Structure-activity relationships of 6-fluoroquinazolines: dual-acting compounds with inhibitory activities toward both TNF-alpha production and T cell proliferation

We synthesized various 6-fluoro-7-(1-piperazino)quinazolines based on the structure of 1 and evaluated their inhibitory activities toward both TNF-alpha production and T cell proliferation responses. Among these compounds, 7a, having the 3,4-(methylenedioxy)phenyl moiety at the C(4)-position of the quinazoline ring, showed both inhibitory activities. Furthermore, the oral treatment with 7a exhibited an anti-inflammatory effect in rats with adjuvant arthritis as well as an inhibitory activity toward LPS-induced TNF-alpha production.     

Inhibitory Synapses on Pacemaker Neurons in the Heart Ganglion of a Stomatopod, Squilla oratoria

The pacemaker neurons of the Squilla heart ganglion are innervated from the CNS through three pairs of extrinsic nerves. One of them, the α-nerve, is inhibitory to the heart beat. The effect of α-nerve stimulation on the pacemaker potential was examined with intracellular electrodes. Without extrinsic nerve stimulation the membrane potential of the pacemaker cell fluctuated spontaneously. On application of a tetanic train of stimuli to the α-nerve the membrane potential was shifted and fixed to a steady level, which with K₂SO₄-filled electrodes was near the peak of hyperpolarization after a spontaneous burst, but was less negative with KCl-filled electrodes. The shift of the membrane potential was due to the summated IPSP's. By changing the level of the membrane potential with injection of the polarizing current the IPSP could be reversed in sign, and the size of the IPSP was linearly correlated with the membrane potential level. During inhibition the membrane conductance increased. The increase depended on divalent cation concentrations in the outside medium. In Ca-rich saline the IPSP was greatly enhanced. In Mg-rich saline it was suppressed. The amplitude of antidromic spikes was reduced during inhibition especially when the spike frequency was high.     

Dietary magnesium increases calcium absorption of ovine small intestine in vivo and in vitro

The purpose of this study was to investigate whether or not an increase in dietary Mg intake increases Ca absorption in the ovine gastrointestinal tract. In an in vivo experiment, an increase in the infused MgCl2 level (0.0, 25.0 and 75.0 mg Mg x kg BW(-1) x day(-1) with 75.0 mg Ca x kg BW(-1) x day(-1) as CaCl2) into the rumen for ten days significantly decreased fecal excretion but increased urinary excretion (P < 0.05) of Ca in five castrated male sheep. Apparent Ca absorption tended to increase (P = 0.067) whilst the retention and plasma concentration of Ca were not changed. In an in vitro experiment with isolated segments from the rumen, upper jejunum, cecum and upper colon under the presence of an electrochemical gradient, the mucosal to serosal Ca flux rate was significantly greater in the presence of 60.0 mM as compared with 1.2 mM MgCl2 (P < 0.05). From these results, we conclude that the mucosal Mg has the ability to increase the Ca absorption in the gastrointestinal tract in sheep when the dietary Mg level is raised.     

Responses of pituitary and adrenal medulla to insulin-induced hypoglycemia in patients with anorexia nervosa

The responses of pituitary and adrenomedullary hormones to insulin-induced hypoglycemia were studied in 10 patients with anorexia nervosa and 7 control females of comparable age. The increases in plasma GH and PRL were significantly smaller in the patients, while the responses of GH to arginine and of PRL to TRH were indistinguishable. Plasma cortisol attained similar peak levels in both groups with higher basal levels and smaller increments in the patients. The response of plasma epinephrine was markedly lower in the patients, although urinary epinephrine showed similar increase in both groups. These results suggest the possibility that the process by which hypoglycemic stimulus causes pituitary and adrenomedullary hormone secretion is deranged in patients with anorexia nervosa.     

Differentiation of rat pheochromocytoma cells by fomitellic acids, specific DNA polymerase inhibitors

Fomitellic acid (FA) A and B are specific inhibitors of DNA polymerase alpha and beta. They showed cytotoxicity against rat pheochromocytoma cells (PC-12 cells) in a concentration-dependent manner. However, after PC-12 cells were cultivated with low concentrations of FAs, the cells extended neurites in greater degree similar to the cells cultivated with nerve growth factor. Another DNA polymerase alpha inhibitor, aphidicolin, also induced neurite outgrowth. Furthermore, PC-12 cells were strongly immunostained with anti-alpha-tubulin or anti-tau antibody after the treatment with FAs. These results suggest that weak inhibition of DNA polymerase activity induces the neurite outgrowth in PC-12 cells.     

Distribution of Fusarium wilt of Bambara nut (Vigna subterranea (L.) Verdc.) in farmers’ fields’ of Busia County in Western Kenya and its management using farmyard manure

A study was carried out to determine Fusarium wilt distribution in Bambara nut farmers’ fields and its management using farm yard manure (FYM). Four villages in Busia County were purposively sampled for the study. The data generated were subjected to analysis of variance and treatment means separated by least significant difference test. Fusarium wilt incidence in the fields ranged from 14.63 to 43.56%. In the greenhouse, FYM reduced the disease incidence by 10.2% and severity by 9.5% on the black landrace and 1.9 and 12.8%, respectively, on the red landrace. In the field, FYM reduced disease incidence by 9.1% and severity by 6.9% on the black landrace and 10.4 and 10.4%, respectively, on the red landrace. Farm yard manure had the lowest area under disease progress curve irrespective of the landrace. The study confirmed the presence of the pathogen in the fields and the ability to manage the disease using FYM.     

Mate preference in males of the cabbage butterfly, Pieris rapae crucivora, changes seasonally with the change in female UV color

We initially investigated whether females of the cabbage butterfly, Pieris rapae crucivora, exhibit a seasonal change in ultraviolet wing color, which is a key stimulus for mate recognition by conspecific males, and whether and how a seasonal change affects the mating behavior of the males. We found that female UV wing color changes seasonally, the color being more pronounced in summer than in spring or autumn. We also demonstrated that male mate preference changes seasonally, concomitantly with the change in female UV color. Specifically, males appearing in summer exhibit a mating preference for summer-form females over spring- or autumn-form females, while those appearing in spring or autumn exhibit no seasonal preference, thereby facilitating more effective mate location. Our results suggest that this field of study will require more strictly controlled experimental investigation in which the seasonal change in UV color is considered when UV-influenced mating behaviors such as mate choice are investigated.     

Development of an ELISA system for tick-borne encephalitis virus infection in rodents

Tick-borne encephalitis (TBE) virus causes severe encephalitis with serious sequelae in humans. An epizootiological survey of wild rodents is effective to detect TBE virus-endemic areas; however, limited serological diagnostic methods are available to detect anti-TBE virus antibodies in wild rodents. In this study, ELISAs for the detection of rodent antibodies against the TBE virus were developed using two recombinant proteins, domain III of the E protein (EdIII) and subviral particles (SPs), as the antigens. As compared with the neutralization test, the ELISA using EdIII had 77.1% sensitivity and 80.0% specificity, and the ELISA using SPs had 91.4% sensitivity and 100% specificity. Furthermore, when the ELISAs were applied to the epizootiological survey in the TBE virus-endemic area, both of the ELISAs was able to detect wild rodents with TBE virus-specific antibodies. This is the first study to show that ELISAs using recombinant antigens can be safe and useful in the detection of TBE virus-infected wild rodents in epizootiological research.