Insecticidal Activity and Properties of TIA-230 (Pyraclofos)

TIA-230 (pyraclofos*), O-[1(4-chlorophenyl)-4-pyrazolyl]o-ethyl S-propyl phosphorothiolate showed high insecticidal activity against the Lepidopterous, Coleopterous, Hemipterous, and Dipterous insect pests, such as Spodoptera litura, Mamestra brassiase, Pseudaletia separata, Plutella xylostella, Pieris rapae, Adoxophyes orana, Chilo suppressalis, Aulacophora femoralis, Phyllotreta striolata, Phaedon brassicae, Henosepilachna vigintioctopunctata, Lissorhoptrus orizophilus, Aphis gossypii, Aphis glycines, Myzus persicae, Hyalopterus pruni, Musca domestica and Culex pipiens molestus. The compound also showed a high acaricidal activity against Tetranychus urticae, Tetranychus kanzawai and Rhizoglyphus echinopus and showed a high nematicidal activity against Meloidogyne incognita. Residual activity by foliar spray of TIA-230 was shown to be higher than those of prothiophos, acephate, methomyl, demethylvinphos, chlorpyrifos-methl, dicofol, fenbutatin oxide and cyhexatin. In field tests, the sprays of 0.017% and 0.035% solution of TIA-230 (wettable powder) were highly effective in controlling the damage to cabbage by Spodoptera litura, Mamestra Brassiase, Plutella xylostella, Pieris rapae and Myzus persicae.Originating text in Japanese.Citation: Sato, Yasuo, Kono, Yoshiaki, Nagano, Masayoshi, Manabe, Yukiaki, Oguchi, Hiroaki, Yamamoto, Yasuhiro. (1985). Insecticidal Activity and Properties of TIA-230 (Pyraclofos). Journal of the Takeda Research Laboratories, 44(42433), 255-266

Semiquantitative Analysis by Scanning Electron Microscopy of Cochlear Hair Cell Damage by Ototoxic Drugs

The ototoxicity of cisplatin and carboplatin in the organ of Corti of the guinea pig was evaluated semiquantitatively. Damage of the stereocilia of outer hair cells (OHCs) observed by scanning electron microscopy (SEM) was classified into normal, grade 1 (10-50% loss of stereocilia), grade 2 (less than 50% remaining stereocilia), or grade 3 (missing stereocilia). The OHCs observed by light microscopy (LM) were classified as remaining or missing cells. Fifty OHCs of each row in the middle part of each turn of the cochlea were counted (a total of 150 cells per turn). Guinea pigs were administered 5 mg/kg of cisplatin or 50 mg/kg of carboplatin intraperitoneally for three consecutive days. In groups 1 and 2, in which both cochleae were fixed in 2.5% glutaraldehyde and 1% osmium tetroxide (OsO4) and observed by SEM, the percentages of damage of the OHC stereocilia were similar in each cochlear turn bilaterally. In group 3, the right cochleae were fixed in OsO4 and observed by phase contrast microscopy as surface preparations. Left cochleae were submitted for SEM observation. Missing and grade 3 cells were observed at similar percentages in each row of each turn. In group 4, succinate dehydrogenase staining was performed in the right cochleae and observed by LM. The degree of damage in the right cochleae was compared with that of the left cochleae which was observed by SEM. On average, the mean numbers of missing cells and cells showing grade 3 damage were similar in each row of each turn. From these similarities of evaluation of ototoxicity at LM and SEM levels, it was concluded that semiquantitative analysis by SEM only is appropriate for the assessment of ototoxicity

Unusual progression of herpes simplex encephalitis with basal ganglia and extensive white matter involvement

