Airway IFN-γ Production During RSV Bronchiolitis is Associated with Eosinophilic Inflammation

Study Objective  

This study was designed to investigate the possible role of IFN-γ in eosinophil degranulation that occurs during respiratory syncytial virus (RSV) bronchiolitis.     

Segmental Colitis Associated with Diverticulosis: Complication of Diverticular Disease or Autonomous Entity?

Segmental colitis associated with diverticulosis (SCAD) is a disease that affects colon harboring diverticula, mostly located in the sigmoid region. It has been considered a rare disease for many years, but new studies may contribute to easier recognition. Although its pathogenesis is not yet well defined, in the past SCAD has been considered a complication of diverticular disease, whilst new endoscopic, histological, and clinical data have encouraged the concept that SCAD includes pathogenetic and therapeutic aspects peculiar to inflammatory bowel diseases. We therefore describe herein current knowledge about this disease, and why it can be considered a truly autonomous entity instead of a complication of diverticular disease.     

Is Hb A2 Elevated in Adults with Sickle-A-Thalassemi (βS/βS; -α/-α)

Thirteen patients with sickle cell anemia (SS) were found to have two a gene deletions with a presumptive genotype of β^s/β^s; -α/-α. Hematological data showed that this group of patients had elevated Hb A₂ level. in order to determine whether the elevation of Hb A² is typical of SS with a two α gene deletion or is due to undiagnosed S-β°-thalassemia with a two a gene deletion we looked for the presence or absence of β°-thalassemia by molecular techniques. The latter included reverse dot-blot hybridization to rule out a β-thalassemia mutation, digestion with Cvn endonuclease followed by Southern blotting and hybridization with a β genomic probe, and, in selected patients, determination of the synthetic α/β ratio. One of the 13 patients had S-β°-thalassemia with a G→A mutation at IVS-11-1 indicating that her genotype was β^s/β° thalassemia; -α/-α. The remaining 12 patients were homozygous for the sickle gene, had relatively elevated Hb levels, increased Hb A₂ values, and Hb F levels similar to those in patients with SS and four or three α genes. At the clinical level, the 12 patients with SS and a two α gene deletion had increased prevalence of avascular necrosis, retinopathy, and splenomegaly, but decreased prevalence of leg ulcers and cerebrovascular accidents. Together, the data indicate that SS with a two a gene deletion (β^s/β^s; -α/α) is a unique subset of patients with SS characterized by distinct hematological and clinical features.     

Circulating VEGF-A,TNF-α, CCL2, IL-6, and IFN-γ as biomarkers of cancer in cancer-associated anti-TIF1-γ antibody-positive dermatomyositis

Clinical Rheumatology - The objective of the current study was to detect plasma profiles of inflammatory cytokines for determining potential biomarkers indicating cancer presence among the...     

Is Age Associated with the Number or Types of Medications Prescribed to Renal Transplant Recipients?

OBJECTIVES: To determine whether age influences the number or types of medications prescribed to younger (aged 18-64) and elderly (aged > or =65) renal transplant recipients 3 years posttransplant. DESIGN: A cross-sectional study involving renal transplant recipients. SETTING: Medical College of Georgia. PARTICIPANTS: A random sample of 100 elderly and 100 younger renal transplant recipients who received posttransplant care at the Medical College of Georgia, were on stable immunosuppressant therapy regimens, and were at least 3 years posttransplant. MEASUREMENTS: Medical and pharmacy data of recipients were evaluated for demographics; presence of a lipid-lowering agent; number of antihypertensives, immunosuppressants, antidiabetic agents, and total medications; number of rejections; dose per kilogram of immunosuppressant(s); infection-related hospitalizations; and measures of blood pressure, blood glucose, serum creatinine, serum tacrolimus/cyclosporine concentrations, total cholesterol, and triglycerides. RESULTS: Elderly recipients were more likely to have diabetes mellitus before the transplant and to develop diabetes mellitus afterwards (P=.04) and were prescribed more total medications (12.40+/-3.72 vs 10.25+/-4.07, P<.001) and antidiabetic agents (0.89+/-0.93 vs 0.42+/-0.77, P<.001) 3 years posttransplant than younger recipients. Elderly recipients also had fewer chronic rejections, more infection-related hospitalizations, lower diastolic blood pressure, and greater fasting blood glucose levels 3 years posttransplant (P<.05) than younger recipients. CONCLUSION: Future investigation should focus on deciphering the implications of the greater numbers of medications prescribed to elderly renal transplant recipients in terms of maximizing desired health outcomes (e.g., graft survival) and minimizing adverse drug-related experiences (e.g., infection).     

