TNF-alpha Production by Peripheral Blood Monocytes in Multiple Sclerosis Patients and Healthy Controls

Background: Aberrant immune responses are evident in the pathogenesis of multiple sclerosis (MS) and it has been proposed that the spectrum of cytokines influence disease outcomes. Leptin and lipopolysaccharide (LPS) of Gram-negative bacteria are both potent cellular stimulators for production of pro-inflammatory cytokines such as tumor necrosis factor-α (TNF-α). The aim of this study was to compare the TNF-α production by peripheral blood monocytes from MS patients with healthy controls.

Methods: Peripheral blood samples were stimulated with LPS or leptin. After blocking the Golgi apparatus, intracellular cytokine production was assessed using a monoclonal antibody against human TNF-α by the flow cytometry technique. Moreover, plasma level measurement of cytokines was performed using enzyme-linked immunosorbent assay (ELISA).

Results: Intracellular levels of TNF-α were 16.80?±?8.21 and 16.52?±?8.23in MS patients and healthy controls which showed no statistically significant difference between them (p?=?0.850). Leptin-stimulated and LPS-stimulated TNF-α production showed no significant difference between MS patients and the control group (p?=?0.263 and p?=?0.191, respectively). However, after treatment with leptin, a weak significant difference was shown between cases and control group (p?=?0.049). There were significant differences between cases and controls regarding serum levels of IL-6 and Toll-like receptor-4 (TLR-4) before and after stimulation with leptin and LPS, separately (p?<?0.05).

Conclusion: Taken together, we cannot definitely conclude that TNF-α does not play an important role in pathogenesis of MS. However, other characteristics of monocyte activation such as IL-6 or TLRs can elucidate implication of peripheral blood monocytes in MS pathogenesis.     

Successful fludarabine‐based hematopoietic stem cell transplantation in a pediatric patient with idiopathic CD4+ lymphocytopenia

Idiopathic CD4+ lymphocytopenia (ICL) is a rare immunodeficiency disease with severe CD4 T‐cell depletion, leading to serious opportunistic infections. The optimal treatment of ICL has not been determined, especially in severe form of the disease. Here, we report an eight‐yr‐old girl with ICL who was successfully treated with fludarabine‐based conditioning HSCT. To the best of our knowledge, this is the first pediatric ICL case that was treated by HSCT. Allogeneic HSCT with a reduced intensity condition (RIC) regimen may be a feasible and curative treatment option in ICL patients with recurrent life‐threatening complications.     

Socioeconomic inequality in screen time frequency in children and adolescents: the weight disorders survey of the CASPIAN IV study

Background

This study aimed to assess the socioeconomic inequality and determinants of screen time (ST) frequency in Iranian children and adolescents.

Methods

This nationwide study was conducted as part of a national school-based surveillance program among 36,486 students consisting of 50.79% boys and 74.23% urban inhabitants, aged 6–18 years, living in urban and rural areas of 30 provinces of Iran. Socioeconomic inequality in ST, including the time spent for ST, watching TV and leisure-time working with computer, was assessed across quintiles of SES using concentration index (C) and slope index of inequality (SII).

Results

Overall, 36,486 students completed the study (response rate 91.25%). Their mean (SD) age was 12.14 (3.36) years. The national estimation of frequency of ST was 31.66% (95% CI 31.16–32.17) with ascending change from 20.80% (95% CI 19.81–21.82) to 36.66% (95% CI 35.47–37.87) from the first to the last quintal of SES. Estimated C value at national level was positive (0.08), which indicate inequality was in favor of low SES groups. Considering the SII values, at national level [? 0.16 (? 0.39, 0.06)], the absolute difference in ST frequency between the bottom and top of the socioeconomic groups had descending trends. In multivariate logistic regression model, family history of obesity, generalized obesity and age were the main significant determinants of prolonged ST, watching TV, and computer working (P < 0.001).

Conclusions

Socioeconomic inequality in ST frequency was in favor of low SES groups. These findings are useful for health policies, better programming and future complementary analyses.

