Background: Trabectedin (T), a marine alkaloid, has shown striking antitumor activity in a variet... more Background: Trabectedin (T), a marine alkaloid, has shown striking antitumor activity in a variety of preclinical models. Clinical investigations have shown that T is effective in myxoid liposarcomas (MLS). In this disease, characterized by the chimeric protein FUS-CHOP, the drug is extremely active (a clinical response rate in 50% of patients). In order to investigate the mechanisms of resistance, a trabectedin resistant cell line, 402−91/ET, derived from MLS 402-91 cells, was developed. Material and Methods: 402-91/ET cell line was made by a stepwise increase in drug concentration. Drug sensitivity was measured by colony assay, MDR related proteins by FACS analysis, the XPG by PCR and Western Blot, the binding of FUS-CHOP by Chip analysis. Results: 402-91/ET cell line shows 10 fold stable resistance to trabectedin. No differences were found in MDR related proteins and in uptake/efflux of T between the parental and resistant cells. The cross resistance to Melphalan and trabectedin was reverted by GSH depletion. The collateral sensitivity of 402-91/ET cells to UV was related to the lack of XPG gene; the transfection of resistant cell line with an expression vector encoding the XPG cDNA reversed the UV hypersensitivity but not the resistance to T. 402−91/ET cell line showed a collateral sensitivity to temozolomide due to methylation of MGMT promoter. In 402−91 cells FUS-CHOP chimera, bound to PTX3 and FN1 promoters, was detached by trabectedin treatment whereas in 402−91/ET cells it was not bound. Conclusion: We developed for the first time a stable model of MLS cell line resistant to trabectedin. The resistance mechanism of 402−91/ET to the drug is probably related to changes in the transcription regulation mediated by FUS-CHOP chimera. Studies are ongoing to elucidate the molecular mechanism by which this process occurs.
... M. Owais Khan Faculty of Eastern Medicine Shifa-ul-Mulk Memorial Hospital Hamdard University ... more ... M. Owais Khan Faculty of Eastern Medicine Shifa-ul-Mulk Memorial Hospital Hamdard University Karachi Pakistan. ... Khalil Ahmad Ansari College of Conventional Medicine Faculty of Pharmacy and Alternative Medicine The Islamia University of Bahawalpur Pakistan. ...
The coexistence of neuroblastic and Schwannian stromal (SS) cells in differentiating neuroblastom... more The coexistence of neuroblastic and Schwannian stromal (SS) cells in differentiating neuroblastoma (NB), and derivation of Schwannian-like cells from neuroblastic clones in vitro, were accepted previously as evidence of a common pluripotent tumor stem line. This paradigm was challenged when SS cells were suggested to be reactive in nature. The advent of microdissection techniques, PCR-based allelic analysis, and in situ fluorescent cytometry made possible the analysis of pure cell populations in fresh surgical specimens, allowing unequivocal determination of clonal origins of various cell subtypes. To overcome the complexity and heterogeneity of three-dimensional tissue structure, we used: (a) Laser-Capture Microdissection to obtain histologically homogeneous cell subtype populations for allelotype analysis at chromosomes 1p36, 11q23, 14q32, and 17q and study of MYCN copy number; (b) multiparametric analysis by Laser-Scanning Cytometry of morphology, DNA content, and immunophenotype...
... Its decoction is prescribed in irregular menstruation. It is used as blood purifier and is fo... more ... Its decoction is prescribed in irregular menstruation. It is used as blood purifier and is found effective in piles, prolapsed uterus and anus and diarrhea (Ahmadi et al., 2010). Justcia adhatoda L. Local name: Baikar, Part used: Leaves. ... In Arabs, this drug Akram et al. 4161 ...
