Spatial learning plays a major role in one's information ... more Spatial learning plays a major role in one's information recording. Arsenic is one of ubiquitous environmental toxins with known neurological effects. However, studies investigating the effects of arsenic on spatial learning and related mechanisms are limited. This study was planned toexaminethe effects of bilateral intra-hippocampal infusion of different concentrations of sodium arsenite (5, 10 and 100nM, 5µl/side) on spatial learning in Wistar rats. Moreover, we evaluated levels of LC3-II, Atg7 and Atg12 as reliable biomarkers of autophagy and caspase-3 and Bax/Bcl-2 ratio as indicators of apoptosis in the hippocampus. Interestingly, low concentrations of sodium arsenite (5 and 10nM) significantly increased spatial acquisition but pre-training administration of sodium arsenite100nM did not significantly alter spatial learning. LC3-II levels were significantly increased in groups treated with sodium arsenite 5 and 10nM and decreased in the group receiving arsenite 100nM compared to the control group. Atg7 and Atg12 levels were obviously higher in all groups treated with sodium arsenite compared to control. However, caspase-3 cleavage and Bax/Bcl-2 ratio were notably greater in 100nM, and lesser in 5nM arsenite group in comparison with control animals. The results of this study showed that the low concentrations of sodium arsenite could facilitate spatial learning. This facilitation could be attributed to neuronal autophagy induced by low concentrations of sodium arsenite. These findings may help to clarify the regulatory pathways for apoptosis and autophagy balance due to sodium arsenite.
Pharmacology, biochemistry, and behavior, Jan 17, 2015
Crocin, as a carotenoid, is one of the main and active constituents of saffron stigmas (Crocus sa... more Crocin, as a carotenoid, is one of the main and active constituents of saffron stigmas (Crocus sativus L.) that is widely used in folk medicine. Several studies have pointed out the potent antioxidant and neuroprotective properties of crocin which may have therapeutic values for management of neurodegenerative disorders such as Alzheimer's disease. Alzheimer's disease is the most common form of dementia among the elderly and is characterized by massive neuronal loss and progressive cognitive impairment. Beta amyloid hypothesis is the main theoretical research framework for Alzheimer's disease which states that extracellular aggregation of beta amyloid results in synaptic loss and eventually cell apoptosis. Recent findings suggest that autophagy and apoptosis are extensively involved in Alzheimer's disease. In order to investigate therapeutic values of crocin, we examined the effect of crocin on memory, cell apoptosis, and autophagy using in vivo models of Alzheimer&#...
Escherichia coli O25b-B2-ST131 are considered virulent extra-intestinal pathogens causing serious... more Escherichia coli O25b-B2-ST131 are considered virulent extra-intestinal pathogens causing serious clinical complications such as urinary tract infection and bacteraemia. Our main objectives in this study were to characterise the multi-drug resistant (MDR) isolates of this lineage in Kuwait, and to demonstrate whether reduced susceptibility is spread clonally. A subset of 83 (10%) non-duplicate and non-selective E. coli O25b-B2-ST131 out of 832 MDR E. coli was identified and collected. Minimum inhibitory concentrations of the isolates were determined and pulsed-field gel electrophoresis was used for typing.The majority (95.2%) of the 83 E. coli O25b-B2-ST131 harboured at least one bla gene with blaCTX-M-15 being the most prevalent. blaCTX-M-2 was present in one isolate. Also one isolate harboured blaCTX-M-56, qnrB1 and blaCMY-2 genes and carried IncF1 plasmids of about 97 kb and160 kb. qnrB and qnrS were found in 8 other blaCTX-M-15 containing isolates. The blaNDM, blaIMP, blaVIM and qnrA were not detected, however, the blaOXA-48 was present in two (2.4%). The majority of isolates harbouring qnr genes demonstrated relatedness (≥85%) by PFGE. However, the diversity in PFGE profiles for the other MDR isolates reflected the changes in population genetics of E. coli O25b-B2-ST131. We identified for the first time the appearance of blaCTX-M-2 in the Middle East and blaCTX-M-56 outside the Latin American countries. The isolate harbouring blaCTX-M-56 also contained qnrB1 and blaCMY-2 genes and carried IncF1 plasmids. The appearance of a highly virulent E. coli O25b-ST131 that is resistant to penicillins, most cephalosproins, β-lactamase inhibitors as well as fluoroquinolones is a cause for concern.
