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Journal of Nutritional Science and... 2024L-Theanine is contained in green tea at 1-3% per dry matter as an amino acid with an umami taste, and the antidepressant effect and protective effect against...
L-Theanine is contained in green tea at 1-3% per dry matter as an amino acid with an umami taste, and the antidepressant effect and protective effect against stress-induced brain atrophy in mice, as well as the related mechanism have been reported. However, effects of theanine on the hippocampus from the proteome analysis and the action mechanism have not been examined. In this study, we mainly investigated the possibility of theanine's cognitive impairment-preventing function and the action mechanism by proteomics in the hippocampus of SAMP8 administered with theanine. In addition to improvement in the aging score with theanine administration, in proteomics, significant suppressions in the expressions of synapsin 2, α-synuclein, β-synuclein, and protein tau were observed by theanine administration, and the expression of CAM kinase II beta and alpha exhibited a significant increase and increasing tendency with theanine administration, respectively. The expression of tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein tended to increase by theanine administration. On the other hand, serotonin/tryptophan, GABA/glutamic acid and glutamine/glutamic acid ratios in the hippocampus showed an increasing tendency, a significant increase, and an increasing tendency with theanine administration, respectively. These results suggested that theanine might have been involved in the improvement of neurodegeneration or cognitive impairment by suppressing the productions of synapsin, synuclein and protein tau which are considered to be produced along with aging and oxidation, and by enhancing the production of serotonin by increasing the expression of CAM kinase II, and further by affecting the metabolism of glutamate.
Topics: Animals; Glutamates; Hippocampus; Mice; Male; Aging; Synapsins; Glutamic Acid; alpha-Synuclein; tau Proteins; Proteomics; Dietary Supplements; Serotonin; Diet; gamma-Aminobutyric Acid; Calcium-Calmodulin-Dependent Protein Kinase Type 2; Cognitive Dysfunction
PubMed: 38945886
DOI: 10.3177/jnsv.70.210 -
Journal of Nutritional Science and... 2024Oleuropein aglycone (OA), which is the absorbed form of oleuropein, is a major phenolic compound in extra virgin olive oil. We analyzed the anti-obesity effect of OA...
Oleuropein aglycone (OA), which is the absorbed form of oleuropein, is a major phenolic compound in extra virgin olive oil. We analyzed the anti-obesity effect of OA intake combined with mild treadmill walking (MTW, 4 m/min for 20 min/d, 5-6 d/wk, without electric shocks and slope) in rats under a high-fat diet (HF). Four-week-old male Sprague-Dawley rats (n=28) were equally divided into four groups: control (HF), 0.08% oleuropein-supplemented HF (HFO), HF with MTW (HF+W), and HFO with MTW (HFO+W) groups. After 28 d, the inguinal subcutaneous fat content and weight gain were significantly lower in the HFO+W group than in the control group. The HFO+W group also had significantly higher levels of urinary noradrenaline secretion, interscapular brown adipose tissue, uncoupling protein 1, brain transient receptor potential ankyrin subtype 1 (TRPA1), vanilloid subtype 1 (TRPV1), and brain-derived neurotrophic factor (BDNF) than the control group. Especially, the HFO+W group showed a synergistic effect on noradrenaline secretion. Therefore, OA combined with MTW may accelerate the enhancement of UCP1 and BDNF levels in rats with HF-induced obesity by increasing noradrenaline secretion after TRPA1 and TRPV1 activation.
Topics: Animals; Male; Uncoupling Protein 1; Iridoid Glucosides; Rats, Sprague-Dawley; Obesity; Adipose Tissue, Brown; Iridoids; Norepinephrine; Diet, High-Fat; TRPA1 Cation Channel; Brain-Derived Neurotrophic Factor; Rats; Anti-Obesity Agents; Walking; Weight Gain; Physical Conditioning, Animal; TRPV Cation Channels
PubMed: 38945884
DOI: 10.3177/jnsv.70.193 -
Yakugaku Zasshi : Journal of the... 2024Venetoclax (VEN) is used in patients with acute myeloid leukemia (AML) and is primarily metabolized by CYP3A4, a major drug-metabolizing enzyme. Patients with AML...
