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61.
62.
Nemec A Pavlica Z Nemec-Svete A Eržen D Milutinović A Petelin M 《Experimental lung research》2012,38(1):9-18
Adjunctive corticosteroid treatment to reduce excessive local inflammatory response in pneumonia is controversial. To study the effects of an early local adjunct dexamethasone treatment on the course of pneumonia and inflammatory/cytokine response, mice were intratracheally inoculated with live Porphyromonas gingivalis and treated with either clindamycin (C), dexamethasone (D), C+D combination, or were not treated (Pg). Six mice from each group were euthanized at 6, 24, 72, and 168 hours after inoculation. Levels of tumor necrosis factor (TNF)-α, soluble TNF-α receptors (sTNFR1 and sTNFR2), interleukin (IL)-1β, and IL-6 in the serum and lung-homogenate supernatant were determined. Lung samples were histopathologically assessed and all findings compared to those found in 24 sham-inoculated mice (phosphate-buffered saline [PBS]). Severe P. gingivalis-induced bronchopneumonia progressed from 24 hours, peaked at 72 hours, and resolved after 168 hours with changes in local and systemic cytokine levels. Clindamycin-treated mice developed only mild bronchopneumonia that resolved fast (72 hours) with an early (6-24 hours) normalization of local and systemic cytokine levels. Similar course of pneumonia and cytokine level changes were observed in mice treated with C+D, but later. Early (6-24 hours) local elevation of sTNFRs was observed in C and C+D groups of mice, whereas nontreated (Pg) mice had increased systemic sTNFRs. Severe bronchopneumonia with delayed resolution was observed in D-group mice, with an early local and systemic decrease in sTNFR1 and persistent elevation of local TNF-α. Clindamycin or a clindamycin-dexamethasone combination treatment significantly improves the course of P. gingivalis-aspiration pneumonia, but more so if clindamycin alone is used. A favorable course of pneumonia seems to be associated with an early elevation of sTNFRs and normalization of TNF-α. 相似文献
63.
Milan M Boninsegna S Scribano L Lobello S Fagiuoli S Fabris P Buda A Martines D 《Infection》2012,40(2):173-179
Background
Pegylated interferon (PEG-IFN) and ribavirin is the most effective treatment for chronic hepatitis C virus (HCV) hepatitis, but the rate of sustained virological response (SVR) remains approximately 50%, and 15–20% of all treated patients have a virological relapse after completing the treatment. Studies on the SVR have failed to discriminate between non-responders and relapsers. 相似文献64.
Grisafi D Tassone E Dedja A Oselladore B Masola V Guzzardo V Porzionato A Salmaso R Albertin G Artusi C Zaninotto M Onisto M Milan A Macchi V De Caro R Fassina A Bordigato MA Chiandetti L Filippone M Zaramella P 《Lung》2012,190(4):419-430
Background
Moderate normobaric hyperoxia causes alveolar and vascular lung derangement in the newborn rat. Endogenous nitric oxide (NO), which promotes lung growth, is produced from the metabolism of l-arginine to l-citrulline in endothelial cells. We investigated whether administering l-citrulline by raising the serum levels of l-arginine and enhancing NO endogenous synthesis attenuates moderate hyperoxia-induced lung injury.Methods
Newborn rats were exposed to FiO2?=?0.6 or room air for 14?days to induce lung derangement and then were administered l-citrulline or a vehicle (sham). Lung histopathology was studied with morphometric features. Lung tissues and bronchoalveolar lavage fluid (BALF) were collected for analysis. Lung vascular endothelial growth factor (VEGF), nitric oxide synthase (eNOS), and matrix metalloproteinase 2 (MMP2) gene and protein expressions were assessed.Results
Serum l-arginine rose in the L-citr?+?hyperoxia group (p?=?0.05), as well as the Von Willebrand factor stained vessels count (p?=?0.0008). Lung VEGF immune staining, localized on endothelial cells, was weaker in the sections under hyperoxia than the l-citr?+?hyperoxia and room air groups. This pattern was comparable with the VEGF gene and protein expression profiles. Mean alveolar size increased in the untreated hyperoxia and sham-treated groups compared with the groups reared in room air or treated with l-citrulline under exposure to hyperoxia (p?=?0.0001). Lung VEGF and eNOS increased in the l-citrulline-treated rats, though this treatment did not change MMP2 gene expression but regulated the MMP2 active protein, which rose in BALF (p?=?0.003).Conclusions
We conclude that administering l-citrulline proved effective in improving alveolar and vascular growth in a model of oxygen-induced pulmonary damage, suggesting better lung growth and matrix regulation than in untreated groups. 相似文献65.
