Clinical and investigative medicine. Medecine clinique et experimentale (Clin Investig Med)

Publisher: Canadian Medical Association; Canadian Society for Clinical Investigation, Canadian Society for Clinical Investigation

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Current impact factor: 1.15

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5-year impact 0.00
Cited half-life 0.00
Immediacy index 0.23
Eigenfactor 0.00
Article influence 0.34
Website Clinical and Investigative Medicine website
Other titles Clinical and investigative medicine (Online), Clinical and investigative medecine, CIM, Médicine clinique et experimentale
ISSN 1488-2353
OCLC 44653587
Material type Document, Periodical, Internet resource
Document type Internet Resource, Computer File, Journal / Magazine / Newspaper

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Canadian Society for Clinical Investigation

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Publications in this journal

  • [Show abstract] [Hide abstract]
    ABSTRACT: Neutrophil gelatinase-associated lipocalin (NGAL) is a protein belonging to the lipocalin superfamily and plays a role in atherosclerosis, renal injury and inflammation. The present study aimed to investigate serum NGAL concentrations in groups of patients with dipper and non-dipper hypertension (HT) and to characterize the relationship between NGAL concentration and circadian blood pressure in hypertensive patients. A total of 41 (22 male, 19 female, mean age: 56.1 ±8.9 years) non-dipper HT patients, 40 (19 male, 21 female, mean age: 54.0 ±10.0 years) dipper HT patients and 42 age- and gender-matched healthy individuals were enrolled in the study. Dipper and non-dipper HT were diagnosed via ambulatory blood pressure monitoring. Serum NGAL concentrations were measured by enzyme-linked immunosorbent assay from blood samples obtained from patients. Serum NGAL concentrations were found to be significantly higher in the non-dipper and dipper HT patient groups in comparison with the control group (84.9 ±23.0 ng/ml and 62.1 ±17.8 vs. 46.6 ± 13.7 ng/ml, p.
    Clinical and investigative medicine. Medecine clinique et experimentale 01/2015; 38(1):E53-62.
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    ABSTRACT: Epicardial fat is visceral adipose tissue that possesses inflammatory properties. Inflammation and obesity are associated with cardiovascular disease and arrhythmogenesis, but little is known about the relationship between epicardial fat and PR-Interval prolongation. The purpose of this study was to investigate the association between epicardial adipose tissue (EAT) volume and PR-interval prolongation as assessed by computed tomography (CT) and Twelve-lead ECGs. Patients (n=287) were referred for 64-slice CT for exclusion of coronary artery disease and EAT volumes were determined. Twelve-lead ECGs were obtained from each subject and were evaluated by two independent readers. Patients with significant PR interval prolongation had higher median EAT volume than patients with normal PR interval. Statistically significant correlations were observed between the EAT volume and the PR interval (p = 0.183, p = 0.003), and QRS duration (p = 0.144, p = 0.018). Multivariate and trend analyses confirmed that EAT volume was independently associated with the presence of PR interval prolongation. The receiver operator characteristics curve of EAT volume showed that an EAT volume >144.4 cm³ was associated with PR interval prolongation. This study indicates that EAT volume is highly associated with PR interval prolongation. Whether epicardial fat plays a role in the pathogenesis of PR interval prolongation requires future investigation.
    Clinical and investigative medicine. Medecine clinique et experimentale 01/2015; 38(1):E45-52.