Venetoclax (VEN) is used in patients with acute myeloid leukemia (AML) and is primarily metabolized by CYP3A4, a major drug-metabolizing enzyme. Patients with AML simultaneously administered VEN and CYP3A4 inhibitors require a more appropriate management of drug-drug interactions (DDIs). Here, we report two cases of patients with AML (54-year-old man and 22-year-old woman) administrated VEN and CYP3A4 inhibitors, such as posaconazole, cyclosporine, or danazol. In the first case, we evaluated the appropriateness of timing for adjusting VEN dosage subsequent to the cessation of posaconazole. Consequently, modifying the VEN dosage in conjunction with the cessation of Posaconazole simultaneously may result in elevated plasma VEN levels. In the second case, plasma VEN concentrations were markedly elevated when co-administered with several CYP3A4 inhibitors. Additionally, in vitro assays were conducted for reverse translational studies to analyze CYP3A4 inhibition. CYP3A4 inhibition by combinatorial administration of cyclosporine A and danazol was demonstrated in vitro, which potentially explains the increasing plasma VEN concentrations observed in clinical settings. Although the acquisition of therapeutic effects is a major priority for patients, frequent therapeutic drug monitoring and dosage adjustments considering DDIs would be important factors in chemotherapy.
Topics: Humans; Sulfonamides; Leukemia, Myeloid, Acute; Cytochrome P-450 CYP3A Inhibitors; Drug Interactions; Male; Young Adult; Middle Aged; Bridged Bicyclo Compounds, Heterocyclic; Female; Drug Monitoring; Cytochrome P-450 CYP3A; Cyclosporine; Triazoles; Antineoplastic Agents
PubMed: 38945852
DOI: 10.1248/yakushi.24-00018 -
Yakugaku Zasshi : Journal of the... 2024Cancer-associated cachexia, a multifactorial syndrome involving loss of muscle mass and anorexia, affects the survival of cancer patients. Anamorelin was the first drug...
Cancer-associated cachexia, a multifactorial syndrome involving loss of muscle mass and anorexia, affects the survival of cancer patients. Anamorelin was the first drug approved in Japan for the treatment of cachexia. However, cases in which anamorelin is discontinued within 3 weeks are often observed in clinical practice. This study aimed to explore the factors associated with continued anamorelin dosing. We retrospectively reviewed records of patients with lung, gastric, pancreatic, and colorectal cancer who started anamorelin at Fukuoka University Hospital from April 2021 to November 2022. Patients were divided into two groups based on the duration of anamorelin administration: 15 patients were classified into the <3 weeks group and 22 were classified into the ≥3 weeks group. The primary objective was to explore the potential factors associated with the continuation of anamorelin, and the secondary objectives were to compare survival and nutritional indices. In the univariate analysis, there were significant differences between the two groups in terms of cancer type (p=0.007) and serum albumin level (p=0.026). In the multivariate analysis, gastric cancer and albumin 2.7 g/dL or less were associated with the continuation of anamorelin. Survival was significantly shorter in the <3 weeks group (p=0.019). This study suggests that the continuation of anamorelin may be influenced by specific tumor types and serum albumin levels. Furthermore, the duration of anamorelin administration may affect patient survival.
Topics: Humans; Cachexia; Retrospective Studies; Male; Female; Aged; Neoplasms; Middle Aged; Oligopeptides; Time Factors; Aged, 80 and over; Serum Albumin; Hydrazines; Drug Administration Schedule
PubMed: 38945851
DOI: 10.1248/yakushi.24-00002 -
Yakugaku Zasshi : Journal of the... 2024An overwhelming surge of information regarding preparedness for postvaccination side effects had caused widespread confusion approximately since April 2021, when the...
