RESUMO
Radiolabeling cidofovir with technetium-99m (99mTc-CDV) is an innovative procedure that enables real-time monitoring of the drug. Essays were performed in vitro, showing high radiolabel stability within 24 h. Blood clearance, biodistribution studies, and scintigraphic images were performed in healthy mice in order to evaluate the profile of the drug in vivo. 99mTc-CDV showed biphasic blood circulation time and significant kidney uptake, indicating that 99mTc-CDV is preferentially eliminated by the renal route. Bones also showed important uptake throughout the experiment. In summary, cidofovir was successfully labeled with technetium-99m and might be used in further studies to track the drug.
Assuntos
Animais , Masculino , Feminino , Camundongos , Técnicas In Vitro , Tecnécio/farmacologia , Cidofovir/farmacologia , Atletismo/classificação , Tempo de Circulação Sanguínea/efeitos adversos , Preparações Farmacêuticas/análise , Rim , MétodosRESUMO
Liposomes are lipid vesicles widely used as nanocarriers in targeted drug delivery systems for therapeutic and/or diagnostic purposes. A strategy to prolong the blood circulation time of the liposomes includes the addition of a hydrophilic polymer polyethylene glycol (PEG) moiety onto the surface of the vesicle. Several studies claim that liposome PEGylation by a single chain length or a combination of PEG with different chain lengths may alter the liposomes' pharmacokinetic properties. Therefore, the purpose of this study was to evaluate the influence of PEG on the biodistribution of pH-sensitive liposomes in a tumor-bearing animal model. Three liposomal formulations (PEGylated or not) were prepared and validated to have a similar mean diameter, monodisperse distribution, and neutral zeta potential. The pharmacokinetic properties of each liposome were evaluated in healthy animals, while the biodistribution and scintigraphic images were evaluated in tumor-bearing mice. High tumor-to-muscle ratios were not statistically different between the PEGylated and non-PEGylated liposomes. While PEGylation is a well-established strategy for increasing the blood circulation of nanostructures, in our study, the use of polymer coating did not result in a better in vivo profile. Further studies must be carried out to confirm the feasibility of the non-PEGylated pH-sensitive liposomes for tumor treatment.
Assuntos
Neoplasias da Mama/fisiopatologia , Polietilenoglicóis/farmacocinética , Tecnécio/química , Animais , Tempo de Circulação Sanguínea , Linhagem Celular Tumoral , Sistemas de Liberação de Medicamentos , Feminino , Humanos , Concentração de Íons de Hidrogênio , Lipossomos , Taxa de Depuração Metabólica , Camundongos , Camundongos Endogâmicos BALB C , Transplante de Neoplasias , Polietilenoglicóis/administração & dosagem , Polietilenoglicóis/química , Distribuição TecidualRESUMO
BACKGROUND: We introduce and demonstrate that the AC biosusceptometry (ACB) technique enables real-time monitoring of magnetic nanoparticles (MNPs) in the bloodstream. We present an ACB system as a simple, portable, versatile, non-invasive, and accessible tool to study pharmacokinetic parameters of MNPs, such as circulation time, in real time. We synthesized and monitored manganese doped iron oxide nanoparticles in the bloodstream of Wistar rats using two different injection protocols. Aiming towards a translational approach, we also simultaneously evaluated cardiovascular parameters, including mean arterial pressure, heart rate, and episodes of arrhythmia in order to secure the well-being of all animals. RESULTS: We found that serial injections increased the circulation time compared with single injections. Immediately after each injection, we observed a transitory drop in arterial pressure, a small drop in heart rate, and no episodes of arrhythmia. Although some cardiovascular effects were observed, they were transitory and easily recovered in both protocols. CONCLUSIONS: These results indicate that the ACB system may be a valuable tool for in vivo, real-time MNP monitoring that allows associations with other techniques, such as pulsatile arterial pressure and electrocardiogram recordings, helping ensuring the protocol safety, which is a fundamental step towards clinical applications.
Assuntos
Tempo de Circulação Sanguínea , Compostos Férricos/sangue , Nanopartículas de Magnetita/química , Magnetometria/métodos , Animais , Arritmias Cardíacas/induzido quimicamente , Pressão Sanguínea , Eletrocardiografia , Compostos Férricos/farmacocinética , Frequência Cardíaca , Magnetismo , Masculino , Tamanho da Partícula , Ratos , Ratos WistarRESUMO
OBJECTIVE: To assess betamethasone (BM) effects on the cerebral hemodynamics of neonates with severe chronic lung disease (CLD). STUDY DESIGN: Intravenous BM was given once daily for 6 consecutive days to 12 infants (birth weight: 698 g [range, 650-884 g], gestational age: 25.3 weeks [range, 25-26.4 weeks]) at a postnatal age of 34 days (range, 28-36 days). Cerebral blood flow velocities (CBFVs) were recorded prospectively in the anterior cerebral artery (ACA) and the lenticulostriate artery (LSA) before, during, and after treatment, using Doppler flowmetry. RESULTS: The decrease in systolic and diastolic velocities was maximum on the 5th day, reaching 32% (95% confidence interval [CI], 23%-42%) and 58% (95% CI, 39%-64%) from baseline in the ACA, and 44% (95% CI, 29%-50%) and 57% (95% CI, 33%-66%) in the LSA, respectively. The resistance index (RI) increased significantly in both arteries during treatment. Return to baseline values was observed after BM was stopped. The change in velocities and RI was independent of arterial blood gas and blood pressure variations. CONCLUSIONS: BM decreased the CBFVs of premature infants, suggesting a vasoconstrictor effect in both superficial and deep arterial vessels. Caution is recommended when BM is used to treat preterm infants with severe CLD.