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    ABSTRACT: Post-treatment hypothyroidism is common in Graves' disease, and clinical guidelines recommend monitoring for it; however, thyroid stimulating hormone (TSH) can remain suppressed in these patients following treatment. The objectives of this study were to explore the proposed pathophysiology behind the phenomenon of post-therapy TSH suppression and to systematically review existing clinical data on post-therapy TSH suppression in patients with Graves' disease. A systematic literature search was performed using EMBASE and PubMed databases, with several combinations of MeSH terms. Bibliography mining was also done on relevant articles to be as inclusive as possible. A total of 18 articles described possible mechanisms for post-therapy TSH suppression. Several of the studies demonstrate evidence of thyrotroph atrophy and hypothesize that this contributes to the ongoing suppression. TSH receptors have been identified in folliculo-stellate cells of the pituitary as well as astroglial cells of the hypothalamus, mediating paracrine feedback. A few studies have demonstrated inverse correlation between autoantibody titres and TSH levels, suggestive of their role in mediating ongoing TSH suppression in patients with Graves' disease. In addition, five studies were identified that provided clinical data on the duration of TSH suppression. Combined data show that 45.5% of patients recover TSH by 3 months after treatment, increasing to 69.3% by 6 months, and plateauing to 73.8% by 12 months (p>0.0001). Sub-analysis also shows that for patients who are TBII negative, 80.7% recover their TSH by 6 months compared with only 58.7% in those who are TBII positive (p= 0.003). Clinical data suggests that TSH recovery is most likely to occur within the first 6 months after treatment, with recovery plateauing at approximately 70% of patients, suggesting that reliance on this assay for monitoring can be very misleading. Furthermore, TBII positivity is associated with lower likelihood of TSH recovery. Pathophysiology behind suppressed TSH involves not only anatomical but also autoimmune mechanisms.
    Clinical and investigative medicine. Medecine clinique et experimentale 01/2015; 38(1):E31-44.
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    ABSTRACT: There is currently no gold standard treatment for unstable intertrochanteric fractures of the elderly. Internal fixation and hemiarthroplasty are two common treatment methods but studies comparing the functional outcomes of these procedures in the elderly are limited. This study evaluates the functional outcomes of hip fracture patients treated either with internal fixation or hemiarthroplasty. Eighty-six elderly (>60 years) patients who presented with isolated, unstable intertrochanteric fractures between 2009 and 2013 were included in the study. According to the classification of Association for Osteosynthesis/Orthopaedic Trauma Association; 12 of the patients had a 31A1.3 fracture type, 36 of the patients had 31A2.2 and 19 had 31A2.3 fracture type, 12 had 31A3.1 and seven had 31A3.3 fracture. Forty-two of 86 hip patients (Group 1) were treated with intramedullary nailing and antirotator proximal femoral nail implant (TST, Turkey), and 44 (Group 2) were treated with cementless bipolar hemiarthroplasty. Preoperative social function (Jensen) score, EQ-5D index score and mobility (Palmer/Parker) scores were obtained. Five dimensions of EQ-5D were obtained at every follow-up visit until 24 months postoperative. There was no statistically significant difference between two groups according to preoperative demographic variables, including mean age and sex and Jensen, Palmer/Parker,EQ-5D index, five dimensions of EQ-5D and American Society of Anesthesiologists scores. At end of 24 months follow-up, health-related quality of life had increased more in Group 1 and they reported better social functioning and mobility scores (p.
    Clinical and investigative medicine. Medecine clinique et experimentale 01/2015; 38(1):E63-72.
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    ABSTRACT: Steroids, inhaled and systemic, are used to treat airway inflammation in patients with asthma; however, steroids are recognized to cause a number of side effects, including osteoporosis. We evaluated the prevalence of osteopenia/osteoporosis in patients with moderate-severe asthma managed through the Edmonton Regional Severe Asthma Centre. We performed a retrospective chart review and analyzed 57 charts on patients with moderate-severe asthma followed through the specialty clinic, and recorded their bone mineral density (BMD). Steroid use was reviewed and the frequency of osteopenia/osteoporosis was compared in patients requiring continuous systemic steroids (Group 1, n=15), intermittent systemic steroids (Group 2, n=15) or inhaled steroids only (Group 3, n=27). The mean age (mean±SD) was 50±14.8 years. Cumulative systemic steroid dose of prednisone equivalent was higher in Group 1 (12.5 mg/day) than Group 2 (3.2 mg/day) (p=0.002). The frequency of osteopenia / osteoporosis was not significantly different between patients in Group 1(67%) and Group 2 (53%, p=0.46) but was significantly greater in patients from Group 1 in comparison with Group 3 (33%, p=0.038). Patients with moderate-severe asthma have a high prevalence of reduced bone density. Many patients treated with intermittent systemic steroids for exacerbations, or who were stable on inhaled steroids, had either osteopenia or osteoporosis before the age of 50. National and international osteoporosis guidelines should emphasize earlier screening for asthma patients; and increase awareness of the detrimental effects of short-term systemic steroids and inhaled steroids on BMD, especially when started at an early age and in northern climates.
