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1.
J Radiol Prot ; 38(2): 763-774, 2018 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-29667600

RESUMEN

INTRODUCTION: The exact level of exposure experienced by nuclear medicine personnel, whose work often requires performing manual procedures involving radioactive isotopes, is associated with the form of radiation source used. The variety of radionuclides and medical procedures, and the yearly increase in the number of patients, as well as the change of the individual dose limit for the lens of the eye from a value of 150 mSv yr-1 to 20 mSv yr-1, mean that issues of eye lens routine dosimetry become interesting from the radiation protection point of view. OBJECTIVE: This paper presents an analysis of the exposure of the eye lenses of nuclear medicine department personnel, as well as those of personnel in the facilities that produce radiopharmaceuticals for the purpose of diagnosis by positron emission tomography, from the viewpoint of the advisability of routine eye lens exposure monitoring, taking into account changes in the dose limit for the lens of the eye. MATERIALS AND METHODS: The paper considers the two most commonly used radionuclides for diagnostic purposes 99mTc, 18F, and-for therapeutic purposes-131I. Dose measurements were made using thermoluminescent detectors. RESULTS: The estimated exposure analysis identifies the cases when the maximum annual value of the personal dose equivalent, in terms of Hp(3), exceeds threefold the new limit value (20 mSv yr-1). CONCLUSIONS: It is recommended that Hp(3) doses be routinely monitored in the group of radiopharmacists who label pharmaceuticals with the radionuclide 99mTc and in chemists working in 18F-FDG quality control departments in production units, where this is carried out manually.


Asunto(s)
Cristalino/efectos de la radiación , Medicina Nuclear , Exposición Profesional/prevención & control , Radiometría/métodos , Humanos , Radioisótopos , Radiofármacos
2.
Appl Opt ; 53(7): 1258-67, 2014 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-24663352

RESUMEN

We studied the transmission characteristics of higher-order rocking filters induced mechanically in birefringent microstructured fibers and standard elliptical core fibers with varying spectral dependence of phase modal birefringence. We demonstrated the effect of birefringence dispersion on polarization mode coupling induced by a point-like force. We also investigated the spectral dependence of the resonance depth and force-induced resonance wavelength shift in mechanical rocking filters. The observed phenomena were explained by a numerical model linking the spectral dependence of the polarization mode coupling coefficient with the dispersion of intrinsic fiber birefringence and applied force.

3.
Bioelectrochemistry ; 150: 108333, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-36463591

RESUMEN

The dielectric properties of the non-glycated and in vitro methylglyoxal-glycated cornea of the rabbit eye were tested in the frequency range of 200 Hz to 100 kHz of the electric field and at temperatures of 25 to 140 °C. The denaturation temperature (Td) for the non-glycated cornea and the non-enzymatically glycated cornea are approximately 45 and 55 °C, respectively. The mechanism of proton conduction up to Td in a glycated cornea requires more energy, i.e. more than twice the activation energy (ΔH) than in non-glycated tissue. The dielectric spectra for both examined tissues showed the same characteristic frequency of about 7 kHz assigned to the orientation relaxation time of the polar side groups inside the corneal stroma. These results may be useful in the surgical treatment of the cornea using conductive keratoplasty and in tissue engineering for clinical applications to regenerate this tissue. The medical use of these physico-biological techniques is important because the human cornea protects all eye tissues from various environmental factors.


Asunto(s)
Córnea , Piruvaldehído , Animales , Humanos , Conejos , Córnea/fisiología , Temperatura , Electricidad
4.
Opt Express ; 20(21): 23320-30, 2012 Oct 08.
Artículo en Inglés | MEDLINE | ID: mdl-23188295

RESUMEN

We report on the sensing characteristics of rocking filters fabricated in two microstructured fibers with enhanced polarimetric sensitivity to hydrostatic pressure. The filter fabricated in the first fiber shows a very high sensitivity to pressure ranging from 16.2 to 43.4 nm/MPa, depending on the resonance order and features an extremely low cross-sensitivity between pressure and temperature 28 ÷ 89 × 10(3) K/MPa. The filter fabricated in the second fiber has an extreme sensitivity to pressure ranging from -72.6 to -177 nm/MPa, but a less favorable cross-sensitivity between pressure and temperature of 1.05 ÷ 3.50 × 10(3) K/MPa. These characteristics allow using the rocking filters for pressure measurements with mbar resolution.


