Erratum to "Crossing double stent retriever technique for refractory terminal internal carotid artery occlusion" [Radiology Case Reports 17 (2022) 1848-1852].

[This corrects the article DOI: 10.1016/j.radcr.2022.03.023.].

Acute internal carotid artery occlusion due to dissection of the paraclinoid segment: Diagnostic usefulness of angiographic findings during stent retriever deployment.

Intracranial artery dissection is an uncommon but possible cause of ischemic stroke, and is usually diagnosed based on imaging findings such as mural hematoma and dissection flap. However, it is challenging to recognize the underlying dissection in cases of acute large vessel occlusion. In this report, we present a case of acute internal carotid artery occlusion, in which the underlying dissection of the paraclinoid segment was found during the thrombectomy procedure. Two thrombectomy procedures failed to recanalize the acute internal carotid artery occlusion without removing any clot. Angiography performed during a Trevo stent retriever deployment in the first pass showed obscure contrast defects in the stent strut with temporary flow restoration. In the next pass, the appearance of the contrast defects changed and a parallel linear contrast appeared on the outside of the vessel wall. These angiographic findings were identified as mural hematoma and dissection flap, indicating dissection of the paraclinoid as the cause of the occlusion. During antiplatelet loading and preparation of a dedicated intracranial stent, the Trevo stent retriever was left deployed again at the occlusion site to maintain the blood flow. After permanent stenting with an Enterprise stent, angiography revealed complete recanalization. The patient recovered fully after the procedure. In the present case, stent retriever deployment revealed the hallmarks of dissection on angiography, such as mural hematoma, dissection flap, and temporal morphological changes, by restoring the blood flow temporarily. Such angiographic findings can provide useful information on the occlusion characteristics and real-time feedback for optimal treatment strategy.

Crossing double stent retriever technique for refractory terminal internal carotid artery occlusion.

Mechanical thrombectomy is highly effective for the recovery of acute ischemic stroke with large vessel occlusion. However, refractory occlusions are still encountered despite the use of currently available devices. In this article, we present a case of refractory terminal internal carotid artery occlusion treated with the "crossing double stent retriever technique." Two thrombectomy procedures with the combined technique using a stent retriever and aspiration catheter failed to recanalize the terminal internal carotid artery occlusion that involved the dominant anterior cerebral artery. We then applied the crossing double stent retriever technique as a rescue technique. Two microcatheters were advanced across the occlusion: one to the anterior cerebral artery and the other to the middle cerebral artery. First, a Trevo NXT 4 mm stent retriever was deployed from the anterior cerebral artery. Next, an additional Trevo NXT 4 mm stent retriever was deployed from the middle cerebral artery, and full immediate restoration of flow was achieved on angiography. Intraprocedural radiological images showed that the 2 microcatheters traversed different pathways, and the 2 stent retrievers completely covered the entire vessel with apparent in-stent clot sign. Both stent retrievers were then pulled back together, and a hard clot was retrieved. Subsequent angiography revealed complete recanalization. The crossing double stent retriever technique seems an effective rescue technique for treating refractory terminal internal carotid artery occlusion, especially with the anatomical feature of branching of the dominant anterior cerebral artery. This technique can facilitate the device-clot-vessel interaction by engaging the clot via 2 different device pathways.

Optimization of 3-aryl-3-ethoxypropanoic acids and discovery of the potent GPR40 agonist DS-1558.

GPR40 agonists stimulate insulin secretion only under the presence of high glucose concentration. Based on this mechanism, GPR40 agonists are believed to be promising novel insulin secretagogues with low risk of hypoglycemia. The optimizations of 3-aryl-3-ethoxypropanoic acids were performed to improve in vitro activity. We discovered compound 29r (DS-1558), (3S)-3-ethoxy-3-(4-{[(1R)-4-(trifluoromethyl)-2,3-dihydro-1H-inden-1-yl]oxy}phenyl)propanoic acid, which was confirmed to have an enhancing effect on glucose-dependent insulin secretion after intravenous glucose injection in SD rats.

Discovery of DS-1558: A Potent and Orally Bioavailable GPR40 Agonist.

GPR40 is a G protein-coupled receptor that is predominantly expressed in pancreatic ß-cells. GPR40 agonists stimulate insulin secretion in the presence of high glucose concentration. On the basis of this mechanism, GPR40 agonists are possible novel insulin secretagogues with reduced or no risk of hypoglycemia. The improvement of in vitro activity and metabolic stability of compound 1 led to the discovery of 13, (3S)-3-ethoxy-3-(4-{[(1R)-4-(trifluoromethyl)-2,3-dihydro-1H-inden-1-yl]oxy}phenyl)propanoic acid, as a potent and orally available GPR40 agonist. Compound 13 (DS-1558) was found to have potent glucose lowering effects during an oral glucose tolerance test in ZDF rats.

