A PCR Analysis of ERα and ERβ mRNA Abundance in Rats and the Effect of Ovariectomy

To study the relative abundance and the changes of both estrogen receptor alpha (ERalpha) and ERbeta mRNA before and after ovariectomy in major organs important to the regulation of calcium homeostasis, we compared the degree of mRNA expression of ERalpha to that of ERbeta in rat tissues by performing competitive reverse transcription polymerase chain reaction (RT-PCR) with internal standards. Both ERalpha and ERbeta were highly expressed in the ovary {ERalpha[(2.2 +/- 0.33) x 10(7) copies/microg of total RNA] > ERbeta[(1.2 +/- 0.33) x 10(5) copies/microg of total RNA]} as we expected. The bone marrow and renal cortex were very important target organs of estrogen because ERalpha was highly expressed approximately 2 x 10(5) copies/microg of total RNA, but marrow cells revealed only a very weak expression of ERbeta [(0.7 +/- 0.21) x 10(2) copies/microg of total RNA]. Both ERalpha and ERbeta were expressed in the trabecular bone [(3.2 +/- 0.56) x 10(3) copy/microg of RNA] and [(2.8 +/- 0.21) x 102 copy/microg of RNA], respectively. However, they were not detected in the cortical bone. In the jejunum, the expression of ERalpha was not detectable, while ERbeta was expressed very weakly [(1.1 +/- 0.24) x 10(2) copies/microg of total RNA]. The thyroid gland expressed low copy numbers of ERbeta [(6.0 +/- 0.23) x 10(2) copies/microg of total RNA], but the parathyroid gland was negative for both ERalpha and ERbeta mRNA. In cultured stromal cells, ERalpha and ERbeta mRNAs were not detected after a 24-h culture; however, the rates of mRNA expression of ERalpha and ERbeta reached approximately 105 copies/microg of total RNA and approximately 10(2) copies/microg of total RNA, respectively, after 9-, 11-, and 13-day cultures. After ovariectomy, the expression of ERalpha mRNA decreased abruptly in the bone marrow and renal cortex, and both ERalpha and ERbeta were barely detected in the trabecular bone. In conclusion, ERalpha might be the main ER in organs important for calcium homeostasis, except in the jejunum. The mRNA expression of ERalpha in the bone marrow and renal cortex decreased abruptly after ovariectomy, which may partially explain why the effect of estrogen deficiency can be amplified and why trabecular bone loss is more predominant than cortical bone loss shortly after surgical or natural menopause.ope

Assessment of Bone Quality using Finite Element Analysis Based upon Micro-CT Images

BACKGROUND: To evaluate the feasibility of a micro-image based finite element model to determine the efficacy of sequential treatments on the bone quality in a rat osteoporosis model. METHODS: Rat osteoporosis and treated osteoporosis models were established with the bone loss, restore and maintain concept. Thirty Sprague-Dawley rats were used in this study. A sham operation or ovariectomy was performed at 20 weeks after birth, which was followed by the respective sequential trials as follows: (1) sham-operation only, (2) ovariectomy only, (3) ovariectomized rats with parathyroid hormone maintenance, (4) ovariectomized rats treated with PTH for 5 weeks and then withdrawal, (5) ovariectomized rats treated with PTH for 5 weeks and then with 17 beta-estradiol, and (6) ovariectomized rats treated with parathyroid hormone for 5 weeks and then treated with zoledronate. The histomorphometry indices were determined using the micro-images from a micro-computed tomogram. Finite element analysis was carried out to determine the mechanical properties (Stiffness and Young's modulus) of the vertebra bodies. The differences in properties between the groups were compared using ANOVA and a Bonferroni's multiple group comparison procedure. RESULTS: The histomorphometry and mechanical properties were significantly better in groups (3) and (6) than in the groups (1) and (2) (p < 0.05). The stiffness (sigma(s)) and Young's modulus (E) was highest in group (3) following by group (6). CONCLUSIONS: Finite element analysis based on micro-images provides a useful tool that reflects the changes in micro-structural and mechanical properties of a rat vertebral body with the bone loss, restore and maintain concept.ope

