Histopathologic Characterization of Mifepristone-induced Ovarian Toxicity in Cynomolgus Monkeys.

Mifepristone, which is an orally active synthetic steroid with antiprogesterone activity, is known as an ovarian toxicant. Because the available data regarding the histopathologic characteristics of ovarian toxicity in nonhuman primates are limited, the present study was undertaken in order to investigate detailed histopathologic changes accompanying mifepristone-induced ovarian toxicity and its relationship to changes in menstrual cycle and circulating sex steroid hormone. Twenty mg/kg of mifepristone was orally administered daily to 4 cynomolgus monkeys for 2 months.

Development of the Japanese Version of the Leeds Assessment of the Neuropathic Symptoms and Signs Pain Scale: Diagnostic Utility in a Clinical Setting.

Objective: We aimed to assess the diagnostic utility of the linguistically validated Japanese version of the Leeds Assessment of Neuropathic Symptoms and Signs Pain Scale (LANSS-J) as a screening tool for neuropathic pain in the clinical setting.

Methods: Patients with neuropathic pain or nociceptive pain who were 20 to 85 years of age were included. Sensitivity and specificity using the original cutoff value of 12 were assessed to evaluate the diagnostic utility of the LANSS-J.

Pregabalin for Neuropathic Pain: Why Benefits Could Be Expected for Multiple Pain Conditions.

Background And Objective: Limited research exists to support the extrapolation of the analgesic efficacy of pregabalin from one neuropathic pain condition to another. This retrospective analysis evaluated similarities in the efficacy of pregabalin for treating neuropathic pain associated with post-herpetic neuralgia (PHN), diabetic peripheral neuropathy (DPN), and spinal cord injury (SCI) in a Japanese population, as a basis for considering the extrapolation of these data to other neuropathic pain conditions.

Methods: Data were analysed across pregabalin doses within each pain condition, from three comparable 13- to 16-week, randomized, double-blind, placebo-controlled trials (RCTs) and the corresponding 52-week, open-label extension trials of pregabalin in Japanese patients with PHN, DPN or SCI.

Spontaneous carcinosarcoma originating from the renal pelvis ina rat.

Carcinosarcoma is a rare neoplasm composed of malignant epithelial and stromal elements, and, for rats, carcinosarcomas in the kidney have not been reported. In a long-term study to gather background data, we encountered a spontaneous carcinosarcoma originating from the renal pelvis with metastasis to the lung. At necropsy, a mass was observed in the abdominal cavity, and white nodules were scattered in lung lobes.

Effectiveness of pregabalin for the treatment of chronic low back pain with accompanying lower limb pain (neuropathic component): a non-interventional study in Japan.

Objective: To evaluate the impact of pregabalin on sleep, pain, function, and health status in patients with chronic low back pain with accompanying neuropathic pain (CLBP-NeP) under routine clinical practice.

Methods: This prospective, non-interventional, observational study enrolled Japanese adults (≥18 years) with CLBP-NeP of duration ≥3 months and severity ≥5 on a numerical rating scale (0= no pain, 10= worst possible pain). Treatment was 8 weeks with pregabalin (n=157) or usual care alone (n=174); choice of treatment was determined by the physician.

Psychometric assessment of the Japanese version of the Revised Fibromyalgia Impact Questionnaire: reliability and validity.

Aim: To assess the psychometric properties of the Japanese version of the Revised Fibromyalgia Impact Questionnaire (JFIQR) in fibromyalgia (FM) patients.

Method: The reliability and validity of the JFIQR were assessed using online data collected from Japanese FM patients. Reliability was evaluated based on test-retest reliability results and internal consistency; validity was evaluated on the basis of concurrent and known-group validity.

Granulomatous nephritis consistent with malakoplakia in a cynomolgus monkey.

Malakoplakia is a rare form of chronic granulomatous inflammation in mammals, and usually affects the urinary tract in humans. In this report, we present a case of granulomatous nephritis consistent with malakoplakia in a 4-year-old male cynomolgus monkey. Gross examination showed that the kidney was markedly enlarged and adhered to the surrounding organs.

Brunner's gland lesions in rats induced by a vascular endothelial growth factor receptor inhibitor.

Vascular endothelial growth factor (VEGF) receptor tyrosine kinase (RTK) inhibitors are reported to cause reversible mucosal hyperplasia (adenosis) in the duodenum of rats; however, the pathogenesis is not fully elucidated. Using lenvatinib, a VEGF RTK inhibitor, we characterized the histologic time course of this duodenal change in rats. At 4 weeks, there was degeneration and necrosis of Brunner's gland epithelium accompanied by neutrophil infiltration around the affected glands.

