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1.
Molecules ; 28(4)2023 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-36838741

RESUMO

Developing highly efficient semiconductor metal oxide (SMOX) sensors capable of accurate and fast responses to environmental humidity is still a challenging task. In addition to a not so pronounced sensitivity to relative humidity change, most of the SMOXs cannot meet the criteria of real-time humidity sensing due to their long response/recovery time. The way to tackle this problem is to control adsorption/desorption processes, i.e., water-vapor molecular dynamics, over the sensor's active layer through the powder and pore morphology design. With this in mind, a KIT-5-mediated synthesis was used to achieve mesoporous tin (IV) oxide replica (SnO2-R) with controlled pore size and ordering through template inversion and compared with a sol-gel synthesized powder (SnO2-SG). Unlike SnO2-SG, SnO2-R possessed a high specific surface area and quite an open pore structure, similar to the KIT-5, as observed by TEM, BET and SWAXS analyses. According to TEM, SnO2-R consisted of fine-grained globular particles and some percent of exaggerated, grown twinned crystals. The distinctive morphology of the SnO2-R-based sensor, with its specific pore structure and an increased number of oxygen-related defects associated with the powder preparation process and detected at the sensor surface by XPS analysis, contributed to excellent humidity sensing performances at room temperature, comprised of a low hysteresis error (3.7%), sensitivity of 406.8 kΩ/RH% and swift response/recovery speed (4 s/6 s).


Assuntos
Óxidos , Umidade , Pós , Óxidos/química
2.
J Infect Dis ; 224(9): 1539-1549, 2021 11 16.
Artigo em Inglês | MEDLINE | ID: mdl-33822119

RESUMO

BACKGROUND: Following the implementation of rotavirus vaccination in 2006, severe acute gastroenteritis (AGE) due to group A rotavirus (RVA) has substantially declined in US children. We report the RVA genotype prevalence as well as coinfection data from 7 US New Vaccine Surveillance Network sites during 3 consecutive RVA seasons, 2014-2016. METHODS: A total of 1041 stool samples that tested positive for RVA by Rotaclone enzyme immunoassay were submitted to the Centers for Disease Control and Prevention (CDC) for RVA genotyping and multipathogen testing. RESULTS: A total of 795 (76%) samples contained detectable RVA when tested at the CDC. Rotavirus disease was highest in children < 3 years of age. Four G types (G1, G2, G9, and G12) accounted for 94.6% of strains while 2 P types (P[4] and P[8]) accounted for 94.7% of the strains. Overall, G12P[8] was the most common genotype detected in all 3 seasons. Stepwise conditional logistic analysis found year and study site were significant predictors of genotype. Twenty-four percent of RVA-positive specimens contained other AGE pathogens. CONCLUSIONS: G12P[8] predominated over 3 seasons, but strain predominance varied by year and study site. Ongoing surveillance provides continuous tracking and monitoring of US genotypes during the postvaccine era.


Assuntos
Gastroenterite , Vigilância da População/métodos , Infecções por Rotavirus/epidemiologia , Rotavirus/isolamento & purificação , Vacinas , Criança , Fezes , Gastroenterite/epidemiologia , Genótipo , Humanos , Lactente , Filogenia , Prevalência , Rotavirus/genética , Estados Unidos/epidemiologia
3.
Drug Dev Ind Pharm ; 39(6): 889-900, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22905673

RESUMO

OBJECTIVE: The suitability of the rabbit as an animal model for the primary screening and selection of the pilot scale batches during the early stages of the formulation development was studied. MATERIALS AND METHODS: Three modified-release formulations of aminophylline consisted of Carbopol® 971P/HPMC K4M (F-I), and HPMC K100M (F-II) or HPMC K4M (F-III) were used. Commercial products were Aminofilin retard 350 mg tablets, Srbolek, Serbia (R-I) and Phyllocontin(®) 350, tablets Purdue Frederic, Canada (R-II). RESULTS: Calculated release rate constants and the ƒ2 values between R-I/F-I (84.1) and R-II/F-III (83.4) indicated similar in vitro release while the coefficient n showed presence of different mechanisms of release from Anomalous transport, Fickian diffusion to Case-II transport. Higher Tmax, was found in the rabbits, dosed with F-II (12.00 h), F-III (10.50 h), and R-II (15.00 h) formulation. The highest Cmax (9.22 mg/L) was obtained with F-II, similar lower values was seen for F-I and F-III, while commercial products showed the lowest values R-I (5.58 mg/L) and R-II (4.18 mg/L). Higher AUC values were detected for all three formulations (from 115.90 to 204.06 mgh/L) in relation to commercial products (105.33 and 113.25 mgh/L). DISCUSSION AND CONCLUSION: The results demonstrated a good correlation of Level A (r(2) = 0.97) for the two formulations (F-I, F-III) and commercial product (R-I) indicates that there is a reasonable assumption that the rabbit might be use as a model for the preliminary comparison of scale up formulations in the early stages of the product development.


