Iron Oxide Nanoparticles Affects Behaviour and Monoamine Levels in Mice

Iron oxide (Fe₂O₃) nanoparticles (NPs) attract the attention of clinicians for its unique magnetic and paramagnetic properties, which are exclusively used in neurodiagnostics and therapeutics among the other biomedical applications. Despite numerous research findings has already proved neurotoxicity of Fe₂O₃-NPs, factors affecting neurobehaviour has not been elucidated. In this study, mice were exposed to Fe₂O₃-NPs (25 and 50 mg/kg body weight) by oral intubation daily for 30 days. It was observed that Fe₂O₃-NPs remarkably impair motor coordination and memory. In the treated brain regions, mitochondrial damage, depleted energy level and decreased ATPase (Mg²⁺, Ca²⁺ and Na⁺/K⁺) activities were observed. Disturbed ion homeostasis and axonal demyelination in the treated brain regions contributes to poor motor coordination. Increased intracellular calcium ([Ca²⁺]_i) and decreased expression of growth associated protein 43 (GAP43) impairs vesicular exocytosis could result in insufficient signal between neurons. In addition, levels of dopamine (DA), norepinephrine (NE) and epinephrine (EP) were found to be altered in the subjected brain regions in correspondence to the expression of monoamine oxidases (MAO). Along with all these factors, over expression of glial fibrillary acidic protein (GFAP) confirms the neuronal damage, suggesting the evidences for behavioural changes.

     

Characterization and genetic distance analysis of isolates of Peronosclerospora sorghi using AFLP fingerprinting

Sorghum downy mildew, caused by the obligate oomycete Peronosclerospora sorghi, has been controlled through the use of resistant cultivars and seed treatment with metalaxyl. A recent outbreak in fields planted with treated seed revealed the presence of a metalaxyl-resistant variant. Here, PCR-based methods including amplification from RAPD primers and two systems of automated AFLP analysis have been used to detect DNA-level genetic variation among 14 isolates including metalaxyl-resistant and susceptible isolates, as well as representatives of common pathotypes 1 and 3 and a new pathotype. In total, 1708 bands were detected after amplification of EcoRI/MseI fragments with 16 primer combinations. Nearly as many amplified products were observed using eight primer pairs with three-base extensions (LI-COR) as with two-base extensions (ABI-Prism genetic capillary system). Approximately 25 % of the bands were polymorphic across the 14 isolates, with the majority of differences specific to the pathotype P1 isolate. The AFLP banding patterns are consistent with metalaxyl resistance and the new pathotype having evolved from pathotype 3.     

Antimycobacterial activities of novel 2-(sub)-3-fluoro/nitro-5,12-dihydro-5-oxobenzothiazolo[3,2-a]quinoline-6-carboxylic acid

Various 2-(sub)-3-fluoro/nitro-5,12-dihydro-5-oxobenzothiazolo[3,2-a]quinoline-6-carboxylic acid derivatives were synthesized from 2-aminothiophenol by a five-step reaction, evaluated for in-vitro and in-vivo antimycobacterial activities against Mycobacterium tuberculosis H37Rv (MTB), multi-drug resistant Mycobacterium tuberculosis (MDR-TB), and Mycobacterium smegmatis (MC2), and also tested for the ability to inhibit the supercoiling activity of DNA gyrase from M. smegmatis. Among the thirty-four synthesized compounds, 2-(3-(diethylcarbamoyl)piperidin-1-yl)-)-3-fluoro-5,12-dihydro-5-oxobenzothiazolo[3,2-a]quinoline-6-carboxylic acid (7l) was found to be the most active compound in vitro with MIC of 0.18 and 0.08 microM against MTB and MTR-TB, respectively. Compound 7l was found to be 2 and 570 times more potent than isoniazid against MTB and MDR-TB, respectively. In the in-vivo animal model 7l decreased the bacterial load in lung and spleen tissues with 2.78 and 3.12-log10 protections, respectively, at the dose of 50 mg/kg body weight.     

Interleukin 6 mediates the lysophosphatidic acid-regulated cross-talk between stromal and epithelial prostate cancer cells

The interaction between stromal and epithelial cells is critical for the initiation and progression of prostate cancer, but the molecular determinants responsible for the cross-talk between these two cell types remain largely unknown. Here, we used a co-culture cell assay to identify messengers involved in the cross-talk between human prostate stromal PS30 and epithelial LNCaP cells. Stimulation with lysophosphatidic acid (LPA) activates the mitogenic ERK signaling pathway in PS30, but not LNCaP, cells. The co-culture of PS30 and LNCaP cells results in the activation of ERK in LNCaP cells and that is further increased in response to stimulation with LPA. Physiologic relevance of the interaction between PS30 and LNCaP cells is demonstrated using LNCaP xenograft tumor assays. Animals implanted with a mixture of both cell types develop larger tumors with higher frequency compared with those injected with LNCaP cells alone. Conditioned medium transfer experiments reveal the PS30-derived inducing factor is soluble and promotes mitogenic ERK and STAT3 signaling pathways in LNCaP cells. Protein analysis demonstrates that treatment of the PS30 cells with LPA induces synthesis of interleukin 6 (IL-6). Antibody neutralization experiments reveal that IL-6 is responsible for the LPA-induced mitogenic signaling and growth of the LNCaP cells. Our findings reveal that the LPA-regulated secretion of IL-6 is an important messenger linking stromal and epithelial prostate cells, which may be exploited for the effective treatment of patients with advanced prostate cancer.     