Lionnet F Hammoudi N Stojanovic KS Avellino V Grateau G Girot R Haymann JP 《Haematologica》2012,97(8):1136-1141
Background
Hemoglobin sickle cell disease is one of the most frequent hemoglobinopathies. Surprisingly, few studies have been dedicated to this disease, currently considered to be a mild variant of homozygous sickle cell disease. The aim of this study was to update our knowledge about hemoglobin sickle cell disease.Design and Methods
The study involved a single center series of 179 patients. Clinical and biological data were collected with special attention to the assessment of pulmonary arterial hypertension and nephropathy.Results
Hemoglobin sickle cell diagnosis was delayed and performed in adulthood in 29% of cases. Prevalence of hospitalized painful vasoocclusive crisis, acute chest syndrome and priapism was 36%, 20% and 20%, respectively. The most common chronic organ complications were retinopathy and sensorineural otological disorders in 70% and 29% of cases. Indeed, prevalence of complications reported in homozygous sickle cell disease, such as nephropathy, suspicion of pulmonary hypertension, strokes and leg ulcers was rather low (13%, 4% and 1%, respectively). Phlebotomy performed in 36% of this population (baseline hemoglobin 11.5 g/dL) prevented recurrence of acute events in 71% of cases.Conclusions
Our data suggest that hemoglobin sickle cell disease should not be considered as a mild form of sickle cell anemia but as a separate disease with a special emphasis on viscosity-associated otological and ophthalmological disorders, and with a low prevalence of vasculopathy (strokes, pulmonary hypertension, ulcers and nephropathy). Phlebotomy was useful in reducing acute events and a wider use of this procedure should be further investigated. 相似文献66.
Petrovic M Petrovic MT Milasinovic G Vujisic-Tesic B Trifunovic D Nedeljkovic I Calovic Z Ivanovic B Tesic M Boricic M Petrovic O Petrovic IM Banovic M Draganic G Ostojic M 《Echocardiography (Mount Kisco, N.Y.)》2012,29(3):267-275
Objectives: The aim of this study was to assess the performance of echocardiographic parameters to predict response to cardiac resynchronization therapy (CRT). Background: CRT reduces morbidity and mortality due to the proper selection of candidates for CRT. Methods: The 12‐month trial was performed on 70 optimally medicated patients with standard inclusion criteria: NYHA class III or IV heart failure, left ventricular ejection fraction (LVEF) ≤ 35%, and QRS ≥ 120 ms. All parameters were evaluated by conventional and tissue Doppler‐based methods. Indicator of positive CRT response was more than 20% in improvement of LVEF. Results: LVEF increased >20% in 42 patients. Out of 43 tested baseline echocardiographic parameters, 12 showed statistical difference between responders and nonresponders. Out of these 12 parameters, six (LVSV, LVSI, LVFS, RVd, VPMR, and PISA) had modest to moderately good ability to predict LVEF response with sensitivity ranging from 62.2% to 82.4%, and specificity ranging from 56.5% to 81.2%. For those parameters, the area under the receiver‐operating characteristic curve for positive response to CRT was ≤0.76. Multivariate regression analysis resulted in selection of LVSI and LVFS as possible predictive independent parameters for a good response. The cutoff value for LVSI was 38.7 mL/m2 (P = 0.045) and for LVFS was 13% (P = 0.032). Conclusions: Contribution of LVSI and LVFS is to be confirmed in larger trials. Simplicity of their assessment by conventional echocardiography could be an argument for adding them to the inclusion criteria for CRT in severe heart failure patients. (Echocardiography 2012;29:267‐275) 相似文献
67.