Colonic Crohn’s Disease Is Associated with Less Aggressive Disease Course Than Ileal or Ileocolonic Disease

Digestive Diseases and Sciences - The literature on disease characteristics of colonic Crohn’s disease (CD) is sparse, especially from Asia, where the burden of inflammatory bowel disease is...     

Gut microbial markers are associated with diabetes onset,regulatory imbalance,and IFN-γ level in NOD Mice

Gut microbiota regulated imbalances in the host's immune profile seem to be an important factor in the etiology of type 1 diabetes (T1D), and identifying bacterial markers for T1D may therefore be useful in diagnosis and prevention of T1D. The aim of the present study was to investigate the link between the early gut microbiota and immune parameters of non-obese diabetic (NOD) mice in order to select alleged bacterial markers of T1D. Gut microbial composition in feces was analyzed with 454/FLX Titanium (Roche) pyro-sequencing and correlated with diabetes onset age and immune cell populations measured in diabetic and non-diabetic mice at 30 weeks of age. The early gut microbiota composition was found to be different between NOD mice that later in life were classified as diabetic or non-diabetic. Those differences were further associated with changes in FoxP3⁺ regulatory T cells, CD11b⁺ dendritic cells, and IFN-γ production. The model proposed in this work suggests that operational taxonomic units classified to S24–7, Prevotella, and an unknown Bacteriodales (all Bacteroidetes) act in favor of diabetes protection whereas members of Lachnospiraceae, Ruminococcus, and Oscillospira (all Firmicutes) promote pathogenesis.     

Gut microbial markers are associated with diabetes onset,regulatory imbalance,and IFN-γ level in NOD Mice

Gut microbiota regulated imbalances in the host''s immune profile seem to be an important factor in the etiology of type 1 diabetes (T1D), and identifying bacterial markers for T1D may therefore be useful in diagnosis and prevention of T1D. The aim of the present study was to investigate the link between the early gut microbiota and immune parameters of non-obese diabetic (NOD) mice in order to select alleged bacterial markers of T1D. Gut microbial composition in feces was analyzed with 454/FLX Titanium (Roche) pyro-sequencing and correlated with diabetes onset age and immune cell populations measured in diabetic and non-diabetic mice at 30 weeks of age. The early gut microbiota composition was found to be different between NOD mice that later in life were classified as diabetic or non-diabetic. Those differences were further associated with changes in FoxP3⁺ regulatory T cells, CD11b⁺ dendritic cells, and IFN-γ production. The model proposed in this work suggests that operational taxonomic units classified to S24–7, Prevotella, and an unknown Bacteriodales (all Bacteroidetes) act in favor of diabetes protection whereas members of Lachnospiraceae, Ruminococcus, and Oscillospira (all Firmicutes) promote pathogenesis.     

Reversible Cardiomyopathy Associated with Multicentric Castleman Disease: Successful Treatment with Tocilizumab, an Anti—Interleukin 6 Receptor Antibody

Multicentric Castleman disease (MCD) is a rare lymphoproliferative disorder characterized by systemic lymphadenopathy and inflammatory symptoms that are associated with the overproduction of interleukin 6 (IL-6). Although several nonlymphoid organs can also be damaged in MCD, only a few cases with cardiac complications have been reported to date. We report a case of congestive heart failure in a female patient with MCD. On admission, her echocardiogram revealed a dilated and diffusely hypokinetic left ventricle. No stenosis was evident in the coronary angiogram. A histopathologic examination of a myocardial biopsy specimen showed mildly hypertrophic myocytes without infiltration of plasma cells or amyloid deposits. Repeated administration of an anti-IL-6 receptor antibody, tocilizumab (formerly known as MRA), gradually improved the ventricular wall motion over 6 months without any additional treatment for heart failure, suggesting the involvement of IL-6 in the pathogenesis of her cardiomyopathy. This report is the first of MCD complicated by heart failure treated successfully with tocilizumab. Administering tocilizumab in cases of MCD with unexplained cardiac dysfunction is worthwhile, because such a complication could be reversible.     

