Stimulation of poly(ADP-ribose) synthesis by free radicals in C3H10T1/2 cells: relationship with NAD metabolism and DNA breakage

We have studied the effect of H2O2 and O2- produced by xanthine and xanthine oxidase on NAD catabolism, poly(ADP-ribose) synthesis, and production of DNA single-strand breaks in C3H10T1/2 cells. The results show a correlation between the induction of DNA single-strand breaks, the decrease of NAD pool, and the accumulation of polymer. New techniques, based on affinity chromatography and reversed-phase high pressure liquid chromatography, have allowed an accurate determination of polymer contents and showed a 20-fold stimulation of polymer biosynthesis induced by active oxygen species. Inhibition experiments performed with 3-aminobenzamide have shown that the decrease in NAD levels after exposure of cells to active oxygen species was caused by stimulation of poly(ADP-ribosyl)ation and of another cellular process.     

Long-Term Effect of Forskolin on the Activation of Adenylyl Cyclase in Astrocytes

Abstract: Long-term (48-h) forskolin treatment of rat astroglial cells led to a slight decrease (30–40%) in the response to isoproterenol, vasoactive-intestinal peptide, guanyl 5'-(βγ-imido)diphosphate, guanosine 5'- O -(3-thiotriphosphate) [GTP(S)], and AIF₄⁻ in crude membrane fractions. In contrast, the acute stimulatory effect of forskolin was increased by 1.25–1.5-fold. These two opposite effects of forskolin were mediated by a cyclic AMP-dependent mechanism. No changes in G_sα, G_iα, or Gβ protein levels could be determined by immunoblotting using specific antisera. No significant differences were observed in the ability of G proteins extracted from control and forskolin-treated cells to reconstitute a full adenylyl cyclase activity in membranes from S49 cyc⁻ cells, lacking G_sα protein. G_sα proteins were detected in two pools of membranes, one in the heavy sucrose fractions and the other in light sucrose fractions. Forskolin treatment of the cells shifted G_sα protein toward the light-density membranes. We did not find any significant change in the distribution of adenylyl cyclase. In contrast to the decreased stimulation of adenylyl cyclase activity by agonists acting via G_sα, observed in the crude membrane fraction, the responses of adenylyl cyclase to forskolin as well as to GTP(S) were increased in the purified plasma membrane fractions. These results may indicate that sensitization of the catalyst appears to be the dominant component in the astroglial cell response to long-term treatment by forskolin.     

Influence of the route of administration on the pharmacokinetics of pirprofen enantiomers in the rat

The pharmacokinetics of the enantiomers of the non-steroidal anti-inflammatory drug pirprofen were studied in male Sprague-Dawley rats after oral and intravenous (iv) doses of the racemate. No significant differences were detected between the enantiomers after oral or iv dosing in t_½, Vd, or ∑Xu. However, the R:S area under the plasma concentration (AUC) ratio after oral doses (0.92 ± 0.13) was slightly but significantly lower than after matching iv doses (1.05 ± 0.036). The absolute bioavailability of the active S-enantiomer (78.5%) after oral doses was higher than the inactive R-enantiomer (69.3%). The plasma protein binding of both enantiomers was saturable over a fivefold range of plasma concentrations. At higher plasma concentrations, the S-enantiomer was less bound than the R-enantiomer. In an in vitro experiment using everted rat jejunum, no chiral inversion was discernible. The dependency of the AUC ratio of the enantiomers on the route of administration may be due to stereoselective first-pass metabolism. © 1993 Wiley-Liss, Inc.     

Improved high-performance liquid chromatographic assay method for the enantiomers of ibuprofen

A rapid, inexpensive and sensitive high-performance liquid chromatographic method for the quantitation of ibuprofen enantiomers from a variety of biological fluids is reported. This method uses a commercially available internal standard and has significantly less interference from endogenous co-extracted solutes than do previously reported methods. The method involves the acid extraction of drug and internal standard [(±)-fenoprofen] from the biological fluid with isooctane—isopropanol (95:5) followed by evaporation and derivatization with enthylchloroformate and R-(+)-α-phenylethylamine. Excellent linearity was observed between the peak-area ratio and enantiomer concentration (r > 0.99) over a concentration range of 0.25–50 μg/ml. This method is suitable for the quantitation of ibuprofen from single-dose pharmacokinetic studies involving either rats or humans.     

