Subclinical entheseal involvement in patients with rheumatoid arthritis

BackgroundEnthesopathy is a common feature of Spondyloarthritis (SpA) but can also be found in rheumatoid Arthritis (RA). Recognizing enthesopathy could be challenging because of low sensitivity and specific clinical testing. To detect enthesopathy, The European League Against Rheumatism (EULAR) recommends magnetic resonance imaging (MRI) or ultrasonography (US).Aim of the workTo investigate the frequency and distribution of entheseal involvement in RA patients and its relation to disease activity.Patients and methods100 RA patients with any symptom in foot and ankle were enrolled. Disease activity score (DAS28), Visual analogue scale (VAS), Health assessment questionnaire-Disability index (HAQ-DI) and Glasgow Ultrasound Enthesitis Scoring System (GUESS) were assessed.ResultsThe mean age of patients was 44.1 ± 12.2 years, disease duration was 7 ± 5.8 years and 86% were females. The mean DAS28 score was 4.3 ± 1.2 and GUESS score was 7.2 ± 4.2; all patients had variable degrees of enthesitis: 30% of patients had mild enthesitis, 42% had moderate enthesitis and 28% had marked enthesitis. GUESS was significantly higher in patients with moderate (7.8 ± 4.9) and high (7.2 ± 3.2) disease activity than in patients with low disease activity (5.2 ± 3.9) and those in remission (6.5 ± 1.9) (p = 0.015). HAQ, Age and ESR significantly correlated with GUESS score (r = 0.19, p = 0.049; r = 0.23, p = 0.023; r = 0.33, p = 0.001 respectively).ConclusionSubclinical enthesitis is remarkable in RA patients. Quadriceps tendon enthesis was mostly affected. Enthesitis is significantly related to age, ESR and HAQ. The presence of enthesitis in RA may represent a potential marker for disease activity.     

Comparing executive functions between patients with chronic asthma and healthy subjects

Objective: Allergic diseases have different levels of prevalence all over the world. Among them, asthma is the most common chronic disease. Up to now, little attention has been paid to the impact of this chronic disease on people's executive functions. The present study aimed at comparing the executive functions in patients with chronic asthma and healthy subjects. Methods: The study population was patients with chronic asthma who were referred to Al-Zahra hospital in Isfahan Province and their visitors who were assigned as the control group. Thirty patients with chronic asthma and 30 patient visitors were enrolled in this study, and three software programs (Wisconsin, Stroop, and Continuous Performance Tests) were used. Results: The results of multivariate variance analysis showed that there is a significant difference between patients with chronic asthma and healthy subjects in terms of set shifting, inhibition, and attention performance. Conclusions: This study revealed that the executive functions of patients with chronic asthma have significant defects.     

Ankylosing spondylitis monocyte-derived macrophages express increased level of A<Subscript>2A</Subscript> adenosine receptor and decreased level of ectonucleoside triphosphate diphosphohydrolase-1 (CD39), A<Subscript>1</Subscript> and A<Subscript>2B</Subscript> adenosine receptors

Macrophages play an important role in the ankylosing spondylitis (AS) auto-inflammatory responses and fibrocartilage destruction. Adenosine is a key modulator of inflammatory conditions. The various effects of adenosine are mediated by its interaction with adenosine receptors (AR). In this study, we investigated the mRNA expression of A₁, A_2A, A_2B, and A₃ adenosine receptors, ectonucleoside triphosphate diphosphohydrolase-1 (CD39), and ecto-5′-nucleotidase (CD73) in the monocyte-derived macrophages from AS patients in comparison to healthy controls. We also explored the correlation between analyzed gene expression and patients’ clinical manifestations. Whole blood-separated monocytes from 23 healthy controls and 23 active AS patients were stimulated by macrophage colony-stimulating factor (M-CSF) for 7 days and differentiated to macrophages. Monocyte and macrophage markers were analyzed by flow cytometry. Analysis of adenosine receptors (ADORA1? ADORA2A? ADORA2B? ADORA3), CD39 and CD73 gene expression was performed by SYBR green real-time PCR. Our results demonstrated monocyte-derived macrophages from AS patients expressed increased level of A_2AAR and reduced level of A₁, A_2BAR, and CD39 mRNA compared to healthy controls. We found an inverse correlation between A_2AAR mRNA expression and Bath Ankylosing Spondylitis Functional Index (BASFI) score in AS patients. According to our results, altered expression level of adenosine-relying system would be involved in AS macrophage dysfunction and inflammation and correlated with functional status in AS patients.     

