The effect of bisphenol A and chlorinated derivatives of bisphenol A on the level of serum vitellogenin in Japanese medaka (Oryzias latipes).

2,2-bis (4-hydroxyphenyl) propane or Bisphenol A (BPA), has been reported to behave as an endocrine disrupter below acute toxic levels, and is widely present in the water environment. Although BPA is easily chlorinated, very little is reported on the effect of chlorinated BPA to the aquatic organisms. In this study, the estrogenic activities of BPA and its chlorinated derivatives were evaluated by the induction of vitellogenin (VTG) in the serum of mature male Japanese medaka. In addition, the effect of sodium hypochlorite on the decomposition of BPA was tested. The relative potencies of estrogenic activities of chlorinated BPA descended in the order 3,3'-diCIBPA>BPA> or =3-CIBPA>3,3',5-triCIBPA, and no estrogenic activity was observed in 3,3',5,5'-tetraCIBPA. Lowest Observed Effect Concentration (LOEC) and No Observed Effect Concentration (NOEC) for both 3-CIBPA and 3,3'-diCIBPA were 500 microg/L and 200 microg/L, respectively. LOEC for 3,3',5-triCIBPA was >500 microg/L. When BPA was reacted with sodium hypochlorite (24 hours; residual chlorine at 1 ppm), however, complete decomposition of BPA and its chlorinated derivatives was observed. The decrease in BPA and its chlorinated derivatives paralleled the decrease in estrogenic potency evaluated by the induction of vitellogenin (VTG) in the serum of mature male Japanese medaka.     

Effects of intracerebroventricular injection of histamine on memory deficits induced by hippocampal lesions in rats

This review was conducted to evaluate the long-term prognosis of children responding to vigabatrin by examining the incidence of increased seizure frequency, loss of efficacy, and appearance of new seizures in a cohort of 196 children (mean age, 68.2 months; range, 2 months to 19 years) with drug-resistant epilepsy, who had received vigabatrin as add-on treatment in clinical trials. The results indicate that an increase in seizure frequency was uncommon, occurring in only 10% of children with highly drug-resistant epilepsy and that it usually appears shortly after the initiation of treatment. It was clearly not dose-dependent and most often occurred in patients with nonprogressive myoclonic epilepsy. No specific seizure type was specially involved and usually the problem reversed on discontinuing vigabatrin. Loss of efficacy was also uncommon (12% of patients), and again no specific seizure type was found to be associated. Epilepsy syndrome does seem to be a better predictor of loss of efficacy because it occurred most often in symptomatic generalized epilepsies and cryptogenic infantile spasms. A total of 21 patients (11%) developed genuinely new types of seizures. Fifteen of these patients developed new partial seizures that had little impact on the patients' overall clinical improvement. The new partial seizures were better tolerated than the initial seizure type which in most cases had disappeared. Approximately 3% of patients experienced new generalized seizures that aggravated their initial condition. These occurred most often in patients with nonprogressive myoclonic epilepsy; therefore vigabatrin should be used with particular caution in such patients.     

Effect of an active metabolite of the antiallergic agent tazanolast on histamine release from rat mast cells

WP-871 (3'-(1H-tetrazol-5-yl)oxanilic acid monohydrate, CAS 114607-46-4) is a monohydrate of a main active metabolite of tazanolast (butyl 3'-(1H-tetrazol-5-yl) oxanilate, CAS 82989-25-1), an orally active antiallergic drug. WP-871 inhibited dose-dependently compound 48/80-induced histamine release from rat peritoneal mast cells. In a similar dose range, WP-871 was effective in inhibiting compound 48/80-induced 45Ca uptake into mast cells from extracellular medium and compound 48/80-induced translocation of protein kinase C from the cytosol to the membrane fraction of mast cells. WP-871 also inhibited inositol trisphosphate production but did not exhibit a direct inhibitory effect on phospholipase C in mast cells. WP-871 caused no increase in cAMP content in mast cells. These results suggest that WP-871 may inhibit histamine release mainly by preventing the increase in intracellular Ca2+ concentration, which is a critical event in signal transduction leading to histamine release in mast cells.     