Asunto(s)
Tecnología de Fibra Óptica/instrumentación , Filtración/instrumentación , Presión Hidrostática , Refractometría/instrumentación , Transductores de Presión , Diseño de Equipo , Análisis de Falla de Equipo , Luz , Miniaturización
5.
Mutat Res ; 716(1-2): 51-8, 2011 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-21875606

RESUMEN

Tobacco smoking is one of the major risk factors in pathogenesis of head and neck squamous cell carcinomas (HNSCC). Many of the chemical compounds present in tobacco are well-known carcinogens which form adducts with DNA. Cells remove these adducts mainly by the nucleotide excision repair pathway (NER). NER also eliminates a broad spectrum of pyrimidine dimers (CPD) and photo-products (6-4PP) induced by UV-radiation or DNA cross-links after cisplatin anti-cancer treatment. In this study DNA damage and repair was examined in peripheral blood lymphocytes obtained from 20 HNSCC patients and 20 healthy controls as well as HTB-43 larynx and SSC-25 tongue cancer cell lines. DNA repair kinetics in the examined cells after cisplatin or UV-radiation treatment were investigated using alkaline comet assay during 240min of post-treatment incubation. MTT assay was used to analyse cell viability and the Annexin V-FITC kit specific for kinase-3 was employed to determine apoptosis after treating the cells with UV-radiation at dose range from 0.5 to 60J/m(2). NER capability was assessed in vitro with cell extracts by the use of a bacterial plasmid irradiated with UV-light as a substrate for the repair. The results show that lymphocytes from HNSCC patients and HTB-43 or SSC-25 cancer cells were more sensitive to genotoxic treatment with UV-radiation and displayed impaired DNA repair. Also evidenced was a higher rate of apoptosis induction after UV-radiation treatment of lymphocytes from the HNSCC patients and the HTB-43 cancer cells than after treatment of those from healthy donors. Finally, our results showed that there was a significant decrease in NER capacity in HTB-43 or SSC-25 cancer cells as well as in peripheral blood lymphocytes of HNSCC patients compared to controls. In conclusion, we suggest that the impaired NER pathway might be a critical factor in pathogenesis of head and neck cancer.


Asunto(s)
Carcinoma de Células Escamosas/genética , Daño del ADN , Reparación del ADN , Neoplasias de Cabeza y Cuello/genética , Apoptosis , Estudios de Casos y Controles , Línea Celular Tumoral , Supervivencia Celular/genética , Cisplatino/farmacología , Femenino , Humanos , Neoplasias Laríngeas/genética , Linfocitos/patología , Masculino , Persona de Mediana Edad , Carcinoma de Células Escamosas de Cabeza y Cuello , Rayos Ultravioleta/efectos adversos
6.
Appl Opt ; 50(21): 3742-9, 2011 Jul 20.
Artículo en Inglés | MEDLINE | ID: mdl-21772355

RESUMEN

We present a compact in-line fiber interferometric sensor fabricated in a boron doped two-mode highly birefringent microstructured fiber using a CO(2) laser. The intermodal interference arises at the fiber output due to coupling between the fundamental and the first order modes occurring at two fiber tapers distant by a few millimeters. The visibility of intermodal interference fringes is modulated by a polarimetric differential signal and varies in response to measurand changes. The proposed interferometer was tested for measurements of the strain and temperature, respectively, in the range of 20-700 °C and 0-17 mstrain. The sensitivity coefficients corresponding to fringe displacement and contrast variations are equal respectively for strain -2.51 nm/mstrain and -0.0256 1/mstrain and for temperature 16.7 pm/°C and 5.74×10(-5) 1/°C. This allows for simultaneous measurements of the two parameters by interrogation of the visibility and the displacement of interference fringes.

7.
Eur Rev Med Pharmacol Sci ; 15(12): 1375-84, 2011 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-22288298

RESUMEN

BACKGROUND AND OBJECTIVES: It cannot be excluded that supplementation with L-arginine, by improving function of endothelium and hypotensive effect, can be advantegeous in prevention of cardiovascular diseases in healthy people. However, reports about hypotensive effect of L-arginine in healthy people are unclear. Moreover, no research including ambulatory blood pressure measurement (ABPM) has been conducted so far. Therefore, the aim of our study was to show if 4-week supplementation of healthy people with L-arginine influences blood pressure measured with ABPM. MATERIALS AND METHODS: The study was carried out on 19 healthy people randomized to 6 g/24-hour, 12 g/24-hours of L-arginine or placebo. ABPM was carried out 4 times: before randomization, after 2 and 4 weeks of supplementation and 2 weeks after finishing supplementation. RESULTS: It was found that 4 weeks of supplementation of healthy people with L-arginine (6 or 12 g/24-hour) led to nonsignificant decrease of systolic and diastolic blood pressure; the decrease was greater during night. CONCLUSION: These findings showed that supplementation with L-arginine is not necessarily advantageous in healthy people.