    Clinical and investigative medicine. Medecine clinique et experimentale 01/2015; 38(1):E23-30.
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    ABSTRACT: Purpose: The aim of this study was to evaluate the effects of pomegranate (PMG) extract and carvacrol (CARV) on methotrexate (MTX)-induced oxidative stress and bone marrow toxicity. Methods: Wistar albino rats (32 rats) were divided into four groups (n=8): Group 1 was control; Group 2 was given a single intraperitoneal injection of methotrexate (20 mg/kg); Group 3 was treated with carvacrol (73 mg/kg i.p.) one day before MTX (20 mg/kg i.p.) injection; and, Group 4 received a single dose of MTX (20 mg/kg i.p) while PMG was administered orally for seven days at 225 mg/kg. After animals were euthanized, blood samples were taken to evaluate hematological parameters and oxidative stress. In addition, the femur was cropped and bone marrow was extracted for examination. Results: White blood cell count, hemoglobin, hematocrit and platelet count were found to be decreased in the MTX group, but these changes were prevented in the groups that received CARV and PMG. Furthermore, decreased bone marrow cellularity was found in the groups treated with MTX, whereas the PMG and CARV groups had cellularity similar to controls. Strikingly, oxidative stress increased in the MTX group, but was ultimately decreased in the rats that received the antioxidants PMG and CARV. Conclusion: Carvacrol and PMG were found to be protective against methotrexate-induced oxidative bone marrow damage. Use of these antioxidants, in combination with chemotherapeutics, may help to reduce some adverse effects of methotrexate.
    Clinical and investigative medicine. Medecine clinique et experimentale 01/2014; 37(2):E93.
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    ABSTRACT: Purpose: The purpose of this study was to investigate the effect of oral isotretinoin, a drug used in the treatment of acne vulgaris, on hearing function determined by serial audiology examinations. Methods: Forty patients with acne vulgaris were included in this study. Nine patients were excluded from the study because of inconsistent follow-up. The hearing of each participant was tested with pure tone audiometry and transient evoked autoacoustic emissions before and two and four weeks after treatment with isotretinoin (0.3-0.6 mg/kg/day) in the remaining 31 patients (62 ears). Results: The differences between the mean values of the pre-treatment and post-treatment pure tone hearing thresholds at 1000, 2000, 4000 and 6000 Hz frequencies were statistically significant (p < 0.05), but there was no significant difference between the pre-treatment and post-treatment values at 250 and 500 Hz frequencies (p > 0.05). The difference between the pre-treatment and post-treatment signal-noise ratio values of the transient evoked autoacoustic emissions was not significantly different (p > 0.05). Conclusion: Our results suggest that the use of isotretinoin may cause bilateral hearing threshold changes. Further animal and human studies are required to investigate and characterize isotretinoin-induced neurophysiological alterations in hearing.
    Clinical and investigative medicine. Medecine clinique et experimentale 01/2014; 37(2):E102.
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    ABSTRACT: Purpose: The purpose of this study was to analyze the effects of estrogen deficiency and hormone replacement therapy (HRT) on fibrinolytic activity in a rat mode of surgically-induced menopause. Methods: Twelve-week-old, sexually mature female Sprague-Dawley rats, each weighing 200-250 g, were randomly divided into four groups: (1) sham-operated group, (2) ovariectomy group, (3) ovariectomy group followed by oral administration of daily 17β-estradiol (0.02 mg/kg/day) (E2) + norethisterone acetate (0.01 mg/kg/day), and (4) ovariectomy group followed by oral administration of daily 17β-estradiol (0.01 mg/kg/day) + drospirenone (0.02 mg/kg/day). Tissue plasminogen activator (tPA) antigen, plasminogen activator inhibitor-1 (PAI-1) antigen, and PAI-1/tPA levels were measured as markers of fibrinolysis in plasma and liver and brain tissue. Results: Compared with sham-operated rats, ovariectomized rats showed higher levels of fibrinolytic activity; however, the increased fibrinolytic activity in plasma and liver tissue was significantly reduced by HRT regimens. No change was observed in the levels of fibrinolytic activity in brain tissue. Conclusions: HRT showed beneficial effects by decreasing fibrinolytic activity related to surgically-induced menopause. Short-term HRT treatment was associated with a shift in the procoagulant-anticoagulant balance toward a procoagulant state.