Assuntos
Química Farmacêutica/métodos , Preparações de Ação Retardada/administração & dosagem , Preparações de Ação Retardada/metabolismo , Absorção Intestinal/fisiologia , Administração Oral , Aminofilina/administração & dosagem , Aminofilina/sangue , Aminofilina/química , Animais , Preparações de Ação Retardada/química , Formas de Dosagem , Avaliação Pré-Clínica de Medicamentos , Absorção Intestinal/efeitos dos fármacos , Coelhos , Comprimidos
4.
Materials (Basel) ; 15(13)2022 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-35806590

RESUMO

Polycrystalline samples of NaCo2-xCuxO4 (x = 0, 0.01, 0.03, 0.05) were obtained from powder precursors synthesized by a mechanochemically assisted solid-state reaction method (MASSR) and a citric acid complex method (CAC). Ceramic samples were prepared by pressing into disc-shaped pellets and subsequently sintering at 880 °C in an argon atmosphere. Effects of low concentrations of Cu doping and the above-mentioned synthesis procedures on the thermoelectric and mechanical properties were observed. The electrical resistivity (ρ), the thermal conductivity (κ) and the Seebeck coefficient (S) were measured simultaneously in the temperature gradient (ΔT) between the hot and cold side of the sample, and the figure of merit (ZT) was subsequently calculated. The ZT of the CAC samples was higher compared with the MASSR samples. The highest ZT value of 0.061 at ΔT = 473 K was obtained for the sample with 5 mol% of Cu prepared by the CAC method. The CAC samples showed better mechanical properties compared to the MASSR samples due to the higher hardness of the CAC samples which is a consequence of homogeneous microstructure and higher density obtained during sintering of these samples. The results confirmed that, besides the concentration of Cu, the synthesis procedure considerably affected the thermoelectric and mechanical properties of NaCo2O4 (NCO) ceramics.

5.
Microsc Res Tech ; 85(4): 1557-1567, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34888993

RESUMO

In the present work, a biomaterial (SBA-16/HA) based on the growth of hydroxyapatite (HA) particles within an organized silica structure SBA-16 (Santa Barbara Amorphous-16) was developed to evaluate its application to act as a porous microenvironment promoting attachment and viability of human dental pulp stem cells of healthy deciduous teeth (SHED). First, SHED were isolated and their phenotypes were evaluated by flow cytometry. The samples of SBA-16/HA were characterized by X-ray diffraction (XRD), small and wide angle X-ray scattering (SWAXS), Fourier transform infrared spectroscopy (FTIR), and scanning electron microscopy (SEM) equipped with energy dispersive spectra detector (EDS). Afterward, cells were cultured in the eluates of the above-mentioned biomaterial aged for 24 hr, 7. and 14 days. Bio-Oss® and dentin particles are involved for comparison and cells are cultured in the eluates of these two materials also. Thiazolyl Blue Tetrazolium bromide assay-MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide assay) was used for the determination of cell viability. The results obtained by all aforementioned characterization methods of SBA-16/HA, revealed a uniform spherical mesoporous structure, an intrinsic characteristic of this material. This material displayed excellent biocompatibility on SHEDs, and even proliferative potential, indicating that SBA-16/HA could potentially serve as a suitable substrate for bone regeneration. Contrary to SBA-16/HA, dentin particles showed low cytotoxicity at all time points, compared to control and Bio-Oss®groups. Our results substantiate the idea that SBA-16/HA has a beneficial effect on SHEDs, thus paving the way toward developing new material for bone replacement.


