-
Chemical & Pharmaceutical Bulletin 2024Agitation and psychosis are key behavioral and psychological symptoms of Alzheimer's disease (AD). For family and caregivers of patients, such symptoms are critical... (Review)
Review
Agitation and psychosis are key behavioral and psychological symptoms of Alzheimer's disease (AD). For family and caregivers of patients, such symptoms are critical factors of distress and increased burden, but medication to treat them is limited. In most cases, drugs for other neuropsychiatric diseases have been used to manage these symptoms in an off-label manner. Due to the complex pathological background of AD and limited clinical data, obtaining proof of concept for the treatment of these symptoms is challenging. However, in 2023, the U.S. Food and Drug Administration approved brexpiprazole as the first and only drug to treat agitation in AD. Several other compounds have been evaluated in clinical situations. This review highlights recent pipelines being developed for agitation and psychosis for patients living with AD.
Topics: Alzheimer Disease; Humans; Psychotic Disorders; Psychomotor Agitation; Antipsychotic Agents
PubMed: 38945937
DOI: 10.1248/cpb.c23-00416 -
Internal Medicine (Tokyo, Japan) 2024
Topics: Humans; Female; Pregnancy; Still's Disease, Adult-Onset; Adult; Postpartum Period; Liver Failure; Pregnancy Complications; Infant, Newborn
PubMed: 38945934
DOI: 10.2169/internalmedicine.R001-24 -
Internal Medicine (Tokyo, Japan) 2024Objective Chimeric antigen receptor (CAR) T cell therapy is an emerging and effective therapy for relapsed or refractory diffuse large B cell lymphoma (R/R DLBCL). The...
Activated CD4 T Cell Proportion in the Peripheral Blood Correlates with the Duration of Cytokine Release Syndrome and Predicts Clinical Outcome after Chimeric Antigen Receptor T Cell Therapy.
Objective Chimeric antigen receptor (CAR) T cell therapy is an emerging and effective therapy for relapsed or refractory diffuse large B cell lymphoma (R/R DLBCL). The characteristic toxicities of CAR T cell therapy include cytokine release syndrome (CRS) and prolonged cytopenia. We investigated the factors associated with these complications after CAR T cell therapy by analyzing lymphocyte subsets following CAR T cell infusion. Methods We retrospectively analyzed peripheral blood samples on days 7, 14, and 28 after tisagenlecleucel (tisa-cel) infusion by flow cytometry at our institution between June 2020 and September 2022. Patients Thirty-five patients with R/R DLBCL who received tisa-cel therapy were included. Results A flow cytometry-based analysis of blood samples from these patients revealed that the proportion of CD4CD25CD127 T cells (hereafter referred to as "activated CD4 T cells" ) among the total CD4 T cells on day 7 after tisa-cel infusion correlated with the duration of CRS (r=0.79, p<0.01). In addition, a prognostic analysis of the overall survival (OS) using time-dependent receiver operating characteristic curves indicated a significantly more favorable OS and progression-free survival of patients with a proportion of activated CD4 T cells among the total CD4 T cells <0.73 (p=0.01, and p<0.01, respectively). Conclusion These results suggest that the proportion of activated CD4 T cells on day 7 after tisa-cel infusion correlates with the CRS duration and predicts clinical outcomes after CAR T cell therapy. Further studies with a larger number of patients are required to validate these observations.
Topics: Humans; Male; Female; Cytokine Release Syndrome; Immunotherapy, Adoptive; Middle Aged; Lymphoma, Large B-Cell, Diffuse; Aged; Retrospective Studies; CD4-Positive T-Lymphocytes; Adult; Treatment Outcome; Receptors, Chimeric Antigen; Prognosis; Receptors, Antigen, T-Cell
PubMed: 38945932
DOI: 10.2169/internalmedicine.2556-23 -
The Journal of Veterinary Medical... Jul 2024An 8-year-old Portuguese Water Dog presented with a 5-month history of left forelimb lameness. There was palmar pain. Ultrasonography revealed enlargement of the left...