Competitive inhibition of delta8-tetrahydrocannabinol and its active metabolites for cannabinoid receptor binding

In vitro binding characteristics of delta8-tetrahydrocannabinol (delta8-THC) and its metabolites, 11-hydroxy-delta8-THC (11-OH-delta8-THC) and 11-oxo-delta8-THC, as well as an inactive metabolite, delta8-THC-11-oic acid, as a cannabinoid receptor site from bovine cortex were examined using the specific agonist [3H]CP-55940. 11-OH-delta8-THC and 11-oxo-delta8-THC strongly inhibited the specific binding of [3H]CP-55940. The Ki values of 11-OH-delta8-THC and 11-oxo-delta8-THC for the specific binding of [3H]CP-55940 were 52 and 143 nM, respectively, whereas that of delta8-THC-11-oic acid was 917 nM. Scatchard plot analyses indicated that 11-OH-delta8-THC and 11-oxo-delta8-THC caused a significant increase in the apparent KD value without changing the apparent Bmax. These results reveal that active metabolites of delta8-THC also competitively bind to the cannabinoid receptor as agonists.     

(+)-SKF-10,047 and dextromethorphan ameliorate conditioned fear stress via dopaminergic systems linked to phenytoin-regulated sigma 1 sites

OBJECTIVE: To assess the dynamic range of radiological images captured with a personal computer frame-grabbing system coupled to an X-ray fluoroscopy machine. METHODS: A 386DX-40 MHz, IBM compatible, computer with an SVGA monochrome graphics subsystem and a 387 co-processor, installed with a Screen Machine frame-grabber and controlled by a program specially written was used. Various systems were examined and the observer's perceptions of the results assessed. RESULTS: The dynamic range available to an ordinary X-ray fluoroscopy system was found to be restricted to about 750 mV. Similar measurements showed that the dynamic range was always restricted to 3/4-1/2 of the full available signal because of a high value of the dark voltage of the TV camera's target on all seven systems measured. The dynamic range of the computer-frame grabber system was found to be significantly wider than the Image Intensifier-TV camera chain but, surprisingly, it was affected by the type of file format used for image storing on disk. Clinical images from a barium meal examination as well as CT images captured after optimisation of the frame-grabber were found to contain large quantities of noise in the first two least significant bit planes making them redundant and limiting the grey levels needed for image display to less than 64. This number was also less than the 80 grey levels that could be discriminated by the human eye on the computer monitor. CONCLUSIONS: It was concluded that 6 bit digitisation would have been sufficient for image capture. The advantages of the wider dynamic range of the frame-grabber and the processing capabilities of the computer were tested for the possibility of improving the perception of detail. However, the results were negative. The limiting spatial resolution measured with a variable density bar pattern at all magnifications was about 0.4 lp/mm lower from that measured directly on the fluoroscopic screen. A detail perception test had the same result. The perception success was significantly lower with the digital images at all but the highest of the exposure rates and despite the use of image processing filters.     

Use of Methionine Alkylation to Prepare Cationic and Zwitterionic Block Copolypeptide Vesicles

We have developed a facile method for preparation of ionic copolypeptide vesicles that requires no protecting groups or expensive components. We prepared amphiphilic copolypeptides containing segments of water-soluble methionine sulfonium residues. These were derived by aqueous phase, direct alkylation of a fully hydrophobic precursor diblock copolypeptide, poly(L-methionine)₆₅-block-poly(L-leucine_0.5-stat-L-phenylalanine_0.5)₂₀ (M₆₅[L_0.5/F_0.5]₂₀), with simple alkylating reagents. Methylation of M₆₅(L_0.5/F_0.5)₂₀ gave the cationic methyl-methionine sulfonium derivative M^M₆₅(L_0.5/F_0.5)₂₀, and carboxymethylation gave the zwitterionic carboxymethyl-methionine sulfonium derivative M^C₆₅(L_0.5/F_0.5)₂₀. Assembly of M^M₆₅(L_0.5/F_0.5)₂₀ or M^C₆₅(L_0.5/F_0.5)₂₀ in water gave rise to vesicles with average diameters of a few microns, which could then be extruded to nanoscale diameters. While the cationic M^M-based vesicles were found to be cytotoxic, the zwitterionic M^C-based vesicles were found to possess minimal cytotoxicity.     

