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Biomedical subjects

S Martin

Publications and source records attributed to S Martin.

At least 19 recordsLinked to original sources
PubMed2006

The metabolic syndrome sensitizes leukocytes for glucose-induced immune gene expression.

Definitions of the metabolic syndrome (MetS) include obesity, dyslipidemia, elevated levels of fasting blood glucose, and blood pressure as criteria, but it is also known that the MetS is associated with chronic, subclinical inflammation. Hyperglycemia (fasting and postprandial) may be important in exacerbating this proinflammatory state. We aimed to assess the impact of oral glucose challenge and in vitro glucose-stimulation on gene expression and secretion of inflammatory parameters in peripheral blood leukocytes and to investigate whether presence of the MetS could "prime" leukocytes to up-regulate proinflammatory markers in response to glucose. Using quantitative real-time PCR, we could show that the expression of intercellular adhesion molecule 1 (ICAM-1), tumor necrosis factor alpha (TNF-alpha), and interleukin 6 (IL-6) significantly increased in peripheral blood leukocytes from "MetS" subjects (n=39) compared to "no MetS" subjects (n=35) 2 h after an oral glucose tolerance test (ICAM-1 +52%, TNF-alpha +107%, and IL-6 +38%) and also in vitro after 72 h cultivation in high-glucose medium (ICAM-1 +74%, TNF-alpha +71%, and IL-6 +44%). Using ELISA and Luminex technique, we further observed a trend towards increased immune mediator concentrations in the corresponding cell culture supernatants from MetS patients (ICAM-1 +21%, TNF-alpha +31%, and IL-6 +175%). Thus, the MetS may support peripheral inflammation by sensitizing leukocytes to up-regulate proinflammatory markers in response to glucose, which in turn increases the risk for type-2 diabetes mellitus and cardiovascular disease.

Gene Expression Regulation↗
PubMed2006

Facial cutaneous cholesterol embolism revealing a tight carotid stenosis: a case report.

We report a case of systemic cholesterol embolisms (CE) with rare localization to the level of the face from a tight carotid stenosis. The case history is that of a 75 year old patient who presented with cholesterol embolisms in the territory of the external carotid artery. The patient underwent successful carotid endarterectomy with no postoperative neurological event.

Aged↗
PubMed2006

Pulmonary rehabilitation for chronic obstructive pulmonary disease.

BACKGROUND: The widespread application of pulmonary rehabilitation in chronic obstructive pulmonary disease (COPD) should be preceded by demonstrable improvements in function attributable to the programs. This review updates that reported in 2001. OBJECTIVES: To determine the impact of rehabilitation on health-related quality of life (QoL) and exercise capacity in patients with COPD. SEARCH STRATEGY: We identified additional RCTs from the Cochrane Airways Group Specialised Register. Searches were current as of July 2004. SELECTION CRITERIA: We selected RCTs of rehabilitation in patients with COPD in which quality of life (QoL) and/or functional (FEC) or maximal (MEC) exercise capacity were measured. Rehabilitation was defined as exercise training for at least four weeks with or without education and/or psychological support. Control groups received conventional community care without rehabilitation. DATA COLLECTION AND ANALYSIS: We calculated weighted mean differences (WMD) using a random-effects model. We requested missing data from the authors of the primary study. MAIN RESULTS: We included the 23 randomized controlled trials (RCTs) in the 2001 Cochrane review. Eight additional RCTs (for a total of 31) met the inclusion criteria. We found statistically significant improvements for all the outcomes. In four important domains of QoL (Chronic Respiratory Questionnaire scores for Dyspnea, Fatigue, Emotional function and Mastery), the effect was larger than the minimal clinically important difference of 0.5 units (for example: Dyspnoea score: WMD 1.0 units; 95% confidence interval: 0.8 to 1.3 units; n = 12 trials). Statistically significant improvements were noted in two of the three domains of the St. Georges Respiratory Questionnaire. For FEC and MEC, the effect was small and slightly below the threshold of clinical significance for the six-minute walking distance (WMD: 48 meters; 95% CI: 32 to 65; n = 16 trials). AUTHORS' CONCLUSIONS: Rehabilitation relieves dyspnea and fatigue, improves emotional function and enhances patients' sense of control over their condition. These improvements are moderately large and clinically significant. Rehabilitation forms an important component of the management of COPD.

Dyspnea↗
PubMed2006

The "in vitro" percutaneous penetration of three antioxidant compounds.

