Quantitative structure-activity studies of substituted benzyl chrysanthemates: 4. Physicochemical properties and the rate of progress of the knockdown symptom induced in house flies

A procedure to evaluate the knockdown activity of pyrethroids against house flies in which metabolic factors could be eliminated as far as possible was established. With piperonyl butoxide and NIA 16388 as the inhibitors of oxidative and hydrolytic metabolism, respectively, the “intrinsic” knockdown potencies of 22 substituted benzyl (1R)-trans-chrysanthemates and related compounds were determined 2.5–3 hr after topical application to house flies. From the intrinsic knockdown potency and the rate of progress of the knockdown symptom from the earliest stage of intoxication, a “penetration” rate constant was estimated by first-order kinetics using a two-compartment model. The rate constant was correlated quantitatively with the hydrophobic parameter of the molecule. The lower the hydrophobicity, the higher the rate constant within the range of compounds used in this study.     

The use of frozen cells in the microtitre serum neutralization test for infectious bovine rhinotracheitis.

Some parameters of the microtitre serum neutralization test were examined when using bovine fetal kidney cells derived from stocks stored in liquid nitrogen. In replicate tests with one serum there was no significant difference (p greater than 0.05) between titres calculated on the basis of cytopathic effect when either two or four wells were used per serum dilution. Also, there was no significant difference between titres calculated on the basis of a cell staining method when either two or four wells were used per serum dilution. When titres obtained by the 2-well-cytopathic effect method were compared with those obtained by the 2-well-stain method differences were not significantly different and it was concluded that the latter method using frozen cells constituted a practical and reproducible test. No significant titre variation occurred in cells serially passaged after having been frozen, or in cells derived from five different fetuses. Titres of sera from 41 cattle conformed to a log normal distribution pattern.     

Canine PHA-stimulated adherent cell enhance interferon-gamma production and proliferation of autologous peripheral blood mononuclear cells

Dendritic cells are specialized antigen‐presenting cells with immuno‐modulating functions that are attractive for clinical applications for cancer immunotherapy. This study examined immunostimulatory functions of phytohemagglutinin (PHA)‐stimulated adherent cells (PHA‐Ad cells) from peripheral blood mononuclear cells (PBMCs) in dogs. PHA‐Ad cells enhanced interferon‐γ from autologous PBMC in vitro. PHA‐Ad cells also stimulated antigen‐independent proliferation of peripheral blood lymphocytes. These results suggest that PHA‐Ad cells from PBMC possess a stimulatory function to evoke anti‐tumour immunity and that they demonstrate potential for therapeutic applications in dogs.     

Anticholinergic effects of artemisinin, an antimalarial drug, in isolated guinea pig heart preparations

Concern has been growing about the cardiac toxicity of antimalarial drugs. Artemisinin, a unique type of antimalarial drug originating from a Chinese medicinal plant, has minimal adverse effects, but it has been reported to inhibit delayed rectifier potassium current, a voltage-gated potassium current. However, no studies have been published concerning the effect of artemisinin on ligand-gated potassium currents. Therefore, in the present study, we examined the influence of artemisinin on the acetylcholine receptor-operated potassium current (IK.ACh), a ligand-gated potassium current, in guinea pig atrial myocytes using a patch clamp technique. Artemisinin (1 to 300 microM) inhibited I(K.ACh) induced by extracellular application of both carbachol (1 microM) and adenosine (10 microM) and that induced by intracellular loading of GTPgammaS (100 microM) in a concentration-dependent manner. Artemisinin inhibited carbachol-induced, adenosine-induced, and GTPgammaS-activated IK.ACh within almost the same concentration range. In left atria, artemisinin (1 to 100 microM) partially reversed the shortening of action potential duration induced by carbachol in a concentration-dependent manner. Carbachol-induced negative inotropic action in left atria was also inhibited by artemisinin (10 to 300 microM). In conclusion, we suggest that the anticholinergic action of artemisinin is mediated through inhibition of IK.ACh via inhibition of the muscarinic potassium channel and/or associated GTP-binding proteins.     

Expression profiles of perforin,granzyme B and granulysin genes during the estrous cycle and gestation in the bovine endometrium

The conceptus is susceptible to destruction by maternal cytotoxic lymphocytes, which have cytotoxic potential. Therefore, it is expected that mechanisms for regulating cytotoxic lymphocytes exist, but little is known about the expression of cytotoxic genes in the endometrium. In the present study, we examined the spatial and temporal expression patterns of the cytotoxic genes perforin, granzyme B, and granulysin during the estrous cycle and gestation in the bovine endometrium. Endometrial tissues were collected from cows during the estrous cycle and gestation. The gene expression patterns of the three cytotoxic genes were examined using quantitative polymerase chain reaction and in situ hybridization, and cytotoxic lymphocyte subsets were characterized using immunohistochemistry. During mid‐ to late gestation in the intercaruncular (ICAR), granulysin expression was significantly increased, and a large number of granulysin‐expressing cells were localized in the luminal epithelium. Perforin and granzyme B displayed similar expression profiles and were highly expressed in the peri‐implantation endometrium, but few cells expressing these genes were found in the endometrial stroma. In conclusion, these findings suggest that in the ICAR epithelium granulysin may play important roles in the establishment and maintenance of gestation during normal pregnancy.     

Shallow dynamic overshoot and energetic deep rupture in the 2011 Mw 9.0 Tohoku-Oki earthquake

Strong spatial variation of rupture characteristics in the moment magnitude (M(w)) 9.0 Tohoku-Oki megathrust earthquake controlled both the strength of shaking and the size of the tsunami that followed. Finite-source imaging reveals that the rupture consisted of a small initial phase, deep rupture for up to 40 seconds, extensive shallow rupture at 60 to 70 seconds, and continuing deep rupture lasting more than 100 seconds. A combination of a shallow dipping fault and a compliant hanging wall may have enabled large shallow slip near the trench. Normal faulting aftershocks in the area of high slip suggest dynamic overshoot on the fault. Despite prodigious total slip, shallower parts of the rupture weakly radiated at high frequencies, whereas deeper parts of the rupture radiated strongly at high frequencies.