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1.
Langmuir ; 30(8): 2206-15, 2014 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-24528207

RESUMO

We present the results of a systematic study on the porosity of silica microparticles and nanowires prepared by glancing angle deposition-metal-assisted chemical etching (GLAD-MACE) and interference lithography-metal-assisted chemical etching (IL-MACE) techniques using the thermoporometry (TPM) method. Good agreement was obtained between our TPM results and published data provided by the suppliers of silica microparticles. TPM characterization of the GLAD-MACE and IL-MACE nanowires was carried out on the basis of parameters obtained from TPM experiments on microparticles. Our nanowires showed a similar trend but lower values of the pore volume and surface area than nanowires prepared by MACE with AgNO3 solution. We attribute the enhanced bioanalysis performance of the GLAD-MACE nanowires based devices to the increased pore volume and total surface area of the nanowires.


Assuntos
Nanofios/química , Dióxido de Silício/química , Nitrato de Prata/química , Nanofios/ultraestrutura , Propriedades de Superfície
2.
Langmuir ; 27(7): 4126-33, 2011 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-21355585

RESUMO

We describe a new method of fabricating large-area, highly scalable, "hybrid" superhydrophobic surfaces on silicon (Si) substrates with tunable, spatially selective adhesion behavior by controlling the morphologies of Si nanowire arrays. Gold (Au) nanoparticles were deposited on Si by glancing-angle deposition, followed by metal-assisted chemical etching of Si to form Si nanowire arrays. These surfaces were chemically modified and rendered hydrophobic by fluorosilane deposition. Au nanoparticles with different size distributions resulted in the synthesis of Si nanowires with very different morphologies (i.e., clumped and straight nanowire surfaces). The difference in nanowire morphology is attributed to capillary force-induced nanocohesion, which is due to the difference in nanowire porosity. The clumped nanowire surface demonstrated the lotus effect, and the straighter nanowires demonstrated the ability to pin water droplets while maintaining large contact angles (i.e., the petal effect). The high contact angles in both cases are explained by invoking the Cassie-Baxter wetting state. The high adhesion behavior of the straight nanowire surface may be explained by a combination of attractive van der Waals forces and capillary adhesion. We demonstrate the spatial patterning of both low- and high-adhesion superhydrophobicity on the same substrate by the simultaneous synthesis of clumped and straight silicon nanowires. The demonstration of hybrid superhydrophobic surfaces with spatially selective, tunable adhesion behavior on single substrates paves the way for future applications in microfluidic channels, substrates for biologically and chemically based analysis and detection where it is necessary to analyze a particular droplet in a defined location on a surface, and as a platform to study in situ chemical mixing and interfacial reactions of liquid pearls.


Assuntos
Nanoestruturas/química , Nanotecnologia/métodos , Silício/química , Molhabilidade , Nanofios/química , Propriedades de Superfície
3.
AIDS Care ; 21(5): 664-71, 2009 May.
Artigo em Inglês | MEDLINE | ID: mdl-19444676

RESUMO

HIV-associated lipoatrophy may affect up to 35% of patients who have received antiretroviral (ARV) regimens for more than one year, and may result in depression, social isolation, and career barriers. Interventions including the injection of dermal fillers for restoration of facial fat loss are being used for treating HIV-associated lipoatrophy. Since reimbursement is often lacking, patients must consider the pros and cons of such interventions, weighed against the other costs of daily life. The primary goal of the study is to provide reliable estimates of the costs of treating HIV-associated lipoatrophy, specifically facial lipoatrophy. Costs are provided for a single site and are estimated from published studies reporting administration patterns of dermal fillers, publicly available list prices, and physician service fees for similar subcutaneous injections of the face. Fourteen studies were identified that reported experience with five dermal fillers used to treat HIV-associated facial lipoatrophy: poly-L-lactic acid, calcium hydroxylapatite, polyalkylimide gel, hyaluronic acid, and silicone oil. Typical courses involve four physician visits, but could vary from 1 to 13. The cost of a course of dermal filler treatment at a single site ranges across four products (all other than hyaluronic acid) from $3690 to $16,544, and is typically not covered by the payers. Physician fees for an entire course of similar outpatient procedures reimbursed by insurers are approximately $500, and may vary according to location, specialty, and market conditions. These procedures need to be repeated per site injected with intervals of 1-3 years. Treatment of HIV-associated lipoatrophy may represent a considerable out-of-pocket expense for many patients with HIV. This could have implications for deciding whether to undergo a restorative procedure, which procedure to undergo, and whether to pursue other options that may include switching ARV regimens.


