[Methods for Recovering Residual Anticancer Drugs in Medical Settings to Improve Working Environments].

We examined the methods for recovering residual anticancer drugs in medical settings to prevent health hazards caused by exposure to anticancer drugs. Presently, the lactose hydrate recovery rates(Lac, an alternative sample for an anticancer drug)were determined using 2 drug recovery methods that are based on a procedure manual(procedure manual method) and smart remote support(remote support method). Using the procedure manual method, 5 healthcare workers recovered Lac after receiving a detailed face-to-face methodological explanation. Using the remote support method, 3 healthcare workers recovered Lac regarded by an instructor waiting at a remote site without using a procedure manual. As a result, the Lac recovery rates were>80% for both methods; however, they showed the need for improvement. Eventually, the issues found presently will be resolved to improve the working environments of healthcare workers, caregivers, and medical service providers.

Periodic sea-level oscillation in Tokyo Bay detected with the Tokyo-Bay seafloor hyper-kilometric submarine deep detector (TS-HKMSDD).

Meteorological-tsunami-like (or meteotsunami-like) periodic oscillation was muographically detected with the Tokyo-Bay Seafloor Hyper-Kilometric Submarine Deep Detector (TS-HKMSDD) deployed in the underwater highway called the Trans-Tokyo Bay Expressway or Tokyo Bay Aqua-Line (TBAL). It was detected right after the arrival of the 2021 Typhoon-16 that passed through the region 400 km south of the bay. The measured oscillation period and decay time were respectively 3 h and 10 h. These measurements were found to be consistent with previous tide gauge measurements. Meteotsunamis are known to take place in bays and lakes, and the temporal and spatial characteristics of meteotsunamis are similar to seismic tsunamis. However, their generation and propagation mechanisms are not well understood. The current result indicates that a combination of muography and trans-bay or trans-lake underwater tunnels will offer an additional tool to measure meteotsunamis at locations where tide gauges are unavailable.

First results of undersea muography with the Tokyo-Bay Seafloor Hyper-Kilometric Submarine Deep Detector.

Tidal measurements are of great significance since they may provide us with essential data to apply towards protection of coastal communities and sea traffic. Currently, tide gauge stations and laser altimetry are commonly used for these measurements. On the other hand, muography sensors can be located underneath the seafloor inside an undersea tunnel where electric and telecommunication infrastructures are more readily available. In this work, the world's first under-seafloor particle detector array called the Tokyo-bay Seafloor Hyper-Kilometric Submarine Deep Detector (TS-HKMSDD) was deployed underneath the Tokyo-Bay seafloor for conducting submarine muography. The resultant 80-day consecutive time-sequential muographic data were converted to the tidal levels based on the parameters determined from the first-day astronomical tide height (ATH) data. The standard deviation between ATH and muographic results for the rest of a 79-day measurement period was 12.85 cm. We anticipate that if the length of the TS-HKMSDD is extended from 100 m to a full-scale as large as 9.6 km to provide continuous tidal information along the tunnel, this muography application will become an established standard, demonstrating its effectiveness as practical tide monitor for this heavy traffic waterway in Tokyo and in other important sea traffic areas worldwide.

Effect of food thickener and jelly wafer on the pharmacokinetics of levofloxacin orally disintegrating tablets.

This study was designed to determine the effects of a food thickener and deglutition aid jelly for oral administration, jelly wafer, on the pharmacokinetics of levofloxacin orally disintegrating tablets. With an increase in immersion time, the disintegration time of levofloxacin orally disintegrating tablets immersed in food thickener was prolonged, whereas that of the tablets immersed in jelly wafer was shortened. The dissolution behavior of non-immersed levofloxacin orally disintegrating tablets was not similar to that of tablets immersed in food thickener, but was similar to that of tablets immersed in jelly wafer. The time to reach the maximum systemic levofloxacin concentration was the same for non-immersed orally disintegrating tablets and tablets immersed in food thickener and jelly wafer. Moreover, there was no significant difference in the maximum concentration after administration between non-immersed orally disintegrating tablets and tablets immersed in food thickener or jelly wafer. These findings suggest that drugs with a high bioavailability, such as levofloxacin, enter the systemic circulation even when administered with a food thickener or jelly wafer.

Effect of deglutition aids on the inhibitory effect of orally disintegrating tablets of voglibose on the postprandial elevation of blood glucose levels: a case investigating the interaction between xanthan gum and voglibose.

