Correlation between the pharmacokinetics of oxindanac and inhibition of serum thromboxane B2 in calves

The pharmacokinetics and pharmacodynamics of the non-steroidal antiinflammatory drug, oxindanac, were assessed simultaneously in calves after intravenous (i.v.) administration at dose rates of 0.5, 1, 2, 4 and 8 mg/kg. Plasma pharmacokinetic data were fitted to either two or three compartment open models. The elimination t1/2 was constant in the dose range 0.5 to 4 mg/kg (20.2-22.8 h) and shorter at 8 mg/kg (14.7 h). The pharmacodynamics of oxindanac were assessed by its inhibition of serum TxB2, an index of platelet cyclo-oxygenase activity. Plots of total plasma oxindanac concentration vs. inhibition of serum TxB2 fitted in all cases a sigmoidal Emax equation. There were no significant differences in the estimates for ED50 (1.6-1.9 micrograms/ml), Hill constant (1.3-2.7) or Emax between the doses used in the in vivo studies or when blood was spiked with oxindanac in vitro. Plots of inhibition of serum TxB2 vs. time were prepared from the pharmacokinetic model equations in each calf in combination with a single sigmoidal Emax plot generated in vitro. These data were not significantly different from the results produced in vivo. It is concluded that oxindanac causes reversible inhibition of platelet cyclo-oxygenase in calves. Its inhibition of serum TxB2 can be predicted from total plasma drug concentration, as described by a multicompartmental model, and sigmoidal Emax enzyme kinetics. It was not necessary to take into account factors such as drug equilibration between plasma and its target site, free vs. total drug concentration or chirality. This simple model may be useful for predicting the pharmacodynamics of oxindanac in other species.     

Correlation between the retention of cardiac glycosides in reversed-phase high-performance liquid chromatography with a diphenylsilyl stationary phase, the structure of their molecules and their biological activity

The separation of mixtures of cardiac glycosides by reversed-phase high-performance liquid chromatography on silica gel with chemically grafted diphenylsilyl groups using water-ethanol as the eluent was carried out. It is shown that the configuration and conformation of the glycoside molecules, and the hydrophilic properties of their aglycones and glycones, influence the separation. The hydrophilic properties of the aglycones are more important than those of the glycones. The glycosides with more hydrophilic aglycones have higher biological activity. This is probably related to the easier transport of these glycosides to the receptor.     

Correlation between the structure and heat treatment of powder particles

Conclusions It was established that nickel (carbonyl), iron, copper, titanium, and zinc powders scatter light according to laws similar to the laws of diffuse scattering.Nearly all the curves of light scattering in suspensions of the powders investigated exhibit inward troughs in angle ranges from 70 to 110°. This is ascribed to the effect of a Rayleigh component of scattering, which is linked with the presence in powders of particles with sizes smaller than the light wavelength.It was found that a correlation exists between the conditions of heat treatment of powders and the light-scattering and reflecting characteristics of the latter.Differences in light scattering by powders are interpreted as a manifestation of differences in the surface condition of the powder particles. In particular, it is claimed that, the closer the character of light scattering and reflection corresponds to the laws of diffuse scattering and reflection, the rougher is the particle surface relief.Translated from Poroshkovaya Metallurgiya, No. 8 (80), pp. 21–26, August, 1969.     

Correlation between the structure and heat treatment of powder particles

Conclusions It has been established that nickel (carbonyl), copper, iron, titanium, and zinc powders reflect light according to laws close to those of diffuse reflection; the intensity of reflection from annealed powders is greater than that from unannealed powders.In an optical investigation of zinc powder (at an angle of incidence of 60° to a plane specimen), reflection of a mixed type is observed. The maximum found in the region of an observation angle of 60° indicates the existence of a mirror component in the reflected light energy.A parallel study of the defectiveness of powders based on measuring the broadening of x-ray diffraction lines demonstrated that the two types of defectiveness (surface and volume) can change either in conformity with or independently of each other.Translated from Poroshkovaya Metallurgiya, No. 10 (82), pp. 12–16, October, 1969.     

Eukaryotic expression of recombinant biglycan. Post-translational processing and the importance of secondary structure for biological activity