Assuntos
Antivirais/efeitos adversos , Materiais Biocompatíveis/economia , Técnicas Cosméticas/economia , Face/cirurgia , Infecções por HIV/complicações , Lipodistrofia/economia , Administração Cutânea , Materiais Biocompatíveis/uso terapêutico , Humanos , Lipodistrofia/etiologia
4.
Indian J Surg Oncol ; 10(2): 342-349, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31168260

RESUMO

Uterine sarcomas are uncommon and aggressive tumors comprising 3-7% of all uterine malignancies. The aim is to evaluate clinical presentation, histopathologic pattern, recurrence pattern, and outcome of patients with uterine sarcomas presenting to a tertiary care cancer center over an 8-year period. A total of 11 cases of uterine sarcoma were diagnosed. The median age of patients at presentation was 51 years (range 30-67 years). Six patients had leiomyosarcoma (54.5%), 4 had endometrial stromal sarcoma (36%), and 1 had adenosarcoma (9%). The main presenting symptoms were abnormal vaginal bleeding, low abdominal pain, and white discharge. Median follow-up was 11 months ranging from 3 to 200 months. Median survivals for leiomyosarcoma, endometrial stromal sarcoma, and adenosarcoma were 6.5, 18, and 56 months. The 3- and 5-year survival by Kaplan-Meier survival analysis of the entire cohort was 30 and 20%. The mitotic index, age, adjuvant therapy (chemotherapy, radiotherapy), and performance of pelvic nodal dissection did not impact survival significantly in the patient with leiomyosarcoma. Stage and histology had the strongest bearing on survival and leiomyosarcoma has the worst survival, whereas adenosarcoma had the best prognosis. Adequately powered prospective studies are required to define the role of radiation therapy and chemotherapy in this rare disease.

6.
J Am Coll Cardiol ; 7(3): 564-72, 1986 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-3950236

RESUMO

Sudden and staged reperfusion after experimental coronary artery occlusion was studied in relation to recovery of cardiac function and postreperfusion arrhythmias. Eighteen closed chest dogs with 3 hour intracoronary balloon occlusion of the proximal left anterior descending coronary artery were studied using two-dimensional echocardiography over a period of 3 weeks after reperfusion. Nine dogs had sudden reperfusion by abrupt balloon deflation. In nine other dogs reperfusion was staged with partial reflow (20 ml/min) for 2 hours through the central lumen of the catheter during persisting intracoronary balloon inflation, followed by balloon deflation and full reperfusion. Within the first 30 minutes of sudden reperfusion, ischemic zone end-diastolic wall thickness increased significantly, from 6.8 +/- 0.3 mm at 3 hours of occlusion to 10.2 +/- 2.6 mm (p less than 0.05). In contrast, at 30 minutes of partial reflow, wall thickness was 7.5 +/- 0.7 versus 6.8 +/- 0.7 mm at 3 hours of occlusion (NS). A small temporary increase in end-diastolic wall thickness was noted when full reflow was established after 2 hours of staged reperfusion. However, wall thickness was normal on the first day in the staged reperfusion series, while sudden reperfusion delayed recovery to 7 days. Function of the ischemic zone failed to improve substantially until day 3 after sudden reperfusion, whereas it improved consistently starting as early as 30 minutes after institution of the staged reperfusion.(ABSTRACT TRUNCATED AT 250 WORDS)