An overwhelming surge of information regarding preparedness for postvaccination side effects had caused widespread confusion approximately since April 2021, when the coronavirus disease 2019 (COVID-19) vaccination had started for the general population in Japan. Notably, this resulted in a remarkably increased shortage of OTC acetaminophen formulations. The aim of this study was to elucidate the actual responses of the public in such an environment, how individuals acquired and understood information related to the management of postvaccination side effects, and how they obtained and used antipyretic analgesics before and after COVID-19 vaccination. We conducted a web-based survey in January 2022, targeting 400 individuals aged ≥20 years, who had received two COVID-19 vaccine doses, and excluded qualified professionals such as physicians and pharmacists. The results revealed that 67% of the respondents had obtained antipyretic analgesics in anticipation of adverse effects after vaccination, whereas 38% had taken these medicines before and/or after the second vaccination. Possible misappropriation of medicines from others, preventive administration, and lack of dosage and administration confirmation are the problems identified in medication acquisition and usage. Additionally, avoidance of antipyretic analgesics based on information without scientific evidence was observed. This study revealed no small amount of inappropriate use of medicines in situations, such as the COVID-19 pandemic, where there is an "infodemic" of mixed-quality information. Pharmacists, as experts in medication, should play a crucial role in promoting appropriate medication usage by consistently staying updated with the latest scientific evidence and proactively supporting OTC drug selection and counseling medication.
Topics: Humans; Antipyretics; Pharmacists; COVID-19 Vaccines; Male; Female; Middle Aged; Adult; Acetaminophen; Japan; Surveys and Questionnaires; Professional Role; Vaccination; Aged; Young Adult; Nonprescription Drugs; COVID-19
PubMed: 38945850
DOI: 10.1248/yakushi.23-00183 -
Yakugaku Zasshi : Journal of the... 2024The Japanese package insert (J-PI) for nirmatrelvir/ritonavir (N/r) (specially approved pharmaceutical) includes numerous warnings about drug interactions. However,...
The Japanese package insert (J-PI) for nirmatrelvir/ritonavir (N/r) (specially approved pharmaceutical) includes numerous warnings about drug interactions. However, discrepancies in the information on drug interaction are reported between J-PI and foreign databases. This study aimed to evaluate various information sources on N/r drug interactions. We categorized and compared information on N/r drug interactions from the J-PI, prescribing information from foreign regulatory agencies, guidance from the National Institutes of Health and University Health Network, the Ontario coronavirus disease 2019 (COVID-19) Science Advisory Table, University of Liverpool, Lexicomp, and the Japanese Society of Pharmaceutical Health Care and Sciences (JSPHCS). We assessed information quantity, missing data in J-PI, predicted change of the area under the blood concentration-time curve (AUC) for nirmatrelvir or co-administered drugs, and the information source consistency. From these information sources, we compiled a dataset with 115 contraindications and 203 precautions for N/r co-administration, and 51 contraindications are missing in J-PI. Among them, at least 12 drugs have large predicted AUC changes with N/r (AUC ≥5-fold or <1/5 of the baseline value). Nine of these 12 drugs are included as contraindications in Lexicomp and the JSPHCS. The consistency among the information sources is low. Information in the J-PI alone may be insufficient and Lexicomp or the JSPHCS guidelines should be useful because of their large amounts of information and wide coverage of drugs with large AUC changes. Due to low source consistency, multiple sources are needed for clinical management.
Topics: Ritonavir; Humans; Drug Interactions; Drug Combinations; COVID-19 Drug Treatment; Lopinavir; Area Under Curve; Japan; Indazoles
PubMed: 38945847
DOI: 10.1248/yakushi.23-00204 -
The Journal of Toxicological Sciences 2024Clothianidin (CLO), a neonicotinoid that is widely used in forests and agricultural areas, was recently reported to cause toxicity in mammals. Although sensitivity to...
