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1.
Lett Appl Microbiol ; 52(5): 527-31, 2011 May.
Artículo en Inglés | MEDLINE | ID: mdl-21355874

RESUMEN

AIMS: The effectiveness of four strains of Bifidobacteria against enterohemorrhagic Escherichia coli O157:H7 infection was studied using a Vero cell model. METHODS AND RESULTS: E. coli O157 was inoculated on the Vero cell line before and after treatment with probiotic. The cytopathic effect (CPE) was evaluated during 24 h of incubation. The results indicated that Shiga toxin activity was inhibited by the probiotic. To prevent a Stx2 CPE, the probiotic needs one log more than the Stx1. CONCLUSION: The Vero cell assay, in particular, is a good model to evaluate the effect of Bifidobacteria inhibiting bacterial attachment because of soluble substances and the competitive aspect and could be used in a variety of foods like milk and yoghurt to protect pathogen bacteria. SIGNIFICANCE AND IMPACT OF THE STUDY: Probiotics could control pathogenic bacteria and Vero cell introduce as a model for evaluation of probiotics against pathogen bacteria.


Asunto(s)
Bifidobacterium/fisiología , Infecciones por Escherichia coli/microbiología , Escherichia coli O157 , Probióticos , Animales , Supervivencia Celular/efectos de los fármacos , Chlorocebus aethiops , Interacciones Microbianas , Toxina Shiga I/toxicidad , Toxina Shiga II/toxicidad , Células Vero
2.
Arch Razi Inst ; 76(1): 95-105, 2021 03.
Artículo en Inglés | MEDLINE | ID: mdl-33818962

RESUMEN

Chemotherapy is the main approach for the treatment of cancer; however, it often causes unpleasant oxidative damages. Therefore, the development of an effective alternative/complementary therapy with improved tumor suppression efficiency and lower adverse effects is highly required. Recently, it has been shown that Cyrtopodion scabrum extract (CsE) is an effective and selective tumor suppressor medicine. The present study investigated the antioxidant activity of Cyrtopodion scabrum homogenate (CsH) and CsE and their effects on attenuating 5-fluorouracil (5-FU)-induced liver dysfunction in rats. A total of 60 male rats (weight: 200-220 g) were divided into six groups and treated for 14 days. The control (group I) and 5-FU (group II) groups received distilled water and 5-FU, respectively. The other four groups were orally administered with CsE, CsH, CsE+5-FU, and CsH+5-FU (groups III to VI), respectively by gavages based on a daily schedule. The 5-FU-induced oxidative damage was evaluated by changes in the weight and food and water intake during the treatment and antioxidant parameters in the liver and serum of the treated rats. The obtained data indicated that the administration of CsH and CsE significantly improved liver function and defense system of antioxidants by attenuating the levels or activities of malondialdehyde, superoxide anion, aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase and decrease of superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, glutathione S-transferase, total antioxidant capacity, glutathione, total protein, and albumin in the liver and serum, induced by 5-FU treatment. The obtained data of the current study suggested that CsH and CsE play a protective role in the imbalance elicited by 5-FU and can be used as alternative/complementary supplements with 5-FU to reduce oxidative damages which is the consequence of reactive oxygen species production in cancerous patients.


Asunto(s)
Antioxidantes , Estrés Oxidativo , Animales , Antioxidantes/metabolismo , Catalasa/metabolismo , Fluorouracilo/efectos adversos , Fluorouracilo/metabolismo , Hígado , Masculino , Ratas
3.
Arch Razi Inst ; 76(1): 107-117, 2021 03.
Artículo en Inglés | MEDLINE | ID: mdl-33818963