Assuntos
Durapatita , Nanocompostos , Idoso , Polpa Dentária , Dentina/química , Durapatita/química , Humanos , Dióxido de Silício/análise , Dióxido de Silício/química , Dióxido de Silício/farmacologia , Células-Tronco , Difração de Raios X
6.
Virus Evol ; 7(1): veab023, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34522389

RESUMO

For over a decade, the New Vaccine Surveillance Network (NVSN) has conducted active rotavirus (RVA) strain surveillance in the USA. The evolution of RVA in the post-vaccine introduction era and the possible effects of vaccine pressure on contemporary circulating strains in the USA are still under investigation. Here, we report the whole-gene characterization (eleven ORFs) for 157 RVA strains collected at seven NVSN sites during the 2014 through 2016 seasons. The sequenced strains included 52 G1P[8], 47 G12P[8], 18 G9P[8], 24 G2P[4], 5 G3P[6], as well as 7 vaccine strains, a single mixed strain (G9G12P[8]), and 3 less common strains. The majority of the single and mixed strains possessed a Wa-like backbone with consensus genotype constellation of G1/G3/G9/G12-P[8]-I1-R1-C1-M1-A1-N1-T1-E1-H1, while the G2P[4], G3P[6], and G2P[8] strains displayed a DS-1-like genetic backbone with consensus constellation of G2/G3-P[4]/P[6]/P[8]-I2-R2-C2-M2-A2-N2-T2-E2-H2. Two intergenogroup reassortant G1P[8] strains were detected that appear to be progenies of reassortment events between Wa-like G1P[8] and DS-1-like G2P[4] strains. Two Rotarix® vaccine (RV1) and two RV5 derived (vd) reassortant strains were detected. Phylogenetic and similarity matrices analysis revealed 2-11 sub-genotypic allelic clusters among the genes of Wa- and DS-1-like strains. Most study strains clustered into previously defined alleles. Amino acid (AA) substitutions occurring in the neutralization epitopes of the VP7 and VP4 proteins characterized in this study were mostly neutral in nature, suggesting that these RVA proteins were possibly under strong negative or purifying selection in order to maintain competent and actual functionality, but fourteen radical (AA changes that occur between groups) AA substitutions were noted that may allow RVA strains to gain a selective advantage through immune escape. The tracking of RVA strains at the sub-genotypic allele constellation level will enhance our understanding of RVA evolution under vaccine pressure, help identify possible mechanisms of immune escape, and provide valuable information for formulation of future RVA vaccines.

7.
J Environ Sci Health B ; 45(7): 626-32, 2010 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-20803366

RESUMO

A headspace solid phase microextraction method (HS-SPME) for simultaneous determination of five pesticides belonging to triazine and organophosphorus pesticide groups in soil samples was developed. Microextraction conditions, such as temperature, extraction time and sodium chloride (NaCl) content were investigated and optimized using 100 microm polydimethyl-siloxane (PDMS) fiber. Detection and quantification were done by gas chromatography-mass spectrometry (GC-MS). Relative standard deviation (RSD) and recovery values for multiple analysis of soil samples fortified at 30 microg kg(- 1) of each pesticide were below 13 % and higher than 70 %, respectively. Limits of detection (LOD) for all the compounds studied were less than 3.2 microg kg(- 1). The proposed method was applied in the analysis of some agricultural soil samples.


Assuntos
Compostos Organofosforados/isolamento & purificação , Resíduos de Praguicidas/isolamento & purificação , Poluentes do Solo/isolamento & purificação , Microextração em Fase Sólida/métodos , Triazinas/isolamento & purificação , Cromatografia Gasosa-Espectrometria de Massas , Compostos Organofosforados/análise , Resíduos de Praguicidas/análise , Poluentes do Solo/análise , Triazinas/análise
8.
Microsc Res Tech ; 83(2): 91-98, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31637811