Assuntos
Arteriopatias Oclusivas/fisiopatologia , Doença das Coronárias/fisiopatologia , Perfusão/métodos , Doença Aguda , Animais , Arritmias Cardíacas/fisiopatologia , Arteriopatias Oclusivas/mortalidade , Doença das Coronárias/mortalidade , Doença das Coronárias/patologia , Cães , Ecocardiografia , Eletrocardiografia , Hemorragia/patologia , Hemorragia/fisiopatologia , Infarto do Miocárdio/patologia , Infarto do Miocárdio/fisiopatologia , Revascularização Miocárdica/instrumentação , Revascularização Miocárdica/métodos , Necrose , Perfusão/instrumentação , Sístole , Fatores de Tempo
7.
J Am Coll Cardiol ; 6(6): 1289-98, 1985 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-4067107

RESUMO

The effect of intravenous nifedipine (5 micrograms/kg) on the recovery of myocardial function after occlusion of the left anterior descending coronary artery was studied in 18 closed chest dogs. Using computer-aided analysis of two-dimensional echocardiograms, systolic and diastolic function of ischemic segments in low papillary left ventricular cross sections were characterized, respectively, as holosystolic fractional area change and early diastolic velocity of luminal area change. The time required for systolic function to return to preocclusion values after a 1 minute untreated control occlusion (n = 12) was 5 to 10 minutes, and after a 2 minute occlusion (n = 6) it was 20 to 30 minutes. When nifedipine was administered during the occlusion, recovery after a 2 minute occlusion was accelerated slightly to 10 to 15 minutes. Recovery times of early diastolic function were substantially longer, and nifedipine effects were more pronounced. After a 1 or 2 minute control coronary occlusion, 60 to 75 minutes or 90 to 105 minutes were needed to return early diastolic function to normal levels. Nifedipine administered during a 1 or 2 minute coronary occlusion improved these recovery times to 10 to 15 minutes. When the dogs were treated with intravenous nifedipine before coronary occlusion, recovery after 1 or 2 minutes of acute ischemia was apparent as early as 2 minutes after reperfusion. Thus, intravenous nifedipine accelerates the recovery of myocardial function after brief periods of ischemia, and when administered before coronary occlusion, it assures very prompt recovery of function.


Assuntos
Circulação Coronária/efeitos dos fármacos , Nifedipino/farmacologia , Animais , Doença das Coronárias/tratamento farmacológico , Diástole , Cães , Ecocardiografia , Ventrículos do Coração/efeitos dos fármacos , Hemodinâmica/efeitos dos fármacos , Sístole , Função Ventricular
8.
Endocrinology ; 134(4): 1745-54, 1994 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-8137739

RESUMO

Because the acute homologous phase of desensitization of the LH/CG-sensitive adenylyl cyclase in porcine follicles is readily demonstrated in a cell-free membrane preparation, it follows that any enzyme(s) required to achieve desensitization must be present in the membranes and must be activated upon LH/CG receptor activation. The purpose of the following studies was to determine whether modulation of endogenous membrane protein kinases, with activators or inhibitors, or addition of exogenous protein kinases affected desensitization of the LH/CG-sensitive adenylyl cyclase. The effects of these potential modulators were evaluated in both the presence and absence of ligand (hCG)-stimulated receptor activation. To this end, membranes were incubated in the presence or absence of hCG (stage 1) and then assayed for adenylyl cyclase activity in the presence or absence of hCG (stage 2). The results showed that although porcine follicular membranes rich in LH/CG-sensitive adenylyl cyclase activity also exhibited cAMP-dependent [protein kinase-A (PKA)], cGMP-dependent (PKG), lipid-dependent (PKC), Ca2+/calmodulin, and casein kinase-I and -II activities, only full hCG-stimulated adenylyl cyclase activity (measured with BSA in stage 1 and hCG in stage 2) was reduced upon addition of exogenous PKC (to the stage 1 incubation). hCG-dependent desensitization of cAMP synthesis (measured with hCG in stages 1 and 2) was unaffected by activators or inhibitors of endogenous PKA, PKC, or PKG, by an inhibitor of casein kinases and kinases in the beta-adrenergic receptor kinase family, or by the addition of exogenous active PKA, PKC, or rhodopsin kinase to the stage 1 incubation. These results suggest that the acute homologous phase of hCG-dependent desensitization of adenylyl cyclase activity in follicular membranes is not regulated by PKA, PKC, PKG, or messenger-independent heparin-sensitive protein kinases.