Asunto(s)
Arginina/farmacología , Presión Sanguínea/efectos de los fármacos , Suplementos Dietéticos , Adulto , Arginina/administración & dosificación , Monitoreo Ambulatorio de la Presión Arterial , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Factores de Tiempo
8.
Bioelectrochemistry ; 142: 107923, 2021 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-34385118

RESUMEN

The relative permittivity and conductivity of healthy and alloxane-induced diabetic rabbits lenses were measured over a frequency range of 500 Hz to 100 kHz in an electric field and at temperatures from 25 to 150 °C. The dielectric spectra for both tissues showed two separate relaxations with a characteristic frequency of around 4 and 25 kHz assigned to the cortical and nuclear zones, respectively. These two dispersions are due to the interfacial polarization at the surface of the α-crystallin molecules. The denaturation temperature for the non-diabetic lens and the diabetic lens is approximately 70 and 80 °C, respectively. Moreover, the relative permittivity and conductivity values are higher in the diabetic lens than in the non-diabetic tissue at the same temperature and frequency. Our dielectric studies provide a better understanding of the thermal stability of crystallin-water complexes in normal and diseased human lenses.


Asunto(s)
Diabetes Mellitus/metabolismo , Impedancia Eléctrica , Cristalino , Animales , Cristalino/citología , Cristalino/metabolismo , Cristalino/patología , Conejos , Temperatura
9.
Bioelectrochemistry ; 135: 107583, 2020 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-32544783

RESUMEN

The dielectric properties of the eye lens were studied for healthy and alloxane-induced diabetic rabbits in the frequency range from 500 Hz to 100 kHz electric field and temperatures from 25 to 50 °C. In the full temperature range, the average relative permittivity and dielectric loss values for a healthy lens are lower than those recorded for diabetic tissue. Dielectric relaxation of polar amino acids on the alpha-crystallin surface with a characteristic frequency of 7 kHz in the range of 25-50 °C for healthy and diabetic samples is accompanied by the activation energy of proton conductivity with an average values of 33 and 39 kJ mol-1, respectively. The permittivity decrement, which characterizes the size of the dielectric dispersion with a central relaxation time of 0.023 ms for a diabetic sample, is more than twice as high as for a healthy sample. Measurements on the rabbit eye lens were carried out at ambient temperature above and below the physiological range, since these conditions provide an appropriate pattern of dielectric behavior for the diagnosis of clinical dysfunction of the human lens.


Asunto(s)
Diabetes Mellitus Experimental/metabolismo , Cristalino/metabolismo , Aloxano , Animales , Impedancia Eléctrica , Conejos , alfa-Cristalinas/metabolismo
10.
Artículo en Inglés | MEDLINE | ID: mdl-30678830

RESUMEN

INTRODUCTION: Ninety four residents of Kowary city (Poland) have been investigated for environmental radon exposure that ranged from 0.24 WLM to 9.6 WLM (activity concentration range: 35-2700 Bq/m3). Kowary was chosen because of uranium mineralisation in its close vicinity. METHOD: Whole population studied was divided into two groups: exposed to low radon activity concentrations resulting in the exposure of ≤0.55 WLM (value corresponding to the exposure to 100 Bq/m3 during whole year), and exposed to high radon activity concentration (>0.55 WLM). In the two groups two selected biomarkers in blood were assessed: the cytokinesis-block micronucleus assay (CBMN) on peripheral blood lymphocytes (PBL), and the levels of anti-p53 antibodies in serum measured because some data indicate increased expression of the antibodies in individuals after exposure to DNA damaging agents including radon. The potential confounding factors known to influence micronuclei (MN) frequency were also measured in serum: vitamin B12, folic acid, as well as total calcium. RESULTS: In the present study no significant correlation was found between MN frequency in PBL and radon exposure. Among all persons investigated only 11 had detectable levels of the anti-p53 antibodies, whereas only 3 persons had positive result. Therefore, the group was too small to perform any meaningful statistical analysis and to conclude on any association. Cigarette smoking did not significantly influence the number of MN. There was a significant positive correlation observed between MN frequency and age, as well as higher MN frequency was detected in women. CONCLUSION: The problem of the radon exposure is still unresolved and needs further studies on bigger human cohorts in order to search for more sensitive biomarkers.


