(E)- and (Z)-1,2,4-triazolylchromanone oxime ethers as conformationally constrained antifungals

A series of 1,2,4-triazolylchromanone oxime ethers were synthesized and tested for in vitro antifungal activity. Many of these derivatives exhibit high activity against Candida albicans, Saccharomyces cerevisiae, Aspergillus niger and Microsporum gypseum.     

Conservation of XYN11A and XYN11B xylanase genes in Bipolaris sorghicola,Cochliobolus sativus,Cochliobolus heterostrophus,and Cochliobolus spicifer

Two types of xylanase gene, XYN11A (XYL1) and XYN11B (XYL2), were amplified by PCR and partially sequenced in four phytopathogenic species of the ascomycete fungal genus Cochliobolus (anamorph genus Bipolaris). Three of the species, C. heterostrophus (B. maydis), C. sativus (B. sorokiniana), and Bipolaris sorghicola (no teleomorph known), are interrelated; the fourth, C. spicifer (B. spicifera), was found, through analysis of the 5.8S RNA and internal transcribed spacer (ITS) sequences of its ribosomal DNA, to be more distantly related to the other three. Isolates from all four species contain orthologous XYN11A and XYN11B genes, but a set of laboratory strains of C. heterostrophus gave no product corresponding to the XYN11B gene. The patterns of evolution of the two xylanase genes and ribosomal DNA sequences are mutually consistent; the results indicate that the two genes were present in the common ancestor of all Cochliobolus species and are evolving independently of each other. Received: 12 July 2001 / Accepted: 6 March 2002     

Extracellular mitochondrial DNA and oxidatively damaged DNA in synovial fluid of patients with rheumatoid arthritis

We investigated whether plasma and synovial fluid (SF) samples from patients with rheumatoid arthritis (RA) contained extracellular mitochondrial DNA (mtDNA) or the oxidatively damaged DNA adduct 8-hydroxy-2'-deoxyguanosine (8-oxodG). Moreover, we correlated the laboratory findings of the patients with RA with their levels of mtDNA and 8-oxodG. SF and plasma samples from 54 patients with RA, SF from 30 non-arthritic control subjects, and plasma from 22 healthy volunteers were collected. The samples were subjected to polymerase chain reaction (PCR) using mitochondrial genomic primers, and the products were analyzed by SDS–polyacrylamide-gel electrophoresis. The intensities of the PCR-amplified bands were quantified and normalized to a reference sample. Furthermore, the SF samples were assayed by enzyme-linked immunosorbent assay for 8-oxodG. Extracellular PCR-amplifiable mtDNA was detected in the SF of 38 of 54 (70%) patients with RA, but not in any of the SF controls. PCR-amplifiable mtDNA was detected in the plasma of 30 of 54 (56%) of patients with RA and in 6 of 22 (27%) of the healthy volunteers. The levels of mtDNA in the plasma and SF samples of patients with RA were significantly higher (P < 0.0001) than in the respective control samples. The presence of both mtDNA and 8-oxodG in SF was significantly correlated with the presence of rheumatoid factor in the patients with RA. Extracellular mtDNA and oxidized DNA were detected in the SF of the great majority of patients with RA, but were absent or present at low levels in the control SF. These findings indicate that endogenous nucleic acid compounds might participate in joint inflammation by activating immune cells in the joints to produce proinflammatory cytokines.     

Increasing intracellular cAMP and cGMP inhibits cadmium-induced oxidative stress in rat submandibular saliva

The effect of cadmium on induction of oxidative stress in rat submandibular saliva and protective role of increasing intracellular cAMP and cGMP by use of specific phosphodiesterase inhibitors, theophylline and sildenafil were investigated. Pure submandibular saliva was collected intraorally by micro polyethylene cannula from anaesthetized rats using pilocarpine as secretagogue. Acute administration of cadmium (10 mg/kg) caused significant oxidative stress by increasing lipid peroxidation by-products (thiobarbituric reactive substances, TBARS) and decreasing total thiols and total antioxidant power of the saliva. Concurrent therapy of rats by theophylline (25 mg/kg) and sildenafil (5 mg/kg) prevented cadmium-induced oxidative stress in saliva. Theophylline and sildenafil inhibited cadmium-induced increase in lipid peroxidation and decrease in total thiols and antioxidant power. It is concluded that cadmium administration results in oxidative stress in rat submandibular saliva, which can be protected by concurrent administration of specific cyclic nucleotide phosphodiesterase inhibitors.     

Ultrastructural changes in the muscles,midgut, hemopoietic organ,imaginal discs and Malpighian tubules of the mosquito Aedes aegypti larvae infected by the fungus Coelomomyces stegomyiae

Fungi belonging to the genus Coelomomyces can infect mosquito larvae and develop within the larval hemocoel. To examine fungal development, Aedesaegypti larvae infected with Coelomomyces stegomyiae Keilin were fixed, embedded and sectioned for both light and electron microscopy. While fungal hyphae of C. stegomyiae did not invade cells other than the cuticular epithelial cells, they did penetrate a number of tissues including muscles, midgut, hemopoietic organ, imaginal discs, and Malpighian tubules. This revised version was published online in July 2006 with corrections to the Cover Date.     