Potentiation of insulin secretion and improvement of glucose intolerance by combining a novel G protein-coupled receptor 40 agonist DS-1558 with glucagon-like peptide-1 receptor agonists.

G protein-coupled receptor 40 (GPR40) is a Gq-coupled receptor for free fatty acids predominantly expressed in pancreatic ß-cells. In recent years, GPR40 agonists have been investigated for use as novel therapeutic agents in the treatment of type 2 diabetes. We discovered a novel small molecule GPR40 agonist, (3S)-3-ethoxy-3-(4-{[(1R)-4-(trifluoromethyl)-2,3-dihydro-1H-inden-1-yl]oxy}phenyl)propanoic acid (DS-1558). The GPR40-mediated effects of DS-1558 on glucose-stimulated insulin secretion were evaluated in isolated islets from GPR40 knock-out and wild-type (littermate) mice. The GPR40-mediated effects on glucose tolerance and insulin secretion were also confirmed by an oral glucose tolerance test in these mice. Furthermore, oral administration of DS-1558 (0.03, 0.1 and 0.3mg/kg) significantly and dose-dependently improved hyperglycemia and increased insulin secretion during the oral glucose tolerance test in Zucker fatty rats, the model of insulin resistance and glucose intolerance. Next, we examined the combination effects of DS-1558 with glucagon like peptide-1 (GLP-1). DS-1558 not only increased the glucose-stimulated insulin secretion by GLP-1 but also potentiated the maximum insulinogenic effects of GLP-1 after an intravenous glucose injection in normal Sprague Dawley rats. Furthermore, the glucose lowering effects of exendin-4, a GLP-1 receptor agonist, were markedly potentiated by the DS-1558 (3mg/kg) add-on in diabetic db/db mice during an intraperitoneal glucose tolerance test. In conclusion, our results indicate that add-on GPR40 agonists to GLP-1 related agents might be a potential treatment compared to single administration of these compounds. Therefore the combinations of these agents are a novel therapeutic option for type 2 diabetes.

Discovery of 3-aryl-3-ethoxypropanoic acids as orally active GPR40 agonists.

The G protein-coupled receptor 40 (GPR40) mediates enhancement of glucose-stimulated insulin secretion in pancreatic ß cells. The GPR40 agonist has been attracting attention as a novel insulin secretagogue with glucose dependency for the treatment of type 2 diabetes. The optimization study of compound 1 led to a potent and bioavailable GPR40 agonist 24, which showed insulin secretion and glucose lowering effects in rat OGTT. Compound 24 is a potential lead compound for a novel insulin secretagogue with a low risk of hypoglycemia.

Novel diphenylmethyl-derived amide protecting group for efficient liquid-phase peptide synthesis: AJIPHASE.

An efficient method for the synthesis of peptides bearing an amide at the C-terminal is described. This method involves the attachment of a C-terminal protecting group bearing long aliphatic chains, followed by the repetition of simple reaction and precipitation steps with the combined advantages of liquid-phase peptide synthesis (LPPS) and solid-phase peptide synthesis (SPPS). Using this method, a hydrophobic peptide was successfully synthesized in good yield and high purity, which cannot be obtained satisfactorily by SPPS.

[Use of intracerebral microdialysis in severe traumatic brain injury].

Brain microdialysis (MD) is a well-established technique to monitor the chemistry of the extracellular space in the brain during neurointensive care. MD may be useful in severe cases of traumatic brain injury (TBI) in which monitoring of intracranial pressure and cerebral perfusion pressure is required. Lactate/pyruvate (L/P) ratio, glucose, glutamate, and glycerol can be measured using a bedside device. The L/P ratio is a sensitive marker of changes in the redox state of cells caused by ischemia. Glycerol is an integral component of cell membranes. Loss of energy due to ischemia eventually leads to an influx of calcium and a decomposition of cell membranes, which liberates glycerol into the interstitial fluid. Thus the L/P ratio and glycerol have become the most important markers of ischemia and cell membrane damage. As the primary source of energy, glucose is an important marker of changes in brain metabolism and the glutamate level is an indirect marker of cell damage. We have monitored MD together with intracranial pressure (ICP) for 55 to 287 (142±74) hours in 8 severe TBI patients. No complications were observed in relation to MD and ICP monitoring. Our preliminary results indicate that MD L/P ratios are higher and more fluctuated in poor outcome patients compared to those in favorable outcome patients. MD in association with other brain monitoring techniques is safe and may be useful in preventing and relieving secondary ischemic injury, predicting outcome and guiding therapy after severe TBI. However, the value of MD as a tool in routine neurointensive care decision-making remains unclear.

