Effect of walking distance on the change in ankle-brachial pressure index in patients with intermittent claudication

Objectives:The ankle-brachial pressure index (ABPI) responses to different exercise intensities on a treadmill were evaluated to clarify the relationship between intermittent claudication and the haemodynamics in the leg.Patients and methods:Thirty patients with intermittent claudication (32 symptomatic legs) due to peripheral arterial occlusive disease were exercised on a treadmill to determine their pain-free walking distance, maximum walking distance (MWD) and recovery time. Each subject was exercised at 25% and 50% of the MWD to determine the effect of work intensity on the drop in ABPI, and the recovery time.Results:In the claudicating legs, 25% of the MWD resulted in almost the same reduction in ABPI as 50% of the MWD, and the MWD. In contrast, the ABPI in the asymptomatic legs (13) was significantly decreased in proportion to the walking distance. The recovery time increased linearly in both the groups, as the walking distance increased.Conclusion:The recovery time of the ABPI correlated well with the intensity of workload, while the drop in ABPI did not

The Retroperitoneum Protects Prosthetic Graft Material from Intraperitoneal Contamination: An Experimental Study

AbstractObjectivesTo evaluate the ability of the retroperitoneum to serve as a barrier, against bacterial contamination, between the peritoneal cavity to the retroperitoneal space.MethodsSeventy rats had a small piece of knitted Dacron graft placed in the retroperitoneal space and 106–109 colony forming unit (cfu) Enterococcus faecalis was injected into the peritoneal cavity. In half the retroperitoneal (RP) group, the retroperitoneum was preserved and in the remainder, the open peritoneal (OP) group, needle holes were created. Grafts were harvested after 1, 4, or 7 days and cultured for E. faecalis. A blood sample was collected from three rats in each group for culture before the graft was harvested.ResultsGraft infection did not develop in any rat injected with 106 or 107 cfu in the RP group, while seven out of the 10 graft cultures of the OP group grew E. faecalis (P=0.003). In rats injected with 108 or 109 cfu, five out of the 10 graft cultures in the RP group and eight out of 10 in the OP group grew E. faecalis. All blood cultures were negative when the injected bacterial count was 107 cfu or less. One out of the three blood cultures was positive at 108 cfu, and all were positive at 109 cfu.ConclusionsThese results suggest that an intact retroperitroneum acts as a protective barrier against intraperitoneal bacterial contamination, particularly when blood cultures are negative

Plasma metabolomics supports the use of long-duration cardiac arrest rodent model to study human disease by demonstrating similar metabolic alterations.

Cardiac arrest (CA) is a leading cause of death and there is a necessity for animal models that accurately represent human injury severity. We evaluated a rat model of severe CA injury by comparing plasma metabolic alterations to human patients. Plasma was obtained from adult human control and CA patients post-resuscitation, and from male Sprague-Dawley rats at baseline and after 20 min CA followed by 30 min cardiopulmonary bypass resuscitation. An untargeted metabolomics evaluation using UPLC-QTOF-MS/MS was performed for plasma metabolome comparison. Here we show the metabolic commonality between humans and our severe injury rat model, highlighting significant metabolic dysfunction as seen by similar alterations in (1) TCA cycle metabolites, (2) tryptophan and kynurenic acid metabolites, and (3) acylcarnitine, fatty acid, and phospholipid metabolites. With substantial interspecies metabolic similarity in post-resuscitation plasma, our long duration CA rat model metabolically replicates human disease and is a suitable model for translational CA research

Adrenomedullin gene expression differences in mice do not affect blood pressure but modulate hypertension-induced pathology in males

Adrenomedullin (AM) is a potent vasodilator peptide in plasma at picomolar levels. Polymorphisms in the human AM gene have been associated with genetic predisposition to diabetic nephropathy and proteinuria with essential hypertension, and numerous studies have demonstrated that endogenous AM plays a role in protecting the heart and kidneys from fibrosis resulting from cardiovascular disease. Elevated plasma levels of AM are associated with pregnancy and sepsis and with cardiovascular stress and hypertension. However, there are no reports of the effects of genetic differences in the expression of the endogenous AM gene and of gender on blood pressure in these circumstances or on the pathological changes accompanying hypertension. To address these questions, we have generated mice having genetically controlled levels of AM mRNA ranging from ≈50% to ≈140% of wild-type levels. These modest changes in AM gene expression have no effect on basal blood pressure. Although pregnancy and sepsis increase plasma AM levels, genetically reducing AM production does not affect the transient hypotension that occurs during normal pregnancy or that is induced by treatment with lipopolysaccharide. Nor does the reduction of AM affect chronic hypertension caused by a renin transgene. However, 50% normal expression of AM enhances cardiac hypertrophy and renal damage in male, but not female, mice with a renin transgene. These observations suggest that the effect of gender on the role of AM in counteracting cardiovascular damage in humans merits careful evaluation