RESUMO

The present in vitro study was aimed at evaluating the morphological changes in the cemento-enamel junction (CEJ) after exposure to acidic beverages using the scanning electron microscopy (SEM). The initial pH and titratable acidity (TA) was analyzed from follow groups: (I) Coca cola, (II) orange juice, (III) Cedevita, (IV) Red Bull, (V) Somersby cider, and (VI) white wine. The CEJ samples (n = 64), obtained from unerupted third molars, were allocated to one control (artificial saliva, n = 16) and six experimental groups (n = 8). The experimental samples were immersed in beverages (50 ml) for 15 min, three times daily, 10 days, and in artificial saliva between immersions. SEM analysis was performed in a blind manner, according to scoring scale. One-way ANOVA and Tukey's post hoc tests, as well as Kruskal-Wallis and Mann-Whitney U test used for statistical analysis. The pH values of the acidic beverages ranged from 2.65 (Coca cola) to 3.73 (orange juice), and TA ranged from 1.90 ml (Coca cola) to 5.70 ml (orange juice) of NaOH to reach pH 7.0. The SEM analysis indicated statistically significant differences between the control samples and those immersed in acidic beverages. The Groups IV, I, and II, showed the highest CEJ damage grade while those of the Group VI were the lowest. All the tested acidic beverages caused morphological changes in the CEJ with a smaller or larger exposure of dentine surface, and were not always related to the pH or TA of acidic beverages.


Assuntos
Ácidos/farmacologia , Bebidas/análise , Dente Serotino/efeitos dos fármacos , Colo do Dente/ultraestrutura , Erosão Dentária/etiologia , Bebidas Gaseificadas , Sucos de Frutas e Vegetais , Humanos , Concentração de Íons de Hidrogênio , Microscopia Eletrônica de Varredura , Colo do Dente/efeitos dos fármacos , Vinho
9.
J Environ Sci Health B ; 44(8): 781-7, 2009 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-20183090

RESUMO

This study was undertaken to compare two different analytical methods for the determination and confirmation of ochratoxin A (OTA) in blood serum, kidney and liver of pigs. Sample clean-up was based on liquid-liquid phase extraction. The detection of OTA was accomplished with high-performance liquid chromatography (HPLC) combined either with fluorescence detection (FL) or electro spray ionization (ESI+) tandem mass spectrometry (MS-MS). Comparative method evaluation was based on the investigation of 90 samples of blood serum, kidney and liver per animal originating from different regions of Serbia. The analytical results are discussed in view of the respective method validation data and the corresponding experimental protocols. In general, analytical data obtained with (LC-MS-MS) liquid chromatography electro spray tandem mass spectro metry detection offered comparable good results at the sub-ppb concentration level. The results indicate that the liquid chromatography electro spray tandem mass spectrometric (LC-MS/MS) method was more specific and sensitive for the analysis and confirmation of ochratoxin A in pig tissues then high pressure liquid chromatography (HPLC) method after methylation of OTA.


Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Ocratoxinas/análise , Espectrometria de Massas por Ionização por Electrospray , Suínos/metabolismo , Espectrometria de Massas em Tandem , Animais , Fracionamento Químico , Rim/metabolismo , Fígado/metabolismo , Metilação , Ocratoxinas/sangue , Reprodutibilidade dos Testes , Espectrometria de Fluorescência , Suínos/sangue
10.
Food Chem ; 271: 469-478, 2019 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-30236704

RESUMO

UV-C irradiation is widely used in the food industry. However, the health effects from dietary exposure to the irradiated pesticide residues retained in foodstuffs are underestimated. In this study, technical chlorpyrifos (TCPF) and its oil in water (EW) and emulsifiable concentrate (EC) formulations were irradiated by UV-C, and their photodegradation products were subjected to toxicity assessment, including determination of acetylcholinesterase (AChE) activity, genotoxicity and oxidative stress using human blood cells as a model system. Toxicity studies were performed using the chlorpyrifos concentrations in the range of those proposed as the maximum residue levels in plant commodities. TCPF, EW and EC photodegradation products induced DNA damage and oxidative stress, and their genotoxicity did not decrease as a function of irradiation time. Irradiated TCPF and EC are more potent AChE inhibitors than irradiated EW. Accordingly, the application of UV-C irradiation must be considered when processing the plants previously treated with chlorpyrifos formulations.