Assuntos
Adenilil Ciclases/metabolismo , Gonadotropina Coriônica/farmacologia , Hormônio Luteinizante/farmacologia , Folículo Ovariano/enzimologia , Proteínas Quinases/farmacologia , Animais , Feminino , Membranas/enzimologia , Inibidores de Proteínas Quinases , Proteínas Quinases/metabolismo , Suínos
9.
J Med Chem ; 31(10): 1872-9, 1988 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-3172122

RESUMO

A series of 6- and 7-aminoacyl derivatives of 7-deacetylforskolin was prepared to provide water-soluble derivatives of the potent cardioactive diterpenoid forskolin. The compounds were evaluated for positive inotropic and blood pressure lowering properties in pharmacological models. Several derivatives displayed potent positive inotropic activity in guinea pig atria (EC50 = 0.16-3.0 micrograms/mL). In the most active compounds, the amino moiety of the aminoacyl chain corresponded to a cyclic amine, and the acyl moiety to a C2-C4 alkanoyl group. In vivo biological evaluation led to the selection of 6-(piperidinoacetyl)-7-deacetylforskolin hydrochloride (49) as a candidate for clinical development.


Assuntos
Fármacos Cardiovasculares , Sistema Cardiovascular/efeitos dos fármacos , Colforsina/análogos & derivados , Animais , Pressão Sanguínea/efeitos dos fármacos , Gatos , Colforsina/farmacologia , Cães , Cobaias , Frequência Cardíaca/efeitos dos fármacos , Camundongos , Ratos , Ratos Endogâmicos SHR , Solubilidade , Estimulação Química , Relação Estrutura-Atividade , Água
10.
J Med Chem ; 44(16): 2675-8, 2001 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-11472221

RESUMO

(-)DRF 2725 (6) is a phenoxazine analogue of phenyl propanoic acid. Compound 6 showed interesting dual activation of PPAR alpha and PPAR gamma. In insulin resistant db/db mice, 6 showed better reduction of plasma glucose and triglyceride levels as compared to rosiglitazone. Compound 6 has also shown good oral bioavailability and impressive pharmacokinetic characteristics. Our study indicates that 6 has great potential as a drug for diabetes and dyslipidemia.


Assuntos
Glicemia/análise , Hipoglicemiantes/síntese química , Oxazinas/síntese química , Fenilpropionatos/síntese química , Receptores Citoplasmáticos e Nucleares/agonistas , Fatores de Transcrição/agonistas , Triglicerídeos/sangue , Animais , Disponibilidade Biológica , Complicações do Diabetes , Diabetes Mellitus/tratamento farmacológico , Hiperlipidemias/complicações , Hiperlipidemias/tratamento farmacológico , Hipoglicemiantes/farmacocinética , Hipoglicemiantes/farmacologia , Resistência à Insulina , Camundongos , Oxazinas/farmacocinética , Oxazinas/farmacologia , Fenilpropionatos/farmacocinética , Fenilpropionatos/farmacologia , Ratos , Ratos Wistar , Estereoisomerismo
11.
J Med Chem ; 42(17): 3265-78, 1999 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-10464013

RESUMO

Several thiazolidinediones having chroman moieties were synthesized and evaluated for their euglycemic and hypolipidemic activities. Some of the analogues having an aminoalkyl group as a linker between the chroman ring and 4-[5-(2,4-dioxo-1, 3-thiazolidinyl)methyl]phenoxy moiety seem to be better than troglitazone. In vitro transactivation assays of PPARgamma have been carried out with these glitazones to understand their molecular mechanism. For the first time we have found that some of the unsaturated thiazolidinediones are superior to their saturated counterpart in the in vivo assay. A more potent thiazolidinedione analogue than troglitazone is reported. Pharmacokinetic studies have shown that protection of the OH group in the chroman moiety leads to a decrease in metabolism, thereby resulting in a superior pharmacological profile.


