Preparation of Tenuifolin from Polygala senega L. Root Using a Hydrolytic Continuous Flow System under High-Temperature, High-Pressure Conditions.

An improved process for preparing tenuifolin (presenegenin 3-ß-d-glucopyranoside) from the root of Polygala senega L. was developed. A crude saponin mixture extracted from P. senega was subjected to hydrolysis, and the reactivity of compounds in the extract was controlled by utilizing the combination of a flow reactor and experimental design. In addition, column chromatography with HP 20, a synthetic polystyrenic adsorbent, allowed the gram-scale preparation of tenuifolin in a continuous manner with fewer steps. This approach shortens the total time required for gram-scale preparation from 16 to 5 h in a continuous manner while improving the yield from 0.59% to 2.08% (w/w).

[Long-Term Complete Response by Chemotherapy for Distant Lymph Node Metastases after Curative Surgery for Ascending Colon Cancer-A Case Report].

A 74-year-old woman underwent right hemicolectomy for ascending colon cancer in March 2013, after which she received adjuvant chemotherapy(UFT plus UZEL)for 6 months. In October 2014, left supraclavicular lymphadenopathy appeared, and it was diagnosed as adenocarcinoma metastasis through fine-needle aspiration cytology. CT revealed swelling of left supraclavicular lymph nodes and para-aortic lymph nodes but no metastases to other organs. Exclusion diagnosis was performed, and they were diagnosed as multiple distant lymph node metastases. Chemotherapy(mFOLFOX6 plus bevacizumab) was started in December 2014, and all swollen lymph nodes shrank and disappeared on CT in July 2015. Furthermore, there was no swelling of lymph nodes or appearance of new lesions on CT in December 2015, as the response to treatment was judged to be complete. In addition, the regimen was changed to FOLFIRI plus bevacizumab because side effects such as peripheral neuropathy were worsening. Although chemotherapy was discontinued in November 2016, there has been no recurrence and a long-term complete response has been sustained.

[A Case of Immediately-Treated Internal Hernia Occurring during Chemotherapy for Liver Metastasis after Gastric GIST Resection].

A 71-year-old man underwent total gastrectomy with Roux-en-Y reconstruction for gastric GIST in October 2017. Liver metastasis was identified in June 2019, and chemotherapy with imatinib was started in July. In December, the patient presented with acute upper abdominal pain and back pain. Abdominal contrast-enhanced CT showed that the jejunum extending from the duodenal stump was dilated. In addition, part of the jejunum had a poor wall contrast effect, with ascites also found surrounding it. We suspected a strangulated ileus and immediately performed emergency surgery. We found an internal hernia with incarceration of the afferent loop at the Petersen's defect. The time from the onset of symptoms to the surgery was relatively short, and the surgery was completed with hernial repair and closure of the hernial orifice without the development of bowel necrosis; the patient's postoperative course was good. Although the frequency of internal hernia after gastrectomy is relatively low, there is a risk that it may be severe if it occurs. Therefore, care should be taken to not cause internal hernias during surgery, and an internal hernia should be considered in the event of sudden abdominal pain after gastric surgery.

Synthesis of Bisdesmosidic Oleanolic Acid Saponins via a Glycosylation-Deprotection Sequence under Continuous Microfluidic/Batch Conditions.

We report the first synthesis of a series of bisdesmosidic oleanolic acid saponins using microflow reactor Comet X-01 via a continuous flow glycosylation-batch deprotection sequence. The main results of this study can be summarized as follows: (1) The microfluidic glycosylation of oleanolic acid at C-28 was achieved in quantitative yield and was applied to the synthesis of six C-28-monoglycosidic saponins. (2) The microfluidic glycosylation of oleanolic acid at C-3 was achieved in good yield without orthoester byproduct formation and was applied to the synthesis of three bisdesmosidic saponins. (3) The continuous synthesis of saponins via a microfluidic glycosylation-batch deprotection sequence was achieved in four steps involving two purifications. Thus, the continuous microfluidic glycosylation-deprotection process is expected to be suitable for the preparation of a library of bisdesmosidic oleanolic acid saponins for in vivo pharmacological studies.