Recurrent Infective Endocarditis Associated With Pyogenic Spondylodiskitis

Infective endocarditis is a life-threatening condition caused by microbial infection of the heart's endocardial surface. This condition can also be associated with bacterial infections of other organs. We experienced an unusual case of recurrent infective endocarditis associated with pyogenic spondylodiskitis. A 70-year-old man presented with persistent fever and lower back pain visited our hospital. The patient had a past history of recurrent infective endocarditis. He was diagnosed with infective endocarditis again based on clinical symptoms and echocardiographic findings. Magnetic resonance imaging was used to evaluate lower back pain, which showed acute spondylodiskitis on L3 and L4 vertebrae. The patient completely recovered following four weeks of antibiotic therapy

Characteristics of Body Fat, Body Fat Percentage and Other Body Composition for Koreans from KNHANES IV

Accurate measurement of fat mass has become increasingly important with the increasing incidence of obesity. We assessed fat and muscle mass of Koreans with the Korea National Health and Nutrition Examination Survey IV (KNHANES IV). We studied 10,456 subjects (aged 20 to 85 yr; 4,476 men, 5,980 women). Fat and muscle mass were measured by dual-energy x-ray absorptiometry. Reference values of body compositions were obtained using the LMS method. The fat mass index (FMI, body fat mass/height2; kg/m2) of Korean men did not correlate with age (P = 0.452), but those of Korean women (P < 0.001) did. The ratio of percentage of fat in the trunk and legs was positively related with age in both the genders. The appendicular lean mass/height2 (kg/m2) of Korean men was negatively related to age (P < 0.001). In women, this ratio increased with age (P < 0.001). When we defined obesity according to the FMI classification, the rates of obesity were 6.1% (FMI > 9 kg/m2) in men and 2.7% (FMI > 13 kg/m2) in women. It is concluded that the muscle mass decreases and obesity increases with aging in Korean men, whereas both fat mass and obesity increase with aging in Korean women

Spontaneous Non-Traumatic Stress Fractures in Bilateral Femoral Shafts in a Patient Treated with Bisphosphonates

Bisphosphonates are potent inhibitors of bone resorption and widely used to treat osteoporosis. Extensive studies have shown that therapy with bisphosphonates improves bone density and decreases fracture risk. However, concerns have been raised about potential over-suppression of bone turnover during long-term use of bisphosphonates, resulting in increased susceptibility to and delayed healing of non-spinal fractures. We report a patient who sustained non-traumatic stress fractures in bilateral femoral shafts with delayed healing after long-term bisphosphonate therapy. She underwent open reduction and surgical internal fixation. Although bisphosphonates effectively prevent vertebral fractures, and their safety has been tested in randomized trials, we must emphasize the need for awareness of the possibility that long-term suppression of bone turnover with bisphosphonates may eventually lead to an accumulation of fatigue-induced damage and adverse skeletal effects such as delayed fracture healing

Identification of Domains Directing Specificity of Coupling to G-proteins for the Melanocortin MC3 and MC4 Receptors

The melanocortin receptors, MC3R and MC4R, are G protein-coupled receptors that are involved in regulating energy homeostasis. Using a luciferase reporter gene under the transcriptional control of a cAMP-responsive element (CRE), the coupling efficiency of the MC4R and MC3R to G-proteins was previously shown to be different. MC4R exhibited only 30-50% of the maximum activity induced by MC3R. To assess the role of the different MC3R and MC4R domains in G-protein coupling, several chimeric MC3R/MC4R receptors were constructed. The relative luciferase activities, which were assessed after transfecting the chimeric receptors into HEK 293T cells, showed that the i3 (3rd intracellular) loop domain has an essential role in the differential signaling of MC3R and MC4R. To reveal which amino acid residue was involved in the MC4R-specific signaling in the i3 loop, a series of mutant MC4Rs was constructed. Reporter gene analysis showed that single mutations of Arg220 to Ala and Thr232 to either Val or Ala increased the relative luciferase activities, which suggests that these specific amino acids, Arg220 and Thr232, in the i3 loop of MC4R play crucial roles in G-protein coupling and the subtype-specific signaling pathways. An examination of the inositol phosphate (IP) levels in the cells transfected with either MC3R or MC4R after being exposed to the melanocortin peptides revealed significant stimulation of IP production by MC3R but no detectable increase in IP production was observed by MC4R. Furthermore, none of the MC4R mutants displayed melanocortin peptide-stimulated IP production. Overall, this study demonstrated that MC3R and MC4R have distinct signaling in either the cAMP- or the inositol phospholipid-mediated pathway with different conformational requirements

