Methionine synthase reductase polymorphisms are associated with serum osteocalcin levels in postmenopausal women

Homocysteine (Hcy) is thought to play an important role in the development of osteoporosis and fracture. Methionine synthase reductase (MTRR) is an enzyme involved in the conversion of Hcy to methionine. We hypothesized that certain genetic polymorphisms of MTRR leading to reduced enzyme activity may cause hyperhomocysteinemia and affect bone metabolism. We therefore examined the associations of the A66G and C524T polymorphisms of the MTRR gene with bone mineral density (BMD) and serum osteocalcin levels in postmenopausal women. Although we did not detect any significant associations between MTRR polymorphisms and BMD or serum osteocalcin levels, we found that the 66G/524C haplotype, which has reduced enzyme activity, was significantly associated with serum osteocalcin levels in a gene-dose dependent manner (P=0.002). That is, the highest osteocalcin levels (34.5+/-16.8 ng/ml) were observed in subjects bearing two copies, intermediate osteocalcin levels (32.6+/-14.4 ng/ml) were observed in subjects bearing one copy, and the lowest levels of osteocalcin (28.8+/-10.9 ng/ml) were observed in subjects bearing no copies. These results suggest that the 66G/524C haplotype of the MTRR gene affect bone turn over rate.

A Case of Hyperthyroidism Associated with Symptomatic Hypercalcemia / 대한내분비학회지

Two of the common causes of hypercalcemia are malignancy and primary hyperparathyroidism. These disorders are easily diagnosed by the clinical manifestations and measurement of the serum intact parathyroid hormone (PTH) level. On the other hand, hyperthyroidism is an uncommon cause of hypercalcemia. The diagnosis of hypercalcemia associated with hyperthyroidism can only be made by excluding the common causes of hypercalcemia and by observing the improvement of the hypercalcemia and its associated symptoms with normalizing the thyroid function. Herein we reported our experience with a 67 year-old woman who presented with nausea and vomiting. She showed elevated serum calcium and phosphorus levels. Serum intact PTH level was 1.1 pg/mL (normal range; 10~65). The results of the thyroid function test were compatible with hyperthyroidism. After resolution of the thyrotoxicosis with combination treatment of methimazol and Lugol's solution, the patient's serum calcium and phosphorus levels were normalized and the symptoms were improved.

Effects of alpha-Lipoic Acid on Bone Metabolism in Rats with Low Bone Mass / 대한내분비학회지

BACKGROUND: Growing evidence has shown a biochemical link between increased oxidative stress and reduced bone density. In our previous study, alpha-lipoic acid (alpha-LA), a thiol antioxidant, suppressed both osteoclastogenesis and bone resorption, and also prevented TNF-alpha-induced apoptosis of osteoblast lineages. The effects of alpha-LA were investigated on bone metabolism in rats with a low bone mass. METHODS: An ovariectomy (OVX) or Talc injection (inflammation-mediated osteopenia, IMO) was performed in 12 week old female Sprague-Dawley rats. Diets containing either 0.3%, 0.5% or 1.0% alpha-LA were administered to the OVX rats for 16 weeks, and to the IMO rats for 21 days. The bone mineral densities (BMD) of the anterior-posterior lumbar spine and total femur were measured using dual-energy X-ray absorptiometry (Hologic QDR 4500-A), with small animal software. The plasma bone specific alkaline phosphatase activity (BSAP) and urinary free deoxypyridinoline concentration (DPD) were determined using enzyme immunoassay methods. RESULTS: The body weights were significantly decreased in the OVX rats on the diets containing 0.3 and 0.5% alpha-LA than in the OVX control. No significant differences in the BMD at either site were noted between rats administered the diets with or without alpha-LA. However, the administration of various doses of alpha-LA noticeably decreased the level of urinary DPD in both the OVX and IMO rats. High doses of alpha-LA (0.5% and/or 1.0%) also decreased the levels of plasma BSAP in both models. CONCLUSION: Although no increase in BMD was demonstrated by the administration of alpha-LA, these results suggest that alpha-LA suppresses the rates of bone turnover in rats with a low bone mass

Effects of Glucocorticoid on Apoptosis of Human Bone Marrow Osteogenic Stromal Cells / 대한내분비학회지

