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1.
Crit Rev Food Sci Nutr ; 62(22): 6132-6152, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-33703975

RESUMO

To date, there exists a debate on the effect of milk added to coffee infusions/beverages concerning the nutritional quality of coffee and the functional properties of its phenolic compounds. Yet, the full nutritional quality and functional properties of a coffee beverage without a significant negative impact on its sensorial profile are highly desired by the consumers. Negative/masking, positive, and neutral effects of milk on the antioxidant activity and bioavailability of coffee phenolics (particularly, chlorogenic acids) have been reported. Some potential factors including the type and amount of milk added, type of coffee beverage, the composition of both milk (protein and fat) and coffee (phenolic compounds), preparation method, assays used to measure antioxidant properties, and sampling size may account for the various reported findings. Interactions between phenolic compounds in coffee and milk proteins could account as the main responsible aspect for the reported masking/negative impact of milk on the antioxidant activity and bioaccessibility/bioavailability of coffee bioactives. However, considering the interactions between milk components and coffee phenolics, which result in the loss of their functionality, the role of milk fat globules and the milk fat globule membrane can also be crucial, but this has not been addressed in the literature so far.HighlightsIn most cases, milk is added to the coffee beverages in several various ways.Effect of milk on the nutritional/functional properties of coffee is controversial.Enough evidence suggests negative effects of milk addition on properties of coffee.Interactions of coffee phenolics and milk proteins could account as the main aspect.The role of milk fat globules and milk fat globule membrane may also be crucial.


Assuntos
Antioxidantes , Café , Animais , Antioxidantes/análise , Bebidas , Leite/química , Proteínas do Leite/metabolismo , Fenóis/metabolismo
2.
Oper Orthop Traumatol ; 30(6): 469-478, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30310933

RESUMO

OBJECTIVE: Description of a novel technique to surgically correct (asymmetric) pectus carinatum and other chest deformities using a metal bar without fixation to the ribs. INDICATIONS: Severe thoracic deformity, extensive psychological strain, social isolation, pain and respiratory complaints. Pseudarthrosis or insufficient correction of a thoracic deformity after prior surgery. Distinctive deformities. CONTRAINDICATIONS: Acute infections. Postoperative intrathoracic scaring in revision cases can be challenging. SURGICAL TECHNIQUE: One-lung ventilation is used. Through two 3-4 cm long bilateral incisions to the thorax, an introducer is guided into the thorax under thoracoscopic supervision and then guided through an intercostal space out of the thorax again. A 1 cm presternal incision is performed and nylon threads are attached to the introducer bilaterally. Then the preshaped metal bar can be placed following the nylon threads. Once the metal bar is placed, the deformity is instantly corrected. Bilateral stabilizers are fixed with wire cerclage. Fixation on the ribs is not necessary. POSTOPERATIVE MANAGEMENT: Postoperative thorax x­ray. Intensive ventilation exercises. Implant removal after 2-3 years. RESULTS: The technique was used in 10 primary pectus carinatum or combined pectus carinatum and excavatum deformities as well as in 6 revision cases (3 female, 13 male, age 13-32 years). Follow-up ranged from 3-15 months postoperatively. Cosmetic results were excellent. Revision surgery required in 2 patients (one rib fracture and one local implant irritation).


Assuntos
Tórax em Funil/cirurgia , Pectus Carinatum , Parede Torácica , Adolescente , Adulto , Remoção de Dispositivo , Feminino , Humanos , Masculino , Pectus Carinatum/cirurgia , Reoperação , Parede Torácica/cirurgia , Resultado do Tratamento , Adulto Jovem
3.
Indian J Cancer ; 53(1): 39-42, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27146736

