Age-Related Changes in Aldehyde Dehydrogenase Activity of Rat Brain, Liver, and Heart

Abstract: Aldehyde dehydrogenase (ALDH) activity was measured in brains, livers, and hearts of 23–26-month-old and 3-month-old rats. A significant increase of ALDH activity was found in whole brain of old rats with both acetaldehyde (39%) and propionylaldehyde (15%) used as substrates. In different brain areas of old rats, with acetaldehyde used as substrate, a significant increase of ALDH activity was found in striatum (30–50%) and cerebral cortex (37%). However, no significant difference in ALDH activity was found in livers and hearts of young and old rats. Preliminary experiments showed a significant increase of aldehyde reductase activity (52%) with p -nitrobenzaldehyde used as substrate in whole brain of old rats compared with young rats. The present work indicates that an increase of ALDH activity in brain of old rats may be an adaptive phenomenon.     

The relationship between sister-chromatid exchange and perturbations in DNA replication in mutant EM9 and normal CHO cells

The majority of the high (12-fold elevated) baseline sister-chromatid exchanges (SCEs) that occur in the CHO mutant line EM9 appear to be a consequence of incorporated BrdUrd, and they arise during replication of DNA containing BrdUrd in a template strand. In normal CHO cells the alkaline elution patterns of DNA newly replicated on a BrdUrd-containing template are significantly altered compared with those seen during the replication on an unsubstituted template. The nascent DNA synthesized on such an altered template is delayed in reaching mature size, possibly because replication forks are temporarily blocked at sites occurring randomly along the template. Transient blockage of replication forks may be a prerequisite for SCE. The delay in replication on BrdUrd-substituted templates was greater in EM9 cells than in parental AA8 cells and was also greater in AA8 cells treated with benzamide, an inhibitor of poly(ADPR) polymerase, than in untreated AA8 cells. Under these conditions, treatment with benzamide also produced a 7-fold increase in SCEs in AA8. An EM9-derived revertant line that has a low baseline SCE frequency showed less delay in replication on BrdUrd-substituted templates than did EM9. However, under conditions where the template strand contained CldUrd, which was shown to produce 4-fold more SCEs than BrdUrd in AA8 cells, the replication delay in AA8 was not any greater in the CldUrd-substituted cells. Thus, other factors besides the delay appear to be involved in the production of SCEs by the template lesions resulting from incorporation of the halogen-substituted pyrimidine molecules.     

Germanium toxicity in selected bacterial and yeast strains

Summary The toxicity of germanium dioxide (GeO₂) to 21 bacterial and 13 yeast strains was investigated in liquid broth medium to obtain information on strains tolerant to high (1 to 2 mg/ml) GeO₂ concentrations.Arthrobacter sp. NRC 32005,enterobacter aerogenes NRC 2926,Klebsiella aerogenes NCTC 418 andPseudomonas putida NRC 5019 were tolerant to 1 mg/ml GeO₂.Bacillus sp. RC607 was able to grow in the presence of 2 mg/ml GeO₂ at pH 10 in broth culture. The yeastsCandida guilliermondii, Candida shehatae andPachysolen tannophilus were the most sensitive to GeO₂ as evidenced by their diminished growth rates at a GeO₂ concentration as low as 0.1 mg/ml. None of the yeast strains tested exhibited growth in the presence of 1 mg/ml GeO₂. The high pH of the medium containing germanium may be partially responsible for the growth inhibition of the yeast cultures. Select bacterial cultures previously exposed to 1 mg/ml GeO₂ could tolerate and grow better at 2 mg/ml GeO₂, suggesting the existence of very efficient adaptive mechanisms. The pH of the medium could modulate GeO₂ tolerance and this effect was found to be strain-dependent.     

Experimental determination of wall shear rate in canine carotid arteries perfused in vitro

The mathematical model of Hung (Tsai and Hung, 1984) is employed to determine the wall shear rate acting on canine carotid arteries perfused in vitro. Model equations for pulsatile flow in a deformable vessel are coupled with experimental data of dynamic pressure drop, flow rate, vessel radius and radial wall motion. Derived quantities, e.g. velocity profiles and wall shear, are obtained for vessels exposed to 'normotensive' hemodynamics, 'hypertension' simulations and perfusions in which the compliance of the vessel wall is deliberately altered. Our results indicate that wall shear varies markedly as a function of the hemodynamic environment. The effects of vessel radius vs flow rate on the development of wall shear are also demonstrated. It is found that convective processes correlate with the magnitude of wall shear in the 'hypertension' simulations. The present findings and complementary published data may explain, at least in part, the variations in vessel wall transport and endothelial cell biology we observe as a function of the hemodynamic environment. For example we have documented that the exposure of canine carotids to 'hypertensive' (vs 'normotensive') hemodynamics is associated with an increased flux of lipoproteins (LDL) into the intima and luminal media. Alternations in wall compliance, on the other hand, profoundly influence endothelial shape, orientation and cytoskeletal array.     