Asunto(s)
Autoanticuerpos/sangre , Autoanticuerpos/inmunología , Exposición a Riesgos Ambientales/efectos adversos , Micronúcleos con Defecto Cromosómico/efectos de la radiación , Radón/toxicidad , Proteína p53 Supresora de Tumor/inmunología , Adulto , Factores de Edad , Anciano , Biomarcadores/sangre , Fumar Cigarrillos/efectos adversos , Daño del ADN/efectos de la radiación , Exposición a Riesgos Ambientales/análisis , Femenino , Humanos , Linfocitos/citología , Masculino , Pruebas de Micronúcleos , Persona de Mediana Edad , Polonia , Radón/análisis , Factores Sexuales , Encuestas y Cuestionarios
11.
Radiat Prot Dosimetry ; 130(3): 325-30, 2008.
Artículo en Inglés | MEDLINE | ID: mdl-18310609

RESUMEN

The specific nature of work in nuclear medicine departments involves the use of isotopes and handling procedures, which contribute to the considerable value of an equivalent dose received, in particular, by the fingertips. Standard nuclear medicine department uses ring dosemeters placed usually at the base of the middle finger. The main aim of the study was to find out whether a relationship exists between the doses recorded by thermoluminescent detectors placed at various locations on the radiopharmacists' hands and the doses recorded by the ring detectors, and to determine the character of that relationship. The correction factor represents a correction value to be used to calculate the doses which might be received by locations on the hand from the dose recorded by the ring dosemeter. The dose recorded by the ring dosemeter is on the average five times lower than that received by the fingertips of thumb, index and middle fingers.


Asunto(s)
Mano/efectos de la radiación , Medicina Nuclear , Radiación Ionizante , Carga Corporal (Radioterapia) , Diseño de Equipo , Dedos/efectos de la radiación , Humanos , Medicina Nuclear/métodos , Servicio de Medicina Nuclear en Hospital/métodos , Exposición Profesional , Monitoreo de Radiación/métodos , Protección Radiológica/métodos , Radiometría , Radiofármacos/análisis , Tecnecio/análisis , Dosimetría Termoluminiscente/métodos , Recursos Humanos
12.
J Clin Invest ; 89(6): 1885-91, 1992 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-1601995

RESUMEN

The oxidative modification of low density lipoprotein (LDL) may play an important role in atherosclerosis. We found that the antioxidant N,N'-diphenyl-1,4-phenylenediamine (DPPD) inhibits in vitro LDL oxidation at concentrations much lower than other reported antioxidants. To test whether DPPD could prevent atherosclerosis, New Zealand White rabbits were fed either a diet containing 0.5% cholesterol and 10% corn oil (control group) or the same diet also containing 1% DPPD (DPPD-fed group) for 10 wk. Plasma total cholesterol levels were not different between the two groups, but DPPD feeding increased the levels of triglyceride (73%, P = 0.007) and HDL cholesterol (26%, P = 0.045). Lipoproteins from DPPD-fed rabbits contained DPPD and were much more resistant to oxidation than control lipoproteins. After 10 wk, the DPPD-fed animals had less severe atherosclerosis than did the control animals: thoracic aorta lesion area was decreased by 71% (P = 0.0007), and aortic cholesterol content was decreased by 51% (P = 0.007). Although DPPD cannot be given to humans because it is a mutagen, our results indicate that orally active antioxidants can have antiatherosclerotic activity. This strongly supports the theory that oxidized LDL plays an important role in the pathogenesis of atherosclerosis.