In this study, we first performed a disintegration test of the voglibose orally disintegrating (V-OD) tablet immersed in jelly-wafer (JW, V-ODims/jw) for 10 min and compared it with the disintegration time of V-OD that was not immersed in JW. We then orally administered the V-ODims/jw tablet to 7 healthy adults and compared the shift in blood glucose levels (BGLs), after loading with a sucrose solution (Suc-sol, 100 g/150 mL), with that after administration of the non-immersed V-OD tablet. The disintegration time of V-ODims/jw tablet was shorter than that of V-OD. When administered to healthy adults, the BGL after loading with Suc-sol was higher with V-ODims/jw tablet administration than with V-OD tablet. We predict that the expression of the efficacy of voglibose is reduced as a result of the interaction between voglibose and the polysaccharide, xanthan gum (XG), since it is a common additive in JW. This study shows that deglutition aids with additives that do not affect pharmacokinetics must be carefully selected for administering along with pharmaceuticals, because of a suggested possibility that the interaction between these pharmaceuticals and the additives in the deglutition aids weaken the drug efficacy. A more careful selection of deglutition aids from the wide selection of medication is especially important when administered to patients who use these deglutition aids often, such as elderly individuals or individuals with a deglutition disorder.

Effect of Food Thickener on the Inhibitory Effect of Mitiglinide Tablets on Post-prandial Elevation of Blood Glucose Levels.

The aim of this study was to examine the effect of food thickener on the pharmacodynamics of mitiglinide (MGN), a drug belonging to a class of rapid-acting insulin secretagogues. First, MGN tablets were coated by immersion in a xanthan gum-based food-thickening agent. This treatment was shown to delay disintegration rates of MGN tablets in vitro. The pharmacodynamics of MGN after ingestion of a single oral dose of an MGN tablet, with or without food thickener immersion, were then examined in an open-label crossover study comprising 5 healthy participants. It was observed that after administration of 75 g of oral glucose, the area under the blood glucose concentration-time curve was larger for treatment with MGN tablets that had been immersed in the food thickener than for nonimmersed tablets. The maximum blood glucose level was also higher in treatments with MGN tablets that had been immersed in food thickener. The extended time of higher glucose levels associated with thickener-immersed MGN tablets given to human volunteers may be associated with the reduced disintegration rates of immersed MGN tablets as observed in the in vitro experiment. Overall, our study suggests that commercially available food thickeners influence the pharmacodynamics of MGN and that their use should therefore be carefully assessed and monitored in certain clinical situations.

Efficacy of Adenine in the Treatment of Leukopenia and Neutropenia Associated with an Overdose of Antipsychotics or Discontinuation of Lithium Carbonate Administration: Three Case Studies.

Because adenine is effective for managing cases of radiation-induced and drug-induced leukopenia, it may be effective in cases of antipsychotic-induced leukopenia and neutropenia. Here, we report our experience with patients with leukopenia and neutropenia caused by an antipsychotic overdose or discontinuation of lithium carbonate, in whom adenine administration ameliorated the white blood cell and neutrophil counts. The progress of patients suggests that adenine is effective in cases of leukopenia and neutropenia associated with lithium carbonate discontinuation and an antipsychotic overdose.

Effects of Food Thickeners on the Inhibitory Effect of Voglibose Oral-disintegrating Tablets on Post-prandial Elevation of Blood Sugar Levels.

The aim of this study was to examine the effects of food thickeners on the pharmacodynamics of voglibose, an α-glucosidase inhibitor. The pharmacodynamics of voglibose were examined in an open-label study in 9 healthy participants after the ingestion of a single oral dose of a voglibose oral-disintegrating tablet, with and without food thickener immersion. The area under the incremental blood sugar concentration-time curve was larger and the rate of increments in the blood sugar concentration was higher with the voglibose oral-disintegrating tablets immersed in the food thickener than with the tablets that were not immersed. Immersing the voglibose oral-disintegrating tablets in the food thickener possibly delayed their disintegration rate. This suggests that commercially available food thickeners may be associated with changes in the disintegration of voglibose oral-disintegrating tablets and should therefore be used carefully in certain clinical situations.

Effect of Food Thickener on Dissolution and Laxative Activity of Magnesium Oxide Tablets in Mice.