Flow Behavior of Native Corn and Potato Starch Granules in Aqueous Suspensions

The flow behavior of native corn and potato starch granule suspensions prepared in a concentrated sucrose solution has been investigated. Measurements were performed using a rotational rheometer with a concentric cylinder geometry. Starch suspensions were dilute to semi-concentrated (1 % to 25 % by volume). Shear and dynamic viscosity were measured by shear flow and dynamic oscillatory testing at 20, 50 and 80 °C. The starch suspensions exhibited essentially Newtonian behavior at all solid contents, although at higher solid volume fractions there was evidence of slight shear thickening. The relative viscosity of suspensions increased with increasing starch granule content, and the data conformed well to Maron-Pierce’s equation. An increase in maximum packing fraction and gravitational depletion of the starch granules with increasing temperature resulted in lower relative viscosities at higher temperatures. Also, the relative viscosities of potato starch granule suspensions with bigger, more oval and anisometric particles were lower than those of corn starch suspensions where granules were closer to sphericity but were angular in shape. Oscillatory shear testing results showed the presence of viscoelastic properties at intermediate solid volume fractions at low frequencies; in addition, the relative shear viscosity was higher than the relative dynamic viscosity, probably due to the formation of shear-induced structures during the shear flow test.     

Effects of Probiotic Bacteria Bacillus on Growth Performance,Digestive Enzyme Activity,and Hematological Parameters of Asian Sea Bass,Lates calcarifer (Bloch)

Probiotics and Antimicrobial Proteins - This study was conducted to evaluate different doses of two species of Bacillus (Bacillus licheniformis and Bacillus subtilis), on growth parameters,...     

Spring Time and Autumn Time Toxic Effects of Copper (II), 3-(2-Furyl) Prop-2-Enal Semicarbazone and [CuCl2(FASC)2] Complex in Mice

In vitro, 3-(2-furyl) prop-2-enal semicarbazone-copper (II) complex [CuCl₂(FASC)₂] presents antimitotic effects. In this work we studied the in vivo seasonal toxic effects in male Swiss mice of CuCl₂, and FASC and the [CuCl₂(FASC)₂] complex. In spring, one injection of CuCl₂8.10^-2 mmol killed 16% of animals after 24 h. Cupric chloride lethal dose was up to 64.10^-2 mmol with 100% mice dead after 24 h. FASC was well tolerated from 0.65 to 1.3 mmol. The complex was 100% lethal with 48.10^-2 mmol. In autumn, mice were more sensitive to CuCl₂ and to the complex with lethal doses up to 32.10^-2 mmol and 8.10^-2 mmol, respectively. On the other hand, FASC was well tolerated. It is concluded that the in vivo toxic effects of CuCl₂ and [CuCl₂(FASC)₂] complex are quite different in spring and autumn.     

Homozygosity mapping in consanguineous families reveals extreme heterogeneity of non-syndromic autosomal recessive mental retardation and identifies 8 novel gene loci

Autosomal recessive gene defects are arguably the most important, but least studied genetic causes of severe cognitive dysfunction. Homozygosity mapping in 78 consanguineous Iranian families with nonsyndromic autosomal recessive mental retardation (NS-ARMR) has enabled us to determine the chromosomal localization of at least 8 novel gene loci for this condition. Our data suggest that in the Iranian population NS-ARMR is very heterogeneous, and they argue against the existence of frequent gene defects that account for more than a few percent of the cases. Mohammad Mahdi Motazacker and Masoud Garshasbi have contributed equally to this work.     

Discordance in diagnosis of osteoporosis using spine and hip bone densitometry

BACKGROUND: Diagnostic discordance for osteoporosis is the observation that the T-score of an individual patient varies from one key measurement site to another, falling into two different diagnostic categories identified by the World Health Organization (WHO) classification system. This study was conducted to evaluate the presence and risk factors for this phenomenon in a large sample of Iranian population. METHODS: Demographic data, anthropometric measurements, and risk factors for osteoporosis were derived from a database on 4229 patients referred to a community-based outpatient osteoporosis testing center from 2000 to 2003. Dual-energy X-ray absorptiometry (DXA) was performed on L1-L4 lumbar spine and total hip for all cases. Minor discordance was defined as present when the difference between two sites was no more than one WHO diagnostic class. Major discordance was present when one site is osteoporotic and the other is normal. Subjects with incomplete data were excluded. RESULTS: In 4188 participants (3848 female, mean age 53.4 +/- 11.8 years), major discordance, minor discordance, and concordance of T-scores were seen in 2.7%, 38.9% and 58.3%, respectively. In multivariate logistic regression analysis, older age, menopause, obesity, and belated menopause were recognized as risk factors and hormone replacement therapy as a protective factor against T-score discordance. CONCLUSION: The high prevalence of T-score discordance may lead to problems in interpretation of the densitometry results for some patients. This phenomenon should be regarded as a real and prevalent finding and physicians should develop a particular strategy approaching to these patients.