Protective effect of aminoguanidine against nephrotoxicity induced by cisplatin in normal rats

The effect of aminoguanidine (AG) on nephrotoxicity induced by cisplatin (CDDP) was investigated. A single dose of CDDP (7.5 mg/kg i.p.) induced nephrotoxicity, manifested biochemically by a significant elevation in serum urea, creatinine and a severe decrease in serum albumin. Moreover, marked increases in kidney weight, urine volume and urinary excretion of albumin were observed. Nephrotoxicity was further confirmed by a significant decrease in glutathione-S-transferase (GST, E.C. 2.5.1.18), glutathione peroxidase (GSH-Px, E.C. 1.11.1.9) and catalase (E.C. 1.11.1.6) and a significant increase in lipid peroxides measured as malondialdhyde (MDA) in kidney homogenates. Administration of AG (100 mg/kg per day p.o.) in drinking water 5 days before and 5 days after CDDP injection produced a significant protection against nephrotoxicity induced by CDDP. The amelioration of nephrotoxicity was evidenced by significant reductions in serum urea and creatinine concentrations. In addition, AG tended to normalize decreased levels of serum albumin. Urine volume, urinary excretions of albumin and GST and kidney weight were significantly decreased. Moreover, AG prevented the rise of MDA and the reduction of GST and GSH-Px activities in the kidney. These results suggest that AG has a protective effect on nephrotoxicity induced by CDDP and it may therefore improve the therapeutic index of CDDP.     

Theoretical studies of biliverdin: energetics of the reduction pathways to bilirubin

Geometries and energies of formation of bilirubin formed by reduction of biliverdin via three meso carbon sites, the , and positions, have been calculated using semiempirical methods. It has been shown that -bilirubin with a ridge-tile conformation forms six intramolecular hydrogen bonds and is the most stable of the three above mentioned positions by at least 22 kcal mol^–1. Reduction pathways for -, - and -bilirubin formations from biliverdin are studied in detail. The roles of loss of conjugation and hydrogen bond formations in stability of different conformers have been discussed. -Bilirubin was fully optimized by using ab initio methods. Fine refinements of calculated results show excellent agreement with experimental results. Electronic supplementary material to this paper can be obtained by using the Springer LINK server located at http://dx.doi.org/10.1007/s00894-002-0078-9.Electronic Supplementary Material available.     

Expression of protective antigen in transgenic plants: a step towards edible vaccine against anthrax

Protective antigen (PA) is the most potent molecule for vaccination against anthrax. In the present study, we have successfully integrated protective antigen gene in nuclear genome of tobacco plants by Agrobacterium mediated leaf-disc transformation method. Expression of protective antigen gene was detected by immunoblot analysis using antisera raised against purified PA. A distinct band of approximately 83kDa lighted up in the protein extracted from transformed plants while there was no such band in untransformed plants. The plant expressed PA showed biological activity just like native PA, which was demonstrated by cytolytic assay on macrophage like cell lines with lethal factor. This study establishes for the first time expression of PA gene in a plant system and thus marks the first milestone towards developing edible vaccine against anthrax.     

Nomega-nitro-L-arginine methylester ameliorates myocardial toxicity induced by doxorubicin

The effects of Nomega-nitro-L-arginine methylester (L-NAME) and L-arginine on cardiotoxicity that is induced by doxorubicin (Dox) were investigated. A single dose of Dox 15 mg/kg i.p. induced cardiotoxicity, manifested biochemically by a significant elevation of serum creatine phosphokinase (CPK) activity [EC 2.7.3.2]. Moreover, cardiotoxicity was further confirmed by a significant increase in lipid peroxides, measured as malon-di-aldehyde (MDA) in cardiac tissue homogenates. The administration of L-NAME 4 mg/kg/d p.o. in drinking water 5 days before and 3 days after the Dox injection significantly ameliorated the cardiotoxic effects of Dox, judged by the improvement in both serum CPK activity and lipid peroxides in the cardiac tissue homogenates. On the other hand, the administration of L-arginine 70 mg/kg/d p.o. did not protect the cardiac tissues against the toxicity that was induced by the Dox treatment. The findings of this study suggest that L-NAME can attenuate the cardiac dysfunction that is produced by the Dox treatment via the mechanism(s), which may involve the inhibition of the nitric oxide (NO) formation. L-NAME may, therefore, be a beneficial remedy for cardiotoxicity that is induced by Dox and can then be used to improve the therapeutic index of Dox.     

