolenic acid in serum lipids, whereas arachidonic and eicosapentaenoic acids remained unchanged in serum triglycerides. In cholesterol esters, however, arachidonic acid was significantly decreased and eicosapentaenoic acid appeared increased only to a low level of significance. In the group put on the olive oil-rich regimen only a significant fall of linoleic acid was obvious in serum triglycerides. The results might indicate a defective desaturation and elongation of linoleic and alpha-linolenic acids and, consequently, a slow formation of arachidonic and eicosapentaenoic acids in patients with mild essential hypertension, which should be considered in dietary studies. After the sunflowerseed oil-rich diet a significant decrease of total cholesterol, low density lipoprotein (LDL) cholesterol and the LDL/high density lipoprotein (HDL) cholesterol ratio was found. Systolic blood pressure during a psychophysiological stress test and urinary sodium excretion appeared significantly lower after the linoleic acid-rich diet. After the linseed oil-rich diet, in addition to total cholesterol, LDL cholesterol and the LDL/HDL cholesterol ratio, serum triglycerides and lecithin cholesterol acyl transferase (LCAT) activity were significantly depressed.(ABSTRACT TRUNCATED AT 250 WORDS)


Assuntos
Pressão Sanguínea/efeitos dos fármacos , Eicosanoides/sangue , Hipertensão/fisiopatologia , Ácidos Linoleicos/farmacologia , Ácidos Linolênicos/farmacologia , Lipídeos/sangue , Lipoproteínas/sangue , Ácidos Oleicos/farmacologia , Adolescente , Adulto , Alimentos Formulados , Humanos , Hipertensão/sangue , Ácido Linoleico , Masculino , Fosfatidilcolina-Esterol O-Aciltransferase/sangue , Distribuição Aleatória , Estresse Fisiológico , Triglicerídeos/sangue , Ácido alfa-Linolênico
15.
Oncol Res ; 8(5): 189-96, 1996.
Artigo em Inglês | MEDLINE | ID: mdl-8884811

RESUMO

5-fluorouracil (5-FU), an inhibitor of thymidylate synthase (EC 2.1.1.45), is clinically used in the treatment of several solid tumors, including colorectal, head and neck, gastric, and pancreatic cancer. The drug effectively inhibits deoxynucleoside triphosphate de novo synthesis. However, this inhibition can be circumvented by increased thymidine kinase (EC 2.7.1.21) activity. In the present study we examined the effects of 5-FU combined with azidothymidine (AZT), a competitive inhibitor of thymidine kinase in human colon tumor cells in vitro, including three 5-FU resistant cell lines. The cells were simultaneously incubated with various concentrations of 5-FU (0.015 to 150 microM) and AZT (20 to 300 microM) for 6 days. 5-FU alone yielded an IC50 of 18 microM in the parental CCL 227 cell line and IC50s of 470 and 1100 microM in the 5-FU resistant cell lines as determined by a MTT chemosensitivity assay. Addition of 100 microM AZT alone, a drug concentration that can be achieved in patients, had no effect on the growth of the cell lines examined. However, when added simultaneously with 5-FU, the IC50s of 5-FU synergistically decreased to 10 microM in the sensitive and to 360 or 760 microM in the resistant cell lines, respectively. Our results demonstrate that the combination of 5-FU with AZT synergistically inhibited the growth of 5-FU resistant cells, suggesting the use of 5-FU in combination with AZT for the treatment of 5-FU sensitive as well as resistant human colon tumors.


Assuntos
Antimetabólitos Antineoplásicos/farmacologia , Neoplasias do Colo/patologia , Fluoruracila/farmacologia , Zidovudina/farmacologia , Resistência a Medicamentos , Sinergismo Farmacológico , Humanos , Orotato Fosforribosiltransferase/metabolismo , Timidina Quinase/metabolismo , Timidina Fosforilase/metabolismo , Timidilato Sintase/metabolismo , Células Tumorais Cultivadas , Uridina Fosforilase/metabolismo
16.
Br J Ophthalmol ; 75(1): 49-52, 1991 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-1991088

RESUMO

A typical finding in dominant infantile optic atrophy (DIOA) is the variation of the phenotypic expression of the DIOA gene even within one family. It is of special interest for genetic consultation to evaluate an examination method for detecting subclinically involved patients. Seven patients of two families were examined. Three of them had the typical symptoms of DIOA: reduced visual acuity, tritan defect, temporal pallor of both optic discs, and a relative central scotoma for white test spots. In visual evoked cortical potentials (VECP) the amplitudes were reduced, and in one patient the latencies were slightly delayed and two patients considerably so. The amplitude of the negative component of the PERG was markedly reduced, while the positive component was normal. In the remaining four family members normal retinal and cortical responses were recorded under standard conditions and visual fields and colour vision (FM 100 hue) were also normal. However, static perimetry with blue test spots showed in two family members enlarged central scotomas, thus proving that they had subclinical DIOA.