Assuntos
Cromanos/síntese química , Hipoglicemiantes/síntese química , Hipolipemiantes/síntese química , Tiazóis/síntese química , Animais , Glicemia/metabolismo , Cromanos/química , Cromanos/farmacocinética , Cromanos/farmacologia , Feminino , Hipoglicemiantes/química , Hipoglicemiantes/farmacocinética , Hipoglicemiantes/farmacologia , Hipolipemiantes/química , Hipolipemiantes/farmacocinética , Hipolipemiantes/farmacologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Ratos , Ratos Wistar , Receptores Citoplasmáticos e Nucleares/agonistas , Relação Estrutura-Atividade , Tiazóis/química , Tiazóis/farmacocinética , Tiazóis/farmacologia , Fatores de Transcrição/agonistas , Triglicerídeos/sangue
12.
J Med Chem ; 42(14): 2569-81, 1999 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-10411477

RESUMO

A series of substituted pyridyl- and quinolinyl-containing 2, 4-thiazolidinediones having interesting cyclic amine as a linker have been synthesized. Both unsaturated thiazolidinediones 5 and saturated thiazolidinediones 6 and their various salts were evaluated in db/db mice for euglycemic and hypolipidemic effects and compared with BRL compound 11 and BRL-49653, respectively. Some of the potent compounds were converted to various salts in order to obtain improved activities. Among all the salts evaluated, the maleate salt of unsaturated TZD 5a was found to be a very potent euglycemic and hypolipidemic compound. Some of the more interesting compounds have also been evaluated in ob/ob mice and compared with rosiglitazone (maleate salt of BRL-49653). Oral glucose tolerance tests were performed in both db/db and ob/ob mice. Pharmacokinetic studies of 5a maleate are also reported. Receptor binding studies of PPARgamma by 5a/5a maleate did not show any significant transactivation of PPARalpha or PPARgamma.


Assuntos
Hipoglicemiantes/síntese química , Hipolipemiantes/síntese química , Piridinas/síntese química , Quinolinas/síntese química , Tiazóis/síntese química , Tiazolidinedionas , Animais , Teste de Tolerância a Glucose , Hipoglicemiantes/química , Hipoglicemiantes/farmacocinética , Hipoglicemiantes/farmacologia , Hipolipemiantes/química , Hipolipemiantes/farmacocinética , Hipolipemiantes/farmacologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Obesos , Piridinas/química , Piridinas/farmacocinética , Piridinas/farmacologia , Quinolinas/química , Quinolinas/farmacocinética , Quinolinas/farmacologia , Ratos , Ratos Wistar , Relação Estrutura-Atividade , Tiazóis/química , Tiazóis/farmacocinética , Tiazóis/farmacologia
13.
J Med Chem ; 42(11): 1927-40, 1999 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-10354401

RESUMO

Several thiazolidinedione derivatives having 5-hydroxy-2,3-dihydro-2, 2,4,6,7-pentamethylbenzofuran moieties and their 5-benzyloxy derivatives and 5-hydroxy-2,4,6,7-tetramethylbenzofuran moieties were synthesized and evaluated in db/db mice. Insertion of an N-Me group into the linker between thiazolidinedione and substituted benzofuran pharmacophores showed considerable improvement in their euglycemic activity. Further improvement has been observed when a pyrrolidine moiety is introduced in the structure to give 5-[4-[N-[3(R/S)-5-benzyloxy-2,3-dihydro-2,2,4,6, 7-pentamethylbenzofuran-3-ylmethyl]-(2S)-pyrrolidin-2- ylmethoxy]pheny lene]thiazolidine-2,4-dione (21a). At a 100 mg/kg/day dose of the maleate salt, compound 21a reduced the plasma glucose and triglyceride to the level of lean littermate, i.e. 8 +/- 1 mM, and is the most potent and efficacious compound reported in this series.


