Changes in DNA methylation patterns in subjects exposed to low-dose benzene

Aberrant DNA methylation patterns, including global hypomethylation, gene-specific hypermethylation/hypomethylation, and loss of imprinting (LOI), are common in acute myelogenous leukemia (AML) and other cancer tissues. We investigated for the first time whether such epigenetic changes are induced in healthy subjects by low-level exposure to benzene, a widespread pollutant associated with AML risk. Blood DNA samples and exposure data were obtained from subjects with different levels of benzene exposure, including 78 gas station attendants, 77 traffic police officers, and 58 unexposed referents in Milan, Italy (personal airborne benzene range, < 6-478 microg/m(3)). Bisulfite-PCR pyrosequencing was used to quantitate DNA methylation in long interspersed nuclear element-1 (LINE-1) and AluI repetitive elements as a surrogate of genome-wide methylation and examine gene-specific methylation of MAGE-1 and p15. Allele-specific pyrosequencing of the H19 gene was used to detect LOI in 96 subjects heterozygous for the H19 imprinting center G/A single-nucleotide polymorphism. Airborne benzene was associated with a significant reduction in LINE-1 (-2.33% for a 10-fold increase in airborne benzene levels; P = 0.009) and AluI (-1.00%; P = 0.027) methylation. Hypermethylation in p15 (+0.35%; P = 0.018) and hypomethylation in MAGE-1 (-0.49%; P = 0.049) were associated with increasing airborne benzene levels. LOI was found only in exposed subjects (4 of 73, 5.5%) and not in referents (0 of 23, 0.0%). However, LOI was not significantly associated with airborne benzene (P > 0.20). This is the first human study to link altered DNA methylation, reproducing the aberrant epigenetic patterns found in malignant cells, to low-level carcinogen exposure.     

Oral manifestations of congenital neutropenia or Kostmann syndrome.

Infantile congenital agranulocytosis or Kostmann syndrome is a rare hereditary kind of severe neutropenia. The typical symptoms, which appear since the first days of life, are abscesses located on various parts of the body: ear, cutis, lung and oral cavity. These abscesses are due to an almost total disimmunity typical of the neutropenia. The aim of this article is to describe the most typical signs of this pathology in the oral cavity, reporting a case observed in our department in Florence, Italy. On the basis of the personally observed case and of the review of the literature, it is possible to consider, as a characteristic finding in Kostmann syndrome, a typical very serious periodontal pathology, which is similar to the prepubertal periodontitis in deciduous dentition. At the age of 19 years the patient showed a dramatic compromise of the masticatory function. It is obvious that the lack of response of the host can obstruct the interaction between the host and the microbic flora, because the lack of neutrophils increases the susceptibility of the patient to every kind of infection, even to periodontitis. A periodontal prophylaxis, since the very first observations, followed by a rigorous maintenance with frequent and regular professional hygienic treatments could be effective in controlling the effects of periodontal disease and could reduce the tragic evolution. We need to recognise that it could be hard to monitor the oral situation correctly in these patients, as they have a continuously poor systemic condition. Finally in these cases the rehabilitative therapy is very problematical.     

Effects of treadmill training on walking economy in Parkinson’s disease: a pilot study

Gait disturbances are frequent in Parkinson’s disease (PD) and are associated with increased energy expenditure during walking. This study evaluated whether the effects of treadmill training are associated with an improvement of walking economy. Ten patients with idiopathic PD underwent treadmill training (30 min, three times a week for 4 weeks). Walking performance (Τimed Up and Go, 6-min and 10-m walking tests) and metabolic function (oxygen uptake, heart and respiratory rate) were evaluated before training, at the end of treatment and after 30 days with two different graded exercises (treadmill and cycloergometer). Training significantly improved walking performance. Oxygen uptake, and heart and respiratory rates were significantly decreased only during graded exercise on the treadmill, but not on the cycloergometer. Treadmill training reduces energy expenditure during walking in PD, but the improvements of metabolic walking economy are associated with the specifically trained motor activity.     

Electron microscopic observations on the accumulation of large granular lymphocytes (pit cells) and Kupffer cells in the liver of rats treated with continuous infusion of interleukin-2

Treatment schedules were investigated for in vivo induction of lymphokine-activated killer cells in the rat liver. Treatment of rats with continuous systemic or regional infusion of recombinant human interleukin-2 with a dose of 4 to 8 x 10(4) U/day during 7 days, resulted in an increase in number of large granular lymphocytes or pit cells in the liver up to 43 times normal. Kupffer cells, nongranular lymphocytes, monocytes and neutrophils also increased in number, but with a maximal fivefold increase this was much less pronounced than for large granular lymphocytes. Kupffer cells showed morphological signs of activation and were frequently seen in mitosis. Frequent mitoses were also observed for large granular lymphocytes, but not for other leukocytes. This indicates that the effect of interleukin-2 treatment on hepatic (sinusoidal) cells was primarily directed to large granular lymphocytes and Kupffer cells. The large granular lymphocyte accumulation occurred mainly intrasinusoidally, but they were also frequently observed in the space of Disse where they are not found in control rats. This may be explained partly by the observed damage or gaps in the endothelial lining. The intrasinusoidal large granular lymphocytes adhered to the endothelium and to Kupffer cells. Higher responses, for all cell types, were found when interleukin-2 was administered regionally, that is, through the hepatic artery rather than through the systemic route (jugular vein), although the differences were not statistically significant. Doses below 4 x 10(4) U/day did not result in significant increases of large granular lymphocytes in the liver.