BACKGROUND: Osteoporosis is one of the most serious side effects of long-term glucocorticoid therapy, but the mechanism of glucocorticoid-induced bone loss remains poorly defined. Glucocorticoid induces decreased bone formation and death of isolated segments of bone (osteonecrosis) suggesting that glucocorticoid excess may affect the birth or death rate of bone cells and thereby reduce their numbers. It has been known that reduction in bone formation is due to reduced proliferation in osteoblast precursor cells and reduced matrix synthesis in mature osteoblast. Here, we present evidence for dexamethasone-induced apoptosis on human bone marrow stromal cells (hBMSC). To understand the mechanism of glucocorticoid-induced osteoporosis, we investigated the effects of glucocorticoid on primary cultured hBMSC. METHEODS: Treatment with dexamethasone at the concentration of 10-9 M for 3~5 days significantly decreased cleavage tetrazolium salt WST-1 level/concentration by mitochondrial dehydrogenase in viable cells. Greater decrease was observed with higher concentration of dexamethasone (10-7 M, and 10-5 M). Apoptosis was measured by annexin V binding/propidium iodide using fluorescence-activated cell sorter (FACS) analysis and nuclear morphology stained with the fluorescence dye, Hoechst 33342. RESULTS: The level/concentration of apoptotic hBMSC (annexin V positive / PI negative) was increased with 10-9 M dexamethasone (1.2% to 5.3%) and further increased with 10-7 M, and 10-5 M concentration (11.7% and 12.5%, respectively). The same result was observed with Hoechst 33342 staining. CONCLUSION: These results indicate that glucocorticoid induces apoptosis on osteoblast precursor cell, hBMSC, and may contribute to decrease bone formation

Serum Leptin Levels in Relation to Quantitative Ultrasound Values of Calcaneus in Korean Postmenopausal Women in Chung-Up District / 대한내분비학회지

BACKGROUND: Obese postmenopausal women usually have a tend to have greater bone mineral density than lean women. This has been attributed to either the mechanical effects of their excessive weight on bone tissue or to their high body fat content. A recent study demonstrated that leptin, the hormone produced in adipocytes, acts on bone metabolism. These findings have prompted speculations on the possible role of leptin in the protective effect of obesity on bone. METHEODS: We studied the relationship between serum leptin levels and quantitative ultrasound (QUS) values of calcaneus in 94 postmenopausal Korean women who were randomly selected from the population of the Chung-Up osteoporosis prevalence study. QUS values, broadband ultrasound attenuation and speed of sound; were measured at the calcaneus. RESULTS: Leptin values were strongly correlated with body mass index (r = 0.478, p< 0.001), confirming a positive relationship between leptin levels and fat mass. In contrast, no significant correlations were observed between serum leptin levels and calcaneal QUS values. CONCLUSION: Our results suggest that circulating plasma leptin does not have a significant influence on QUS values of calcaneus in Korean postmenopausal women.

A Case of Primary Biliary Cirrhosis in Association with Sjorgen's Syndrome Developing Features of Systemic Lupus Erythematosus / 대한류마티스학회지

Primary biliary cirrhosis (PBC)is a chronic inflammatory disease characterized by fibrous obliteration of intrahepatic bile ductules.Although the etiopathogenesis of PBC remains unclear,several studies suggest that a disordered immune response may be involved.This disease is commonly associated with various autoimmune diseases,such as Sjogren's syndrome,scleroderma, rheumatoid arthritis,Hashimoto's thyroiditis,polymyositis,and pernicious anemia.More than 80%of cases with PBC are accompanied by at least one autoimmune disorder,and 40%by two or more. Sjogren's syndrome,defined by dry eyes and xerostomia,may be found in 69 to 81%of PBC patients. However, concurrent coexistence of PBC and systemic lupus erythematosus (SLE)has been rarely described in the literature.We report a 46-year-old female with PBC and Sjogren's syndrome who also satisfied a classification criteria of SLE.

Bilateral Renal Parenchymal Malacoplakia Presenting as Fever and Acute Renal Failure / 대한신장학회잡지

Malacoplakia is a rare, chronic inflammatory disorder characterized by abnormal macrophage function and cell infiltration into normal tissues. We report a 72 year old male with bilateral renal parenchymal malacoplakia who presented with high fever and acute renal failure. The patient had anemia, leukocytosis, thrombocytopenia and bilateral nephromegaly with reduced renal function. Blood and urine cultures showed no micro-organisms. A kidney biopsy revealed diffuse interstitial histiocytic infiltration with intracellular inclusion bodies(Michaelis-Gutmann body). He was treated with antibiotics, and bethanechol, ascorbic acid without improvement. Following treatment with an intravenous methylprednisolone pulse therapy, clinical improvement was made. Renal parenchymal malacoplakia should be considered in the differential diagnosis when presented with high fever, enlarged kidneys and acute renal failure.