Assuntos
Hipoglicemiantes/síntese química , Hipolipemiantes/síntese química , Pirrolidinas/síntese química , Tiazóis/síntese química , Animais , Glicemia/metabolismo , Feminino , Hipoglicemiantes/química , Hipoglicemiantes/farmacocinética , Hipoglicemiantes/farmacologia , Hipolipemiantes/química , Hipolipemiantes/farmacocinética , Hipolipemiantes/farmacologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Pirrolidinas/química , Pirrolidinas/farmacocinética , Pirrolidinas/farmacologia , Ratos , Ratos Wistar , Receptores Citoplasmáticos e Nucleares/agonistas , Relação Estrutura-Atividade , Tiazóis/química , Tiazóis/farmacocinética , Tiazóis/farmacologia , Fatores de Transcrição/agonistas , Triglicerídeos/sangue
14.
J Med Chem ; 41(10): 1619-30, 1998 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-9572887

RESUMO

A series of [[(heterocyclyl)ethoxy]benzyl]-2,4-thiazolidinediones have been synthesized by the condensation of corresponding aldehyde 1 and 2,4-thiazolidinedione followed by hydrogenation. Both unsaturated thiazolidinedione 2 and its saturated counterpart 3 have shown antihyperglycemic activity. Many of these compounds have shown superior euglycemic and hypolipidemic activity compared to troglitazone (CS 045). The indole analogue DRF-2189 (3g) was found to be a very potent insulin sensitizer, comparable to BRL-49653 in genetically obese C57BL/6J-ob/ob and 57BL/KsJ-db/db mice. Pharmacokinetic and tissue distribution studies conducted on BRL-49653 and DRF-2189 (3g) indicate that these drugs are well-distributed in target tissues. On the basis of euglycemic activity as well as enhanced selectivity against reduction of triglycerides in plasma, DRF-2189 (3g) has been selected for further evaluation.


Assuntos
Hipoglicemiantes , Hipolipemiantes , Indóis , Tiazóis , Tiazolidinedionas , Animais , Glicemia/metabolismo , Avaliação Pré-Clínica de Medicamentos , Hipoglicemiantes/síntese química , Hipoglicemiantes/química , Hipoglicemiantes/farmacocinética , Hipoglicemiantes/farmacologia , Hipolipemiantes/síntese química , Hipolipemiantes/química , Hipolipemiantes/farmacocinética , Hipolipemiantes/farmacologia , Indóis/síntese química , Indóis/química , Indóis/farmacocinética , Indóis/farmacologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Ratos , Ratos Wistar , Rosiglitazona , Relação Estrutura-Atividade , Tiazóis/síntese química , Tiazóis/química , Tiazóis/farmacocinética , Tiazóis/farmacologia , Distribuição Tecidual , Triglicerídeos/sangue
15.
Biochem Pharmacol ; 34(19): 3415-9, 1985 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-4052091

RESUMO

The effect of rifampicin on the biological properties of bovine brain tubulin was investigated. Assembly of microtubules was almost completely blocked by rifampicin, whereas the depolymerization was not affected. The drug was found to inhibit both colchicine and GTP binding to tubulin. Association of rifampicin with tubulin was confirmed by spectrophotometric method. Binding of rifampicin was found to be dependent both on temperature and time. At 0 degrees for 1 hr 0.84 moles of rifampicin were bound per mole of tubulin.