RESUMO

BACKGROUND: The objectives of the present study were to compare the effect of adjuvant chemotherapy for breast cancer on serum insulin levels, serum leptin levels, and body composition in early stage breast cancer patients. MATERIALS AND METHODS: 17 breast cancer patients underwent 6 cycles of docetaxel (75 mg), epirubicine (100 mg) and cyclophosphamide (500 mg) (TEC). Anthropometrical and foot-to-foot body fat analyzer BIA, serum glucose, insulin, lipids, HOMA-IR and leptin were compared pre- and post-treatment. RESULTS: There was no statistically significant weight gain after treatment; however, there was an overall trend toward weight gain (69.7 ± 9.8 kg vs 71.03 ± 9.8; P= 0.05). From baseline to the end of the study, percentage of body fat and body fat mass showed an upward trend at the end of chemotherapy (1%; 2 kg P> 0.05). Pre and post-treatment period, leptin was strongly correlated with insulin and HOMA-IR (Spearman's pre-T; r = 0.74; P <0.001, r = 0.66; P = 0.004 post-T; r = 0.549; P =0.022, r = 0.51; P =0.036, respectively). Insulin levels were significantly increased in the post-treatment period (P < 0.05). On correlation analysis, post-T insulin levels were correlated with leptin, weight, fat-mass and fat percentage (Spearman's r = 0.549; P=.022, r = 0.567; P= 0.018, r = 0.498, P= 0.042, r = 0.502; P= 0.040, respectively). DISCUSSION: High insulin and leptin levels, important factors that were previously shown to be related to breast cancer outcome, and insulin resistance may be increased in taxane based chemotherapy regimen. These data may have broad implications for diet and lifestyle strategies for the prevention and treatment of cancers.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Composição Corporal/efeitos dos fármacos , Neoplasias da Mama/sangue , Neoplasias da Mama/tratamento farmacológico , Insulina/sangue , Leptina/sangue , Neoplasias da Mama/patologia , Quimioterapia Adjuvante , Ciclofosfamida/administração & dosagem , Docetaxel , Epirubicina/administração & dosagem , Feminino , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Taxoides/administração & dosagem
4.
J BUON ; 18(3): 767-74, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24065497

RESUMO

PURPOSE: To investigate the depression and anxiety levels and the factors that affect patients receiving chemotherapy and their relatives with the Beck Depression Inventory (BDI) and State-Trait Anxiety Inventory (STAI) scoring system. METHODS: 330 patients and 330 relatives of these patients were enrolled in this study. The study forms including the questions regarding the patient demographic characteristics, BDI, and STAI were completed during face-to-face interviews by trained interviewers for the determination of the psychological status of the patients and their relatives. BDI and STAI were validated for Turkish population by studies made before. RESULTS: According to BDI scale, 96 (29.1%) patients had mild and 60 (18.2%) had severe depression. Seventy-one (21.5%) relatives had mild and 24 (7.3%) had severe depression. Anxiety evaluation was made by STAI scale and a statistical difference emerged between patients and relatives (patients: 44.93±8.8 vs relatives: 43.27±8.5, p=0.015). The depression and anxiety levels were higher in women, in people with low socio-economic level, in people having a time period between diagnosis and participation in the study longer than 6 months, and in people having relapsing disease. CONCLUSION: Since there are many emotional and psychological disorders in patients and their relatives, much attention should be paid in order to diagnose and treat their psychiatric disorders and enough information about their disease should be given.


Assuntos
Ansiedade/etiologia , Depressão/etiologia , Família/psicologia , Recidiva Local de Neoplasia/complicações , Neoplasias/complicações , Qualidade de Vida , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Ansiedade/diagnóstico , Ansiedade/psicologia , Quimiorradioterapia , Depressão/diagnóstico , Depressão/psicologia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/psicologia , Recidiva Local de Neoplasia/terapia , Estadiamento de Neoplasias , Neoplasias/psicologia , Neoplasias/terapia , Prognóstico , Psicometria , Fatores de Risco , Inquéritos e Questionários , Turquia , Adulto Jovem
5.
J BUON ; 15(3): 462-9, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-20941811

RESUMO

PURPOSE: Advanced pancreatic cancer (APC) has a poor prognosis and chemotherapy remains the primary treatment modality. Gemcitabine (GEM) and 5-fluorouracil (5-FU) are the most active drugs in the treatment of pancreatic cancer. This study evaluated the efficacy and tolerability of the combination of these agents in APC. METHODS: Forty-four patients with APC were treated with GEM and infusional 5-FU with high dose leucovorin (LV5FU2) (GEMFUFOL regimen). RESULTS: A total of 240 chemotherapy cycles were administered. The overall response rate was 27.2%, and all responses were partial. Furthermore, disease stabilization was observed in 12 patients (27.2%). Median survival time and one-year survival rate were 9 months and 36.4%, respectively. The overall grade 3 or 4 adverse events were very low and mostly hematological. CONCLUSION: GEMFUFOL is still an active regimen for the treatment of APC and has an acceptable toxicity.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Pancreáticas/tratamento farmacológico , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Desoxicitidina/administração & dosagem , Desoxicitidina/análogos & derivados , Feminino , Fluoruracila/administração & dosagem , Humanos , Leucovorina/administração & dosagem , Masculino , Pessoa de Meia-Idade , Neoplasias Pancreáticas/mortalidade , Gencitabina
6.
J BUON ; 15(3): 572-6, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-20941830