RESUMEN

The role of oxidative stress in female fertility is a compelling area for research. According to traditional medicine, Cichorium intybus, known as Kasni, is believed to improve fertility. For this purpose, the effects of C. intybus distillate (CI) on blood antioxidant status were assessed in rats with carbon tetrachloride (CCl4)-induced toxicity. The rats were assigned to four experimental groups of Control, CI, CCl4, and CI+CCl410 (n=10 in each group). The level of antioxidant enzymes, such as glutathione peroxidase (GPx), glutathione reductase (GR), and catalase (CAT), as well as lipid peroxidation and reduced glutathione (GSH) level, were measured in serum samples. In the second part of the study, the antioxidant activity and phytochemical composition of the hydrodistillate of C. intybus aerial parts were determined by DPPH radical scavenging and gas chromatography-mass spectrometry analysis, respectively. The administration of CCl4 decreased the enzyme activities of GPx, GR, and CAT which were significantly ameliorated after CI administration. The decreased level of serum GSH following CCl4 administration was not considerably elevated in the CI+CCl4 group. Furthermore, the level of malondialdehyde in the serum of CI+CCl4 rats was decreased, compared to the CCl4 group. The main compositions of the essential oil from the C. intybus distillate were the antioxidants of Pulegone (8.10%), Piperitenone (7.68%), dihydroactinidiolide (5.0%), and carvone (4.18%). The antioxidant activity of the distillate was obtained at 75µg/l using the DPPH (2,2-diphenyl-1-picryl-hydrazyl-hydrate) test. In general, the results of the present study demonstrated that C. intybus distillate, as a safe herbal remedy, can attenuate CCl4-induced oxidative damages via boosting the endogenous antioxidant defense system.


Asunto(s)
Tetracloruro de Carbono , Cichorium intybus , Extractos Vegetales , Animales , Ratas , Antioxidantes , Hígado , Fitoterapia
5.
J Parasit Dis ; 40(4): 1223-1225, 2016 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-27876920

RESUMEN

The objective of the present study was to examine the virulence of Toxoplasma gondii RH strain tachyzoites in embryonated eggs after continuous passage in Vero cell line. The first T. gondii tachyzoites was considered low passage (no passage) and then passaged for 80 times on Vero as high passage. Groups of 9-day-old embryonated eggs with ten eggs in each group were inoculated with 102,103 and 104 of low or high-passage T. gondii tachyzoites, and any mortality was recorded. Suitable samples from different tissues (liver, heart, and brain) of the dead embryos were collected for histopathological study. In this study, the mortality in group 103 and 104 was observed, but there was no significant differences in mortality rate in T. gondii low passage and high passage. This finding exactly correspond to previous studies that were performed in mice as animal model for T. gondii RH strain. Thus on base of this study we could introduce the embryonated eggs as an appropriate animal model to evaluate the virulence of T. gondii tachyzoites.

6.
J Parasit Dis ; 40(3): 699-706, 2016 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-27605770

RESUMEN

It has been shown that mice, particularly the BALB/c ones, are susceptible to infection by some of the apicomplexan parasites. To compare the susceptibility of the inbred BALB/c, outbred BALB/c and C57 BL/6 to Besnoitia caprae inoculation and to determine LD50, 30 male inbred BALB/c, 30 outbred BALB/c and 30 C57 BL/6 mice were assigned into 18 groups of 5 mice. Each group was inoculated intraperitoneally with 12.5 × 10(3), 25 × 10(3), 5 × 10(4), 1 × 10(5), 2 × 10(5) tachyzoites and a control inoculum of DMEM, respectively. The inbred BALB/c was found the most susceptible strain among the experienced mice strains so the LD50 per inbred BALB/c mouse was calculated as 12.5 × 10(3.6) tachyzoites while the LD50 for the outbred BALB/c and C57 BL/6 was 25 × 10(3.4) and 5 × 10(4) tachyzoites per mouse, respectively. To investigate the impact of different routes of inoculation in the most susceptible mice strain, another seventy five male inbred BALB/c mice were inoculated with 2 × 10(5) tachyzoites of B. caprae via various inoculation routes including: subcutaneous, intramuscular, intraperitoneal, infraorbital and oral. All the mice in the oral and infraorbital groups survived for 60 days, whereas the IM group showed quicker death and more severe pathologic lesions, which was then followed by SC and IP groups. Therefore, BALB/c mouse is a proper laboratory model and IM inoculation is an ideal method in besnoitiosis induction and a candidate in treatment, prevention and testing the efficacy of vaccines for besnoitiosis.