Extended-spectrum beta-lactamases (ESBLs) are bacterial enzymes that confer resistance to advance... more Extended-spectrum beta-lactamases (ESBLs) are bacterial enzymes that confer resistance to advanced generation cephalosporins and can lead to therapeutic failures. There has been no analysis of factors associated with the risk of acquisition of ESBLs in neonates in an intensive care unit from northern India. The CTX-M ESBL enzymes impart resistance against advanced generation cephalosporins (e.g. cefotaxime) and CTX-M variants have become the most prevalent ESBLs worldwide. The CTX-M-15 enzyme in particular is increasingly being reported from Escherichia coli isolates from northern India together with TEM-1. Moreover, E. coli is the most common cause of neonatal sepsis. Accordingly, this study aimed to: (i) characterize the mode of transmission of bla(CTX-M) and bla(TEM) among ESBL-producing E. coli strains isolated from patients admitted to a neonatal intensive care unit (NICU), and (ii) identify factors associated with the acquisition of the said strains in male and female neonates. A total of 97 ESBL-producers was identified among 266 E. coli strains isolated from 238 neonates. The isolates were screened for bla(CTX-M), bla(TEM), armA, rmtA and rmtB, the last three genes being responsible for aminoglycoside resistance. PCR amplified bla(CTX-M) genes were cloned and sequenced. Five bla(CTX-M-15), two rmtB, two bla(TEM-1) and thirteen class1 integrons were detected. All the bla(CTX-M-15) positive isolates, except one, were clonally related. Both univariate and multivariate analyses of factors for the acquisition of the said strains were performed with respect to the sex of the neonates. 'Length of stay in the NICU' was found to be the single independent factor associated with ESBL acquisition. In conclusion, our data suggest that male neonates who are colonized or infected by ESBL-producing E. coli have a longer stay in the NICU compared to their female counterparts. This prolonged stay may be due to male neonates becoming colonized/infected earlier than their female counterparts. Plasmid-mediated-conjugal transfer was found to be the mechanism of transfer of the bla(CTX-M-15) resistance marker in the described setting.
Integrons have been observed to be frequently associated with uropathogenic bacteria. This study ... more Integrons have been observed to be frequently associated with uropathogenic bacteria. This study aimed at 1) determining the prevalence of class 1 integrons among ESBLl-producing uropathogenic Escherichia coli, and 2) analyzing resistance genes associated with different phylogenetic groups of the integron-positive isolates with special reference to bla(CTX-M) and bla(TEM). Twenty-three ESBL-producing E. coli were studied. Enterobacterial repetitive intergenic consensus-PCR (ERIC-PCR) displayed 14 major patterns. Pulse field Gel electrophoresis-typing of 8 randomly selected integron-positive strains ruled out any correlation between genotype and antibiotype. Genomic DNA from 14 strains was PCR-positive for class 1 integrons, bla(CTX-M-15) and bla(TEM-1)-like genes. Integron-sequencing revealed "aadA5-dfrA17-dfrA7" as the most prevalent gene cassette. Our findings unveil the increasing role of the bla(CTX-M) genes in antibiotic resistance and emphasize on the significance of appropriate empirical treatment for Urinary tract infections. Moreover, this is the first study which reports bla(CTX-M) located on genomic DNA of bacteria from India.
Micelles in aqueous media have either a polar region or a region of high-charge density, accompan... more Micelles in aqueous media have either a polar region or a region of high-charge density, accompanied by an electrostatic potential of up to a few hundred millivolts at the micellar surface and a nonpolar hydrophobic region in the micellar core. The kinetics in micellar solutions is governed by ...
Conductivity measurements have been carried out on aqueous solutions of two antidepressant drugs ... more Conductivity measurements have been carried out on aqueous solutions of two antidepressant drugs (nortriptyline hydrochloride and clomipramine hydrochloride) with four cationic surfactants (monomeric: cetyltrimethylammonium bromide, tetradecylammonium bromide; dimeric: 1,5-pentanediyl-␣--bis(hexadecyldimethylammonium bromide), 1,4-butanediyl-␣,-bis(hexadecyldimethylammonium bromide) as well as with sodium chloride. Counterions from NaCl adsorb to the charged headgroup of the drug molecules and reduce the repulsion, hence cmc decreases. cmc values decreased with the addition of surfactants indicating mixed micelle formation. Experimental mole fraction of surfactants in micelle (X 1 ) and their ideal values (X id 1 ) also support this explanation. Interaction parameter, β, and excess free energy of micellization are negative suggesting synergism in mixed state. Activity coefficients are less than unity which means non-ideal mixing.
