Search

Background Xanthan gum-based food thickeners (XG-FTs) are often ingested by patients with dysphagia to prevent aspiration during drug treatment. Reportedly, XG-FTs affect tablet disintegration, drug dissolution rates, and reduce the efficacy of postprandial antihyperglycemic agents. The absorption rate and quantity of fluoroquinolone antimicrobial agents correlate with drug efficacy, raising concern about the impact of XG-FTs. Previously, we reported that film-coated tablets were less susceptible to the effects of XG-FT than conventional and orally disintegrating tablets. Here, we compare the effect of XG-FTs on dissolution profiles of three oral fluoroquinolone-based film-coated tablets by evaluating the dissolution of crushed products, fine granules, and film-coated fine granules. Methods We examined formulations of tosufloxacin tosylate monohydrate (TFLX), levofloxacin hemihydrate (LVFX), and ciprofloxacin hydrochloride hydrate (CPFX). The formulations were immersed in 20 mL of 1.5% (w/v) XG-FT aqueous solution for 2.5 min followed by a dissolution test using the paddle method according to the Japanese Pharmacopoeia (dissolution test solution pH 1.2; volume 900 mL; temperature 37 ± 0.5 °C). The dissolution profile was evaluated according to the dissolution quantity indicated in product specifications and guidelines for bioequivalence testing of generic drugs. The 15-min mean dissolution rate was determined for a formulation immersed in 1.5% (w/v) XG-FT aqueous solution and compared with that for a non-immersed formulation (control). Fluoroquinolone film-coated tablets were mixed with starch-based FTs, guar gum-based FTs, or XG-FTs to observe their appearances. Results The dissolution profile of LVFX film-coated tablets was not affected by XG-FTs, but the dissolution of TFLX and CPFX was delayed. For crushed film-coated tablets, the 15-min mean dissolution rate was significantly delayed for all three fluoroquinolones when compared with that of uncrushed products. The dissolution profile of TFLX film-coated fine granules was unchanged by XG-FTs. CPFX film-coated tablets and crushed products produced a gel-like precipitate when mixed with XG-FTs and failed to meet product-dissolution specifications. A gel-like precipitate was also observed with guar gum-based FTs. Conclusion The effect of XG-FTs on the dissolution profile of film-coated fluoroquinolone formulations varied depending on the formulation. The CPFX formulation formed a gel-like precipitate when immersed in XG-FTs resulting in a significantly delayed dissolution.

A 68-year-old Japanese male presented with atrophic erythematous white lesions with peripheral dark reddish rims on his back. Multiple ulcers were detected from his stomach to his large intestine using endoscopy. Although the patient was given high doses of a steroid, aspirin, dipyridamole, and intravenous immunoglobulin therapy, he died of gastrointestinal hemorrhage, perforation and septic shock. An autopsy examination revealed pauci-inflammatory thrombotic microangiopathy with endothelial cell injury, fibrous occlusive arteriopathy, and vascular C5b-9 deposition in the wall of the gastrointestinal tract from the esophagus to the large intestine as well as in the dermis of the skin.

In addition to photoperiod, thermoperiod (or thermocycle) might be an important Zeitgeber for entraining the circadian oscillator controlling adult eclosion rhythm in the Indian meal moth Plodia interpunctella Hubner (Lepidoptera: Pyralidae). This is confirmed by exposing larvae receiving diapause-preventing treatments to various thermocycles with different means and amplitudes of temperature. The thermocycles investigated in the present study are TC 8 : 16 h, TC 12 : 12 h, TC 16 : 8 h and TC 20 : 4 h, where T and C represent thermophase (30 °C) and cryophase (20 °C), respectively. For all thermocycles, the peak of adult eclosion rhythm occurs at around the mid-thermophase. This indicates that the larvae use both ‘temperature-rise’ and ‘temperature-fall’ signals to adjust the eclosion phase in each thermocycle. The absence (DD) or presence (LL) of light affects this time-keeping system slightly under the given thermocycle. The rhythmic adult eclosion noted after exposure of larvae to 30 °C DD for 14 days is recorded in the thermocycles (TC 12 : 12 h, DD; mean temperature = 25 °C) with different amplitudes of 27.5/22.5 °C, 26.5/23.5 °C and 25.5/24.5 °C. The peak in adult eclosion advances in time as the amplitude of the temperature cycle decreases. In the temperature cycle of 25.5/24.5 °C, a peak occurs at the end of the cryophase, 2 h before the temperature-rise. The adult eclosion rhythm is also observed under various thermocycles (TC 12 : 12 h, DD) consisting of different temperature levels (30 to 20 °C) with different amplitudes. It is found that the temporal position of the peak advances significantly when the amplitude of the thermocycle becomes lower.