7.
J Parasit Dis ; 40(3): 845-7, 2016 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-27605795

RESUMEN

Recently chickens are considered as an important intermediate hosts for Neospora caninum. Free range chickens expose to infection with N. caninum oocysts because they feed from the ground therefore they could be a good index of the environmental contamination. We studied N. caninum infection in free range chickens by serological. One hundred and fifty chickens purchased from five regions from Fars province and their blood were used for serological testing. Antibodies to N. caninum were found in 26 (17.33 %) of 150 serum samples by MAT. This study is the first to describe the presence of antibodies to N. caninum in chicken in Iran. These serological results indicate a widespread exposure of free range chickens to N. caninum in south of Iran.

8.
J Parasit Dis ; 39(4): 624-7, 2015 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-26688623

RESUMEN

Besnoitia caprae is a tissue cyst-forming protozoan that infects goats and has considerable economic importance in certain regions of Asia and Africa. Murine macrophage J774 cell line was inoculated with tachyzoites of Besnoitia caprae (BC-Pars isolate) collected from mice. A significant growth of tachyzoites was observed in J774. Mice were inoculated with tachyzoites harvested from J774 cell culture. Skin samples from the mice infected with tachyzoites of BC-Pars were PCR positive. One mouse showed alopecia and skin lesions on 45 DPI. Dermal lesions started from around right eye and gradually developed more and more. After euthanasia on 60 DPI, histopathological evaluation of skins around the eye showed necrosis of the epidermis and follicular adnexa with chronic inflammatory cell infiltration. Histopathological sections of their skin showed the presence of necrosis and mononuclear cell infiltration. To the authors' knowledge, this is the first report of successful production of Besnoitia caprae tachyzoites was achieved in vitro by suspension culture technique. Another interesting finding is the report of the alopecia and skin lesions around the eye in mouse that quite similar to lesions of goats due to infection of Besnoitia caprae.

9.
J Parasit Dis ; 39(2): 241-4, 2015 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-26064008

RESUMEN

To date, there are no reports regarding comparison between different bird species in Neospora. caninum infection. In the present study 70 embryonated eggs from quail, partridge, broiler and egg laying chickens were divided into 7 groups equally. Six groups in each species were inoculated with different dilutions (10, 10(2), 10(3), 10(4), 10(5), and 10(6)) of tachyzoites/embryonated egg in the chorioallantoic membrane and the seventh group was considered as control. The mortality rates and clinical signs were studied. All the egg laying chickens and some of the broiler chickens and quails showed neurologic signs like. The results revealed that the mortality rate was dose dependent in broiler chicken embryonated eggs. But mortality rate was dose independent in egg laying chickens and quail. Partridge revealed 100 % mortality rate in all doses. The LD50 in broiler chicken embryonated was 10(2.3). In conclusion, LD50 in the broiler chickens is the lowest between different animal models which shows that the broiler chicken embryonated egg is the best animal model for experimental inducing of neosporosis. Partridge is the most susceptible bird to N. caninum infection. These results reinforce that there is genetic susceptibility to N. caninum in chickens like mice and provide new insights to reach an inexpensive and available animal model for N. caninum infection.

10.
J Parasit Dis ; 39(2): 328-31, 2015 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-26064029

RESUMEN

Theileria infected cell line was isolated from the prescapular lymph node of an adult crossbred cow. Molecular study confirmed this cell line of bovine lymphocyte has been transformed by the Theileria lestoquardi. This strain of T. lestoquardi designated Ka-6 and sheep were inoculated with this strain didn't show any clinical signs of theileriosis which shows the significance of this cell line to develop a tissue-culture vaccine against malignant ovine theileriosis. Contrary to accepted belief that the T. lestoquardi not capable of causing disease in cattle, the present study describes the first isolation and establishment of in vitro culture of T. lestoquardi-infected cell line from a naturally infected cow with typical singes of acute theileriosis.