Clomipramine hydrochloride (CLP) is an antidepressant drug which shows temperature dependent phas... more Clomipramine hydrochloride (CLP) is an antidepressant drug which shows temperature dependent phase separation, also known as the cloud point (CP). Increase in pH decreases the CP of the drug solution. Addition of ureas/thioureas at a fixed pH (6.25) decreases/increases the CP. In ureas, presence of >C O bond causes a decrease in repulsions among positively charged drug molecules. However, >C S bond (of thioureas) behaves oppositely and hence CP increases. Cationic and non-ionic surfactants form mixed micelles and hence increase the CP. Anionic surfactants, at low concentrations, retard micellization and increase the CP. At higher concentrations, these surfactants also form mixed micelles and, due to charge opposite to the drug molecules, reduce the repulsion among micelles and act as CP suppressors. Increase in solution pH/drug concentration at different fixed concentrations of CTAB causes the CP to decrease/increase. Dye solubilization results with the drug have provided proof to the above explanation.
Nine accessions of two wild species of Vigna viz., V. hainiana and V. trilobata, and five accessi... more Nine accessions of two wild species of Vigna viz., V. hainiana and V. trilobata, and five accessions of sub-species of Vigna viz., V. mungo var. silvestris and V. radiata var. radiata grown at Indian Institute of Pulses Research, Kanpur, India during 2010 were observed to ...
Asia. M. nigra has been used in Unani medicine as antitussive, diuretic, expectorant and hypotens... more Asia. M. nigra has been used in Unani medicine as antitussive, diuretic, expectorant and hypotensive. It has wide range of medicinal uses and can be used either as single drug or compound drugs to treat different ailments. The phenolic compounds of M. nigra have anti ...
Development of brain metastasis in patients with breast carcinoma correlates with poor outcome. I... more Development of brain metastasis in patients with breast carcinoma correlates with poor outcome. Identification of tumor characteristics associated with breast cancer brain metastases (BCBM) could help identify patients at risk. We studied 209 patients with BCBM. We evaluated a panel of proteins relevant to the biology of breast carcinoma on tissue microarrays of 133 primary tumors and 56 BCBM, including paired samples from 43 patients, and correlated the findings with the clinical outcome. The median survival after BCBM diagnosis was 19 months (95% confidence interval, 13-23 months). Patients presenting with solitary metastasis had a significantly longer median survival than those with multiple lesions (25 versus 11 months, P ≤ 0.0001). We found no significant discordance in the expression of tested markers, but identified a possible association between the expression of basal cytokeratin CK5/6 in the primary carcinoma and the development of multiple rather than solitary brain metastases. Expression of antigens commonly associated with breast carcinoma does not differ significantly between the primary tumor and the corresponding brain metastases. Although no specific immunoprofile identifies breast carcinomas that develop brain metastases, we observed a possible association between CK5/6 expression in the primary tumor and multiple versus solitary BCBM.
Annals of Clinical Microbiology and Antimicrobials, 2007
Background: Urinary tract infections (UTIs) remain the common infections diagnosed in outpatients... more Background: Urinary tract infections (UTIs) remain the common infections diagnosed in outpatients as well as hospitalized patients. Current knowledge on antimicrobial susceptibility pattern is essential for appropriate therapy. Extended-Spectrum beta-Lactamase (ESBL) producing bacteria may not be detected by routine disk diffusion susceptibility test, leading to inappropriate use of antibiotics and treatment failure. The aim of this study was to determine the distribution and antibiotic susceptibility patterns of bacterial strains isolated from patients with community acquired urinary tract infections (UTIs) at Aligarh hospital in India as well as identification of ESBL producers in the population of different uropathogens.
ABSTRACT Anatomical responses of salt tolerant, moderate tolerant and sensitive wheat accessions/... more ABSTRACT Anatomical responses of salt tolerant, moderate tolerant and sensitive wheat accessions/varieties were investigated at 10, 15 and 20 dS m-1 levels of NaCl salinity in a pot experiment in addition to control (2.5 dS m-1). Salinity induced specific changes in the ...