Clothianidin (CLO), a neonicotinoid that is widely used in forests and agricultural areas, was recently reported to cause toxicity in mammals. Although sensitivity to chemicals varies between sexes and developmental stages, studies that comprehensively evaluate both males and females are limited. Therefore, in this study we utilized murine models to compare the sex-specific differences in behavioral effects following CLO exposure at different developmental stages. We orally administered CLO to male and female mice as a single high-dose solution (80 mg/kg) during the postnatal period (2-week-old), adolescence (6-week-old), or maturity (10-week-old), and subsequently evaluated higher brain function. The behavioral battery test consisted of open field, light/dark transition, and contextual/cued fear conditioning tests conducted at three and seven months of age. After the behavioral test, the brains were dissected and prepared for immunohistochemical staining. We observed behavioral abnormalities in anxiety, spatial memory, and cued memory only in female mice. Moreover, the immunohistochemical analysis showed a reduction in astrocytes within the hippocampus of female mice with behavioral abnormalities. The behavioral abnormalities observed in female CLO-treated mice were consistent with the typical behavioral abnormalities associated with hippocampal astrocyte dysfunction. It is therefore possible that the CLO-induced behavioral abnormalities are at least in part related to a reduction in astrocyte numbers. The results of this study highlight the differences in behavioral effects following CLO exposure between sexes and developmental stages.
Topics: Animals; Female; Neonicotinoids; Guanidines; Male; Behavior, Animal; Thiazoles; Hippocampus; Sex Characteristics; Fear; Astrocytes; Anxiety; Mice; Sex Factors; Spatial Memory; Administration, Oral; Insecticides
PubMed: 38945841
DOI: 10.2131/jts.49.301 -
Brain and Behavior Jul 2024Pregnant women may need to undergo non-obstetric surgery under general anesthesia owing to medical needs, and pregnant women frequently experience sleep disturbances...
Subsequent maternal sleep deprivation aggravates cognitive impairment by modulating hippocampal neuroinflammatory responses and synaptic function in maternal isoflurane-exposed offspring mice.
INTRODUCTION
Pregnant women may need to undergo non-obstetric surgery under general anesthesia owing to medical needs, and pregnant women frequently experience sleep disturbances during late gestation. Preclinical studies demonstrated that maternal isoflurane exposure (MISO) or maternal sleep deprivation (MSD) contributed to cognitive impairments in offspring. Research studies in mice have revealed that SD can aggravate isoflurane-induced cognitive deficits. However, it remains unclear whether MSD aggravates MISO-induced cognitive deficits in offspring. The purpose of this research was to explore the combined effects of MSD and MISO on offspring cognitive function and the role of neuroinflammation and synaptic function in the process of MSD + MISO.
METHODS
Pregnant mice were exposed to 1.4% isoflurane by inhalation for 4 h on gestational day (GD) 14. Dams were then subjected to SD for 6 h (12:00-18:00 h) during GD15-21. At 3 months of age, the offspring mice were subjected to the Morris water maze test to assess cognitive function. Then the levels of inflammatory and anti-inflammatory markers and synaptic function-related proteins were assessed using molecular biology methods.
RESULTS
The results of this study demonstrated that MISO led to cognitive dysfunction, an effect that was aggravated by MSD. In addition, MSD exacerbated the maternal isoflurane inhalation, leading to an enhancement in the expression levels of interleukin (IL)-1β, IL-6, and tumor necrosis factor-alpha and a reduction in the hippocampal levels of IL-10, synaptophysin, post-synaptic density-95, growth-associated protein-43, and brain-derived neurotrophic factor.
CONCLUSION
Our findings revealed that MSD aggravated the cognitive deficits induced by MISO in male offspring mice, and these results were associated with neuroinflammation and alternations in synaptic function.
