29 research outputs found
Pharmacokinetic Modeling of [ 18 F]MC225 for Quantification of the P-Glycoprotein Function at the Blood-Brain Barrier in Non-Human Primates with PET
[18F]MC225 has been developed as a weak substrate of P-glycoprotein (P-gp) aimed to measure changes in the P-gp function at the blood–brain barrier with positron emission tomography. This study evaluates [18F]MC225 kinetics in non-human primates and investigates the effect of both scan duration and P-gp inhibition. Three rhesus monkeys underwent two 91-min dynamic scans with blood sampling at baseline and after P-gp inhibition (8 mg/kg tariquidar). Data were analyzed using the 1-tissue compartment model (1-TCM) and 2-tissue compartment model (2-TCM) fits using metabolite-corrected plasma as the input function and for various scan durations (10, 20, 30, 60, and 91 min). The preferred model was chosen according to the Akaike information criterion and the standard errors (%) of the estimated parameters. For the 91-min scan duration, the influx constant K1 increased by 40.7% and the volume of distribution (VT) by 30.4% after P-gp inhibition, while the efflux constant k2 did not change significantly. Similar changes were found for all evaluated scan durations. K1 did not depend on scan duration (10 min—K1 = 0.2191 vs 91 min—K1 = 0.2258), while VT and k2 did. A scan duration of 10 min seems sufficient to properly evaluate the P-gp function using K1 obtained with 1-TCM. For the 91-min scan, VT and K1 can be estimated with a 2-TCM, and both parameters can be used to assess P-gp function
Osteochondral lesion of the tibial plafond treated with a retrograde osteochondral autograft: a report of two cases
Background: Osteochondral lesions (OCLs) of the tibial plafond (OLTPs) are rare, and few studies provide treatment recommendations. We describe two cases of an OLTP that were treated with retrograde osteochondral autograft.
Case Reports: The first case was a 27-year-old basketball player and the second case was a 38-year-old soccer player. We harvested osteochondral autografts from the nonweight-bearing area of the lateral femoral condyle of the patient’s ipsilateral knees. The grafts were reversed and inserted into the bone tunnel reaching the OLTPs starting proximally and moving distally. The first patient was able to play professional basketball 14 months after the procedure and continues to play 5 years and 6 months later. The second patient was able to play recreational soccer 9 months after the procedure and continues to play 4 years later.
Conclusion: Use of the retrograde osteochondral autograft produced satisfactory results including the return to sports. The retrograde osteochondral autograft can be considered recommendable for treating OLTPs
Use of positron emission tomography for real-time imaging of biodistribution of green tea catechin.
The aim of this study was to achieve real-time imaging of the in vivo behavior of a green tea polyphenol, catechin, by positron emission tomography (PET). Positron-labeled 4″ -[(11)C]methyl-epigallocatechin gallate ([(11)C]Me-EGCG) was orally administered to rats, and its biodistribution was imaged for 60 min by using a small animal PET system. As the result, images of [(11)C]Me-EGCG passing through the stomach into the small intestines were observed; and a portion of it was quantitatively detected in the liver. On the other hand, intravenous injection of [(11)C]Me-EGCG resulted in a temporal accumulation of the labeled catechin in the liver, after which almost all of it was transferred to the small intestines within 60 min. In the present study, we succeeded in obtaining real-time imaging of the absorption and biodistribution of [(11)C]Me-EGCG with a PET system
Neuroprotective Role of Astroglia in Parkinson Disease by Reducing Oxidative Stress Through Dopamine-Induced Activation of Pentose-Phosphate Pathway
Oxidative stress plays an important role in the onset and progression of Parkinson disease. Although released dopamine at the synaptic terminal is mostly reabsorbed by dopaminergic neurons, some dopamine is presumably taken up by astroglia. This study examined the dopamine-induced astroglial protective function through the activation of the pentose-phosphate pathway (PPP) to reduce reactive oxygen species (ROS). In vitro experiments were performed using striatal neurons and cortical or striatal astroglia prepared from Sprague-Dawley rats or C57BL/6 mice. The rates of glucose phosphorylation in astroglia were evaluated using the [ 14 C]deoxyglucose method. PPP activity was measured using [1- 14 C]glucose and [6- 14 C]glucose after acute (60 min) or chronic (15 hr) exposure to dopamine. ROS production was measured using 2′,7′-dichlorodihydrofluorescein diacetate. The involvement of the Kelch-like ECH-associated protein 1 (Keap1) or nuclear factor-erythroid-2-related factor 2 (Nrf2) system was evaluated using Nrf2 gene knockout mice, immunohistochemistry, and quantitative reverse transcription polymerase chain reaction analysis for heme oxygenase-1. Acute exposure to dopamine elicited increases in astroglial glucose consumption with lactate release. PPP activity in astroglia was robustly enhanced independently of Na + -dependent monoamine transporters. In contrast, chronic exposure to dopamine induced moderate increases in PPP activity via the Keap1/Nrf2 system. ROS production from dopamine increased gradually over 12 hr. Dopamine induced neuronal cell damage that was prevented by coculturing with astroglia but not with Nrf2-deficient astroglia. Dopamine-enhanced astroglial PPP activity in both acute and chronic manners may possibly reduce neuronal oxidative stress
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Evaluation of in vivo selective binding of [11C]doxepin to histamine H1 receptors in five animal species
The specific binding of [(11)C]doxepin, which has been used as a radioligand for mapping histamine H(1) receptors in human brain by positron emission tomography, was evaluated in five animal species. In mice the [(11)C]doxepin uptake was reduced by treatment with cold doxepin and two H(1) receptor antagonists, but not with H(2)/H(3) antagonists. The specific binding evaluated with treatment with (+)-chlorpheniramine (H(1) antagonist) was in the range of 10-30% in mouse, rat, rabbit, and monkey, but was not detected in guinea pig