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Amantadine intoxication occurred despite moderate renal dysfunction. This may have been affected by the use of donepezil, and we require careful attention to these combinations.

Hypertensive disorders of pregnancy cause maternal organ damage. Therefore, appropriate management with antihypertensive medication is required from the first trimester. We aimed to clarify the antihypertensive drug prescription trends in pregnant women with hypertension in Japan. The administrative data of pregnant outpatients aged 16-49 years who visited acute hospitals between 2013 and 2020 were included. The annual antihypertensive drug prescription trends were evaluated based on their prescription proportions. The most prescribed drug in 2020 was nifedipine, followed by methyldopa and amlodipine. The proportion of nifedipine prescriptions significantly increased from 33.5 to 40.8% during the study period, whereas that of methyldopa significantly decreased from 16.6 to 11.6%. There was no change in the prescription trend of amlodipine. Dihydropyridine calcium channel blockers were the most commonly prescribed drug for pregnant women with hypertension.

The temporal trends in prescribing anti-seizure medicines (ASMs) for pregnant women with epilepsy are unclear. In this study, we investigated the trends in ASM prescriptions in pregnant Japanese women with epilepsy.Administrative data (as of December 2021), pertaining to Japanese pregnant outpatient women with epilepsy, aged 16-49 years, who visited hospitals between January 1, 2016 and December 31, 2020 were included in the study. Annual prescription trends in ASMs during this period were calculated based on the proportions. The Cochran-Armitage trend test was used to evaluate the proportion of prescriptions for each ASM.The numbers of pregnant women with epilepsy were 404, 421, 368, 378, 386 for the years 2016, 2017, 2018, 2019, and 2020, respectively. As of 2020, levetiracetam had the highest proportion of prescriptions, followed by lamotrigine and valproic acid. From 2016 to 2020, the proportions of levetiracetam and lamotrigine prescribed for pregnant women with epilepsy have increased significantly from 19.1% to 30.8% and from 12.1% to 18.4%, respectively. In contrast, there was no temporal change in the proportion of valproic acid prescribed, which was 12.4% in 2016 and 10.1% in 2020.Our findings suggest that the trends in the prescription of ASMs in Japanese pregnant women outpatients with epilepsy have shifted toward ASMs with a lower teratogenic risk.

The multikinase inhibitor, regorafenib, is known to exert its antitumor effects by targeting several kinases, inhibiting interstitial intracellular signaling and suppressing tumor cell proliferation. Regorafenib causes gastrointestinal perforation and gastrointestinal fistula as adverse events, and discontinuation is recommended if these adverse events occur during administration. However, there are no prescribed standards for re-administration after discontinuation and for administration in patients with a history of gastrointestinal perforation. Herein, we report a case of gastrointestinal perforation in a patient, with a history of gastrointestinal microperforation, undergoing bevacizumab therapy, within a few days of starting regorafenib; this had a significant effect on the prognosis. The site of gastrointestinal perforation was consistent with previously reported sites around the tumor and at the anastomotic site. Based on a review of literature and our experience with the case presented here, we recommend that administration of regorafenib to patients with a history of gastrointestinal perforation should be avoided to the extent possible. Moreover, in case of prior administration of a drug reported to cause gastrointestinal perforation, such as an anti-VEGFR drug, the risk of gastrointestinal perforation should be considered during the administration of regorafenib. In the event of complaints, such as abdominal pain, gastrointestinal perforation should be considered as a differential diagnosis and appropriate tests and treatments should be initiated at an early stage.

New chiral C2 symmetric N-heterocyclic carbene (NHC) ligands with a binaphthyl backbone have been synthesized. X-ray crystallographic analysis of the new NHC–AuCl complex revealed that the phenyl groups of the binaphthyl backbone sterically regulated the direction of the nitrogen substituents of the imidazolylidene which would induce enantioselectivity in reactions. The new cationic NHC–Au(I) complexes efficiently catalyzed the cyclization of a 1,6-ene–yne and the intermediate of the cyclization was trapped by MeOH to afford the final product in high yields with up to 44% ee.