    Clinical and investigative medicine. Medecine clinique et experimentale 01/2014; 37(2):E85.
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    ABSTRACT: Purpose: Sedentary behavior has been proposed as an independent cardio-metabolic risk factor even in adults who are physically active through recreational activity. Because little is known about the metabolic effects of sedentariness in seniors, the relationship between sedentary behavior and cardio-metabolic risk was examined in physically active older adults. Methods: Fifty-four community dwelling men and women > 65 years of age (mean 71.5 years) were enrolled in this cross-sectional observational study. Subjects were in good health and free of known diabetes. Activity levels (sedentary, light, moderate to vigorous activity time per day) were recorded with accelerometers worn continuously for 7 days. Cardio-metabolic risk factors measured consisted of the American Heart Association diagnostic criteria for metabolic syndrome (waist circumference, triglycerides, high-density lipoprotein, systolic blood pressure and fasting glucose) as well as low-density lipoprotein (LDL). The relationships between activity measures and cardio-metabolic risk factors were examined. Significant variables were then entered into a stepwise multivariate regression model. Results: All but one subject achieved exercise levels recommended by the American College of Sports Medicine. The average proportion of time spent at a sedentary activity level each day was 72.7%. From the regression analysis, the only significant association found between cardio-metabolic risk outcomes and activity predictors was between LDL and sedentary time, with LDL detrimentally associated with average sedentary time per day (Standardized Beta Correlation Coefficient 0.302, p < 0.05). Conclusion: Sedentary behavior is associated with an adverse metabolic effect on LDL in seniors, even those who meet guideline recommendations for an active "fit" adult.
    Clinical and investigative medicine. Medecine clinique et experimentale 01/2014; 37(2):E108.
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    ABSTRACT: Purpose: There is evidence of a social disparity pertaining to the epidemiology and burden of illness of diabetes. The purpose of this study was to assess the association between household income strata and therapeutic goal achievement rates for LDL-cholesterol (LDL-C) (< 2.5 mmol/L) in Canadian diabetic patients. Methods: Data (household income, cardiovascular risk factors, drug profile, clinical and laboratory variables) were obtained from a previous cross-sectional study of diabetic patients who filled a prescription for a lipid-lowering drug in selected pharmacies across Canada. Telephone interviews were conducted. Physicians, identified by the participating patients, were requested to complete a short questionnaire for clinical data. Achievement of LDL-C goals according to the Canadian diabetes guidelines were assessed and incorporated into regression models corresponding to household income strata. Results: Seven household income strata were defined in the cohort (from less than 20,000 CDN$, up to 70,000 CDN$ by increments of 10,000 CDN$). LDL-C goals were attained in 34% of patients in the total cohort. There were no significant differences amongst household income strata for LDL-C goal achievement (p = 0.80). There were no significant differences in patient characteristics (age, sex, BMI) and cardiovascular risks according to the household income strata in this cohort, except age more than 65 in the lower income strata. Conclusion: This study demonstrates that household income was not a factor to achieve therapeutic goals for LDL-C for patients with diabetes in this dataset, although goal attainment was less than ideal overall. Future studies should address limitations of this work including small sample size, recruitment bias and lack of data on third party insurance coverage.
    Clinical and investigative medicine. Medecine clinique et experimentale 01/2014; 37(1):E47.