Objective: In this study we investigated the genetic relatedness of multi-drug resistant Acinetob... more Objective: In this study we investigated the genetic relatedness of multi-drug resistant Acinetobacter baumannii isolates in Kuwait. Methods: One hundred clinical A. baumannii isolates were collected. gyrB multiplex PCR was performed to identify the isolates at species level. Antibiotic susceptibility testing was performed according to the EUCAST guidelines. PCR was used to amplify and consequently sequence bla (OXA-like) carbapenemases, bla(NDM), bla(PER), bla(GES), bla(VIM) and bla(IMP). Pulsed-field gel electrophoresis (PFGE) was employed and analysed by BioNumerics v.7.1 to characterise the isolates. Multi-locus sequence typing (MLST) was performed according to the Institute Pasteur MLST Databases (www.pasteur.fr/mlst) on the strains representing different PFGE types. The MLST results were analysed by eBurst. Results: bla(OXA-23) was identified in 84% of A. baumannii isolates, bla(OXA-24) in 18%, GES-1 type in 15% and PER-1 in 15%. bla (OXA-58), VIM, IMP and blaNDM were not dete...
In this study we investigated the genetic relatedness of multi-drug resistant Acinetobacter bauma... more In this study we investigated the genetic relatedness of multi-drug resistant Acinetobacter baumannii isolates in Kuwait. One hundred and ten clinical A. baumannii isolates were collected. gyrB multiplex PCR was performed to identify the isolates at species level. Antibiotic susceptibility testing was performed according to the EUCAST guidelines. PCR was used to amplify and consequently sequence bla (OXA-like) carbapenemases, bla(NDM), bla(PER), bla(GES), bla(VIM) and bla(IMP). Pulsed-field gel electrophoresis (PFGE) was employed and analysed by BioNumerics v.7.1 to characterise the isolates. Multi-locus sequence typing (MLST) was performed according to the Institute Pasteur MLST Databases (www.pasteur.fr/mlst) on the strains representing different PFGE types. The MLST results were analysed by eBurst. bla(OXA-23) was identified in 84% of A. baumannii isolates, bla(OXA-24) in 18%, GES-1 type in 15% and PER-1 in 15%. bla (OXA-58), VIM, IMP and blaNDM were not detected. PFGE analysis r...
Background: The aim of this study was to determine if ertapenem (ERT) has the potency to induce c... more Background: The aim of this study was to determine if ertapenem (ERT) has the potency to induce carbapenem resistance in gram-negative bacteria, especially non-fermenters, in hospitals. Methods: Matched gram-negative bacterial isolates, responsible for hospital-acquired infections in 2007, were collected from the Freeman Hospital, Newcastle, (FHN) from wards where ERT was given and the Edinburgh Royal Infirmary (ERI) where meropenem (MERO) was the only carbapenem used. MICs of the carbapenems were determined by the agar dilution method following the CLSI guidelines. Single-step challenge experiments were performed with ERT and MERO; viable titres and antibiotic resistance levels (population analysis) for each strain were determined by plating diluted cultures onto IST agar plates containing concentrations of ERT and MERO at 1/4, 1/2, 1, 2, and 4x MIC. Surviving colonies were counted after overnight incubation at 37°C. A colony was purified, subcultured onto antibiotic-free media and...
