qq' -> qq': a second look at the IR divergences

The transport properties of the quark-gluon plasma is important both from the point of view of the astrophysical systems and the heavy ion collisions. Therefore, accurate calculations of the elastic scattering cross-sections of $qq' \to qq'$ and q\qbar' \to q\qbar' processes are required. At the tree-diagram level exchange of massless gluons leads to divergent cross sections for such processes. An effective way to remove the infrared divergence is to introduce a Debye mass as an infrared regulator into the gluon propagator for the thermal gluons. In this work we find that at the two-gluon exchange level such a technique fails to remove the divergences. In a chiral symmetry broken phase the mass could be introduced following the standard procedure which cures the divergence. But in a chirally symmetric phase chiral invariant mass of the fermions needs to be considered.Comment: 4 pages, latex, 1 figur

Targeting Mitochondrial Cell Death Pathway to Overcome Drug Resistance with a Newly Developed Iron Chelate

Background: Multi drug resistance (MDR) or cross-resistance to multiple classes of chemotherapeutic agents is a major obstacle to successful application of chemotherapy and a basic problem in cancer biology. The multidrug resistance gene, MDR1, and its gene product P-glycoprotein (P-gp) are an important determinant of MDR. Therefore, there is an urgent need for development of novel compounds that are not substrates of P-glycoprotein and are effective against drug-resistant cancer. Methodology/Principal Findings: In this present study, we have synthesized a novel, redox active Fe (II) complex (chelate), iron N- (2-hydroxy acetophenone) glycinate (FeNG). The structure of the complex has been determined by spectroscopic means. To evaluate the cytotoxic effect of FeNG we used doxorubicin resistant and/or sensitive T lymphoblastic leukemia cells and show that FeNG kills both the cell types irrespective of their MDR phenotype. Moreover, FeNG induces apoptosis in doxorubicin resistance T lymphoblastic leukemia cell through mitochondrial pathway via generation reactive oxygen species (ROS). This is substantiated by the fact that the antioxidant N-acetyle-cysteine (NAC) could completely block ROS generation and, subsequently, abrogated FeNG induced apoptosis. Therefore, FeNG induces the doxorubicin resistant T lymphoblastic leukemia cells to undergo apoptosis and thus overcome MDR. Conclusion/Significance: Our study provides evidence that FeNG, a redox active metal chelate may be a promising ne

Clinicopathological characteristics of patients of certain molecular subtypes and elevated postoperative cancer antigen 15.3 levels and its correlation with menopausal status

Context: It is well established that breast cancer subtypes differ in their outcome and treatment response. Aim: To observe tumor characteristics of different molecular subgroup and patients with postoperative (PO) raised cancer antigen 15.3 (CA 15.3) group and variation of tumor nature between pre- and post-menopausal breast cancer patients. Materials and Methods: Blood samples and tumor blocks were collected from 95 nonmetastatic female breast cancer patients. Immunohistochemical stains for estrogen receptors (ER), progesterone receptor (PR), and HER2/Neu were used to classify molecular subtypes. CA 15.3 level was detected by ELISA. Significance levels were ascertained by Pearson Chi-square test. Results: Prevalence of luminal A tumor with grade 3 was high. Triple negative and ER positive (ER+) types showed tumors with high grade and high lymph node (LN) metastasis. More nodal involvement was noticed in patients with PO raised CA 15.3. In addition, premenopausal patients with triple-negative and ER+ subtypes exhibited more aggressive tumors which were characterized by high grade and large numbers of LN metastasis. Conclusion: Clinicopathological characteristics of certain molecular subtypes and influence of menopausal status on it can predict disease recurrence or overall survival of breast cancer patients