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    ABSTRACT: Purpose: The multifunctional RNA-binding protein, CUGBP1, regulates splicing, stability and translation of mRNAs. Previous studies have shown that CUGBP1 is expressed at high levels in the liver, although its role in hepatocellular carcinoma is unknown. Our aim was to determine if CUGBP1 could regulate hepatocellular carcinoma growth. Methods: Expression levels of CUGBP1 were analyzed in 70 hepatic carcinoma and 20 normal hepatic tissue samples by immunohistochemistry (IHC). Using lentivirus-mediated short hairpin RNA (shRNA), CUGBP1 expression in human hepatocellular carcinoma HepG2 cells was knocked-down. The effect of CUGBP1 on hepatic cancer cell growth was investigated. Results: CUGBP1 was expressed in 85.7% hepatocellular carcinoma specimens compared with 50% in normal liver specimens. CUGBP1 silencing remarkably decreased the proliferation of HepG2 cells, as determined by MTT assay. Flow cytometry analysis showed that knock-down of CUGBP1 led to G0/G1 phase cell cycle arrest, accompanied by sub-G1 accumulation. Moreover, depletion of CUGBP1 resulted in downregulation of cyclin B1 and upregulation of cyclin D1. Conclusion: These results suggest that CUGBP1 is essential for the growth of hepatocellular carcinoma cells. Knockdown of CUGBP1 might be a potential therapeutic approach for human hepatocellular carcinoma.
    Clinical and investigative medicine. Medecine clinique et experimentale 01/2014; 37(1):E10.
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    ABSTRACT: Purpose: Abnormal gastrointestinal permeability (GIP) has been implicated in a number of diseases, including chronic intestinal inflammatory disorders such as Crohn's as well as non-intestinal immunologic diseases such as diabetes and multiple sclerosis. Although evidence in the literature demonstrates mucosal abnormalities of the digestive barrier in asthma, previous studies have assessed only colonic permeability, while ignoring the mucosal-associated lymphoid tissue (MALT) rich areas of the small intestine. Alterations in GIP may lead to increased entry of allergenic proteins from the gut lumen into the systemic circulation, thus priming and activating the adaptive immune system and leading to inappropriate allergen sensitization and/or deregulated extra-intestinal inflammation. This study examines GIP in adults with moderate to severe asthma. Methods: Patients ingested a mixed-sugar solution and urine was collected. GIP was assayed using high-performance liquid chromatography. Demographics, atopy (assessed by allergen skin testing) and sputum cell counts were also assessed. Results: Fourteen patients with moderate to severe asthma were studied, half of whom were found to have abnormal GIP. Abnormal GIP did not correlate with sputum cell counts and there was no apparent association between atopy and intestinal permeability. Conclusion: This study demonstrated our ability to identify abnormal GIP in the MALT-rich, immunogenic small intestine of patients with asthma. The absence of a correlation between airway inflammation and increased GIP suggests that these two parameters are not causally linked, but rather define distinct entities that could separately or sequentially be involved with the development and propagation of asthma over time.
    Clinical and investigative medicine. Medecine clinique et experimentale 01/2014; 37(2):E53.
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    ABSTRACT: Purpose: Tetramethylpyrazine (TMP) is an effective Chinese plant-derived medicine for colitis in the clinic, but the underlying molecular mechanisms of its use remain poorly understood. The purpose of this study was to investigate the mechanisms involved in its therapeutic action. Methods: A colitis mouse model was induced by oxazolone enema. TMP was administered at 80 mg/kg/day and sulphasalazine (SASP) was used as positive control and administered at 100 mg/kg/day for the treatment of colitis. On the fourth day after enema, mice were sacrificed. The inflammatory response was assessed by the disease activity index and histology. Colon mucosa was isolated and biochemically analyzed. In addition, in vitro studies were performed to evaluate the activity of TMP in Caco-2 cells. Results: Our results showed that TMP improved the colonic inflammatory status as evidenced by histological findings, as well as SASP. These effects were associated with a decrease in nucleus translocation of NF-κB. Paired with this inhibitive activity, there was a decrease in downstream signaling, such as C-MYC, iNOS and COX-2. In vitro assays revealed that TMP inhibited NF-κB translocation and its downstream production of inflammatory factors, such as TNF-α, IL-6 and IL-8, and that ROS production that was induced by LPS in Caco-2 cells. Conclusion: TMP improved the colitis induced by oxazoline, and its activity was associated with inhibition of NF-κB translocation, and subsequent inhibition of pro-inflammatory factor production and oxidative stress.