Syntheses and mucosal adjuvant activity of simplified oleanolic acid saponins possessing cinnamoyl ester.

A series of new simplified oleanolic acid saponins with a glycosyl ester moiety at C28, were efficiently prepared. Furthermore, the effect of nasal administration of the synthetic oleanolic acid saponins on the nasal anti-influenza virus antibody titer against secondary nasal inoculation of the influenza split vaccine was examined. The result revealed cinnamoyl saponin as a suitable candidate vaccine adjuvant.

[A Case of Strangulation Ileus with Hemorrhagic Shock Caused by an Internal Hernia of the Small Intestine].

PATIENT: An 81-year-old man. Past medical history: distal gastrectomy and Roux-en-Y reconstruction. CHIEF COMPLAINT: epigastric pain, nausea, and hematemesis. History of present illness: the man developed epigastric pain, nausea, and hematemesis the day before visiting our hospital. Upper gastrointestinal endoscopy revealed that the small intestinal mucosa was extensively congested, and a clinical condition due to the previous gastric surgery was suspected. Therefore, the man was admitted to our department. The patient was diagnosed with strangulation ileus by contrast-enhanced abdominal CT, and was referred for emergency surgery. At the time of entering the operating room 3 hours later, his abdomen was remarkably swollen. After anesthesia induction, his blood pressure dropped to 40-49 mmHg, and he was in a state of shock. Strangulation ileus was caused by an internal hernia of the small intestine through the gap between the mesenteric sutures of the Roux-en-Y reconstruction. The small intestinal wall was significantly discolored and remarkably expanded due to bleeding into the small intestine. We determined that mass resection of the small intestine posed high risk, and performed only reduction of the small intestinal hernia. Since strangulated ileus causing hemorrhagic shock is rare, we describe the case and review the literature on the topic.

Endoscopic drainage with a metallic stent for obstructive jaundice caused by bile duct metastasis of breast cancer: A case report.

Key Clinical Message: Bile duct metastasis of breast cancer is rare. It often causes obstructive jaundice which makes the patient interrupt state of treatment. Endoscopic drainage for obstructive jaundice is effective and less invasive treatment option also in this case. Abstract: A 66-year-old breast ductal carcinoma patient developed obstructive jaundice, presenting with epigastric discomfort and dark-colored urine. Computed tomography and endoscopic retrograde cholangiopancreatography revealed bile duct stenosis. Brushing cytology and tissue biopsy confirmed bile duct metastasis, a self-expandable metallic stent was placed/replaced endoscopically, and chemotherapy was continued, extending the patient's life.

Location of focal vasospasm provoked by ergonovine maleate within coronary arteries in patients with vasospastic angina pectoris.

This study examined whether coronary focal vasospasm occurs in a nonuniform distribution within the coronary tree and whether a longitudinal plaque distribution pattern is present in patients with vasospastic angina using 3-dimensional intravascular ultrasound analysis. Of 121 patients with clinically suspected angina without fixed stenosis in the coronary arteries, vasospasm was provoked in 82 patients with 92 lesions (42 focal, 50 diffuse) by intravenous ergonovine maleate injection. Most focal vasospasms occurred in the proximal third of the coronary arteries (proximal 28, mid 8, distal 6, p <0.01), corresponding to the historical high-risk zones for acute coronary occlusion. More plaque burden also existed in the proximal third of the coronary arteries in patients with focal vasospasm.

Plasma low-density lipoprotein reduction and structural effects on coronary atherosclerotic plaques by atorvastatin as clinically assessed with intravascular ultrasound radio-frequency signal analysis: a randomized prospective study.