Topics: Animals; Isoflurane; Female; Cognitive Dysfunction; Pregnancy; Sleep Deprivation; Mice; Hippocampus; Prenatal Exposure Delayed Effects; Neuroinflammatory Diseases; Anesthetics, Inhalation; Synapses; Male; Mice, Inbred C57BL; Maternal Deprivation; Brain-Derived Neurotrophic Factor
PubMed: 38945806
DOI: 10.1002/brb3.3610 -
Brain and Behavior Jul 2024Semantic fluency is the ability to name items from a given category within a limited time, which relies on semantic knowledge, working memory, and executive function....
INTRODUCTION
Semantic fluency is the ability to name items from a given category within a limited time, which relies on semantic knowledge, working memory, and executive function. Similar to patients with Parkinson's disease (PD), patients with progressive supranuclear palsy (PSP) scored lower than healthy adults in the well-established semantic fluency test. However, it is unclear how unique are the produced words. This study examined the relationship between semantic fluency and words' uniqueness in patients with PSP.
METHODS
Twenty-seven patients with PSP Richardson's syndrome (PSP-RS), 37 patients with PD, and 41 healthy controls (HC) performed a standard semantic fluency test (animals), and their verbal responses were audio-recorded. We used the uniqueness to reflect the ability to produce both original and effective work, that is, creativity.
RESULTS
The PSP-RS group produced fewer correct words and fewer unique words than the PD and HC groups. Moreover, the correlation between fluency and uniqueness was positive in the HC and PD groups but negative in the PSP-RS group. Importantly, the actual levodopa dose was positively correlated with the fluency but negatively correlated with the uniqueness in PSP-RS. The PSP-RS patients who took a greater dose of levodopa tended to produce more correct words but fewer unique words.
CONCLUSIONS
These results suggested that levodopa may modulate semantic fluency and uniqueness in the early stages of PSP-RS.
Topics: Humans; Supranuclear Palsy, Progressive; Male; Female; Aged; Semantics; Levodopa; Parkinson Disease; Middle Aged; Neuropsychological Tests; Antiparkinson Agents
PubMed: 38945805
DOI: 10.1002/brb3.3606 -
Food Research International (Ottawa,... Aug 2024Lipids from cow milk fat globule membranes (MFGMs) and extracellular vesicles (EVs) are considered beneficial for neurodevelopment, cognitive maintenance and human...
Lipids from cow milk fat globule membranes (MFGMs) and extracellular vesicles (EVs) are considered beneficial for neurodevelopment, cognitive maintenance and human health in general. Nevertheless, it is largely unknown whether intake of infant formulas and medical nutrition products rich in these particles promote accretion of specific lipids and whether this affects metabolic homeostasis. To address this, we carried out a 16-week dietary intervention study where mice were supplemented with a MFGM/EV-rich concentrate, a control diet supplemented with a whey protein concentrate and devoid of milk lipids, or regular chow. Assessment of commonly used markers of metabolic health, including body weight, glucose intolerance and liver microanatomy, demonstrated no differences across the dietary regimes. In contrast, in-depth lipidomic analysis revealed accretion of milk-derived very long odd-chain sphingomyelins and ceramides in blood plasma and multiple tissues of mice fed the MFGM/EV diet. Furthermore, lipidomic flux analysis uncovered that mice fed the MFGM/EV diet have increased lipid metabolic turnover at the whole-body level. These findings help fill a long-lasting knowledge gap between the intake of MFGM/EV-containing foods and the health-promoting effects of their lipid constituents. In addition, the findings suggest that dietary sphingomyelins or ceramide-breakdown products with very long-chains can be used as structural components of cellular membranes, lipoprotein particles and signaling molecules that modulate metabolic homeostasis and health.
Topics: Animals; Sphingolipids; Extracellular Vesicles; Mice; Glycolipids; Lipid Metabolism; Lipid Droplets; Glycoproteins; Lipidomics; Mice, Inbred C57BL; Male; Sphingomyelins; Ceramides; Diet; Liver; Dietary Supplements
PubMed: 38945615
DOI: 10.1016/j.foodres.2024.114601