Asunto(s)
Antioxidantes/farmacología , Arteriosclerosis/prevención & control , Colesterol/metabolismo , Lipoproteínas LDL/metabolismo , Fenilendiaminas/farmacología , Administración Oral , Animales , Antioxidantes/química , Arteriosclerosis/metabolismo , Colesterol/administración & dosificación , Colesterol/sangre , Humanos , Cinética , Masculino , Oxidación-Reducción , Fenilendiaminas/química , Conejos , Relación Estructura-Actividad
13.
Opt Express ; 15(21): 13547-56, 2007 Oct 17.
Artículo en Inglés | MEDLINE | ID: mdl-19550623

RESUMEN

We demonstrate experimentally that bending loss in large mode area photonic crystal fibers oscillates with wavelength. To do so we carried out loss measurements for different fiber bend radii and for different angular orientations. These results confirm the oscillatory behavior of bending loss vs. wavelength as predicted recently by numerical analysis [J. Olszewski et al., Opt. Express 13, 6015 (2005)]. We also found good agreement between our measurement results and our simulations relying on a finite element method with perfectly matched layers and an equivalent index model.

14.
Eur J Surg Oncol ; 32(2): 133-8, 2006 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-16412601

RESUMEN

AIM: To measure the absorbed doses of radiation to hands of medical staff performing sentinel node biopsy in breast cancer patients. METHODS: The study was conducted in 2004, during sentinel node biopsies in 13 breast cancer patients (T1/T2N0). Sentinel nodes were identified with the use of combined radiotracer/blue dye technique (lymphoscintigraphy--99mTc on albumin carrier, surgery after 24 h; blue dye; intraoperative detection of gamma radiation). Highly sensitive thermoluminescent dosimeters (TLD) made of LiF were used to assess the absorbed doses of radiation during the procedure. During lymphoscintigraphy and during surgical procedure a total of 57 TLDs was placed on different parts of hands of medical staff. RESULTS: Maximal dose recorded during lymphoscintigraphy by TLDs placed on the hands of the physician injecting the radiotracer was 164 microSv. Mean recorded doses were higher for non-dominant hand, especially for distal parts of the index finger, third finger and thumb. During the surgical procedure, TLDs placed on the hands of medical staff recorded much lower doses of radiation than during lymphoscintigraphy. The highest dose was recorded by TLD placed on the pulp of the dominant hand index finger (22 microSv) of the operating surgeon. Mean doses recorded by TLDs placed on the hands of the operating surgeon ranged from 2 to 8 microSv. The absorbed dose of radiation to hands of the scrub nurse was similar to that absorbed to hands of the operating surgeon. CONCLUSION: The maximum recorded dose during sentinel node biopsy in this study was 2200 times smaller than current 1-year dose limit.


Asunto(s)
Neoplasias de la Mama/diagnóstico por imagen , Mano/efectos de la radiación , Cuerpo Médico de Hospitales , Exposición Profesional/análisis , Radiofármacos/administración & dosificación , Biopsia del Ganglio Linfático Centinela , Agregado de Albúmina Marcado con Tecnecio Tc 99m/administración & dosificación , Neoplasias de la Mama/patología , Neoplasias de la Mama/cirugía , Femenino , Humanos , Polonia , Dosis de Radiación , Cintigrafía , Medición de Riesgo , Dosimetría Termoluminiscente
15.
B-ENT ; 2(2): 47-9, 2006.
Artículo en Inglés | MEDLINE | ID: mdl-16910286

RESUMEN

A comparative assessment of toxic element concentrations in serum and tissue bioptates in patients with laryngeal papilloma or cancer was performed. Examinations were conducted in 60 patients (40 men and 20 women) aged 20-88 years (average 59 +/- 05). Patients were divided into 3 groups; 20 patients with laryngeal papilloma were in group I, 20 with laryngeal cancer were in group II, and 20 with deviated nasal septums were included as a control group (III). Diagnosis of laryngeal papilloma (removed by direct microlaryngoscopy--Kleinsasser method) and laryngeal cancer (removed by the Rethi method) was histopatologically confirmed in patients from groups I and II, respectively. Patients in the control group received functional surgery to repair deviated nasal septums. Serum and tissue samples were obtained from all patients before surgery. Aluminum and lead concentrations were analysed by inductively coupled plasma atomic emission spectrometry (ICP-AES) using a Spectroflame M spectrometer. The considerable rise of aluminum and lead concentration in tissue bioptates and aluminum in serum in groups I and II in comparison to the control group suggests that these elements may play a significant part in the aetiology and development of precancerous lesions and laryngeal cancers. Measuring toxic chemical element concentrations in tissue bioptates can be useful in the diagnosis and estimation of development of precancerous lesions of the larynx as well as laryngeal cancer. Toxic elements concentration may play a significant role in carcinogenesis and may determine trends in cancer aetiology.


