Sporotrichosis Successfully Treated with Terbinafine and Potassium Iodide: Case Report and Review of the Literature

Sporotrichosis is rare in Turkey. We report a 40-year-old woman who had subcutaneous sporotrichosis caused by sporothrix schenckii that was successfully treated with terbinafine (250 mg, twice a day) for a period of 6 months. She received a saturated solution of potassium iodide orally for two months. Terbinafine and potassium iodide are suggested to be the agents of choice for treatment of subcutaneous sporotrichosis.     

On the origin of genomic adaptation at high temperature for prokaryotic organisms

For a long time, the central issue of evolutionary genomics was to find out the adaptive strategy of nucleic acid molecules of various microorganisms having different optimal growth temperatures (Topt). Long-standing controversies exist regarding the correlations between genomic G+C content and Topt, and this debate has not been yet settled. We address this problem by considering the fact that adaptation to growth at high temperature requires a coordinated set of evolutionary changes affecting: (i) nucleic acid thermostability and (ii) stability of codon-anticodon interactions. In the present study, we analyzed 16 prokaryotic genomes having intermediate G+C content and widely varying optimal growth temperatures. Results show that elevated growth temperature imposes selective constraints not only on nucleic acid level but also affects the stability of codon-anticodon interaction. We observed a decrease in the frequency of SSC and SSG codons with the increase in Topt to avoid the formation of side-by-side GC base pairs in the codon-anticodon interaction, thereby making it impossible for a genome to increase GC composition uniformly through the whole coding sequence. Thus, we suggest that any attempt to obtain a generalized relation between genomic GC composition and optimal growth temperature would hardly evolve any satisfactory result.     

Correlations between genomic GC levels and optimal growth temperatures: some comments

Regarding the existence of any specific correlation between optimal growth temperature and genomic GC levels, Musto et al. [FEBS Lett. 573 (2004) 73] have recently performed analysis on 20 prokaryotic families and showed that in most of the families there exists a positive correlation between these two parameters. On the basis of these results they claimed that optimal growth temperature is one of the factors that influence genomic GC composition in prokaryotes. In a subsequent article, Marashi and Ghalanbor [Biochem. Biophys. Res. Commun. 325 (2004) 381] have demonstrated that the correlation values change substantially when very few points in some of the families were excluded from the data set of Musto et al. [FEBS Lett. 573 (2004) 73]. But Marashi and Ghalanbor have not provided any reason behind this. The points excluded by Marashi and Ghalanbor are actually the outliers in the data set, which strongly affect the correlation coefficients. But the presence of outliers in large data set hardly had any effect on the correlation values. Marashi and Ghalanbor have excluded points from only those families that have small sample sizes and observed a substantial change in correlation coefficient values. Therefore, we argue that any conclusion drawn for a small sample size having outliers is always questionable. Although Musto's approach is a novel one, but to make any generalization one needs to be careful about the flawlessness in the data set.     

Implication of proprotein convertases in the processing and spread of severe acute respiratory syndrome coronavirus

Severe acute respiratory syndrome coronavirus (SARS-CoV) is the etiological agent of SARS. Analysis of SARS-CoV spike glycoprotein (S) using recombinant plasmid and virus infections demonstrated that the S-precursor (proS) exists as a approximately 190 kDa endoplasmic reticulum form and a approximately 210 kDa Golgi-modified form. ProS is subsequently processed into two C-terminal proteins of approximately 110 and approximately 80 kDa. The membrane-bound proprotein convertases (PCs) furin, PC7 or PC5B enhanced the production of the approximately 80 kDa protein. In agreement, proS processing, cytopathic effects, and viral titers were enhanced in recombinant Vero E6 cells overexpressing furin, PC7 or PC5B. The convertase inhibitor dec-RVKR-cmk significantly reduced proS cleavage and viral titers of SARS-CoV infected cells. In addition, inhibition of processing by dec-RVKR-cmk completely abrogated the virus-induced cellular cytopathicity. A fluorogenically quenched synthetic peptide encompassing Arg(761) of the spike glycoprotein was efficiently cleaved by furin and the cleavage was inhibited by EDTA and dec-RVKR-cmk. Taken together, our data indicate that furin or PC-mediated processing plays a critical role in SARS-CoV spread and cytopathicity, and inhibitors of the PCs represent potential therapeutic anti-SARS-CoV agents.     

