Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan最新文献

In an aging society, there is a growing interest in functional foods that offer anti-aging benefits. Food-derived bioactive compounds such as carotenoids and polyphenols can enhance skin elasticity and delay aging. However, the mechanisms by which these orally ingested compounds directly impact the skin are not fully understood. Recent studies on exosomes have suggested significant physiological functions, including their potential for intercellular communication. Similar to mammalian exosomes, plant-derived exosomes are known for their functional roles, including cross-kingdom communication, and their ability to target specific organs in animal models as delivery vehicles. The authors have been investigating the anti-aging effects of kale and have previously reported its benefits on cognitive function and skin aging in mouse models. Long-term oral administration of glucoraphanin-enriched kale suppresses the senescence symptoms in skin and hair and increases type I collagen and antioxidant enzyme expression in skin tissues, indicating its role in promoting skin health. Exosome-like nanoparticles (ELNs) from glucoraphanin-enriched kale appear to modulate the expression of extracellular matrix-related genes. Kale-derived ELNs exhibit great potential for ameliorating skin aging, suggesting their ability to promote skin health through targeted cellular mechanisms and supporting their use as an active natural compound in nutraceuticals and functional beverages.

Veterinary drugs are used worldwide to prevent and treat diseases and promote growth in animals, fisheries, and beekeeping. Despite their effectiveness, the illegal and improper use of these drugs can result in livestock and fishery products, potentially impacting human health by causing allergic reactions, cytotoxicity, and antimicrobial resistance. To mitigate these adverse effects, the Japanese government established a positive list system in 2006. Maximum residue levels (MRLs) have been defined for approximately 300 veterinary drugs. The regulation of certain antimicrobial drugs without defined MRLs uses in zero tolerance. Residual veterinary drugs in meat, fish, eggs, milk, and honey are inspected to ensure compliance with legal limits. Initially, samples are screened using bioassay and LC-MS/MS. If residues are detected, they are confirmed and quantified using more precise methods. We have detailed the detection of residual norfloxacin in honey. Additionally, we are currently developing new analytical methods. This study introduces an analytical method for the residue screening of sulfonamides and quinolones. After residue detection by bioassay, the same test solutions were analyzed by LC-MS/MS for accurate identification and quantification. This method has also proven to be more environmentally friendly compared to other quantitative methods. We present the ingenuity used to realize the combined method, performance evaluation results, examples of applications to actual samples, and future prospects.

Serotonergic neurons play a critical role in processing reward and aversive information. Rewarding stimuli activate serotonergic neurons in the dorsal raphe nucleus (DRN), whereas optogenetic activation of DRN serotonergic neurons induces reward-like effects. However, the pharmacological enhancement of serotonin neurotransmission does not induce rewarding or aversive effects. These findings suggest the presence of another serotonergic neuron that plays a role opposite to that of the DRN in processing reward and aversion information. Previous reports suggested that the median raphe nucleus (MRN) processes negative emotional stimuli. To elucidate the function of MRN serotonergic neurons in these processes, we recorded the changes in serotonergic activity in mice in response to rewarding and aversive stimuli. We also used optogenetic manipulation to determine whether these changes could induce rewarding and aversive behaviors. The activity of MRN serotonergic neurons decreased in response to rewarding stimuli and increased after aversive stimuli. Optogenetic inhibition of MRN serotonergic neurons induced reward-related behavior, while optogenetic stimulation induced aversion-related behavior. Furthermore, we found that the projection pathway from MRN serotonergic neurons to the interpeduncular nucleus is crucial for these processes. These results indicate that MRN serotonergic neurons play a pivotal role in processing reward and aversive information, functioning oppositely to DRN neurons.

Pre-eclampsia, a type of hypertensive disorders of pregnancy (HDP), is characterized by hypertension and organ dysfunction that develops or worsens after 20 weeks of gestation. Although symptomatic management using antihypertensive medications has been adopted, definitive treatments other than pregnancy termination remain unavailable to halt disease progression. Research on heme oxygenase (HO)-1, a molecule with anti-inflammatory and antioxidative properties, has shown that a pharmacological increase in placental HO-1 expression and activity may ameliorate this condition; therefore, HO-1 is a promising therapeutic target for this disorder. Medications with properties that can be used during pregnancy are strong candidates for repurposing. In this article, I discuss the potential applications of proton pump inhibitors in the prevention or treatment of preeclampsia by presenting our foundational research and subsequent observational and interventional clinical studies.

Semaphorins and their receptors plexins are axon guidance molecules that navigate axons to their final destinations during neural development. Semaphorins and plexins exert distinct roles in regulating biological functions such as the immune system and bone homeostasis. They also participate in the development and progression of various diseases such as osteoporosis and allergic diseases. This review describes the varied phenotypes revealed by the analysis of semaphorin or plexin knockout mice and discusses the association with pathogenesis and therapy of atherosclerosis, agenesis of the corpus callosum, and neuropsychiatric diseases. The deletion of semaphorin 4D in atherosclerosis-prone Apolipoprotein E-deficient mice mitigated atherosclerotic lesions, indicating its crucial involvement in the progression of atherosclerosis. Semaphorin 4D is also implicated in apoptosis induced by the estrogen-dependent generation of soluble semaphorin 4D and the active form of plexin-B1 in the postnatal vaginal opening in mice. Plexin-A1 knockout BALB/cA mice exhibited the agenesis of corpus callosum. This study indicates the crucial role of plexin-A1 in the midline crossing of callosal pioneer axons projecting from the cerebral cortex during the early phase of callosal formation. Adult plexin-A1-deficient mice exhibit reduced prepulse inhibition deficit, an endophenotype of schizophrenia, in addition to excessive self-grooming. Parvalbumin-expressing interneurons in the medial prefrontal cortex are significantly decreased in plexin-A1 knockout mice. In the parvalbumin neurons, oxidative stress is significantly increased in plexin-A1 knockout mice. Accordingly, plexin-A1 deficiency may augment oxidative stress in parvalbumin neurons, thereby impairing the parvalbumin neuron network and leading to behavioral abnormalities relevant to neuropsychiatric diseases.