BACKGROUND: Plaque stabilization by statins is important for reduction of cardiovascular events but has not been demonstrated enough in vivo. We examined whether statins clinically alter the structure of coronary atherosclerotic plaques using intravascular ultrasound (IVUS) radio-frequency (RF) signal analysis. METHODS: Fifty consecutive patients undergoing percutaneous coronary intervention were enrolled. Intravascular ultrasound radio-frequency signals were acquired from non-percutaneous coronary intervention-targeted echolucent plaques. The patients were randomly assigned into 2 groups: group S (n = 25) taking atorvastatin 10 mg/d and group C (n = 25) as control. After 6-month follow-up, IVUS-RF signals were sampled at the same plaque sites. Several regions of interest were placed on each plaque. Intravascular ultrasound radio-frequency parameters were blindly calculated in all regions of interests (group S, n = 148; group C, n = 191). Targeted plaque volumes were also measured. Those data were compared between baseline and follow-up. RESULTS: In group S after 6 months, plasma low-density lipoprotein level was significantly decreased (133 +/- 13 to 87 +/- 29 mg/dL, P < .0001), integrated backscatter of IVUS-RF signals was substantially increased (-53.8 +/- 4.5 to -51.2 +/- 4.9 dB, P < .0001), and plaque volume was significantly reduced, whereas no change was demonstrated in group C. CONCLUSIONS: These results suggest that statins alter properties as well as volumes of coronary plaques within 6 months, which may be related to plasma low-density lipoprotein reduction. Intravascular ultrasound radio-frequency signal analysis may be useful to evaluate the effects of drugs on stabilization of coronary atherosclerotic plaques.

Syntheses, crystal structures and antimicrobial activities of monomeric 8-coordinate, and dimeric and monomeric 7-coordinate bismuth(III) complexes with tridentate and pentadentate thiosemicarbazones and pentadentate semicarbazone ligands.

Novel bismuth(III) complexes 1-4 with the tridentate thiosemicarbazone ligand of 2N1S donor atoms [Hmtsc (L1); 2-acetylpyridine (4N-morpholyl thiosemicarbazone)], the pentadentate double-armed thiosemicarbazone ligand of 3N2S donor atoms [H2dmtsc (L3); 2,6-diacetylpyridine bis(4N-morpholyl thiosemicarbazone)] and the pentadentate double-armed semicarbazone ligand of 3N2O donor atoms [H2dasc (L4b); 2,6-diacetylpyridine bis(semicarbazone)], were prepared by reactions of bismuth(III) nitrate or bismuth(III) chloride and characterized by elemental analysis, thermogravimetric and differential thermal analysis (TG/DTA), FTIR and NMR (1H and 13C) spectroscopy. The crystal and molecular structures of complexes 1, 2a, 2b and 4b, and the "free" ligand L1 were determined by single-crystal X-ray structure analysis. The dimeric 7-coordinate bismuth(III) complex [Bi(dmtsc)(NO3)]2, 1, and the monomeric 7-coordinate complexes [Bi(Hdasc)(H2O)](NO3)2.H2O (major product), 2a, and [Bi(dasc)(H2O)]NO3.H2O (minor product), 2b, all with pentagonal bipyramidal bismuth(III) centers, are depicted with one electron pair (6s2) of the bismuth(III) atom, deprotonated forms of multidentate thiosemicarbazone or semicarbazone ligands, and monodentate NO3 or H2O ligands, respectively. These complexes are related to the positional isomers of one electron pair of the bismuth(III) atom; 1 has an electron pair positioned in the pentagonal plane (basal position), while 2a and 2b have an electron pair in the apical position. The monomeric 8-coordinate complex [Bi(mtsc)2(NO3)], 4b, which was obtained by slow evaporation in MeOH of the 1.5 hydrates 4a, was depicted with one electron pair of the bismuth(III) atom, two deprotonated mtsc- ligand and one nitrate ion. On the other hand, crystals of the complex "[Bi(mtsc)Cl2]", 3, prepared by a reaction of BiCl3 with L1 showed several polymorphs (3a, 3b, 3c and 3d) due to coordination and/or solvation of dimethyl sulfoxide (DMSO) used in the crystallization. Bismuth(III) complexes 1 and 4a showed selective and effective antibacterial activities against Gram-positive bacteria. The structure-activity relationship was discussed.

Synthesis, structural characterization and antimicrobial activities of 12 zinc(II) complexes with four thiosemicarbazone and two semicarbazone ligands.