CEFTRIAXONE RELATED ADVERSE DRUG REACTIONS IN CHILDREN IN A TERTIARY CARE HOSPITAL, KOLKATA, WEST BENGAL, INDIA

Ceftriaxone is a third-generation cephalosporin antibiotic, which has broad-spectrum activity against Gram-positive and Gram-negative bacteria. It is a frequently used antibiotic in children worldwide. Studies revealed a number of adverse reactions related to this third generation antibiotic. A survey was done where data related with adverse drug reactions (ADRs) were collected for three months from the Department of Pediatrics of a tertiary care hospital, Kolkata, West Bengal, India and then evaluated. In the study, fifteen ADRs were detected. Ceftriaxone itself or its combinations correlated with more than thirty three percent (33.4%) adverse reaction cases in this study. Most common adverse drug reactions in the present study population were different types of rashes like urticaria and maculopapular eruptions

Iron N-(2-hydroxy acetophenone) glycinate (FeNG), a non-toxic glutathione depletor circumvents doxorubicin resistance in Ehrlich ascites carcinoma cells in vivo

Multidrug resistance-associated protein 1 (MRP1) reduces intracellular anticancer drug accumulation either by co transporting them with glutathione (GSH) or extruding drug-GSH conjugates outside of the cell. Thus, MRP1 confers multidrug resistance (MDR) and worsen successful chemotherapeutic treatment against cancer. Although the exact mechanism of MRP1 involved in MDR remains unknown, the elevated level of intracellular GSH is considered as a key factor responsible for MDR in cancer. Hence the quest for non-toxic molecules that are able to deplete intracellular GSH has profound importance to subdue MDR. The present preclinical study depicts the resistance reversal potentiality of an iron complex; viz. Ferrous N-(2-hydroxy acetophenone) glycinate (FeNG) developed by us in doxorubicin resistant Ehrlich ascites carcinoma (EAC/Dox) cells. FeNG potentiate cytotoxic effect of doxorubicin on EAC/Dox cells ex vivo and also increases the survivability EAC/Dox bearing Swiss albino mice in vivo as well. Moreover, in vivo administration of FeNG significantly depletes intracellular GSH with ensuant increase in doxorubicin concentration in EAC/Dox cells without alternation of MRP1 expression. In addition, intra-peritoneal (i.p.) application of FeNG in normal or EAC/Dox bearing mice does not cause any systemic toxicity in preliminary trials in mouse Ehrlich ascites carcinoma model. Therefore, the present report provides evidence that FeNG may be a promising new resistance modifying agent against drug resistant cancers

ROS and RNS induced apoptosis through p53 and iNOS mediated pathway by a dibasic hydroxamic acid molecule in leukemia cells

Anticancer drugs induce apoptosis to cancer cells and also exhibit undesired toxicity to normal cells. Therefore development of novel agents triggering apoptosis and have low toxicity towards normal cells is most important. Hydroxamic acids suppress tumour cell growth through apoptosis but the underlying mechanism is poorly understood. Herein, we describe the apoptotic potential of a dibasic hydroxamic acid derivative, viz., oxayl bis (N-phenyl) hydroxamic acid (OBPHA), which induces apoptosis through generation of both ROS and NO in doxorubicin resistant T-lymphoblastic leukemia, CEM/ADR5000 cells. Present study discloses that OBPHA selectively kills cancerous cells irrespective of their drug resistant phenotype. We also determined the crystal structure of OBPHA to understand the structural requirements for apoptosis; the study reveals that the presence of substituted hydroxamic acid groups (–CO–NH–OH) favours the generation of NO possibly through auto degeneration. Along with the induction of caspase 3 mediated intrinsic apoptosis; OBPHA also activates p53 dependent signalling cascade and downregulates HDAC3 expression in a time dependent manner possibly due to increased ROS and NO production and simultaneous decrease in cellular GSH level. Thus ROS and NO mediated downstream signalling are essential for the anticancer effect of OBPHA. Therefore OBPHA, having a structurally relevant pharmacophore provides important insight into the development of new ROS and RNS generating chemicals inducing p53 dependent apoptosis

Structure and Mass spectral study of Iron Complex.

<p>(A)Chemical Structure of iron complex, iron (II) N-(2-hydroxyacetophenone) glycinate (FeNG). (B) Mass fragments of FeNG.</p

Activation of caspase 3 in CEM/ADR5000 cells after FeNG treatment.