Acinetobacter baumannii is one of the most important opportunistic pathogens that causes serious ... more Acinetobacter baumannii is one of the most important opportunistic pathogens that causes serious health care associated complications in critically ill patients. In the current study we report on the diversity of the clinical multi-drug resistant (MDR) A. baumannii in Kuwait by molecular characterization. One hundred A. baumannii were isolated from one of the largest governmental hospitals in Kuwait. Following the identification of the isolates by molecular methods, the amplified bla OXA-51-like gene product of one isolate (KO-12) recovered from blood showed the insertion of the ISAba19 at position 379 in bla OXA-78. Of the 33 MDR isolates, 28 (85%) contained bla OXA-23, 2 (6%) bla OXA-24 and 6 (18%) bla PER-1 gene. We did not detect bla OXA-58, bla VIM, bla IMP, bla GES, bla VEB, and bla NDM genes in any of the tested isolates. In three bla PER-1 positive isolates the genetic environment of bla PER-1 consisted of two copies of ISPa12 (tnpiA1) surrounding the bla PER-1 gene on a highly stable plasmid of ca. 140-kb. Multilocus-sequence typing (MLST) analysis of the 33 A. baumannii isolates identified 20 different STs, of which six (ST-607, ST-608, ST-609, ST-610, ST-611, and ST-612) were novel. Emerging STs such as ST15 (identified for the first time in the Middle East), ST78 and ST25 were also detected. The predominant clonal complex was CC2. Pulsed-field gel electrophoresis and MLST defined the MDR isolates as multi-clonal with diverse lineages. Our results lead us to believe that A. baumannii is diverse in clonal origins and/or is undergoing clonal expansion continuously while multiple lineages of MDR A. baumannii circulate in hospital ward simultaneously.
International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases, Jan 30, 2015
In most hospitals, chlorhexidine is used as skin antiseptic prior to clinical procedures, in dres... more In most hospitals, chlorhexidine is used as skin antiseptic prior to clinical procedures, in dressings and when bathing patients. We hereby report, for the first time, the isolation of a clinical Klebsiella oxytoca isolate with reduced sensitivity to chlorhexidine from a foot ulcer of a diabetic patient, which is a common and serious complication associated with diabetes. The Minimum Inhibitory Concentration of the K. oxytoca isolate to chlorhexidine was found to be 30mg/L and the Minimum Bactericidal Concentration was 60mg/L. An increased resistance to ethidium bromide (MIC 200mg/L) was also observed. Molecular tests revealed that the isolate contained blaCTXM15, blaTEM-1 and blaSHV. The other resistant genes detected were qnrB1 and aac(6')-Ib-cr. The resistant determinants were located on a class I integron integrase (intI1) containing qacE gene. DNA sequencing showed homology to K. oxytoca plasmid pACM1. Identification of K. oxytoca with reduced sensitivity to chlorhexidine r...
A cohort of spring-born beef calves demonstrated limited genetic and phenotypic diversity of Esch... more A cohort of spring-born beef calves demonstrated limited genetic and phenotypic diversity of Escherichia coli O157 when kept in a state of isolation. Despite this, there was a difference in the pulsed-field gel electrophoresis and phage types of isolates shed by cattle at pasture compared with those shed by the same cattle when weaned and housed.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2001
Many neurons die as the normal brain develops. How this is regulated and whether the mechanism in... more Many neurons die as the normal brain develops. How this is regulated and whether the mechanism involves neurotrophic molecules from target cells are unknown. We found that cultured neurons from a key forebrain structure, the dorsal thalamus, develop a need for survival factors including brain-derived neurotrophic factor (BDNF) from their major target, the cerebral cortex, at the age at which they innervate it. Experiments in vivo have shown that rates of dorsal thalamic cell death are reduced by increasing cortical levels of BDNF and are increased in mutant mice lacking functional BDNF receptors or thalamocortical projections; these experiments have also shown that an increase in the rates of dorsal thalamic cell death can be achieved by blocking BDNF in the cortex. We suggest that the onset of a requirement for cortex-derived neurotrophic factors initiates a competitive mechanism regulating programmed cell death among dorsal thalamic neurons.