The rhythm of adult eclosion in the Indian meal moth Plodia interpunctella Hubner (Lepidoptera: Pyralidae) is investigated under various photoperiods and temperatures aiming to determine the nature of the temperature compensation and the free-running period. Insects that are committed to a nondiapause larval development show diel rhythms of adult eclosion at 30, 25 and 20 °C. At 30 °C, the eclosion peak (i.e. the mean time of eclosion) occurs approximately 20 h after lights off under an LD 4 : 20 h photocycle, and at approximately 15 h under an LD 20 : 4 h photocycle. At 25 °C, the peak of eclosion occurs approximately 19 h after lights off under an LD 2 : 20 h photocycle and at approximately 16 h under an LD 20 : 4 h photocycle. At 20 °C, the eclosion peak is significantly advanced under long days of >12 h (i.e. approximately 20 h after lights off under an LD 4 : 20 h photocycle and approximately 9 h under an LD 20 : 4 h photocycle), indicating an effect of both lights-off and lights-on signals on the timing of the adult eclosion. To determine the involvement of a self-sustained oscillator, the rhythm of adult eclosion is examined under darkness at different temperatures (30 to 21 °C). The mean free-running periods are 22.4, 22.8, 22.0 and 22.5 h at 30, 24, 23 and 22 °C, respectively, indicating that the eclosion rhythm is temperature-compensated. However, this rhythm does not free-run under constant darkness at 21 °C. Because a clear diel rhythm is observed under 24-h photocycles at 20 °C, the oscillator might be damped out within 24 h at the lower temperature.

背景:悪性褐色細胞腫の骨盤内再発はきわめてまれである. 今回われわれは, 原発腫瘍摘出11年後にダグラス窩に再発した悪性褐色細胞腫の1例を経験したので報告する.症例:48歳, 女性. 右副腎褐色細胞腫にて右副腎摘出術施行. 11年後に肝転移を認め肝部分切除術が施行されたが, カテコールアミン高値が持続し, 画像診断にてダグラス窩に腫瘤をめたため, 腫瘤摘出術を施行した. 摘出術後, 血圧, カテコールアミン値はすみやかに低下した. 摘出腫瘤の捺印標本には大小不同の目立つ異型細胞が多数みられ, 細胞質は微細顆粒状であった. 核クロマチンは増量し, 大型の核小体が1ないし数個認められた. 病理組織学的検索では, 付属器表面とダグラス窩に限局した転移と, 子宮筋層内への浸潤を認めた.結論:細胞診による褐色細胞腫の良・悪判定はきわめて困難で, 良性腫瘍であってもその異型性の強さから癌や肉腫と誤診されることもまれではない. 本症例は, 原発巣摘出11年後に起こったダグラス窩転移であったが, 細胞学的にも褐色細胞腫の特徴を示していた.

We isolated two plasmids, pS51A and pS51B which were 5782 bp and 4854 bp in size, respectively, from the third generation cephalosporin-resistant E. cloacae suspected to express metallo-beta-lactamase, and analyzed their structures. These two plasmids encode RNA I/RNA II genes for replication origin, relaxase genes of mobABCD for plasmid transfer, and several open reading frames. According to the classification of mobilizable plasmids by gene organization of the relaxases, pS51A and pS51B belong to the ColE1 superfamily of mobilizable plasmids, commonly detected in Enterobacteriaceae. The metallo-beta-lactamase gene was not identified in either pS51A or pS51B by homology search of the putative open reading frames. Open reading frames encoded in pS51A include E. coli protein L-like, E. coli heat shock protein-like, and E. coli plasmid replication initiation protein-like, and those encoded in pS51B include helix-turn-helix protein-like, E. coli plasmid replication initiation protein-like, and Salmonella replication initiation protein-like. These plasmids are stably maintained in one strain of E. cloacae, thus, the encoded gene functions may confer growth advantage to the host cell.