RESUMO

PURPOSE: To evaluate the levels of asymmetric dimethylarginine (ADMA), an endothelin and nitric oxide (NO) synthase inhibitor, in patients with node-positive breast cancer who had undergone surgery and in a control group including healthy individuals. The effects of taxane-based chemotherapy on endothelin-1 (ET-1) and ADMA levels in the patient group were also studied. METHODS: Body mass index (BMI), serum lipids (total cholesterol, LDL-cholesterol, HDL-cholesterol and triglycerides), ADMA and ET-1 were studied in 19 healthy individuals and in 19 patients with stage II and III, lymph node-positive breast cancer receiving taxane-based chemotherapy. RESULTS: ET-1 (34.3±12.8 vs. 13.8±4.5 pg/mL; p<0.001) and ADMA (0.87±0.18 vs. 0.68±0.24 µmol/L; p=0.024) levels were significantly higher in the breast cancer group compared to the control group. A significant reduction was noted in ET-1 (34.3±12.8 vs. 27.3±4.3 pg/mL; p=0.021) and ADMA (0.87±0.18 vs. 0.73±0.15 µmol/L; p=0.014) levels in patients following 6 cycles of adjuvant chemotherapy to baseline values. CONCLUSION: The present study demonstrated significantly higher levels of ET-1 and ADMA in the breast cancer group compared to the control group, which were reduced significantly with adjuvant taxane-based chemotherapy. It is apparent that prospective studies are needed to understand the effect of reducing ET-1 and ADMA levels on patient survival. We believe that the present study will provide guidance to relevant future studies.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Arginina/análogos & derivados , Neoplasias da Mama/tratamento farmacológico , Endotelina-1/sangue , Adulto , Idoso , Arginina/sangue , Índice de Massa Corporal , Neoplasias da Mama/sangue , Quimioterapia Adjuvante , Docetaxel , Feminino , Humanos , Lipídeos/sangue , Pessoa de Meia-Idade , Taxoides/administração & dosagem
7.
J BUON ; 14(2): 265-9, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19650177

RESUMO

PURPOSE: To investigate the complementary/alternative medicine (CAM) applications and factors affecting its use among cancer patients in the western region of Turkey. PATIENTS AND METHODS: Face-to-face interview technique was used. Patients were asked to answer a questionnaire about their socio-demographic features, their level of knowledge about the disease and CAM application features. RESULTS: 220 adult cancer patients (79 male) were evaluated. Ninety-three (42.3%) were using at least one CAM method, the most common being herbal products which were preferred by 81 (36.3%) patients. Stinging nettle (Urtica dioica) was the most commonly used herbal product. Next was nutritional support, preferred by 45 (20.3%) patients. Eighty- nine (44.5%) of 200 patients who knew the diagnosis and 4 of 20 (20%) who did not were using CAM. In the patient group with awareness of the diagnosis, CAM application was significantly higher (p=0.034). CAM applications were detected in 34 of 70 (48.5%) patients with recurrent disease while 54 of 150 (36%) patients without recurrent disease were using CAM. The CAM applications were significantly higher in the group with recurrent disease (p=0.006). Fifty-three of 103 (51.4%) patients who had advanced disease were using CAM, while only 40 of 117 (34.1%) patients with local or locally advanced disease were using it. CAM applications were significantly higher in the group with advanced disease (p=0.030). Besides, knowing the diagnosis and disease recurrence were also independent risk factors for CAM usage [odds ratio (OR(: 3.1; 95% confidence interval (CI): 1.0-9.8 and OR: 2.2; 95% CI: 1.2-4.0 respectively]. As a result, nearly half of the patients (42.3%) in this region were using at least one of the CAM methods. CONCLUSION: The severity of the disease (recurrence and dissemination) and patients' awareness of the diagnosis were the most important factors affecting the CAM applications.