Influence of gestation on jugular plasma thyroxine levels in Murrah buffalo and Karan Swiss cows

Plasma samples from 106 pregnant Karan Swiss (Brown Swiss x Sahiwal) cows and 108 Murrah buffalo were tested for thyroxine (T(4)) levels to determine the relationship between the hormonal changes and advancing pregnancy in the two species. All samples were collected within 2 months (January and February) to avoid seasonal interference on T(4) levels. In pregnant cows, the concentration of T(4) increased sharply during the first trimester, reaching a peak at the third month of gestation followed by a gradual decline until the last month of pregnancy. In pregnant buffalo, peripheral plasma T(4) levels fluctuated slightly throughout pregnancy without exhibiting a specific trend. Statistical analysis revealed that the magnitude of T(4) levels was significantly lower in buffalo (P < 0.01) than in the cows throughout pregnancy and that the hormonal patterns of the two species were significantly different (P < 0.05) during gestation. It was hypothesized from this study that T(4) requirements for the fetal buffalo calf may be lower than that for the fetal cattle calf since the buffalo gestation period is a month longer and the metabolic rate lower vis-a-vis the cow.     

Magnetically controlled targeted micro-carrier systems

Magnetically controlled targeted drug delivery systems are aimed at concentrating drugs at a defined target site, with the aid of a magnetic field. This technique has been developed specifically for directing drugs away from the reticuloendothelial system (RES). Literature on this topic suggests that these delivery systems are capable of altering the distribution of chemotherapeutic agents in the body. Hence these delivery devices offer the possibility of improving the therapeutic efficacy of the associated drugs. This paper reviews the work done to date towards the development and evaluation of biodegradable and non-biodegradable magnetic targeted drug delivery systems and outlines their future prospects and limitations in cancer chemotherapy.     

Characterization of a protease with alpha- and beta-fibrinogenase activity from the Western diamondback rattlesnake, Crotalus atrox.

A metalloprotease from the rattlesnake Crotalus atrox venom was isolated and purified from multiple-step chromatographies including anion-exchange chromatography, gel permeation and reversed-phase HPLC. The fraction was shown to be homogeneous as judged by SDS-gel electrophoresis. It also showed a high proteolytic activity against alpha- and beta-chains of fibrinogen molecules. Further characterization of the purified fraction with fibrinogenase activity indicated that it is a single-chain protease with a molecular mass of about 24 kDa and an acidic isoelectric point. It is relatively heat stable up to about 65 degrees C, inhibited by EDTA, beta-mercaptoethanol, but not by phenylmethanesulfonyl fluoride, N alpha-p-tosyl-L-phenylalanine chloromethyl ketone and N alpha-p-tosyl-L-lysine chloromethyl ketone, soybean trypsin inhibitor and aprotinin. Amino acid analysis showed that the enzyme possesses an amino acid composition very similar to some metalloproteases characterized before from the closely related rattlesnake venoms. N-Terminal sequence analysis of the enzyme corroborated some similarity between this enzyme and the reported sequences of these enzymes characterized from the Crotalidae snake family. This study indicated the presence of a novel fibrinogenase (termed Catroxase) with N-terminal sequence different from the metalloprotease with hemorrhagic activity isolated from the same Western diamondback rattlesnake.     

Nucleotide sequence of cDNA for Acacia confusa trypsin inhibitor and implication of post-translation processing.

Synthetic oligonucleotides corresponding to all possible sequences of N-terminal and C-terminal region of Acacia confusa trypsin inhibitor were used to generate ACTI-related sequences using the polymerase chain reaction on the cDNAs encoding ACTI of the seeds of legume, A. confusa. The deduced amino acid sequence agreed with that determined by the peptide analysis except an extra amino acid residue, serine, was found at the junction of A and B chain, which was removed by post-translation processing with specific protease(s). The substrate specificity of the protease(s) was found to cleave at the C-terminal sites of asparagine and serine, which was also shown to be the same case for another plant protein, abrin, isolated from legume, Abrus precatorius.