DNA damage induced by industrial solid waste leachates in Drosophila melanogaster: a mechanistic approach

Genomic stability requires that error-free genetic information be transmitted from generation to generation, a process that is dependent upon efficient DNA repair. Industrial leachates which contain mixtures of diverse chemicals are a major environmental concern. The interaction between these chemicals may have synergistic, antagonistic, or simply additive effects on biological systems. In the present study, the Comet assay was used to measure the DNA damage produced by leachates of solid wastes from flashlight battery, pigment, and tanning factories in the midgut cells and brain ganglia of Drosophila melanogaster mutants deficient in DNA repair proteins. Larvae were allowed to feed for 48 or 72 hr on diets containing 0.1, 0.5, and 2.0% (v/v) of the leachates. Physicochemical analysis run on the solid wastes, leachates, and treated larvae detected elevated levels of heavy metals. Leachates produced significantly greater levels of DNA damage in mutant strains mei41 (deficient in cell cycle check point protein), mus201 (deficient in excision repair protein), mus308 (deficient in postreplication repair protein), and rad54 (deficient in double strand break repair protein) than in the OregonR(+) wild-type strain. Larvae of the ligaseIV mutant (deficient in double strand break repair protein) were hypersensitive only to the pigment plant waste leachate. Conversely, the dnase2 mutant (deficient in protein responsible for degrading fragmented DNA) was more sensitive to DNA damage induction from the flashlight battery and tannery waste leachates. Our data demonstrate that repair of DNA damage in organisms exposed to leachates is dependent upon several DNA repair proteins, indicative of the involvement of multiple overlapping repair pathways. The study further suggests the usefulness of the Comet assay for studying the mechanisms of DNA repair in Drosophila.     

High-resolution analysis of genetic alterations in small bowel carcinoid tumors reveals areas of recurrent amplification and loss

Carcinoid tumors of the small intestine are characterized by an indolent clinical course, secretion of neuropeptides, and resistance to standard cytotoxic chemotherapy. To evaluate the molecular events underlying carcinoid tumorigenesis, we used high-resolution arrays of single nucleotide polymorphisms to study chromosomal gains and losses in 24 primary and metastatic small bowel carcinoid tumors derived from 18 patients. Regions of gain or loss comprising whole chromosomes or large chromosomal regions constituted the most common class of anomalies. Loss of all or most of chromosome 18 was the commonest finding, evident in 11 of the 18 cases. Heterozygosity was also lost on chromosome arms 9p and 16q. The amplitude of observed gains was modest in comparison to those reported in some other tumor types. One focal region of recurrent gain on 14q mapped to the locus of the gene encoding the antiapoptotic protein DAD1, and immunohistochemical staining confirmed DAD1 protein expression in tumor samples. This detailed study of an uncommon neoplasm provides a basis to investigate putative oncogenes and tumor suppressor genes in intestinal carcinoid tumors.     

Thermoluminescence dosimetry measurements of brachytherapy sources in liquid water

Radiation therapy dose measurements are customarily performed in liquid water. The characterization of brachytherapy sources is, however, generally based on measurements made with thermoluminescence dosimeters (TLDs), for which contact with water may lead to erroneous readings. Consequently, most dosimetry parameters reported in the literature have been based on measurements in water-equivalent plastics, such as Solid Water. These previous reports employed a correction factor to transfer the dose measurements from a plastic phantom to liquid water. The correction factor most often was based on Monte Carlo calculations. The process of measuring in a water-equivalent plastic phantom whose exact composition may be different from published specifications, then correcting the results to a water medium leads to increased uncertainty in the results. A system has been designed to enable measurements with TLDs in liquid water. This system, which includes jigs to support water-tight capsules of lithium fluoride in configurations suitable for measuring several dosimetric parameters, was used to determine the correction factor from water-equivalent plastic to water. Measurements of several 125I and 131Cs prostate brachytherapy sources in liquid water and in a Solid Water phantom demonstrated a correction factor of 1.039 +/- 0.005 at 1 cm distance. These measurements are in good agreement with a published value of this correction factor for an 125I source.     

