Autoimmune diseases and myelodysplastic syndromes

Immune dysregulation and altered T‐cell hemostasis play important roles in the pathogenesis of myelodysplastic syndromes (MDS). Recent studies suggest an increased risk of MDS among patients with autoimmune diseases. Here, we investigated the prevalence of autoimmune diseases among MDS patients, comparing characteristics and outcomes in those with and without autoimmune diseases. From our study group of 1408 MDS patients, 391 (28%) had autoimmune disease, with hypothyroidism being the most common type, accounting for 44% (n = 171) of patients (12% among all MDS patients analyzed). Other autoimmune diseases with ≥5% prevalence included idiopathic thrombocytopenic purpura in 12% (n = 46), rheumatoid arthritis in 10% (n = 41), and psoriasis in 7% (n = 28) of patients. Autoimmune diseases were more common in female MDS patients, those with RA or RCMD WHO subtype, and those who were less dependent on red blood cell transfusion. Median overall survival (OS) was 60 months (95% CI, 50–70) for patients with autoimmune diseases versus 45 months (95% CI, 40–49) for those without (log‐rank test, P = 0.006). By multivariate analysis adjusting for revised IPSS and age >60 years, autoimmune diseases were a statistically significant independent factor for OS (HR 0.78; 95% CI, 0.66–0.92; P = 0.004). The rate of acute myeloid leukemia (AML) transformation was 23% (n = 89) in MDS patients with autoimmune disease versus 30% (n = 301) in those without (P = 0.011). Patient groups did not differ in response to azacitidine or lenalidomide treatment. Autoimmune diseases are prevalent among MDS patients. MDS patients with autoimmune diseases have better OS and less AML transformation. Am. J. Hematol. 91:E280–E283, 2016. © 2016 Wiley Periodicals, Inc.     

Comparison of three techniques for generation of tolerogenic dendritic cells: siRNA, oligonucleotide antisense, and antibody blocking

In recent years, a new view of dendritic cells (DCs) as a main regulator of immunity to induce and maintain tolerance has been established. In vitro manipulation of their development and maturation is a topic of DC therapeutic application, which utilizes their inherent tolerogenicity. In this field, the therapeutic potential of antisense, siRNA, and blocking antibody are an interesting goal. In the present study, the efficiency of these three methods--siRNA, antisense, and blocking antibody--against CD40 molecule and its function in DCs and BCL1 cell line are compared. DCs were separated from mouse spleen and then cultured in vitro using Lipofectamine 2000 to deliver both silencers; the efficacy of transfection was estimated by flow cytometry. mRNA expression and protein synthesis were assessed by real time-PCR and flow cytometry, respectively. By Annexin V and propidium iodine staining, we could evaluate the viability of transfected cells. Knocking down the CD40 gene into separate groups of DCs by siRNA, antisense, and blocking antibody treated DCs can cause an increase in IL-4, decrease in IL-12, IFN-γ production, and allostimulation activity. Our results indicated that, in comparison to antisense and blocking antibody, siRNAs appear to be quantitatively more efficient in CD40 downregulation and their differences are significant.     

Intracameral bevacizumab for rubeotic glaucoma secondary to retinal vein occlusion

Two patients with ischaemic central retinal vein occlusion were treated with intracameral bevacizumab in order to affect the outcome of their disease. In addition, both patients underwent episodes of cycloablative and pan-retinal laser treatment. The patients were followed for more than 6 months and achieved some stability with a combination of these modalities.     

Congenital rubella syndrome after rubella vaccination in 1–4 weeks periconceptional period

Objective  To examine weather exposure to rubella vaccine during 1–4 wk periconceptional period can cause congenital rubella syndrome (CRS). Methods  This prospective study was performed in 60 pregnant women who received rubella vaccine inadvertently 1–4 wk pre or post conception. Time of conception was determined by last menstrual period (LMP) and first trimester sonography. In addition to gathering mother’s obstetric and demographic information, all neonates were evaluated for CRS signs by systemic physical examination and anti rubella IgG and IgM antibody titers in cord blood samples. Results  A total of 60 pregnant women with the median gestational age of 38 weeks were studied. The mean maternal age was 22 years and 58.3% of pregnancies were unintended. In 90% of mothers there were no post vaccination side effects (fever, lymphadenopathy, arthritis, arthralgia). None of the mothers had a history of drug abuse, smoking or teratogenic exposures. Mean neonatal weight was 3100grs and 6.7% of them were premature. No signs of CRS were found in the neonates based on systemic physical exam at birth and one month later. Mean value of cord blood anti rubella IgG titere was 148/28±67/26 lu/ml. cord blood anti rubella IgM was negative in all of the neonates. Conclusion  In this study inadvertent rubella vaccination 1–4 wk before and after conception did not cause CRS in neonates and according to all reasearches pregnancy termination is not indicated in these cases.     