Shinya Abe1,2, Gaku Inoue1,2, Satoru Yamada1,3, Junichiro Irie1,3, Hiroyuki Nojima2, Kaoru Tsuyusaki2, Kensuke Usui2, Koichiro Atsuda2, Toshikazu Yamanouchi41Diabetes Center, Kitasato Institute Hospital, 2Center for Clinical Pharmacy and Clinical Sciences, Kitasato University, 3Department of Internal Medicine, Keio University School of Medicine, 4Department of Internal Medicine, University of Teikyo School of Medicine, Tokyo, JapanObjective: This study aimed to compare the glucose-lowering effect and glycemic variability of insulin glargine with those of insulin detemir.Material and methods: This was an open-label, single-center, randomized, two-way crossover study in patients with diabetes on basal-bolus insulin therapy, with neutral protamine Hagedorn (NPH) insulin as basal insulin. Patients switched from NPH insulin to a course either of insulin glargine followed by insulin detemir, or insulin detemir followed by insulin glargine, continuing the same dose of the prior bolus of insulin. To evaluate the glucose-lowering effect, daily glycemic profiles were recorded for 72 hours by continuous glucose monitoring (CGM) in an outpatient setting. The mean amplitude of glycemic excursions, standard deviation (SD), and the mean of daily difference (MODD) were used to assess intraday and day-to-day glycemic variability.Results: Eleven patients were enrolled and nine completed the study. Mean blood glucose calculated from CGM values was significantly lower with insulin glargine compared with insulin detemir (9.6 ± 2.4 mmol/L versus 10.4 ± 2.8 mmol/L, P = 0.038). The SD was significantly lower with insulin glargine versus insulin detemir (2.5 ± 0.9 mmol/L vs 3.5 ± 1.6 mmol/L, P = 0.011). The MODD value was significantly lower with insulin glargine than with insulin detemir (2.2 ± 1.1 mmol/L vs 3.6 ± 1.7 mmol/L, P = 0.011). There was no significant difference between the two insulin analogs in terms of hypoglycemia.Conclusion: This study suggests that insulin glargine leads to more effective and more stable glycemic control than the same dose of insulin detemir.Keywords: continuous glucose monitoring, insulin detemir, insulin glargine&nbsp

The behavior of the permeation flux in crossflow filtration of Corynebacterium glutamicum broth was studied. In the beginning of filtration the permeation flux changed in accordance with the cake filtration model. The permeation flux agreed with the value calculated from the weight of the cell layer formed on the membrane per unit filtration area and the specific resistance of the cell layer measured in dead-end filtration. After cell deposition on the membrane, permeation resistance rapidly increased. The increase was due to the formation of the gel layer of the proteins and polysaccharides in the supernatant of the broth. When the circulation flow rate was raised, the weight of the cell layer reduced. However, the beginning of the rapid increase of permeation resistance came earlier and the apparent specific resistance of the cell layer increased. The higher the circulation flow rate, the higher the permeation flux at the beginning of the rapid increase of resistance. When the transmembrane pre...

Filtration behaviors in the unsteady-state phase of crossflow filtration of broths of Bacillus subtilis, Escherichia coli, and Lactobacillus delbrueckii, which are rod-shaped, were studied from the viewpoint of the changes in the specific resistance and in the structure of the microbial cake formed on the membrane surface. The permeation flux followed the cake filtration law at the initial stage of the crossflow filtration of the broths of B. subtilis and E. coli, where the cells deposited randomly on the membrane. In the case of the crossflow filtration of a L. delbrueckii broth, the period of random deposition was shorter. The specific resistance for the cake formed at the initial stage agreed with that measured in dead-end filtration. Then, the specific resistance started to increase in comparison with that measured in dead-end filtration due to shear-induced arrangement of the cells. The extent of the increase in specific resistance became higher and the time taken to start the cell arrangement became shorter with increasing circulation flow rate. The increase in specific resistance due to the shear-induced arrangement was more appreciable in the crossflow filtration of the broth of L. delbrueckii than that of B. subtilis and E. coli. The average permeation flux was increased considerably by applying periodical backwashing with appropriate time intervals. The permeation flux was well predicted by the cake filtration law, since the cells deposited in a way similar to that for dead-end filtration during a sufficiently short period of crossflow filtration in a backwashing mode.

Following a study of liquid film flow, experimental results are presented on the variation of the liquid drop flow rate along the axis of a bend tube, the profile of the liquid drop flow rate at the bend exit, and the mean diameter and the distribution of liquid drops entrained in the gas core in an air-mixture flowing upward in an annular drop flow regime through a C-shaped bend of 144-mm radius of curvature with a 24-mm-inside-diameter tube lying in a vertical plane. In orer to study the effect of gravity on flow direction, some experiments are also carried out on downward and horizontal flows in the bend, and on a straight horizontal flow. The flow of liquid drops is greatly influenced by the secondary flow caused by centrifugal force within the gas core, and exhibits some notable features as well as liquid film flow.

We examined the usefulness of the leukocyte migration test (LMT) in the identification of agents causing drug-induced liver injury (DILI).In 14 patients who were tentatively diagnosed as having DILI in Kitasato Institute Hospital, pharmacists collected and evaluated drug information and patients' medication histories to identify causative agents. Simultaneously, LMT and drug lymphocyte stimulation test (DLST) were performed. Furthermore, scoring was performed according to the diagnostic criteria established by the International Consensus Meeting (ICM) and the Digestive Disease Week-Japan 2004 (DDW-J).LMT-positive agents showed a higher ICM score compared to DLST-positive agents. The rate of LMT-positive agents was examined with respect to ICM assessment, and 0%, 25%, 33%, and 100% of agents regarded as unrelated/unlikely, possible, probable, and highly probable showed positive reactions on LMT, respectively; the rate of LMT-positive agents increased with the degree of the agent's involvement. When the results of LMT were applied to the DDW-J criteria, there was a correlation with the ICM criteria in comparison to scoring based on the results of DLST.LMT may be useful for identifying agents causing DILI. Furthermore, the collection and evaluation of drug and patient information and in vitro testing in the identification of causative agents may support more reliable diagnosis.