Design and synthesis of a novel enediynyl pentapeptide with predominantly beta-turn structural motif and its potential as a fluorescence-based chemosensor

A novel enediynyl pentapeptide in the protected form 1 was synthesized and characterized. It exists predominantly in beta-turn structural motif as revealed by variable temperature NMR and CD spectroscopy. In the presence of transition metal ions and gold nanoparticles, the fluorescence intensity of the peptide got enhanced with remarkable quantum yield with the Z-enediynyl -amino acid acting as a fluorophoric reporter. The interesting photophysical behaviors with alkali and alkaline earth metal ions are also reported.     

Photoisomerization as a trigger for Bergman cyclization: synthesis and reactivity of azoenediynes

Cyclic enediynes 1a and 2a containing stable E-azo moiety (azoenediynes) have been synthesized. These compounds upon irradiation with long wavelength UV isomerize to the Z-compounds 1b and 2b, which can be thermally reisomerized to the Z compounds. Reactivity studies toward BC using DSC predictably indicate higher reactivity for the Z-isomers. Our studies may provide a novel way to modulate the reactivity of enediynes under thermal or photochemical conditions.     

On invariants of a 2-D proteome map derived from neighborhood graphs

We consider the problem of the construction of invariants for characterization of 2-D maps, such as 2-D proteome maps, 2-D NMR spectral maps, etc., that in addition to facilitating cataloguing such maps, can be used for comparison of maps and numerical evaluation of their degree of similarity. A novel approach, based on the concept that the nearest neighborhood of points (spots) on a map are sufficiently flexible to allow one not only to vary the number of points used for characterization of the map but also the density of information on their relative positions, is put forward. The method is illustrated with the Coomassie brilliant blue stained 2-D gel electrophoresis patterns of the proteomes from liver cells of healthy male Fisher F344 rats and the rats treated with four peroxisome proliferators.     

On-line screening of conformationally constrained nicotines and anabasines for agonist activity at the alpha3beta4- and alpha4beta2-nicotinic acetylcholine receptors using immobilized receptor-based liquid chromatographic stationary phases

Liquid chromatography columns containing stationary phases based upon immobilized nicotinic acetylcholine receptors (nAChRs) were used to screen a series of conformationally constrained nicotine and anabasine derivatives for agonist activity. The alpha3beta4 nAChR and alpha4beta2 nAChR subtypes were used to prepare the chromatographic columns and [(3)H] epibatidine dihydrochloride ([(3)H] EB) was used as the marker ligand. Single displacement experiments were conducted with the test ligands and with nicotine and carbachol. Nicotine was used as an internal control for compounds with agonist activity and carbachol was used as an internal control for compounds with very weak agonistic activity (K(d) > 4700 nM for alpha3beta4). The displacement of [(3)H] EB by each of the test compounds and internal controls was calculated and expressed as Deltaml. Functional studies were then conducted using a stably transfected cell line that expresses the alpha3beta4 nAChR and EC(50) values were determined for the test compounds and the internal controls. A comparison of the Deltaml and EC(50) values indicated that 9/11 compounds had been correctly identified as agonists or non-agonists of the alpha3beta4 nAChR. A similar comparison could not be made for the alpha4beta2 nAChR, since the intact cell line was not available for testing. The results of the study suggest that the immobilized nAChR columns can be used for the rapid on-line screening of compounds for their relative affinities for the immobilized receptor and as an initial determination of qualitative functional activities.