Role of Interferon Gamma Release Assay in Active TB Diagnosis among HIV Infected Individuals

Background

A rapid and specific test is urgently needed for tuberculosis (TB) diagnosis especially among human immunodeficiency virus (HIV) infected individuals. In this study, we assessed the sensitivity of Interferon gamma release assay (IGRA) in active tuberculosis patients who were positive for HIV infection and compared it with that of tuberculin skin test (TST).

Methodology/Principal Findings

A total of 105 HIV-TB patients who were naïve for anti tuberculosis and anti retroviral therapy were included for this study out of which 53 (50%) were culture positive. Of 105 tested, QuantiFERON-TB Gold in-tube (QFT-G) was positive in 65% (95% CI: 56% to 74%), negative in 18% (95% CI: 11% to 25%) and indeterminate in 17% (95% CI: 10% to 24%) of patients. The sensitivity of QFT-G remained similar in pulmonary TB and extra-pulmonary TB patients. The QFT-G positivity was not affected by low CD4 count, but it often gave indeterminate results especially in individuals with CD4 count <200 cells/µl. All of the QFT-G indeterminate patients whose sputum culture were positive, showed ≤0.25 IU/ml of IFN-γ response to phytohemagglutinin (PHA). TST was performed in all the 105 patients and yielded the sensitivity of 31% (95% CI: 40% to 22%). All the TST positives were QFT-G positives. The sensitivity of TST was decreased, when CD4 cell counts declined.

Conclusions/Significance

Our study shows neither QFT-G alone or in combination with TST can be used to exclude the suspicion of active TB disease. However, unlike TST, QFT-G yielded fewer false negative results even in individuals with low CD4 count. The low PHA cut-off point for indeterminate results suggested in this study (≤0.25 IU/ml) may improve the proportion of valid QFT-G results.     

High-resolution linkage mapping for the non-brittle rachis locus btr1 in cultivated × wild barley (Hordeum vulgare)

Brittle rachis is an important trait to elucidate the domestication process in barley. Brittle rachis in wild barley (Hordeum vulgare ssp. spontaneum (C. Koch.) Thell) is controlled by two dominant complementary genes, Btr1 and Btr2. Cultivated barley (H. vulgare L. ssp. vulgare) lost the brittle rachis character during domestication as a result of mutation at the Btr1 or Btr2 locus. In this study, a high-resolution map of the btr1 locus was constructed using an F₂ population of cultivar (cv. ‘Kanto Nakate Gold’) × wild barley (line OUH602). We cloned and sequenced 26 AFLP markers linked with the btr1 and btr2 loci. Ten converted STS markers were located on the short arm of chromosome 3H only, and at least 9 of the 10 STS markers were allelic with their original AFLPs. Efficient conversion of co-dominant STS markers using BAC clones was successful. No suppression of recombination was observed in the btr1 region even though wild barley was used as one of the parents. Initial results of BAC screening confirmed the resolution power of the developed high resolution map.     

Therapeutic application of natural inhibitors against snake venom phospholipase A(2)

Natural inhibitors occupy an important place in the potential to neutralize the toxic effects caused by snake venom proteins and enzymes. It has been well recognized for several years that animal sera, some of the plant and marine extracts are the most potent in neutralizing snake venom phospholipase A(2) (svPLA(2)). The implication of this review to update the latest research work which has been accomplished with svPLA(2) inhibitors from various natural sources like animal, marine organisms presents a compilation of research in this field over the past decade and revisiting the previous research report including those found in plants. In addition to that the bioactive compounds/inhibitor molecules from diverse sources like aristolochic alkaloid, flavonoids and neoflavonoids from plants, hydrocarbones -2, 4 dimethyl hexane, 2 methylnonane, and 2, 6 dimethyl heptane obtained from traditional medicinal plants Tragia involucrata (Euphorbiaceae) member of natural products involved for the inhibitory potential of phospholipase A(2) (PLA(2)) enzymes in vitro and also decrease both oedema induced by snake venom as well as human synovial fluid PLA(2). Besides marine natural products that inhibit PLA(2) are manoalide and its derivatives such as scalaradial and related compounds, pseudopterosins and vidalols, tetracylne from synthetic chemicals etc. There is an overview of the role of PLA(2) in inflammation that provides a rationale for seeking inhibitors of PLA(2) as anti-inflammatory agents. However, more studies should be considered to evaluate antivenom efficiency of sera and other agents against a variety of snake venoms found in various parts of the world. The implications of these new groups of svPLA(2) toxin inhibitors in the context of our current understanding of snake biology as well as in the development of new novel antivenoms therapeutics agents in the efficient treatment of snake envenomations are discussed.     

Microwave assisted synthesis of 2-(4-substituted piperazin-1-yl)-1,8-naphthyridine-3-carbonitrile as a new class of serotonin 5-HT3 receptor antagonists

A series of novel 2-(4-substituted piperazin-1-yl)-1,8-naphthyridine-3-carbonitrile 6 were prepared by microwave irradiation and conventional heating. The intermediate, 2-oxo-1,2-dihydro-1,8-naphthyridine-3-carbonitrile 3, was prepared from 2-aminonicotinaldehyde 1 and ethyl cyanoacetate 2 in the presence of piperidine under solvent free condition. The synthesized compounds were evaluated for 5-HT3 antagonisms in longitudinal muscle-myenteric plexus (LMMP) preparation from Guinea pig ileum against 5-HT3 agonist, 2-methyl-5-HT. Among the compounds tested, 2-(4-allylpiperazin-1-yl)-1,8-naphthyridine-3-carbonitrile 6d showed most favorable 5-HT3 receptor antagonism in the Guinea pig ileum.