Atherosclerotic Carotid Plaque Composition and Incident Stroke and Coronary Events

BackgroundIncreasing evidence suggests that atherosclerotic plaque composition rather than plaque size is linked to ischemic cardiovascular events, yet largescale population-based data in asymptomatic individuals remain scarce.ObjectivesThis study sought to investigate carotid plaque composition in relation to incident stroke and coronary heart disease (CHD) in a population-based setting.MethodsBetween 2007 and 2012, 1,349 persons (mean age 72 years, 49.5% women) from the population-based Rotterdam Study who were free from a history of stroke or CHD, in whom carotid ultrasonography showed subclinical atherosclerosis, and who underwent high-resolution magnetic resonance imaging of the carotid arteries to assess plaque characteristics. These included the presence of specific plaque components (intraplaque hemorrhage [IPH], lipid-rich necrotic core, and calcification), and measures of plaque size (maximum plaque thickness and presence of stenosis of more than 30%). Individuals were continuously followed for the occurrence of stroke or CHD until January 1, 2015. The authors used Cox regression models to assess the association of the plaque characteristics with the incidence of stroke and CHD, with adjustments for age, sex, and cardiovascular risk factors.ResultsDuring a median of 5.1 years’ follow-up for stroke and 4.8 years for CHD, 51 individuals had a stroke and 83 developed CHD. Independent of maximum plaque thickness and cardiovascular risk factors, the presence of IPH was associated with incident stroke and CHD (fully adjusted hazard ratio: 2.42 [95% confidence interval: 1.30 to 4.50], and 1.95 [95% confidence interval: 1.20 to 3.14]). Presence of a lipid-rich necrotic core and calcification were not associated with stroke or CHD.ConclusionsThe presence of IPH in the carotid atherosclerotic plaque is an independent risk factor for stroke and CHD. These findings indicate the promise of IPH as a marker of plaque vulnerability in healthy persons with subclinical atherosclerosis.     

Iron status in women with and without gestational diabetes mellitus

ObjectiveGestational diabetes mellitus (GDM) affects approximately 7% of all pregnancies. Pregnancy, mostly because of the mitochondria-rich placenta, is a condition that favors oxidative stress. A transitional metal, especially iron, which is particularly abundant in the placenta, is important in the production of free radicals. Also, studies have shown that free radicals have a role in GDM. As there are little data about iron status in GDM, this study was performed to compare iron status in GDM and control group.Research Design and MethodsIn this case-control study, 34 women with diagnosed GDM were compared with 34 non-GDM women in the control group at 24–28 weeks of pregnancy in terms of iron status, including ferritin, serum iron, total iron-binding capacity (TIBC), hemoglobin (Hb), mean corpuscular volume (MCV), and mean corpuscular hemoglobin (MCH).ResultsIn this study, concentration of serum ferritin, iron, transferrin saturation and hemoglobin, MCV, and MCH was significantly higher in the GDM group and TIBC was significantly lower in this group (P<.05). No significant association was observed with the other variables including familial history of diabetes and GDM.ConclusionOur findings indicate an association between increased iron status and GDM. The role of iron excess from iron supplementation in the pathogenesis of GDM needs to be examined.     

Percutaneous treatment of spontaneous left main coronary artery dissection extending to the left anterior descending and circumflex arteries possibly triggered by thrombolytic therapy

Spontaneous coronary artery dissection is a rare cause of myocardial infarction and the role of thrombolytic therapy in this setting is not known. A case of acute ST elevation myocardial infarction is presented, with initial positive response to thrombolytic therapy and subsequent marked worsening of ST elevation due to extensive dissection, possibly triggered by thrombolytic therapy, which was successfully treated with percutaneous coronary intervention.     

Serum immunoglobulin A concentration is a reliable biomarker for liver fibrosis in non-alcoholic fatty liver disease

AIM: To evaluate the diagnostic accuracy of serum Immunoglobulin A (IgA) for differentiating early stage nonalcoholic fatty liver disease (NAFLD) from nonalcoholic steatohepatitis (NASH).METHODS: All cases had fatty liver change confirmed by ultrasound and aminotransferases of at least twice the normal level. Clinical and biochemical data, including serum IgA, were obtained from 50 histologically proven NAFLD cases and 54 healthy controls. Fasting whole blood samples were obtained from the study population. Immunoturbidimetric methods were used to measure the IgA levels. All NAFLD cases were hospitalized for liver biopsy. Liver specimens were examined for steatosis, steatohepatitis and fibrosis within hepatocytes. Patients were categorized into two groups: NASH and non-NASH. Variables were compared within cases (NASH vs non-NASH) and controls. Cut-off values of serum IgA were evaluated using analysis of receiver operating characteristic (ROC curves). Associations between the variables were tested using calculations of correlation coefficients. Statistical significances were assigned to P values < 0.05.RESULTS: The extent of liver fibrosis correlated positively with IgA levels. Subjects with no fibrosis in their liver biopsies had a lower IgA level (301.5 ± 91.2 mg/dL) than subjects with any degree of fibrosis (388.8 ± 140.8 mg/dL), (P = 0.01). IgA levels were higher in NASH cases, and its value was significantly higher for higher degrees of fibrosis. Patients with perisinusoidal or pericellular fibrosis had significantly higher levels of IgA (403.5 ± 133.9 mg/dL, 418.2 ± 129.5 mg/dL) compared to those without it (301.8 ± 94.9 mg/dL, 297.7 ± 91.5 mg/dL), respectively. No significant correlation was found between steatosis grade and serum IgA levels. Based on ROC analysis, the best predictive IgA cutoff value for detecting liver fibrosis was 360 mg/dL (61% sensitivity, 81% specificity).CONCLUSION: The serum IgA level is useful to evaluate the severity of liver fibrosis and can be used serially for evaluation and follow-up of NAFLD cases.     

