Pro- and Anti-inflammatory Cytokines in Steatosis and Steatohepatitis

Fatty liver disease is a problem in both bariatric patients and in patients with moderate obesity. Tumor necrosis factor (TNF)-alpha has been frequently measured in nonalcoholic steatohepatitis (NASH) with or without diabetes, but less is known about interleukin (IL)-6 and IL-10. Moderately obese patients (n = 80) with histologically proven steatosis (n = 29) and NASH (n = 51) were recruited. Serum levels of cytokines were documented along with clinical information. The aim was to identify the correlates of such biomolecules in a stable population. Diabetes tended to be more associated with NASH (52.5% instead of 41.4%, P = 0.015), with no difference of age, gender, or body mass index regarding steatosis. For the entire population, cytokine changes were not significant, including TNF-alpha and IL-6. In diabetics only, all markers tended to diminish with NASH, especially IL-10 (P = 0.000). IL-10 correlated with homeostatic model assessment index (P = 0.000) and other variables of glucose homeostasis in diabetes, thus representing a major marker of the disease. (1) Generally inconsistent changes in pro- and anti-inflammatory cytokines occurred when NASH was globally compared to steatosis. (2) In contrast, downregulation of IL-6 and IL-10 was perceived in diabetics with NASH. (3) Arterial hypertension did not play a role in these circumstances. (4) IL-10 maintained strong correlations with glucose metabolism indices. (5) TNF-alpha could not be incriminated for progressive liver damage, as values failed to increase in NASH. (6) Investigations of IL-10 and other counterregulatory cytokines are lacking in this context and deserve further studies.

Relationship between limb movement speed and associated contraction of the trunk muscles

Rapid shoulder movement is preceded by contraction of the abdominal muscles to prepare the body for the expected disturbance to postural equilibrium and spinal stability provoked by the reactive forces resulting from the movement. The magnitude of the reactive forces is proportional to the inertia of the limb. The aim of the study was to investigate if changes in the reaction time latency of the abdominal muscles was associated with variation in the magnitude of the reactive forces resulting from variation in limb speed. Fifteen participants performed shoulder flexion at three different speeds (fast, natural and slow). The onset of EMG of the abdominal muscles, erector spinae and anterior deltoid (AD) was recorded using a combination of fine-wire and surface electrodes. Mean and peak velocity was recorded for each limb movement speed for five participants. The onset of transversus abdominis (TrA) EMG preceded the onset of AD in only the fast movement condition. No significant difference in reaction time latency was recorded between the fast and natural speed conditions for all muscles. The reaction time of each of the abdominal muscles relative to AD was significantly delayed with the slow movement compared to the other two speeds. The results indicate that the reaction time latency of the trunk muscles is influenced by limb inertia only with limb movement below a threshold velocity.

Non-expression of insulin-like growth factor-I receptor is associated with apoptosis: an ultrastructural study on rat ameloblasts

Insulin-like growth factor-I (IGF-I) is a preiotrophic polypeptide which appears to have roles both as a circulating endocrine hormone and as a locally synthesized paracrine or autocrine tissue factor. IGF-I plays a major role in regulating the growth of cells in vivo and in vitro and initiates metabolic and mitogenic processes in a wide variety of cell types by binding to specific type I receptors in the plasma membrane, In this study, we report the distribution of IGF-I receptors in odontogenic cells at the ultrastructural level using the high resolution protein A-gold technique, In the pre-secretory stage, very little gold label was visible over the ameloblasts and odontoblasts, During the secretory stage the label was mostly seen in association with the cell membranes and endoplasmic reticulum of the ameloblasts. Lysosome-like elements in the post-secretory stage were labelled as well as multivesicular dense bodies, Very little labelling was encountered in the ameloblasts in the transitional stage, where apoptotic bodies were clearly visible, The maturation stage also exhibited labelling of the secretory-like granules in the distal surface. The presence of gold particles over the plasma membrane is an indication that IGF-I receptor is a membrane-bound receptor. Furthermore, the intracellular distribution of the label over the endoplasmic reticulum supports the local synthesis of the IGF-I receptor. The absence of labelling over the transitional ameloblasts suggests that the transitional stage may require the non-expression of IGF-I as a prerequiste or even a trigger for apoptosis.