Caffeic acid, chlorogenic acid and oraposide, a natural glycoside, are phenyl-propanoid compounds. These natural products have been reported to have antioxidant activities such as the scavenging of superoxide anions and hydroxyl radicals. These compounds could be used in the dermocosmetic field to protect the skin from oxidative stress induced by UV radiation. To this end, the permeation of caffeic acid, chlorogenic acid, and oraposide, through pig-ear skin was evaluated in vitro. The percutaneous permeation of these three compounds through pig skin was measured and compared using Franz diffusion cells. At appropriate intervals, up to 72 h, diffusion samples were analyzed using an HPLC assay. After 48 h of drug contact the permeation was also evaluated with a fluorescent microscope on vertical microtomed pig skin sections. In this study on excised pig skin, the flux value was found to be equal to 0.32 and 0.48 microgcm(-2)h(-1) for caffeic and chlorogenic acids, respectively; for oraposide the levels were below the limit of detection and the flux was not evaluated. These results were corroborated by fluorescent microscopy. Caffeic and chlorogenic acids were found in all skin sections, and these might represent a systemic activity, whereas oraposide remained in the upper superficial layer of the skin. This latter phenomenon seems to be interesting for dermocosmetic applications.

Animals↗
PubMed2006

Immunohistochemical features of PrP(d) accumulation in natural and experimental goat transmissible spongiform encephalopathies.

Scrapie is a transmissible spongiform encephalopathy (TSE) or prion disease, which naturally affects sheep and goats. Immunohistochemical epitope mapping of abnormal PrP accumulations (PrP(d)) in brain can help in characterizing sheep TSE sources or strains and in identifying potential bovine spongiform encephalopathy (BSE) infections of sheep. Natural and experimental TSE infections of goats were examined to determine whether the epitope mapping approach could also be applied to aid recognition of BSE infection in goats. Goats experimentally infected with the SSBP/1 or CH1641 sheep scrapie strains or with cattle BSE, together with four field cases of natural TSE in goats, were examined immunohistochemically with six different antibodies. CH1641 and SSBP/1 infections in goats, as in sheep, showed PrP(d) accumulations which were mainly intracellular. Some differences in targeting, particularly of Purkinje cells, was evident in inter-species comparisons of CH1641 and SSBP/1. PrP(d) labelling of goat BSE experimental cases showed extensive intracellular and extracellular accumulations, also similar to those in sheep BSE. Intra-neuronal PrP(d) in both goat and sheep BSE was labelled only by antibodies recognizing epitopes located C-terminally of residue His99, whereas in natural sheep TSE sources, and in sheep and goat SSBP/1, PrP(d) was also detected by antibodies to epitopes located between residues Trp93 and His99. Testing of four natural goat TSE samples showed one case in which epitope mapping characteristics and the overall patterns of PrP(d) accumulation was identical with those of experimental goat BSE. The four natural goat scrapie cases examined showed some degree of immunohistochemical phenotype variability, suggesting that multiple strains exist within the relatively small UK goat population.

Animals↗
PubMed2006

Chemokines as risk factors for type 2 diabetes: results from the MONICA/KORA Augsburg study, 1984-2002.

AIMS/HYPOTHESIS: The chemokines monocyte chemoattractant protein-1 (MCP-1), IL-8 and interferon-gamma-inducible protein-10 (IP-10) are released by adipocytes and appear to be involved in atherosclerosis. We hypothesised that these chemokines may be risk factors for the development of type 2 diabetes. SUBJECTS AND METHODS: Using a case-cohort design based on data from the population-based Monitoring of Trends and Determinants in Cardiovascular Disease (MONICA)/Kooperative Gesundheitsforschung in der Region Augsburg/Cooperative Health Research in the Region of Augsburg (KORA Augsburg) study, chemokine levels at baseline were analysed in 526 individuals with and 1,695 individuals without incident type 2 diabetes. The mean follow-up time was 10.8 years. RESULTS: MCP-1 was associated with type 2 diabetes, largely independently of classic risk factors, whereas various clinical and metabolic parameters as well as lifestyle factors were major confounders of the association of IL-8 and IP-10 with type 2 diabetes. Further adjustment for C-reactive protein (CRP) and IL-6 had no impact on the observed associations. The hazard ratio (HR) for subjects with systemic concentrations of all three chemokines (MCP-1, IL-8 and IP-10) above the respective median compared with those with all chemokines below or equal to the median was 1.79 (95% CI 1.18-2.72) and was comparable with the HR for elevated CRP and IL-6 together (adjusted for age, sex, survey, BMI, systolic blood pressure, total cholesterol:HDL cholesterol ratio, physical activity, alcohol intake, smoking and parental history of diabetes). CONCLUSIONS/INTERPRETATION: Elevated concentrations of MCP-1, IL-8 and IP-10 are associated with incident type 2 diabetes. Whereas the association of IL-8 and IP-10 with diabetes was attenuated by multivariable adjustment, high MCP-1 levels contributed to diabetes risk independently of previously described clinical, metabolic and immunological risk factors.

Blood Pressure↗
PubMed2006

[Primary care in general internal medicine: relevant information in 2005].

