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Introduction Mycoplasma genitalium is a known causative pathogen for some sexually transmitted infections. Nucleic acid amplification tests are a recommended method for detecting M. genitalium. A transcription-mediated amplification (TMA) nucleic acid amplification test to detect M. genitalium, the Aptima Mycoplasma genitalium assay was approved by the Food and Drug Administration in the United States and has been used in other countries. The purpose of this study is to determine the sensitivity of TMA test as the detection limit for 20 strains. Method The sensitivity of the TMA test was re-examined using 20 strains in vitro and the detection limit was estimated by comparison with the MgPa quantitative real-time PCR (qPCR) method. The M. genitalium strains used were isolated from Denmark, Norway, Sweden, France and Japan, and included macrolide or fluoroquinolone resistance. Stock strains were used at several dilutions, with each dilution of each strain examined using both TMA test and qPCR methods. Result and conclusion Estimated DNA loads of M. genitalium as the detection limit were 0.03–0.87 genome equivalents/mL. Sensitivity for TMA test was almost 100-fold higher than for the qPCR method.

Background Baloxavir marboxil has demonstrated safety and efficacy in treating adult and adolescent outpatients with acute influenza (CAPSTONE-1 trial). Here, we report a subgroup analysis of outcomes in adolescents from the trial. Methods CAPSTONE-1 was a randomized, double-blind, placebo-controlled study. Eligible adolescent outpatients (aged 12-17 years of age) were randomized in a ratio of 2:1 to a single dose of baloxavir 40/80 mg if less than/greater than or equal to 80 kg or placebo. The main outcomes were the time to alleviation of symptoms (TTAS), duration of infectious virus detection, and incidence of adverse events (AEs). Results Among 117 adolescent patients, 90 (77%) comprised the intent-to-treat infected population (63 baloxavir and 27 placebo; 88.9% A(H3N2)). The median TTAS was 38.6 hours shorter (95% confidence interval: −2.6, 68.4) in the baloxavir group compared with placebo (median TTAS, 54.1 hours vs 92.7 hours, P = .0055). The median time to sustained cessation of infectious virus detection was 72.0 hours for baloxavir compared with 120.0 hours for placebo recipients (P < .0001). Treatment-emergent PA/I38X-substituted viruses were detected in 5 of the 51 (9.8%) baloxavir recipients. In the safety population (76 baloxavir and 41 placebo), AEs were less common in baloxavir than placebo recipients (17.1% vs 34.1%; P = .0421). In the baloxavir group, no AEs except for diarrhea were reported in 2 or more patients. Conclusions Baloxavir demonstrated clinical and virologic efficacy in the otherwise healthy adolescents with acute influenza compared with placebo. There were no safety concerns identified. These results were similar to the adult population in CAPSTONE-1 and support baloxavir as a treatment option in adolescents., Single-dose baloxavir marboxil was clinically and virologically effective in otherwise healthy adolescent influenza patients (12-17 years) in CAPSTONE-1 randomized, double-blind, placebo-controlled study. This analysis supports the use of baloxavir marboxil in an adolescent population with uncomplicated influenza.

BACKGROUND Baloxavir marboxil (baloxavir) is a polymerase acidic protein (PA) endonuclease inhibitor with clinical efficacy in the treatment of uncomplicated influenza, including in outpatients at increased risk for complications. The postexposure prophylactic efficacy of baloxavir in the household setting is unclear. METHODS We conducted a multicenter, double-blind, randomized, placebo-controlled trial to evaluate the postexposure prophylactic efficacy of baloxavir in household contacts of index patients with confirmed influenza during the 2018–2019 season in Japan. The participants were assigned in a 1:1 ratio to receive either a single dose of baloxavir or placebo. The primary end point was clinical influenza, as confirmed by reverse-transcriptase–polymerase-chain-reaction testing, over a period of 10 days. The occurrence of baloxavir-selected PA substitutions associated with reduced susceptibility was assessed. RESULTS A total of 752 household contacts of 545 index patients were randomly assigned to receive baloxavir or placebo. Among the index patients, 95.6% had influenza A virus infection, 73.6% were younger than 12 years of age, and 52.7% received baloxavir. Among the participants who could be evaluated (374 in the baloxavir group and 375 in the placebo group), the percentage in whom clinical influenza developed was significantly lower in the baloxavir group than in the placebo group (1.9% vs. 13.6%) (adjusted risk ratio, 0.14; 95% confidence interval [CI], 0.06 to 0.30; P

