Long-term modulatory effect of Mycobacterium vaccae treatment on histopathologic changes in a murine model of asthma.

BACKGROUND: Mycobacteria are being investigated for modulation of inflammation in asthma and atopic disorders by eliciting particularly strong protective TH1 immune responses. OBJECTIVE: To investigate the long-term effects of intratracheally administered Mycobacterium vaccae on an experimental murine model of asthma. METHODS: BALB/c mice were placed in 4 groups: long-term M. vaccae, M. vaccae, asthma, and control groups. All groups but controls were sensitized intraperitoneally and challenged intratracheally with ovalbumin. The long-term M. vaccae and M. vaccae groups were treated with M. vaccae intratracheally simultaneously during challenges. Finally, mice in the long-term M. vaccae group were rechallenged with ovalbumin nebulization 24 days later. Evaluations of lung histopathologic findings and serum cytokine levels were performed. RESULTS: Comparison of the long-term M. vaccae group with the asthma model group revealed that the number of hyperplasic goblet cells in small and large airways (small airway: P < .05; large airways: P < .01) and thickness of basement membrane in large airways were significantly less in the long-term M. vaccae group. Furthermore, numbers of hyperplasic goblet cells in small airways (P < .05) and basement membrane in the large airway (P < .05), as well as inflammation in small airways (P < .01), were significantly less in the M. vaccae group when compared with the asthma model group. Interferon-gamma secretion from splenocytes of the M. vaccae group was significantly higher than the asthma model and long-term M. vaccae groups. CONCLUSION: Intratracheal administration of M. vaccae exerted a long-lasting ameliorating effect on airway histopathologic features of a murine asthma model.     

The Role of Serum Procalcitonin Levels in Predicting Ascitic Fluid Infection in Hospitalized Cirrhotic and Non-cirrhotic Patients

Objective: To determine the role of serum procalcitonin levels in predicting ascites infection in hospitalized cirrhotic and non-cirrhotic patients.Methods: A total of 101 patients (mean age: 63.4±1.3, 66.3% were males) hospitalized due to cirrhosis (n=88) or malignancy related (n=13) ascites were included in this study. Spontaneous bacterial peritonitis (SBP, 19.8%), culture-negative SBP (38.6%), bacterascites (4.9%), sterile ascites (23.8%) and malign ascites (12.9%) groups were compared in terms of procalcitonin levels in predicting ascites infection. Receiver operating characteristic (ROC) curves were used to evaluate the diagnostic performance of procalcitonin levels and predicting outcome of procalcitonin levels was compared with C-reactive protein (CRP).Results: Culture positivity was determined in 26.7% of overall population. Serum procalcitonin levels were determined to be significantly higher in patients with positive bacterial culture in ascitic fluid compared to patients without culture positivity (median (min-max): 4.1 (0.2-36.4) vs. 0.4 (0.04-15.8), p<0.001). Using ROC analysis, a serum procalcitonin level of <0.61 ng/mL in SBP (area under curve (AUC): 0.981, CI 95%: 0.000-1.000, p<0.001), <0.225 ng/mL in culture-negative SBP (AUC: 0.743, CI 95%: 0.619-0.867, p<0.001), <0.42 ng/mL in SBP and culture-negative SBP patients (AUC: 0.824, CI 95%: 0.732-0.916, p<0.001), and <1.12 ng/mL in bacterascites (AUC: 0.837, CI 95%: 0.000-1.000, p=0.019) were determined to accurately rule out the diagnosis of bacterial peritonitis. Predictive power of serum procalcitonin levels in SBP + culture-negative SBP group (AUCs: 0.824 vs 0.622, p=0.004, Fig 4), culture-positive SBP (AUCs: 0.981 vs 0.777, p=0.006, Fig 5) and (although less powerfull) in culture-negative SBP (AUCs: 0.743 vs 0.543, p=0.02, Fig 6) were found significantly higher than CRP.Conclusion: According to our findings determination of serum procalcitonin levels seems to provide satisfactory diagnostic accuracy in differentiating bacterial infections in hospitalized patients with liver cirrhosis related ascites.     

Treatment failure may lead to accelerated fibrosis progression in patients with chronic hepatitis C

Chronic hepatitis C (CHC) patients with treatment failure (TF) remain at risk of continuing fibrosis progression. However, it has not been investigated whether there is an increased risk of accelerated fibrosis progression after failed interferon‐based therapy. We aimed to investigate long‐term influence of TF on fibrosis progression compared with untreated patients with CHC. We studied 125 patients with CHC who underwent paired liver biopsies from 1994 to 2012. Patients with advanced fibrosis were excluded from the analysis. Sixty‐three patients had TF, and 62 patients were treatment‐naïve (TN). Annual fibrosis progression rate (FPR) was calculated, and significant fibrosis progression (SFP) was defined as ≥2 stage increase in fibrosis during follow‐up. Multiple regression analyses were performed to find out independent predictors of FPR and SFP. Demographic characteristics and duration between paired liver biopsies were similar in TF and TN groups. Baseline alanine aminotransferase and gamma‐glutamyl transferase (GGT) levels (71 ± 31 vs 47 ± 22, P < 0.001 and 49 ± 39 vs 36 ± 28, P = 0.027, respectively), baseline mean fibrosis stage (2.2 ± 0.7 vs 1.9 ± 0.7, P = 0.018) and histologic activity index (6.3 ± 1.9 vs 4.3 ± 1.6, P < 0.001) were higher in the TF group compared with the TN group. In regression analyses, the strongest independent predictor of fibrosis progression was the GGT level (OR: 1.03, 95%CI 1.01–1.5, P < 0.001). Treatment experience (OR: 5.97, 95%CI 1.81–19.7, P = 0.003) also appeared as an independent predictor of both FPR and SFP. Failed interferon‐based CHC treatment may lead to accelerated FPR in the long‐term compared with the natural course.     

