Folic acid effects on s-adenosylmethionine, s-adenosylhomocysteine, and DNA methylation in patients with intermediate hyperhomocysteinemia.

OBJECTIVE: Folic acid (FA) supplementation decreases homocysteine (tHcy) levels. However, little is known about the effects of FA treatment on DNA methylation or plasma S-adenosylmethionine (AdoMet) and S-adenosylhomocysteine (AdoHcy) concentrations. The purpose of this study was to investigate the effects of FA supplementation on AdoMet, AdoHcy, and genomic DNA methylation in hyperhomocysteinemic subjects without end-stage renal disease. METHODS: To evaluate the effects of 5 mg FA/d for 8 weeks, we recruited 7 hyperhomocysteinemic MTHFR677TT patients (tHcy >30 µmol/L) with normal renal function. RESULTS: FA supplementation induced a decrease in tHcy (from 51.1 ± 21 at baseline to 26.1 ± 27 µmol/L after folate supplementation; p < 0.01). A parallel increase was seen in plasma AdoMet concentrations and the AdoMet/AdoHcy ratio (p < 0.05). However, FA supplementation had no effect on global DNA methylation levels in the present study. CONCLUSIONS: Supraphysiologic FA supplementation can modulate biochemical markers in one-carbon metabolism such as tHcy, AdoMet, and the AdoMet/AdoHcy ratio in hyperhomocysteinemic subjects. However, the reduction in homocysteinemia and the increased availability of methyl compounds provided by vitamin supplementation may not be sufficient to affect genomic DNA methylation.

[Erdheim-Chester disease: normal skeletal radiography in a patient with extensive bone involvement]. / Malattia di Erdheim-Chester: normalità della radiografia tradizionale in un paziente con diffuso coinvolgimento osseo.

Erdheim-Chester disease is a rare disorder of unknown cause, characterized by systemic histiocytic infiltration; the long bones of the limbs are usually affected symmetrically, and a direct radiography of the involved skeletal segments is able to show a pattern of typical abnormalities. However, the patient we describe suffered of serious clinical symptoms in the lower limbs, but the direct radiography of the legs did not show any abnormality; this finding seems very remarkable and, to our knowledge, has not been reported previously in the literature. Therefore we discuss the role of the imaging procedures in the diagnosis of Erdheim-Chester disease. Differently from other authors, we did not obtain any clinical improvement in our patient by steroid treatment alone, that is generally considered the first therapeutic option for Erdheim-Chester disease with only skeletal involvement.

Liver stellate cells and aminoterminal peptide of type III procollagen in chronic hepatitis C treated with interferon.

BACKGROUND/AIMS: Fibrogenesis plays a crucial role in development of cirrhosis, and liver stellate cells, activated to myofibroblasts expressing alpha-smooth muscle actin, are responsible for deposition of fibrous matrix; aminoterminal peptide of type III procollagen is a serum marker of active fibrogenesis. Interferon can slow ongoing fibrogenesis in chronic viral hepatitis, but it remains unclear whether the drug acts by a direct effect on stellate cells or by inhibiting the necro-inflammatory process. The aim of this study was to evaluate, in selected cases of chronic hepatitis C, whether changes in stellate cell expression induced by interferon correlated with changes in serum levels of procollagen or with clinical response to the therapy, in order to further investigate the mechanism of interferon's effect on fibrogenesis. METHODOLOGY: We studied 30 patients with chronic hepatitis C, treated with interferon and followed for more than 6 months. Before and after-treatment evaluation included histological scores for portal activity, lobular activity and fibrosis; immunohistochemical scores for alpha-actin expression by activated stellate cells in liver biopsy; and radioimmunoassay for procollagen in serum. According to the clinical response to interferon, the patients were subdivided into sustained responders, delayed relapsers, early relapsers and non-responders. RESULTS: We found that alpha-actin scores, portal and lobular activity scores and procollagen levels were all significantly lower after the treatment in responder patients, whereas in non-responders the after-interferon values were not different from the basal values. Moreover we found that the patients who were still clinical responders at the time of after-therapy evaluation, but relapsed subsequently (delayed relap-sers), still showed a pattern of "low fibrogenesis", like the sustained responders. On the contrary, the patients who had already relapsed at the time of after-interferon evaluation (early relapsers) showed a pattern of "high fibrogenesis", like the non-responders. CONCLUSIONS: Since all the patients had received a similar treatment for a similar period, our results suggest that fibrogenesis activity in a defined time is related to the clinical response present in that time, and is influenced by short-term variations in necro-inflammatory activity induced by interferon, rather than by interferon itself.

[Pyogenic sacroiliitis complicated by iliopsoas muscle abscess]. / Sacroileite infettiva complicata da ascesso del muscolo ileopsoas.

Both pyogenic sacroiliitis and iliopsoas muscle abscess are uncommon infectious entities, and their coexinstence has been reported in very few patients. We present here the case of a woman who developed a large iliopsoas abscess as a consequence of a pyogenic sacroiliitis, initially misdiagnosed as a common sciatica and treated with corticosteroids. The patient was cured by the surgical drainage of the abscess and a long-lasting antibiotic treatment. We discuss diagnostic difficulties linked to the two infectious entities, their possible pathogenic connections, the role of imaging procedures, and therapeutic options. We conclude that pyogenic sacroiliitis and the potential evolution to an iliopsoas abscess must be taken into consideration in the differential diagnosis of lower back pain, especially if fever is a concomitant sign.