Abstract Dietary conjugated linoleic acid (CLA) and the antihypertensive drug, telmisartan, have both been shown to modify cardiovascular risks. The effects of a combination of these two agents have, however, not been investigated. This 20 week study sought to assess the therapeutic potential of a CLA/telmisartan co‐administration in rats fed a high‐fructose high‐fat diet. Thirty‐three male Sprague–Dawley rats were randomly assigned to five experimental groups, including control, losartan, telmisartan, CLA, and CLA + telmisartan‐treated animals. Body weight, blood pressure, and blood levels of lipids, glucose, insulin, and inflammatory markers were measured. Co‐administration of CLA and telmisartan resulted in significant ( P < 0.05) reductions in body weight, visceral fat, serum total cholesterol, triglycerides, glucose, plasma insulin concentrations, and systolic blood pressure compared with those in the control group. Moreover, plasma levels of IL1‐α and IFN‐γ were reduced and levels of IL1‐β, IL‐4, IL‐6, and IL‐10, plus TNF‐α were increased in the co‐therapy group, compared with controls. In conclusion, this study suggests that a combination of CLA with telmisartan may modify several risk factors of cardiovascular disease commonly seen in metabolic syndrome. This combination of nutraceuticals and pharmaceuticals may be a safe and cost‐effective strategy in a number of high‐risk subjects. Future studies will further document clinical benefits of such combination therapy.
Plasmids are important antibiotic resistance determinant carriers that can disseminate various drug resistance genes among species or genera. By using a high throughput sequencing approach, two groups of plasmids of Escherichia coli (named E1 and E2, each consisting of 160 clinical E. coli strains isolated from different periods of time) were sequenced and analyzed. A total of 20 million reads were obtained and mapped onto the known resistance gene sequences. As a result, a total of 9 classes, including 36 types of antibiotic resistant genes, were identified. Among these genes, 25 and 27 single nucleotide polymorphisms (SNPs) appeared, of which 9 and 12 SNPs are nonsynonymous substitutions in the E1 and E2 samples. It is interesting to find that a novel genotype of blaKLUC, whose close relatives, blaKLUC-1 and blaKLUC-2, have been previously reported as carried on the Kluyvera cryocrescens chromosome and Enterobacter cloacae plasmid, was identified. It shares 99% and 98% amino acid identities with Kluc-1 and Kluc-2, respectively. Further PCR screening of 608 Enterobacteriaceae family isolates yielded a second variant (named blaKLUC-4). It was interesting to find that Kluc-3 showed resistance to several cephalosporins including cefotaxime, whereas blaKLUC-4 did not show any resistance to the antibiotics tested. This may be due to a positively charged residue, Arg, replaced by a neutral residue, Leu, at position 167, which is located within an omega-loop. This work represents large-scale studies on resistance gene distribution, diversification and genetic variation in pooled multi-drug resistance plasmids, and provides insight into the use of high throughput sequencing technology for microbial resistance gene detection.
Background: Diets high in fructose may result in abnormalities in glucose and lipid metabolism. Purpose: To investigate the effects of a high‐fructose diet on liver fatty acid composition. Methods: Male Sprague‐Dawley rats were divided into two groups: a control group (n=5) receiving standard chow diet, and treatment group (n=7) receiving a diet containing 10% w/w lard and 60% w/w fructose for 20 weeks. Fatty acid profile of various lipid fractions in the liver of these animals was characterized. Results: Total liver lipids including cholesterol and triacyglycerol (TAG) were significantly higher in the treated group as compared to controls. The livers from treated animals had significantly lower levels of C16:0 and higher levels of C18:1 in the TAG fraction, and lower levels of C18:1c11, C18:2c9, C20:1c11, C20:1c13 along with higher levels of C16:1 and C18:1c9 in the free fatty acid fraction. The levels of C16:0, C18:2c9, C20:1c11, C20:1c13, C20:2c11 and C24:0 were significantly increased in the phosholipid fraction of the treated animals. Conclusions: High intakes of fructose change liver lipid composition and fatty acid profile in rats. TAG and phospholipid fractions seem to be affected more. These changes may lead to alterations in hepatocyte functions including lipid metabolism and may modify cardiovascular risk.