The prognostic value of CD147/EMMPRIN is associated with monocarboxylate transporter 1 co-expression in gastric cancer

The aim of the present work was to assess the role of monocarboxylate transporters (MCTs), namely MCT1 and MCT4 as well as MCT/CD147 co-expression in gastric tissues and evaluate their clinico-pathological significance in gastric carcinoma. For that, we analysed the immunohistochemical expression of MCT1, MCT4 and CD147, in a large series of gastric samples, including non-neoplastic, tumour and metastatic tissues. A significant decrease in MCT4 plasma membrane expression was observed from non-neoplastic to gastric primary malignant tissues and to lymph-node metastasis and both MCT1 and MCT4 correlated with CD147. Importantly, both MCT4 and CD147 were more frequently expressed in Lauren`s intestinal-type tumours and MCT1/CD147 co-expression was associated with advanced gastric carcinoma, Lauren`s intestinal type, TNM staging and lymph-node metastasis. Our results showed that the prognostic value of CD147 was associated with MCTI co-expression in gastric cancer cells, supporting the view that CD147 plasma membrane activity is dependent on MCT co-expression. (C) 2009 Elsevier Ltd. All rights reserved.

Intestinal mucosa-associated microflora in ulcerative colitis patients before and after restorative proctocolectomy with an ileoanal pouch

PURPOSE: This study was designed to identify the mucosa-associated microflora in patients with severe ulcerative colitis before and after restorative proctocolectomy with ileoanal pouch construction in comparison with historic controls. METHODS: Ten patients with a diagnosis of ulcerative colitis were evaluated. Mucus was collected during colonoscopy from all segments of the colon and terminal ileum before surgery, and from the ileal pouch two and eight months after ileostomy closure. The prevalence and mean concentration of the mucosa-associated microflora were compared over time and with historic controls. RESULTS: Veillonella sp was the most prevalent bacterium in patients and controls. Klebsiella sp was significantly more prevalent in the ileum of controls, was not found in patients with ulcerative colitis, and after proctocolectomy returned to values found in controls. Some bacteria such as Enterobacter sp, Staphylococcus sp (coag-), Bacteroides sp (npg), Lactobacillus sp, and Veillonella sp had higher mean concentrations in the ileal pouch of patients after surgery than in controls. CONCLUSION: No bacterium was identified that could be exclusively responsible for the maintenance of the inflammatory process. The mucosa-associated microflora of patients with ulcerative colitis underwent significant changes after proctocolectomy with ileal pouch construction and returned to almost normal values for some bacteria.

Single nucleotide polymorphism C/T-13910, located upstream of the lactase gene, associated with adult-type hypolactasia: Validation for clinical practice

Objectives: To validate C/T-13910 polymorphism associated with primary hypolactasia for clinical practice. Design and methods: Lactose breath test and PCR-RFLP for the C/T-13910 polymorphism were performed. Results: Twenty-seven of 28 patients with genotype CC had positive breath tests, all twenty-two patients with genotypes CT or TT had negative breath tests. Agreement of tests was high (p<0.0001; Kappa Index 0.96). Conclusion: C/T-13910 polymorphism detection may be a new tool for primary hypolactasia diagnosis. (C) 2008 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

Leptospirosis pulmonary haemorrhage syndrome is associated with linear deposition of immunoglobulin and complement on the alveolar surface

Leptospirosis is a zoonotic infection associated with severe diseases such as leptospirosis pulmonary haemorrhage syndrome (LPHS). The cause of pulmonary haemorrhage is unclear. Understanding which mechanisms and processes are involved in LPHS will be important in treatment regimens under development for this life-threatening syndrome. In the present study, we evaluated 30 lung specimens from LPHS patients and seven controls using histology and immunohistochemistry (detection of IgM, IgG, IgA and C3) in order to describe the pathological features associated with this syndrome. Immunoglobulin deposits were detected on the alveolar surface in 18/30 LPHS patients. Three staining patterns were observed for the immunoglobulins and C3 in the lung tissues of LPHS patients: AS, delicate linear staining adjacent to the alveolar surface, which was indicative of a membrane covering the luminal surface of type I and II pneumocyte cells; S, heterogeneous staining which was sporadically distributed along the alveolar septum; and IA, weak, focal intra-alveolar granular staining. Human LPHS is associated with individual and unique histological patterns that differ from those of other causes of pulmonary haemorrhage. In the present study, it was found that the linear deposition of immunoglobulins (IgA, IgG and IgM) and complement on the alveolar surface may play a role in the pathogenesis of pulmonary haemorrhage in human leptospirosis.