11.
J Cereb Blood Flow Metab ; 20(12): 1717-24, 2000 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-11129788

RESUMEN

The distribution volume (DV) of 6-[F-18]fluoro-L-DOPA (FDOPA) in the cerebellum recently has been linked using positron emission tomography (PET) to plasma large neutral amino acid (LNAA) concentrations in monkeys. In this article the authors provide additional experimental support for this relation by directly measuring the DV as the steady-state tissue to plasma radioactivity ratio in rats using a labeled LNAA analog 3-O-methyl-6-[F-18]FDOPA (OMFD), a compound that has no known specific enzyme or receptor interactions in brain tissue. The measured DV for OMFD (tissue OMFD concentration/plasma OMFD concentration) was found to be inversely related to plasma LNAA concentrations. The relation (DV = 1.5-0.00094*[LNAA], R--2 = 0.79) resulted in an 8% DV decrease per 100 nmol/mL plasma LNAA increase within the observed range of 330 to 510 nmol/mL. This was similar to recent noninvasive observations with FDOPA PET in vervet monkeys and with 6-[F-18]Fluoro-m-tyrosine PET in squirrel monkeys. The OMFD striatum to cerebellum (Str/Cb) ratio was greater than 1.0 for all measurements, averaging 1.09 +/- 0.04, and was approximately equal to the Str/Cb LNAA ratio of 1.12 +/- 0.05. This current study verifies the variation of DV of OMFD or FDOPA as a function of plasma LNAA concentrations and suggests the possibility of using OMFD for measuring cerebral LNAA noninvasively with PET.


Asunto(s)
Barrera Hematoencefálica/fisiología , Encéfalo/diagnóstico por imagen , Encéfalo/metabolismo , Dihidroxifenilalanina/análogos & derivados , Dihidroxifenilalanina/farmacocinética , Tomografía Computarizada de Emisión/métodos , Aminoácidos Neutros/análisis , Aminoácidos Neutros/sangre , Animales , Cerebelo/irrigación sanguínea , Cerebelo/química , Cerebelo/metabolismo , Cuerpo Estriado/irrigación sanguínea , Cuerpo Estriado/química , Cuerpo Estriado/metabolismo , Masculino , Enfermedad de Parkinson/diagnóstico por imagen , Enfermedad de Parkinson/metabolismo , Ratas , Ratas Sprague-Dawley , Distribución Tisular
12.
J Cereb Blood Flow Metab ; 16(4): 667-78, 1996 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-8964807

RESUMEN

In this work, we introduce 6-[18F]fluoro-L-m-tyrosine (6-FMT) and compare its in-vivo kinetic and bio-chemical behaviors in monkeys and rodents with those of 4-FMT and 6-[18F]fluoro-L-3, 4-dihydroxyphenylalanine (DOPA) (FDOPA). These radiofluorinated m-tyrosine presynaptic dopaminergic probes, resistant to peripheral 3-O-methylation, offer a nonpharmacological alternative to the use of catechol-O-methyltransferase inhibitors. Like FDOPA, 4-FMT and 6-FMT are analogs that essentially follow the L-DOPA pathway of central metabolism. After i.v. administration in nonhuman primates and rodents, these new radiofluorinated m-tyrosine analogs accumulate selectively in striatal structures and allow for the detection of additional innervation sites (e.g., brain stem) rich in aromatic amino acid decarboxylase. Bio-chemical analyses in rodents and monkeys revealed the specificity of their central and peripheral metabolism. Molecular and enzymatic mechanisms involved in their retention in central brain structures are consistent with involvement of dopaminergic neurons. The high signal-to-noise ratios observed make these radiofluorinated m-tyrosine analogs outstanding candidates for probing the integrity of central dopaminergic mechanisms in humans.