Asunto(s)
Aluminio/análisis , Biopsia , Neoplasias Laríngeas/química , Plomo/análisis , Papiloma/química , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Neoplasias Laríngeas/cirugía , Masculino , Persona de Mediana Edad , Tabique Nasal/anomalías , Tabique Nasal/cirugía , Papiloma/cirugía , Espectrofotometría Atómica
16.
Bioelectrochemistry ; 110: 32-40, 2016 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-27015448

RESUMEN

The main goal of this paper is the in vitro study of healthy and osteoarthritis (OA) human cartilage using the dielectric spectroscopy in the alpha-dispersion region of the electric field and in the temperatures from 25 to 140°C. The activation energy of conductivity needed to break the bonds formed by water in the extracellular matrix takes the average values of 61kJ/mol and 44kJ/mol for the control and OA cartilages, respectively. At 28°C, the small difference appears in the permittivity decrement between the control and OA cartilages, while the conductivity increment is about 2 times higher for the control tissue than that for the OA tissue. At 75°C, the conductivity increment for both of these samples is 8 times higher than their respective permittivity decrement. In addition, at 140°C the values of these both parameters for the OA tissue decrease by 8 times as compared to those recorded for the control sample. The relaxation frequency of about 10kHz is similar for both of these samples. The knowledge on dielectric properties of healthy and OA cartilage may prove relevant to tissue engineering focused on the repair of cartilage lesions via the layered structure designing.


Asunto(s)
Cartílago Articular/metabolismo , Fémur/metabolismo , Osteoartritis/metabolismo , Agua/metabolismo , Adulto , Colágeno/metabolismo , Espectroscopía Dieléctrica , Glicosaminoglicanos/metabolismo , Humanos , Persona de Mediana Edad , Temperatura
17.
Bioelectrochemistry ; 101: 132-7, 2015 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-25308935

RESUMEN

This paper aims at the presentation of the results of in vitro research on the dielectric properties of the cornea specimen collected from the rats subjected to in vivo hypothermia. The average values of the relative permittivity and dielectric loss are about 40% higher for the hypothermic cornea than those for the normothermic tissue at the same water content of 12% for both samples and at 25°C. Whereas, at 50°C this effect of increase in the dielectric properties of the hypothermic cornea when compared to the normothermic one is observed clearly only in the relative permittivity of about 19%. In the temperature range of 25-50°C, the activation energy of conductivity associated with the release of loosely bound water takes the average values of 45kJ/mol and 30kJ/mol for the normothermic and hypothermic corneas, respectively. The study provided information on dielectric polarization and conductance mechanisms in the cornea which may be helpful in interpreting clinical results of human cornea examination, currently obtained by means of such electrodiagnostic methods as conductive keratoplasty, electroretinography or electrooculography.


Asunto(s)
Córnea/fisiología , Hipotermia/fisiopatología , Animales , Córnea/química , Espectroscopía Dieléctrica/métodos , Electrofisiología/métodos , Masculino , Ratas Wistar , Temperatura
18.
J Med Chem ; 40(6): 1026-40, 1997 Mar 14.
Artículo en Inglés | MEDLINE | ID: mdl-9083493

RESUMEN

Carboxyalkyl peptides containing a biphenylylethyl group at the P1' position were found to be potent inhibitors of stromelysin-1 (MMP-3) and gelatinase A (MMP-2), in the range of 10-50 nM, but poor inhibitors of collagenase (MMP-1). Combination of a biphenylylethyl moiety at P1', a tert-butyl group at P2', and a methyl group at P3' produced orally bioavailable inhibitors as measured by an in vivo model of MMP-3 degradation of radiolabeled transferrin in the mouse pleural cavity. The X-ray structure of a complex of a P1-biphenyl inhibitor and the catalytic domain of MMP-3 is described. Inhibitors that contained halogenated biphenylylethyl residues at P1' proved to be superior in terms of enzyme potency and oral activity with 2(R)-[2-(4'-fluoro-4-biphenylyl)ethyl]-4(S)-n-butyl-1,5-pentane dioic acid 1-(alpha(S)-tert-butylglycine methylamide) amide (L-758,354, 26) having a Ki of 10 nM against MMP-3 and an ED50 of 11 mg/kg po in the mouse pleural cavity assay. This compound was evaluated in acute (MMP-3 and IL-1 beta injection in the rabbit) and chronic (rat adjuvant-induced arthritis and mouse collagen-induced arthritis) models of cartilage destruction but showed activity only in the MMP-3 injection model (ED50 = 6 mg/kg iv).


