Antimicrobial activity of sesquiterpene lactones isolated from traditional medicinal plant, Costus speciosus (Koen ex.Retz.) Sm

<p>Abstract</p> <p>Background</p> <p><it>Costus speciosus </it>(Koen ex.Retz.) Sm (Costaceae) is an Indian ornamental plant which has long been used medicinally in traditional systems of medicine. The plant has been found to possess diverse pharmacological activities. Rhizomes are used to treat pneumonia, rheumatism, dropsy, urinary diseases, jaundice, skin diseases and leaves are used<b/>to treat mental disorders.</p> <p>Method</p> <p>Antibacterial and antifungal activities were tested using Disc diffusion method and Minimum Inhibitory <b>Concentration </b>(MIC). Column chromatography was used to isolate compounds from hexane extract. X-ray crystallography technique and GC-MS analysis were used to identify the compounds</p> <p>Results</p> <p>Antibacterial and antifungal activities were observed in hexane, chloroform, ethyl acetate and methanol extracts. Hexane extract of <it>C.speciosus </it>showed good activity against tested fungi also. Two sesquiterpenoid compounds were isolated (costunolide and eremanthin) from the hexane extract. Both the compounds did not inhibit the growth of tested bacteria. But, both the compounds inhibited the tested fungi. The compound costunolide showed significant antifungal activity. The MIC values of costunolide were; 62.5 μg/ml against <it>Trichophyton mentagrophytes</it>, 62. μg/ml against <it>T. simii</it>, 31.25 μg/ml against <it>T. rubrum </it>296, 62.5 μg/ml against <it>T. rubrum </it>57, 125 μg/ml against <it>Epidermophyton floccosum</it>, 250 μg/ml against <it>Scopulariopsis </it>sp, 250 μg/ml against <it>Aspergillus niger</it>, 125 μg/ml against <it>Curvulari lunata</it>, 250 μg/ml against <it>Magnaporthe grisea</it>.</p> <p>Conclusion</p> <p>Hexane extract showed promising antibacterial and antifungal activity. The isolated compound costunolide showed good antifungal activity.</p

Troponin utilization in patients presenting with atrial fibrillation/flutter to the emergency department: retrospective chart review

Abstract Background There are few recommendations about the use of cardiac markers in the investigation and management of atrial fibrillation/flutter. Currently, it is unknown how many patients with atrial fibrillation/flutter undergo troponin testing, and how positive troponin results are managed in the emergency department. We sought to look at the emergency department troponin utilization patterns. Methods We performed a retrospective chart review of patients with atrial fibrillation/flutter presenting to the emergency department at three centers. Outcome measures included the rates of troponins ordered by emergency doctors, number of positive troponins, and those with positive troponins treated as acute coronary syndrome (ACS) by consulting services. Results Four hundred fifty-one charts were reviewed. A total of 388 (86%) of the patients had troponins ordered, 13.7% had positive results, and 4.9% were treated for ACS. Conclusions Troponin tests are ordered in a high percentage of patients with atrial fibrillation/flutter presenting to emergency departments. Five percent of our total patient cohort was diagnosed as having acute coronary syndrome by consulting services

Direct Gene Transfer with IP-10 Mutant Ameliorates Mouse CVB3-Induced Myocarditis by Blunting Th1 Immune Responses

Background: Myocarditis is an inflammation of the myocardium that often follows the enterovirus infections, with coxsackievirus B3 (CVB3) being the most dominant etiologic agent. We and other groups previously reported that chemokine IP-10 was significantly induced in the heart tissue of CVB3-infected mice and contributed to the migration of massive inflammatory cells into the myocardium, which represents one of the most important mechanisms of viral myocarditis. To evaluate the direct effect of IP-10 on the inflammatory responses in CVB3 myocarditis, herein an IP-10 mutant deprived of chemo-attractant function was introduced into mice to antagonize the endogenous IP-10 activity, and its therapeutic effect on CVB3-induced myocarditis was evaluated. Methodology/Principal Findings: The depletion mutant pIP-10-AT, with an additional methionine after removal of the 5 N-terminal amino acids, was genetically constructed and intramuscularly injected into BALB/c mice after CVB3 infection. Compared with vector or no treatment, pIP-10-AT treatment had significantly reduced heart/body weight ratio and serum CK-MB level, increased survival rate and improved heart histopathology, suggesting an ameliorated myocarditis. This therapeutic effect was not attributable to an enhanced viral clearance, but to a blunted Th1 immune response, as evidenced by significantly decreased splenic CD4 + /CD8 + IFN-c + T cell percentages and reduced myocardial Th1 cytokine levels. Conclusion/Significance: Our findings constitute the first preclinical data indicating that interfering in vivo IP-10 activit