An 8-year-old Portuguese Water Dog presented with a 5-month history of left forelimb lameness. There was palmar pain. Ultrasonography revealed enlargement of the left median nerve. Subsequent MRI also showed enlargement of the median nerve in the distal palmar to the mid-forearm region. Rapid intraoperative diagnosis suggested Malignant peripheral nerve sheath tumors (MPNST) and a neurotomy was performed. The lameness had almost disappeared in 1 month after surgery. Recurrence occurred 26 months postoperatively and the forelimb was amputated. At 950 days after the neurotomy, radiography revealed lung metastasis, and the dog died 988 days after the neurotomy. Neurotomy for MPNST should be performed with caution until more information is available regarding methods for early detection, margin determination, and indication determination for neurotomy.
PubMed: 38945917
DOI: 10.1292/jvms.24-0038 -
Nihon Yakurigaku Zasshi. Folia... 2024Ensitrelvir fumaric acid (Xocova hereafter ensitrelvir) is a novel anti-SARS-CoV-2 drug for COVID-19. Hokkaido University and Shionogi & Co., Ltd. engaged in joint... (Review)
Review
Ensitrelvir fumaric acid (Xocova hereafter ensitrelvir) is a novel anti-SARS-CoV-2 drug for COVID-19. Hokkaido University and Shionogi & Co., Ltd. engaged in joint research targeting SARS-CoV-2 3C-like (3CL) protease at an early stage and started clinical trials in July 2021. In February 2022, an application was filed for manufacture and sales approval for the indication of "SARS-CoV-2 infection,". Ensitrelvir recieved the first emergency regulatory approval from the Ministry of Health, Labour and Welfare (MHLW) in Japan in November 2022, and has obtained standard approval in March 2024. This emergency approval was based on the confirmed safety in a Phase 2/3 study (T1221) conducted in Japan and other Asian countries (Korea and Vietnam) in patients with mild/moderate COVID-19 and the presumed efficacy in Phase 3 Part (SCORPIO-SR), and the standard approval is based on efficacy from the Phase 3 part. In the Phase 3 part, ensitrelvir administered orally 375/125 mg once daily for five days, in patients with irrespective of risk factors for severe complications and vaccination status, demonstrating a significant reduction vs placebo in the time to resolution of five typical Omicron-related symptoms (stuffy or runny nose, sore throat, cough, feeling hot or feverish, and low energy or tiredness), and also showed a significant reduction in viral RNA on day 4 relative to placebo (P < 0.001). In the Phase 2/3 study, there were no serious adverse events or deaths, indicating good tolerability and safety. We hope that ensitrelvir will contribute as a new treatment option for patients suffering from COVID-19 symptoms.
Topics: Humans; COVID-19 Drug Treatment; SARS-CoV-2; Tablets; Clinical Trials as Topic; COVID-19; Antiviral Agents; Treatment Outcome; Fumarates; Indazoles; Triazines; Triazoles
PubMed: 38945910
DOI: 10.1254/fpj.24017 -
Nihon Yakurigaku Zasshi. Folia... 2024The development of genetically-encoded fluorescent probes for the detection of intracellular calcium ions and various neurotransmitters has progressed significantly in... (Review)
Review
The development of genetically-encoded fluorescent probes for the detection of intracellular calcium ions and various neurotransmitters has progressed significantly in recent years, and there is a growing need for techniques that rapidly and efficiently image these signals in the living brain for pharmacological studies of the central nervous system. In this article, we discuss one-photon fluorescence microscopy techniques used for brain activity imaging, particularly wide-field imaging and head-mounted miniaturized microscopy, and introduce their basic principles, recent advances, and applications in pharmacological research. Wide-field calcium imaging is suitable for mesoscopic observation of cortical activity during behavioral tasks in head-fixed awake mice, while head-mounted miniaturized microscopes can be attached to the animal's head to image brain activity associated with naturalistic behaviors such as social behavior and sleep. One-photon microscopy allows for the development of a simple and cost-effective imaging system using an affordable excitation light source such as a light-emitting diode. Its excitation light illuminates the entire field of view simultaneously, making it easy to perform high-speed imaging using a high-sensitivity camera. In contrast, the short wavelength of the excitation light limits the field of observation to areas on or near the brain surface due to its strong light scattering. Moreover, the out-of-focus fluorescence makes it difficult to obtain images with a high signal-to-noise ratio and spatial resolution. The use of one-photon microscopy in brain activity imaging has been limited compared to two-photon microscopy, but its advantages have recently been revisited. Therefore, this technique is expected to become a useful method for pharmacologists to visualize the activity of the living brain.