Background: Trabectedin (T), a marine alkaloid, has shown striking antitumor activity in a variet... more Background: Trabectedin (T), a marine alkaloid, has shown striking antitumor activity in a variety of preclinical models. Clinical investigations have shown that T is effective in myxoid liposarcomas (MLS). In this disease, characterized by the chimeric protein FUS-CHOP, the drug is extremely active (a clinical response rate in 50% of patients). In order to investigate the mechanisms of resistance, a trabectedin resistant cell line, 402−91/ET, derived from MLS 402-91 cells, was developed. Material and Methods: 402-91/ET cell line was made by a stepwise increase in drug concentration. Drug sensitivity was measured by colony assay, MDR related proteins by FACS analysis, the XPG by PCR and Western Blot, the binding of FUS-CHOP by Chip analysis. Results: 402-91/ET cell line shows 10 fold stable resistance to trabectedin. No differences were found in MDR related proteins and in uptake/efflux of T between the parental and resistant cells. The cross resistance to Melphalan and trabectedin was reverted by GSH depletion. The collateral sensitivity of 402-91/ET cells to UV was related to the lack of XPG gene; the transfection of resistant cell line with an expression vector encoding the XPG cDNA reversed the UV hypersensitivity but not the resistance to T. 402−91/ET cell line showed a collateral sensitivity to temozolomide due to methylation of MGMT promoter. In 402−91 cells FUS-CHOP chimera, bound to PTX3 and FN1 promoters, was detached by trabectedin treatment whereas in 402−91/ET cells it was not bound. Conclusion: We developed for the first time a stable model of MLS cell line resistant to trabectedin. The resistance mechanism of 402−91/ET to the drug is probably related to changes in the transcription regulation mediated by FUS-CHOP chimera. Studies are ongoing to elucidate the molecular mechanism by which this process occurs.
... M. Owais Khan Faculty of Eastern Medicine Shifa-ul-Mulk Memorial Hospital Hamdard University ... more ... M. Owais Khan Faculty of Eastern Medicine Shifa-ul-Mulk Memorial Hospital Hamdard University Karachi Pakistan. ... Khalil Ahmad Ansari College of Conventional Medicine Faculty of Pharmacy and Alternative Medicine The Islamia University of Bahawalpur Pakistan. ...
The coexistence of neuroblastic and Schwannian stromal (SS) cells in differentiating neuroblastom... more The coexistence of neuroblastic and Schwannian stromal (SS) cells in differentiating neuroblastoma (NB), and derivation of Schwannian-like cells from neuroblastic clones in vitro, were accepted previously as evidence of a common pluripotent tumor stem line. This paradigm was challenged when SS cells were suggested to be reactive in nature. The advent of microdissection techniques, PCR-based allelic analysis, and in situ fluorescent cytometry made possible the analysis of pure cell populations in fresh surgical specimens, allowing unequivocal determination of clonal origins of various cell subtypes. To overcome the complexity and heterogeneity of three-dimensional tissue structure, we used: (a) Laser-Capture Microdissection to obtain histologically homogeneous cell subtype populations for allelotype analysis at chromosomes 1p36, 11q23, 14q32, and 17q and study of MYCN copy number; (b) multiparametric analysis by Laser-Scanning Cytometry of morphology, DNA content, and immunophenotype...
... Its decoction is prescribed in irregular menstruation. It is used as blood purifier and is fo... more ... Its decoction is prescribed in irregular menstruation. It is used as blood purifier and is found effective in piles, prolapsed uterus and anus and diarrhea (Ahmadi et al., 2010). Justcia adhatoda L. Local name: Baikar, Part used: Leaves. ... In Arabs, this drug Akram et al. 4161 ...