Spatial learning plays a major role in one's information ... more Spatial learning plays a major role in one's information recording. Arsenic is one of ubiquitous environmental toxins with known neurological effects. However, studies investigating the effects of arsenic on spatial learning and related mechanisms are limited. This study was planned toexaminethe effects of bilateral intra-hippocampal infusion of different concentrations of sodium arsenite (5, 10 and 100nM, 5µl/side) on spatial learning in Wistar rats. Moreover, we evaluated levels of LC3-II, Atg7 and Atg12 as reliable biomarkers of autophagy and caspase-3 and Bax/Bcl-2 ratio as indicators of apoptosis in the hippocampus. Interestingly, low concentrations of sodium arsenite (5 and 10nM) significantly increased spatial acquisition but pre-training administration of sodium arsenite100nM did not significantly alter spatial learning. LC3-II levels were significantly increased in groups treated with sodium arsenite 5 and 10nM and decreased in the group receiving arsenite 100nM compared to the control group. Atg7 and Atg12 levels were obviously higher in all groups treated with sodium arsenite compared to control. However, caspase-3 cleavage and Bax/Bcl-2 ratio were notably greater in 100nM, and lesser in 5nM arsenite group in comparison with control animals. The results of this study showed that the low concentrations of sodium arsenite could facilitate spatial learning. This facilitation could be attributed to neuronal autophagy induced by low concentrations of sodium arsenite. These findings may help to clarify the regulatory pathways for apoptosis and autophagy balance due to sodium arsenite.
Pharmacology, biochemistry, and behavior, Jan 17, 2015
Crocin, as a carotenoid, is one of the main and active constituents of saffron stigmas (Crocus sa... more Crocin, as a carotenoid, is one of the main and active constituents of saffron stigmas (Crocus sativus L.) that is widely used in folk medicine. Several studies have pointed out the potent antioxidant and neuroprotective properties of crocin which may have therapeutic values for management of neurodegenerative disorders such as Alzheimer's disease. Alzheimer's disease is the most common form of dementia among the elderly and is characterized by massive neuronal loss and progressive cognitive impairment. Beta amyloid hypothesis is the main theoretical research framework for Alzheimer's disease which states that extracellular aggregation of beta amyloid results in synaptic loss and eventually cell apoptosis. Recent findings suggest that autophagy and apoptosis are extensively involved in Alzheimer's disease. In order to investigate therapeutic values of crocin, we examined the effect of crocin on memory, cell apoptosis, and autophagy using in vivo models of Alzheimer&#...
Escherichia coli O25b-B2-ST131 are considered virulent extra-intestinal pathogens causing serious... more Escherichia coli O25b-B2-ST131 are considered virulent extra-intestinal pathogens causing serious clinical complications such as urinary tract infection and bacteraemia. Our main objectives in this study were to characterise the multi-drug resistant (MDR) isolates of this lineage in Kuwait, and to demonstrate whether reduced susceptibility is spread clonally. A subset of 83 (10%) non-duplicate and non-selective E. coli O25b-B2-ST131 out of 832 MDR E. coli was identified and collected. Minimum inhibitory concentrations of the isolates were determined and pulsed-field gel electrophoresis was used for typing.The majority (95.2%) of the 83 E. coli O25b-B2-ST131 harboured at least one bla gene with blaCTX-M-15 being the most prevalent. blaCTX-M-2 was present in one isolate. Also one isolate harboured blaCTX-M-56, qnrB1 and blaCMY-2 genes and carried IncF1 plasmids of about 97 kb and160 kb. qnrB and qnrS were found in 8 other blaCTX-M-15 containing isolates. The blaNDM, blaIMP, blaVIM and qnrA were not detected, however, the blaOXA-48 was present in two (2.4%). The majority of isolates harbouring qnr genes demonstrated relatedness (≥85%) by PFGE. However, the diversity in PFGE profiles for the other MDR isolates reflected the changes in population genetics of E. coli O25b-B2-ST131. We identified for the first time the appearance of blaCTX-M-2 in the Middle East and blaCTX-M-56 outside the Latin American countries. The isolate harbouring blaCTX-M-56 also contained qnrB1 and blaCMY-2 genes and carried IncF1 plasmids. The appearance of a highly virulent E. coli O25b-ST131 that is resistant to penicillins, most cephalosproins, β-lactamase inhibitors as well as fluoroquinolones is a cause for concern.