Topics: Animals; Brain; Microscopy, Fluorescence; Humans; Pharmacology
PubMed: 38945906
DOI: 10.1254/fpj.24012 -
Biological & Pharmaceutical Bulletin 2024Primary hepatocytes are valuable for studying liver diseases, drug-induced liver injury, and drug metabolism. However, when cultured in a two-dimensional (2D)...
Suppression of the Epithelial-Mesenchymal Transition and Maintenance of the Liver Functions in Primary Hepatocytes through Dispersion Culture within a Dome-Shaped Collagen Matrix.
Primary hepatocytes are valuable for studying liver diseases, drug-induced liver injury, and drug metabolism. However, when cultured in a two-dimensional (2D) environment, primary hepatocytes undergo rapid dedifferentiation via an epithelial-mesenchymal transition (EMT) and lose their liver-specific functions. On the other hand, a three-dimensional (3D) culture of primary hepatocyte organoids presents challenges for analyzing cellular functions and molecular behaviors due to strong cell-cell adhesion among heterogeneous cells. In this study, we developed a novel dispersion culture method of hepatocytes within a dome-shaped collagen matrix, overcoming conventional limitations. The expression levels of EMT-related genes were lower in rat primary hepatocytes cultured using this method for 4 d than in cells cultured using the 2D method. Furthermore, albumin production, a marker of liver function, declined sharply in rat primary hepatocytes cultured in two dimensions from 6.40 µg/mL/48 h on day 4 to 1.35 µg/mL/48 h on day 8, and declined gradually from 4.92 µg/mL/48 h on day 8 to 3.89 µg/mL/48 h on day 14 in rat primary hepatocytes cultured using our new method. These findings indicate that the newly developed culture method can suppress EMT and maintain liver functions for 14 d in rat primary hepatocytes, potentially expanding the utility of primary hepatocyte cultured by using conventional 3D methods.
Topics: Animals; Hepatocytes; Epithelial-Mesenchymal Transition; Cells, Cultured; Collagen; Male; Liver; Rats; Cell Culture Techniques; Rats, Sprague-Dawley; Albumins
PubMed: 38945897
DOI: 10.1248/bpb.b24-00180 -
Journal of Nutritional Science and... 2024This study examined the relationship between the frequency of consuming cold or hot meal/drink during summer and the nutritional status, appetite, and energy intake...
This study examined the relationship between the frequency of consuming cold or hot meal/drink during summer and the nutritional status, appetite, and energy intake among Japanese older people. The cross-sectional study was conducted in August 2021, targeting 60 adults aged 65 y and older. The Mini Nutritional Assessment (MNA) was used for nutritional status evaluation, the Simplified Nutritional Appetite Questionnaire (SNAQ) for appetite scoring, and food frequency questionnaire to assess energy intake. Participants reported on the frequency of consuming cold or hot meal/drink during the summer. Those who reported consuming hot meals "moderate" (p=0.033) or "frequent" (p=0.005) during summer had a higher BMI than those who reported minimal consumption. Participants who reported "frequent" consumption of hot meals in summer had higher MNA scores than those who reported "minimal" consumption (p=0.014). Participants who reported a "frequent" consumption of hot meals had higher SNAQ scores compared to those who reported "minimal" (p<0.001) or "moderate" (p=0.001). Similarly, participants who reported a "frequent" consumption of hot drinks had higher SNAQ scores than those reporting "minimal" (p=0.021) or "moderate" (p=0.008). The nutritional status and appetite during summer in Japanese older people were associated with the frequency of consuming hot meals and drinks.
