Further Obervations on the Use of the Medicinal Plant, Vernonia amygdalina (Del). By a Wild Chimpanzee, Its Possible Effect on Parasote Load, and Its Phytochemistry

This is the second detailed case study of the use of V. amygdalina (Del) by a wild chimpanzee suffering from gastrointestinal upset (flatulence and diarrhea). The female, who was followed for approximately 5 hours over a two-day period, recovered from her symptoms by the afternoon of the second day. Laboratory examination of two decal samples, one collected approximately 1 hour and another 20.5 hours after ingestion of the plant's bitter pith, revealed a notable drop in the degree of parasitic infection by a Ternidens sp. Bioassay of the plant consumed by the female confirmed that the two most abundant and bioactive constituents, vernodalin and vernonioside B1, were present. Vernonioside B1 was found to occur at significant levels in both the leaves and pith, but the cytotoxic vernodalin was found only in the leaves. This suggests that vernonioside B1 and its naturally occurring aglycones are likely to be the bioactive constituents ingested by chimpanzees. The estimated amount of vernonioside B1 ingested by this female was found to be approximately equal to the amount contained in a traditional Tongwe medicinal preparation from a cold water extract of the leaves to treat similar gastrointestinal disorders in adult human patients. This report provides new evidence for the effectiveness of medicinal plant use in primates and strongly supports the current hypothesis regarding the use of V. amygdalina for the control of symptoms from parasitic and gastrointestinal illness by wild chimpanzees

A Proposal of Order Planning Method with Consideration of Multiple Organizations in Manufacturing System

Part 3: Production Management Theory and MethodologyInternational audienceManufacturing system includes multiple business organizations having different decision criteria such as factories, salespersons and customers. It is important to maximize the overall profit while considering the objectives of each organization by appropriate adjustment. In this study, we propose the order planning method using the credibility about salespersons. This proposed method adjusts the due date between the salesperson and the customer by considering the margin time, and then derives effective production schedule by solving the optimization problem that minimizes the weighted sum of the tardiness from due date and makespan. Several computational experiments are conducted so as to evaluate the effectiveness of the proposed method

Mechanical Characterization of Dissolving Microneedles: Factors Affecting Physical Strength of Needles

Dissolving microneedles (MNs) are novel transdermal drug delivery systems that can be painlessly self-administered. This study investigated the effects of experimental conditions on the mechanical characterization of dissolving MNs for quality evaluation. Micromolding was used to fabricate polyvinyl alcohol (PVA)-based dissolving MN patches with eight different cone-shaped geometries. Axial force mechanical characterization test conditions, in terms of compression speed and the number of compression needles per test, significantly affected the needle fracture force of dissolving MNs. Characterization using selected test conditions clearly showed differences in the needle fracture force of dissolving MNs prepared under various conditions. PVA-based MNs were divided into two groups that showed buckling and unbuckling deformation, which occurred at aspect ratios (needle height/base diameter) of 2.8 and 1.8, respectively. The needle fracture force of PVA-based MNs was negatively correlated with an increase in the needle’s aspect ratio. Higher residual water or higher loading of lidocaine hydrochloride significantly decreased the needle fracture force. Therefore, setting appropriate methods and parameters for characterizing the mechanical properties of dissolving MNs should contribute to the development and supply of appropriate products

Zandelisib (ME-401) in Japanese patients with relapsed or refractory indolent non-Hodgkin's lymphoma : an open-label, multicenter, dose-escalation phase 1 study

The selective phosphatidylinositol 3-kinase delta inhibitor zandelisib demonstrated favorable safety and efficacy [objective response rate (ORR) 79%] in patients with B-cell malignancies in a phase 1b study in the US and Switzerland. In this phase 1 dose-escalation study (NCT03985189), 9 Japanese patients with relapsed/refractory indolent non-Hodgkin's lymphoma (R/R iNHL) received zandelisib on a continuous daily schedule (45 or 60 mg) until progressive disease/unacceptable toxicity. No dose-limiting toxicities were observed. The maximum tolerated dose was not reached. At a median follow-up of 17.5 months, Grade >= 3 treatment-emergent adverse events that occurred in 2 or more patients were neutrophil count decreased (55.6%; 5/9) and diarrhea (33.3%; 3/9) Immune-related toxicities, including hepatobiliary disorder, aspartate/alanine aminotransferase increased, diarrhea/colitis, organizing pneumonia, stomatitis, and rash, led to zandelisib discontinuation in 4 patients. The investigator-assessed ORR, based on modified Lugano criteria, was 100%, including 2 complete responses (22.2%; in follicular lymphoma patients receiving 60 mg/day). Median duration of response, progression-free survival, and time to response were 7.9, 11.1, and 1.9 months, respectively. Zandelisib demonstrated a manageable safety profile at 60 mg, the recommended phase 2 dose (RP2D) in Japanese patients. The RP2D resulted in favorable pharmacokinetics and anti-tumor efficacy in Japanese patients with R/R iNHL