PPARγ activator,rosiglitazone: Is it beneficial or harmful to the cardiovascular system?

Rosiglitazone is a synthetic agonist of peroxisome proliferator-activated receptor γ which is used to improve insulin resistance in patients with typeⅡdiabetes.Rosiglitazone exerts its glucose-lowering effects by improving insulin sensitivity.Data from various studies in the past decade suggest that the therapeutic effects of rosiglitazone reach far beyond its use as an insulin sensitizer since it also has other benefits on the cardiovascular system such as improvement of contractile dysfunction,inhibition of the inflammatory response by reducing neutrophil and macrophage accumulation,and the protection of myocardial injury during ischemic/reperfusion in different animal models.Previous clinical studies in typeⅡdiabetes patients demonstrated that rosiglitazone played an important role in protectingagainst arteriosclerosis by normalizing the metabolic disorders and reducing chronic inflammation of the vascular system.Despite these benefits,inconsistent findings have been reported,and growing evidence has demonstrated adverse effects of rosiglitazone on the cardiovascular system,including increased risk of acute myocardial infarction,heart failure and chronic heart failure.As a result,rosiglitazone has been recently withdrawn from EU countries.Nevertheless,the effect of rosiglitazone on ischemic heart disease has not yet been firmly established.Future prospective clinical trials designed for the specific purpose of establishing the cardiovascular benefit or risk of rosiglitazone would be the best way to resolve the uncertainties regarding the safety of rosiglitazone in patients with heart disease.     

Is the metabolic syndrome, with or without diabetes, associated with progressive disability in older Mexican Americans?

BACKGROUND: The metabolic syndrome (MetS) is highly prevalent in the growing U.S. Latino population. We hypothesize that MetS, with or without diabetes, is associated with progressive disability in older Mexican Americans. METHODS: Data from Mexican Americans 60-98 years old participating in the Sacramento Area Latino Study on Aging (SALSA) were analyzed from baseline through 3 years (3 years of follow-up). Disability was assessed by self-reported limitations in activities of daily living (ADLs), instrumental ADLs (IADLs), and mobility/strength tasks. MetS (46% of sample) was defined by National Cholesterol Education Program (NCEP) Adult Treatment Panel III criteria. Diabetes (DM, 33%) was defined by fasting blood sugar>125 mg/dL, physician diagnosis, and/or medication use. Four metabolic groups were defined: MetS with diabetes (MetS+DM+, n=402); MetS without diabetes (MetS+DM-, n=330); diabetes without MetS (MetS-DM+, n=125); and neither (MetS-DM-, n=749). Generalized estimating equation (GEE) regression models were used to evaluate the effect of metabolic group on physical limitations and disability changes over time. RESULTS: Diabetes, with or without MetS, was associated with a higher percent rate of increase over 3 years in ADL and IADL disability than was no diabetes, even after controlling for demographics, body mass index (BMI), and incident disease. The mean ADL score had a 35% higher rate of increase (higher = more impairment) for the MetS+DM+ group and 68% higher for the MetS-DM+ group. Results for IADL were similar. The baseline MetS, without or with diabetes, was associated with a significantly higher rate of increase in mobility/strength limitations (8% and 36.5%, respectively). CONCLUSIONS: In older Mexican Americans, MetS is associated with progressive limitations in mobility and strength. Preventing progressive mobility/strength limitations may require assessing and treating these impairments in people with MetS regardless of the presence of diabetes. However, preventing the progression of MetS without to MetS with diabetes may be important to limit the progression of ADL and IADL disability found in people with MetS and diabetes.     