Assuntos
Terapias Complementares/estatística & dados numéricos , Neoplasias/terapia , Fitoterapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Satisfação do Paciente , Prognóstico , Inquéritos e Questionários , Turquia , Adulto Jovem
9.
J BUON ; 13(3): 421-4, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-18979560

RESUMO

The frequency of new neoplastic diseases among patients cured of testicular cancer is higher than in normal population. For these patients, synchronous occurrence of multiple neoplasms is not common. Also, less than 1% of all cases of breast cancer occur in males. We present herein a case having both breast and concurrent pancreatic cancer after being effectively treated for testicular cancer. To the best of our knowledge, this is the first case of synchronous breast and pancreatic cancer in a male patient following testicular cancer. Second cancer is the most severe long-term complication of chemotherapy or radiotherapy for patients with testicular cancer and the possibility of multiple cancers has to be taken into consideration when multiple lesions are present.


Assuntos
Neoplasias da Mama Masculina/patologia , Carcinoma Ductal de Mama/patologia , Neoplasias Primárias Múltiplas/patologia , Neoplasias Pancreáticas/patologia , Neoplasias Testiculares/diagnóstico , Neoplasias da Mama Masculina/cirurgia , Carcinoma Ductal de Mama/cirurgia , Evolução Fatal , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Primárias Múltiplas/terapia , Neoplasias Pancreáticas/terapia , Tomografia por Emissão de Pósitrons , Neoplasias Testiculares/terapia
10.
Surg Endosc ; 22(4): 1008-13, 2008 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-17763904

RESUMO

BACKGROUND: The reduction in peritoneal fibrinolysis is believed to be the pathogenetic mechanism of adhesion formation. The general conclusion based on previous clinical and experimental studies is that laparoscopic procedures produce less adhesion formation. The association between this beneficial effect of laparoscopic cholecystectomy and peritoneal fibrinolytic changes is not clear. Therefore, the authors aimed to compare the effects of open and laparoscopic cholecystectomy on peritoneal fibrinolysis. For this purpose, fibrinolytic parameters in peritoneal fluid were investigated 24 h after laparoscopic and open cholecystectomies. METHODS: In a prospective clinical study, peritoneal fluid was sampled via a drain 24 h after laparoscopic (n = 10) and open (n = 9) cholecystectomies. Activities and concentrations of tissue plasminogen activator (tPA), plasminogen activator inhibitor type 1 (PAI-1), and tPA/PAI-1 complex were determined by enzyme-linked immunosorbent assay (ELISA) kits. RESULTS: In peritoneal fluids, tPA and tPA/PAI-1 complex concentrations were higher in the open cholecystectomy group (p = 0.009 and p < 0.001, respectively), but tPA activity and PAI-1 concentrations did not differ between the groups (p = 0.514 and p = 0.716, respectively). CONCLUSIONS: Fibrinolytic changes in peritoneal fluid have several similarities in open and laparoscopic cholecystectomies with regard to tPA activity and PAI-1 levels. However, higher tPA levels after the open procedure probably are secondary to more intense tissue handling leading to mesothelial release of tPA.


Assuntos
Líquido Ascítico/química , Colecistectomia Laparoscópica , Colecistectomia/métodos , Inibidor 1 de Ativador de Plasminogênio/análise , Ativador de Plasminogênio Tecidual/análise , Idoso , Ensaio de Imunoadsorção Enzimática , Feminino , Fibrinólise , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Estatísticas não Paramétricas
11.
Minerva Anestesiol ; 73(12): 629-33, 2007 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-18046293