Asunto(s)
Encéfalo/metabolismo , Dihidroxifenilalanina/análogos & derivados , Dopamina/metabolismo , Tirosina/análogos & derivados , Animales , Chlorocebus aethiops , Dihidroxifenilalanina/farmacocinética , Radioisótopos de Flúor , Distribución Tisular , Tirosina/farmacocinética
13.
J Nucl Med ; 42(1): 96-105, 2001 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-11197989

RESUMEN

UNLABELLED: We have synthesized and evaluated 8-[18F]fluoropenciclovir (FPCV) and compared it with 8-[18F]fluoroganciclovir (FGCV) for monitoring the expression of herpes simplex virus type 1 thymidine kinase (HSV1 -tk) reporter gene in cell culture and in vivo. METHODS: C6 rat glioma cells stably transfected with HSV1-tk (C6-stb-tk+) and control C6 cells were evaluated for their ability to accumulate FGCV versus FPCV. For in vivo studies, 15 mice were injected by tail vein with increasing levels of an adenoviral vector carrying HSV1-tk. Forty-eight hours later the mice were injected with FPCV and killed 3 h later. The percentage injected dose per gram (%ID/g) liver was then determined. Two additional mice were studied by microPET and autoradiography using FPCV to image adenoviral-mediated hepatic HSV1-tk reporter gene expression. A tumor-bearing mouse (C6 control and C6-stb-tk+) was imaged with FDG, FGCV, and FPCV. Two mice carrying tumors expressing two different reporter genes, HSV1-tk and dopamine type 2 receptor (D2R), were also imaged by microPET using FPCV (day 1) and 3-(2'-[18F]fluoroethyl)spiperone (FESP) (day 2). RESULTS: FPCV shows a significantly greater accumulation in C6-stb-tk+ cells than does FGCV (P < 0.05). Over identical ranges of adenoviral administration, mouse liver shows a higher %ID/g liver for FPCV (0%-9%) compared with our previously reported results with FGCV (0%-3%). In C6 control and C6-stb-tk+ tumor-bearing mice, FPCV has a greater accumulation than does FGCV for equal levels of HSV1-tk gene expression. In mice carrying tumors expressing either HSV1-tk or D2R reporter genes, there is a corresponding retention of FPCV and FESP, respectively. CONCLUSION: These results indicate that FPCV is a better reporter probe than is FGCV for imaging lower levels of HSV1 -tk gene expression in vivo. The results also reveal the ability to monitor the expression of two distinct reporter genes in the same animal using reporter probes specific for each gene.


Asunto(s)
Aciclovir/análogos & derivados , Antivirales , Radioisótopos de Flúor , Genes Reporteros , Herpesvirus Humano 1/genética , Timidina Quinasa/genética , Tomografía Computarizada de Emisión , Adenoviridae , Animales , Células Cultivadas , Expresión Génica , Vectores Genéticos , Guanina , Herpesvirus Humano 1/enzimología , Ratones , Ratas , Receptores de Dopamina D2/genética
14.
J Nucl Med ; 42(8): 1225-34, 2001 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-11483684

RESUMEN

UNLABELLED: 9-[4-[(18)F]fluoro-3-(hydroxymethyl)butyl]guanine ([(18)F]FHBG) has been used as a reporter probe to image expression of herpes simplex virus type-1 thymidine kinase (HSV1-tk) reporter gene in living animals. Our aim was to study the kinetics, biodistribution, stability, dosimetry, and safety of [(18)F]FHBG in healthy human volunteers, preparatory to imaging patients undergoing HSV1-tk gene therapy. METHODS: [(18)F]FHBG was synthesized with a specific activity of 37,000--444,000 GBq/mmol and a radiochemical purity > 99%. Ten healthy volunteers consented to participate in the study. A transmission scan was obtained before bolus injection of 70.3--229.4 MBq [(18)F]FHBG into a hand vein, followed by dynamic PET imaging with 4 consecutive emission scans. Warmed hand-vein blood was withdrawn at various times after injection for blood time--activity measurements. Electrocardiography, blood pressure, and blood and urine pharmacologic parameters were measured before and after injection of the [(18)F]FHBG tracer (n = 5). The stability of [(18)F]FHBG in the urine was analyzed. Attenuation-corrected images were reconstructed using the ordered-subsets expectation maximization algorithm. Image region-of-interest time-activity data were used with the MIRD program to estimate absorbed radiation dosages. RESULTS: [(18)F]FHBG had rapid blood clearance; only 8.42% +/- 4.76% (mean +/- SD) of the peak blood activity remained at approximately 30 min. The average ratio of plasma activity to whole-blood activity during the study was 0.91 +/- 0.04. Penetration of [(18)F]FHBG across the blood-brain barrier was not observed. The primary routes of clearance were renal and hepatobiliary. High activities were observed in the bladder, gut, liver, and kidneys, but <0.0002% of the injected dose per gram was observed in other tissues. In the urine, 83% of activity 180 min after injection was stable [(18)F]FHBG. Blood and urine pharmacologic parameters did not change significantly after injection of the [(18)F]FHBG tracer. The bladder absorbed the highest radiation dose. CONCLUSION: [(18)F]FHBG has the desirable in vivo characteristics of stability, rapid blood clearance, low background signal, biosafety, and acceptable radiation dosimetry in humans. This study forms the foundation for using [(18)F]FHBG in applications to monitor HSV1-tk reporter gene expression.