BackgroundSingle-dose baloxavir rapidly reduces influenza virus titers and symptoms in patients with uncomplicated influenza, but viruses with reduced in vitro susceptibility due to amino acid substitutions at position 38 of polymerase acidic protein (PA/I38X) sometimes emerge.MethodsWe evaluated the kinetics, risk factors, and effects on clinical and virologic outcomes of emergence of PA/I38X-substituted viruses.ResultsViruses containing PA/I38X substitutions were identified 3–9 days after baloxavir treatment in 9.7% (36/370) of patients, of whom 85.3% had transient virus titer rises. Median time to sustained cessation of infectious virus detection was 192, 48, and 96 hours in the baloxavir recipients with PA/I38X-substituted viruses, without PA/I38X-substituted viruses, and placebo recipients, respectively. The corresponding median times to alleviation of symptoms were 63.1, 51.0, and 80.2 hours, respectively. After day 5, symptom increases occurred in 11.5%, 8.0%, and 13.0%, respectively, and in 8.9% of oseltamivir recipients. Variant virus emergence was associated with lower baseline neutralizing antibody titers.ConclusionsThe emergence of viruses with PA/I38X substitutions following baloxavir treatment was associated with transient rises in infectious virus titers, prolongation of virus detectability, initial delay in symptom alleviation, and uncommonly with symptom rebound. The potential transmissibility of PA/I38X-substituted viruses requires careful study.Clinical Trial RegistrationNCT02954354.

Baloxavir acid (BXA), derived from the prodrug baloxavir marboxil (BXM), potently and selectively inhibits the cap-dependent endonuclease within the polymerase PA subunit of influenza A and B viruses. In clinical trials, single doses of BXM profoundly decrease viral titers as well as alleviating influenza symptoms. Here, we characterize the impact on BXA susceptibility and replicative capacity of variant viruses detected in the post-treatment monitoring of the clinical studies. We find that the PA I38T substitution is a major pathway for reduced susceptibility to BXA, with 30- to 50-fold and 7-fold EC50 changes in A and B viruses, respectively. The viruses harboring the I38T substitution show severely impaired replicative fitness in cells, and correspondingly reduced endonuclease activity in vitro. Co-crystal structures of wild-type and I38T influenza A and B endonucleases bound to BXA show that the mutation reduces van der Waals contacts with the inhibitor. A reduced affinity to the I38T mutant is supported by the lower stability of the BXA-bound endonuclease. These mechanistic insights provide markers for future surveillance of treated populations.

Baloxavir marboxil (BXM) demonstrated a rapid and profound decline in infectious viral titer 1 day after BXM administration. Rapid reduction in virus titer is a characteristic of BXM. There may be a possibility that drug carryover effects have impacts on the observed antiviral effects due to the poor correlation that was observed between viral titer reduction and alleviation of influenza symptoms. Here, we report possible carryover effects of baloxavir acid (BXA), an active form of BXM, on infectious titer testing. Our findings indicate that there is little impact of BXA carryover on the infectious titer testing.