Assuntos
Rifampina/farmacologia , Tubulina (Proteína)/metabolismo , Animais , Química Encefálica , Bovinos , Cromatografia em Gel , Colchicina/metabolismo , Dapsona/farmacologia , Guanosina Trifosfato/metabolismo , Cinética , Substâncias Macromoleculares , Microtúbulos/efeitos dos fármacos , Microtúbulos/fisiologia , Fenobarbital/farmacologia , Rifampina/metabolismo , Espectrofotometria
16.
Invest Radiol ; 35(8): 479-85, 2000 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-10946975

RESUMO

RATIONALE AND OBJECTIVES: To evaluate the efficacy of a novel tumor receptor-specific small-peptide-near-infrared dye conjugate for tumor detection by optical imaging. METHODS: A novel, near-infrared dye-peptide conjugate was synthesized and evaluated for tumor-targeting efficacy in a well-characterized rat tumor model (CA20948) known to express receptors for the chosen peptide. A simple continuous-wave optical imaging system, consisting of a near-infrared laser diode, a cooled CCD camera, and an interference filter, was used in this study. RESULTS: Tumor retention of two non-tumor-specific dyes, indocyanine green and its derivatized analogue, bis-propanoic acid cyanine dye (cypate), was negligible. In contrast, the receptor-specific peptide-cypate conjugate (cytate) was retained in the CA20948 tumor, with an excellent tumor-tonormal-tissue ratio in the six rats examined. CONCLUSIONS: Optical detection of tumors with a receptor-targeted fluorescent contrast agent has been demonstrated. This result represents a new direction in cancer diagnosis and patient management.


Assuntos
Meios de Contraste , Diagnóstico por Imagem , Fluorescência , Corantes Fluorescentes , Neoplasias Experimentais/diagnóstico , Peptídeos , Animais , Verde de Indocianina/análogos & derivados , Lasers , Masculino , Óptica e Fotônica , Neoplasias Pancreáticas/diagnóstico , Neoplasias da Próstata/diagnóstico , Ratos
17.
BMC Cancer ; 4: 26, 2004 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-15207007

RESUMO

BACKGROUND: We determined the effect of andrographolide and one of its novel semi-synthetic analog, DRF 3188, on the cell cycle of MCF 7 breast cancer cells. METHODS: The effect of the compounds on cell cycle was determined using FACS and western blot analysis of cell cycle proteins. Hollow fibre assay was used to determine if the compounds had the same effect on the cell cycle in vitro and in vivo. RESULTS: Our results from the in vitro and in vivo experiments show that both the compounds block the cell cycle at the G0-G1 phase through the induction of the cell cycle inhibitor, p27, and the concomitant decrease in the levels of Cdk4. CONCLUSION: The results show that the novel semi-synthetic analog, DRF3188, and andrographolide bring about the anti cancer activity by a similar mechanism.


Assuntos
Antineoplásicos/farmacologia , Neoplasias da Mama/tratamento farmacológico , Diterpenos/farmacologia , Animais , Neoplasias da Mama/patologia , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Citometria de Fluxo , Humanos , Camundongos , Ensaios Antitumorais Modelo de Xenoenxerto
18.
Radiat Res ; 97(3): 499-510, 1984 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-6729026

RESUMO

Anti-thymine glycol antibodies were elicited by immunizing rabbits with thymine glycol monophosphate (TMP-glycol) conjugated by carbodiimide to BSA. The antibodies produced are specific for thymine glycol as measured by immunoprecipitation of TMP-glycol-RSA conjugates and hapten inhibition of reactivity with OsO4-treated DNA in an enzyme immunoassay. Using the enzyme immunoassay, the antibody is capable of detecting femtomole and picomole levels of thymine glycol in direct and competitive assays, respectively. This immunochemical assay is potentially suitable for measuring the production and repair of thymine glycol damage in cellular DNA.


Assuntos
Formação de Anticorpos , DNA/efeitos da radiação , Timina/análogos & derivados , Animais , Especificidade de Anticorpos , Ensaio de Imunoadsorção Enzimática , Coelhos , Timina/imunologia
19.
Metabolism ; 49(11): 1417-23, 2000 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-11092504