Biglycan is a small chondroitin sulfate proteoglycan found in many tissues and is structurally related to decorin, fibromodulin, and lumican. The biological function of biglycan is poorly understood, although several studies have indicated interaction with other extracellular matrix components. We have initiated studies of structural and functional domains of biglycan by transient eukaryotic expression using the vaccinia virus/T7 bacteriophage expression system. A recombinant vaccinia virus, vBGN4 encoding the mature biglycan core protein as a polyhistidine fusion protein under control of the T7 phage promoter was expressed in HT-1080 cells and UMR106 cells. The structure of the recombinant biglycan secreted by these cells was defined by analyzing molecules labeled in the presence of [35S]sulfate, [3H]glucosamine, and [35S]methionine. Glycoforms of biglycan were separated by imidazole gradient elution, under non-denaturing conditions, and comprised: a large proteoglycan form substituted with two chondroitin sulfate chains of molecular mass approximately 34 kDa (HT-1080 cells) or approximately 40 kDa (UMR106 cells); a small proteoglycan form substituted with two chondroitin sulfate chains with a median molecular mass approximately 28 kDa; and a core protein form secreted devoid of glycosaminoglycan chains. All the glycoforms were substituted with two N-linked oligosaccharides, and the disaccharide composition of the two glycosaminoglycan populations were identical. Approximately 70% of the recombinant biglycan secreted by HT-1080 cells was substituted with chondroitin sulfate chains, whereas about 50% of the biglycan expressed by UMR106 cells was substituted with chondroitin sulfate chains. Infection with vBGN4 in both HT-1080 and UMR106 cells resulted in the production of approximately 10 mg of biglycan/10(9) cells per 24 h. The native recombinant biglycan was shown to bind to collagen type V and the complement protein, C1q. However, when the secondary structure of recombinant biglycan was disrupted by exposure to 4 M guanidine hydrochloride, the affinity for collagen type V was dramatically reduced. These data demonstrate the importance of secondary structure to the function of this small proteoglycan.     

Antibodies to the food mutagens, 2-amino-1-methyl-6-phenylimidazo [4,5-b]pyridine and 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline: useful for immunoassay and immunoaffinity chromatography of biological samples

Monoclonal mouse IgG1 and IgG3 antibodies were developed to the food mutagens, 2-amino-1-methyl-6-phenylimidazo[4,5-b] pyridine (PhIP) and 2-amino-3,4,8-trimethylimidazo[4,4-f] quinoxaline (4,8-DiMeIQx) in order to make specific and sensitive detection and purification systems suitable for biological samples. The antibodies were developed with the strategy that cross-reaction with analogues modified in the N2-position was desirable. Competitive enzyme-linked immunosorbent assays (ELISA) with 50% inhibition by 0.4-6 pmol food mutagen were developed. The epitopes recognized by the antibodies have been characterized by ELISA using 52 synthetic analogues and metabolites of PhIP, 4,8-DiMeIQx, and other food mutagens. One of the anti-PhIP antibodies only recognizes PhIP and those PhIP-analogues which have minor modifications in the N2-amino group, whereas the other, 7B7-1, is less stringent and also recognizes several other modified metabolites, including bulky adducts at the N2-amino group e.g. the major guanine and deoxyguanosine adducts isolated from PhIP-modified DNA. The antibodies to DiMeIQx also recognize the food mutagens 2-amino-3,4-dimethylimidazo[4,5-f]quinoxaline (4-MeIQx), 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (8-MeIQx), and the corresponding quinolines (4-MeIQ and 8-MeIQ). Two of these antibodies only bind analogues with minor modifications in the free amino group, whereas analogues with major modifications in this position, including a deoxyguanosine adduct, react with the third antibody. Urine samples and faecal extracts from 3H-PhIP or 2-14C-DiMeIQx dosed rats were analysed by these ELISA assays, and high correlations between radioactivity and response in the ELISA assays were observed. Urine samples and faecal extracts from 3H-PhIP-dosed rats were purified on an affinity column containing the less stringent anti-PhIP antibody, 7B7-1. The affinity column was found by high performance liquid chromatography (HPLC) analysis to concentrate exclusively labelled material. This affinity column also bound PhIP-related materials from dilute samples of acid hydrolysed PhIP-DNA with high efficiency. Only approximately 40% of the 4,8-DiMeIQx related materials found in dilute acid hydrolysed samples of 4,8-DiMeIQx-DNA was bound by an affinity column containing the less stringent anti-4,8-DiMeIQx antibody, 2C5-1. We conclude that our anti-PhIP and anti-DiMeIQx antibodies can be used to determine the presence of these food mutagens and some of their activated or conjugated metabolites in complex biological samples.     

Minimum structure of diapause hormone required for biological activity

Diapause hormone is a 24-amino acid peptide amide, and its C-terminal penta-peptide amide structure of FGPRL-NH2 is believed to be essential for biological activity. The penta-peptide amide, the shorter peptide amides, and their derivatives and analogs were prepared to determine the minimal structure for biological activity. The C-terminal amide group of penta-peptide amide was not replaced with the other functional groups, but Gly, the 4th amino acid from the C terminal, could be substituted with an other amino acid while maintaining the biological activity. The shorter peptide amide, PRL-NH2, possessed low but significant activity, indicating the minimum structure of diapause hormone. By modifying its N-terminal, the aromatic ring of Phe is shown to enhance the activity of PRL-NH2.     

Insect growth regulators. XXV. Chemical approach to the correlation of dynamic structure and biological activity of juvenile hormone analogues

On the basis of flexibility of the carbon skeleton of a juvenoid molecule, an analysis of its steric properties required to induce a biological effect in insects Dysdercus cingulatus and Tenebrio molitor, is presented. Steric analyses of "branched" juvenoids and some derivatives of farnesoic acid differing in position of the double bonds, are also described.     