    Clinical and investigative medicine. Medecine clinique et experimentale 01/2014; 37(1):E1.
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    ABSTRACT: Purpose: Diastolic heart failure is characterized by the presence of heart failure symptoms despite preserved systolic function. Cytokines released during allergic reactions may impair diastolic heart function, either through their direct toxic effects or by inducing coronary artery spasm. The purpose of this study was to examine the effects of acute allergic reactions on diastolic heart function. Methods: Fifty patients, randomly selected from those who were admitted to the emergency room between May 2010 and December 2010 with the complaints of rash and itching, and who were subsequently diagnosed with allergic reactions based on the clinical and laboratory findings, were included in the study as the allergy group. Thirty healthy volunteers, in whom the diagnosis of allergy was ruled out based on the clinical and laboratory data, were use as the control group. Diastolic heart functions were evaluated in patients presenting with allergic reaction as well as in control subjects. Results: There was no significant difference between the two groups in terms of basal systolic functions, diameters of the cavities and wall thicknesses, and biochemical parameters. Color M mode flow progression velocities, E ratios, E/A ratios and mitral lateral annulus tissue Doppler velocities measured by echocardiography at Day 0 and Day 5 were significantly altered in the allergy group (p < 0.05). Conclusion: Impairment in diastolic functions was observed following acute allergic reactions. Acute allergic reactions could be a cause of mortality and morbidity if they lead to the development of diastolic heart failure.
    Clinical and investigative medicine. Medecine clinique et experimentale 01/2014; 37(2):E70.
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    ABSTRACT: Purpose: Esophageal varices are a dangerous complication of liver cirrhosis. The development of cost effective, noninvasive means for prediction of large esophageal varices could reduce the use of upper gastrointestinal endoscopy in variceal screening and also provide an alternative way to confirm the results of conventional endoscopic diagnosis. Previously proposed predictive models are neither sensitive nor specific. Methods: A retrospective study based on a group of 104 liver cirrhosis patients was performed. Multiple statistical approaches were used to evaluate the association of large esophageal varices with 20 individual and six compound clinical laboratory variables. A new predictive model was developed. Results: Univariate analysis suggested that eight out of 26 variables were significantly associated with large esophageal varices. Further stepwise logistic regression eventually identified three variables (hemoglobin level, portal vein diameter and the ratio of platelet count/spleen diameter) that contributed significantly to the final regression model. Receiver operating characteristic (ROC) curve analysis showed that this new regression model achieved 77.8% and 72% of diagnostic sensitivity and specificity, respectively, for the prediction of large esophageal varices. In our study group, its diagnostic accuracy (AUROC=0.814) was found to be significantly higher than six predictive models previously published. Conclusions: No single variable offers self-sufficient predictive function for large esophageal varices. A comprehensive model using multiple variables significantly improves the predictive accuracy in screening the most at risk patients with potential variceal hemorrhage.
    Clinical and investigative medicine. Medecine clinique et experimentale 01/2014; 37(1):E38.
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    ABSTRACT: Purpose: Postconditioning, a series of brief ischemia-reperfusion sequences given before an ischemic heart undergoes sustained reperfusion, has been shown to lessen ischemia/reperfusion injury. The current study establishes a rabbit model of myocardial ischemia-reperfusion and studied the effects of pulmonary remote postconditioning in this model. Methods: Serum levels of creatine kinase (CK), superoxide dismutase (SOD), and malondialdehyde (MDA), protein expression of endothelial nitric oxide synthase (eNOS), Rho kinase (ROCK- 2), and protein kinase B (Akt) in myocardial cells and the apoptosis index of myocardial cells were examined. Results: Pulmonary remote postconditioning decreased CK, significantly decreased MDA, and increased SOD. Postconditioning significantly increased eNOS protein expression. Administration of eNOS inhibitor, L-NAME, dramatically suppressed the postconditioning-induced eNOS protein expression and serum SOD level, but significantly increased MDA level. The two longer sessions of postconditioning increased Akt, although this increase was not accompanied by changes in levels of the Akt inhibitor, ROCK-2. Blocking eNOS activity with L-NAME had no visible effect on either Akt or ROCK-2. Conclusion: Our results suggest a role for Akt in remote postconditioning-induced myocardial protection, but do not support an involvement of eNOS in Akt-mediated action.