Assuntos
Betametasona/farmacologia , Circulação Cerebrovascular/efeitos dos fármacos , Recém-Nascido Prematuro , Pneumopatias/tratamento farmacológico , Artéria Cerebral Anterior/patologia , Tempo de Circulação Sanguínea , Doença Crônica , Feminino , Idade Gestacional , Humanos , Recém-Nascido , Doenças do Prematuro/tratamento farmacológico , Fluxometria por Laser-Doppler/métodos , Pneumopatias/patologia , Masculino , GravidezRESUMO
Pulse oximetry during breath-holding (BH) in normal residents at high altitude (3510 m) shows a typical graph pattern. Following a deep inspiration to total lung capacity (TLC) and subsequent breath-holding, a fall in oxyhemoglobin saturation (SaO(2) is observed after 16 s. The down-pointed peak in SaO(2) corresponds to the blood circulation time from the alveoli to the finger where the pulse oximeter probe is placed. This simple maneuver corroborates the measurement of circulation time by other methods. This phenomenon is even observed when the subject breathes 88% oxygen (PIO(2) = 403 mmHg for a barometric pressure of 495 mmHg). BH time is, as expected, prolonged under these circumstances. Thus the time delay of blood circulation from pulmonary alveoli to a finger is measured non-invasively. In the present study we used this method to compare the circulation time in 20 healthy male high altitude residents (Group N with a mean hematocrit of 50%) and 17 chronic mountain sickness patients (Group CMS with a mean hematocrit of 69%). In the two study groups, the mean circulation time amounted to 15.94 +/-2.57 s (SD) and to 15.66 +/-2.74 s, respectively. The minimal difference was not significant. We conclude that the CMS patients adapted their oxygen transport rate to the rise in hematocrit and blood viscosity.
Assuntos
Doença da Altitude/fisiopatologia , Dedos/irrigação sanguínea , Hipóxia/fisiopatologia , Oximetria/métodos , Alvéolos Pulmonares/irrigação sanguínea , Respiração , Aclimatação , Altitude , Doença da Altitude/sangue , Tempo de Circulação Sanguínea , Viscosidade Sanguínea , Estudos de Casos e Controles , Doença Crônica , Hematócrito , Humanos , Hipóxia/sangue , Masculino , Oxigênio/sangue , Oxiemoglobinas/metabolismoRESUMO
Schistosoma mansoni is responsible for lesions that can alter the hemodinamic of the portal venous circulation, lung arterial and venous sistemic systems. Therefore, hemodinamic changes in the ocular circulation of mansonic schistosomotic patients with portal hypertension and hepatofugal venous blood flow is also probable. The purpose of this study was to determine the fluorescein contrast arrival time at the retina of young patients with the hepatosplenic form of schistosomiasis, clinically and surgically treated. The control group included 36 non schistosomotic patients, mean age of 17.3 years, and the case group was represented by 25 schistosomotic patients, mean age of 18.2 years, who were cared for at The University Hospital (Federal University of Pernambuco, Brazil), from 1990 to 2001. They underwent digital angiofluoresceinography and were evaluated for the contrast arrival time at the early retinal venous phase of the exam. Both groups were ophthalmologically examined at the same hospital (Altino Ventura Foundation, Recife, Brazil), using the same technique. There was retardation of the retinal contrast arrival time equal or more than 70 sec in the eyes of three schistosomotic patients (12%) and in none of the control group, however, the mean contrast arrival time between the two groups were not statistically different. These findings lend support to the hypothesis that there could be a delay of the eye venous blood flow drainage.
Assuntos
Meios de Contraste/farmacocinética , Fluoresceína/farmacocinética , Hepatopatias Parasitárias/fisiopatologia , Vasos Retinianos/fisiopatologia , Esquistossomose mansoni/fisiopatologia , Esplenopatias/fisiopatologia , Adolescente , Adulto , Animais , Tempo de Circulação Sanguínea , Estudos de Casos e Controles , Criança , Feminino , Angiofluoresceinografia , Seguimentos , Humanos , Hepatopatias Parasitárias/metabolismo , Masculino , Vasos Retinianos/efeitos dos fármacos , Vasos Retinianos/metabolismo , Esquistossomose mansoni/metabolismo , Esplenopatias/metabolismoRESUMO
Schistosoma mansoni is responsible for lesions that can alter the hemodinamic of the portal venous circulation, lung arterial and venous sistemic systems. Therefore, hemodinamic changes in the ocular circulation of mansonic schistosomotic patients with portal hypertension and hepatofugal venous blood flow is also probable. The purpose of this study was to determine the fluorescein contrast arrival time at the retina of young patients with the hepatosplenic form of schistosomiasis, clinically and surgically treated. The control group included 36 non schistosomotic patients, mean age of 17.3 years, and the case group was represented by 25 schistosomotic patients, mean age of 18.2 years, who were cared for at The University Hospital (Federal University of Pernambuco, Brazil), from 1990 to 2001. They underwent digital angiofluoresceinography and were evaluated for the contrast arrival time at the early retinal venous phase of the exam. Both groups were ophthalmologically examined at the same hospital (Altino Ventura Foundation, Recife, Brazil), using the same technique. There was retardation of the retinal contrast arrival time equal or more than 70 sec in the eyes of three schistosomotic patients (12 percent) and in none of the control group, however, the mean contrast arrival time between the two groups were not statistically different. These findings lend support to the hypothesis that there could be a delay of the eye venous blood flow drainage