2-Alkynyl-8-aryl-9-methyladenines as novel adenosine receptor antagonists: their synthesis and structure-activity relationships toward hepatic glucose production induced via agonism of the A(2B) receptor

Novel adenosine antagonists, 2-alkynyl-8-aryl-9-methyladenine derivatives, were synthesized as candidate hypoglycemic agents. These analogues were evaluated for inhibitory activity on N-ethylcarboxamidoadenosine (NECA)-induced glucose production in primary cultured rat hepatocytes. In general, aromatic moieties at the 8-position and alkynyl groups at the 2-position had significantly increased activity compared to unsubstituted compounds. The preferred substituents at the 8-position of adenine were the 2-furyl and 3-fluorophenyl groups. In modifying the alkynyl side chain, change of the ring size, cleavage of the ring, and removal of the hydroxyl group were well tolerated. The order of the stimulatory effects of adenosine agonists on rat hepatocytes was NECA > CPA > CGS21680, which is consistent with involvement of the A(2B) receptor. In Chinese hamster ovary cells stably transfected with human A(2B) receptor cDNA, one of the compounds potent in hepatocytes, 15o (IC(50) = 0.42 microM), antagonized NECA-induced stimulation of cyclic AMP production (IC(50) = 0.063 microM). This inhibitory effect was much more potent than those of FK453, KF17837, and L249313 which have been reported to be respectively A(1), A(2A), and A(3) selective antagonists. These findings agree very well with the result that, compared to 15o, these selective antagonists for each receptor subtype showed only marginal effects in rat hepatocytes. These results suggest that adenosine agonist-induced glucose production in rat hepatocytes is mediated through the A(2B) receptor. Furthermore, 15o showed hypoglycemic activity in an animal model of noninsulin-dependent diabetes mellitus, the KK-A(y) mice. It is possible that inhibition of hepatic glucose production via the A(2B) receptor could be at least one of the mechanisms by which 15o exerts its in vivo effects. Further elaboration of this group of compounds may afford novel antidiabetic agents.     

Fat-suppressed T2-weighted MRI of the liver: comparison of respiratory-triggered fast spin-echo, breath-hold single-shot fast spin-echo, and breath-hold fast-recovery fast spin-echo sequences

The purpose of our study was to compare the value of respiratory-triggered fast spin-echo, breath-hold single-shot fast spin-echo, and breath-hold fast-recovery fast spin-echo sequences in detecting hepatic lesions. Fat-suppressed T2-weighted magnetic resonance (MR) images obtained with the three sequences in 36 patients with 138 lesions and nine patients without lesions were prospectively analyzed. Quantitative and qualitative analyses, including receiver operating characteristic (ROC) analyses, were performed. The mean lesion-to-liver contrast-to-noise ratio (CNR) for hepatic lesions was highest with the respiratory-triggered fast spin-echo sequence. On the basis of receiver-operating characteristic analyses, tumor detection rates were higher with the breath-hold fast-recovery fast spin-echo sequence (Az = 0.94) than with the respiratory-triggered fast spin-echo sequence (AZ = 0.80, P < 0.0001) or the single-shot fast spin-echo sequence (Az = 0.77, P < 0.0001). The image quality with the breath-hold fast-recovery fast spin-echo sequence was acceptable in all patients. The breath-hold fast-recovery fast spin-echo sequence provided the highest tumor detection in a short imaging time, although the mean lesion-to-liver CNRs were inferior to those of the respiratory-triggered fast spin-echo and the breath-hold single-shot fast spin-echo sequences.     

Noncontrast MR angiography for supraaortic arteries using inflow enhanced inversion recovery fast spin echo imaging

Purpose:

To depict supraaortic arteries using (3D fast spin echo (FSE) combined with slab selective inversion recovery for noncontrast magnetic resonance angiography (MRA) in healthy volunteers, and to investigate the property of the inflow enhanced inversion recovery FSE (IFIR‐FSE) for background suppression and inflow effects.

Materials and Methods:

IFIR‐FSE with no image subtraction was used to visualize the aortic arch, subclavian arteries, carotid arteries, and vertebral arteries in 10 healthy volunteers. Simulations were performed to achieve both high background suppression and inflow effects by adjusting the inversion time (TI) and wait time after data acquisition. The effect of inflow was investigated with TIs of 800, 1200, 1600, and 2000 msec. Contrast between artery and these background tissues were measured with scan protocols based on simulation results.

Results:

IFIR‐FSE images showed good visualization of the supraaortic arteries and allowed separation of arteries from veins without image subtraction. The proposed method demonstrated that a high contrast between arteries and background tissues can be acquired with various TIs, which was in good agreement with the simulation. A TI over 1600 msec was favorable in terms of background suppression, arterial signal intensity, and inflow effects.

Conclusion:

Inflow enhanced inversion recovery cardiac‐triggered 3D FSE imaging can be used for supraaortic artery imaging without contrast agents. J. Magn. Reson. Imaging 2012;35:957–962. © 2011 Wiley Periodicals, Inc.     

Successful Treatment of Immune Thrombocytopenic Purpura with Intracranial Hemorrhaging and Duodenal Bleeding Following SARS-CoV-2 Vaccination

Several vaccines have been developed for coronavirus disease 2019 - caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) - in record time. A few cases of immune thrombocytopenic purpura (ITP) following SARS-CoV-2 vaccination have been reported. We herein report a 90-year-old man who received the Pfizer-BioNTech SARS-CoV-2 vaccine (BNT162b2) and developed severe thrombocytopenia with intracranial hemorrhaging and duodenal bleeding, consistent with vaccine-related ITP. He was successfully treated with intravenous immunoglobulin, prednisolone, and eltrombopag and discharged without cytopenia. Vaccine-related ITP should be suspected in patients presenting with abnormal bleeding or purpura after vaccination.     