Effect of memantine on plasma concentrations of carbamazepine and phenytoin in rats: A controlled experimental study

Background: Elderly patients, especially those with Alzheimer's disease, may be prescribed memantine and an antiepileptic drug concurrently.Objective: The aim of this study was to compare the interaction of memantine with phenobarbital (an enzyme inducer) and chloramphenicol (an enzyme inhibitor) on plasma concentrations of carbamazepine (CBZ), CBZ-10,11-epoxide (CBZE), and phenytoin in an experimental model.Methods: Eight groups of rats (200-230 g) were treated for 14 days each. In groups 1 and 2, phenobarbital 50 mg/kg was administered daily as an enzyme inducer 60 minutes before CBZ 50 mg/kg or phenytoin 30 mg/kg administration, respectively. In groups 3 and 4, chloramphenicol 300 mg/kg was administered daily as an enzyme inhibitor 60 minutes before CBZ or phenytoin administration, respectively. In groups 5 and 6, memantine 20 mg/kg was administered daily 60 minutes before CBZ or phenytoin, respectively. In group 7, CBZ alone was administered daily; in group 8, phenytoin alone was administered daily. Two hours after the last intragastric gavage, animals were anesthetized with ether and 2 mL of blood was drawn from the heart into a syringe containing EDTA. A validated method developed in this study was used for simultaneous determination of CBZ, CBZE, and phenytoin concentrations in rat plasma.Results: The study comprised 8 groups of 9 male adult Wistar rats each. Compared with groups 7 and 8, concurrent use of CBZ or phenytoin with phenobarbital (groups 1 and 2) was associated with significantly lower mean (SEM) plasma concentrations of CBZ (3.45 [0.16] vs 2.20 [0.21] μg/mL; P < 0.001) and phenytoin (3.68 [0.09] vs 1.63 [0.15] μg/mL; P < 0.001) and a significantly higher plasma CBZE concentration (9.85 [0.29] vs 11.18 [0.29] μg/mL; P < 0.05). Concurrent use of CBZ or phenytoin with chloramphenicol (groups 3 and 4) was associated with significantly higher plasma concentrations of CBZ (4.81 [0.17] μg/mL; P < 0.001) and phenytoin (6.24 [0.22] μg/mL; P < 0.001) and a significantly lower plasma CBZE concentration (3.88 [0.25] μg/mL; P < 0.001). Concurrent use of CBZ or phenytoin with memantine (groups 5 and 6) was not associated with a significant change in the plasma concentration of CBZ, CBZE, or phenytoin.Conclusion: Memantine was not associated with a significant change in the plasma concentration of CBZ, CBZE, or phenytoin in this experimental model.     

Prevention of post-focal thermal damage by formation of bubbles at the focus during high intensity focused ultrasound therapy

Safety concerns exist for potential thermal damage at tissue-air or tissue-bone interfaces located in the post-focal region during high intensity focused ultrasound (HIFU) treatments. We tested the feasibility of reducing thermal energy deposited at the post-focal tissue-air interfaces by producing bubbles (due to acoustic cavitation and/or boiling) at the HIFU focus. HIFU (in-situ intensities of 460-3500 W/cm2, frequencies of 3.2-5.5 MHz) was applied for 30 s to produce lesions (in turkey breast in-vitro (n = 37), and rabbit liver (n = 4) and thigh muscle in-vivo (n = 11)). Tissue temperature was measured at the tissue-air interface using a thermal (infrared) camera. Ultrasound imaging was used to detect bubbles at the HIFU focus, appearing as a hyperechoic region. In-vitro results showed that when no bubbles were present at the focus (at lower intensities of 460-850 W/cm2), the temperature at the interface increased continuously, up to 7.3 +/- 4.0 degrees C above the baseline by the end of treatment. When bubbles formed immediately after the start of HIFU treatment (at the high intensity of 3360 W/cm2), the temperature increased briefly for 3.5 s to 7.4 +/- 3.6 degrees C above the baseline temperature and then decreased to 4.0 +/- 1.4 degrees C above the baseline by the end of treatment. Similar results were obtained in in-vivo experiments with the temperature increases (above the baseline temperature) at the muscle-air and liver-air interfaces at the end of the high intensity treatment lower by 7.1 degrees C and 6.0 degrees C, respectively, as compared to the low intensity treatment. Thermal effects of HIFU at post-focal tissue-air interfaces, such as in bowels, could result in clinically significant increases in temperature. Bubble formation at the HIFU focus may provide a method for shielding the post-focal region from potential thermal damage.     

Expression Analysis of <Emphasis Type="Italic">CYFIP1</Emphasis> and <Emphasis Type="Italic">CAMKK2</Emphasis> Genes in the Blood of Epileptic and Schizophrenic Patients

Schizophrenia and epilepsy are two prevalent neurological disorders with high global burden to the society. Genome-wide studies have identified potential underlying causes for these neurological diseases. In the present case-control study, we have assessed expression of CYFIP1 and CAMKK2 genes in the blood samples of epileptic and schizophrenic patients compared with healthy subjects. A total of 180 subjects including 40 epileptic patients, 50 schizophrenic patients, and 90 healthy individuals participated in the study. Expression of the mentioned genes was measured using TaqMan real-time PCR. The results demonstrated a significant upregulation of CYFIP1 gene expression in epileptic patients (P?=?0.029). CAMKK2 was downregulated in female schizophrenic patients compared with female healthy individuals (P?=?0.048). These results may provide new insight into the pathogenesis of epilepsy and schizophrenia and suggest these genes as potential therapeutic targets for these neurological disorders. Future studies should evaluate these results in larger cohorts of patients.