In antimicrobial susceptibility test for enterobacteriaceae, the efficacies of carpapenems are predicted by the minimum inhibitory concentration (MIC) of imipenem, and that of fluoroquinolones are predicted by the MIC of levofloxacin. To assess its judgement, we compared the MICs of imipenem, meropenem, panipenem, and doripenem for carbapenems, and ciprofloxacin, levofloxacin, tosufloxacin and pazufloxacin for fluoroquinolones of clinically isolated enterobacteria, Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca, Serratia marcescens, Enterobacter cloacae and Citrobacterfreundii, those resistant to the third generation cephalosporin. MIC distributions in low concentration range are estranged in some strains, conspicuously S. marcescens, E. cloacae and C. freundii: meropenem and doripenem displayed low MIC value than imipenem and panipenem. Since the estrangements are appeared MIC value of less than 8 microg/ml, the interpretive results (susceptible, intermediate, resistant) are not affected. In fluoroquinolones, all 4 agents showed almost identical MIC distributions, thus the MIC of levofloxacin is accepted to use the reference for other fluoroquinolones. The existence of the strains harboring carbapenem-resistant gene displaying low MIC value of carbapenems was reported. For the sensitive detection of the candidate of carbapenem-resistant strains, cut-off value of each carbapenem should be reconsidered, and also other phonotype analysis should be applied. Genomic analysis also would be required to detect the carbapenem-resistant gene.

We analyzed the antibiotic resistant genes, metallo-beta-lactamase and extended-spectrum beta-lactamase (ESBL), in highly resistant Enterobacter cloacae isolated at Showa University Hospital from April to June 2008. Thirty eight strains of E. cloacae were isolated. Of these strains, 35 demonstrating resistant to either cefotaxime (Minimum inhibitory concentration: MICor = 32 microg/ml), ceftadizime (MICor = 16 microg/ml), or aztreonam (MICor = 16 microg/ml) were selected for the analysis. The strains were subjected to a Double-disk synergy test (DDST) using sodium mercaptoacetic acid (SMA) and ceftadizime. As a result, 7 strains showed an enlargement of inhibition zone diameter by SMA. Among 7 SMA responded strains, 6 strains carried the bla(IMP-1) or bla(IMP-11) gene. There were 2 strains sensitive to imipenem (MIC1 microg/ml) in SMA responded strains, and one carried bla(IMP-11) gene. ESBL genes were detected in 5 strains, bla(CTX-M3) gene from 3 strains, and bla(CTX-M14) gene from 2 strains. All of the ESBL harboring strains showed an enlargement of inhibition zone diameter in DDST using clavulanic acid and ceftadizime, cefotaxime, aztreonam or cefepime. Among 35 strains, one strain carried both bla(IMP-1) and bla(CTX-M3) genes. In addition to the AmpC beta-lactamase, increase of the E. cloacae strains carrying these resistant genes cause the complex antibiotic resistant patterns. Especially, strains carrying bla(IMP) gene, which exhibit low imipenem MIC value may be induced to be resistant strains under the existence of imipenem. Analysis of resistant genes would be a beneficial for the measure the spread of drug-resistant E. cloacae.

A preliminary numerical study for electrospray thrusters is carried out including the interaction between solid tungsten and the ionic liquid, 1-ethyl-3-methyl imidazolium tetrafluoroborate (EMI-BF4). Classical molecular dynamics is used to investigate the behavior of a nano-droplet of EMI-BF4 on a tungsten plate. The diameter of the droplets are approximately 1 and 2 nm, which includes 8 and 27 EMI-BF4 molecules, for a total of 192 and 648 atoms. As for the tungsten plate, the thickness and the diameter are approximately 1 nm and 7 nm, respectively. Following the equilibration of the tungsten-ionic liquid system, a strong electric field is applied in two ways: by assuming a constant and uniformly distributed electric field and by assigning charges to the tungsten atoms, thus simulating a surface charge distribution. Ion emission is observed from the liquid in both cases.