Background Baloxavir marboxil (baloxavir) is an antiviral drug that inhibits the viral "cap-snatching" step in virus RNA transcription initiation. In Phase 2 study, baloxavir significantly shortend the time to alleviation of symptoms (TTAS) and showed significantly greater reduction in influenza virus titer compared with placebo. This provides additional outcomes including efficacy against virus types/subtypes and pharmacokinetic/pharmacodynamic (PK/PD) analysis. Methods Subgroup analyses by virus types/subtype were conducted for the primary and key secondary endpoints. Blood samples were collected totally at 2 to 5 points including Day 2 after baloxavir dosing. PK/PD analyses were conducted for TTAS and change in virus titer using the liner model and the Emax model, respectively. Results The median TTAS in each baloxavir dose group was significantly shorter than in the placebo group for patients with A/H1N1pdm virus, and was numerically shorter than the placebo group for patients with A/H3N2 and type B virus. Baloxavir significantly reduced virus titer within 1 day after treatment: for A/H1N1pdm, A/H3N2, and B virus, all 3 doses of baloxavir marboxil reduced virus titer on Day 2 to a greater extent than placebo. No clear PK/PD relationships were found for the TTAS, but the larger reduction in virus titer was observed in increasing C24. Conclusion These results support that baloxavir marboxil will be effective against a range of virus types/subtypes.

BACKGROUND Baloxavir marboxil is a selective inhibitor of influenza cap-dependent endonuclease. It has shown therapeutic activity in preclinical models of influenza A and B virus infections, including strains resistant to current antiviral agents. METHODS We conducted two randomized, double-blind, controlled trials involving otherwise healthy outpatients with acute uncomplicated influenza. After a dose-ranging (10 to 40 mg) placebo-controlled trial, we undertook a placebo- and oseltamivir-controlled trial of single, weight-based doses of baloxavir (40 or 80 mg) in patients 12 to 64 years of age during the 2016-2017 season. The dose of oseltamivir was 75 mg twice daily for 5 days. The primary efficacy end point was the time to alleviation of influenza symptoms in the intention-to-treat infected population. RESULTS In the phase 2 trial, the median time to alleviation of influenza symptoms was 23.4 to 28.2 hours shorter in the baloxavir groups than in the placebo group (P

Atypical hemolytic uremic syndrome (aHUS) in allograft kidney transplantation is caused by various factors including rejection, infection, and immunosuppressive drugs. We present a case of a 32 year old woman with aHUS four years after an ABO-incompatible kidney transplantation from a living relative. The primary cause of end-stage renal disease was unknown; however, IgA nephropathy (IgAN) was suspected from her clinical course. She underwent pre-emptive kidney transplantation from her 60 year old mother. The allograft preserved good renal function [serum creatinine (sCr) level 110-130 μmol/L] until a sudden attack of abdominal pain four years after transplant, with acute renal failure (sCr level, 385.3 μmol/L), decreasing platelet count, and hemolytic anemia with schizocytes. On allograft biopsy, there was thrombotic microangiopathy in the glomeruli, with a cellular crescent formation and mesangial IgA and C3 deposition. Microvascular inflammation, such as glomerulitis, peritubular capillaritis, and arteriole endarteritis were also detected. A disintegrin-like and metalloproteinase with thrombospondin type 1 motifs 13 (ADAMTS13) did not decrease and Shiga toxin was not detected. Donor-specific antibodies or autoantibodies, including anti-neutrophil cytoplasmic antibody and anti-glomerular basement membrane (anti-GBM) antibody, were negative. The patient was diagnosed with aHUS and received three sessions of plasmapheresis and methylprednisolone pulse therapy, followed by oral methylprednisolone (0.25-0.5 mg/kg) instead of tacrolimus. She temporarily required hemodialysis (sCr level, 658.3 μmol/L). Thereafter, her sCr level improved to 284.5 μmol/L without dialysis therapy. This case is clinically considered as aHUS after kidney transplantation, associated with various factors, including rejection, glomerulonephritis, and toxicity from drugs such as tacrolimus.