Asunto(s)
Regulación Enzimológica de la Expresión Génica/genética , Genes Reporteros , Guanina , Herpesvirus Humano 1/enzimología , Radiofármacos , Timidina Quinasa/genética , Adulto , Calibración , Femenino , Guanina/efectos adversos , Guanina/análogos & derivados , Guanina/farmacocinética , Humanos , Procesamiento de Imagen Asistido por Computador , Masculino , Radiometría , Radiofármacos/efectos adversos , Radiofármacos/farmacocinética , Timidina Quinasa/biosíntesis , Distribución Tisular , Tomografía Computarizada de Emisión
15.
J Nucl Med ; 39(11): 2003-11, 1998 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-9829598

RESUMEN

UNLABELLED: We are developing procedures to repeatedly and noninvasively image the expression of transplanted reporter genes in living animals and in patients, using PET. We have investigated the use of the Herpes Simplex Virus type 1 thymidine kinase gene (HSV1-tk) as a reporter gene and [8-14C]-ganciclovir as a reporter probe. HSV1-tk, when expressed, leads to phosphorylation of [8-14C]-ganciclovir. As a result, specific accumulation of phosphorylated [8-14C]-ganciclovir should occur almost exclusively in tissues expressing the HSV1-tk gene. METHODS: An adenoviral vector was constructed carrying the HSV1-tk gene along with a control vector. C6 rat glioma cells were infected with either viral vector and uptake of [8-3H]-ganciclovir was determined. In addition, 12 mice were injected with varying levels of either viral vector. Adenovirus administration in mice leads primarily to liver infection. Forty-eight hours later the mice were injected with [8-14C]-ganciclovir, and 1 hr later the mice were sacrificed and biodistribution studies performed. Digital whole-body autoradiography also was performed on separate animals. HSV1-tk expression was assayed, using both normalized HSV1-tk mRNA levels and relative HSV1-TK enzyme levels, in both the cell culture and murine studies. RESULTS: Cell culture, murine tissue biodistribution and murine in vivo digital whole-body autoradiography all demonstrate the feasibility of HSV1-tk as a reporter gene and [8-14C]-ganciclovir as an imaging reporter probe. A good correlation (r2 = 0.86) between the [8-14C]-ganciclovir percent injected dose per gram tissue from HSV1-tk positive tissues and HSV1-TK enzyme levels in vivo was found. An initial study in mice with [8-18F]-fluoroganciclovir and microPET imaging supports further investigation of [8-18F]-fluoroganciclovir as a PET reporter probe for imaging HSV1-tk gene expression. CONCLUSION: These results demonstrate the feasibility of using [8-14C]-ganciclovir as a reporter probe for the HSV1-tk reporter gene, using an in vivo adenoviral mediated gene delivery system in a murine model. The results form the foundation for further investigation of [8-18F]-fluoroganciclovir for noninvasive and repeated imaging of gene expression with PET.