Efficacy of the tubercidin antileishmania action associated with an inhibitor of the nucleoside transport

Tubercidin (TUB) is an adenosine analog with potent antiparasite action, unfortunately associated with severe host toxicity. Prevention of TUB toxicity can be reached associating nitrobenzylthioinosine (NBMPR), an inhibitor of the purine nucleoside transport, specifically target to the mammal cells. It was demonstrated that this nucleoside transport inhibitor has no significant effect in the in vitro uptake of TUB by Schistosoma mansoni and Trypanosoma gambiense. Seeking to evaluate if the association of these compounds is also effective against leishmania, we analyzed the TUB-NBMPR combined treatment in in vitro cultures of promastigote forms of Leishmania (L.) amazonensis, Leishmania (L.) chagasi, Leishmania (L.) major, and Leishmania (V.) braziliensis as well as in cultures of amastigote forms of L. (L.) amazonensis, mice macrophages infected with L. (L.) amazonensis, and in vivo tests in BALB/c mice infected with L. (L.) amazonensis. We demonstrated that TUB-NBMPR combined treatment can be effective against leishmania cells protecting mammalian cells from TUB toxicity.

Factors associated with mortality in patients with bloodstream infection and pneumonia due to Stenotrophomonas maltophilia

Severe infections caused by Stenotrophomonas maltophilia are associated with high mortality, and strategies to improve the clinical outcome for infected patients are needed. A retrospective cohort study of patients with bloodstream infection (BSIs) and pneumonia caused by S. maltophilia was conducted. Multivariate analysis was performed to access factors associated with 14-day mortality. A total of 60 infections were identified. Among these, eight (13%) were pneumonias and 52 were BSIs; 33.3% were primary, 13% were central venous catheter (CVC)-related and 40% were secondary BSIs. Fifty-seven (85%) patients had received previous antimicrobial therapy; 88% had CVC, 57% mechanical ventilation and 75% were in the intensive care unit at the onset of infection. Malignancy (45%) was the most frequent underlying disease. The mean of the Acute Physiology and Chronic Health Evaluation II (APACHE II) scores was 17 and for the Sepsis-related Organ Failure Assessment (SOFA) score, it was 7 points. The overall and 14-day mortality were, respectively, 75% and 48%. Forty-seven (78%) patients were treated and, of these, 74% received trimethoprim-sulfamethoxazole. Independent risk factors associated with mortality were SOFA index > 6 points (0.005) and septic shock (0.03). The Kaplan-Meier estimations curves showed that patients with APACHE II score > 20 and SOFA score > 10 had a survival chance of, respectively, less than 8% and less than 10% (P <= 0.001) at 21 days after the first positive S. maltophilia culture. Our results suggest that the independent factors associated with outcome in patients with infection caused by S. maltophilia are septic shock and higher SOFA index.

Prevalence of, and risk factors for Kaposi`s sarcoma-associated herpesvirus infection among blood donors in Brazil: A multi-center serosurvey

Kaposi`s sarcoma-associated herpesvirus (KSHV) is endemic in the Amazon and rare in southern regions of Brazil. However, geographical distribution and epidemiological correlates of infection in this large country are still poorly defined. To estimate the seroprevalence of, and risk factors for, KSHV infection in Brazil, a multi-center study was conducted among 3,493 first-time voluntary unpaid blood donors from Salvador, Sao Paulo and Manaus. Antibodies against KSHV were detected using a whole-virus ELISA validated prior to the serosurvey. Antibodies against the latency-associated nuclear antigen (LANA) were detected by immuno-fluorescence assay (IFA) among ELISA-positive sera and a random sample of ELISA-negative sera. Overall, seroprevalence of KSHV by whole-virus ELISA was 21.7% (95% confidence interval (Cl): 20-23.4%) in men and 31.7% (95% Cl: 29-34.3%) in women (P<0.0001). KSHV antibodies were detected by IFA-LANA in 3% (95% Cl: 2-4.3%) of 867 ELISA-positive samples and in none of 365 randomly selected ELISA-negative samples. In multivariate analysis, KSHV seroprevalence by whole-virus ELISA was independently associated with female sex (odds ratio [OR] = 1.6, 95% Cl: 1.4-1.9); residence in the Amazon (OR = 1.4, 95% Cl: 1.2-1.8; compared to Salvador); Caucasian ethnicity (OR = 1.3, 95% Cl: 1.1-1.6) and herpes simplex virus type 2 (HSV-2) infection (OR = 1.3, 95% Cl: 1.1-1.6). KSHV seroprevalence did not significantly increase with age, nor was it associated with self-reported sexual behavior. KSHV seroprevalence is high among Brazilian blood donors, particularly from the Amazon region. This study supports the co-existence of sexual and non-sexual routes of KSHV transmission in this population.