Background Baloxavir marboxil (BXM), a selective cap-dependent endonuclease inhibitor, has demonstrated efficacy + safety for influenza in otherwise healthy patients. We present subgroup analyses for (i) United States vs. Japan (J), (ii) time (t) of treatment (early: ≥0 to ≤24 hours, vs. late: >24 to ≤48 hours), and (iii) influenza type B infections from the global Ph 3 trial (16/17 season). Methods A multicenter, randomized, double-blind, placebo (PLC)- and oseltamivir (OV)-controlled study recruited patients in Japan (n = 846) and United States (n = 590). Inclusion criteria: age 12–64 years, fever + flu symptoms, and ≤48 hours from symptom onset. Patients (20–64 years) randomized (2:2:1) to a single oral dose of BXM, PLC, or 75 mg OV BID for 5 days; patients 12–19 years were randomized (2:1) to receive BXM or PLC. BXM dose: 40/80 mg for BW Results BXM reduced the median TTAS by 30.6 hours versus PLC (87.3 versus 117.9 hours, P = 0.1373) in the US pop and t to cessation of viral shedding: 24 versus 72 hours for PLC (P < .0001). Median TTAS in the United States versus J pop was longer, due to imbalances between groups. In both early/late treatments from symptom onset, BXM reduced TTAS versus PLC (Table 1). Regardless of the t to treatment from symptom onset, BXM reduced virus titer significantly from BL versus PLC and OV (Table 2). No significant reduction in TTAS was seen, while BXM reduced virus titer versus PLC and OV in type B virus infection. Conclusion Outcomes for United States were aligned with the Ph 3 Results. Early treatment with BXM leads to a significantly faster TTAS vs. PLC. BXM caused significant viral titer reduction regardless of treatment time versus OV. BXM reduced virus titer vs. PLC and OV in type B virus infection. Disclosures K. Kawaguchi, Shionogi & Co., Ltd.: Employee, Salary. S. Portsmouth, Shionogi Inc: Employee, Salary. T. Shishido, Shionogi & Co., Ltd.: Employee, Salary.T. Uehara, Shionogi & Co., Ltd.: Employee, Salary. F. Hayden, Shionogi & Co., Ltd.: Scientific Advisor, Consulting fee (donated) and travel support for attending 6th ESWI meeting, 10–13 September 2017, Latvia, to present phase 3 OWH results.

New π-conjugated polymers with dibenzo[d,d′]benzo[1,2-b:4,5-b′]difuran (DBBDF) unit in the main chains were synthesized. Copolymerization of 6,12-diiodo-DBBDF with p-diethynylbenzene or 2,7-diethynylfluorene derivative under Sonogashira–Hagiwara coupling-reaction condition gave the corresponding copolymer. The resulting copolymers were soluble in organic solvents such as tetrahydrofuran and chloroform. In UV–vis absorption spectra, both copolymers showed red-shifted spectra compared to their monomer units. In the chloroform solutions, the copolymer with DBBDF and p-diethynylbenzene units showed yellowish-green emission, while the copolymer with DBBDF and 2,7-diethynylfluorene units did greenish-blue emission.

Unsymmetrical heteroacenes, 11-phenylbenzofuro[3,2-b]carbazole (Ph-BFC) and its alkoxylated derivatives, were readily synthesized by palladium-catalyzed double N-arylation of arylamines. They characteristically form antiparallel cofacial pi-stacking arrangements, which may result from their unsymmetrical structures. Their physical properties show their potential for application as active layers in organic field-effect transistors.

Ladder-type heteroacenes containing pyrrole or furan rings, indolo[3,2-b]carbazoles and dibenzo[d,d‘]benzo[1,2-b:4,5-b‘]difurans, were effectively synthesized from the common intermediates, 2,5-bis(o-chloroaryl)hydroquinones. The key reactions are palladium-catalyzed double N-arylation of aniline and intramolecular O-arylation, which enable regioselective ring closure. In addition to the parent indolo[3,2-b]carbazole and dibenzo[d,d‘]benzo[1,2-b:4,5-b‘]difuran, their derivatives with an alkyl or cyano group were first synthesized. Photophysical and electrochemical studies showed that the obtained heteroacenes have lower HOMO energy levels and larger band gaps than the corresponding hydrocarbon acene, pentacene. An X-ray analysis of dibenzo[d,d‘]benzo[1,2-b:4,5-b‘]difuran revealed that it was packed in herringbone fashion.

