Utility of Dexrazoxane for the Attenuation of Epirubicin-Induced Genetic Alterations in Mouse Germ Cells

Dexrazoxane has been approved to treat anthracycline-induced cardiomyopathy and extravasation. However, the effect of dexrazoxane on epirubicin-induced genetic alterations in germ cells has not yet been reported. Thus, the aim of this study was to determine whether dexrazoxane modulates epirubicin-induced genetic damage in the germ cells of male mice. Our results show that dexrazoxane was not genotoxic at the tested doses. Furthermore, it protected mouse germ cells against epirubicin-induced genetic alterations as detected by the reduction in disomic and diploid sperm, spermatogonial chromosomal aberrations, and abnormal sperm heads. The attenuating effect of dexrazoxane was greater at higher dose, indicating a dose-dependent effect. Moreover, sperm motility and count were ameliorated by dexrazoxane pretreatment. Epirubicin induced marked biochemical changes characteristic of oxidative DNA damage including elevated 8-hydroxy-2ʹ-deoxyguanosine levels and reduction in reduced glutathione. Pretreatment of mice with dexrazoxane before epirubicin challenge restored these altered endpoints. We conclude that dexrazoxane may efficiently mitigate the epirubicin insult in male germ cells, and prevent the enhanced risk of abnormal reproductive outcomes and associated health risks. Thus, pretreating patients with dexrazoxane prior to epirubicin may efficiently preserve not only sperm quality but also prevent the transmission of genetic damage to future generations.     

Risk factors associated with E. coli causing neonatal calf diarrhea

Calf diarrhea is one of the major health challenges in cattle herds. The bacteriological examination of fecal samples collected from apparently healthy and diarrheic calves' revealed isolation of 26 E. coli isolates out of 56 calves with an incidence of 46.4%. Serogroups O1, O26, O44, O55, O115, O119, O125, O146, and O151 were identified from the collected fecal samples. Using PCR all isolates was positive for ompA gene species specific for E. coli. While stx1 and eaeA genes detected with incidence of 3.8 and 19.2% respectively from the isolates. The presence of stx2 gene was negative in the fecal isolates. Among colostrum samples 4 E. coli isolates were detected and serogrouped to O26, O55 and O119. They were negative for eaeA, stx1 and stx2 except strain number 4 (O55) was positive for stx1. E. coli strains were sensitive to norfloxacin (80.7%) and resistant to ampicillin and cefotaxime (100% each). Based on our findings, there was no association between occurrence of E. coli and age of calf (2–14 days), while bottle feeding calf colostrum may be a source of E. coli contamination.     

Synthesis,biological evaluation,and molecular docking of new series of antitumor and apoptosis inducers designed as VEGFR-2 inhibitors

Based on quinazoline, quinoxaline, and nitrobenzene scaffolds and on pharmacophoric features of VEGFR-2 inhibitors, 17 novel compounds were designed and synthesised. VEGFR-2 IC₅₀ values ranged from 60.00 to 123.85 nM for the new derivatives compared to 54.00 nM for sorafenib. Compounds 15_a, 15_b, and 15_d showed IC₅₀ from 17.39 to 47.10 µM against human cancer cell lines; hepatocellular carcinoma (HepG2), prostate cancer (PC3), and breast cancer (MCF-7). Meanwhile, the first in terms of VEGFR-2 inhibition was compound 15_d which came second with regard to antitumor assay with IC₅₀ = 24.10, 40.90, and 33.40 µM against aforementioned cell lines, respectively. Furthermore, Compound 15_d increased apoptosis rate of HepG2 from 1.20 to 12.46% as it significantly increased levels of Caspase-3, BAX, and P53 from 49.6274, 40.62, and 42.84 to 561.427, 395.04, and 415.027 pg/mL, respectively. Moreover, 15_d showed IC₅₀ of 253 and 381 nM against HER2 and FGFR, respectively.     

Antiviral susceptibility testing of cytomegalovirus: criteria for detecting resistance to antivirals

Testing cytomegaloviruses for antiviral susceptibility is increasing especially since the reports of 'resistance' to ganciclovir and foscarnet (Erice et al., 1989; Knox et al., 1991). There is however no standardized method for susceptibility testing nor are there criteria for designating an isolate as sensitive or resistant. In a previous paper we utilized a plaque reduction assay and suggested that a resistant strain be defined as one requiring > 12 microM ganciclovir for inhibition of 50% of viral plaques. (Drew et al., 1991) This concentration was chosen because it was at least four-fold greater than the mean concentration required to inhibit pretherapy isolates. In this paper we present the results of testing a large number of isolates prior to and during therapy with either ganciclovir or foscarnet. By analyzing the results of these assays we propose revised criteria for susceptibility of cytomegalovirus 相似文献   

