Lewis acid promoted fluorine-alkoxy group exchange reactions for the synthesis of 5-alkoxy-4,4-difluoroisoxazoline systems.

Fluorine-alkoxy group exchange reactions of fluorinated isoxazoline derivatives promoted by Lewis acids to give various 5-alkoxylated 4,4-difluoroisoxazolines via SN1 type processes in good to excellent yields are reported. Sterically demanding phenol substrates such as 2,6-diphenylphenol gave novel aryl substituted products via electrophilic aromatic substitution.

Soluble Klotho causes hypomineralization in Klotho-deficient mice.

The type I transmembrane protein αKlotho (Klotho) serves as a coreceptor for the phosphaturic hormone fibroblast growth factor 23 (FGF23) in kidney, while a truncated form of Klotho (soluble Klotho, sKL) is thought to exhibit multiple activities, including acting as a hormone, but whose mode(s) of action in different organ systems remains to be fully elucidated. FGF23 is expressed primarily in osteoblasts/osteocytes and aberrantly high levels in the circulation acting via signaling through an FGF receptor (FGFR)-Klotho coreceptor complex cause renal phosphate wasting and osteomalacia. We assessed the effects of exogenously added sKL on osteoblasts and bone using Klotho-deficient (kl/kl) mice and cell and organ cultures. sKL induced FGF23 signaling in bone and exacerbated the hypomineralization without exacerbating the hyperphosphatemia, hypercalcemia and hypervitaminosis D in kl/kl mice. The same effects were seen in rodent bone models in vitro, in which we also detected formation of a sKL complex with FGF23-FGFR and decreased Phex (gene responsible for X-linked hypophosphatemic rickets (XLH)/osteomalacia) expression. Further, sKL-FGF23-dependent hypomineralization in vitro was rescued by soluble PHEX. These data suggest that exogenously added sKL directly participates in FGF23 signaling in bone and that PHEX is a downstream effector of the sKL-FGF23-FGFR axis in bone.

How do we manage the gastrectomy for gastric cancer after coronary artery bypass grafting using the right gastroepiploic artery? Report of two cases and a review of the literature.

BACKGROUND: Recently, the right gastroepiploic artery (RGEA) has been used in coronary artery bypass grafting (CABG) as an alternative arterial graft. Unfortunately, an increased incidence of gastric cancers has been reported after CABG using the RGEA. Handling of the RGEA during gastrectomy in these patients may cause lethal complications, which sometimes reduces the feasibility of curative dissection of lymph nodes at the base of the graft. CASE PRESENTATIONS: We describe two cases of gastric cancer undergoing gastrectomy after CABG with the use of RGEA. To avoid the potentially fatal coronary event during gastrectomy, safe handling of the conduit including preparations for injuries and prevention of vessel spasm was performed in both cases, accompanied by an adequate monitoring of the systemic circulation. Intraoperative frozen section examination showed no lymph node metastasis around the graft in any of the cases; therefore, complete lymph node dissection at the base of the graft was not undertaken. No complications occurred during the operation. In addition to these two cases, twenty-four cases reported in the literatures were reviewed (a total of 26 cases). Ten early and 16 advanced gastric cancers were included. Among the 16 advanced gastric cancer cases, an alternative graft was employed in 8 due to the resection of an original graft to complete lymph node dissection. Mere handling of a graft often caused lethal complications suggesting that the operation should be completed by isolation of the graft. A pedicled graft harvesting via the ante-gastric route was popular. However, a skeletonized harvesting with resection of the pyloric branches of the RGEA would be better because this would interrupt the original lymph flow, which could eliminate the need for lymph node dissection and graft isolation. Among the 10 cases having early gastric cancers, 6 were found within 1.5 years after CABG. Early detection in these 6 cases was possible due to the use of gastric fiberscopic examination before and after CABG, which gave them opportunities to receive a less extensive operation such as endoscopic mucosal resection. CONCLUSION: Adequate intraoperative care as well as an optimal lymph node dissection considering the graft harvesting method at the first CABG leads to successful gastrectomy after CABG using the RGEA graft. Therefore, this operation should be carried out with careful management by both gastrointestinal and cardiovascular surgeons.

Excitatory neurotoxic properties of pontamine sky blue make it a useful tool for examining the functions of focal brain parts.

Pontamine sky blue (PSB) is used in brain studies to mark the position of microelectrode and micropipette tips. However, few studies have been made on the effects of PSB on neurons; therefore we examined these effects. When puffed on isolated sensory ganglion cells of rats, PSB increased membrane conductance, depolarized membrane potential, and reduced the amplitude of action potentials. When dripped on frog sympathetic ganglion, much like hexamethonium, PSB decreased the amplitude of compound action potentials of the postganglionic strand. A bath application of PSB to sartorius muscle fibers that had been treated with tetrodotoxin depolarized the membrane potential and increased the frequency and amplitude of miniature end-plate potentials. All these effects were reversible. When injected into the rat's pontine part corresponding to the location of the canine pontine defecation reflex center, PSB produced repetitive colorectal contractions and irreversibly abolished them in response to anal-canal stimulation. The excitatory and blocking effects of PSB and its staining ability make it a useful tool for examining the functions of focal brain parts.

Synergistic fungicidal activities of polymyxin B and ionophores, and their dependence on direct disruptive action of polymyxin B on fungal vacuole.

Polymyxin B (PMB) acts selectively on Gram-negative bacteria by electrostatic and hydrophobic interactions with anionic cell envelope components such as phospholipids and lipopolysaccharides. In this study, PMB was shown to exhibit marked fungicidal activity against yeasts and filamentous fungi in combination with ionophores such as salinomycin (SAM) and monensin (MON), which can selectively interact with monovalent cations. Ca(2+)-selective ionophores, A23187 and ionomycin, were absolutely ineffective in enhancing the fungicidal activity of PMB. SAM and MON increased the rate of cellular uptake of PMB possibly in favor of its intracellular action on the organelle. PMB could indeed directly disrupt the spherical membrane-enclosed architecture of the isolated vacuoles equally in the absence and presence of the ionophores. The loss of energy barrier for transmembrane transport of monovalent cations is considered to be a cause of enhanced incorporation of larger cationic compounds such as PMB across fungal plasma membrane.

A small, incidentally detected pancreatic somatostatinoma: report of a case.

We report an asymptomatic 72-year-old woman with a small, incidentally detected, pancreatic somatostatinoma. The tumor, measuring 1 cm in diameter, showed a hypervascular pattern of contrast enhancement on computed tomography, and was found angiographically to receive a blood supply from the posterior superior pancreaticoduodenal artery. The results of preoperative hormonal assays all were normal. No assay for somatostatin was performed. No abnormality in either the pituitary or parathyroid was found. We thus considered the tumor to be a sporadic, nonfunctioning endocrine cell tumor, and enucleation was carried out. As some tumor cells in the resected specimen showed immunoreactivity for somatostatin, a diagnosis of somatostatinoma was made. Therefore, the possibility of somatostatinoma should be kept in mind when making a differential diagnosis of pancreatic endocrine tumors in cases where even a small hypervascular tumor is detected on enhanced computed tomography.

Successful treatment of Fournier's gangrene with the assistance of preoperative computed tomography in an elderly man: report of a case.

An 87-year-old man presented with inguinal pain and swelling, and was later diagnosed as having Fournier's gangrene. The information gained from preoperative computed tomography (CT) proved very useful for defining the extent of necrosis, and emergency surgery saved his life. Thus, CT should be performed prior to treatment of Fournier's gangrene, even in an emergency situation.