The present study examined the dissolution of magnesium oxide (MgO) from MgO tablets placed in a food thickening agent (food thickener) and its effects on laxative activity. We prepared mixtures of MgO tablets suspended in an aqueous suspension and food thickeners in order to evaluate the dissolution of MgO. The results of the dissolution tests revealed that agar-based food thickeners did not affect the MgO dissolution. In contrast, some xanthan gum-based food-thickener products show dissolution rates with certain mixtures containing disintegrated MgO tablets suspended in a food thickener that decrease over time. However, other xanthan gum-based food-thickener products show dissolution rates that decrease immediately after mixing, regardless of the time they were allowed to stand. In order to investigate the laxative activity of MgO, we orally administered a mixture of MgO suspension and food thickener to mice and observed their bowel movements. The animal experiments showed that when agar-based food thickeners were used, the laxative activity of MgO was not affected, but it decreased when xanthan gum-based food thickeners were used.

Stabilization of the Serum Lithium Concentration by Regulation of Sodium Chloride Intake: Case Report.

To avoid fluctuation of the serum lithium concentration (CLi), sodium chloride (NaCl) intake was regulated in oral alimentation. A 62-year-old woman was hospitalized and orally administered 400 mg of lithium carbonate a day to treat her mania. Her CLi was found to be 0.75-0.81 mEq/L. Vomiting made it difficult for the patient to ingest meals orally, and therefore parenteral nutrition with additional oral intake of protein-fortified food was initiated. On day 22, parenteral nutrition was switched to oral alimentation to enable oral intake of food. The total NaCl equivalent amount was decreased to 1.2 g/d, and the CLi increased to 1.15 mEq/L on day 26. Oral alimentation with semi-solid food blended in a mixer was immediately initiated. Although the total NaCl equivalent amount was increased to 4.5-5.0 g/d, her CLi remained high at 1.14-1.17 mEq/L on days 33 and 49, respectively. We investigated oral administration of NaCl (1.8 g/d) on day 52. The total NaCl equivalent amount was increased to 6.3-6.8 g/d, and the CLi decreased to 1.08-0.97 mEq/L on days 63 and 104, respectively. After the start of the orally administered NaCl, her diet was changed to a completely blended diet on day 125. The total NaCl equivalent amount was increased to 9.0-14.5 g/d, and the CLi decreased to 0.53 mEq/L on day 152; therefore, the oral administration of NaCl was discontinued on day 166. The CLi was found to be 0.70-0.85 mEq/L on days 176 and 220.

[Effect of food thickener on disintegration and dissolution of magnesium oxide tablets].

It has been reported that magnesium oxide tablets are excreted in a non-disintegrated state in the stool of patients when the tablets are administered after being immersed in a food thickener. Therefore we examined whether immersion in a food thickener affects the pharmacological effect in patients taking magnesium oxide tablets, and whether immersion affects its disintegration and solubility. The mean dosage (1705 mg/d) was higher for patients who took tablets after immersion in a food thickener than for those who took non-immersed tablets (1380 mg/d). The disintegration time and dissolution rate of the immersed tablets were lower than those of non-immersed tablets in vitro. Furthermore, components that constitute the food thickener and differences in composition concentrations differentially affect the disintegration and solubility of magnesium oxide tablets. This suggests that commercially available food thickeners are likely to be associated with changes in the degradation of magnesium oxide tablets, and they therefore should be carefully used in certain clinical situations.

Dose-dependent valproate-induced alopecia in patients with mental disorders.

Drug-induced hair loss may occur as a side effect in patients treated with valproate. However, few studies have reported a relationship between the blood levels of valproate and the occurrence of hair loss. We report three cases of alopecia that occurred in patients who received sodium valproate for mental disorders. In all three cases, alopecia appeared after long-term valproate exposure with a plasma concentration of 100 µg/ml approximately. However, the alopecia resolved in all cases after dose reduction or treatment discontinuation. Therefore, alopecia may develop in patients with chronic exposure to high plasma concentrations of valproate. Based on these findings, we believe that patients with high plasma concentrations of valproate should be closely monitored for the occurrence of side effects, particularly alopecia.

Assessment of clonidine orally disintegrating tablet for pre-anesthetic medication in pediatric surgery.

