Methyl-supplemented nutrition delays the development of autoimmune disease in pristane-induced murine lupus.

The aetiology and progression of systemic lupus erythematosus (SLE) resulted from a complex sequence of events generated both from genetic and epigenetic processes. In the current research, the effect of methyl-supplemented nutrition on the development of SLE was studied in the pristane-induced mouse model of the disease. The results clearly demonstrated decreased anti-dsDNA antibody and proteinuria levels, modulation of cytokines and protected renal structures in the group of treated mice. An additional increase in the DNA methylation of mouse B lymphocytes was also observed. The beneficial effect of the diet is due to the methyl-containing micronutrients with possible anti-inflammatory and immunomodulating effects on cell proliferation and gene expression. Since these components are responsible for maintaining the physiological methylation level of DNA, the results point to the central role of methylation processes in environmentally triggered lupus. As nutrition represents one of the major epigenetic factors, these micronutrients may be considered novel agents with significant therapeutic outcomes.

Impact of folic acid on regulatory B lymphocytes from patients with systemic lupus erythematosus in vitro.

BACKGROUND: Epigenetic modifications of genomes are of particular interest as numerous studies indicate the correlation between DNA methylation and the development of systemic lupus. As a major methyl group donor, folic acid is an important participant in this process. The aim of this study is to determine the effect of low or high dose folate co-culturing with peripheral blood mononuclear cells (PBMCs) on the secretion of interleukin (IL)10 from regulatory cells from lupus patients or from healthy volunteers. METHODS: PBMCs from lupus patients and healthy volunteers were isolated and separated CD19+ B cell populations were cultured in the presence of 4 µg/mL or of 16 µg/mL of folic acid and the DNA methylation level as well as the percentages of B lymphocytes were measured. In another experiment, PBMCs were stimulated in vitro for IL10 production with 1 µg/mL recombinant human CD40L and with 2.5 µg/mL unmethylated CpG dinucleotides and cultured in the presence of 4 µg/mL or of 16 µg/mL of folic acid. RESULTS: Although co-culturing with low or high folic acid concentrations had no effect on the methylation level of B lymphocytes, particular patients showed an increase in the population of CD19+ IL10+ as well as of CD19- IL10+ cells. CONCLUSION: The observed increase may be a consequence of additional indirect or direct methylation of DNA in specific loci of the targeted cells. However, further analysis would clarify the exact mechanism of action of folate and would reveal its immunomodulating potential in this autoimmune disease.

Methyl- rich diet ameliorates lupus-like disease in MRL/lpr mice.

Genetic susceptibility is necessary but not sufficient for systemic lupus erythematosus (SLE) to appear indicating that environmental factors are also key components in the disease onset. Aberrant DNA methylation profile positively correlates with the development of lupus-like disease in MRL/lpr mice. In the present study, we evaluate the effect of long term administration of methyl-rich diet in MRL mice. The results showed that supplemented diet decreased the levels of proteinuria and of anti-dsDNA antibodies and modulated cytokine profiles. Limited kidney failure and prevented development of skin lesions in MRL/lpr mice were another positive effects of the high-dose methyl diet. These data suggest that it is possible to modulate the disease course by altering the amount of particular dietary micronutrients and that nutrition-mediated changes in DNA methylation may have potential clinical relevance.

The challenge to prove a rare cause of secondary arterial hypertension. A case report of a pediatric renal solitary fibrous tumor.

BACKGROUND: Childhood hypertension is getting more attention in recent years. We present a case report of a rare cause of secondary arterial hypertension in a teenage girl - a solitary fibrous tumor of the kidney. The case demonstrates that standard imaging techniques, computed tomography and magnetic resonance imaging, are not fully reliable in the diagnosis of renovascular hypertension. CASE: A 15-year old girl was admitted to the Pediatric Department because of episodes of stiffness in the limbs, accompanied by pale skin and lips, dated 4 months back. During these episodes, high blood pressure up to 160/100 mmHg was measured. A 24-hour blood pressure monitoring demonstrated arterial hypertension stage II. Renovascular hypertension was suspected, but the computed tomography examination of the abdomen showed normal-sized renal arteries. In the left kidney hilum, an intraparenchymal formation was discovered. The data presented a non-specific lesion with a wide differential diagnosis. Given the fact that the patient had been treated with an ACE-inhibitor, serum renin level could not be correctly interpreted. The lesion was removed through a laparoscopic intervention. Intraoperatively, the tumor was compressing a small intra-renal vessel - a finding that hadn`t been discovered by the previous imaging studies. The final pathologist diagnosis was: solitary fibrous tumor. During the next six months of follow-up, the maximal blood pressure values of the patient were up to 120/80 mmHg. CONCLUSIONS: Solitary fibrous tumors of the kidneys are infrequent in children. The presented case displays a rare form of initial clinical manifestation of this tumor. It is also a demonstration that standard imaging techniques are not able to get a precise visualization of the small intra-renal vessels. At the same time, the decision of whether or not to perform a more invasive procedure should be based on the clinical conditions and risks of the individual patient.

Propranolol treatment of infantile subglottic hemangioma: a report of two cases and a literature review.

Infantile hemangioma is one of the most common benign tumors of infancy. The natural evolution includes rapid growth followed by gradual involution. Airway hemangiomas are not that common, but they can lead to dyspnoea, as well as to life-threatening complications.Two children aged 3 months were admitted to the Pediatric Department with difficulties in breathing and with biphasic stridor. They had previously been hospitalized because of the same symptoms and misdiagnosed as having an upper respiratory tract infection. The previous treatment included intravenous or inhaled corticosteroids, without any significant improvement. Laryngoscopy was performed for both of the children. There was a mass in the subglottic area with the appearance of a hemangioma causing significant airway stenosis. We started treatment with propranolol at a dose of 1 mg/kg/day twice daily. The dose was gradually increased up to 3 mg/kg/day, under close monitoring. In the first 7 to 10 days after initiation of treatment, we observed a significant improvement of the respiratory distress. The second laryngoscopy showed an almost complete involution of the mass in the subglottis. The focus of this article will be primarily on the clinical presentation and the therapeutic response of subglottic hemangioma, along with a literature review on the subject.