Study for collecting background data on Wistar Hannover [Crl:WI(Han)] rats in general toxicity studies--comparative data to Sprague Dawley rats.

The purpose of the present study was to collect background data from repeated dose toxicity studies in Wistar Hannover [Crl:WI(Han)] (hereafter Wistar Han) rats with dosing periods of 4, 13 and 26 weeks from four safety research facilities of pharmaceutical companies and contract research organizations participating in the International Genetic Standardization (IGS) rat forum supported by Charles River Laboratories Japan, Inc. The data from Wistar Han rats were compared with those from Sprague Dawley Crl:CD(SD) rats. In addition, the effects of restricted feeding of SD rats were also investigated by one facility.

Spontaneous gingivitis related to hair penetration in rats.

Maxillary gingivae from male and female Crl:CD(SD) rats at 12, 16, 21, and 34 weeks of age were examined histologically. The incidence of gingivitis was approximately 40%, with no age or sex predilection, and was most frequent between the first and second molar. Lesions were characterized by acute focal neutrophilic infiltration into the gingival mucosa, occasionally with inflammatory exudate.

Comparison of neuropathy-inducing effects of eribulin mesylate, paclitaxel, and ixabepilone in mice.

Chemotherapy-induced neurotoxicity is a significant problem associated with successful treatment of many cancers. Tubulin is a well-established target of antineoplastic therapy; however, tubulin-targeting agents, such as paclitaxel and the newer epothilones, induce significant neurotoxicity. Eribulin mesylate, a novel microtubule-targeting analogue of the marine natural product halichondrin B, has recently shown antineoplastic activity, with relatively low incidence and severity of neuropathy, in metastatic breast cancer patients.

Histopathological characteristics of luteal hypertrophy induced by ethylene glycol monomethyl ether with a comparison to normal luteal morphology in rats.

Ethylene glycol monomethyl ether (EGME) is a known reproductive toxicant that induces luteal hypertrophy in rat ovaries. In this study, we characterized the histopathological features of corpora lutea (CL) from EGME-treated rats and compared them with normal CL formation and regression. Normally cycling female Sprague-Dawley rats were treated with 5-bromo-2'-deoxyuridine (BrdU) intraperitoneally on the morning of estrus and their ovaries were examined 1 (metestrus), 4 (estrus), 8 (estrus), or 12 (estrus) days later to observe the transition of BrdU-labeled cells within in the CL.

Comparison of the hemagglutination of formalinized American channel catfish (Ictalurus punctatus) erythrocytes between formalinized and live Aeromonas hydrophila isolated from the catfish rearing in Kasumigaura lake in Japan.

Formalinized Aeromonas (A.) hydrophila agglutinated loosely with the formalinized American channel catfish erythrocytes (FACCE), while live A. hydrophila agglutinated tightly with the FACCE.

Ataxia and peripheral nerve hypomyelination in ADAM22-deficient mice.

Background: ADAM22 is a member of the ADAM gene family, but the fact that it is expressed only in the nervous systems makes it unique. ADAM22's sequence similarity to other ADAMs suggests it to be an integrin binder and thus to have a role in cell-cell or cell-matrix interactions. To elucidate the physiological functions of ADAM22, we employed gene targeting to generate ADAM22 knockout mice.

Peripheral Primitive Neuroectodermal Tumor (Peripheral Neuroepithelioma) in a Dog.

A peripherally located primitive neuroectodermal tumor (peripheral PNET) originating in subcutaneous tissues was observed in an adult Beagle. The highly aggressive tumor spread rapidly and metastasized to various organs. The neoplasm was diagnosed as a peripheral PNET on the basis of morphologic and immunohistochemical characteristics such as small round tumor cells, rosette formations, many interdigitating cytoplasmic processes, neurosecretory granules and microtubules, and positive immunohistochemical reactions to neurogenic markers.

Differential age-dependent trophic responses of nodose, sensory, and sympathetic neurons to neurotrophins and GDNF: potencies for neurite extension in explant culture.

The age-dependent trophic responses of sympathetic, sensory, and nodose neurons to the neurotrophins NGF, BDNF, and NT-3 and to glial cell line-derived neurotrophic factor (GDNF) were examined by an explant culture system. Superior cervical ganglia (SCG), dorsal root ganglia (DRG), and nodose ganglia (NG) were removed from rat embryos (E18), neonatals (< or = 1 day old), young adults (3-6 months old), and aged adults (> 24 months old). The ganglia were cultured with and without each neurotrophic factor; the neurite extension and neurite density were then assessed.