Salvage of long-term central venous catheters during an outbreak of Pseudomonas putida and Stenotrophomonas maltophilia infections associated with contaminated heparin catheter-lock solution

objective. To describe the management of patients with long-term central venous catheters (CVCs) during an outbreak of infection due to Pseudomonas putida and Stenotrophomonas maltophilia associated with contaminated heparin catheter-lock solution. design. Descriptive study. setting. Private, 250-bed tertiary-care hospital. methods. In March 2003, we identified 2 febrile cancer patients with P. putida bacteremia. Over 2 days, 7 cases of bacteremia were identified; lots of syringes prefilled with heparin catheter-lock solution, supplied by a compounding pharmacy, were recalled and samples were cultured. More cases of bacteremia appeared during the following days, and any patient who had had a catheter lock infused with the suspect solution was asked to provide blood samples for culture, even if the patient was asymptomatic. Isolates that were recovered from culture were typed by pulsed-field gel electrophoresis. Antimicrobial salvage treatment of long-term CVCs was attempted. results. A total of 154 patients had had their catheter lock infused with solution from the lots that were suspected of being contaminated. Only 48 of these patients had CVCs. By day 7 of the outbreak, 18 of these patients had become symptomatic. Twenty-six of the remaining 30 asymptomatic patients then also provided blood samples for culture, 10 of whom developed fever shortly after samples were collected. Thirty-two patients were identified who had P. putida bacteremia; 9 also had infection due to S. maltophilia. Samples from 1 of the 3 lots of prefilled syringes in use at the time of the outbreak also grew P. putida on culture. Molecular typing identified 3 different clones of P. putida from patients and heparin catheter-lock solution, and 1 clone of S. maltophilia. A total of 27 patients received antimicrobial therapy regimens, some of which included decontamination of the catheter lock with anti- infective lock solution. Of 27 patients, 19 (70%) retained their long-term CVC during the 6-month follow-up period. conclusions. To our knowledge, this is one of the largest prospective experiences in the management of bloodstream infection associated with long-term CVCs. The infections were caused by gram-negative bacilli and were managed without catheter removal, with a high response rate. We emphasize the risks of using intravenous formulations of medications supplied by compounding pharmacies that produce large quantities of drugs.

Very early prediction of response to HCV treatment with PEG-IFN-alfa-2a and ribavirin in HIV/HCV-coinfected patients

The objective of this study was to find very early viral kinetic markers to predict nonresponse to hepatitis C virus (HCV) therapy in a group of human immunodeficiency virus (HIV)/HCV-coinfected patients. Twenty-six patients (15 HCV genotype-1 and 11 genotype-3) were treated with a 48-week regimen of peginterferon-alfa-2a (PEG-IFN) (180 mu g/week) and weight-based ribavirin (11 mg/kg/day). Samples were collected at baseline; 4, 8, 12, 18, 24, 30, 36 and 42 h; days 2, 3, 4, 7, 8, 15, 22, 29, 43 and 57 then weekly and monthly. Five patients discontinued treatment. Seven patients (27%) achieved a sustained virological response (SVR). Nadir HCV RNA levels were observed 1.6 +/- 0.3 days after initiation of therapy, followed by a 0.3- to 12.9-fold viral rebound until the administration of the second dose of PEG-IFN, which were not associated with SVR or HCV genotype. A viral decline < 1.19 log for genotype-1 and < 0.97 log for genotype-3, 2 days after starting therapy, had a negative predictive value (NPV) of 100% for SVR. The day 2 virological response had a similar positive predictive value for SVR as a rapid virological response at week 4. In addition, a second-phase viral decline slope (i.e., measured from day 2 to 29) < 0.3 log/week had a NPV = 100% for SVR. We conclude that first-phase viral decline at day 2 and second-phase viral decline slope (< 0.3 log/week) are excellent predictors of nonresponse. Further studies are needed to validate these viral kinetic parameters as early on-treatment prognosticators of nonresponse in patients with HCV and HIV.