Atypical hemolytic uremic syndrome (aHUS) in allograft kidney transplantation is caused by various factors including rejection, infection, and immunosuppressive drugs. We present a case of a 32 year old woman with aHUS four years after an ABO-incompatible kidney transplantation from a living relative. The primary cause of end-stage renal disease was unknown; however, IgA nephropathy (IgAN) was suspected from her clinical course. She underwent pre-emptive kidney transplantation from her 60 year old mother. The allograft preserved good renal function [serum creatinine (sCr) level 110-130 μmol/L] until a sudden attack of abdominal pain four years after transplant, with acute renal failure (sCr level, 385.3 μmol/L), decreasing platelet count, and hemolytic anemia with schizocytes. On allograft biopsy, there was thrombotic microangiopathy in the glomeruli, with a cellular crescent formation and mesangial IgA and C3 deposition. Microvascular inflammation, such as glomerulitis, peritubular capillaritis, and arteriole endarteritis were also detected. A disintegrin-like and metalloproteinase with thrombospondin type 1 motifs 13 (ADAMTS13) did not decrease and Shiga toxin was not detected. Donor-specific antibodies or autoantibodies, including anti-neutrophil cytoplasmic antibody and anti-glomerular basement membrane (anti-GBM) antibody, were negative. The patient was diagnosed with aHUS and received three sessions of plasmapheresis and methylprednisolone pulse therapy, followed by oral methylprednisolone (0.25-0.5 mg/kg) instead of tacrolimus. She temporarily required hemodialysis (sCr level, 658.3 μmol/L). Thereafter, her sCr level improved to 284.5 μmol/L without dialysis therapy. This case is clinically considered as aHUS after kidney transplantation, associated with various factors, including rejection, glomerulonephritis, and toxicity from drugs such as tacrolimus.

月経前症候群 (PMS) は月経を有する婦人の40％にみられ, 女性のQOLを著しく阻害している。その発症原因は不明の点が多く, 診断基準や治療法も確立されたものは無い。そこでPMS患者33名に加味逍遥散を中心とした漢方薬エキスを投与して, その有効性をみることにした。効果を客観的にみるためにPMSスコアを作成した。治療開始前に (1) 精神症状, (2) 頭痛, (3) 乳房痛, (4) 浮腫, (5) 下腹痛, 腰痛の5項目について症状の強さによってスコア0 (症状無し), スコア1 (症状は有るが我慢できる), スコア2 (薬無しでは耐えられない) を記入してもらい, 2周期後に再びスコアを記入してもらった。33例中24例が症状改善し, スコアは平均4.4から1.5に低下し, 引き続き漢方薬の服用を希望した。4例が効果少なく, 他の治療法を希望した。5例は2周期後の評価ができなかった。以上の結果からPMSには加味逍遥散を中心とした漢方療法が非常に有効であることが分かった。

The development of embryos, larvae and juveniles of the Ryukyu-ayu, Plecoglossus altivelisryukyuensis are described based on laboratory-reared specimens.The eggs were spherical, 0.98–1.18 mm (mean 1.06 mm)in diameter with an adherent membrane. The incubation period after fertilizationwas approximately 155 h at a water temperature of 19.7–22.0°C(mean 20.7°C). Newly hatched larvae were 5.0–5.9 mm(mean 5.5 mm) in body length (BL) with 59–62 myotomes.Within 5 days after hatching, the larvae had attained 6.4–8.2 mm(mean 7.8 mm) BL and had completely consumed their yolk.Notochord flexion began at 13.7 mm BL and was completedby 16.3 mm BL. The rudimental dorsal, anal, pelvic andadipose fins appeared at 14.7, 16.3, 21.8 and 21.8 mm BL, respectively.All fin rays reached the same fixed number of adult fish at about28 mm BL. The comb-like teeth began to form at approximately30 mm BL and were fully developed at about 40–50 mm BL.The proportions of P. a. ryukyuensis specimens,which were consistent with adult fish, occurred at approximately40 mm BL.