Alleviation effects of Ce~(3 ) on inhibition of photochemical activity caused by linolenic acid in spinach chloroplast

Linolenic acid has great effects on the structure and function of chloroplast. The function of Ce3 on the improvement of chloro-plast photoreduction activity and oxygen evolution damaged by linolenic acid in spinach by in vitro investigation was studied. Results showed that adding Ce3 to the linolenic acid treated chloroplast could greatly decrease the reduction linolenic acid exerted on the whole chain electron transport rate and the photoreduction activity of photosystem II (PSII) and photosystem I (PSI) as well as the oxygen evolution rate of chloroplast. It indicated that Ce3 had the ability to relieve the inhibition of the photochemical reaction of chloroplast caused by lino-lenic acid to some extent.     

Correlation between endoscopic severity and the clinical activity index in ulcerative colitis

OBJECTIVE: The aim of this study was to examine the relationship between a new activity index and the endoscopic severity assessed by sigmoidoscopy in patients with ulcerative colitis. METHODS: We evaluated the sigmoidoscopic severity and Activity Index (AI) in 37 patients with distal colitis, 23 with left-sided colitis, and 36 with total colitis, in which the severity was divided into three categories: grade 1 = mildly active, grade 2 = moderately active, and grade 3 = severely active. We examined the relationship between the AI or clinical parameters and the endoscopic severity in all 96 cases. RESULTS: The AI was found to be significantly correlated with the degree of sigmoidoscopic activity in all cases, as well as in those with distal colitis, left-sided colitis, or total colitis. When patients with both grade 1 sigmoidoscopic activity and AI values of less than 150 were regarded to have mild colitis and patients with either grade 2 or grade 3 sigmoidoscopic activity and AI values of more than 150 were regarded to have moderate or severe colitis, 10 of 37 (27%) in the distal colitis, one of 23 (4.3%) in the left-sided colitis, and four of 36 (11.1%) in the total colitis groups were thus misclassified regarding the distinction between mild colitis and moderate or severe colitis. Three of four patients with severity of grade 1, indicating AI values of more than 150, had total colitis, whereas the remaining one had left-sided colitis. On the other hand, 10 of 11 patients with severity of grades 2 or 3 with AI values of less than 150 had distal colonic involvement. When the endoscopic activity was equivalent, the highest mean AI values occurred in total colitis whereas the lowest mean AI values were found in distal colitis. CONCLUSIONS: The AI well reflects the sigmoidoscopic activity. High AI values with a low sigmoidoscopic severity are thus considered to reflect extensive involvement, whereas a high sigmoidoscopic severity with low AI values is thought to indicate the involvement of the distal colon.     

Correlation between head direction cell activity and spatial behavior on a radial arm maze.

This study assessed the activity of head direction (HD) cells during performance of a spatial reference memory task on a radial arm maze. Rats were trained to select a maze arm located in a constant position in relation to a salient extramaze visual landmark. HD cell discharge properties remained relatively stable across task acquisition in most rats. Following acquisition, rotation of the landmark by 90° or 180° usually led to a corresponding shift in the maze arm selected and the HD cell's preferred firing direction. When the cell's preferred direction did not shift, rats usually selected the wrong arm. HD cell activity was not influenced by the rat's approach to the goal, reward consumption, or exit from the reward area. This demonstration of landmark control over behavior and the cell's preferred direction supports the hypothesis that HD cells contribute to an absolute representation of the environment that can be used to guide spatial behavior. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Mg(2+)-mediated binding of 6-substituted quinolones to DNA: relevance to biological activity

The interaction of a number of novel 6-substituted quinolone derivatives with DNA in the presence/absence of magnesium ions has been investigated by fluorometric techniques. The drug-single-stranded nucleic acid interaction is invariantly mediated by the metal ion. In all cases optimal complex formation is found at physiological Mg2+ concentration. From titrations at different [Mg2+] the binding constant for the ternary drug-DNA-Mg2+ complex (KT) has been evaluated. Interestingly, a good relationship is found between KT and gyrase poisoning activity of the test quinolones (IC50), which confirms that DNA-affinity of the quinolone, modulated by Mg2+, plays an important role in poisoning the cleavable gyrase-DNA complex and, consequently, in eliciting antibacterial activity in this family of drugs. The results obtained with different 6-substituted compounds supports the idea that position 6 of the drug, besides playing a pharmacokinetic role, is involved in recognition of the enzyme pocket. Our data do not support a mechanism of action based upon quinolone intercalation into B-DNA.     

Behavioral inhibition and electrodermal activity during deception.

Tested the assumption that the act of inhibiting ongoing behavior requires physiological work. In a guilty knowledge test (GKT) paradigm, 30 undergraduates were induced to attempt to deceive the experimenter on 2 separate occasions while electrodermal activity was measured. For 20 of the 30 Ss, overt behaviors (changes in eye movement and facial expression) were recorded during the 2nd GKT. Results indicate that the incidence of these behaviors decreased during Ss' deceptive responses. This behavioral inhibition coincided with increases in skin conductance level. In addition to suggesting nonverbal correlates of deception, findings indicate that long-term behavioral inhibition may be a factor in psychosomatic disease. (14 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)