An Augmented SMS Intervention to Improve Access to Antenatal CD4 Testing and ART Initiation in HIV-Infected Pregnant Women: A Cluster Randomized Trial

BackgroundLess than one-third of HIV-infected pregnant women eligible for combination antiretroviral therapy (ART) globally initiate treatment prior to delivery, with lack of access to timely CD₄ results being a principal barrier. We evaluated the effectiveness of an SMS-based intervention to improve access to timely antenatal ART.MethodsWe conducted a stepped-wedge cluster randomized trial of a low-cost programmatic intervention in 20 antenatal clinics in Gaborone, Botswana. From July 2011-April 2012, 2 clinics were randomly selected every 4 weeks to receive an ongoing clinic-based educational intervention to improve CD₄ collection and to receive CD₄ results via an automated SMS platform with active patient tracing. CD₄ testing before 26 weeks gestation and ART initiation before 30 weeks gestation were assessed.ResultsThree-hundred-sixty-six ART-naïve women were included, 189 registering for antenatal care under Intervention and 177 under Usual Care periods. Of CD₄-eligible women, 100 (59.2%) women under Intervention and 79 (50.6%) women under Usual Care completed CD₄ phlebotomy before 26 weeks gestation, adjusted odds ratio (aOR, adjusted for time that a clinic initiated Intervention) 0.87 (95% confidence interval [CI]0.47–1.63, P = 0.67). The SMS-based platform reduced time to clinic receipt of CD₄ test result from median of 16 to 6 days (P<0.001), was appreciated by clinic staff, and was associated with reduced operational cost. However, rates of ART initiation remained low, with 56 (36.4%) women registering under Intervention versus 37 (24.2%) women under Usual Care initiating ART prior to 30 weeks gestation, aOR 1.06 (95%CI 0.53–2.13, P = 0.87).ConclusionsThe augmented SMS-based intervention delivered CD₄ results more rapidly and efficiently, and this type of SMS-based results delivery platform may be useful for a variety of tests and settings. However, the intervention did not appear to improve access to timely antenatal CD₄ testing or ART initiation, as obstacles other than CD₄ impeded ART initiation during pregnancy.     

Kinetics of Cr(VI) Removal by Iron Filings in Some Soils

In this research, kinetics of Cr(VI) reduction by iron filings was investigated through a batch study in seven different soils. Chromate reduction experiments were carried out for initial Cr(VI) concentrations ranging from 20 to 100 mgkg^?1 and iron filings dosage of 0 to 5% w/w. The experimental data were analyzed using various kinetic models including zero-order, pseudo first-order, power function, Elovich, and diffusion parabolic. Results showed that the Cr(VI) reduction efficiency in the presence of all studied soils increased with increasing iron filings dosage and decreased with increasing the initial Cr(VI) concentration. The reaction rates considerably depended on pH and were higher in acidic soils. The diffusion parabolic model was the best kinetic model as evidenced by the highest determination coefficient (r²) and the lowest standard error of the estimate (SE). The rate-limiting step(s) may be transport of chromate anions across a liquid film at the interface of soil-liquid, transport in liquid-filled macropores of iron filings aggregates, or diffusion in micropores and along the particle's surface.     

Isoenzyme variation patterns and species concept in Astragalus gossypinus and Astragalus persicus complexes (Fabaceae) in Iran

Isoenzyme electrophoresis was employed to examine the relationships of 21 individuals representing four populations of Astragalus gossypinus complex as well as 20 individuals representing five populations of Astragalus persicus complex. A total of 27 bands from three enzyme systems (superoxide dismutase, esterase, and peroxidase) were obtained. UPGMA clustering method resulted in two distinct clusters for different populations corresponding to the two species complexes analysed. In both species, populations distributed on Alborz mountain range in northern Iran form separated clusters from those distributed on Zagros mountain range in the West. The results also show that both species complexes exhibit a high diversity based on Shannon–Weaver diversity index (H′) compared with other species of Astragalus reported previously. The mean number of bands per each presumed isoenzyme ranges from 2.14 to 3.57. The value of Euclidean distance ranges from 1.251 to 3.152. Our data suggest that both species should be circumscribed wider than that treated by most taxonomists, and several taxonomic names should be reduced under synonymy of the corresponding species.     

Nuclear delivery mechanism of herpes simplex virus type 1 genome

Herpes simplex virus type 1 (HSV-1) is a widespread human pathogen infecting more than 80% of the population worldwide. Its replication involves an essential, poorly understood multistep process, referred to as uncoating. Uncoating steps are as follows: (1) The incoming capsid pinpoints the nuclear pore complex (NPC). (2) It opens up at the NPC and releases the highly pressurized viral genome. (3) The viral genome translocates through the NPC. In the present review, we highlight recent advances in this field and propose mechanisms underlying the individual steps of uncoating. We presume that the incoming HSV-1 capsid pinpoints the NPC by hydrophobic interactions and opens up upon binding to NPC proteins. Genome translocation is initially pressure-driven.