The purpose of this study is to assess orally-disintegrating (OD) tablet of clonidine hydrochloride (CL) for a pre-operative sedation in pediatric surgery. Sedation score and plasma CL concentration of OD formulation was compared with original preparation, CL lollipop, in pediatric patients. Fourteen patients (age: 3.9+/-2.3 years, weight: 16.9+/-5.0 kg) for OD group and 9 patients (age: 4.4+/-3.1 years, weight: 17.2+/-7.0 kg) for lollipop group received 4 microg/kg of CL preparation. Pre-operative sedation was evaluated by 5-point scoring systems at entering the operating room. Plasma CL concentrations were determined 120 min after administration of CL preparation. The changes in systolic blood pressure (SBP), diastolic blood pressure (DBP) and heart rate (HR) were also assessed before and after administration of CL preparation. Every patient in OD group had satisfactory sedation (sedation score: 2 and 3), whereas, 3 (33%) in lollipop group had unsatisfactory sedation (sedation score: 0 and 1). Plasma CL concentration in OD group was significantly higher than those in lollipop group (0.75+/-0.15 vs. 0.42+/-0.21 ng/ml, p<0.01). There was no significant difference in hemodynamic parameters (SBP, DBP and HR) between before and after administration of CL preparation in both OD and lollipop group. We conclude that OD is superior preparation of CL for pre-operative sedation in pediatric surgery.

Sedation and plasma concentration of clonidine hydrochloride for pre-anesthetic medication in pediatric surgery.

Clonidine hydrochloride has been used for pre-anesthetic medication to provide a pre-operative sedation in pediatric surgery. The purpose of this study is to determine the plasma clonidine concentration, which gives satisfactory sedation in pediatric surgery. Sixteen pediatric patients (age: 1-11 years, weight: 9-33 kg) received either 2 or 4 microg/kg of clonidine lollipop before entering the operating room. Plasma clonidine concentrations were determined 120 min after administration of clonidine lollipop. Pre-operative sedation was evaluated by 5-point scoring systems at entering the operating room. The changes in systolic blood pressure (SBP), diastolic blood pressure (DBP) and heart rate (HR) were also assessed before and after administration of clonidine lollipop. The patients with satisfactory sedation had higher plasma clonidine concentration than that of the patients with unsatisfactory sedation (0.45+/-0.16 ng/ml vs. 0.26+/-0.16 ng/ml, p<0.05). The clonidine concentrations in the satisfactory group ranged from 0.28 to 0.81 ng/ml. There was no significant difference in hemodynamic parameters (SBP, DBP and HR) before and after administration of clonidine lollipop in both satisfactory and unsatisfactory sedation groups. Plasma clonidine concentration of 0.3-0.8 ng/ml would be sufficient to produce satisfactory sedation without changes in hemodynamic parameters in pediatric surgery.

The hypnotic and analgesic effects of oral clonidine during sevoflurane anesthesia in children: a dose-response study.

UNLABELLED: Although clonidine has both hypnotic and analgesic actions, the dose relationship for each actions is still unknown in a clinical setting when clonidine is used as a premedication in children. We studied 80 ASA physical status I children (age range, 3-8 yr). Subjects were randomly divided into two groups (minimum alveolar anesthetic concentration [MAC]-Awake group, n = 40; MAC-Tetanus group, n = 40). Each patient received one dose of clonidine from 1 to 5 microg/kg orally, 100 min before arrival at the operating room. Anesthesia was induced and maintained with sevoflurane in oxygen and air. Before tracheal intubation, end-tidal sevoflurane was decreased stepwise by 0.2% at the start of 1.2%, a verbal command was given to the patients, and MAC-awake was determined in each patient. We also investigated MAC-tetanus, determined with transcutaneous electric tetanic stimulations, after tracheal intubation in each patient by observing the motor response to a transcutaneous electric tetanic stimulus to the ulnar nerve at a sevoflurane concentration decreased stepwise by 0.25% at the start of 2.75%. The initial reduction in MAC-tetanus was not as steep as that in MAC-awake. Clonidine reduced MAC-tetanus by 40% at the maximal dose of 5 microg/kg, whereas MAC-awake was already reduced by 50% at 2 microg/kg. We conclude that separate dose-response relationships for oral clonidine are present regarding the hypnotic and analgesic effects in children undergoing sevoflurane anesthesia. IMPLICATIONS: Separate dose-response relationships for oral clonidine were found regarding the hypnotic and analgesic effects in children undergoing sevoflurane anesthesia.