Evaluation of phenolic contents and antioxidant activity of various solvent extracts of Sonchus asper (L.) Hill

<p>Abstract</p> <p>Background</p> <p><it>Sonchus asper </it>(SA) is traditionally used for the treatment of various ailments associated with liver, lungs and kidneys. This study was aimed to investigate the therapeutic potential of nonpolar (hexane, SAHE; ethyl acetate, SAEE and chloroform, SACE) and polar (methanol, SAME) crude extracts of the whole plant.</p> <p>Methods</p> <p>To achieve these goals, several parameters including free-radical (DPPH^•, ABTS^•+, H₂O₂and ^•OH) scavenging, iron chelating activity, scavenging of superoxide radicals, total flavonoids and total phenolic content (TPC) were examined.</p> <p>Results</p> <p>The SA extracts presented a remarkable capacity to scavenge all the tested reactive species with IC₅₀values being found at the μg ⁄ ml level. The SAME was shown to have the highest TPCs while lowest IC₅₀values for the DPPH^•, ABTS^•+radical scavenging capacities and iron chelating scavenging efficiency, moreover, SAME had best activities in scavenging of superoxide radicals and hydrogen peroxide as well as potently scavenged the hydroxyl radicals.</p> <p>Conclusion</p> <p>These results suggest the potential of <it>S. asper </it>as a medicine against free-radical-associated oxidative damage.</p

BNP controls early load-dependent regulation of SERCA through calcineurin

Heart failure is characterised by reduced expression of sarcoplasmic reticulum calcium-ATPase (SERCA) and increased expression of B-type natriuretic peptide (BNP). The present study was performed to investigate causality of this inverse relationship under in vivo conditions in the transversal aortic constriction mouse model (TAC). Left ventricular SERCA-mRNA expression was significantly upregulated in TAC by 32% after 6 h, but not different from sham after 24 h. Serum proANP and BNP levels were increased in TAC after 24 h (BNP +274%, p < 0.01; proANP +60%, p < 0.05), but only proANP levels were increased after 6 h (+182%, p < 0.01). cGMP levels were only increased 24 h after TAC (+307%, p < 0.01), but not 6 h after TAC. BNP infusion inhibited the increase in SERCA expression 6 h after TAC. In BNP-receptor-knockout animals (GC-A), the expression of SERCA was still significantly increased 24 h after TAC at the mRNA level by 35% (p < 0.05), as well as at the protein level by 25% (p < 0.05). MCIP expression as an indicator of calcineurin activity was regulated in parallel to SERCA after 6 and 24 h. MCIP-mRNA was increased by 333% 6 h after TAC, but not significantly different from sham after 24 h. In the GC-A-KO mice, MCIP-mRNA was significantly increased in TAC compared to WT after 24 h. In mice with BNP infusion, MCIP was significantly lower 6 h after TAC compared to control animals. In conclusion, mechanical load leads to an upregulation of SERCA expression. This is followed by upregulation of natriuretic peptides with subsequent suppression of SERCA upregulation. Elevated natriuretic peptides may suppress SERCA expression by inhibition of calcineurin activity via activation of GC-A

Reconstruction of metabolic pathways for the cattle genome

<p>Abstract</p> <p>Background</p> <p>Metabolic reconstruction of microbial, plant and animal genomes is a necessary step toward understanding the evolutionary origins of metabolism and species-specific adaptive traits. The aims of this study were to reconstruct conserved metabolic pathways in the cattle genome and to identify metabolic pathways with missing genes and proteins. The MetaCyc database and PathwayTools software suite were chosen for this work because they are widely used and easy to implement.</p> <p>Results</p> <p>An amalgamated cattle genome database was created using the NCBI and Ensembl cattle genome databases (based on build 3.1) as data sources. PathwayTools was used to create a cattle-specific pathway genome database, which was followed by comprehensive manual curation for the reconstruction of metabolic pathways. The curated database, CattleCyc 1.0, consists of 217 metabolic pathways. A total of 64 mammalian-specific metabolic pathways were modified from the reference pathways in MetaCyc, and two pathways previously identified but missing from MetaCyc were added. Comparative analysis of metabolic pathways revealed the absence of mammalian genes for 22 metabolic enzymes whose activity was reported in the literature. We also identified six human metabolic protein-coding genes for which the cattle ortholog is missing from the sequence assembly.</p> <p>Conclusion</p> <p>CattleCyc is a powerful tool for understanding the biology of ruminants and other cetartiodactyl species. In addition, the approach used to develop CattleCyc provides a framework for the metabolic reconstruction of other newly sequenced mammalian genomes. It is clear that metabolic pathway analysis strongly reflects the quality of the underlying genome annotations. Thus, having well-annotated genomes from many mammalian species hosted in BioCyc will facilitate the comparative analysis of metabolic pathways among different species and a systems approach to comparative physiology.</p