Nikpay M ?eda O Tremblay J Petrovich M Gaudet D Kotchen TA Cowley AW Hamet P 《Hypertension research》2012,35(6):585-591
Links between substance use habits, obesity, stress and the related cardiovascular outcomes can be, in part, because of loci with pleiotropic effects. To investigate this hypothesis, we performed genome-wide mapping in 119 multigenerational families from a population in the Saguenay-Lac-St-Jean region with a known founder effect using 58,000 single-nucleotide polymorphisms and 437 microsatellite markers to identify genetic components of the following factors: habitual alcohol, tobacco and coffee use; response to mental and physical stress; obesity-related traits; and heart rate (HR) and blood pressure (BP) measures. Habitual alcohol and/or tobacco users had attenuated HR responses to mental stress compared with non-users, whereas hypertensive individuals had stronger HR and systolic BP responses to mental stress and a higher obesity index than normotensives. Genetic mappings uncovered numerous shared genes among substance use, stress response, obesity and hemodynamic traits, including CAMK4, CNTN4, DLG2, FHIT, GRID2, ITPR2, NOVA1 and PRKCE, forming network of interacting proteins, sharing synaptic function and display higher and patterned expression profiles in brain-related tissues; moreover, pathway analysis of shared genes pointed to long-term potentiation. Subgroup genetic mappings uncovered additional shared synaptic genes, including CAMK4, CNTN5 and DNM3 (hypertension-specific); CNTN4, DNM3, FHIT and ITPR1 (sex-specific), having protein interactions with genes driven from general analysis. In summary, consistent with the observed phenotypic correlations, we found substantial overlap among genomic determinants of these traits in synapse, which supports the notion that the neural synapse may be a shared interface behind substance use, stress, obesity, HR, BP as well as the observed sex- and hypertension-specific genetic differences. 相似文献
68.
Popović M Smiljanić K Dobutović B Syrovets T Simmet T Isenović ER 《Journal of thrombosis and thrombolysis》2012,33(2):160-172
Vascular endothelium, as a key regulator of hemostasis, mediates vascular dilatation, prevents platelet adhesion, and inhibits
thrombin generation. Endothelial dysfunction caused by acute or chronic inflammation, such as in atherosclerosis, creates
a proinflammatory environment which supports leukocyte transmigration toward inflammatory sites, and at the same time promotes
coagulation, thrombin generation, and fibrin deposition in an attempt to close the wound. Life-long persistent infection with
human cytomegalovirus (HCMV) has been associated with atherosclerosis. In vivo studies have revealed that HCMV infection of
the vessel wall affects various cells including monocytes/macrophages, smooth muscle cells (SMCs) and endothelial cells (ECs).
HCMV-infected SMCs within vascular lesions display enhanced proliferation and impaired apoptosis, which contribute to intima-media thickening, plaque formation and restenosis. Monocytes play a central role in the process of viral dissemination, whereas
ECs may represent a viral reservoir, maintaining persistent infection in HCMV-infected atherosclerotic patients following
the primary infection. Persistent infection leads to dysfunction of ECs and activates proinflammatory signaling involving
nuclear factor κB, specificity protein 1, and phosphatidylinositol 3-kinase, as well as expression of platelet-derived growth
factor receptor. Activation of these pathways promotes enhanced proliferation and migration of monocytes and SMCs into the
intima of the vascular wall as well as lipid accumulation and expansion of the atherosclerotic lesion. Moreover, HCMV infection
induces enhanced expression of endothelial adhesion molecules and modifies the proteolytic balance in monocytes and macrophages.