A short and efficient synthesis of (+)-aureol (1), a structurally novel and biologically important marine natural product, was achieved starting with readily available (+)-Wieland-Miescher ketone analogue 7 via (-)-neoavarone (10) and (-)-neoavarol (11). The method features salcomine oxidation of the phenol derivative 9 to deliver 10 and BF 3 .OEt 2 -induced rearrangement/cyclization reaction of 11 to produce 1 as the crucial steps. The improved biomimetic synthesis required only 9 steps and proceeds in 31% overall yield.

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This study aimed to identify work-related language competencies required in the manufacturing industry and to provide guidelines for designing English programs that have groups with widely differing language levels and wide-ranging job experience. For this purpose, a questionnaire comprising 65 job-related tasks was used. 2,360 Japanese employees in manufacturing companies were asked to self-rate their abilities to perform the specified tasks in English on a 5-point scale and to indicate whether they had ever performed such tasks before. The data was analyzed according to English proficiency 1) to identify the types of tasks performed at each score level and 2) to examine whether the experience of performing the tasks would affect their self-ratings. Results indicated that the higher the subjects' language proficiency, the more tasks they had performed. Moreover, the subjects with task experience assessed their abilities more highly than those without experience. Further analysis revealed that the tasks requiring productive skills exerted a greater influence on the subjects' self-ratings. Based on the results, a list of tasks was compiled so that educators and trainers can refer to it when designing an English program that meets the specific needs of existing and new company employees in the manufacturing industry.

2511 Background: S-222611 is an oral, reversible ErbB tyrosine kinase inhibitor of EGFR and HER2 with potent pre-clinical activity. MTD was not reached during dose-escalation, even at the maximum d...

1-Aquo- and 1-ethyloxonio-5-carbasilatranes 2 and 3 were synthesized. X-ray crystallographic analysis revealed that 2 has a nearly ideal trigonal bipyramidal structure, in which the water molecule is located at the apical position. This water molecule is exchangeable with the other Lewis bases, such as H218O and HMPA. Theoretical calculations suggested that 2 would acquire the stabilization energy (20 kcal mol-1) by complexation. Deprotonation of 2 by pyridine and not by m-nitroaniline showed that the pKa value is smaller than that of free water, and that the water molecule is activated by complexation.

endocervixとectocervixの細胞診を同一症例において, 同時に綿棒とDr. Stormbyによって考案されたサイトブラシを用いて採取し, ブラシと綿棒の細胞材料のとれ方を比較した.両者の問で疑陽性, 陽性の検出率には有意の差はなかった.endocervixからの検体においてブラシ法および綿棒法の腺細胞シート数を数え, 対象者の年齢別に検討した. 若年者から高齢者に至るすべての年代において, サイトブラシを用いた方が有意に腺細胞シートの出現率も高く, シート数も多かった.妊婦においてもサイトブラシの方が綿棒よりも大量の腺細胞が採取された.ectocervixからの検体について両者の扁平上皮細胞のとれ方を比較したところ, ブラシ法のほうが綿棒法よりも細胞量が多かった.すなわちサイトブラシは綿棒よりも腺および扁平上皮細胞ともに大量に採取され, 子宮口の狭小な婦人や, squamo-columnar junctionの上昇した高齢者や妊産婦に適した細胞採取器具であるといえる.

A study was undertaken to evaluate the efficacy of the Cytobrush compared with the cotton-tipped applicator for obtaining cells from the uterine cervix. Four consecutive Papanicolaou smears were obtained in 1,000 patients during a single clinic visit. In every patient, a total of four smears on two slides were submitted: one slide contained endocervical material obtained with a cotton-tipped applicator and with the Cytobrush and the other slide contained ectocervical material obtained with both a cotton-tipped applicator and the Cytobrush. In endocervical smears, the Cytobrush technique produced numerous groups and clusters of cervical columnar cells in contrast to the use of the cotton swab. This was particularly true in older patients and pregnant women. In ectocervical smears, the detection of the squamous component was also higher in the Cytobrush smear than in cotton swab smears. However, the cell yield was not influenced by the cell sampling sequence in either endocervical or ectocervical specimens. It is the conclusion of this study that the utility of the Cytobrush technique for collecting specimens for endocervical and ectocervical smears is greater and provides a higher yield of cells than the cotton swab technique. Wider use of this simple procedure is encouraged.