Asunto(s)
Dipéptidos/farmacología , Inhibidores de la Metaloproteinasa de la Matriz , Inhibidores de Proteasas/farmacología , Animales , Artritis/tratamiento farmacológico , Sitios de Unión , Cartílago/efectos de los fármacos , Cristalografía por Rayos X , Dipéptidos/síntesis química , Dipéptidos/química , Dipéptidos/metabolismo , Modelos Animales de Enfermedad , Gelatinasas/antagonistas & inhibidores , Interleucina-1/administración & dosificación , Interleucina-1/farmacología , Espectroscopía de Resonancia Magnética , Metaloproteinasa 1 de la Matriz , Metaloproteinasa 2 de la Matriz , Metaloendopeptidasas/antagonistas & inhibidores , Ratones , Modelos Moleculares , Estructura Molecular , Inhibidores de Proteasas/síntesis química , Inhibidores de Proteasas/química , Inhibidores de Proteasas/metabolismo , Conejos , Ratas , Proteínas Recombinantes/antagonistas & inhibidores , Relación Estructura-Actividad , Transferrina/metabolismo , Zinc/química , Zinc/metabolismo
19.
Biotechniques ; 34(1): 81-7, 2003 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-12545544

RESUMEN

Current baculovirus expression systems typically produce soluble proteins that accumulate within the infected insect cell or are secreted into the growth medium. A system has now been developed for the incorporation of foreign proteins, along with the matrix protein, polyhedrin, into baculovirus occlusion bodies. Initial studies showed that a recombinant virus expressing a translational fusion between polyhedrin and GFP did not form occlusion bodies. However, a baculovirus coexpressing native polyhedrin and the polyhedrin-GFP fusion protein formed occlusion bodies that fluoresced under UV light, demonstrating that they included the polyhedrin-GFP fusion protein. This was confirmed by immunoblot analysis. Thus, incorporation of a foreign protein into occlusion bodies depends on an interaction between native polyhedrin and the polyhedrin fusion protein. Electron microscopy demonstrated that the occlusion bodies containing GFP also incorporated virions as expected. These ColorPol occlusion bodies were as infectious to insect larvae as occlusion bodies produced by wild-type virus. This new system expands the capabilities for foreign gene expression by baculoviruses, which has implications for biopesticide design, novel vaccine delivery systems, and fusion protein purification applications.


Asunto(s)
Baculoviridae/genética , Baculoviridae/metabolismo , Proteínas Luminiscentes/metabolismo , Proteínas Virales/genética , Proteínas Virales/metabolismo , Animales , Baculoviridae/inmunología , Células Cultivadas , Regulación Viral de la Expresión Génica/genética , Vectores Genéticos/genética , Proteínas Fluorescentes Verdes , Proteínas Luminiscentes/genética , Sustancias Macromoleculares , Organismos Modificados Genéticamente , Spodoptera/inmunología , Transformación Genética , Proteínas Virales/biosíntesis
20.
Appl Biochem Biotechnol ; 13(1): 29-35, 1986 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-3019239

RESUMEN

The effect of the bifunctional crosslinking reagent glutaraldehyde on the activity of the restriction enzymes Bam HI, Hind III, EcoRI, and Tthlll I was investigated. The four enzymes exhibited differential sensitivity to inactivation. Tthlll I was the most sensitive, with activity losses occurring at levels of 0.0025% and above. Hind III was the most stable of the four and remained fully active at concentrations as high as 0.075%. Addition of BSA to incubation mixtures generally had a stabilizing effect. Implications of these results for the design of glutaraldehyde-based methods for the immobilization of restriction endonucleases are discussed.


Asunto(s)
Aldehídos/farmacología , Enzimas de Restricción del ADN/antagonistas & inhibidores , Glutaral/farmacología , Tampones (Química) , Reactivos de Enlaces Cruzados , Estabilidad de Medicamentos , Electroforesis en Gel de Poliacrilamida , Técnicas In Vitro , Albúmina Sérica Bovina , Espectrofotometría Ultravioleta
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