Evaluation of interventions to reduce catheter-associated bloodstream infection: Continuous tailored education versus one basic lecture

Background: This study evaluated the impact of 2 models of educational intervention on rates of central venous catheter-associated bloodstream infections (CVC-BSIs). Methods: This was a prospective observational study conducted between January 2005 and June 2007 in 2 medical intensive care units (designated ICU A and ICU B) in a large teaching hospital. The study was divided into in 3 periods: baseline (only rates were evaluated), preintervention (questionnaire to evaluate knowledge of health care workers [HCWs] and observation of CVC care in both ICUs), and intervention (in ICU A, tailored, continuous intervention; in ICU B, a single lecture). The preintervention and intervention periods for each ICU were compared. Results: During the preintervention period, 940 CVC-days were evaluated in ICUA and 843 CVC-days were evaluated in ICU B. During the intervention period, 2175 CVC-days were evaluated in ICUA and 1694 CVC-days were evaluated in ICU B. Questions regarding CVC insertion, disinfection during catheter manipulation, and use of an alcohol-based product during dressing application were answered correctly by 70%-100% HCWs. Nevertheless, HCWs` adherence to these practices in the preintervention period was low for CVC handling and dressing, hand hygiene (6%-35%), and catheter hub disinfection (45%-68%). During the intervention period, HCWs` adherence to hand hygiene was 48%-98%, and adherence to hub disinfection was 82%-97%. CVC-BSI rates declined in both units. In ICUA, this decrease was progressive and sustained, from 12CVC-BSIs/1000 CVC-days at baseline to 0 after 9 months. In ICU B, the rate initially dropped from 16.2 to 0 CVC-BSIs/1000 CVC-days, but then increased to 13.7 CVC-BSIs/1000 CVC-days. Conclusion: Personal customized, continuous intervention seems to develop a ""culture of prevention"" and is more effective than single intervention, leading to a sustained reduction of infection rates.

Chronic American trypanosomiasis: parasite persistence in endomyocardial biopsies is associated with high-grade myocarditis

Myocyte diameter, fractional area of collagen, intensity of myocarditis and parasite persistence (explored by immunohistochemistry and PCR) were evaluated in serial sections of endomyocardial biopsies from 29 outpatients with chronic chagasic cardiopathy. The patients, 25 males and four females with a mean (S.D.) age of 43 (9) years, were subsequently followed up for 3-2861 days (median=369 days). During this follow-up, 16 (55%) of the patients died. The biopsies revealed myocarditis in 25 (86%) of the patients and high-grade myocarditis in 14 (56%). Although immunohistochemistry failed to demonstrate Trypanosoma cruzi antigens in any of the samples, five (33%) of the 15 biopsies successfully tested in the PCR-based assay for T. cruzi DNA were found positive, indicating parasite persistence. There was a significant positive association between myocardial parasite persistence and high-grade myocarditis (P= 0.014); five (71%,) of the seven endomyocardial biopsies with high-grade myocarditis that were successfully tested in the PCR assays showed persistent T. cruzi DNA. The survival time of the patients was not, however, found to be significantly associated with myocardial parasite persistence, any of the morphometric measurements taken, or the presence or intensity of myocarditis.

Narrowed lumen of the right coronary artery in chronic chagasic patients is associated with ischemic lesions of segmental thinnings of ventricles

Thinning of myocardial segments, mainly at the apex and basal posterior region of left ventricle, are frequent lesions in chronic chagasic cardiopathy (CCC), but still without a well determined etiology. Previously we found severe myocardial microvascular dilatation that could cause ischemia in watershed regions. In this study we analyzed whether narrowness in epicardial coronary arteries in CCC might explain these thinned ventricular lesions. Two groups of dilated hearts with similar weights were compared: eleven hearts from patients with CCC versus four hearts from patients with dilated cardiomyopathy (IDCM). As normal controls we studied three non dilated normal weight hearts. There were no atherosclerotic plaques in the main branches of epicardial coronary arteries and cross-sectional luminal areas of proximal and distal segments were histologically measured. It was found that CCC hearts presented a lower mean luminal area in the right coronary artery (RCA) branch than IDCM, in proximal (4.3 +/- 1.4 vs 6.6 +/- 2.0 mm(2); p = 0.02) and in distal (1.6 +/- 1.0 vs 3.4 +/- 0.9 mm(2); p = 0.01) segments, with no statistical differences with normal hearts (2.7 +/- 1.3 and 1.5 +/- 0.3 mm(2)) in proximal (p = 0.2) and distal (p = 0.11) sections. In conclusion thinning of ventricular wall in CCC patients seems to be ischemic lesions in the peripheral territory irrigated by the right coronary artery, possibly due to a steal phenomenon by the left coronary, induced by micro vessels dilatation.