<p>(A) Effect of FeNG and caspase inhibitors on the activity of caspase-3 of CEM/ADR5000 cells. Cells were treated with either vehicle (medium) control or FeNG (10⁻⁴ M) for 12 h, 24 h, 48 h, 72 h or caspases inhibitors; Ac-DEVD-cho (caspase 3 specific inhibitor) and z-VAD-fmk (pan caspase inhibitor) alone (50 µM) or in combination with FeNG for 72 h. After completion of these treatments, cells were harvested and cell lysates were prepared. The enzymatic activity of cell lysates towards tetrapeptide chromogenic substrates Ac-DEVD-AMC was determined. Caspase activities are expressed as fold change of control and presented as mean±SD of three independent experiments. Differences between untreated control and FeNG treated cells are significant ***P<0.001, by unpaired Student's t test. (B) Effects of caspase inhibitor on FeNG induced cell death of CEM/ADR5000 cells. Cells were either left untreated or treated with FeNG (10⁻³ M or10⁻⁴ M) or Ac-DEVD-cho (50 µM) and z-VAD-fmk (50 µM) alone or in combination with FeNG for 72 h and cell death was monitored by MTT assay. Value represents the mean ± SD of three independent experiments with four replicates in each. Significant difference at *P<0.05, **P<0.01, respectively, from only FeNG treated cells. (C) Effect of FeNG on the cleavage patterns of PARP in CEM/ADR5000 cells. Cells were grown at standard culture conditions as mentioned in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0011253#s4" target="_blank">Materials and methods</a>, and treated with FeNG (10⁻⁴ M) for 24 h to 72 h, and cell lysates were prepared. Immunoblot analysis was performed to identify the full (116 kDa) and cleaved (89 kDa) PARP using specific primary antibodies. Loading was checked by immunoblotting of β -actin. Bands were visualized by Lumi glow detection system. Data shown are representative of three independent experiments. (D) Densitometric quantitation of cleaved (89 kDa) frgments of PARP in the cytoplasm. Immunoreactive bands were quantitated and expressed as the ratio of each band density to corresponding loading control (β actin) band density and values were represented after normalization to untreated control.</p

Reactive oxygen species (ROS) plays an important role in FeNG induced apoptosis.

<p>(A) CEM/ADR5000 cells were either kept untreated or treated with FeNG (10⁻⁴ M) and intra cellular ROS generation was measured [in terms of peroxide using dichlorofluorescein diacetate (DCF-DA)] as described under <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0011253#s4" target="_blank"><i>Materials and Methods</i></a> at different time points. Data are expressed as percent of control and are presented as mean±SD of 3 independent experiments. Differences between control and FeNG treated cells are significant *P<0.05, **P<0.01, ***P<0.001, by unpaired Student's <i>t</i> test. (B) NAC completely abrogated FeNG induced ROS generation in CEM/ADR5000 cells. Cells were either kept untreated or pretreated with NAC (5 mM) for 1 h. Then the cells were further cultured for 2 h, 4 h, 6 h and 8 h in the presence or absence of FeNG (10⁻⁴ M) and intra cellular ROS generation was measured. (C) Represents that NAC protects CEM/ADR5000 cells from FeNG induced cell death. CEM/ADR5000 cells were either left untreated or pretreated with different concentration of NAC for 1 h. The cells were then treated with FeNG (10⁻³ M or10⁻⁴ M) for 72 h and cell death was monitored by MTT assay. Value represents the mean ± SD of three independent experiments with four replicates in each. Significant difference at *P<0.05, ***P<0.001, respectively, from only FeNG treated cells. (D) FeNG depletes intra cellular glutathion (GSH) contents of CEM/ADR5000 cells. Cells were either kept untreated or treated with FeNG (10⁻⁴ M) for indicated time points and intra cellular GSH was measured as described under <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0011253#s4" target="_blank"><i>Materials and Methods</i></a>. Results are presented as mean±SD of 3 independent experiments. Differences between untreated control and FeNG treated cells are significant **P<0.01, ***P<0.001, by unpaired Student's <i>t</i> test.</p