Assuntos
Clorpirifos/efeitos da radiação , Clorpirifos/toxicidade , Raios Ultravioleta , Acetilcolinesterase , Inibidores da Colinesterase , Humanos , Inseticidas/efeitos da radiação , Inseticidas/toxicidade , Estresse Oxidativo
11.
Environ Toxicol Pharmacol ; 25(3): 334-41, 2008 May.
Artigo em Inglês | MEDLINE | ID: mdl-21783871

RESUMO

Carbofuran toxicity on rats was studied during subchronic exposure. Female and male rats were administered carbofuran in drinking water in concentrations of 25, 100 and 400ppm for a period of 90 days. Clinical symptoms, water consumption, body weight gain, organ weight, pathological and histopathological changes in the liver and kidneys were observed and biochemical and haematological examinations were carried out. The results obtained show that carbofuran administered to rats caused a significant decrease in water consumption as well as in brain, serum and erythrocyte cholinesterase activities. Statistically significant increases in relation to the control were found in the serum enzyme activities. The haematological data showed that carbofuran had no significant effect on Hb concentration and total RBC, but total WBC showed a significant statistical decrease. The histopathological changes in liver and kidneys were observed. However, cell regeneration in the liver and kidneys was found in all test groups.

12.
Front Psychiatry ; 9: 271, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29988422

RESUMO

Schizophrenia and treatment of this disorder are often accompanied with metabolic syndrome and cardiovascular issues. Alterations in the serum level of innate immune mediators, such as interleukin-33 (IL-33) and its receptor IL-33R (ST2) and Galectin-3 (Gal-3) were observed in these conditions. Moreover, these parameters are potential prognostic and therapeutic markers. There is also accumulating evidence that these molecules play a role in neuroinflammation. Therefore, in this study we have investigated the serum level of Gal-3, IL-33 and soluble ST2 (sST2) in different stages of schizophrenia. Gal-3 levels were elevated in remission and lower in schizophrenia exacerbation in comparison with controls. Levels of IL-33 and sST2 are higher in schizophrenia exacerbation in comparison with controls and patients in remission. This initial analysis of new markers of neuroinflammation suggested their involvement in schizophrenia pathophysiology and/or cardiometabolic comorbidity.

13.
Melanoma Res ; 28(1): 8-20, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29135861

RESUMO

Melanoma, an aggressive skin tumor with high metastatic potential, is associated with high mortality and increasing morbidity. Multiple available chemotherapeutic and immunotherapeutic modalities failed to improve survival in advanced disease, and the search for new agents is ongoing. The aim of this study was to investigate antimelanoma effects of O,O-diethyl-(S,S)-ethylenediamine-N,N'di-2-(3-cyclohexyl) propanoate dihydrochloride (EE), a previously synthesized and characterized organic compound. Mouse melanoma B16 cell viability was assessed using acid phosphatase, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, sulforhodamine B, and lactate dehydrogenase assays. Apoptosis and autophagy were investigated using flow cytometry, fluorescence and electron microscopy, and western blotting. In vivo antitumor potential was assessed in subcutaneous mouse melanoma model after 14 days of treatment with EE. Tumor mass and volume were measured, and RT-PCR was used for investigating the expression of autophagy-related, proapoptotic, and antiapoptotic molecules in tumor tissue. Investigated organic compound exerts significant cytotoxic effect against B16 cells. EE induced apoptosis, as confirmed by phosphatidyl serine externalisation, caspase activation, and ultrastructural features typical for apoptosis seen on fluorescence and electron microscopes. The apoptotic mechanism included prompt disruption of mitochondrial membrane potential and oxidative stress. No autophagy was observed. Antimelanoma action and apoptosis induction were confirmed in vivo, as EE decreased mass and volume of tumors, and increased expression of several proapoptotic genes. EE possesses significant antimelanoma action and causes caspase-dependent apoptosis mediated by mitochondrial damage and reactive oxygen species production. Decrease in tumor growth and increase in expression of proapoptotic genes in tumor tissue suggest that EE warrants further investigation as a candidate agent in treating melanoma.