2例の中胚葉性混合腫瘍と1例の横紋筋肉腫を経験したので, その剥離細胞像を中心に報告する.症例1: 68歳の中胚葉性混合腫瘍例.子宮体部より腟腔へ突出している腫瘤からの擦過スメアにて多数の非上皮性異型細胞がみられたが, これらの細胞にheterologous elementsに特徴的な所見はなかった.これらの細胞とは別に少数の腺癌細胞も認められた.組織学的には腺癌部分とchondroid類似の構造を有する肉腫部分からなる中胚葉性混合腫瘍であった.症例2: 78歳の中胚葉性混合腫瘍例.子宮体部の腫瘤から術中捺印細胞診を行ったところ, 扁平上皮癌を思わせる異型細胞や, 腺癌細胞が多数みられ, 一部には非上皮性の異型細胞がみられたが, heterdogous elementsに特徴的な所見はなかった. 組織学的には扁平上皮化生を伴った腺癌部分と, 横紋筋肉腫よりなる中胚葉性混合腫瘍であった.症例3: 77歳の横紋筋肉腫例.子宮体部より腟腔へ突出している腫瘤からの擦過スメアにて非上皮性異型細胞が多数みられ, その一部には横紋が認められた.組織学的にはpleomorphic typeの横紋筋肉腫であった.

Several five-membered heterocycles having a phenylazo substituent, 3-phenylazotetronic acids (2a-n), 3-phenylazotetramic acids (4a-i), 4-phenylazo-5-isoxazolinones (6a-g, 8a-f) and 5-phenylazo-4-thiazolidinones (10a-f, 12a-e), were synthesized and tested for antimicrobial activities. Tetronic acid and tetramic acid derivatives (2 and 4) inhibited the growth of gram-positive bacteria. 5-Isoxazolinone and 4-thiazolidinone derivatives (8 and 10) showed inhibitory activities against fungi as well as bacteria.

Trimetazidine, 1-(2, 3, 4-trimethoxybenzyl) piperazine, was examined in relation to its influence on the inotropic action of strophanthin-G in electrically driven isolated guinea-pig atria. Trimetazidine slightly diminished the effect of strophanthin-G in high Ca, high K, and low K media as well as in Locke's solution. The early stage reduction of the effect of strophanthin-G caused by a low Ca medium was prevented by the presence of trimetazidine. In a low Na medium, the effect of strophanthin-G was manifested by trimetazidine. From these results, it may be assumed that trimetazidine augments the posi-tive inotropic action of strophanthin-G through its prevention of the loss of available calcium ions in atria kept in a low Ca or low Na medium.

Several five-membered heterocycles having a phenylazo substituent, 3-phenylazotetronic acids (2a-n), 3-phenylazotetramic acids (4a-i), 4-phenylazo-5-isoxazolinones (6a-g, 8a-f) and 5-phenylazo-4-thiazolidinones (10a-f, 12a-e), were synthesized and tested for antimicrobial activities. Tetronic acid and tetramic acid derivatives (2 and 4) inhibited the growth of gram-positive bacteria. 5-Isoxazolinone and 4-thiazolidinone derivatives (8 and 10) showed inhibitory activities against fungi as well as bacteria.

Twenty patients with molar pregnancy, ten normal pregnant women and ten healthy nonpregnant women were given 30 g of arginine intravenously. The serum concentration of growth hormone, prolactin and chorionic somatomammotropin (CS) was determined by radioimmunoassay. In addition, serum 17β-estradiol, estriol and progesterone were also measured. Arginine infusion induced a sharp rise of GH in patients with molar pregnancy and in nonpregnant subjects, but the response in normal pregnancy was blunted. The response of PRL was high in patients with molar pregnancy, blunted in normal pregnancy and very small in nonpregnant subjects. CS did not respond at all to arginine infusion both in normal pregnancy and molar pregnancy. The high response to arginine of PRL, normal response of GH and low baseline secretion and no response of CS may be characteristic of molar pregnancy.