We report a 51-year old male with herpes simplex encephalitis (HSE) showing unusual progression and magnetic resonance (MR) findings. The initial neurological manifestation of intractable focal seizure with low-grade fever persisted for three days, and rapidly coma, myoclonic status, and respiratory failure with high-grade fever emerged thereafter. The polymerase chain reaction (PCR) result of cerebrospinal fluid (CSF) was positive for HSV-1 DNA. In the early stage, MR images (MRI) were normal. On subsequent MR diffusion-weighted (DW) and fluid-attenuated inversion recovery (FLAIR) images, high-intensity areas first appeared in the left frontal cortex, which was purely extra-temporal involvement, and extended into the basal ganglia, then the white matter, which are relatively spared in HSE. Antiviral therapy and immunosuppressive therapy did not suppress the progression of HSE, and finally severe cerebral edema developed into cerebral herniation, which required emergency decompressive craniectomy. Histological examination of a biopsy specimen of the white matter detected perivascular infiltration and destruction of basic structure, which confirmed non specific inflammatory change without obvious edema or demyelination. The present case shows both MR and pathological findings in the white matter in the acute stage of HSE

Thirteen-week Intravenous Toxicity Study of a Novel Humanized Anti-Human Death Receptor 5 Monoclonal Antibody, CS-1008, in Cynomolgus Monkeys

CS-1008, a humanized monoclonal antibody that is agonistic to human death receptor 5, was intravenously administered to cynomolgus monkeys twice a week for 13 weeks at 3 different dose levels (5, 15 and 42 mg/kg) in order to evaluate its potential toxicity. A control group received phosphate buffered saline containing 0.01% polysorbate 80. Each of the 4 groups consisted of 3 male and 3 female cynomolgus monkeys. No animal in any group died during the dosing period. No toxic changes in clinical signs, food consumption, body weight, electrocardiography, ophthalmology, urinalysis, hematology, blood chemistry, gross pathology, organ weights or histopathology were noted in any group during the dosing period. In the toxicokinetic analysis, the values for the maximum concentration of CS-1008 in plasma and the area under the curve generally increased with increasing dose. No clear differences in the toxicokinetic parameters or profiles were observed between the sexes. Development of anti-CS-1008 antibodies was not detected in any sample. The no-observed adverse-effect level (NOAEL) of CS-1008 in cynomolgus monkeys under the conditions of this study was concluded to be 42 mg/kg in both sexes, when administered intravenously twice a week for 13 weeks. This study supports the development of CS-1008 as a therapeutic biopharmaceutical

Two cases of possible neuro-Sweet disease with meningoencephalitis as the initial manifestation

We report 2 cases that were considered to be neuro-Sweet disease. They initially manifested with meningoencephalitis and no skin lesions, and rapidly improved with corticosteroid therapy. In both cases, patients complained of meningitic symptoms such as fever and headache, and HLA-B54 and -Cw1 turned out to be positive over the clinical course. Cerebrospinal fluid analysis showed increased levels of lymphocytes and protein. In case #1, fluid-attenuated inversion recovery (FLAIR), magnetic resonance imaging (MRI) and diffusion-weighted images (DWI) showed high-intensity signals in the right dorsal medulla oblongata, bilateral dorsal midbrain, and left thalamus. In case #2, FLAIR and DWI showed high-intensity signals in the bilateral cerebellar cortex and left caudate nucleus. Symptoms and MRI images were markedly improved in both cases after corticosteroid pulse therapy. According to published diagnostic criteria, these 2 cases were considered possible neuro-Sweet disease. These cases suggest that the combination of meningoencephalitis and HLA specificity is important to consider the possibility of neuro-Sweet disease, even without skin lesions

Early detachment of neuromuscular junction proteins in ALS mice with SODG93A mutation

The transgenic animals with mutant copper/zinc superoxide dismutase (SOD1) DNA develop paralytic motor neuron disease resembling human amyotrophic lateral sclerosis (ALS) patients and are commonly used as models for ALS. In the transgenic (Tg) mice with the G93A mutation of the human SOD1 gene SOD1G93A mice), the loss of ventral root axons and the synapses between the muscles and the motor neurons suggested that the motor neuron degeneration might proceed in a dying-back degeneration pattern. To reveal the relationship between axonal degeneration and the progression of the muscle atrophy in the SOD1G93A mice, we investigated the status of the neuromuscular junction along the disease progression. As a presynaptic or postsynaptic marker of neuromuscular junction (NMJ), anti-synaptic vesicle protein 2 (anti-SV2) antibody and α-bungarotoxin (α-BuTX) were chosen in this study and, as a marker of synaptic cleft, anti-agrin antibody was chosen in this study. In the immunohistochemistry of α-BuTX and anti-SV2 antibody, the percentages of double positive NMJs among α-BuTX single positive were decreased in Tg mice through time from ten weeks. The number of postsynaptic acethylcholine receptor (AChR) clusters did not decrease in Tg mice even at the end stage. Immunohistochemistry of α-BuTX and anti-agrin antibody revealed that the increase of immunopositive area of anti-agrin antibody around the muscle fiber in Tg mice from ten weeks of age. In this study, we revealed that the detachment of nerve terminals started at ten weeks in Tg mice. The levels of AChR did not change throughout 5–20 weeks of age in both groups of mice, and AChR remains clustering at NMJs, suggesting that the muscle abnormality is the result of detachment of nerve terminals