Assuntos
Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Cicloexanos/farmacologia , Etilenodiaminas/farmacologia , Melanoma Experimental/patologia , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Propionatos/farmacologia , Animais , Autofagia , Técnicas In Vitro , Melanoma Experimental/tratamento farmacológico , Camundongos , Camundongos Endogâmicos C57BL , Espécies Reativas de Oxigênio/metabolismo , Células Tumorais Cultivadas
14.
Arch Med Res ; 37(7): 866-70, 2006 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-16971227

RESUMO

BACKGROUND: Alpha-1 antitrypsin (AAT) is an important serine protease inhibitor in human plasma. Its major physiological role is to inhibit neutrophil elastase (NE) in the lower respiratory tract and protect lung tissue from destruction. Recent studies indicated an etiological role of NE in lung cancer development. The aim of this study was to investigate the association of alpha-1 antitrypsin deficiency (AATD) with lung cancer in patients with four different histological types of cancer: squamous cell carcinoma, adenocarcinomas, large cell carcinoma and small cell carcinoma. METHODS: Phenotyping was carried out by isoelectric focusing (pH 4.2-4.9). We compared the frequency of AATD phenotypes in 186 lung cancer patients with the value obtained in our previous study in a healthy Serbian population (3.7%) using the Fisher exact test. RESULTS: Allele frequencies in patients were Pi *M 0.9677, Pi *Z 0.0215, Pi *S 0.0081 and Pi *other rare 0.0027. Eleven of the 186 lung cancer patients (5.9%) were AATD heterozygotes with moderate deficiencies (PiMZ and PiMS). When this value was compared with AATD heterozygote frequency obtained in the healthy individuals (3.7%), the difference was close to the level of significance (p = 0.055). However, individuals with AATD phenotypes had a higher risk of developing squamous cell lung cancer then those with non-deficient AAT variants (OR = 4.51, 95% CI = 1.66-12.29). CONCLUSIONS: Our findings provide evidence of an association between AAT phenotypes with moderate deficiency and squamous cell lung cancer.


Assuntos
Carcinoma de Células Escamosas/epidemiologia , Neoplasias Pulmonares/epidemiologia , Deficiência de alfa 1-Antitripsina/diagnóstico , Adulto , Idoso , Feminino , Frequência do Gene , Humanos , Masculino , Pessoa de Meia-Idade , Fenótipo , Fumar , Iugoslávia/epidemiologia , alfa 1-Antitripsina/genética , Deficiência de alfa 1-Antitripsina/genética
15.
Anal Sci ; 22(5): 753-6, 2006 May.
Artigo em Inglês | MEDLINE | ID: mdl-16770057

RESUMO

The kinetics of streptomycin degradation by hydrogen peroxide at pH 7.4 was investigated. The reaction was catalyzed by traces of Cu(II) ions, and it was followed spectrophotometrically at 322 nm by applying the initial-rate method. The kinetic parameters of the reaction are reported, and a rate equation is suggested. From the dependence of the relative rate constants on the temperature, the activation energy was calculated to be 57.5 kJ/mol. Based on this reaction, a kinetic method for streptomycin determination is proposed. The calibration graph is linear in the ranges 1.94 - 15.48 microg/cm(3) and 0.15 - 1.94 microg/cm(3). The influence of foreign ions and molecules on the accuracy of the determinations was investigated. The proposed kinetic method has high selectivity and good sensitivity, and enabled to determine streptomycin in pharmaceutical samples.


Assuntos
Antibacterianos/análise , Cobre/química , Peróxido de Hidrogênio/química , Preparações Farmacêuticas/química , Estreptomicina/análise , Calibragem , Cinética , Preparações Farmacêuticas/normas , Sensibilidade e Especificidade , Espectrofotometria Ultravioleta
16.
J Med Chem ; 37(12): 1874-81, 1994 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-8021927

RESUMO

IBI [2-(4'-isothiocyanatobenzyl)imidazoline, 3] has been shown to cause slow-onset, long-lasting contractions of rat thoracic aorta through a non-alpha-adrenergic receptor (non-alpha-AR) mediated mechanism. A series of IBI-related anlogs 7-14 and 16 was prepared to determine the structural requirements for the interaction with non-alpha-AR in rat aortic strips. All IBI analogs produced concentration-dependent contractile responses on rat thoracic aorta. Whereas the actions of analogs 7, 14, and 16 were partly mediated by alpha-ARs, the stimulatory activities of the remaining IBI analogs were unaffected by phenoxybenzamine pretreatment, suggesting that a non-alpha-adrenergic mechanism is involved. We have shown that the contractile actions of IBI and analogs 10-13 were not blocked with the imidazoline/guanidinium receptive site (IGRS) ligands idazoxan, cirazoline, or clonidine. However, the calcium channel blockers nifedipine or verapamil shifted the concentration-response curve of IBI and its analogs 10-13 to the right and reduced the maximal contractile responses. The action of IBI on rat thoracic aorta was reduced by the omission of extracellular calcium in the medium. These results suggest that the stimulatory activities of IBI and analogs 10-13 are not related to the activation of alpha-AR or IGRS receptors and are likely coupled to the voltage-dependent Ca2+ channels.