Bilateral Renal Parenchymal Malacoplakia Presenting as Fever and Acute Renal Failure / 대한신장학회잡지

Malacoplakia is a rare, chronic inflammatory disorder characterized by abnormal macrophage function and cell infiltration into normal tissues. We report a 72 year old male with bilateral renal parenchymal malacoplakia who presented with high fever and acute renal failure. The patient had anemia, leukocytosis, thrombocytopenia and bilateral nephromegaly with reduced renal function. Blood and urine cultures showed no micro-organisms. A kidney biopsy revealed diffuse interstitial histiocytic infiltration with intracellular inclusion bodies(Michaelis-Gutmann body). He was treated with antibiotics, and bethanechol, ascorbic acid without improvement. Following treatment with an intravenous methylprednisolone pulse therapy, clinical improvement was made. Renal parenchymal malacoplakia should be considered in the differential diagnosis when presented with high fever, enlarged kidneys and acute renal failure.

Imaging with Magnetization Transfer Technique on the Intracranial Tumors

PURPOSE: To measure the magnetization transfer ratio(MTR) of intracranial tumors and to evaluate the difference of the character and the border of tumors on magnetization transfer image. MATERIALS AND METHODS: We prospectively reviewed magnetization transfer imaging(MTI) findings of intracranial tumors of 13 patients. 1.0T MRI machine was used. T1 weighted image(TRITE=700/14) and T1 weighted magnetization transfer image were obtained. The offset and bandwidth of magnetization transfer pulse were 1000 Hz and 250Hz, respectively. Postcontrast images were also obtained. MTR was measured at lesion area. RESULTS: The mean of normal MTR of white matter and gray matter in 7 normal volunteers were 37% and 29%, respectively. The MTR of each tumor was as follows;metastatic tumors(mean 16.3%), meningioma(mean 27.3%), oligodendroglioma(mean 20.2%), glomus jugulare tumor(mean 17.3%), gliomatosis cerebri(mean 27. 0%). The contrast of lesions were better at magnetization transfer image than at T1 weighted image. CONCLUSION: The MTR of the intracranial tumors is lower than normal tissue. Measurement of MTR at muirpie areas within the tumor can be useful for evaluation of indistinct border of the tumor.

Magnetization Transfer Ratio of Brain Tissue: Normal Value and Effect of TR/TE

PURPOSE: Magnetization transfer imaging(MTI) is a new imaging contrast technique. Our MT pulse sequence is designed as fixed time interval between echo and MT pulse. This study was peformed to evaluate the influence of variations in TR/TE on MTR in T1 weighted image of normal brain tissue on this kind of MT pulse sequence. MATERIALS AND METHODS: Seven healthy volunteers in twenties of age as the objectives, MRI was taken under various TR/TE(TR/TE ;700/14, 650/14, 750/14, 700/20 and 1500/20 msec). MTR was calculated from signal intensities measured at the same point in both pre and post MT images and statisticslly analyzed. The MR imager used in this study was 1.0T Magnetom 42SP(Siemens, Erlangen, Germany) and the parameters of additional MT pulse sequence were offset 1000Hz and bandwidth 250Hz, and posteriorly located to echo with 7.7 msec fixed interval. Offset of this MT pulse was variable. RESULT: In white matter of brain tissue from a normal person, MTR was 34-39%(average 37%) for TR and TE of 700/14 in T1WI and 33-36%(average 35%) for TR/TE of 650/14, and 34-38%(average 35%) for TR/TE of 750/14 which showed no statistical difference. However, in case of 1500/20 of TR/TE, MTR was 26-28%(average 26%) which is statistically significant. With TR/TE of 700/14 as the standrd value, the MTR of gray and white matter were 37% and 29% respectively, showing a definite difference of statistical means. Signal from CSF in ventricles is rarely influenced by MT pulse. CONCLUSION: Conclusively, a subtle variation in TR/TE in T1WI has little influence on MTR but wide range of variation in TR/TE as in proton density image induces significant difference in MTR on this kind of MT pulse sequence. Therefore, the exchangeable usage of MTR data would be possible in narrow range of TR/TE change but difficult in wide range of variation.