Effect of Physical Exercise on Experimental Steroid-Induced Myopathy

BACKGROUND: Steroid myopathy is an unexpected side effect to the prolonged therapeutic use of steroids. To treat steroid myopathy, the followings are recommended; reduction of the steroid dose, usage of a nonfluorinated steroid, and conversion to an alternate day regimen. As muscle loading is encouraged in maintaining normal muscle properties, it is also apparent that physical exercise may be useful in the prevention and treatment of steroid myopathy. METHOD: The experiment was designed to investigate the effects of exercise on steroid myopathy. Rats being treated with triamcinolone acetonide (TA) (5 mg/kg/day) for 7 days exercised on a treadmill (speed 20m/min, 30 min/day, 3 days/week) for 2 weeks. The extensor digitorum longus (EDL) and soleus were then examined histochemically and ultrastructurally. RESULTS: Rats treated with TA showed significant loss of body and muscle weight. In the TA treated group, cross-sectional areas of type II fibers of both EDL and soleus were decreased in comparison with the controls. Necrotic changes were found only in type II fibers of the soleus. Recovery from the weight loss with type II fiber atrophy was more pronounced in the exercise group than that of the sedentary group, but was not significant statistically. Ultrastructural abnormalities, that consisted of subsarcolemmal mitochondrial accumulation, mitochondrial vacuolation, increased number of mitochondria in autophagic vacuoles, and dilatation of sarcoplasmic reticulum, were seen in TA treated muscles. These injuries were significantly reduced by the exercise, however, complete recovery could not be seen. CONCLUSIONS: These results suggest that treadmill exercise for 2 weeks partially ameliorate steroid myopathy in.

Expression of Vascular Endothelial Growth Factor and Its Relation with Neovascularization and Apoptosis in Grading of Astrocytic Tumors

BACKGROUND: The vascular endothelial growth factor (VEGF) is known as a potent mediator of brain tumor angio-genesis, vascular permeablity, and glioma growth. This study was designed to study the balance between growth and death signals in different grades of astrocytic tumors. METHODS: Using immunohistochemistry, the relationship between the expression of VEGF and microvessel count and density were evaluated in 62 cases of astrocytic tumors including 33 low grade astrocytomas, 6 anaplastic astrocytomas, and 23 glioblastomas. In order to determine the apoptotic index (AI), the in situ end-labeling method was applied. RESULTS: VEGF was expressed on the tumor cell cytoplasm. Of 62 tumors, 44 (77%) were weak to strong postive for VEGF, but 18 cases were not reactive. VEGF positivity was correlat-ed with WHO grades of the astrocytic tumors; low grade astrocytomas (52%), anaplastic astrocytomas (83%), and glioblastomas (96%). Mean microvessel count and density were significantly higher in VEGF-positive tumors (75.7 and 4.1%) than in VEGF-negative tumors (43.9 and 2.5%). Apoptotic cells were readily found in the astrocytic tumors; the highest value of AI was observed in glioblastomas (8.6%) and the lowest in anaplastic astrocytomas (1.9%). It seemed that the grade of malignancy was not related with AI values. CONCLUSIONS: These results suggest that VEGF promotes angiogenesis with tumor cell growth against apoptotic cell death in the human astrocytomas.

Usefulness of MR Imaging in the Staging of Brain Abscess: Comparison between Experimental Models and Clinical Cases

PURPOSE: The purpose of this study is to evaluate the usefulness of MR imaging in the staging of brain abscesses and to determine the correlations between pathologic and MR findings. MATERIALS AND METHODS: Experimental brain abscesses were induced by direct inoculation of 1ml suspension of l06/ml Streptococcus pneumoniae into the brain parenchyma of ten New Zealand white rabbits. The evolution of abscess formation was divided into four stages, based on pathological criteria: early cerebritis (days 1 to 5), late cerebritis (days 6 to 10), early capsular (days 11 to 15), and late capsular (day 16 and later). The brain abscess of each animal was examined by MR imaging and light microscopy at 3, 8, 13, and 28 days; T1-weighted, T2-weighted and Gd-enhanced images were obtained. The MR images and pathologic findings of 13 pathologically confirmed clinical cases were compared to MR images of the experimental model. RESULTS: In the experimental model, signal intensity of the abscess content was at all stages hypointense on T1-weighted and hyperintense on T2-weighted images. In all ten cases, Gd-enhanced images showed an ill-defined contrast-enhanced lesion at the early cerebritis stage, and in four of seven cases, irregular ring enhancement at the late cerebritis stage. Pathologic specimens at this latter stage revealed prominent vascular proliferation and infiltration of chronic inflammatory cells. Signal intensity of the abscess wall during the capsular stage showed isointense relative brain parenchyma on T1-weighted images and this was hypointense on T2-weighted images. Gd-enhanced images demonstrated smooth ring enhancement of the abscess wall. At the early capsular stage, pathologic specimens revealed a discrete necrotic center surrounded by infiltration of reticulin and some collagen; at the late capsular stage, these specimens showed marked infiltration of collagen. In clinical cases, the signal intensity of abscess content was at all stages hypointenseon T1-weighted and hyperintense on T2-weighted images. Gd-enhanced images demonstrated ill-defined subtle contrast enhancement at the early cerebritis stage and irregular ring enhancement at the late cerebritis stage. In all cases, signal intensity of the abscess wall during the capsular stage was hypointense on T2-weighted images; at this stage, the abscess wall was showed a pattern of smooth ring enhancement. In clinical cases, hypointensity of the abscess wall, as seen on T2-weighted images, and the enhancement pattern of this wall were identical to these findings in the experimental model. CONCLUSION: In an experimental model, correlation between sequential MR findings can be used to predict the stage of a brain abscess; in clinical cases essential indicators are hypointensity and enhancement pattern of the abscess wall, as seen on T2-weighted images. In cases of brain abscess, MRI is a useful diagnostic modality, and in such cases, also helps determine the most suitable treatment.

Effects of Gangliosides on DNA Synthesis in U1242 MG Glioma Cells

Exogenously added gangliosides modulate the growth and differentiation of a variety of cells in vitro including human gliomas. GM1, Gdla and GTlb gangliosides inhibit both PDGF-stimulated and serum-stimulated DNA synthesis of Swiss 3T3 cells and U1242 MG cells in a dose responsive manner. The inhibitory effect is counteracted in a dose-responsive fashion by serum, and that ganglioside-induced inhibition is essentially abolished in 10% serum. Because of the potentially important role that gangliosides play in growth regulation of human gliomas, this phenomenon was studied in detail using the human glioma cell line U1242 MG. Low doses of serum stimulate DNA synthesis of U1242 MG cells which is inhibited in a dose-responsive fashion by ganglioside GMI. However, serum itself counteracts the inhibitory effect of ganglioside in a dose-responsive way. On the other hand GM,, Gdla and GTlb stimulate DNA synthesis in quiescent U1242 MG cells in both sparse and confluent conditions, indicating that ganglioside-stimulated DNA synthesis is dependent on the phase of cellular growth rather than celluar density. The growth stimulatory effect of the three gangliosides is more potent on quiescent, confluent cells than quiescent, sparse cells. Gangliosides stimulate radiolabeling of and 35% of nuclei with (3H) thymidine in quiescent, sparse and quiescent, confluent cells respectively. These results demonstrate that exogenously added gangliosides can have different effects on progression of human glioma cells, support of the bimodal behavior model of gangliosides. The effects are mainly related to cell cycle depending on the growth phase of the cells rather than the cell density.