Objective: In this study we investigated the genetic relatedness of multi-drug resistant Acinetob... more Objective: In this study we investigated the genetic relatedness of multi-drug resistant Acinetobacter baumannii isolates in Kuwait. Methods: One hundred clinical A. baumannii isolates were collected. gyrB multiplex PCR was performed to identify the isolates at species level. Antibiotic susceptibility testing was performed according to the EUCAST guidelines. PCR was used to amplify and consequently sequence bla (OXA-like) carbapenemases, bla(NDM), bla(PER), bla(GES), bla(VIM) and bla(IMP). Pulsed-field gel electrophoresis (PFGE) was employed and analysed by BioNumerics v.7.1 to characterise the isolates. Multi-locus sequence typing (MLST) was performed according to the Institute Pasteur MLST Databases (www.pasteur.fr/mlst) on the strains representing different PFGE types. The MLST results were analysed by eBurst. Results: bla(OXA-23) was identified in 84% of A. baumannii isolates, bla(OXA-24) in 18%, GES-1 type in 15% and PER-1 in 15%. bla (OXA-58), VIM, IMP and blaNDM were not dete...
In this study we investigated the genetic relatedness of multi-drug resistant Acinetobacter bauma... more In this study we investigated the genetic relatedness of multi-drug resistant Acinetobacter baumannii isolates in Kuwait. One hundred and ten clinical A. baumannii isolates were collected. gyrB multiplex PCR was performed to identify the isolates at species level. Antibiotic susceptibility testing was performed according to the EUCAST guidelines. PCR was used to amplify and consequently sequence bla (OXA-like) carbapenemases, bla(NDM), bla(PER), bla(GES), bla(VIM) and bla(IMP). Pulsed-field gel electrophoresis (PFGE) was employed and analysed by BioNumerics v.7.1 to characterise the isolates. Multi-locus sequence typing (MLST) was performed according to the Institute Pasteur MLST Databases (www.pasteur.fr/mlst) on the strains representing different PFGE types. The MLST results were analysed by eBurst. bla(OXA-23) was identified in 84% of A. baumannii isolates, bla(OXA-24) in 18%, GES-1 type in 15% and PER-1 in 15%. bla (OXA-58), VIM, IMP and blaNDM were not detected. PFGE analysis r...
Background: The aim of this study was to determine if ertapenem (ERT) has the potency to induce c... more Background: The aim of this study was to determine if ertapenem (ERT) has the potency to induce carbapenem resistance in gram-negative bacteria, especially non-fermenters, in hospitals. Methods: Matched gram-negative bacterial isolates, responsible for hospital-acquired infections in 2007, were collected from the Freeman Hospital, Newcastle, (FHN) from wards where ERT was given and the Edinburgh Royal Infirmary (ERI) where meropenem (MERO) was the only carbapenem used. MICs of the carbapenems were determined by the agar dilution method following the CLSI guidelines. Single-step challenge experiments were performed with ERT and MERO; viable titres and antibiotic resistance levels (population analysis) for each strain were determined by plating diluted cultures onto IST agar plates containing concentrations of ERT and MERO at 1/4, 1/2, 1, 2, and 4x MIC. Surviving colonies were counted after overnight incubation at 37°C. A colony was purified, subcultured onto antibiotic-free media and...