Twelve zinc(II) complexes with thiosemicarbazone and semicarbazone ligands were prepared and characterized by elemental analysis, thermogravimetric and differential thermal analysis (TG/DTA), FT-IR and 1H and 13C NMR spectroscopy. Seven three-dimensional structures of zinc(II) complexes were determined by single-crystal X-ray analysis. Their antimicrobial activities were evaluated by MIC against four bacteria (B. subtilis, S. aureus, E. coli and P. aeruginosa), two yeasts (C. albicans and S. cerevisiae) and two molds (A. niger and P. citrinum). The 5- and 6-coordinate zinc(II) complexes with a tridentate thiosemicarbazone ligand (Hatsc), ([Zn(atsc)(OAc)](n) 1, [Zn(Hatsc)(2)](NO(3))(2).0.3H(2)O 2, [ZnCl(2)(Hatsc)] 3 and [Zn(SO(4))(Hatsc)(H(2)O)].H(2)O 4 [Hatsc=2-acetylpyridine(thiosemicarbazone)]), showed antimicrobial activities against test organisms, which were different from those of free ligands or the starting zinc(II) compounds. Especially, complex 2 showed effective activities against P. aeruginosa, C. albicans and moderate activities against S. cerevisiae and two molds. These facts are in contrast to the results that the 5- or 6-coordinate zinc(II) complexes with a tridentate 2-acetylpyridine-4N-morpholinethiosemicarbazone, ([Zn(mtsc)(2)].0.2EtOH 5, the previously reported catena-poly [Zn(mtsc)-mu-(OAc-O,O')](n) and [Zn(NO(3))(2)(Hmtsc)] [Hmtsc=2-acetylpyridine (4N-morpholyl thiosemicarbazone)]), showed no activities against the test microorganisms. The 5- and 6-coordinate zinc(II) complexes with a tridentate 2-acetylpyridinesemicarbazone, ([Zn(OAc)(2)(Hasc)] 6 and [Zn(Hasc)(2)](NO(3))(2) 7 [Hasc=2-acetylpyridine(semicarbazone)]), showed no antimicrobial activities against bacteria, yeasts and molds. Complex [ZnCl(2)(Hasc)] 8, which was isostructural to complex 3, showed modest activity against Gram-positive bacterium, B. subtilis. The 1:1 complexes of zinc(II) with pentadentate thiosemicarbazone ligands, ([Zn(dmtsc)](n) 9 and [Zn(datsc)](n) 10 [H(2)dmtsc=2,6-diacetylpyridine bis(4N-morpholyl thiosemicarbazone) and H(2)datsc=2,6-diacetylpyridine bis(thiosemicarbazone)]), did not inhibit the growth of the test organisms. On the contrary, 7-coordinate zinc(II) complexes with one pentadentate semicarbazone ligand and two water molecules, ([Zn(H(2)dasc)(H(2)O)(2)](OAc)(2).5.3H(2)O 11 and [Zn(H(2)dasc)(H(2)O)(2)](NO(3))(2).H(2)O 12 [H(2)dasc=2,6-diacetylpyridine bis(semicarbazone)]), showed modest to moderate activities against bacteria. Based on the X-ray structures, the structure-activity correlation for the antimicrobial activities was elucidated. The zinc(II) complexes with 4N-substituted ligands showed no antimicrobial activities. In contrast to the previously reported nickel(II) complexes, properties of the ligands such as the ability to form hydrogen bonding with a counter anion or hydrated water molecules or the less bulkiness of the 4N moiety would be a more important factor for antimicrobial activities than the coordination number of the metal ion for the zinc(II) complexes.

Pioglitazone induces regression of coronary atherosclerotic plaques in patients with type 2 diabetes mellitus or impaired glucose tolerance: a randomized prospective study using intravascular ultrasound.