Resveratrol Prevents Endothelial Cells Injury in High-Dose Interleukin-2 Therapy against Melanoma

Immunotherapy with high-dose interleukin-2 (HDIL-2) is an effective treatment for patients with metastatic melanoma and renal cell carcinoma. However, it is accompanied by severe toxicity involving endothelial cell injury and induction of vascular leak syndrome (VLS). In this study, we found that resveratrol, a plant polyphenol with anti-inflammatory and anti-cancer properties, was able to prevent the endothelial cell injury and inhibit the development of VLS while improving the efficacy of HDIL-2 therapy in the killing of metastasized melanoma. Specifically, C57BL/6 mice were injected with B16F10 cells followed by resveratrol by gavage the next day and continued treatment with resveratrol once a day. On day 9, mice received HDIL-2. On day 12, mice were evaluated for VLS and tumor metastasis. We found that resveratrol significantly inhibited the development of VLS in lung and liver by protecting endothelial cell integrity and preventing endothelial cells from undergoing apoptosis. The metastasis and growth of the tumor in lung were significantly inhibited by HDIL-2 and HDIL-2 + resveratrol treatment. Notably, HDIL-2 + resveratrol co-treatment was more effective in inhibiting tumor metastasis and growth than HDIL-2 treatment alone. We also analyzed the immune status of Gr-1+CD11b+ myeloid-derived suppressor cells (MDSC) and FoxP3+CD4+ regulatory T cells (Treg). We found that resveratrol induced expansion and suppressive function of MDSC which inhibited the development of VLS after adoptive transfer. However, resveratrol suppressed the HDIL-2-induced expansion of Treg cells. We also found that resveratrol enhanced the susceptibility of melanoma to the cytotoxicity of IL-2-activated killer cells, and induced the expression of the tumor suppressor gene FoxO1. Our results suggested the potential use of resveratrol in HDIL-2 treatment against melanoma. We also demonstrated, for the first time, that MDSC is the dominant suppressor cell than regulatory T cell in the development of VLS

Multi-messenger observations of a binary neutron star merger

On 2017 August 17 a binary neutron star coalescence candidate (later designated GW170817) with merger time 12:41:04 UTC was observed through gravitational waves by the Advanced LIGO and Advanced Virgo detectors. The Fermi Gamma-ray Burst Monitor independently detected a gamma-ray burst (GRB 170817A) with a time delay of ~1.7 s with respect to the merger time. From the gravitational-wave signal, the source was initially localized to a sky region of 31 deg2 at a luminosity distance of 40+8-8 Mpc and with component masses consistent with neutron stars. The component masses were later measured to be in the range 0.86 to 2.26 Mo. An extensive observing campaign was launched across the electromagnetic spectrum leading to the discovery of a bright optical transient (SSS17a, now with the IAU identification of AT 2017gfo) in NGC 4993 (at ~40 Mpc) less than 11 hours after the merger by the One- Meter, Two Hemisphere (1M2H) team using the 1 m Swope Telescope. The optical transient was independently detected by multiple teams within an hour. Subsequent observations targeted the object and its environment. Early ultraviolet observations revealed a blue transient that faded within 48 hours. Optical and infrared observations showed a redward evolution over ~10 days. Following early non-detections, X-ray and radio emission were discovered at the transient’s position ~9 and ~16 days, respectively, after the merger. Both the X-ray and radio emission likely arise from a physical process that is distinct from the one that generates the UV/optical/near-infrared emission. No ultra-high-energy gamma-rays and no neutrino candidates consistent with the source were found in follow-up searches. These observations support the hypothesis that GW170817 was produced by the merger of two neutron stars in NGC4993 followed by a short gamma-ray burst (GRB 170817A) and a kilonova/macronova powered by the radioactive decay of r-process nuclei synthesized in the ejecta

Pan-cancer analysis of whole genomes

Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale(1-3). Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4-5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter(4); identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation(5,6); analyses timings and patterns of tumour evolution(7); describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity(8,9); and evaluates a range of more-specialized features of cancer genomes(8,10-18).Peer reviewe