RESUMO

BACKGROUND: We aimed to evaluate the efficacy of subhypnotic doses of midazolam and propofol for peripartum nausea and vomiting during regional anesthesia for elective cesarean section in order to prevent emesis in at least 50% of patients. METHODS: A prospective, double blind, placebo-controlled study was carried out. Patients were randomly allocated to one of three groups to receive placebo (saline, N=28), propofol (20 mg bolus and 1.0 mg x kg(-1) x h(-1) infusion, N=30), and midazolam (1 mg bolus and 1.0 mg x h(-1) infusion, N=30) at subhypnotic doses intravenously (i.v.) immediately after the umbilical cord was clamped. Bupivacaine hydrochloride (8-10 mg) and fentanyl (10 microg) were injected into the intervertebral space for spinal anesthesia. Blood pressure was monitored at 2 min intervals and intraoperative postdelivery emetic episodes and ephedrine consumption were recorded. The study was carried out at the Anesthesiology Department, Hacettepe University, Turkey, hospitalized care. We included 90 parturients with ASA physical status I and II between the ages of 20 and 38 years undergoing spinal anesthesia for elective cesarean delivery to evaluate the efficacy of subhypnotic doses of propofol and midazolam and, in particular, the incidence of nausea, retching, and vomiting intraoperatively. RESULTS: The incidence of nausea, retching, and vomiting was significantly higher in the control group, compared to the propofol and midazolam groups. Total ephedrine consumption was significantly higher in the control group compared to the propofol and midazolam groups. CONCLUSION: A subhypnotic dose of midazolam (1 mg x h(-1)) was as effective as the subhypnotic dose of propofol (1 mg x kg(-1) x h(-1)) for the prevention of nausea and vomiting in parturients undergoing cesarean section under spinal anesthesia.


Assuntos
Raquianestesia , Cesárea , Hipnóticos e Sedativos/uso terapêutico , Midazolam/uso terapêutico , Náusea e Vômito Pós-Operatórios/prevenção & controle , Adulto , Método Duplo-Cego , Feminino , Humanos , Gravidez
12.
J Int Med Res ; 30(5): 520-4, 2002.
Artigo em Inglês | MEDLINE | ID: mdl-12449522

RESUMO

The aim of this study was to evaluate the effects of granisetron and granisetron plus droperidol combination therapy on post-operative nausea and vomiting (PONV) in 60 patients who had undergone elective laparoscopic cholecystectomy. Induction of anaesthesia was achieved using 5 mg/kg thiopentone, 2 micrograms/kg fentanyl and 0.5 mg/kg atracurium, and anaesthesia was maintained with 2-2.5% sevoflurane. The patients were randomly assigned to two groups: group G (granisetron) (n = 30) patients received 3 mg granisetron and group GD (granisetron plus droperidol) (n = 30) patients received 3 mg granisetron and 1.25 mg droperidol shortly before the induction of anaesthesia. PONV incidence was recorded post-operatively at 15 min, 30 min, 60 min, 2 h, 4 h, 12 h and 24 h. While PONV prophylaxis provided almost complete emetic control in patients who received the granisetron plus droperidol combination, patients who received granisetron prophylaxis alone experienced PONV more frequently at 30 min and 60 min post-operatively. We conclude that addition of a low dose of droperidol to granisetron prophylaxis is more effective than granisetron prophylaxis alone for successful control of PONV.


Assuntos
Antieméticos/administração & dosagem , Colecistectomia Laparoscópica/efeitos adversos , Droperidol/administração & dosagem , Granisetron/administração & dosagem , Náusea/prevenção & controle , Complicações Pós-Operatórias/prevenção & controle , Vômito/prevenção & controle , Adulto , Sinergismo Farmacológico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
13.
Eur J Endocrinol ; 136(3): 304-6, 1997 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-9100556

RESUMO

Hypoglycemia resulting from the combination of sulfonylurea and sulfonamides is a recognized drug interaction. Hypoglycemia induced by sulfonamides alone may be encountered less frequently. Because of their structural similarities to sulfonylureas, sulfonamides are liable to facilitate hypoglycemia by increasing insulin release in susceptible individuals. Sulfonamides can potentiate the hypoglycemic effect of sulfonylurea agents when given in combination. We describe a malnourished patient with severe infection who developed hypoglycemia during high-dose trimethoprim/sulfamethoxazole therapy. Elevated C-peptide concentrations during the hypoglycemic episode indicate that hypoglycemia resulted from increased endogenous insulin secretion. As malnourished patients are prone to hypoglycemia, we suggest that they should be monitored carefully if they are on sulfonamide therapy.