Combination of pegylated IFN-α2b with imatinib increases molecular response rates in patients with low- or intermediate-risk chronic myeloid leukemia

Biologic and clinical observations suggest that combining imatinib with IFN-α may improve treatment outcome in chronic myeloid leukemia (CML). We randomized newly diagnosed chronic-phase CML patients with a low or intermediate Sokal risk score and in imatinib-induced complete hematologic remission either to receive a combination of pegylated IFN-α2b (Peg-IFN-α2b) 50 μg weekly and imatinib 400 mg daily (n = 56) or to receive imatinib 400 mg daily monotherapy (n = 56). The primary endpoint was the major molecular response (MMR) rate at 12 months after randomization. In both arms, 4 patients (7%) discontinued imatinib treatment (1 because of blastic transformation in imatinib arm). In addition, in the combination arm, 34 patients (61%) discontinued Peg-IFN-α2b, most because of toxicity. The MMR rate at 12 months was significantly higher in the imatinib plus Peg-IFN-α2b arm (82%) compared with the imatinib monotherapy arm (54%; intention-to-treat, P = .002). The MMR rate increased with the duration of Peg-IFN-α2b treatment (< 12-week MMR rate 67%, > 12-week MMR rate 91%). Thus, the addition of even relatively short periods of Peg-IFN-α2b to imatinib markedly increased the MMR rate at 12 months of therapy. Lower doses of Peg-IFN-α2b may enhance tolerability while retaining efficacy and could be considered in future protocols with curative intent.     

Treatment of pig serum-induced rat liver fibrosis with Boschniakia rossica, oxymatrine and interferon-α

AIM: To investigate the effect of Boschniakia rossica (BR), oxymatrine (OM) and interferon-alpha (IFN-α) lb on the therapy of rat liver fibrosis and its mechanism. METHODS: By establishing a rat model of pig serum-induced liver fibrosis, liver/weight index and serum alanine transaminase (ALT) were observed to investigate the therapeutic effect of BR, OM and IFN-α Radioimmunoassay was utilized to measure procollagen type Ⅲ (PCⅢ) and collagen type Ⅳ (CⅣ). RT-PCR was used to assay the expression of liver transforming growth factor- beta 1 (TGF-β1) mRNA. Immunohistochemistry of alpha-smooth muscle actin (α-SMA) and pathologic changes of liver tissues were also under investigation. RESULTS: Serum PCⅢ and CⅣ in BR, OM and IFN-α groups were significantly declined compared with those in model group, and their RT-PCR revealed that TGF-β1 mRNA expression was also reduced more than that in model group. Immunohistochemistry demonstrated that α-SMA also declined more than that in model group. Serum ALT in IFN-α, control and model groups was within normal level. Serum ALT in BR group had no significant difference from those of IFN-α, control and model groups. Serum ALT in ON group was significantly higher than those in BR, IFN-α,model, and control groups. CONCLUSION: BR, OM and IFN-α can prevent pig serum-induced liver rat fibrosis by inhibiting the activation of hepatic stellate cells and synthesizing collagen. OM has hepatotoxicity to rat liver fibrosis induced by pig serum.     

Treatment of pig serum-induced rat liver fibrosis with Boschniakia rossica, oxymatrine and interferon-α

AIM: To investigate the effect of Boschniakia rossica (BR), oxymatrine (OM) and interferon-alpha (IFN-α) 1b on the therapy of rat liver fibrosis and its mechanism. METHODS: By establishing a rat model of pig serum-induced liver fibrosis, liver/weight index and serum alanine transaminase (ALT) were observed to investigate the therapeutic effect of BR,OM and IFN-α. Radioimmunoassay was utilized to measure procollagen type Ⅲ (PCⅢ) and collagen type Ⅳ (CIV). RT-PCR was used to assay the expression of liver transforming growth factor- beta 1 (TGF-β1) mRNA. Immunohistochemistry of alpha-smooth muscle actin (α-SMA) and pathologic changes of liver tissues were also under investigation. RESULTS: Serum PCⅢ and CIV in BR, OM and IFN-α groups were significantly declined compared with those in model group, and their RT-PCR revealed that TGF-β1 mRNA expression was also reduced more than that in model group. Immunohistochemistry demonstrated that α-SMA also declined more than that in model group. Serum ALT in IFN-α, control and model groups was within normal level. Serum ALT in BR group had no significant difference from those of IFN-α, control and model groups. Serum ALT in OM group was significantly higher than those in BR, IFN-α, model, and control groups. CONCLUSION: BR, OM and IFN-α can prevent pig serum-induced liver rat fibrosis by inhibiting the activation of hepatic stellate cells and synthesizing collagen. OM has hepatotoxicity to rat liver fibrosis induced by pig serum.