As a consequence, infected endothelium recruits naive monocytes from the blood stream, and the concomitant interaction between
infected ECs and monocytes enables virus transfer to migrating monocytes. Endothelial damage promotes thrombin generation
linking inflammation and coagulation. HCMV, in turn, enhances the thrombin generation. The virus carries on its surface the
molecular machinery necessary to initiate thrombin generation, and in addition, may interact with the prothrombinase protein
complex thereby facilitating thrombin generation. Thus, infection of endothelium may significantly increase the production
of thrombin. This might not only contribute to thrombosis in patients with atherosclerosis, but might also induce thrombin-dependent
proinflammatory cell activation. This review summarizes the existing evidence on the role of HCMV in vascular inflammation. 相似文献
69.
Ruzicka J Stengl M Bolek L Benes J Matejovic M Krouzecky A 《Blood coagulation & fibrinolysis》2012,23(4):285-289
Selective incircuit blood cooling could be an effective anticoagulation strategy during hemodialysis. However, it is currently unknown what blood temperature would ensure sufficient anticoagulation. Similarly, no information exists about potential interindividual variability in response to graded hypothermia. Therefore, the aim of this study was to analyze effects of profound hypothermia on human coagulation. Furthermore, a mathematical relationship between blood temperatures and coagulation was sought to predict individual responses to blood cooling. It was designed as a laboratory study. Thromboelastography (TEG) measurements were taken at a temperature range of 38-12°C. To enable measurements below 20°C, the TEG device was placed into an air conditioned chamber allowing for setting of the temperatures over a wide range. The data were analyzed by regression analysis for pooled and individual measurements. Decreasing temperatures always led to a progressive reduction in blood coagulation by delaying the initiation of thrombus formation, as well as by decreasing the speed of its creation and growth. However, the response to cooling was not uniform and the interindividual variability exists. The relationship between blood temperature and coagulation is not linear but exponential (parameters R and K) and sigmoid (parameter α-angle). The lower the blood temperature, the more significant effect on blood coagulation decline. To predict an individual response of the coagulation system over a wide range of temperatures, a mathematical modeling can be used. 相似文献
70.
Tahrani AA Ali A Raymond NT Begum S Dubb K Mughal S Jose B Piya MK Barnett AH Stevens MJ 《American journal of respiratory and critical care medicine》2012,186(5):434-441
Rationale: Diabetic peripheral neuropathy is common and causes significant morbidity. Obstructive sleep apnea (OSA) is also common in patients with type 2 diabetes. Because OSA is associated with inflammation and oxidative stress, we hypothesized that OSA is associated with peripheral neuropathy in type 2 diabetes. Objectives: To assess the relationship between OSA and peripheral neuropathy in patients with type 2 diabetes. Methods: A cross-sectional study of adults with type 2 diabetes recruited randomly from the diabetes clinic of two UK hospitals. Measurements and Main Results: Peripheral neuropathy was diagnosed using the Michigan Neuropathy Screening Instrument. OSA (apnea-hypopnea index ≥ 5 events/h) was assessed using home-based, multichannel respiratory monitoring. Serum nitrotyrosine was measured by ELISA, lipid peroxide by spectrophotometer, and microvascular function by laser speckle contrast imaging. Two hundred thirty-four patients (mean [SD] age, 57 [12] yr) were analyzed. OSA prevalence was 65% (median apnea-hypopnea index, 7.2; range, 0-93), 40% of which were moderate to severe. Neuropathy prevalence was higher in patients with OSA than those without (60% vs. 27%, P < 0.001). After adjustment for possible confounders, OSA remained independently associated with diabetic neuropathy (odds ratio, 2.82; 95% confidence interval, 1.44-5.52; P = 0.0034). Nitrotyrosine and lipid peroxide levels (n = 102, 74 with OSA) were higher in OSA and correlated with hypoxemia severity. Cutaneous microvascular function (n = 71, 47 with OSA) was impaired in OSA. Conclusions: We describe a novel independent association between diabetic peripheral neuropathy and OSA. We identified increased nitrosative/oxidative stress and impaired microvascular regulation as potential mechanisms. Prospective and interventional studies are needed to assess the impact of OSA and its treatment on peripheral neuropathy development and progression in patients with type 2 diabetes. 相似文献