Differential cellular analysis of bronchoalveolar lavage fluid obtained at various stages during the development of bleomycin-induced pulmonary fibrosis in the rat

The purpose of this study was to analyze the cellular components of bronchoalveolar lavage fluid throughout the development of bleomycin-induced pulmonary fibrosis in the rat. Animals were killed and lavaged at various times after the administration of a single intratracheal injection of bleomycin. The results demonstrate that a significant influx of inflammatory cells appear in the lavage fluid as early as Day 1 after bleomycin treatment. Polymorphonuclear leukocytes are the first cells to appear and significant concentrations persist for as long as 1 month after bleomycin treatment. There is a very transient yet significant influx of eosinophils on Day 7 after bleomycin treatment. Lymphocytes are present from 3 to 14 days after bleomycin treatment; greater than 97% are T-cells and less than 3% are B-cells. There is a 1:1 ratio of W3/25+ cells (helper cell activity) to OX8+ cells (suppressor cell activity) comprising the lymphocyte population. The blood and lymphoid tissue of these animals contain a normal 2:1 ratio of these subsets. The data demonstrate that specific T-cell populations are present in the air spaces of the lung in response to bleomycin-induced pulmonary fibrosis in this model.     

Recombinant GH replacement in hypopituitary adults improves endothelial cell function and reduces calculated absolute and relative coronary risk

OBJECTIVE: Adult GH deficiency (GHD) is linked to endothelial dysfunction and vascular disease. We examined the effect of 12 months of GH therapy on endothelial function, C-reactive protein (CRP) and coronary risk. DESIGN: Open-design intervention study. PATIENTS: Fourteen GH-deficient patients (nonsmokers, without diabetes, hypertension or vascular disease) studied before, 6 months and 12 months after GH therapy. MEASUREMENTS: Flow-mediated dilatation (FMD), carotid intima-media thickness (IMT) thrombomodulin (TM), E-selectin, CRP, lipid profile, blood pressure and anthropometric data were recorded. We used the Framingham equation to calculate coronary risk. RESULTS: FMD improved (7.5 +/- 1.62 vs. 11.93 +/- 1.52, P = 0.038). Overall there was no change in IMT, TM, E-selectin or CRP. The correlation between TM and FMD showed a trend for statistical significance (r = -0.54, P = 0.056). Changes in CRP correlated with change in IGF-1 (r = -0.67, P = 0.012); E-selectin correlated with high density lipoprotein (HDL)-cholesterol (r = -0.60, P = 0.028), triglycerides (r = 0.68, P = 0.01) and waist-to-hip ratio (WHR) (r = 0.71, P = 0.006). Systolic (127.36 +/- 4.47 vs. 120.36 +/- 3.50, P = 0.017) and diastolic (84.71 +/- 2.73 vs. 76.93 +/- 2.03, P = 0.005) blood pressure decreased. HDL-cholesterol increased (0.70 +/- 0.05 vs. 0.93 +/- 0.06, P = 0.001). WHR decreased (0.90 +/- 0.02 to 0.88 +/- 0.02, P = 0.043) without changes in weight or body mass index (BMI). Ten-year absolute (P = 0.009) and relative (P = 0.002) cardiac risk decreased. CONCLUSION: Biophysical test of endothelial function (FMD) improved after 12 months of GH therapy but there was no significant change in biochemical endothelial or inflammatory markers. Calculated coronary risk decreased mainly due to reduction in systolic and diastolic blood pressure and increase in HDL-cholesterol.     

A survey of antibiotic administration practices involving patients with sepsis in UK critical care units

International Journal of Clinical Pharmacy - Background Alternative administration methods are emerging as a key area of research to improve clinical efficacy of antibiotics and address concerns...     

Interactions between the perception of age and ethnicity in faces: an event-related potential study

Face perception models propose that different facial attributes are processed by anatomically distinct neural pathways that partially overlap. Whether these attributes interact functionally is an open question. Our goal was to determine if there are interactions between age and ethnicity processing and, if so, at what temporal epoch these interactions are evident. We monitored event-related potentials on electroencephalography while subjects categorized faces by age or ethnicity in two conditions: a baseline in which the other of these two properties not being categorized was held constant and an interference condition in which it also varied, as modelled after the Garner interference paradigm. We found that, when participants were categorizing faces by age, variations in ethnicity increased the amplitude of the right face-selective N170 component. When subjects were categorizing faces by ethnicity, variations in age did not alter the N170. We concluded that there is an asymmetric pattern of influence between age and ethnicity on early face-specific stages of visual processing, which has parallels with behavioural evidence of asymmetric interactions between identity and expression processing of faces.     

Viral Infection of Engrafted Human Islets Leads to Diabetes

Type 1 diabetes (T1D) is characterized by the destruction of the insulin-producing β-cells of pancreatic islets. Genetic and environmental factors both contribute to T1D development. Viral infection with enteroviruses is a suspected trigger for T1D, but a causal role remains unproven and controversial. Studies in animals are problematic because of species-specific differences in host cell susceptibility and immune responses to candidate viral pathogens such as coxsackievirus B (CVB). In order to resolve the controversial role of viruses in human T1D, we developed a viral infection model in immunodeficient mice bearing human islet grafts. Hyperglycemia was induced in mice by specific ablation of native β-cells. Human islets, which are naturally susceptible to CVB infection, were transplanted to restore normoglycemia. Transplanted mice were infected with CVB4 and monitored for hyperglycemia. Forty-seven percent of CVB4-infected mice developed hyperglycemia. Human islet grafts from infected mice contained viral RNA, expressed viral protein, and had reduced insulin levels compared with grafts from uninfected mice. Human-specific gene expression profiles in grafts from infected mice revealed the induction of multiple interferon-stimulated genes. Thus, human islets can become severely dysfunctional with diminished insulin production after CVB infection of β-cells, resulting in diabetes.     

New Insights Into Gestational Glucose Metabolism: Lessons Learned From 21st Century Approaches

Pregnancy presents a unique physiological challenge that requires changes coordinated by placentally and non–placentally derived hormones to prepare the mother for the metabolic stress presented by fetal development and to ensure appropriate nutrient allocation between mother and fetus. Of particular importance is the maintenance of normal glucose metabolism during pregnancy. Here, we describe physiological changes in glucose metabolism during pregnancy and highlight new insights into these adaptations that have emerged over the past decade using novel methodologies, specifically genome-wide association studies (GWAS) and metabolomics. While GWAS have identified some novel associations with metabolic traits during pregnancy, the majority of the findings overlap with those observed in nonpregnant populations and individuals with type 2 diabetes (T2D). Metabolomics studies have provided new insight into key metabolites involved in gestational diabetes mellitus (GDM). Both of these approaches have suggested that a strong link exists between GDM and T2D. Most recently, a role of the gut microbiome in pregnancy has been observed, with changes in the microbiome during the third trimester having metabolic consequences for the mother. In this Perspectives in Diabetes article, we highlight how these new data have broadened our understanding of gestational metabolism, and emphasize the importance of future studies to elucidate differences between GDM and T2D.