Endovascular trapping for vertebral artery fusiform aneurysm in a patient with idiopathic thrombocytopenic purpura.

A 56-year-old woman with adult idiopathic thrombocytopenic purpura (ITP) diagnosed 17 years previously presented with a fusiform aneurysm manifesting as chronic headache. She had suffered no major hemorrhagic complications, although her platelet counts were between 3.0 x 10(9)/l and 50.0 x 10(9)/l. Magnetic resonance angiography identified a fusiform aneurysm of the right vertebral artery. Endovascular trapping after high-dose gammaglobulin with steroid therapy was performed. The patient received antiplatelet therapy to prevent thromboembolic events. The parent artery and aneurysm were completely occluded with no hemorrhagic complications. Endovascular treatment is considered safe in patients with ITP, although careful periprocedural management of platelet count is required.

Haplofungins, novel inositol phosphorylceramide synthase inhibitors, from Lauriomyces bellulus SANK 26899 I. Taxonomy, fermentation, isolation and biological activities.

In the course of screening for antifungal agents, we have discovered eight novel compounds, haplofungin A, B, C, D, E, F, G and H, from a culture broth of the fungus strain Lauriomyces bellulus SANK 26899. Haplofungins are composed of an arabinonic acid moiety linked through an ester to a modified long alkyl chain and show potent inhibitory activities against fungal inositol phosphorylceramide (IPC) synthase. Haplofungin A inhibited the activity of IPC synthase from Saccharomyces cerevisiae with an IC(50) value of 0.0015 microg ml(-1). This inhibitor also suppressed the growth of Candida glabrata at the MIC value of 0.5 microg ml(-1).

Haplofungins, new inositol phosphorylceramide synthase inhibitors, from Lauriomyces bellulus SANK 26899 II. Structure elucidation.

Eight new inositol phosphorylceramide synthase inhibitors: haplofungin A, B, C, D, E, F, G and H, were discovered in a culture broth of the fungus Lauriomyces bellulus SANK 26899. The planar structures for these haplofungins were elucidated by various spectroscopic analyses and a GC/MS analysis of their degradation products. All eight compounds were found to comprise an arabinonic acid moiety linked through an ester bond to a modified long alkyl chain.

Haplofungins, novel inositol phosphorylceramide synthase inhibitors, from Lauriomyces bellulus SANK 26899 III. Absolute structure of haplofungin A.

The absolute structure of haplofungin A, a potent fungal inositol phosphoceramide (IPC) synthase inhibitor from Lauriomyces bellulus SANK 26899, was determined by chiral GC/MS analysis, NMR and X-ray crystallographic analysis of the derivatives of degradation products.

Stromal cell derived factor-1 (SDF-1)/CXCL12 attenuates diabetes in mice and promotes pancreatic beta-cell survival by activation of the prosurvival kinase Akt.

OBJECTIVE: Diabetes is caused by a deficiency of pancreatic beta-cells that produce insulin. Approaches to enhance beta-cell mass by increasing proliferation and survival are desirable. We determined whether stromal cell-derived factor (SDF)-1/CXCL12 and its receptor, CX chemokine receptor (CXCR)4, are important for the survival of beta-cells. RESEARCH DESIGN AND METHODS: Mouse pancreata and clonal beta-cells were examined for expression of SDF-1 and CXCR4, activation of AKT and downstream signaling pathways by SDF-1, and protection against apoptosis and diabetes induced by streptozotocin (STZ). RESULTS: CXCR4 is expressed in beta-cells, and SDF-1 is expressed in microvascular endothelial cells within the islets and in surrounding interstitial stromal tissue. Transgenic mice overexpressing SDF-1 within their beta-cells (RIP-SDF-1 mice) are resistant to STZ-induced beta-cell apoptosis and diabetes. In MIN6 beta-cells, a CXCR4 antagonist (AMD3100) induces apoptosis, increases reactive oxygen species, decreases expression levels of the anti-apoptotic protein Bcl-2, and reduces phosphorylation of the proapoptotic protein Bad. Active phosphorylated prosurvival kinase Akt is increased both in the beta-cells of RIP-SDF-1 mice and in INS-1 cells treated with SDF-1 and sensitive to AMD3100. Inhibition of AKT expression by small interfering RNA attenuates the ameliorative effects of SDF-1 on caspase-dependent apoptosis induced by thapsigargin or glucose deprivation in INS-1 beta-cells. Specific inhibition of Akt activation by a soluble inhibitor (SH-5) reverses the anti-apoptotic effects of SDF-1 in INS-1 cells and mouse islets. CONCLUSIONS: SDF-1 promotes pancreatic beta-cell survival via activation of Akt, suggesting that SDF-1 agonists may prove beneficial for treatment of diabetes.

