Extremely Stable Zeolites Developed via Designed Liquid-Mediated Treatment.

Improving the stability of porous materials for practical applications is highly challenging. Aluminosilicate zeolites are utilized for adsorptive and catalytic applications, wherein they are sometimes exposed to high-temperature steaming conditions (∼1000 °C). As the degradation of high-silica zeolites originates from the defect sites in their frameworks, feasible defect-healing methods are highly demanded. Herein, we propose a method for healing defects to create extremely stable high-silica zeolites. High-silica (SiO2/Al2O3 > 240) zeolites with *BEA-, MFI-, and MOR-type topologies could be stabilized by significantly reducing the number of defect sites via a liquid-mediated treatment without using additional silylating agents. Upon exposure to extremely high temperature (900-1150 °C) steam, the stabilized zeolites retain their crystallinity and micropore volume, whereas the parent commercial zeolites degrade completely. The proposed self-defect-healing method provides new insights into the migration of species through porous bodies and significantly advances the practical applicability of zeolites in severe environments.

Design, Synthesis, and Preliminary Evaluation of SPECT Probes for Imaging ß-Amyloid in Alzheimer's Disease Affected Brain.

In this study, we synthesized of a series of 2-phenyl- and 2-pyridyl-imidazo[1,2- a]pyridine derivatives and examine their suitability as novel probes for single-photon emission computed tomography (SPECT)-based imaging of ß-amyloid (Aß). Among the 11 evaluated compounds, 10 showed moderate affinity to Aß(1-42) aggregates, exhibiting half-maximal inhibitory concentrations (IC50) of 14.7 ± 6.07-87.6 ± 39.8 nM. In vitro autoradiography indicated that 123I-labeled triazole-substituted derivatives displayed highly selective binding to Aß plaques in the hippocampal region of Alzheimer's disease (AD)-affected brain. Moreover, biodistribution studies performed on normal rats demonstrated that all 123I-labeled probes featured high initial uptake into the brain followed by a rapid washout and were thus well suited for imaging Aß plaques, with the highest selectivity observed for a 1 H-1,2,3-triazole-substituted 2-pyridyl-imidazopyridine derivative, [123I]ABC577. This compound showed good kinetics in rat brain as well as moderate in vivo stability in rats and is thus a promising SPECT imaging probe for AD in clinical settings.

Preclinical properties and human in vivo assessment of 123I-ABC577 as a novel SPECT agent for imaging amyloid-ß.

Non-invasive imaging of amyloid-ß in the brain, a hallmark of Alzheimer's disease, may support earlier and more accurate diagnosis of the disease. In this study, we assessed the novel single photon emission computed tomography tracer (123)I-ABC577 as a potential imaging biomarker for amyloid-ß in the brain. The radio-iodinated imidazopyridine derivative (123)I-ABC577 was designed as a candidate for a novel amyloid-ß imaging agent. The binding affinity of (123)I-ABC577 for amyloid-ß was evaluated by saturation binding assay and in vitro autoradiography using post-mortem Alzheimer's disease brain tissue. Biodistribution experiments using normal rats were performed to evaluate the biokinetics of (123)I-ABC577. Furthermore, to validate (123)I-ABC577 as a biomarker for Alzheimer's disease, we performed a clinical study to compare the brain uptake of (123)I-ABC577 in three patients with Alzheimer's disease and three healthy control subjects. (123)I-ABC577 binding was quantified by use of the standardized uptake value ratio, which was calculated for the cortex using the cerebellum as a reference region. Standardized uptake value ratio images were visually scored as positive or negative. As a result, (123)I-ABC577 showed high binding affinity for amyloid-ß and desirable pharmacokinetics in the preclinical studies. In the clinical study, (123)I-ABC577 was an effective marker for discriminating patients with Alzheimer's disease from healthy control subjects based on visual images or the ratio of cortical-to-cerebellar binding. In patients with Alzheimer's disease, (123)I-ABC577 demonstrated clear retention in cortical regions known to accumulate amyloid, such as the frontal cortex, temporal cortex, and posterior cingulate. In contrast, less, more diffuse, and non-specific uptake without localization to these key regions was observed in healthy controls. At 150 min after injection, the cortical standardized uptake value ratio increased by ∼ 60% in patients with Alzheimer's disease relative to healthy control subjects. Both healthy control subjects and patients with Alzheimer's disease showed minimal (123)I-ABC577 retention in the white matter. These observations indicate that (123)I-ABC577 may be a useful single photon emission computed tomography imaging maker to identify amyloid-ß in the human brain. The availability of an amyloid-ß tracer for single photon emission computed tomography might increase the accessibility of diagnostic imaging for Alzheimer's disease.