Asunto(s)
Antivirales , Ganciclovir , Genes Reporteros , Herpesvirus Humano 1/enzimología , Timidina Quinasa/genética , Tomografía Computarizada de Emisión , Adenoviridae , Animales , Autorradiografía , Células Cultivadas , Estudios de Factibilidad , Expresión Génica , Genes Virales , Herpesvirus Humano 1/genética , Humanos , Hígado/diagnóstico por imagen , Ratones , Ratas , Distribución Tisular , Tomografía Computarizada de Emisión/métodos
16.
Biochem Pharmacol ; 62(10): 1409-15, 2001 Nov 15.
Artículo en Inglés | MEDLINE | ID: mdl-11709201

RESUMEN

The transport of 6-[18F]fluoro-L-3,4-dihydroxyphenylalanine ([18F]FDOPA) across the blood-brain barrier (BBB) and neuronal membranes was compared with that of L-3,4-dihydroxyphenylalanine (L-DOPA) in rats. The carotid injection method was used as a direct measurement of [18F]FDOPA, 1-[14C]-L-DOPA, and 3-[14C]-L-DOPA transport across the BBB, while isolated nerve terminals were used to examine neuronal membrane transport of [3H]-L-DOPA. [18F]FDOPA appeared to use the same large neutral amino acid carrier for BBB transport as L-DOPA and L-phenylalanine. In addition, carbidopa [L-alpha-hydrazino-alpha-methyl-beta-(3,4-dihydroxyphenyl)propionic acid] was found not to have direct interference with the transport carrier on the BBB, but indirectly inhibited aromatic L-amino acid decarboxylase (AAAD) activity in brain endothelium by depletion of pyridoxal phosphate, a necessary cofactor of the enzyme. In striatal and cortical synaptosomes, [3H]-L-DOPA uptake was inhibited by non-radioactive L-DOPA, FDOPA, and 6-fluoro-L-meta-tyrosine (6-FMT). The inhibition was significantly greater in terminals isolated from the striatum than in those from the cerebral cortex. FDOPA, 6-FMT, and L-DOPA equally inhibited the neuronal transport of [3H]-L-DOPA. This suggests that FDOPA and 6-FMT compete with L-DOPA at similar transport sites at the neuronal membrane.


Asunto(s)
Barrera Hematoencefálica/fisiología , Dihidroxifenilalanina/análogos & derivados , Dihidroxifenilalanina/farmacocinética , Neuronas/metabolismo , Animales , Transporte Biológico/efectos de los fármacos , Membrana Celular/metabolismo , Radioisótopos de Flúor , Levodopa/farmacocinética , Masculino , Modelos Animales , Ratas , Ratas Sprague-Dawley
17.
Nucl Med Biol ; 26(5): 529-35, 1999 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-10473191

RESUMEN

The synthesis of two new dopamine transporter ligands, 3beta-(4-fluoromethylphenyl)tropane-2beta-carboxylic acid methyl ester and 3beta-(2-fluoromethylphenyl)tropane-2beta-carboxylic acid methyl ester, and their spectral characterization are described. The precursors for these ligands were prepared by TiCl4 catalyzed chloromethylation of 3beta-phenyltropane-2beta-carboxylic acid methyl ester followed by separation of the isomeric product mixture of 2- and 4-chloromethylphenyltropane derivatives. Reaction of the chloromethyl analogs with no-carrier-added [18F]fluoride ion followed by high performance liquid chromatography purification provided the corresponding [18F]fluoromethyltropanes, in good radiochemical yields, useful for imaging the brain dopamine transporter system in vivo with positron emission tomography.


Asunto(s)
Encéfalo/metabolismo , Proteínas Portadoras/metabolismo , Cocaína/análogos & derivados , Radioisótopos de Flúor/farmacocinética , Glicoproteínas de Membrana , Proteínas de Transporte de Membrana , Proteínas del Tejido Nervioso , Encéfalo/diagnóstico por imagen , Proteínas Portadoras/análisis , Cocaína/síntesis química , Cocaína/farmacocinética , Dopamina/metabolismo , Proteínas de Transporte de Dopamina a través de la Membrana Plasmática , Humanos , Conformación Molecular , Estructura Molecular , Tomografía Computarizada de Emisión/métodos
18.
Nucl Med Biol ; 26(8): 897-903, 1999 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-10708303