During the year 2005, the chief residents of the University Medical Outpatient Clinic of Lausanne have done a database of useful articles for daily practice, scientifically validated and with excellent didactic quality, from 10 electronic journals. They have used those selected articles in personal meetings between the chief residents on a regular basis and the possibility to access the database by the junior physicians. Six of these articles concerning different topics (depression, tuberculosis detection, anticoagulation at home, cholinesterase inhibitors, insomnia and therapies, transdermal nitroglycerin and tendinopathies) are presented.

Administration, Cutaneous↗
PubMed2006

Transportation of prion protein across the intestinal mucosa of scrapie-susceptible and scrapie-resistant sheep.

To determine the mechanisms of intestinal transport of infection, and early pathogenesis, of sheep scrapie, isolated gut-loops were inoculated to ensure that significant concentrations of scrapie agent would come into direct contact with the relevant ileal structures (epithelial, lymphoreticular, and nervous). Gut loops were inoculated with a scrapie brain pool homogenate or normal brain or sucrose solution. After surgery, animals were necropsied at time points ranging from 15 min to 1 month and at clinical end point. Inoculum-associated prion protein (PrP) was detected by immunohistochemistry in villous lacteals and in sub-mucosal lymphatics from 15 min to 3.5 h post-challenge. It was also detected in association with dendritic-like cells in the draining lymph nodes at up to 24 h post-challenge. Replication of infection, as demonstrated by the accumulation of disease-associated forms of PrP in Peyer's patches, was detected at 30 days and sheep developed clinical signs of scrapie at 18-22 months post-challenge. These results indicate discrepancies between the routes of transportation of PrP from the inoculum and sites of de novo-generated disease-associated PrP subsequent to scrapie agent replication. When samples of homogenized inoculum were incubated with alimentary tract fluids in vitro, only trace amounts of protease-resistant PrP could be detected by western blotting, suggesting that the majority of both normal and abnormal PrP within the inoculum is readily digested by alimentary fluids.

Animals↗
PubMed2006

P-glycoprotein and 'lipid rafts': some ambiguous mutual relationships (floating on them, building them or meeting them by chance?).

P-glycoprotein (P-gp) is an active membrane transporter responsible for cell detoxification against numerous amphiphilic compounds, leading to multidrug resistance in tumor cells. It displays entangled connections with its membrane environment since it recognizes its substrates within the cytosolic leaflet and it also translocates some endogenous lipids to the exoplasmic leaflet. Regarding its relationships with membrane microdomains, 'lipid rafts', a literature analysis concludes that (i) P-gp also exists in rafts and non-raft membrane domains, depending on the cell considered, the experimental conditions and the method used to test it; (ii) cholesterol has a positive influence on P-gp function, and this may be a direct effect of the free cholesterol present in membrane or an indirect effect mediated by the cholesterol-enriched microdomains; (iii) when present in rafts, P-gp interacts with protein partners regulating its activity; (iv) P-gp is a lipid translocase that handles the raft-constituting lipids with particular efficiency, and it also influences membrane trafficking in the cell.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2006

Increased TNF-alpha and decreased TGF-beta expression in peripheral blood leukocytes after acute myocardial infarction.

Inflammation contributes to the development of atherosclerosis and cardiovascular events. Counteracting pro- and anti-inflammatory responses of serum cytokines have been reported, but the relevance of TNF-alpha, TGF-beta and IL-6 gene expression in peripheral blood leukocytes and their contribution to systemic inflammation in atherosclerosis, especially after acute myocardial infarction (AMI), has not been investigated yet. Using quantitative RT-PCR, we determined temporal cytokine mRNA expression alterations in blood cells from patients with AMI (n = 51). Serum cytokine concentrations were analyzed in parallel using the ELISA technique. TNF-alpha mRNA expression rates and serum concentrations were significantly elevated in AMI patients compared to controls (n = 77), while mRNA expression and serum content of TGF-beta were decreased. Interestingly, we found no statistically significant correlation between transcript and protein levels, indicating that gene expression in leukocytes may be an independent sign for systemic inflammation. While IL-6 was significantly increased in serum from AMI patients with positive correlation to left ventricular dysfunction and negative correlation to ejection fraction, IL-6 mRNA levels did not differ between patients and controls. Gene expression alterations indicate a sophisticated regulation of counteracting TNF-alpha and TGF-beta cytokine expression in peripheral blood leukocytes after AMI with bias towards a pro-inflammatory situation.

Adult↗
PubMed2006

Dose-dependent induction of IL-6 by plant-derived proteases in vitro.