Similarities of the neuronal circuit for the induction of fictive vomiting between ferrets and dogs.

Previous studies suggested that the following neuronal circuit participates in the induction of vomiting by afferent vagal stimulation in decerebrated paralyzed dogs: (1) afferent fibers of the vagus nerve, (2) neurons of the solitary nucleus (NTS), (3) neurons of the prodromal sign center near the semicompact part of the nucleus ambiguus (scAMB), (4) neurons of the central pattern generator in the reticular area adjacent to the compact part of nucleus ambiguus (cAMB), (5) respiratory premotor neurons in the caudal medulla, (6) motor neurons of the diaphragm and abdominal muscles. However, the commonality of this neuronal circuit in different species has not yet been clarified. Thus, this study was conducted to clarify this point. This study clarified for the first time that fictive vomiting in decerebrated paralyzed ferrets could be induced by vagal stimulation, and could be identified by centrifugal activity patterns of the phrenic and abdominal muscle nerves. The distributions of c-Fos immunoreactive neurons in the NTS, scAMB and cAMB areas in ferrets that exhibited fictive vomiting were denser than those in ferrets that did not. Application of the nonNMDA receptor antagonist into the 4th ventricle produced the reversible suppression of fictive vomiting. The NK1 receptor immunoreactive puncta were found in the reticular area adjacent to the scAMB. Microinjections of NK1 receptor antagonist into the reticular areas on both sides abolished fictive vomiting. All these results in the ferrets are identical with results previously obtained in dogs and cats. Therefore, this suggests that the above neuronal circuit commonly participates in the induction of emesis in these animal species.

Quantitative evaluation of central-type benzodiazepine receptors with [(125)I]Iomazenil in experimental epileptogenesis: II. The rat cortical dysplasia model.

[(123)I]Iomazenil (IMZ) is a specific ligand for central-type benzodiazepine receptors (BZRs) and is available for single photon emission computed tomography (SPECT) to detect epileptogenic foci. We have recently demonstrated time-dependent alterations of [(125)I]IMZ binding in the rat kainate model of temporal lobe epilepsy. Quantitative evaluation of central-type benzodiazepine receptors with [(125)I]Iomazenil in experimental epileptogenesis. I. The rat kainate model of temporal lobe epilepsy. In the present study, we investigated regional changes in central-type BZRs in the cortical dysplasia (CD) model of epilepsy in rats. Pregnant rats were irradiated at day 17 of gestation with 1.2 Gy to produce CD in their pups, and in vitro autoradiography with [(125)I]IMZ was performed at 8 weeks after birth. Intact rats at the same age were used as controls. [(125)I]IMZ binding was significantly decreased in various cortical regions of the in utero irradiated rats, including the bilateral frontal cortex (down to 92-93% of control), cingulate cortex (91-92%), hippocampal areas CA1 (95%), CA2 (94-95%) and CA4 (95-96%), and caudate/putamen (90-94%). In addition, amygdala-kindling was significantly facilitated in the CD model, especially during the late phase of kindling, suggesting seizure susceptibility of this model. These results may replicate the clinical usefulness of central-type BZRs neuroimaging for detection of human epileptogenic CD and indicate dysfunction of GABA-A/BZR-mediated inhibition responsible for the seizure susceptibility.