    Clinical and investigative medicine. Medecine clinique et experimentale 01/2014; 37(1):E26.
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    ABSTRACT: Purpose: The purpose of this review is to consider the state of oxidative stress, failure of the antioxidant systems and mitochondrial failure as the main physiopathological mechanisms leading to multiple organ dysfunction during sepsis. Principal findings: Sepsis is a clinical syndrome caused by a severe infection that triggers an exaggerated inflammatory response. Involved in the pathogenesis of sepsis are the activation of inflammatory, immune, hormonal, metabolic and bioenergetic responses. One of the pivotal factors in these processes is the increase of reactive species accompanied by the failure of the antioxidant systems, leading to a state of irreversible oxidative stress and mitochondrial failure. In a physiological state, reactive species and antioxidant systems are in redox balance. The loss of this balance during both chronic and infectious diseases leads to a state of oxidative stress, which is considered to be the greatest promoter of a systemic inflammatory response. The loss of the redox balance, together with a systemic inflammatory response during sepsis, can lead to progressive and irreversible mitochondrial failure, energy depletion, hypoxia, septic shock, severe sepsis, multiple organ dysfunction and death of the patient. Conclusion: Knowledge of the molecular processes associated with the development of oxidative stress should facilitate the development of effective therapies and better prognosis for patients with sepsis and organ dysfunction.
    Clinical and investigative medicine. Medecine clinique et experimentale 01/2014; 37(2):E58.
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    ABSTRACT: Purpose: Leukotriene B4 (LTB4) and extracellular matrix metalloproteinase (EMMPRIN) have been suggested as modulators of atherosclerotic plaque instability. This study sought to evaluate the potential diagnostic implication of LTB4 and EMMPRIN in patients with acute coronary syndrome (ACS). Methods: Patients (n=153) who underwent coronary angiography, including 105 patients diagnosed with ACS, were divided into four groups: stable angina pectoris (SAP, n=19), unstable angina pectoris (UAP, n=39), acute myocardial infarction (AMI, n=66) and control (with normal coronary angiography, n=29). EMMPRIN expression in peripheral blood mononuclear cells was determined by flow cytometry and serum LTB4 levels were measured by ELISA. To examine whether LTB4 can regulate the expression of EMMPRIN and matrix metalloproteinases (MMPs) in macrophages, differentiated THP-1 macrophages were stimulated with different concentrations of LTB4 (10-10-10-7mmol/L). Expression of EMMPRIN was evaluated by Western blotting. MMP-9 mRNA expression and enzymatic activity were determined by RT-PCR and SDS-PAGE gelatin zymography. Result: Serum LTB4 concentration was significantly higher in AMI and UAP groups, compared with control and SAP groups (p < 0.01). Subgroups analysis showed that LTB4 was significantly higher in the AMI < 24h group, compared with the AMI > 24h group. Expression of EMMPRIN on circulating monocytes was significantly higher in patients with UAP and AMI ( > 24h), compared with control, SAP and AMI ( < 24h) groups (p < 0.05). In vitro study showed LTB4 up-regulated the expression of EMMPRIN, as well as the expression and activity of MMP-9, in cultured THP-1-derived macrophages (p < 0.05). Conclusion: LTB4 and EMMPRIN are associated with the pathogenesis of ACS and may be potential biomarkers for patients with ACS.
    Clinical and investigative medicine. Medecine clinique et experimentale 01/2013; 36(6):E282.