RESUMEN

Dopamine reuptake transporter binding kinetics of 2beta-carbomethoxy-3beta-(4-[18F]fluoromethylphenyl)tropane (p-FWIN) and 2beta-carbomethoxy-3beta-(2-[18F]fluoromethylphenyl)tropane (o-FWIN) were determined in vervet monkeys using positron emission tomography (PET). Ligand localization was rapid and specific to the striatum with kinetic estimates comparable with those of 11C-labeled WIN 35,428 (CWIN). Binding was more specific with p-FWIN than with CWIN or o-FWIN. The relatively longer half-life of the 18F radiolabel enabled longer acquisition times with p-FWIN, resulting in less variability in the kinetic estimates.


Asunto(s)
Química Encefálica , Proteínas Portadoras/metabolismo , Glicoproteínas de Membrana , Proteínas de Transporte de Membrana , Proteínas del Tejido Nervioso , Radiofármacos/síntesis química , Receptores Dopaminérgicos/metabolismo , Tropanos/síntesis química , Animales , Encéfalo/diagnóstico por imagen , Chlorocebus aethiops , Cocaína/análogos & derivados , Cocaína/farmacocinética , Proteínas de Transporte de Dopamina a través de la Membrana Plasmática , Inhibidores de Captación de Dopamina/farmacocinética , Procesamiento de Imagen Asistido por Computador , Ligandos , Norepinefrina/metabolismo , Radiofármacos/farmacocinética , Radiofármacos/farmacología , Ratas , Ratas Sprague-Dawley , Serotonina/metabolismo , Tomografía Computarizada de Emisión , Tropanos/farmacocinética , Tropanos/farmacología
19.
Nucl Med Biol ; 27(2): 157-62, 2000 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-10773544

RESUMEN

A new method for the preparation of 8-[(18)F]fluoroguanine derivatives based on a direct radiofluorination reaction has been developed. The radiofluorination of ganciclovir (1a) with [(18)F]F(2) was carried out in absolute ethanol in the presence of tetraethylammonium hydroxide at room temperature to give 8-[(18)F]fluoroganciclovir (3a) in an approximately 1% radiochemical yield. Similarly, 8-[(18)F]fluoropenciclovir (3b), 8-[(18)F]fluoroacyclovir (3c), and 8-[(18)F]fluoroguanosine (3d) were synthesized from penciclovir (1b), acyclovir (1c), and guanosine (1d), respectively, using [(18)F]F(2). The structural analyses of the final products (3a, 3b, 3c, and 3d) were carried out after (18)F decay by (1)H, (13)C, and (19)F nuclear magnetic resonance and high resolution mass spectroscopy.


Asunto(s)
Expresión Génica , Guanina/análogos & derivados , Guanina/síntesis química , Radiofármacos/síntesis química , Tomografía Computarizada de Emisión/métodos , Aciclovir/análogos & derivados , Aciclovir/química , Ganciclovir/química , Guanosina/química , Marcaje Isotópico , Espectroscopía de Resonancia Magnética
20.
Appl Radiat Isot ; 44(3): 527-36, 1993 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-8472025

RESUMEN

The regioselective radiofluorodestannylation of 6-trimethylstannyl-L-m-tyrosine derivative 6 with [18F]F2 and [18F]acetyl hypofluorite afforded, after acid hydrolysis, 6-[18F]fluoro-L-m-tyrosine (8a) in radiochemical yields of 23 and 17%, respectively. Similarly, 4-[18F]fluoro-L-m-tyrosine (13a) was synthesized in 11% radiochemical yield from the corresponding 4-trimethylstannyl-L-m-tyrosine derivative 11 using [18F]F2. The structural analyses of precursors (6,11), intermediates, and the final products (after 18F decay), were carried out by 1H, 13C, 19F, 119Sn-NMR and high resolution mass spectroscopy.


Asunto(s)
Tirosina/análogos & derivados , Radioisótopos de Flúor , Tirosina/síntesis química
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