Rubella vaccine: new horizon in prevention of congenital rubella syndrome in the India

Rubella is a contagious viral disease, which mainly affects the fetus, if the mother is infected in the 1st trimester of her pregnancy. All adolescent girls (aged 11 to 19 y) and women of childbearing age are at risk of developing rubella. This disease is mild and self-limiting, and incubation period is 2-3 weeks. Humans are the only hosts for rubella. Rubella infection during pregnancy may lead to abortions, stillbirth or congenital deformities (birth defects). Moreover it is surprising to know that over 200,000 babies are born with birth defects because of Rubella infection during pregnancy in the Indian sub-continent. The risk of fetal infection is highest in first trimester; the infection rate declines between 12-28 weeks, suggesting that the placenta may prevent transfer of virus but not completely. The incidence of defects is inversely related to the time of maternal infection. Rubella outbreaks have been reported from many countries in South East Asian region with congenital rubella syndrome (CRS) due to maternal rubella being on the increase in many countries. In India, although the endemicity of rubella is established, the majority of cases remain undiagnosed, being subclinical or clinically mild. Consequently, in spite of evidence of CRS in all States of India, no distinct policy has been envisaged for assessing the burden of rubella, and no control measures against this silent crippling disease are in place. The European Regional Committee of the World Health Organization has adopted the goals of "Elimination of CRS" in the Health for All programs. There is no treatment for rubella. Vaccination is the only way to prevent all these complications.     

Arbuscular Mycorrhizal Dependency of Acacia melanoxylon R.Br.

Arbuscular mycorrhizal dependency of Acacia melanoxylon R.Br. was determined under three experimental set up conditions viz, natural soils, coal mine disturbed soils and artificially inoculated conditions. Mycorrhizal dependency of the plant varied significantly with the type of soil and varied between 30 and 62?%. The mycorrhizal dependency of A. melanoxylon in coal mine disturbed soils could be correlated with the degree of disturbance of the soil. The maximum dependency (61?%) was recorded in 7 incline soil. Mycorrhizal dependency indirectly reveals the biomass response varied according to the type of inoculations. Glomus fasciculatum (Gerdemann and Trappe) inoculated seedlings have shown highest dependency followed by Acaulospora foveata (Trappe and Janos) inoculated seedlings. The extent of mycorrhizal dependency has shown a direct correlation with mycorrhizal colonization.     

Characterization of respiratory deposition of fluticasone-salmeterol hydrofluoroalkane-134a and hydrofluoroalkane-134a beclomethasone in asthmatic patients

BackgroundFixed combination fluticasone-salmeterol is the most used anti-inflammatory asthma treatment in North America, yet no studies report the actual respiratory tract dose or the distribution of drug within the lungs. Inflammation due to asthma affects all airways of the lungs, both large and small. Inhaled steroid delivery to airways results from a range of drug particle sizes, with emphasis on smaller drug particles capable of reaching the peripheral airways. Previous studies suggested that smaller drug particles increase pulmonary deposition and decrease oropharyngeal deposition.ObjectivesTo characterize the dose of fluticasone-salmeterol hydrofluoroalkane-134a (HFA) (particle size, 2.7 μm) delivered to asthmatic patients and examine the drug distribution within the lungs. The results were compared with the inhalation delivery of HFA beclomethasone (particle size, 0.7 μm).MethodsA crossover study was conducted in asthmatic patients with commercial formulations of fluticasone-salmeterol and HFA beclomethasone radiolabeled with technetium Tc 99m. Deposition was measured using single-photon emission computed tomography/computed tomography gamma scintigraphy.ResultsTwo-dimensional planar image analysis indicated that 58% of the HFA beclomethasone and 16% of the fluticasone-salmeterol HFA were deposited in the patient's lungs. The oropharyngeal cavity and gut analyses indicated that 77% of the fluticasone-salmeterol HFA was deposited in the oropharynx compared with 35% of the HFA beclomethasone.ConclusionsThe decreased peripheral airway deposition and increased oropharyngeal deposition of fluticasone-salmeterol HFA was a result of its larger particle size. The smaller particle size of HFA beclomethasone allowed a greater proportion of lung deposition with a concomitant decrease in oropharyngeal deposition.