Extended-spectrum beta-lactamases (ESBLs) are bacterial enzymes that confer resistance to advance... more Extended-spectrum beta-lactamases (ESBLs) are bacterial enzymes that confer resistance to advanced generation cephalosporins and can lead to therapeutic failures. There has been no analysis of factors associated with the risk of acquisition of ESBLs in neonates in an intensive care unit from northern India. The CTX-M ESBL enzymes impart resistance against advanced generation cephalosporins (e.g. cefotaxime) and CTX-M variants have become the most prevalent ESBLs worldwide. The CTX-M-15 enzyme in particular is increasingly being reported from Escherichia coli isolates from northern India together with TEM-1. Moreover, E. coli is the most common cause of neonatal sepsis. Accordingly, this study aimed to: (i) characterize the mode of transmission of bla(CTX-M) and bla(TEM) among ESBL-producing E. coli strains isolated from patients admitted to a neonatal intensive care unit (NICU), and (ii) identify factors associated with the acquisition of the said strains in male and female neonates. A total of 97 ESBL-producers was identified among 266 E. coli strains isolated from 238 neonates. The isolates were screened for bla(CTX-M), bla(TEM), armA, rmtA and rmtB, the last three genes being responsible for aminoglycoside resistance. PCR amplified bla(CTX-M) genes were cloned and sequenced. Five bla(CTX-M-15), two rmtB, two bla(TEM-1) and thirteen class1 integrons were detected. All the bla(CTX-M-15) positive isolates, except one, were clonally related. Both univariate and multivariate analyses of factors for the acquisition of the said strains were performed with respect to the sex of the neonates. 'Length of stay in the NICU' was found to be the single independent factor associated with ESBL acquisition. In conclusion, our data suggest that male neonates who are colonized or infected by ESBL-producing E. coli have a longer stay in the NICU compared to their female counterparts. This prolonged stay may be due to male neonates becoming colonized/infected earlier than their female counterparts. Plasmid-mediated-conjugal transfer was found to be the mechanism of transfer of the bla(CTX-M-15) resistance marker in the described setting.
Integrons have been observed to be frequently associated with uropathogenic bacteria. This study ... more Integrons have been observed to be frequently associated with uropathogenic bacteria. This study aimed at 1) determining the prevalence of class 1 integrons among ESBLl-producing uropathogenic Escherichia coli, and 2) analyzing resistance genes associated with different phylogenetic groups of the integron-positive isolates with special reference to bla(CTX-M) and bla(TEM). Twenty-three ESBL-producing E. coli were studied. Enterobacterial repetitive intergenic consensus-PCR (ERIC-PCR) displayed 14 major patterns. Pulse field Gel electrophoresis-typing of 8 randomly selected integron-positive strains ruled out any correlation between genotype and antibiotype. Genomic DNA from 14 strains was PCR-positive for class 1 integrons, bla(CTX-M-15) and bla(TEM-1)-like genes. Integron-sequencing revealed "aadA5-dfrA17-dfrA7" as the most prevalent gene cassette. Our findings unveil the increasing role of the bla(CTX-M) genes in antibiotic resistance and emphasize on the significance of appropriate empirical treatment for Urinary tract infections. Moreover, this is the first study which reports bla(CTX-M) located on genomic DNA of bacteria from India.
Micelles in aqueous media have either a polar region or a region of high-charge density, accompan... more Micelles in aqueous media have either a polar region or a region of high-charge density, accompanied by an electrostatic potential of up to a few hundred millivolts at the micellar surface and a nonpolar hydrophobic region in the micellar core. The kinetics in micellar solutions is governed by ...
Conductivity measurements have been carried out on aqueous solutions of two antidepressant drugs ... more Conductivity measurements have been carried out on aqueous solutions of two antidepressant drugs (nortriptyline hydrochloride and clomipramine hydrochloride) with four cationic surfactants (monomeric: cetyltrimethylammonium bromide, tetradecylammonium bromide; dimeric: 1,5-pentanediyl-␣--bis(hexadecyldimethylammonium bromide), 1,4-butanediyl-␣,-bis(hexadecyldimethylammonium bromide) as well as with sodium chloride. Counterions from NaCl adsorb to the charged headgroup of the drug molecules and reduce the repulsion, hence cmc decreases. cmc values decreased with the addition of surfactants indicating mixed micelle formation. Experimental mole fraction of surfactants in micelle (X 1 ) and their ideal values (X id 1 ) also support this explanation. Interaction parameter, β, and excess free energy of micellization are negative suggesting synergism in mixed state. Activity coefficients are less than unity which means non-ideal mixing.
