A new role for monoamine oxidases in the modulation of macrophage-inducible nitric oxide synthase gene expression

This report focuses on the modulatory role of endogenous H(2)O(2) on lipopolysaccharide (LPS)/interferon-gamma (IFN-gamma)-induced inducible nitric oxide synthase (NOS2) gene expression in rat peritoneal macrophages. Exogenously added H(2)O(2) was initially found to inhibit the synthesis of NOS2, which prompted us to assess the effect of the activity of monoamine oxidase (MAO) and semicarbazide-sensitive amine oxidase (SSAO) as H(2)O(2)-forming enzymes on NOS2 gene expression. In the presence of their substrates, tyramine for MAO and benzylamine for SSAO, intracellular synthesis of H(2)O(2) took place with concomitant inhibition of LPS/IFN-gamma-induced NOS2 protein synthesis, as detected by Western blotting, flow cytometry, and immunofluorescence microscopy analyses. Pargyline and semicarbazide, specific inhibitors of MAO and SSAO, respectively, canceled this negative effect of MAO substrates on NOS2 expression. In the presence of Fe(2+) and Cu(2+) ions, inhibition of NOS2 expression was enhanced, suggesting the participation in this regulation of species derived from Fenton chemistry. In addition, the negative effect of H(2)O(2), generated by MAOs, was found to be exerted on NOS2 mRNA levels. These data offer a new insight in the control of NOS2 expression through the intracellular levels of H(2)O(2) and other reactive oxygen species (ROS). The hypothesis can be raised that the inhibition of NOS by H(2)O(2) could constitute a protective mechanism against the cytotoxic consequences of the activation of ROS-generating enzymes, thus providing a new, singular role for the MAO family of proteins.     

Breast MRI: Early experience with a 3-D fat-suppressed Gradient Echo Sequence in the evaluation of breast lesions

The early clinical experience with a 3-Dimensional Fourier Transform Gradient Echo sequence with fat suppression in the evaluation of breast masses is reported. Ten female patients with breast malignancies were pre-operatively evaluated with this sequence and the results compared with the pathological specimens. The scanning protocol included a noncontrast sequence followed by an immediate post-contrast sequence (completed 4.5 min after intravenous contrast injection) and a delayed sequence. Images were assessed for maximum lesion and parenchymal enhancement, lesion size and additional enhancing abnormalities. In six patients, malignant masses enhanced maximally on the immediate post-contrast sequence with parenchyma enhancing maximally on delayed images. In three cases, there was preferential enhancement of malignant lesions over normal parenchyma but to a similar degree on both post-contrast sequences. In one case, both the lesion and parenchyma enhanced maximally on the delayed sequence. Magnetic resonance assessed lesion size accurately and also detected satellite malignancies in one case. However, lesion grade, associated in situ carcinoma and lymphovascular invasion did not impact on lesion enhancement. In this small series, a contrast-enhanced, fat-suppressed 3-D Gradient Echo Sequence detected breast carcinoma with high sensitivity. The technique holds promise but further evaluation is required.     

Inflammatory bowel disease and predisposition to osteopenia

The prevalence of osteopenia in children with inflammatory bowel disease (IBD) is unknown. The effect of nutritional state, disease activity, and steroid therapy on bone mineral content (BMC) of whole body, lumbar spine, and left femoral neck measured by dual energy x ray absorptiometry in 32 children with IBD was assessed by comparison with 58 healthy local school children. Using the control data, a predicted BMC was calculated taking into account bone area, age, height, weight, and pubertal stage. The measured BMC in children with IBD was expressed as a percentage of this predicted value (% BMC). Mean (SD) % BMC was significantly reduced for the whole body and left femoral neck in the children with IBD (97.0 (4.5)% and 93.1 (12.0)% respectively, p < 0.05). Of the children with IBD, 41% had a % BMC less than 1 SD below the mean for the whole body and 47% at the femoral neck. Reduction in % BMC was associated with steroid usage but not with the magnitude of steroid dose, disease activity, or biochemical markers of bone metabolism. In conclusion, osteopenia is relatively common in childhood IBD and may be partly related to the previous use of steroids.