Background: We have consistently observed that dietary phytosterols significantly reduce plasma cholesterol concentrations and atherosclerosis in apo E-KO mice. We investigated long-term effects of phytosterol treatment on gene expression in the liver of these mice. Methods: Male apo E-KO mice were fed an atherogenic diet supplemented with (n=8) or without (n=7) 2% (w/w) phytosterol mixtures for 14 weeks. Liver specimens were collected and frozen immediately. mRNA was extracted from these samples, and subjected to microarray analyses. Results: The expression of 137 genes was significantly changed in the phytosterol-treated group, as compared to controls. Various database searches indicated that these genes are involved in a number of metabolic pathways including lipid metabolism, inflammation, glucose metabolism, protein metabolism, heme biosynthesis and others. These changes were associated with significant reductions in plasma cholesterol levels and the severity of atherosclerosis. Conclusions: Anti-atherogenic and cholesterol-lowering effects of plant sterols in apo E-KO mice may be mediated through beneficial alterations in the expression of genes in various pathways involved in pathogenesis of atherosclerosis. Further studies warrant mechanisms by which dietary phytosterols regulate gene expression. Acknowledgements: Supported by NSERC, CIHR, and Heart and Stroke Foundation.
In order to get insights into plasmid evolution and the dissemination of multidrug resistance, we performed extensive comparative genomics analyses of the Klebsiella pneumoniae plasmid pKF3-94 and some of its related plasmids. pKF3-94 is one of three plasmids isolated from the K. pneumoniae strain KF3. Of the 144 putative genes it harbors, 69 can be functionally assigned to be involved in transfer conjugation, transfer leading, antimicrobial resistance, transposon function, and plasmid replication. Comparison of plasmid replicon sequence types revealed that pKF3-94 carries two replicons that are distinct from those carried on the two sibling K. pneumonia plasmids pKF3-70 and pKF3-140, thereby allowing pKF3-94 to coexist with these latter plasmids in the same host cell. Comparative genomics analyses further showed that pKF3-94 is more similar to plasmids pK1HV and pC15-k, which were isolated from different K. pneumonia strains, than to pKF3-70 and pKF3-140. Interestingly, pK1HV contains a unique 49 kb region rich in mobile genetic elements and drug resistance genes, while pKF3-94 and pC15-k share a 15 kb homology region partitioned into a region rich in drug resistance genes and one containing a replicon. It is conceivable, therefore, that pK1HV and pC15-k have both arisen from a common pKF3-94-like plasmid. The comparisons lend further support for the role horizontal gene transfer plays in genome evolution and in the dissemination of genetic elements including drug resistance genes.
Thermoanaerobacter tengcongensis is a rod-shaped, gram-negative, anaerobic eubacterium that was isolated from a freshwater hot spring in Tengchong, China. Using a whole-genome-shotgun method, we sequenced its 2,689,445-bp genome from an isolate, MB4 T (Genbank accession no. AE008691 ). The genome encodes 2588 predicted coding sequences (CDS). Among them, 1764 (68.2%) are classified according to homology to other documented proteins, and the rest, 824 CDS (31.8%), are functionally unknown. One of the interesting features of the T. tengcongensis genome is that 86.7% of its genes are encoded on the leading strand of DNA replication. Based on protein sequence similarity, the T. tengcongensis genome is most similar to that of Bacillus halodurans , a mesophilic eubacterium, among all fully sequenced prokaryotic genomes up to date. Computational analysis on genes involved in basic metabolic pathways supports the experimental discovery that T. tengcongensis metabolizes sugars as principal energy and carbon source and utilizes thiosulfate and element sulfur, but not sulfate, as electron acceptors. T. tengcongensis , as a gram-negative rod by empirical definitions (such as staining), shares many genes that are characteristics of gram-positive bacteria whereas it is missing molecular components unique to gram-negative bacteria. A strong correlation between the G + C content of tDNA and rDNA genes and the optimal growth temperature is found among the sequenced thermophiles. It is concluded that thermophiles are a biologically and phylogenetically divergent group of prokaryotes that have converged to sustain extreme environmental conditions over evolutionary timescale. [Supplemental material is available online at http://www.genome.org .]
Background: High fat, high carbohydrate diets are supposedly contributing to the increased prevalence of obesity, diabetes and other metabolic disorders associated with coronary artery disease. We have examined long-term effects of a defined high fat/high fructose diet on several cardiovascular risk factors in rats. Methods: Male Sprague Dawley rats fed either regular chow (n=5) or a commercial diet containing 10% lard and 60% fructose (n=7) for 20 weeks. Plasma lipids, glucose, insulin and cytokine levels were measured. Body weight, food consumption, water consumption, and systolic blood pressure were recorded. Results: Systolic blood pressure plus serum triglycerides, total cholesterol, and insulin levels were significantly higher in the treated rats, as compared to controls. Body weight and plasma glucose levels were comparable between the groups. Conclusions: Long-term consumption of diets high in fat and fructose significantly increase several independent cardiovascular risk factors without causing obesity in rats. Longer studies warrant investigation of these changes on development of atherosclerotic lesions. Acknowledgements: Supported by NSERC, CIHR, and the Heart and Stroke Foundation.
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