Clomipramine hydrochloride (CLP) is an antidepressant drug which shows temperature dependent phas... more Clomipramine hydrochloride (CLP) is an antidepressant drug which shows temperature dependent phase separation, also known as the cloud point (CP). Increase in pH decreases the CP of the drug solution. Addition of ureas/thioureas at a fixed pH (6.25) decreases/increases the CP. In ureas, presence of >C O bond causes a decrease in repulsions among positively charged drug molecules. However, >C S bond (of thioureas) behaves oppositely and hence CP increases. Cationic and non-ionic surfactants form mixed micelles and hence increase the CP. Anionic surfactants, at low concentrations, retard micellization and increase the CP. At higher concentrations, these surfactants also form mixed micelles and, due to charge opposite to the drug molecules, reduce the repulsion among micelles and act as CP suppressors. Increase in solution pH/drug concentration at different fixed concentrations of CTAB causes the CP to decrease/increase. Dye solubilization results with the drug have provided proof to the above explanation.
Nine accessions of two wild species of Vigna viz., V. hainiana and V. trilobata, and five accessi... more Nine accessions of two wild species of Vigna viz., V. hainiana and V. trilobata, and five accessions of sub-species of Vigna viz., V. mungo var. silvestris and V. radiata var. radiata grown at Indian Institute of Pulses Research, Kanpur, India during 2010 were observed to ...
Asia. M. nigra has been used in Unani medicine as antitussive, diuretic, expectorant and hypotens... more Asia. M. nigra has been used in Unani medicine as antitussive, diuretic, expectorant and hypotensive. It has wide range of medicinal uses and can be used either as single drug or compound drugs to treat different ailments. The phenolic compounds of M. nigra have anti ...
Development of brain metastasis in patients with breast carcinoma correlates with poor outcome. I... more Development of brain metastasis in patients with breast carcinoma correlates with poor outcome. Identification of tumor characteristics associated with breast cancer brain metastases (BCBM) could help identify patients at risk. We studied 209 patients with BCBM. We evaluated a panel of proteins relevant to the biology of breast carcinoma on tissue microarrays of 133 primary tumors and 56 BCBM, including paired samples from 43 patients, and correlated the findings with the clinical outcome. The median survival after BCBM diagnosis was 19 months (95% confidence interval, 13-23 months). Patients presenting with solitary metastasis had a significantly longer median survival than those with multiple lesions (25 versus 11 months, P ≤ 0.0001). We found no significant discordance in the expression of tested markers, but identified a possible association between the expression of basal cytokeratin CK5/6 in the primary carcinoma and the development of multiple rather than solitary brain metastases. Expression of antigens commonly associated with breast carcinoma does not differ significantly between the primary tumor and the corresponding brain metastases. Although no specific immunoprofile identifies breast carcinomas that develop brain metastases, we observed a possible association between CK5/6 expression in the primary tumor and multiple versus solitary BCBM.
Annals of Clinical Microbiology and Antimicrobials, 2007
Background: Urinary tract infections (UTIs) remain the common infections diagnosed in outpatients... more Background: Urinary tract infections (UTIs) remain the common infections diagnosed in outpatients as well as hospitalized patients. Current knowledge on antimicrobial susceptibility pattern is essential for appropriate therapy. Extended-Spectrum beta-Lactamase (ESBL) producing bacteria may not be detected by routine disk diffusion susceptibility test, leading to inappropriate use of antibiotics and treatment failure. The aim of this study was to determine the distribution and antibiotic susceptibility patterns of bacterial strains isolated from patients with community acquired urinary tract infections (UTIs) at Aligarh hospital in India as well as identification of ESBL producers in the population of different uropathogens.
ABSTRACT Anatomical responses of salt tolerant, moderate tolerant and sensitive wheat accessions/... more ABSTRACT Anatomical responses of salt tolerant, moderate tolerant and sensitive wheat accessions/varieties were investigated at 10, 15 and 20 dS m-1 levels of NaCl salinity in a pot experiment in addition to control (2.5 dS m-1). Salinity induced specific changes in the ...
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