In this study, five types of mono-acylated anthocyanins were isolated from colored-fleshed potato (Solanum tuberosum L.) and black carrot (Daucus carota subsp. sativus), and their gastrointestinal absorption was evaluated based on the plasma profiles of rats. The absorption amounts of mono-acylated anthocyanins were slightly higher or at least similar to those of non-acylated anthocyanins, which carry the same aglycone, when the purified anthocyanins were orally administered. The absorption amounts of petunidin 3-O-(6′′-O-(4′′′-O-p-coumaroyl-α-L-rhamnopyranosyl)-β-D-glucopyranoside)-5-O-β-D-glucopyranoside isolated from purple-fleshed potato were 1.3 to 2.3-fold higher than those of three types of cyanidin 3-O-(2′′-xylopyranosyl-6′′-O-(6′′′-O-acyl-β-D-glucopyranosyl))- β-D-galactopyranosides isolated from black carrot, whereas pelargonidin 3-O-(6′′-O-(4′′′-O-p-coumaroyl-α-L-rhamnopyranosyl)-β-D-glucopyranoside)-5-O-β-D-glucopyranoside isolated from red-fleshed potato exhibited an exceptionally poor absorption profile, as demonstrated by the comparison of the area under the plasma concentration curves during 8 h after oral administration normalized to the orally administered dose. The gastrointestinal absorption of mono-acylated anthocyanins was tended to determine by their structures, including aglycone moieties, attached sugars, and the balance of the entire molecule. Our findings suggested that the branched acylated sugars attached to position 3 tended to suppress the absorption of mono-acylated anthocyanins from the gastrointestinal tract. Furthermore, the poor intestinal absorption of mono-acylated anthocyanins in the mixtures was likely due to the competitive absorption of these molecules with contaminants that co-occur in plant materials such as organic acids.
Sodium polystyrene sulfonate (SPS) is well used for hyperkalemia. A recent study has shown that SPS may bind to other drugs in the digestive tract. However, there are few reports about the effect of concomitant drug use on serum potassium level variations. Therefore, this study aimed to investigate the effect of concomitant drug use on the variation of serum potassium levels among patients taking SPS. In total, 632 patients were newly prescribed with SPS from 2017 to 2019, and 186 patients were evaluated in this study. Further, the association between increase in serum potassium levels and concomitant drug use was investigated. We classified patients into the Grade 1 (G1) group and the Grade 2–4 (G2–4) group according to baseline serum potassium level by Common Terminology Criteria for Adverse Events (CTCAE) v5.0. There was the significant decrease in serum potassium and chloride levels and the increase in serum sodium levels after SPS treatment. In addition, therapy with SPS might improve renal function. The concomitant use of imidapril in the G1 group (odds ratio: 4.4, 95% confidence interval: 1.1–11.7, p = 0.0394) and nifedipine in the G2–4 group (odds ratio: 7.3, 95% confidence interval: 1.5–35.5, p = 0.0139) were significantly associated with the increase in serum potassium levels after SPS treatment. These associations might be affected by not only adverse drug reactions but also binding of other drugs to SPS. Hence, concomitant drug use may affect the efficacy of SPS.
With societal aging, the number of patients with aspiration pneumonia is increasing. However, because the relationship between drug use and the development of aspiration pneumonia is not fully understood, improvements in information on the possibility of drug-induced aspiration pneumonia are urgently needed. Hence, in this study, we investigated the relationship between the use of anxiolytics and the development of aspiration pneumonia by using data from the Japan Adverse Drug Event Report (JADER) database. We found that anxiolytics had a signal for the development of aspiration pneumonia with a reporting odds ratio (ROR) of 3.2 (95% confidence interval: 2.5–4.1), and seven of eight anxiolytics for which the development of aspiration pneumonia was reported in the JADER database had a signal as well. Of note, the possibility of the development of aspiration pneumonia was mentioned only in the package inserts of clobazam among the package inserts or risk management plans (RMPs) of these anxiolytics. These results suggest the need for including information on the possibility of aspiration pneumonia development in drug package inserts and RMPs so as to prevent anxiolytic-associated aspiration pneumonia or facilitate its early detection.
Virgin gibbsite (GB) and calcined gibbsite (denoted as GB200, GB400, GB600, GB800, and GB1000), were prepared at 200°C, 400°C, 600°C, 800°C, and 1000°C, and the characteristics of prepared GB samples were investigated. The amount of the hydroxyl group, the specific surface area, and the micropore volume of GB400 were higher than those of other GB samples. Additionally, the crystal structure of GB changed significantly from the gibbsite phase to transitional states at our calcination temperatures. Furthermore, we showed the adsorption capacity of various dyes using GB samples. The prepared GB400, GB600, and GB800 showed adsorption capacity of Red, Blue, and Green, respectively. However, other GB samples did not show a dye adsorption capacity. Moreover, the adsorption mechanism of Red and Blue using GB400 and GB600 was related to the number of hydroxyl groups, specific surface area, and micropore volumes in this study. Finally, the relationship between the amount of Red and Blue adsorbed and the number of total organic carbons decreased was positively correlated with the values of 0.974 and 0.935, respectively. In our prepared GB sample, both dyes and organic carbons were simultaneously removed during the adsorption treatment.