BACKGROUND: A large clinical trial clarified that pioglitazone reduces cardiovascular events in diabetic patients. However, effects of pioglitazone on structure of coronary atherosclerotic plaques have not been demonstrated. We examined whether pioglitazone reduces volumes of coronary atherosclerotic plaques using intravascular ultrasound (IVUS). METHODS: Twenty-six consecutive patients with type 2 diabetes mellitus (DM) or impaired glucose tolerance (IGT) undergoing percutaneous coronary intervention (PCI) were enrolled. Echolucent plaques without significant stenosis were selected in IVUS video images at non-PCI-influenced coronary segments and volumetric analysis of the targeted plaques was performed. The patients were randomly assigned into 2 groups: pioglitazone group consisted of 13 patients taking pioglitazone 15 mg/day for initial 14 days after PCI and subsequent 30 mg/day during 6-month follow-up, and control group with 13 patients as control. The plaque volumes and some parameters such as plasma lipid profiles and high-sensitive C-reacting protein (hs-CRP) levels were compared between baseline and the follow-up in those groups. RESULTS: In the pioglitazone group after 6 months, the plaque volume was significantly reduced (101.3+/-32.1 to 94.6+/-33.6 mm(3), -7.2%; p=0.0023), plasma triglyceride was significantly decreased (- 14.9%) and high density lipoprotein cholesterol was substantially increased (+20.0%) without any significant change in low density lipoprotein cholesterol (LDL-C). Also, hs-CRP level tended to be decreased. However, no significant change in plaque volumes and those parameters was observed in the control group. CONCLUSIONS: Pioglitazone may induce regression of coronary atherosclerotic plaques without LDL-C reduction in patients with DM and IGT.

Magnetic circular dichroism study of directly fused porphyrins.

The magnetic circular dichroism (MCD) spectra of doubly and triply linked fused bisporphyrins (2MD and 2MT, M = Ni, Zn, Cu, Pd, and H2) and triply linked higher oligomers (3ZnT and 4ZnT) have been measured, and their Q-bands assigned based on the results of INDO/s calculations. In contrast to the Faraday A term observed for the Q(0,0) band of Ni(II) tetraphenylporphyrin, a single positive Faraday B term was observed for the lowest energy transition of the fused systems. The calculations indicated that the molecular orbitals (MOs) of the directly fused porphyrins consist of linear combinations of the constituent monomeric MOs, and that the effect of lowering the symmetry is always larger on the lowest unoccupied molecular orbital (LUMO) than on the highest occupied molecular orbital (HOMO). On the basis of Michl's perimeter model, these features can be correlated with the observed positive MCD signs in the near infrared region. A weak absorption band at 600-700 nm for the fused dimers can be assigned to a short-axis polarized Q transition.

Homoleptic lanthanide triple-deckers of 5,15-diazaporphyrin with D2h symmetry.

Two novel homoleptic diazaporphyrinato lanthanide sandwich com-plexes M(2)(DAP)(3) [M = Ce (1), Eu (2); DAP= 2,8,12,18-tetra-ethyl-3,7,13,17-tetramethyl-5,15-diazaporphyrinate] were synthesized by a one-pot reaction of the corresponding M(acac)(3).nH(2)O (acac = acetylacetonate) with metal-free D(2)(h) type diazaporphyrin, H(2)DAP. The spectroscopic and electrochemical properties are compared with those of complexes based on D(4)(h) symmetry porphyrin ligands.

Usefulness of rapid quantitative measurement of myoglobin and troponin T in early diagnosis of acute myocardial infarction.

BACKGROUND: New equipment, the Cardiac Reader(TM), which can measure blood concentrations of troponin T (T) and myoglobin (M) in only 15 min at the bedside was evaluated for early diagnosis of acute myocardial infarction (AMI). METHODS AND RESULTS: A total of 34 consecutive patients with AMI who came to hospital within 24 h after onset were studied. Blood samples were collected from the patients at admission and 6, 12, 24, 48 h after onset to qualitatively and quantitatively measure T, M and creatine kinase-MB fraction. There were 20 patients with positive results by qualitative troponin T test and 29 with positive results by quantitative test. Of the patients who visited hospital within 3 h of onset, 17% were positive by the qualitative test and 67% cases had positive results in the quantitative test. The patients were divided into 2 groups according to the flow grade in the infarct-related coronary artery. In the TIMI 0-1 group (n=28), serum myoglobin concentrations were higher than in the TIMI 3-4 group (n=6) at admission and at their peak. CONCLUSION: The rapid quantitative test of T and M is useful for early diagnosis of AMI and as an indicator of its severity, which can be evaluated from the myoglobin concentration in the hyper-acute phase.