Oral administration of proteases such as bromelain and papain is commonly used in patients with a wide range of inflammatory conditions, but their molecular and cellular mechanisms of action are still poorly understood. The aim of our study was to investigate the impact of these proteases on the release of interleukin-6 (IL-6) and other cytokines in the recently described modified mixed lymphocyte culture (MMLC) test system which is based on the mutual interaction of cells of the innate and adaptive immunity. Bromelain and papain enhanced IL-6 production dose-dependently up to 400-fold in MMLC before and up to 30-fold after neutralization of LPS content of proteases using polymyxin B, indicating that IL-6 induction by protease treatment was attributable to both protease action and LPS content of enzyme preparations. The production of IFNgamma and IL-10 was not altered by bromelain or papain, indicating a selective and differential immune activation. Both proteases impaired cytokine stability, cell proliferation and expression of cell surface molecules like CD14 only marginally, suggesting no impact of these mechanisms on protease-mediated cytokine release. These findings might provide the mechanistic rationale for the current use of proteases in wound healing and tissue regeneration since these processes depend on IL-6 induction.

Analysis of Variance↗
PubMed2006

Altered chemokine levels in individuals at risk of Type 1 diabetes mellitus.

AIMS: The hypothesis was tested in an exploratory study that individuals at high risk of developing Type 1 diabetes mellitus have altered systemic levels of cytokines and chemokines. SUBJECTS AND METHODS: Forty-two non-diabetic first-degree relatives of patients with Type 1 diabetes mellitus were recruited. Of these, 18 had multiple islet autoantibodies (islet cell antibody, glutamic acid decarboxylase antibody, IA-2 antibody). Follow-up for 9-11 years confirmed high vs. moderate diabetes risk in islet autoantibody-positive vs. -negative relatives. Cytokines and chemokines were determined by enzyme-linked immunosorbent assay (ELISA). RESULTS: Serum concentrations of classic Th1-associated cytokines (IFN-gamma, IL-12, IL-18) or Th2/Treg-associated cytokines (IL-5, IL-10, IL-13) did not significantly differ in high vs. moderate diabetes risk group. However, of six chemokines analysed, levels of CCL3 and CCL4 were increased (P = 0.0442 and P = 0.0334) while CCL2 was decreased (P = 0.0318) in the multiple islet autoantibody-positive group. No significant differences were seen for CCL5, CCL11, CXCL10. There was a significant correlation between the two closely related chemokines CCL3 and CCL4 in individuals at risk (r = 0.84, P = 0.00005), but not in the autoantibody-negative group. CONCLUSION: Relatives at high risk of developing Type 1 diabetes mellitus have abnormal cellular immune regulation at the level of systemic chemokines. The up-regulation of CCL3 and CCL4 vs. down-regulation of CCL2 suggests opposed functions of these chemokines in the disease process. These findings need to be confirmed by independent studies.

Autoantibodies↗
PubMed2006

Anastomotic ulceration following small bowel transplantation.

We describe, for the first time, anastomotic ulcers (AU) following bowel transplantation at the Hospital for Sick Children. Two children presented with rectal bleeding, 6 and 9 months, following the transplantation. Isolated ulcers were identified at the ileo-colonic and the colo-colonic anastomosis site. The ulcers resolved, but recurred 6 and 7 months after the initial presentation. Both patients were positive for adenovirus in the stool and were treated with rapamycin. The histology revealed granulation tissue formation with mild inflammation in the adjacent mucosa, without evidence of rejection or infection. A literature search revealed 10 studies reporting 29 patients who developed AU following various surgical etiologies, none of which was bowel transplant. Numerous factors that are unique to the post-transplant period may predispose to such ulcer and are discussed in detail. Physicians and surgeons should be aware of this multifactorial complication, among other etiologies, as a cause of anemia or rectal bleeding following intestinal transplantation.

Anastomosis, Surgical↗
PubMed2006

Salmonella produces an O-antigen capsule regulated by AgfD and important for environmental persistence.

In this study, we show that Salmonella produces an O-antigen capsule coregulated with the fimbria- and cellulose-associated extracellular matrix. Structural analysis of purified Salmonella extracellular polysaccharides yielded predominantly a repeating oligosaccharide unit similar to that of Salmonella enterica serovar Enteritidis lipopolysaccharide O antigen with some modifications. Putative carbohydrate transport and regulatory operons important for capsule assembly and translocation, designated yihU-yshA and yihVW, were identified by screening a random transposon library with immune serum generated to the capsule. The absence of capsule was confirmed by generating various isogenic Deltayih mutants, where yihQ and yihO were shown to be important in capsule assembly and translocation. Luciferase-based expression studies showed that AgfD regulates the yih operons in coordination with extracellular matrix genes coding for thin aggregative fimbriae and cellulose. Although the capsule did not appear to be important for multicellular behavior, we demonstrate that it was important for survival during desiccation stress. Since the yih genes are conserved in salmonellae and the O-antigen capsule was important for environmental persistence, the formation of this surface structure may represent a conserved survival strategy.

Bacterial Capsules↗