Assuntos
Aorta Torácica/efeitos dos fármacos , Tolazolina/análogos & derivados , Animais , Aorta Torácica/fisiologia , Canais de Cálcio/efeitos dos fármacos , Dioxanos/farmacologia , Idazoxano , Imidazóis/farmacologia , Técnicas In Vitro , Masculino , Contração Muscular/efeitos dos fármacos , Nifedipino/farmacologia , Ratos , Ratos Sprague-Dawley , Receptores Adrenérgicos alfa/efeitos dos fármacos , Tolazolina/síntese química , Tolazolina/química , Tolazolina/farmacologia , Verapamil/farmacologia
17.
J Med Chem ; 41(7): 1034-41, 1998 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-9544203

RESUMO

The R- and S-isomers of 3,5-dinitro-o-tyrosine (6a,b) have been synthesized through the use of chemoenzymatic synthesis and shown to bind differentially with the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropanoic acid (AMPA, 3) receptors. The phenolic functional group of these o-tyrosine analogues was designed to act as a bioisostere of the gamma-carboxyl group of glutamate. The S-isomer of 3,5-dinitro-o-tyrosine (6b) was 6.5 times more potent than the R-isomer (6a) in inhibiting [3H]AMPA binding with IC50 values of 13 +/- 7 and 84 +/- 26 microM, respectively. The phenolic group was important for binding affinity since the methoxy compound 7 was less potent than the phenolic compound 6 in inhibiting the binding of AMPA. The free amino group was also shown to be important since the N-acetyl analogue 15 and the N-t-BOC compounds 16 and 17 exhibited very low affinity for the AMPA receptors. AMPA receptor functional tests showed that the o-tyrosine analogues are antagonists and that the S-isomer 6b (IC50 = 630 +/- 140 microM) was more potent than the racemate 6 (IC50 = 730 +/- 88 microM) while the R-isomer 6a was inactive up to 1 mM concentration, which is consistent with the S-isomer having higher binding affinity than the R-isomer.


Assuntos
Quinazolinas/síntese química , Receptores de AMPA/antagonistas & inibidores , Tirosina/análogos & derivados , Animais , Desenho de Fármacos , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Quinazolinas/química , Quinazolinas/farmacologia , Ratos , Tirosina/química , Tirosina/farmacologia
18.
J Med Chem ; 42(18): 3588-601, 1999 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-10479290

RESUMO

A series of 3-fluoromethyl-1,2,3,4-tetrahydroisoquinolines (3-fluoromethyl-THIQs) was proposed, and their phenylethanolamine N-methyltransferase (PNMT) and alpha(2)-adrenoceptor affinities were predicted through the use of comparative molecular field analysis (CoMFA) models. These compounds were synthesized and evaluated for affinity at PNMT and the alpha(2)-adrenoceptor. It was discovered that these compounds are some of the most selective inhibitors of PNMT versus the alpha(2)-adrenoceptor known. To determine the ability of these compounds to penetrate the blood-brain barrier (BBB), a series of THIQs possessing a variety of calculated partition coefficients (Clog P) were assayed using an in vitro BBB model. This study found a good correlation between lipophilicity (Clog P) and BBB permeability, which indicated that THIQs possessing Clog P values of at least 0.13-0.57 should have some penetration into the brain. Two compounds [3-fluoromethyl-7-N-(4-chlorophenyl)aminosulfonyl-THIQ (18) and 3-fluoromethyl-7-cyano-THIQ (20)] possess calculated partition coefficients greater than 0.57 and display selectivities (alpha(2)-adrenoceptor K(i)/PNMT K(i)) greater than 200 and thus represent promising leads in the development of highly selective inhibitors of PNMT with the ability to penetrate the BBB.