RESUMO

The euglycemic and hypolipidemic activities of PAT5A, a novel pyridine analog of thiazolidinedione, have been evaluated in different animal models. Administration of PAT5A to db/db mice resulted in dose-dependent decreases in plasma glucose, triglyceride, and insulin levels, and an improved glucose tolerance. The glucose-lowering activity of PAT5A was better than that of troglitazone and comparable to that of rosiglitazone. In addition, PAT5A showed better lipid-lowering activity than troglitazone or rosiglitazone. A similar profile was seen in ob/ob mice. In high-fat-fed Sprague Dawley rats, PAT5A treatment reduced plasma triglyceride and total cholesterol levels. An in vitro peroxisome proliferator activated receptor gamma (PPARgamma) transactivation assay in HEK-293 cells showed poor transactivation for PAT5A compared with rosiglitazone. PAT5A did not show any PPARalpha- or PPARdelta-activating properties. Ex vivo study in db/db mice treated with PAT5A showed decreased activity of liver glucose 6-phosphatase, a key enzyme in gluconeogenesis. A 28-day probe toxicity study in Wistar rats did not show any treatment-related alterations in hematologic and biochemical parameters, nor any macroscopic and microscopic changes in the vital organs, whereas rosiglitazone treatment increased liver and heart weights. Our results indicate that PAT5A is a potent insulin sensitizer and hypolipidemic compound with a weak PPARgamma activation potential. Both in vivo and in vitro results suggest that PAT5A improves glucose kinetics and lipid levels through mechanisms not related to PPAR activation.


Assuntos
Hipoglicemiantes/farmacologia , Hipolipemiantes/farmacologia , Pirrolidinas/farmacologia , Receptores Citoplasmáticos e Nucleares/agonistas , Tiazóis/farmacologia , Tiazolidinedionas , Fatores de Transcrição/agonistas , Animais , Colesterol na Dieta/administração & dosagem , Glucose-6-Fosfatase/metabolismo , Hipoglicemiantes/toxicidade , Hipolipemiantes/toxicidade , Fígado/efeitos dos fármacos , Fígado/enzimologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Pirrolidinas/toxicidade , Ratos , Ratos Sprague-Dawley , Receptores Citoplasmáticos e Nucleares/genética , Tiazóis/toxicidade , Fatores de Transcrição/genética , Ativação Transcricional/efeitos dos fármacos
20.
J Clin Pharmacol ; 34(11): 1126-32, 1994 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-7876406

RESUMO

The diuretic effects, pharmacokinetics, and safety of CI-977, a new centrally acting selective kappa-opioid agonist, were determined in 16 healthy subjects. Subjects received single intramuscular doses of CI-977 (5, 15, or 25 micrograms) or placebo 1 week apart according to a randomized, double-blind, placebo-controlled, four-period, crossover design. Serial blood and urine specimens were collected after each dose. Significant dose-related decreases in negative free water clearance and urine osmolality and increases in urine volume were observed after administration of 15- and 25-micrograms doses of CI-977. CI-977 had no effect on urine electrolyte excretion or serum antidiuretic hormone. Absorption of CI-977 was rapid with individual tmax values ranging from 0.17 to 1.5 hours. Cmax and AUC(0-infinity) increased proportionally with dose. Individual elimination half-life values ranged from 0.6 to 3.3 hours and were independent of dose. Changes in free water clearance were related to CI-977 Cmax (r2 = 0.29, P = 0.0001) and AUC(0-4 hr) (r2 = 0.32, P = 0.0001) values. The most frequently reported adverse events after CI-977 administration were dizziness, fatigue, paresthesia, headache, vasodilatation (facial flushing), emotional lability, high feeling, and abnormal thinking. The frequency and intensity of adverse events increased with increasing CI-977 dose. In conclusion, CI-977 Cmax and AUC(0-infinity) increased in proportion to dose over the range of 5 to 25 micrograms; decreases in negative free water clearance were related to CI-977 dose and Cmax and AUC(0-4 hr) values; and the frequency and intensity of adverse events increased with increasing CI-977 dose.


Assuntos
Benzofuranos/farmacologia , Diuréticos/farmacologia , Pirrolidinas/farmacologia , Receptores Opioides kappa/agonistas , Adulto , Benzofuranos/efeitos adversos , Benzofuranos/farmacocinética , Estudos Cross-Over , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pirrolidinas/efeitos adversos , Pirrolidinas/farmacocinética
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