Three-dimensional fast recovery fast spin-echo imaging of the inner ear and the vestibulocochlear nerve

The aim of this study was to assess the performance of three-dimensional fast recovery fast spin-echo (3DFRFSE) for imaging of the inner ear as well as the facial and vestibulocochlear nerves. We evaluated 3DFRFSE sequences, comparing it with 3D fast spin-echo (3DFSE) in a water phantom and in 12 normal volunteers. We also examined 66 patients using 3DFRFSE sequence and assessed the visualization of their pathologies. In a water phantom study, signal intensity (SI) on 3DFRFSE was higher than that on 3DFSE at the same TR ranging from 1500 to 6000 ms. In normal volunteers, 3DFRFSE with TR of 2800 ms showed comparable SI, and signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) superior to those on 3DFSE with TR of 5000 ms. In clinical setting, 3DFRFSE was useful in demonstrating anatomic details in the labyrinth and pathologic findings of inner ear. The 3DFRFSE can provide high-resolution heavily T2-weighted images (T2WI) with shorter scan time than 3DFSE without significant disadvantage. The 3DFRFSE is a beneficial technique for evaluation of lesions in the inner ear as well as the facial and vestibulocochlear nerves. Electronic Publication     

Changes in myometrial and junctional zone thickness and signal intensity: demonstration with kinematic T2-weighted MR imaging

PURPOSE: To demonstrate uterine contractions by evaluating changes during time in the thickness of the myometrium and junctional zone and in signal intensity of the uterus with T2-weighted fast magnetic resonance (MR) images in a kinematic fashion. MATERIALS AND METHODS: Sagittal MR imaging was performed with T2-weighted fast spin-echo (FSE) and multiphase-multisection single-shot FSE (SSFSE) in 60 premenopausal patients during free breathing. SSFSE MR images were evaluated with cine display. The pattern of uterine contractions and changes in signal intensities of the uterine structures were evaluated. Thickness of both myometrium and junctional zone, and their signal intensities, were measured during 15 phases of SSFSE and FSE MR imaging. RESULTS: Slow-massive (mean, 55%), middle-cycle (mean, 80%), and fine (mean, 93%) contractions were observed. Shape of junctional zones dynamically changed during time, showing focal (mean, 58%) and diffuse (mean, 82%) thickening and wavelike motions (mean, 88%). Ratio of thickness of the myometrium to junctional zone with FSE MR imaging was not significantly different from the mean ratio during 15 phases of SSFSE MR imaging, although maximum percentage of change of the ratio during 15 phases was 42.5%-56.8%. The signal intensities of the myometrium (97%) and junctional zone (75%) changed during time. CONCLUSION: Kinematic T2-weighted SSFSE MR images demonstrate uterine contractions related to dynamic changes in thickness and signal intensities of the myometrium and junctional zone, and these findings might affect the diagnosis of uterine disease.     

Studies on criteria for clinicopathological diagnosis of allergic granulomatous angiitis (AGA)]

Comparative studies in the evaluation of criteria for clinicopathological diagnosis of AGA which was proposed by Japanese Health and Welfare Ministry (JHWM) in 1988 and American College of Rheumatology (ACR) in 1990 were conducted. Twenty seven Japanese patients with AGA and 231 Japanese controlled patients with polyarteritis nodosa (PAN) and Wegener's granulomatosis (WG) were used as material patients who had been provided a second questionnaire in 1984 sponsored by the JHWM. As a result, the JHWM criteria was 85.2% in sensitivity and 96.5% in specificity, which was superior to the ACR criteria being 74.1% in sensitivity and 93.9% in specificity. These results were due to the low sensitivity and low accuracy in paranasal sinus abnormality and pulmonary infiltrates which were included in the ACR criteria. Furthermore, the JHWM criteria could be diagnosed as AGA using not only the histopathological findings but by the clinical symptoms alone. The controlled patients who were overdiagnosed as AGA using ACR criteria were thought to be included as patients with WG. On the other hand, the controlled patients who were overdiagnosed as AGA using JHWM criteria were thought to be included as patients with overlap syndrome of AGA and PAN. Accuracy of polyneuropathy, muscle weakness, melena and pretibial edema were over 60%, indicating that these clinical symptoms were available for vasculitis symptoms of the JHWM criteria.     

A new evaluation method for neurosensory disturbance in the chin of patients undergoing mandibular sagittal split ramus osteotomy: an application of the heat flux technique.

OBJECTIVE: To examine neurosensory changes in the chin following bilateral sagittal split ramus osteotomy (BSSRO) using the heat flux technique. STUDY DESIGN: Twelve healthy adults (C-group) and 23 patients undergoing BSSRO (P-group) were examined. The warm sense threshold (WHF) and cold sense threshold (CHF) in the chin of these patients were measured by the heat flux technique. In the P-group, touch sensation also was measured with a visual analog scale (VAS) and the Semmes-Weinstein monofilament test (SW test). RESULTS: Both WHF and CHF were significantly larger in the P-group than in the C-group (P = .024). Touch sensation (VAS and SW test) were damaged in some patients of the P-group. However, no correlation was revealed between thermal sensation (WHF and CHF) and touch sensation (VAS and SW test) in the P-group. CONCLUSIONS: These results suggest that the thermal sensation in the chin was damaged after BSSRO. The heat flux technique appears to be one of the useful methods for the examination of neurosensory disturbance in the chin.