Assuntos
Anti-Infecciosos Urinários/efeitos adversos , Anti-Infecciosos/efeitos adversos , Hipoglicemia/induzido quimicamente , Distúrbios Nutricionais/complicações , Pneumonia por Pneumocystis/complicações , Pneumonia por Pneumocystis/tratamento farmacológico , Sulfametoxazol/efeitos adversos , Trimetoprima/efeitos adversos , Anti-Infecciosos/uso terapêutico , Anti-Infecciosos Urinários/uso terapêutico , Quimioterapia Combinada , Feminino , Humanos , Pessoa de Meia-Idade , Sulfametoxazol/uso terapêutico , Trimetoprima/uso terapêutico
15.
Unfallchirurg ; 96(6): 319-22, 1993 Jun.
Artigo em Alemão | MEDLINE | ID: mdl-8342060

RESUMO

The records of eight patients with traumatic knee dislocation and operative treatment in 1981-1991 were reviewed. In this retrospective study the average follow-up was 6 years and indicated good results concerning stability and functional use of the knee. The vascular complications, especially the ischemic syndrome are associated with an emergency situation that requires immediate reduction.


Assuntos
Luxações Articulares/cirurgia , Traumatismos do Joelho/cirurgia , Adulto , Feminino , Seguimentos , Humanos , Luxações Articulares/diagnóstico por imagem , Traumatismos do Joelho/diagnóstico por imagem , Ligamentos Articulares/diagnóstico por imagem , Ligamentos Articulares/lesões , Ligamentos Articulares/cirurgia , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/diagnóstico por imagem , Radiografia , Amplitude de Movimento Articular/fisiologia
16.
J Med Chem ; 30(6): 1094-7, 1987 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-3585906

RESUMO

The resolution of the hypoglycemic agent (+/-)-2-tetradecyloxiranecarboxylic acid (3) as its d- and l-ephedrine salts is presented. The active enantiomer (R)-(+)-3 was also synthesized by the Sharpless chiral epoxidation procedure and its methyl ester (R)-(+)-4 was shown to be identical with the corresponding ester from the resolved acid. Single-crystal X-ray structure analysis of the diastereomeric salt of (+)-3 and (-)-ephedrine allowed assignment of (+)-3 as the R configuration. The effects on fatty acid oxidation and glucose tolerance of the racemic and enantiomeric forms of 3, 4, and the CoA ester of 3 are presented. A postulated mechanism of action for the active enantiomer as an enantioselective, active-site-directed, irreversible inhibitor of carnitine palmitoyl transferase is suggested.


Assuntos
Compostos de Epóxi/síntese química , Éteres Cíclicos/síntese química , Ácidos Graxos/síntese química , Hipoglicemiantes/síntese química , Animais , Carnitina O-Palmitoiltransferase/antagonistas & inibidores , Compostos de Epóxi/farmacologia , Ácidos Graxos/metabolismo , Ácidos Graxos/farmacologia , Hipoglicemiantes/farmacologia , Conformação Molecular , Ratos , Estereoisomerismo , Relação Estrutura-Atividade
17.
J Med Chem ; 29(11): 2184-90, 1986 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-3783579

RESUMO

A series of alkylglycidic acid analogues and derivatives were synthesized and tested for their ability to inhibit long-chain fatty acid oxidation in vitro and to lower blood sugar in rats. The extent of inhibition of carnitine acyl transferase, the enzyme at the mitochondrial membrane necessary to transport long-chain fatty acids into the mitochondria for subsequent beta-oxidation, was determined for the series. Structure-activity relationships using in vitro inhibition of [1-14C]palmitic acid oxidation in rat hemidiaphragm muscle indicate that potent activity resides mainly in 2-alkyl (C12-C16) glycidates. Replacement of the oxirane ring with cyclopropyl, thiirane, or other rings diminishes activity, as does substitution of the glycidate ring at the 3-position. In vivo potency in the rat glucose tolerance test roughly parallels the hemidiaphragm results. The lead compound, methyl 2-tetradecylglycidate (8), is a potent hypoglycemic agent following oral administration to several animal species. The hypoglycemic analogues interfere with fatty acid oxidation by specific and irreversible inhibition of mitochondrial carnitine palmitoyl transferase-A.


Assuntos
Compostos de Epóxi/síntese química , Éteres Cíclicos/síntese química , Hipoglicemiantes/síntese química , Propionatos/síntese química , Animais , Carnitina O-Palmitoiltransferase/antagonistas & inibidores , Compostos de Epóxi/farmacologia , Ácidos Graxos/metabolismo , Hipoglicemiantes/farmacologia , Oxirredução , Propionatos/farmacologia , Ratos , Relação Estrutura-Atividade
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