SAMP8 マウスの連鎖解析による記憶学習障害候補責任遺伝子の同定

富山大学・富生命博甲第60号・AKBOR MARUF MOHAMMAD・2014/03/21・★論文非公開★富山大

Bioequivalence evaluation of two capsule formulations of amoxicillin in healthy adult male bangladeshi volunteers: A single-dose, randomized, open-label, two-period crossover study

AbstractBackground: Amoxicillin, a semisynthetic penicillin antibiotic, is widely prescribed in Bangladesh due to its extended spectrum and its rapid and extensive oral absorption with good tolerability. Although a number of generic oral formulations of amoxicillin are available in Bangladesh, a study of the bioequivalence and pharmacokinetic properties of these formulations has not yet been conducted in a Bangladeshi population.Objective: The aim of this study was to assess the pharmacokinetic properties and bioequivalence of 2 formulations of amoxicillin 500-mg capsules (test, SK-mox®; reference, Amoxil-Bencard®) using serum data.Methods: This single-dose, randomized, open-label, 2-period crossover study was conducted in healthy male subjects in compliance with the Declaration of Helsinki and International Conference on Harmonisation guidelines. Subjects were assigned to receive the test or the reference drug as a single-dose, 500-mg capsule under fasting conditions after a 1-week washout period. After oral administration, blood samples were collected and analyzed for amoxicillin concentration using a validated high-performance liquid chromatography method. The pharmacokinetic parameters were determined using a noncompartmental method. The formulations were considered bioequivalent if the natural log-transformed ratios of pharmacokinetic parameters were within the predetermined equivalence range of 80% to 125%, according to the US Food and Drug Administration (FDA) requirement.Results: Twenty-four healthy adult male Bangladeshi volunteers (mean [SD] age, 26.92 [3.37] years; age range, 23–34 years; mean [SD] body mass index, 23.O9 [1.58] kg/m2) participated in the study. Using serum data, the values obtained for the test and reference formulations, respectively, were as follows: Cmax, 9.85 (2.73) and 10.63 (2.12) μg/mL; Tmax, 1.29 (0.58) and 1.33 (0.49) hours; and AUC0–12, 27.09 (7.62) and 28.56 (6.30) μg/mL · h−1. No period, sequence, or formulation effects were observed; however, significant variation was found among subjects with regard to AUC0–12 (P < 0.001), AUC0−∞ (P = 0.002), area under the moment curve (AUMC) from 0 to 12 hours (P < 0.001), and AUMC0−∞ (P = 0.017). All CIs for the parameters measured were within the FDA-accepted limits of 80% to 125%.Conclusion: The present study suggests that the test 500-mg amoxicillin capsule was bioequivalent to the reference 500-mg capsule according to the FDA regulatory definition, in this population of healthy adult male Bangladeshi volunteers

Pattern of Adverse Drug Reactions Due to Cancer Chemotherapy in Tertiary Care Teaching Hospital in Bangladesh

ABSTRACT: The objective of the present study was to evaluate the pattern of adverse drug reactions (ADRs) occurring in cancer patients treated with chemotherapy in tertiary care hospitals in Bangladesh. A prospective hospital based study over a period of six month was carried out in the Department of oncology, Bangabandhu Sheikh Mujib Medical University and Dhaka Medical College Hospital. The data were subjected to descriptive analysis. A total of 50 patients having ADRs due to cancer chemotherapy were randomly selected. Adverse drug reactions were mostly occurred in the age group between 41-50 years (26%). Considering socio-economic status of cancer patients married persons (82%) have significantly higher risk than unmarried (18%). Prevalence of breast cancer (20%), cervical cancer (14%) and leukemia (16%) were higher and they were treated mostly by adjuvant chemotherapy (46%) and secondly by chemotherapy (38%) alone. In most cases ADRs were developed in patients receiving alkylating agents (40%) and antimetabolites (40%) as anticancer therapy. The five certain ADRs observed in the current study were nausea, stomatitis, alopecia, myelosuppression and increased ESR level in both male and female patients. Moreover, hematological system was affected severely by alkylating agents and antimetabolites. Similar studies covering more patients from different regions are needed to validate our findings

Therapeutic Potential of Thymoquinone in Glioblastoma Treatment: Targeting Major Gliomagenesis Signaling Pathways

Glioblastoma multiforme (GBM) is one of the most devastating brain tumors with median survival of one year and presents unique challenges to therapy because of its aggressive behavior. Current treatment strategy involves surgery, radiotherapy, immunotherapy, and adjuvant chemotherapy even though optimal management requires a multidisciplinary approach and knowledge of potential complications from both the disease and its treatment. Thymoquinone (TQ), the main bioactive component of Nigella sativa L., has exhibited anticancer effects in numerous preclinical studies. Due to its multitargeting nature, TQ interferes in a wide range of tumorigenic processes and counteract carcinogenesis, malignant growth, invasion, migration, and angiogenesis. TQ can specifically sensitize tumor cells towards conventional cancer treatments and minimize therapy-associated toxic effects in normal cells. Its potential to enter brain via nasal pathway due to volatile nature of TQ adds another advantage in overcoming blood-brain barrier. In this review, we summarized the potential role of TQ in different signaling pathways in GBM that have undergone treatment with standard therapeutic modalities or with TQ. Altogether, we suggest further comprehensive evaluation of TQ in preclinical and clinical level to delineate its implied utility as novel therapeutics to combat the challenges for the treatment of GBM

Polymorphic SERPINA3 prolongs oligomeric state of amyloid beta.

Molecular chaperon SERPINA3 colocalizes with accumulated amyloid peptide in Alzheimer's disease (AD) patient's brain. From the QTL analysis, we narrowed down Serpina3 with two SNPs in senescence-accelerated mouse prone (SAMP) 8 strain. Our study showed SAMP8 type Serpina3 prolonged retention of oligomeric Aβ 42 for longer duration (72 hr) while observing under transmission electron microscope (TEM). From Western blot results, we confirmed presence of Aβ 42 oligomeric forms (trimers, tetramers) were maintained for longer duration only in the presences of SAMP8 type Serpina3. Using SH-SY5Y neuroblastoma cell line, we observed until 36 hr preincubated Aβ 42 with SAMP8 type Serpina3 caused neuronal cell death compared to 12 hr preincubated Aβ 42 with SAMR1 or JF1 type Serpina3 proteins. Similar results were found by extending this study to analyze the effect of polymorphism of SERPINA3 gene of the Japanese SNP database for geriatric research (JG-SNP). We observed that polymorphic SERPINA3 I308T (rs142398813) prolonged toxic oligomeric Aβ 42 forms till 48 hr in comparison to the presence wild type SERPINA3 protein, resulting neuronal cell death. From this study, we first clarified pathogenic regulatory role of polymorphic SERPINA3 in neurodegeneration