A Case of Miller-Fisher Syndrome with Syndrome of Inappropriate Secretion of Antidiuretic Hormone

We report a 72-year-old woman with Miller-Fisher syndrome (MFS) with syndrome of inappropriate secretion of antidiuretic hormone (SIADH). She developed diplopia and unsteady gait a week after an upper respiratory infection. Neurologic examination revealed ophthalmoplegia, ataxia, symmetrical weakness, numbness, and areflexia. She underwent intravenous immunoglobulin therapy. Her serum sodium concentration decreased to 119 mEq/L on day 12. She had low plasma osmolarity (254 mosm/kg), high urine osmolarity (457 mosm/kg), and high urine sodium level (73 mEq/L), while the blood level of antidiuretic hormone was normal. Anti-GD1b immunoglobulin G (IgG), -GQ1b IgG, -GT1a IgG, and -Gal-C IgM antibodies were positive. We diagnosed her with MFS overlapping with SIADH. Four weeks after onset, her symptoms recovered. The elevation of anti-GD1b, -GQ1b, and -GT1a antibodies that recognize disialosyl residue may be pathologically related to SIADH

Thrombolysis with Low-Dose Tissue Plasminogen Activator 3–4.5 h After Acute Ischemic Stroke in Five Hospital Groups in Japan

Clinical data from Japan on the safety and real-world outcomes of alteplase (tPA) thrombolysis in the extended therapeutic window are lacking. The aim of this study was to assess the safety and real-world outcomes of tPA administered within 3-4.5 h of stroke onset. The study comprised consecutive acute ischemic stroke patients (n = 177) admitted across five hospitals between September 2012 and August 2014. Patients received intravenous tPA within <3 or 3-4.5 h of stroke onset. Endovascular therapy was used for tPA-refractory patients. In the 3-4.5 h subgroup (31.6 % of patients), tPA was started 85 min later than the <3 h group (220 vs. 135 min, respectively). However, outcome measures were not significantly different between the <3 and 3-4.5 h subgroups for recanalization rate (67.8 vs. 57.1 %), symptomatic intracerebral hemorrhage (2.5 vs. 3.6 %), modified Rankin Scale score of 0-1 at 3 months (36.0 vs. 23.4 %), and mortality (6.9 vs. 8.3 %). We present data from 2005 to 2012 using a therapeutic window <3 h showing comparable results. tPA following endovascular therapy with recanalization might be superior to tPA only with recanalization (81.0 vs. 59.1 %). Compared with administration within 3 h of ischemic stroke onset, tPA administration within 3-4.5 h of ischemic stroke onset in real-world stroke emergency settings at multiple sites in Japan is as safe and has the same outcomes

Life and dietary factors of incidence in immediate allergic response against foods in 18 months old infants

Using the method of questionnaires, we surveyed 2,114 infants aged 18 months old to know how life and dietary styles are related to incidence of immediate allergic response against foods. 12.0% in the surveyed children was found as having immediate allergic response against foods, and 91.5% of them omitted foods including hen's egg (73.2%), foods containing hen's egg (46.5%), cow's milk (31.6%), foods containing cow's milk (24.6%), and sea foods (15.8%). Life and dietary factors of incidence in immediate allergic response against foods was found in the surveyed infants who were first time nursing for their parents, or who was breast-feeding baby without any bottle-feeding. Early weaning before 4 months old was not found as a trigger of incidence of immediate allergic response against foods. These results suggested that some factors were present in life and dietary styles to cause immediate allergic response against foods in 18 months old infants