Topics: Humans; Aged; Male; Nutritional Status; Female; Appetite; Japan; Cross-Sectional Studies; Energy Intake; Meals; Seasons; Aged, 80 and over; Nutrition Assessment; Hot Temperature; Surveys and Questionnaires; Body Mass Index; Feeding Behavior; Diet; East Asian People
PubMed: 38945895
DOI: 10.3177/jnsv.70.288 -
Journal of Nutritional Science and... 2024The purpose of this study was to examine whether 4 wk of daily ingestion of milk fat globule membrane (MFGM) combined with exercise training improves physical... (Randomized Controlled Trial)
Randomized Controlled Trial
Effects of Milk Fat Globule Membrane Supplementation Following Exercise Training on Physical Performance in Healthy Young Adults: A Randomized Double-Blind, Placebo-Controlled Pilot Trial.
The purpose of this study was to examine whether 4 wk of daily ingestion of milk fat globule membrane (MFGM) combined with exercise training improves physical performance-muscle strength, agility and muscle power-in healthy young adults. The study was designed as a randomized, double-blind, and placebo-controlled trial. Twenty healthy young adults received either an MFGM powder containing 1.6 g of fat and 160 mg of sphingomyelin or an isocaloric placebo powder daily throughout 4 wk of power or agility training. Physical performance tests and body composition measurements were conducted before and after the 4-wk intervention. Ingestion of MFGM did not affect isometric or isokinetic muscle strength, but it was associated with a greater increase in vertical jump peak power compared with placebo. There were no significant changes in body weight or lean body mass during the intervention period in either group, and no significant differences between groups. We conclude that daily MFGM supplementation combined with exercise training has the potential to improve physical performance in young adults; however, further studies with larger sample sizes should be conducted to obtain more evidence supporting achievement of improved physical performance through MFGM supplementation.
Topics: Humans; Double-Blind Method; Glycolipids; Lipid Droplets; Glycoproteins; Male; Young Adult; Female; Dietary Supplements; Muscle Strength; Body Composition; Exercise; Pilot Projects; Adult; Physical Functional Performance; Body Weight; Sphingomyelins; Muscle, Skeletal
PubMed: 38945893
DOI: 10.3177/jnsv.70.273 -
Journal of Nutritional Science and... 2024Determining the optimal body weight for individuals with severe motor and intellectual disabilities (SMID) lacks a standardized approach. In this study, we aimed to...
Determining the optimal body weight for individuals with severe motor and intellectual disabilities (SMID) lacks a standardized approach. In this study, we aimed to develop a formula to estimate the ideal body weight for each SMID patient, considering factors such as reduced muscle and bone mass. We analyzed data from 111 SMID patients (56 male, 55 female; age range 20 to 73 y) who underwent blood tests measuring creatinine (Cr) and cystatin C (cysC) for clinical reasons between Feb. 2018 and Feb. 2023. To create the optimal body weight formula, we utilized three variables: height, estimated glomerular filtration (eGFR)-Cr, and eGFR-cysC. The validity of the formula was assessed by comparing the measured triceps subcutaneous fat thickness (TSF) to the reference TSF (%TSF), evaluating how accurately it reflects the appropriate physique. The derived optimal body weight formula is as follows: Optimal body weight=(height)×(18.5-25.0)×{1-0.41×(1-eGFR-cysC/eGFR-Cr)}×0.93. Our formula demonstrated validity when using %TSF as an indicator. Establishing a method to determine optimal body weight in SMID patients, considering their low muscle and bone mass, is crucial for accurate nutritional assessment and subsequent nutritional management.
Topics: Humans; Female; Male; Middle Aged; Adult; Aged; Intellectual Disability; Creatinine; Young Adult; Body Weight; Cystatin C; Glomerular Filtration Rate; Nutrition Assessment; Ideal Body Weight; Body Height; Subcutaneous Fat; Motor Disorders
PubMed: 38945890
DOI: 10.3177/jnsv.70.248