Hemorheological changes with strontium ranelate treatment do not seem to be related to its claimed prothrombotic effects

Strontium ranelate is claimed to be related with increased risk of thromboembolic events. No explanation of this increased incidence of thromboembolism has been identified. However, growing evidence has clearly demonstrated the involvement of blood rheology in any thrombotic process. The aim of this study was to assess hemorheological changes with strontium ranelate treatment in elderly women with osteoporosis. This study was designed in a prospective manner. Twenty-two elderly women diagnosed with osteoporosis were included. During a 2-month treatment period, participants received strontium ranelate 2 g/day. Hemorheological parameters including erythrocyte deformability, erythrocyte aggregation and plasma viscosity were measured before and after 2 months therapy with strontium ranelate. The median age of the patients was 70.0 (range = 65-80) years. After 60 days of treatment, there was no statistically significant change in hemorheological parameters. None of the subjects developed clinical venous thromboembolic event (VTE) during the 2-month period of strontium ranelate treatment. Our study demonstrated that in elderly women, treatment of osteoporosis with strontium ranelate did not change hemorheological parameters over 2 months of time. However, its long-term effects on hemorheologic parameters should be evaluated further with a larger sample.     

Coexistence of osteoporosis (OP) and coronary artery disease (CAD) in the elderly: it is not just a by chance event

Cardiovascular disease (CVD) and OP are common age-related conditions. In both cross-sectional and longitudinal epidemiologic studies, low bone mass has been related to increased frequency of CVD. But available data in geriatric population is limited. In this study we aimed to seek the possible relationship between CAD and low bone mineral density (BMD) in a large number of geriatric patients. A total of 2235 patients aged 65 years or more were included in this cross-sectional study. All patients underwent a complete geriatric assessment and evaluated for CAD and cardiovascular risk factors. BMD was measured by dual-energy X-ray absorptiometry at the lumbar spine (L1-L4) and femoral neck. BMD results were classified into three groups; normal (T-score: ≥-1.0×S.D.), osteopenia (T-score between -1.0 and -2.5×S.D.), and OP (T-score: ≤-2.5×S.D.). CAD was present in 397 (29.7%) of 1335 patients with OP, in 199 (27.4%) of 726 patients with osteopenia and in 34 (19.5%) of 174 patients with normal BMD. Multivariate regression analysis revealed that presence of OP or osteopenia increased the prevalence of CAD as an independent correlate (OR=1.643; 95% CI=1.068-2.528, p=0.030). This study highlights the need for careful evaluation of elderly patients with low BMD for possible CAD.     

The association between homocysteine (hcy) and serum natural antioxidants in elderly bone mineral densitometry (BMD)

Previous studies showed oxidative stress had an important impact on osteoclastic and osteoblastic functions. Oxidative stress or low levels of antioxidants are supposed to reduce BMD and cause osteoporosis. hcy, gamma glutamyltransferase (GGT), uric acid, albumin and total bilirubin are simple laboratory parameters that are related with oxidative stress. In this study we compare the serum hcy and antioxidant levels in patients with osteoporosis, osteopenia and control subjects. A total of 2190 elderly persons (1348 patients with osteoporosis, 643 patients with osteopenia and 199 control subjects) who were referred to the outpatient clinic of the Department of Internal Medicine, Division of Geriatric Medicine at Hacettepe University Hospital for comprehensive geriatric assessment were included in this cross-sectional study. Mean age of subjects were 72.30±6.34 in osteoporosis group, 71.92±6.90 in osteopenia and 71.86±5.88 in control group (p: 0.260). Multivariate regression analysis revealed that hypertension (HT) (OR: 0.675, 95% CI: 0.534-0.854, p: 0.001), diabetes mellitus (DM) (OR: 1.669, 95% CI: 1.301-2.142, p: <0.001), age (OR: 1.025, 95% CI: 1.006-1.044, p: 0.009), male gender (OR: 0.451, 95% CI: 0.358-0.569, p<0.001), uric acid (OR: 0.893, 95% CI: 0.837-0.952, p: 0.001), hcy (OR: 1.042, 95% CI: 1.023-1.061, p<0.001), albumin (OR: 0.521, 95% CI: 0.376-0.724, p<0.001), GGT (OR: 1.010, 95% CI: 1.003-1.017, p: 0.003), creatinine (OR: 0.630, 95% CI: 0.459-0.864, p: 0.004) were independent variables predicting the occurrence of osteoporosis. This study shows there is an imbalance between natural antioxidative and oxidative markers in patients with osteoporosis. Higher serum uric acid and albumin levels are associated with a lower prevalence of osteoporosis whereas higher hcy and GGT levels are associated lower BMD and higher osteoporosis prevalence.