Mechanisms of central antitussives

This paper provides an overview of our current understanding of the central mechanisms of cough and antitussives. Systemic administration of 8-OH-DPAT at doses of 0.1 and 0.3 mg/kg, i.p. markedly reduced the number of coughs in rats in a dose-dependent manner. The antitussive effect of 8-OH-DPAT, dihydrocodeine and dextromethorphan significantly was reduced by pretreatment with methysergide, but not ketanserin. Therefore, it is possible to speculate that the 5-HT1 receptors, in particular the 5-HT1A receptors, may be more important than others with respect to the effect of antitussive drugs. DAMGO, a selective mu-opioid receptor agonist, and U-50,488H, a highly selective kappa-opioid receptor agonist, have potent antitussive effects when administered either i.c. or i.p. However, we did not observe a cough-depressant effect of DPDPE, a selective delta-opioid receptor agonist. These results indicate that the antitussive effects of opioids are mediated predominantly by mu- and kappa-opioid receptors. On the other hand, naloxonazine, a selective mu 1-opioid receptor antagonist, had no effect on the antitussive effects associated with i.c.v. DAMGO. These results indicate that mu 2-rather than mu 1-opioid receptors are involved in mu-opioid receptor-induced antitussive effects. Antitussive effects of dextromethorphan and noscapine were significantly and dose-dependently reduced by pretreatment with rimcazole, a specific antagonist of sigma sites. However, rimcazole did not have a significant effect on the antitussive effect of morphine. These results suggest that sigma sites may be involved in the antitussive mechanism of non-narcotic antitussive drugs.     

Separation of proteins and viruses using two-phase aqueous micellar systems

We discuss the utilization of a novel two-phase aqueous nonionic micellar system for the purification and concentration of biomolecules, such as proteins and viruses, by liquid-liquid extraction. The nonionic surfactant n-decyl tetra(ethylene oxide), C10E4, phase separates in water into two coexisting aqueous micellar phases by increasing temperature. The mild interactions of the C10E4 nonionic surfactant with biomolecules, combined with the high water content of the two coexisting micellar phases, suggest the potential utility of two-phase aqueous C10E4 micellar systems for the purification and concentration of biomolecules. In this paper, we review our recent experimental and theoretical studies involving the partitioning of several water-soluble proteins, including cytochrome c. soybean trypsin inhibitor, ovalbumin, bovine serum albumin, and catalase, in the two-phase aqueous C10E4 micellar system. In addition, we present results of our preliminary experimental investigation on the partitioning of bacteriophages, including phiX174, P22, and T4.     

Low-noise current optoelectronic integrated receiver with internalequalizer for gigabit-per-second long-wavelength optical communications

An equalizer, which is essential in order to improve the sensitivity of receiver optoelectronic integrated circuits (OEICs) at a gigabit-per-second data rate, has been monolithically integrated on an InP substrate with a p-i-n photodiode and a high-impedance high-electron-mobility-transistor (HEMT) amplifier. The receiver operated up to 1.6 Gb/s and showed low noise current characteristics. The minimum noise current is less than 4 pA/√Hz. The sensitivity calculated from the noise current characteristics is -28.4 dBm for 1.6-Gb/s signals. The receiver chip, which was assembled on a ceramic mount, exhibited a sensitivity of -30.4 dBm at 1.2 Gb/s and 1.3-μm wavelength. The performance is as good as those of receiver OEICs with an external equalizer and sufficient for practical use in gigabit-per-second optical communication system     

Modification of morphine-induced place preference by diabetes

The effects of diabetes on morphine-induced place preference in mice were examined. Morphine caused dose-related place preference in both diabetic and non-diabetic mice. This morphine-induced place preference in diabetic mice was greater than that in non-diabetic mice. The morphine (5 mg/kg)-induced place preference in both diabetic and non-diabetic mice was significantly antagonized by pretreatment with beta-funaltrexamine, a selective mu-opioid receptor antagonist, but not with naloxonazine, a selective mu1-opioid receptor antagonist. The morphine (5 mg/kg)-induced place preference in non-diabetic mice was attenuated by pretreatment with either naltriben, a selective delta2-opioid receptor antagonist, or 7-benzylidenenaltrexone. a selective delta1-opioid receptor antagonist. Moreover, the morphine (10 mg/kg)-induced place preference in non-diabetic mice was antagonized by pretreatment with 7-benzylidenenaltrexone (0.7 mg/kg). Although 7-benzylidenenaltrexone had no effect on the place preference induced by 5 mg/kg morphine in diabetic mice, it reduced the place preference induced by 3 mg/kg morphine. Furthermore, the morphine (5 mg/kg)-induced place preference in diabetic mice was significantly antagonized by co-pretreatment with beta-funaltrexamine (10 mg/kg) and 7-benzylidenenaltrexone (0.7 mg/kg). 2-Methyl-4a alpha-(3-hydroxyphenyl)- 1,2,3,4,4a,5,12,12a alpha-octahydroquinolino[2,3,3-g]isoquinoline (TAN-67), a non-peptide delta-opioid receptor agonist, produced place preference in diabetic, but not in non-diabetic mice. These results support the hypothesis that the morphine-induced place preference is mainly mediated through the activation of the mu2-opioid receptor. Furthermore, the enhancement of the morphine-induced place preference in diabetic mice may be due to the up-regulation of delta-opioid receptor-mediated functions.