     

Ischaemic cerebrovascular events in HIV infection: a cohort study

Several case reports and series described ischaemic cerebrovascular events in HIV infection. However, the exact prevalence and the clinical features of these events are unknown. We performed a cohort study on 772 consecutive HIV infected patients and evaluated the rate of transient ischaemic attacks (TIA) and of completed stroke. A total prevalence of 1.9% for TIA (0.8%) and stroke (1.2%) was calculated resulting in an annual incidence rate of 216 per 100000. The prevalence was highest in the later stages of the infection. Stroke patients had a poorer immunological state than the TIA and the cohort patients. Probable (n = 3) and possible (n = 2) vasculitis and cardiogenic embolism (n = 2) could be detected as aetiology, the remaining patients had a cryptogenic event. Our data suggest that ischaemic cerebrovascular events are more common in HIV infected patients than in the general population and that a part of these events might be caused by HIV associated vasculitis or vasculopathy.     

Contrast transcranial Doppler ultrasound in the detection of right-to-left shunts: comparison of Echovist-200 and Echovist-300, timing of the Valsalva maneuver,and general recommendations for the performance of the test

BACKGROUND AND PURPOSE: Cardiac right-to-left shunts (RLS) can be identified by transesophageal echocardiography (TEE) as well as by transcranial Doppler ultrasound (TCD) using contrast agents, such as Echovist-200 or Echovist-300 in conjunction with a Valsalva maneuver (VM) as provocation procedure. Both Echovist preparations are in use. Currently, the appropriate timing of the VM is still under debate. Methods: Sixty-four patients were investigated by both TEE and bilateral TCD of the middle cerebral arteries. The following protocol was applied in a randomized way: (1) no VM, (2) VM for 5 s starting with the beginning of Echovist-300 injection, (3) VM for 5 s starting 5 s after the beginning of Echovist-300 injection, (4) VM for 5 s starting 10 s after the beginning of Echovist-300 injection, and (5) VM for 5 s starting 5 s after the beginning of Echovist-200 injection. Results: In 27 patients, an RLS was demonstrated by both TEE and contrast TCD (shunt-positive). Twenty-two patients were negative in both investigations, no patient was positive on TEE but negative on TCD, 15 patients were only positive on at least one TCD investigation but negative on TEE. Tests 3 and 5 were the most appropriate ones; test 3 was slightly superior to test 5. Conclusions: TCD using Echovist-300 or Echovist-200 is a sensitive method to identify TEE-proven cardiac RLS. To achieve the best diagnostic accuracy, the VM should be performed for a duration of 5 s starting at 5 s following the beginning of contrast injection.     

Absence of circulating microemboli in patients with atrial fibrillation undergoing electric cardioversion

Electrical cardioversion (CV) of atrial fibrillation (AF) is associated with an increased risk of stroke, and its appropriate prevention is still a matter of debate. It is known that, besides dislodgement of pre-existing intra-atrial thrombi, the "stunned" atrium after CV is an important cause of thrombus formation and subsequent embolism. We investigated whether CV of AF is associated with occurrence of circulating microemboli (ME) representing a sensitive marker of the actual thromboembolic activity. Twenty-nine patients (22 men) aged 54 +/- 13 years suffering from valvular (n = 5) or nonvalvular (n = 24) AF were studied. All but 1 patient (with recent-onset AF) had been put on oral anticoagulation (INR >2.0) for at least 3 weeks before and 4 weeks after successful CV. In all patients, exclusion of internal carotid artery stenosis and atrial thrombus was performed prior to CV. Five unilateral 1-hour transcranial Doppler ME monitorings over the middle cerebral artery were performed (1) before CV, and (2) immediately, (3) 4-6 h, (4) 24 h, and (5) 2-4 weeks after CV. Total absence of circulating ME was found before CV as well as during a cumulative monitoring time of 115 h after successful CV. Electrical CV of AF after at least 3 weeks of effective anticoagulation is not associated with occurrence of cerebral circulating ME. This finding requires further investigation including high-risk patients with AF undergoing CV based on different treatment protocols.