Assuntos
Antagonistas de Receptores Adrenérgicos alfa 2 , Isoquinolinas/síntese química , Feniletanolamina N-Metiltransferase/antagonistas & inibidores , Glândulas Suprarrenais/enzimologia , Animais , Ligação Competitiva , Barreira Hematoencefálica , Bovinos , Clonidina/metabolismo , Inibidores Enzimáticos/síntese química , Inibidores Enzimáticos/farmacologia , Compostos de Flúor/síntese química , Compostos de Flúor/farmacologia , Isoquinolinas/farmacologia , Modelos Moleculares , Permeabilidade
19.
Eur J Drug Metab Pharmacokinet ; 19(2): 107-17, 1994.
Artigo em Inglês | MEDLINE | ID: mdl-8001591

RESUMO

Metabolic pathways and the pharmacokinetic profile of mefenorex ((+/-)N-(3-chloropropyl)-1-methyl-2-phenylethylamine), and its main metabolite amphetamine (1-methyl-2-phenylethylamine) have been studied in two healthy volunteers, after a single oral dose of mefenorex (1.2 mg/kg body weight for a male subject and 2.4 mg/kg body weight for a female subject). Urinary concentrations were determined by gas chromatography (GC) and metabolite structure was identified by GC/MS following derivatization of urine extracts. The ratio of this metabolite to unchanged drug in urine samples, collected up to 5 h following administration, was essentially the same after either of the administered doses. The calculated Kel for mefenorex after the higher dose was in the range of 0.191-0.272 h-1, with a biological half life (t1/2) of 3.98-2.55 h, depending on the method of calculation used. The elimination of amphetamine was much slower with a Kel ranging from 0.039-0.073 h-1 and a t1/2 from 9.5-17.8 h. Depending on the dose administered, the rate constant of metabolite formation was 0.129 and 0.685 h-1 for low and high doses, respectively. Urinary excretion of Rondimen amounted to 11.9% within 72 h after administration. Of this amount, 1.5% represented unchanged drug and 10.4% represented metabolites. In addition to amphetamine 3 other metabolites were identified: p-hydroxy mefenorex, p-hydroxy amphetamine and p-hydroxy-m-methoxy mefenorex.


Assuntos
Anfetaminas/farmacocinética , Depressores do Apetite/farmacocinética , Administração Oral , Anfetamina/urina , Anfetaminas/administração & dosagem , Anfetaminas/urina , Depressores do Apetite/administração & dosagem , Biotransformação , Feminino , Cromatografia Gasosa-Espectrometria de Massas , Meia-Vida , Humanos , Masculino , Software , Solubilidade
20.
Meat Sci ; 97(4): 459-67, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24769144

RESUMO

Fermented dry sausages (FDS) without nitrite added, fortified with bioactive phenol and flavonoid compounds originating from the ethanol extract of Kitaibelia vitifolia were food matrix for investigation of its antioxidant and antimicrobial potency. These activities were researched in order to improve the sausages' shelf-life, safety, and provide health benefits to consumers as well. The oxidative stability of the FDS, containing two different levels of natural preservative, was evaluated using five different contemporary methods for antioxidative activity. The activity was tested on the 20th day of the refrigerated storage. Minimum inhibitory concentrations of the sausage extract were determined against six microorganisms, using a micro dilution method. Determined optimal effective concentration of dissolved K. vitifolia extract (12.5 g/kg of meat dough) revealed strong antioxidant activity, and moderate antimicrobial activity against Escherichia coli (minimum inhibitory concentrations=15.625 µg/mL). The modified sausages had typical chemical-physical characteristics of FDS, controlled on 0, 13, 26 d of ripening and 20, 40 and 60 d of storage.


Assuntos
Antibacterianos/farmacologia , Antioxidantes/farmacologia , Escherichia coli/efeitos dos fármacos , Conservantes de Alimentos/farmacologia , Malvaceae/química , Produtos da Carne , Extratos Vegetais/farmacologia , Animais , Dieta , Fermentação , Flavonoides/farmacologia , Microbiologia de Alimentos , Conservação de Alimentos/métodos , Humanos , Produtos da Carne/microbiologia , Testes de Sensibilidade Microbiana , Nitritos , Oxirredução , Fenóis/farmacologia , Suínos
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