Poor medication compliance in children can affect treatment efficacy. We examined the impact of a picture book created by pharmacists to improve medication compliance in children. Our study aim was to assess the effects of the pharmacist-created picture book on medication compliance in children and their parents in collaboration with an outpatient pharmacy. This study included 74 children [recovery rate 28/74 (37.8%)] aged 3-6 years and their parents between March 2023 and March 2024. In the item "Have you experienced any difficulties in giving medication to your child?" the proportion of respondents answering, "Always" or "Sometimes" decreased from 78.3% (18/23) to 34.7% (8/23) after reading the picture book (p<0.01). When answering the question "What specific situations have you found challenging when giving medication?" the number of responses decreased from (an average/mean) of 1.5 situations before reading the picture book to 1 situation. Regarding whether guardians felt a greater appreciation for the importance of giving medication to their children after reading the book, 64.3% answered "Yes," the highest response. A positive correlation (correlation coefficient=0.77, p<0.01) was observed between "Is the child interested in taking the medication?" and "Is the child able to take the medicine? Pharmacists need to raise public awareness of the importance of medication adherence. Since picture books are likely to be repeatedly read aloud, they are considered effective. The results of this study suggest that pharmacist-created picture books may contribute to improving medication compliance in children.

Although odor is an important indicator of herbal medicine quality, an objective odor evaluation method remains undiscovered. Quantitative measurement using previous methods is complicated as Citrus Unshiu Peel (Chimpi) emits an odor when broken. To establish odor evaluation methods for herbal medicines using chimpi as an example, we developed a reproducible method for breaking samples and an objective odor evaluation method using an electronic nose (e-nose). First, an odor-emitting device (OED) was fabricated by modifying a pill cutter, which suppressed the spread of odor components into the room air while cutting the samples. The odor was emitted from chimpi with an OED and measured using an e-nose. The cut length was then measured. The sensor intensity was positively correlated with the cut length (r=0.840-0.927) in the same sample, and the intensity per unit length (INPULTH) calculated from the sensor intensity and cut length enables the comparison of the sensor intensity among different samples. In addition, average d-limonene emission level measured by GC-MS was positively correlated with average INPULTH (r=0.999), which suggests that this OED and e-nose method enables the comparison of the sensor intensity and d-limonene emissions. INPULTH also positively correlated with other seven monoterpenes such as p-cymene, β-myrcene, β-phellandrene, α-pinene, β-pinene, γ-terpinene, and α-terpinolene (r=0.701-0.865). Therefore, monoterpene content can be evaluated by measuring the odor in the same way as d-limonene. In conclusion, we developed a simple odor intensity evaluation method optimized for chimpi to establish an odor evaluation method for herbal medicines.

The neural cell death in cerebral infarction is suggested to be ferroptosis-like cell death, involving the participation of 15-lipoxygenase (15-LOx). Ferroptosis is induced by lipid radical species generated through the one-electron reduction of lipid hydroperoxides, and it has been shown to propagate intracellularly and intercellularly. At lower oxygen concentration, it appeared that both regiospecificity and stereospecificity of conjugated diene moiety in lipoxygenase-catalysed lipid hydroperoxidation are drastically lost. As a result, in the reaction with linoleic acid, the linoleate 9-peroxyl radical-ferrous lipoxygenase complex dissolves into the linoleate 9-peroxyl radical and ferrous 15-lipoxygenase. Subsequently, the ferrous 15-lipoxygenase then undergoes one-electron reduction of 13-hydroperoxy octadecadienoic acid, generating an alkoxyl radical (pseudoperoxidase reaction). A part of the produced lipid alkoxyl radicals undergoes cleavage of C-C bonds, liberating small molecular hydrocarbon radicals. Particularly, in ω-3 polyunsaturated fatty acids, which are abundant in the vascular and nervous systems, the liberation of small molecular hydrocarbon radicals was more pronounced compared to ω-6 polyunsaturated fatty acids. The involvement of these small molecular hydrocarbon radicals in the propagation of membrane lipid damage is suggested.

Drug-induced acute kidney injury (AKI) is a serious adverse drug reaction, which results in a significant decline in renal function and is known to progress to chronic kidney disease (CKD). Therefore, appropriate drug therapy is important to avoid the risk of drug-induced AKI and CKD, which are serious concerns in clinical practice. In this study, using the medical information database of Hamamatsu University Hospital, we investigated the risk factors that accelerate the onset of drug-induced AKI or its progression to CKD in patients who received aminoglycoside antibiotics (AGs) or glycopeptide antibiotics (GPs), which are strongly associated with drug-induced AKI and CKD. We performed logistic regression analysis using patients' background, laboratory test results, and concomitant drug use, among other such factors as explanatory variables and drug-induced AKI or CKD onset as objective variables to explore the risk factors for drug-induced AKI and CKD. Our results showed that co-administration of amphotericin B, piperacillin-tazobactam and other AGs and GPs, increased serum creatinine (Scr) and chloride concentrations, serum lactate dehydrogenase activity, and decreased serum albumin concentration were risk factors for drug-induced AKI onset. Moreover, a reduced blood urea nitrogen : Scr ratio at drug-induced AKI onset served as a risk factor for CKD. These results suggest that careful monitoring of the aforementioned factors is important to ensure appropriate usage of these drugs in patients treated with AGs and GPs.