Prevalence of Hepatitis B Virus Seromarkers in Young Adults Vaccinated at Birth; Impact on the Epidemiology of Hepatitis B Infection in Iran

Background:

The epidemiological impact and the duration of protection provided by infant hepatitis B (HB) vaccination are unknown.

Objectives:

This study was designed to determine the hepatitis B virus (HBV) infection seromarkers in young adults who have been vaccinated against HBV as the first group of Iranian neonates during 1993 and 1994.

Patients and Methods:

We recruited 510 young adults with a history of complete HB vaccination at birth. HBV seromarkers (HB surface antigen (HBs Ag), antibody against HBs Ag (Anti-HBs), and antibody against HB core antigen (Anti-HBc) were measured using ELISA method. Anti-HBs titers ≥ 10 IU/L were considered protective and titers more than 300 IU/L were indicative of a natural boosting. Positive results for Anti-HBc and HBs Ag were considered as breakthrough infection and possible vaccine failure, respectively. The history of acute symptomatic clinical hepatitis was also investigated.

Results:

Anti-HBs seropositivity rate was detected in 224 of 510 [95% CI: 39-47] young adults. Breakthrough infection (positive sera for Anti-HBc without chronic infection) was observed in 18 [95% CI: 2.5-3.5] subjects. There were neither HBs Ag positive results nor symptomatic hepatitis cases.

Conclusions:

The study results indicated that the neonatal HBV immunization induced a long-term protection against HBV and was very efficacious in reducing chronic HBV infection rate in vaccinated young adults in Iran.     

Age at natural menopause and risk of type 2 diabetes: a prospective cohort study

Aims/hypothesis

In this study, we aimed to examine the association between age at natural menopause and risk of type 2 diabetes, and to assess whether this association is independent of potential mediators.

Methods

We included 3639 postmenopausal women from the prospective, population-based Rotterdam Study. Age at natural menopause was self-reported retrospectively and was treated as a continuous variable and in categories (premature, <40 years; early, 40–44 years; normal, 45–55 years; and late menopause, >55 years [reference]). Type 2 diabetes events were diagnosed on the basis of medical records and glucose measurements from Rotterdam Study visits. HRs and 95% CIs were calculated using Cox proportional hazards models, adjusted for confounding factors; in another model, they were additionally adjusted for potential mediators, including obesity, C-reactive protein, glucose and insulin, as well as for levels of total oestradiol and androgens.

Results

During a median follow-up of 9.2 years, we identified 348 individuals with incident type 2 diabetes. After adjustment for confounders, HRs for type 2 diabetes were 3.7 (95% CI 1.8, 7.5), 2.4 (95% CI 1.3, 4.3) and 1.60 (95% CI 1.0, 2.8) for women with premature, early and normal menopause, respectively, relative to those with late menopause (p _trend <0.001). The HR for type 2 diabetes per 1 year older at menopause was 0.96 (95% CI 0.94, 0.98). Further adjustment for BMI, glycaemic traits, metabolic risk factors, C-reactive protein, endogenous sex hormone levels or shared genetic factors did not affect this association.

Conclusions/interpretation

Early onset of natural menopause is an independent marker for type 2 diabetes in postmenopausal women.

     

PEGylation of cationic liposomes encapsulating soluble Leishmania antigens reduces the adjuvant efficacy of liposomes in murine model

Although there have been several attempts to develop a vaccine against leishmaniasis, no vaccine in human has been developed yet. Liposomes consisting of 1, 2‐dioleoyl‐3‐trimethylammonium‐propane (DOTAP) encapsulating soluble Leishmania antigens (SLA) enhance protective immunity of SLA against Leishmania major infection in mice. However, they immobilized at the injection site because of their positive charge. To overcome the problem, shielding the surface charge with polyethylene glycol (PEGylation) was chosen in this study. Liposomal SLA consisting different concentrations of PEG (1.9%‐15% mol) were prepared. BALB/c mice were immunized three times in 3 weeks intervals with different formulations. Lesion development and parasite burden in footpad and spleen were evaluated to specify the type of generated immune response and extent of protection. Th1/Th2 cytokine profiles and IgG isotypes were also analysed. The maximum protection was observed in mice immunized with Lip‐SLA or pLip‐SLA (1.9%) due to smaller footpad swelling, reduction in parasite load, an increase in IgG2a and IFN‐γ production. Our results showed that immunization of mice with a high level of PEG (>7.5%) did not improve protective immunity of liposomal SLA. The presence of PEG, particularly more than 3.75%, is not recommended for protection against leishmaniasis.