Assuntos
Potenciais Evocados Visuais/fisiologia , Atrofias Ópticas Hereditárias/fisiopatologia , Campos Visuais , Adolescente , Adulto , Idoso , Percepção de Cores/fisiologia , Defeitos da Visão Cromática/diagnóstico , Eletrorretinografia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Atrofias Ópticas Hereditárias/genética , Escotoma/diagnóstico , Acuidade Visual , Testes de Campo Visual/métodos
17.
J Chromatogr A ; 894(1-2): 105-16, 2000 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-11100853

RESUMO

Capillary electrophoresis in entangled polymer solutions was applied to determine the molecular mass and polydispersity of polyelectrolytes. The separation selectivities of different polyethylene glycols as buffer additive can be correlated to their average molecular mass. A universal curve correlating the selectivity and the molecular mass could be obtained by using the instrinsic viscosity of the polyethylene glycol. The separation of poly(2-vinylpyridine) standards was compared to the separation of poly(4-vinylpyridine) standards. An indirect detection system was developed to characterize the cationic polyelectrolyte polydiallyldimethyl ammonium chloride. Various polymers with oppositely charged groups (polycarboxybetaines) were investigated with respect to structure dependence, pH dependence and molecular mass dependence of interand intramolecular association.


Assuntos
Eletrólitos/química , Eletroforese Capilar/métodos , Soluções Tampão
18.
Anticancer Res ; 22(1A): 439-43, 2002.
Artigo em Inglês | MEDLINE | ID: mdl-12017329

RESUMO

The aim of this study was to analyze the toxicity and response rate of capecitabine in patients with recurrent ovarian cancer resistant to platinum and paclitaxel. Fourteen patients were enrolled in this phase I/II protocoL Capecitabine was administered orally in a dose of 2500 mg/m2/24 hours. A single therapy cycle consisted of a 2-week treatment, followed by a 2-week treatment-free interval. Patients were eligible for response evaluation if they completed more than one cycle of capecitabine. Cessation of chemotherapy due to toxicity was necessary in two patients. Diarrhea and hand-foot syndrome were the most common side-effects. In twelve patients eligible for response, there was one complete responder (8.3%), two partial responders (16.7%) and no change in three patients (25.0%). Progression of disease occurred in six patients (50.0%). Capecitabine exhibits antitumoral activity in ovarian cancer resistant to platinum and paclitaxel and should be evaluated in further studies.


Assuntos
Antimetabólitos Antineoplásicos/uso terapêutico , Desoxicitidina/análogos & derivados , Desoxicitidina/uso terapêutico , Recidiva Local de Neoplasia/tratamento farmacológico , Neoplasias Ovarianas/tratamento farmacológico , Adulto , Idoso , Antimetabólitos Antineoplásicos/efeitos adversos , Capecitabina , Desoxicitidina/efeitos adversos , Resistência a Múltiplos Medicamentos , Feminino , Fluoruracila/análogos & derivados , Humanos , Pessoa de Meia-Idade , Compostos Organoplatínicos/farmacologia , Paclitaxel/farmacologia
19.
Anticancer Res ; 21(3B): 2005-10, 2001.
Artigo em Inglês | MEDLINE | ID: mdl-11497290

RESUMO

BACKGROUND: Despite a substantial body of epidemiological evidence, there is only a limited indication that gonadotropins and steroids have growth regulating functions in ovarian cancer. To elucidate the role of gonadotropins in regulating steroid metabolism in human ovarian cancer, we analyzed the modulation of estradiol secretion by FSH and hCG and the gonadotropic regulation of hCG secretion in vitro. Furthermore, we analyzed estradiol and hCG levels in serum and cyst fluids of patients with ovarian cancer. MATERIALS AND METHODS: OVCAR3 cells were incubated with estradiol (1, 5, 10 nM), FSH (100 microg/L) and hCG (10, 25 microg/L). Growth stimulation was evaluated by MTT assay. Estradiol was measured in the supernatant after incubation with hCG and FSH, while hCG was measured after FSH incubation. FSH, estradiol and hCG levels were measured in serum and cyst fluids of patients with ovarian cancer. RESULTS: OVCAR3 cells responded to hCG and FSH by increased estradiol secretion (p<0.001), while estradiol led to a dose-dependent stimulation of cell growth (p<0.05). 100 microg/L FSH led to a 75% decrease of hCG secretion (p<0.001). CONCLUSION: Gonadotropins stimulate estradiol secretion in ovarian cancer cells and modulate steroid dependent growth stimulation. FSH modulates hCG related growth stimulation in ovarian cancer. These results were supported by in vivo measurements in ovarian cancer patients.


Assuntos
Gonadotropinas/metabolismo , Neoplasias Ovarianas/tratamento farmacológico , Divisão Celular , Gonadotropina Coriônica/metabolismo , Relação Dose-Resposta a Droga , Feminino , Hormônio Foliculoestimulante/metabolismo , Humanos , Neoplasias Ovarianas/sangue , Fatores de Tempo , Células Tumorais Cultivadas
20.
Methods Mol Med ; 39: 485-92, 2001.
Artigo em Inglês | MEDLINE | ID: mdl-21340804

RESUMO

The IGF-1 receptor (IGF-1-R) belongs to the tyrosine kinase growth factor receptor family. It is structurally similar to, but distinct from, the insulin receptor, with which it shares a 70% homology. As expected, it crossreacts with insulin and, vice versa, insulin receptor crossreacts with IGF-1. Numerous studies suggest that IGF-1-R is very important for mitogenesis and is essential for phenotype transformation, at least in rodents (1). In particular, the IGF-1-R has been described in human breast cancer (2-4) and ovarian cancer (5) tissues and in cultured human breast cancer cell lines (6,7).

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