This study aimed to develop a contamination-less bead milling technology using zirconia beads, by optimizing milling parameters. We evaluated the effects of bead milling parameters on milling time and metal contamination; focusing on bead diameter, rotation speed, and bead filling rate as they are the critical parameters determining bead milling efficiency. We studied the milling time required to grind a drug to 0.2 μm size and quantified the extent of metal contamination that arises from the grinding procedure. With optimal bead milling parameters, the minimum concentration of the metal contaminants was 1.27 ± 0.08 μg/mL (zirconium: 0.73 ± 0.09 μg/mL; yttrium: 0.35 ± 0.03 μg/mL; aluminum: 0.19 ± 0.05 μg/mL), when the rotation speed, bead diameter, and bead filling rate were set to 2 m/s, 0.3 mm, and 75% (v/v), respectively. Additionally, under optimized conditions, it was possible to reduce the metal contamination per weight of the drug by increasing the drug concentration to up to 40% (w/w). Under the optimized conditions for drug concentrations of 30–40% (w/w), metal contamination from the grinding process was minimized and reduced to < 10 μg/g, which is comparable to that achieved by the NanoCrystal® technology. These results indicate that contamination-less bead milling using zirconia beads can be achieved when bead milling parameters are optimized.
We characterized the absorption, distribution, metabolism, and excretion of tetrabromobisphenol A (TeBBPA) in C57BL/6 mice. After TeBBPA dosing, we monitored the mice and collected samples for 24 h. Most TeBBPA was excreted in the feces at 12 h. At 24 h, 71% of administered TeBBPA was found in the feces and TeBBPA-conjugates were detected at 17.8%. We also detected debrominated metabolites of TeBBPA, including tribromobisphenol A (TriBBPA), dibromobisphenol A (DiBBPA), and monobromobisphenol A (MoBBPA). TeBBPA, TriBBPA, 2,2′-DiBBPA and MoBBPA were detected in dam’s blood between 30 min and 1 h. Moreover, TriBBPA and 2,2′-DiBBPA were detected in milk at 30 min. The primary metabolites of TeBBPA were formed by conjugation, whereas debromination represented a minor metabolism pathway. Moreover, our findings demonstrated that the parent TeBBPA compound and its debrominated metabolites were distributed into the maternal milk of mice and transferred to the nursing pups following TeBBPA oral administration.
Frailty is defined as an age-related decline in physiological reserve and increased vulnerability to stress. As frailty is a multifaceted condition, there is no effective pharmacotherapy for it yet. Ninjin’yoeito (NYT) and Kamikihito (KKT), traditional Japanese medicines (Kampo medicines), are promising in treating multifaceted conditions of frailty including fatigue and mental anxiety. However, their effects are still unclear. In this study, the effects of NYT and KKT on different types of frailty in naturally aged mice were explored by survival, physical aspects (Frailty Assessment Scores and muscle strength measurements), psychological aspects (sucrose splash test for motivation-related behavior), and social aspects (rescue-like behavior test for prosocial behavior). Mice aged 22-months were fed a diet containing 3% NYT or 3%KKT for 13 weeks until the age of 25 months. Behavioral alterations in old mice were compared with those in adult mice (five months old). Throughout the study period, Old-control mice showed frailty-like symptoms, including elevation of frailty assessment score, reduction of muscle strength and motivation for self-care, and rescue-like behavior compared to adult mice. NYT increased the survival rate of old mice and suppressed the declines in their frailty assessment score, muscle strength, and motivation for self-care. KKT reduced decreases in the frailty assessment score, motivation for self-care, and rescue-like behavior in old mice. These results suggest that NYT and KKT alleviate general frailty-like symptoms in old mice. Additionally, NYT may extend lifespan. These findings suggest that NYT and KKT may be helpful for improving the multifaceted symptoms of frailty.
Delta-toxin produced by Clostridium perfringens types B and C is a β-pore-forming cytotoxin. Here, using site-directed mutagenesis, we identified the amino acid residues that contribute to delta-toxin oligomerization and binding. We replaced Lys-43 and Ser-109 located in the β-sandwich domain and Arg-200 located in the rim domain. Substitution of alanine for Ser-109 caused reductions in both cytotoxicity and oligomerization. However, exchange of Lys-43 for alanine resulted in a reduction in the cytotoxicity. Replacement of Arg-200 with alanine led to drastic reductions cytotoxicity and cell binding. Our results demonstrate that Ser-109 plays a role in oligomerization, and that Arg-200 is critical for binding of the toxin.
The purpose of this study is to construct the consultation system based on the touch panel type screening check for dementia (TPCD) results from a pharmacy to psychiatric specialists at an advanced treatment hospital, and to evaluate the effectiveness of resulting in dementia diagnosis. We herein report three cases that demonstrate the significance of TPCD in the course of study. Cases 1 was successful case from a 78-year-old man in which pharmacists recommended individuals scored 11 on the TPCD to visit psychiatrists at Fukuoka University Hospital, an advanced medical hospital, based on the results of TPCD. He was practically diagnosed with mild cognitive impairment (MCI). Cases 2 was partially successful case from a 78-year-old woman. Her TPCD score resulted only 9. The pharmacist effectively utilized tracing report to notify the patient’s cardiologist about the results of the TPCD performed at the pharmacy as she wished. On the other hand, Case 3 showed that patient whose TPCD score resulted 2 could receive no treatment due to advanced stage of dementia despite our consulting with family doctor based on the TPCD scores. These cases suggest that the pharmacy near an advanced medical hospital should play a role to provide accessibility between the patients with suspected dementia and psychiatric specialists and make opportunities to consult specialists earlier before progressing towards a dementia following MCI collaborated with community interprofessionals.