Pleofungins, novel inositol phosphorylceramide synthase inhibitors, from Phoma sp. SANK 13899. I. Taxonomy, fermentation, isolation, and biological activities.

In the course of a screening for inositol phosphorylceramide (IPC) synthase inhibitors, the novel inhibitors pleofungins A, B, C, and D were found in a mycelial extract of a fungus, Phoma sp. SANK13899. Purification was performed by 50% methanol and ethyl acetate extraction, reversed phase open-column chromatography, and HPLC separations. Pleofungin A inhibited the IPC synthase of Saccharomyces cerevisiae and Aspergillus fumigatus at IC(50) values of 16 and 1.0 ng/ml, respectively. The inhibitor also suppressed the growth of Candida albicans, Cryptococcus neoformans, and A. fumigatus at MIC values of 2.0, 0.3, and 0.5 mug/ml, respectively. These biological properties indicate that pleofungins belong to a novel class of IPC synthase inhibitors efficacious against A. fumigatus.

Pleofungins, novel inositol phosphorylceramide synthase inhibitors, from Phoma sp. SANK 13899. II. Structural elucidation.

Pleofungins (formerly called F-15078) A, B, C and D, novel depsipeptide antifungal antibiotics, were found in a mycelium extract of the producing fungus, Phoma sp. SANK 13899. The structures of pleofungins A, B, C and D were elucidated mainly by various NMR studies. The absolute configurations of the amino acids and N-methyl amino acids of pleofungin A constituents in the hydrolysate were determined by the application of advanced Marfey's method in combination with gas chromatography/mass spectrometry analysis of their silylation products with N-methyl-N-(tert-butylsilyl)trifluoroacetamide. Two alpha-hydroxy acid constituents, alpha-hydroxyisocaproic acid and alpha-hydroxyisovaleric acid, were isolated from the hydrolysate and their stereochemistries were determined by their specific rotations.

Deletion of OSH3 gene confers resistance against ISP-1 in Saccharomyces cerevisiae.

Sphingolipids have been reported to regulate the growth and death of mammalian and yeast cells, but their precise mechanisms are unknown. In this paper, it was shown that the deletion of the oxysterol binding protein homologue 3 (OSH3) gene confers hyper resistance against ISP-1, an inhibitor of sphingolipid biosynthesis, in the yeast Saccharomyces cerevisiae. Furthermore, the overexpression of the ROK1 gene, which directly binds to Osh3p, conferred resistance against ISP-1, and the deletion of the KEM1 gene, which regulates microtubule functions, exhibited ISP-1 hypersensitivity. And yet, an ISP-1 treatment caused an abnormal mitotic spindle formation, and the ISP-1-induced cell cycle arrest was rescued by the deletion of the OSH3 gene. Taken together, it is suggested that the expression levels of the OSH3 gene influence the ISP-1 sensitivity of S. cerevisiae, and the sphingolipids are necessary for normal mitotic spindle formation in which the Osh3p may play a pivotal role.

Duodenum-preserving resection of the pancreatic head with the ultrasonic coagulating shears.

Duodenum-preserving resection of the pancreatic head is a risk factor for pancreatic fistula because of the wide surface of the transected pancreas. We report on a 72-year-old woman undergoing this procedure for cystadenoma in the pancreatic head using the ultrasonic coagulating shears. The soft pancreatic parenchyma was extensively transected around the cyst with the coagulating shears. Suture of the cut stump was not necessary due to absence of bleeding. The distal pancreatic duct was well preserved for pancreatojejunostomy. We oversewed the possible opening of the main pancreatic duct on the remaining pancreas attached to the duodenum after confirming the location by intrabiliary dye injection. The postoperative course was uneventful. The draining fluid amylase level was low and there were no viscous materials from the drains. We compared histologic changes of a porcine pancreas transected with the coagulating shears or electrocautery to evaluate the sealing effect of the transected surface. The cut stump was covered by a continuing layer of thick protein coagulum in cases of coagulating shears, but by a disrupted layer of coagulating necrosis with charring in cases of electrocautery. The coagulating shears are useful for pancreatic transection in duodenum-preserving resection of the pancreatic head to prevent bleeding and pancreatic fistula from the cut surface.

[Complete response in a case of recurrent gastric cancer treated with TS-1].

We report the case of 72-year-old man with recurrent gastric cancer who was successfully treated with TS-1. We performed only non-curative operation because the tumor had infiltrated the pancreas head and aspiration pneumonia complications developed under the anesthetic. Abdominal CT revealed local recurrence and metastasis of the paraaortic lymph node after 3 months, so we started TS-1 chemotherapy. One course consisted of daily oral administration of 100 mg TS-1 for 4 weeks and withdrawal for 2 weeks. The recurrent lesions disappeared completely after 1 course. Furthermore, this therapy was continued for 3 courses without any side effects.