Synthesis of some N-galactosides of 3-aryl-5-benzyl (or substituted benzyl)-1,2,4-triazin-6(1H)-/ones or thiones of expected biological activity

The 1-(2,3,4,6-tetra-O-acetyl-beta-D-galactopyranosyl)-3-aryl-5-benzyl (or substituted benzyl)-1,2,4-triazin-6(1H)-/ones or thiones were prepared via galactosidation of 3-aryl-5-benzyl (or substituted benzyl)-1,2,4-triazin-6(1H)-/ones or thiones with 2,3,4,6-tetra-O-acetyl-alpha-D-galactopyranosyl bromide. The structure of the new galactosyl derivatives was based on both spectroscopic and chemical evidences.     

Synthesis of some new 2-alpha-L-arabinopyranosyl-1,2,4-triazines as potential antitumor chemotherapeutics

Synthetic routes towards different 2-alpha-L-arabinopyranosyl-3-thioxo-2,3-dihydro-1,2,4-triazin-5(4H)-/ones or thiones were investigated. Primary human anticancer screening of two selected compounds resulted in an active compound against SF-268 (CNS) cell line.     

Characterisation of two novel types of hexactinomyxon spores (Myxozoa) with subsidiary protrusions on their caudal processes

Two types of hexactinomyxon spores, Hexactinomyxon type 1 nov. and Hexactinomyxon type 2 nov., are reported from freshwater tubificid oligochaetes, Limnodrilus hoffmeisteri and L. udekemianus. Spores are triradially symmetrical and comprise a spore body, style and 6 caudal processes. The caudal processes arise from the division of each of the 3 valve cells into an equal pair of projections at the base of the style. One of each pair is fused conspicuously to its nearest neighbour for the initial 1/5 to 1/4 of their total length. Distally, each process possesses subsidiary protrusions which are irregularly distributed and irregularly shaped extensions of the valve cell. Scanning electron microscopy of Hexactinomyxon type 2 nov. revealed that these protrusions are a seamless extension of the valve cell wall which branch distally, occasionally laterally, and terminate in a distinct bulbous structure; they also form the terminus of each process. The small subunit ribosomal DNA gene (18S) of both hexactinomyxon types was amplified through a nested PCR, then digested with the restriction enzymes Dde I and Hha I. The resultant cleavage patterns suggested the presence of 2 forms. Subsequent partial sequencing of 18S rDNA confirmed the identification of 2 novel types.     

Unexpected inhibition of S-adenosyl-L-homocysteine hydrolase by a guanosine nucleoside

A series of shape-modified flexible nucleosides ('fleximers', 1, 2, and 3) was modeled, synthesized and subsequently assayed against S-adenosyl-L-homocysteine hydrolase (SAHase). No inhibitory activity was observed for the adenosine fleximer, which served as a substrate, but moderate inhibitory activity was exhibited by the guanosine fleximers. This is the first known report of a guanosine nucleoside analogue possessing activity against SAHase.     

Value of Dynamic Susceptibility Contrast Perfusion MRI in the Acute Phase of Transient Global Amnesia

Purpose

Transient global amnesia (TGA) is a transitory, short-lasting neurological disorder characterized by a sudden onset of antero- and retrograde amnesia. Perfusion abnormalities in TGA have been evaluated mainly by use of positron emission tomography (PET) or single-photon emission computed tomography (SPECT). In the present study we explore the value of dynamic susceptibility contrast perfusion-weighted MRI (PWI) in TGA in the acute phase.

Methods

From a MRI report database we identified TGA patients who underwent MRI including PWI in the acute phase and compared these to control subjects. Quantitative perfusion maps (cerebral blood flow (CBF) and volume (CBV)) were generated and analyzed by use of Signal Processing In NMR-Software (SPIN). CBF and CBV values in subcortical brain regions were assessed by use of VOI created in FIRST, a model-based segmentation tool in the Oxford Centre for Functional Magnetic Resonance Imaging of the Brain (FMRIB) Software Library (FSL).

Results

Five TGA patients were included (2 men, 3 women). On PWI, no relevant perfusion alterations were found by visual inspection in TGA patients. Group comparisons for possible differences between TGA patients and control subjects showed significant lower rCBF values bilaterally in the hippocampus, in the left thalamus and globus pallidus as well as bilaterally in the putamen and the left caudate nucleus. Correspondingly, significant lower rCBV values were observed bilaterally in the hippocampus and the putamen as well as in the left caudate nucleus. Group comparisons for possible side differences in rCBF and rCBV values in TGA patients revealed a significant lower rCBV value in the left caudate nucleus.

Conclusions

Mere visual inspection of PWI is not sufficient for the assessment of perfusion changes in TGA in the acute phase. Group comparisons with healthy control subjects might be useful to detect subtle perfusion changes on PWI in TGA patients. However, this should be confirmed in larger data sets and serial PWI examinations.