New polygalacturonases from Trichoderma reesei: characterization and their specificities to partially methylated and acetylated pectins

Two extracellular isoenzymes of polygalacturonases PG1 and PG2 were isolated from 3-day-old culture filtrates of Trichoderma reesei. The two enzymes were purified to homogeneity by ion-exchange, gel filtration and hydrophobic interaction chromatographies. PG1 and PG2 exhibit similar molecular weights from gel filtration and SDS-PAGE. Their properties, including optimal pH and temperature, thermal stability and Km were compared. Characterization of substrate specificity showed that the two enzymes had higher affinity toward PGA (B0100) derived from sugar beet pectin (SBP) than PGA from lime pectin. A series of SBPs with different distribution patterns of methyl and acetyl groups, produced by treatment with either plant pectin methylesterase (P-series) or fungal pectin methylesterase (F-series) or base catalysis (B-series), was used as substrates for PG1 and PG2. Substrates with a low degree of esterification were preferred substrates. The activities of PG1 and PG2 were strongly correlated to the degree of methylation and very little effect from acetylation. The products generated by digestion of selected lime and SBPs were analysed using matrix assisted laser desorption ionisation time of flight (MALDI TOF) MS. A mode of action revealed a random cleavage pattern for PG1 and PG2, confirming that these enzymes are endopolygalacturonases.     

Parallel Characterization of Anaerobic Toluene- and Ethylbenzene-Degrading Microbial Consortia by PCR-Denaturing Gradient Gel Electrophoresis, RNA-DNA Membrane Hybridization, and DNA Microarray Technology

A mesophilic toluene-degrading consortium (TDC) and an ethylbenzene-degrading consortium (EDC) were established under sulfate-reducing conditions. These consortia were first characterized by denaturing gradient gel electrophoresis (DGGE) fingerprinting of PCR-amplified 16S rRNA gene fragments, followed by sequencing. The sequences of the major bands (T-1 and E-2) belonging to TDC and EDC, respectively, were affiliated with the family Desulfobacteriaceae. Another major band from EDC (E-1) was related to an uncultured non-sulfate-reducing soil bacterium. Oligonucleotide probes specific for the 16S rRNAs of target organisms corresponding to T-1, E-1, and E-2 were designed, and hybridization conditions were optimized for two analytical formats, membrane and DNA microarray hybridization. Both formats were used to characterize the TDC and EDC, and the results of both were consistent with DGGE analysis. In order to assess the utility of the microarray format for analysis of environmental samples, oil-contaminated sediments from the coast of Kuwait were analyzed. The DNA microarray successfully detected bacterial nucleic acids from these samples, but probes targeting specific groups of sulfate-reducing bacteria did not give positive signals. The results of this study demonstrate the limitations and the potential utility of DNA microarrays for microbial community analysis.     

Responses of Glossina austeni to sticky panels and odours

The responses of male tsetse Glossina austeni Newstead (Diptera: Glossinidae) towards blue and white sticky legged panels, baited with odour attractants, and towards modified panels were studied in the Jozani forest of Unguja Island, Zanzibar. Increasing the height of the body of a standard panel from 30 to 60 or 90 cm, increased the catch two-fold. Increasing the height of the legs (from 15 to 60 or 120 cm) or raising the device more than 5 cm above the ground reduced the catch significantly. The legs of the panels were the preferred landing sites of the flies, irrespective of the height of the body of the panel. Acetone (300 mg/h) combined with cow urine (60-130 mg/h) significantly increased the catches two- to threefold during the rainy season, but not during the dry season. Acetone had no effect during the dry season and its effect during the rainy season was less consistent. There was no effect of octenol (2.5-12.5 mg/h), used alone or in combination with acetone. Likewise, the catch did not increase through the addition of cow sebum, pig urine (60-860 mg/h), pig urine combined with acetone and octenol. The observed seasonal differences in the response of G. austeni towards odours are discussed in relation to host location strategies.     

Bayesian Estimation Using Ranked Set Sampling

Bayesian Estimation of the parameter of a distribution is considered using Ranked set sampling (RSS). It is shown that for at least one RSS plan, the Bayes estimator has smaller Bayes risk than the Bayes estimator using simple random sampling (SRS). Furthermore, for exponential family with conjugate prior, the Bayes estimator of the mean using balanced RSS dominates, in terms of its Bayes risk, the Bayes estimator of the mean using SRS. This procedure is used to estimate the average Milk yield of four hundreds and two sheep. The empirical efficiency supports the theoretical findings.