The Relation between Birth Weight and Insulin Resistance in Korean Adolescents

Low birth weight is associated with insulin resistance and type 2 diabetes in adults. The fetal programming hypothesis has shown that insulin resistance and its associated metabolic disturbances result from a poor gestational environment, for which low birth weight is a surrogate. An at-home questionnaire survey was performed on 660 middle school students (12-15 years) in Seoul, Korea, and 152 cases were randomly selected based on their birth weight. Subjects were divided into three groups according to birth weight. We recorded their birth weight and measured their current anthropometric data, blood pressure, lipid profile, HOMA-IR, and HOMA-β, and compared these parameters among the groups. The relation of birth weight to physiological characteristics in adolescence was examined. Systolic blood pressure, lipid profiles, and fasting plasma glucose, HOMA-β were not significantly different among the groups, but diastolic blood pressure was lower in the third tertile. Insulin, C-peptide, and HOMA-IR were higher in the lower birth weight tertile. After adjustment for confounding factors, birth weight was inversely related to diastolic blood pressure, insulin, C-peptide, and HOMA-IR. We conclude that low birth weight may predict the risk of the insulin resistance and its progression over age, and that adequate gestational nutrition is therefore necessary to prevent low birth weight

Short- and Long-Term Results of Triple Valve Surgery: A Single Center Experience

Triple valve surgery is usually complex and carries a reported operative mortality of 13% and 10-yr survival of 61%. We examined surgical results based on our hospital's experience. A total of 160 consecutive patients underwent triple valve surgery from 1990 to 2006. The most common aortic and mitral valve disease was rheumatic disease (82%). The most common tricuspid valve disease was functional regurgitation (80%). Seventy-four percent of the patients were in New York Heart Association (NYHA) class III and IV. Univariate and multivariable analyses were performed to identify predictors of early and late survival. Operative mortality was 6.9% (n=11). Univariate factors associated with mortality included old age, preoperative renal failure, postoperative renal failure, pulmonary complications, and stroke. Of them, postoperative renal failure and stroke were associated with mortality on multivariable analysis. Otherwise, neither tricuspid valve replacement nor reoperation were statistically associated with late mortality. Survival at 5 and 10 yr was 87% and 84%, respectively. Ninety-two percent of the patients were in NYHA class I and II at their most recent follow-up. Ten-year freedom from prosthetic valve endocarditis was 97%; from anticoagulation-related hemorrhage, 82%; from thromboembolism, 89%; and from reoperation, 84%. Postoperative renal failure and stroke were significantly related with operative mortality. Triple valve surgery, regardless of reoperation and tricuspid valve replacement, results in acceptable long-term survival

Effect of Zoledronic Acid on Acro-Osteolysis and Osteoporosis in a Patient with Hajdu-Cheney Syndrome

Hajdu-Cheney syndrome is a rare, autosomal dominant skeletal dysplasia marked by acro-osteolysis of the distal phalanges and severe osteoporosis. Although there are more than 60 reports published to date, proper treatment and subsequent outcome have been scarce. Herein, we report a progress of anti-resorptive therapy with zoledronic acid, in a woman with Hajdu-Cheney syndrome. Results suggest that anti-resorptive therapy may be important in delaying the progress of osteoporosis and preventing fractures, but not necessarily acro-osteolysis itself

Relationship between Silent Gastroesophageal Reflux and Food Sensitization in Infants and Young Children with Recurrent Wheezing

It is known that early childhood wheezing associated with sensitization to allergens, including food, has an increased risk of developing asthma later during school age. Gastroesophageal reflux (GER) is well known to be associated with asthma. The purpose of this study was to determine whether there is an association between silent GER and food sensitization in infants and young children with recurrent wheezing. Eighty-five infants or young children with recurrent wheezing, and no gastrointestinal symptoms, underwent 24 hr esophageal pH monitoring, as well as total serum IgE and specific IgE testing for eggs and milk. Among the 85 subjects, 48.2% had significant GER. There was no significant difference in the GER between atopic and non-atopic recurrent wheezers (41.7% and 50.8%, respectively). The sensitization rate to food (eggs or milk) was 12.2% and 20.5% in the GER and non-GER groups, respectively and showed no statistically significant difference between the two groups (P=0.34). In conclusion, about half of infants and young children with recurrent wheezing and no gastrointestinal symptoms have silent GER. The silent GER may not contribute to food sensitization in infants and young children with recurrent wheezing