Acinetobacter baumannii is one of the most important opportunistic pathogens that causes serious ... more Acinetobacter baumannii is one of the most important opportunistic pathogens that causes serious health care associated complications in critically ill patients. In the current study we report on the diversity of the clinical multi-drug resistant (MDR) A. baumannii in Kuwait by molecular characterization. One hundred A. baumannii were isolated from one of the largest governmental hospitals in Kuwait. Following the identification of the isolates by molecular methods, the amplified bla OXA-51-like gene product of one isolate (KO-12) recovered from blood showed the insertion of the ISAba19 at position 379 in bla OXA-78. Of the 33 MDR isolates, 28 (85%) contained bla OXA-23, 2 (6%) bla OXA-24 and 6 (18%) bla PER-1 gene. We did not detect bla OXA-58, bla VIM, bla IMP, bla GES, bla VEB, and bla NDM genes in any of the tested isolates. In three bla PER-1 positive isolates the genetic environment of bla PER-1 consisted of two copies of ISPa12 (tnpiA1) surrounding the bla PER-1 gene on a highly stable plasmid of ca. 140-kb. Multilocus-sequence typing (MLST) analysis of the 33 A. baumannii isolates identified 20 different STs, of which six (ST-607, ST-608, ST-609, ST-610, ST-611, and ST-612) were novel. Emerging STs such as ST15 (identified for the first time in the Middle East), ST78 and ST25 were also detected. The predominant clonal complex was CC2. Pulsed-field gel electrophoresis and MLST defined the MDR isolates as multi-clonal with diverse lineages. Our results lead us to believe that A. baumannii is diverse in clonal origins and/or is undergoing clonal expansion continuously while multiple lineages of MDR A. baumannii circulate in hospital ward simultaneously.
International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases, Jan 30, 2015
In most hospitals, chlorhexidine is used as skin antiseptic prior to clinical procedures, in dres... more In most hospitals, chlorhexidine is used as skin antiseptic prior to clinical procedures, in dressings and when bathing patients. We hereby report, for the first time, the isolation of a clinical Klebsiella oxytoca isolate with reduced sensitivity to chlorhexidine from a foot ulcer of a diabetic patient, which is a common and serious complication associated with diabetes. The Minimum Inhibitory Concentration of the K. oxytoca isolate to chlorhexidine was found to be 30mg/L and the Minimum Bactericidal Concentration was 60mg/L. An increased resistance to ethidium bromide (MIC 200mg/L) was also observed. Molecular tests revealed that the isolate contained blaCTXM15, blaTEM-1 and blaSHV. The other resistant genes detected were qnrB1 and aac(6')-Ib-cr. The resistant determinants were located on a class I integron integrase (intI1) containing qacE gene. DNA sequencing showed homology to K. oxytoca plasmid pACM1. Identification of K. oxytoca with reduced sensitivity to chlorhexidine r...
A cohort of spring-born beef calves demonstrated limited genetic and phenotypic diversity of Esch... more A cohort of spring-born beef calves demonstrated limited genetic and phenotypic diversity of Escherichia coli O157 when kept in a state of isolation. Despite this, there was a difference in the pulsed-field gel electrophoresis and phage types of isolates shed by cattle at pasture compared with those shed by the same cattle when weaned and housed.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2001
Many neurons die as the normal brain develops. How this is regulated and whether the mechanism in... more Many neurons die as the normal brain develops. How this is regulated and whether the mechanism involves neurotrophic molecules from target cells are unknown. We found that cultured neurons from a key forebrain structure, the dorsal thalamus, develop a need for survival factors including brain-derived neurotrophic factor (BDNF) from their major target, the cerebral cortex, at the age at which they innervate it. Experiments in vivo have shown that rates of dorsal thalamic cell death are reduced by increasing cortical levels of BDNF and are increased in mutant mice lacking functional BDNF receptors or thalamocortical projections; these experiments have also shown that an increase in the rates of dorsal thalamic cell death can be achieved by blocking BDNF in the cortex. We suggest that the onset of a requirement for cortex-derived neurotrophic factors initiates a competitive mechanism regulating programmed cell death among dorsal thalamic neurons.
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