柱前手性衍生化反相高效液相色谱法拆分地佐西平对映异构体的研究

用乙酰葡萄糖异硫氰酸酯(GITC)作柱前手性衍生化试剂,以反相高效液相色谱法成功地拆分了地佐西平对映异构体。在此基础上建立了地佐西平对映异构体纯度和血药浓度测定方法。已用于测定右旋地佐西平的光学纯度和小鼠血药浓度。     

Kinematics of the chest cage and spine during breathing in healthy individuals and in patients with adolescent idiopathic scoliosis.

STUDY DESIGN: The lung function test by a Plethysmograph enabled calculations to be made of the total lung capacity and vital capacity. A Motion Analysis System (Elite, BTS Inc., Milano, Italy) was used to observe and record chest cage and spinal movements and as to correlate lung function with the chest cage and spine kinematics. OBJECTIVES: To determine the three-dimensional kinematics and the shape and size changes of the chest cage and thoracic spine motion during deep breathing in healthy and scoliotic individuals. SUMMARY OF BACKGROUND DATA: Lateral flexion plus rotation of the involved vertebrae around a vertical axis causing a decrease in lung function is the main disfigurement of scoliosis. Reports show that even after spinal fusion, reduced vital capacity associated with an increased residual volume are detected. Factors such as angle of scoliosis, length of the spinal column involved, and duration of the deformity influence pulmonary function but do not significantly affect its reduction. Mechanical inefficiency during breathing has not been studied. METHODS: Three-dimensional kinematics of the chest cage and spine during breathing were studied in 41 scoliotic patients and in 20 healthy individuals. Three-dimensional chest cage motions relative to the spine and thoracic spine motions relative to T12 were calculated. To examine stiffness of the spine, lateral bending angles were calculated. The lung function test, which including spirometry and lung subdivision, also was performed for the scoliotic patients. RESULTS: Significant differences (P < 0.05) were found in the movements of the upper level of the chest cage in anteroposterior and vertical directions, ranging from 16.7 to 28.6 mm in healthy individuals and from 12.1 to 24.2 mm in scoliotic patients. The thoracic spine displayed two-dimensional movements posteriorly and vertically during breathing, whereas less movement was seen in scoliotic patients. In addition, overall the scoliotic spine showed signs of stiffness in lateral bending. CONCLUSIONS: The range of movement of the chest cage and spine is more limited in the scoliotic cases. This overall stiffness of the chest cage and the spine may contribute to the mechanical inefficiency and impairment of pulmonary function found in scoliotic patients.     

Quantitative Ultrasound and Symptomatic Vertebral Fracture Risk in Chinese Women

Quantitative ultrasound (QUS) is emerging as a simple, inexpensive and noninvasive method for assessing bone quality and assessing fracture risk. We assessed the usefulness of a contact calcaneal ultrasonometer by studying normal premenopausal women (group I, n= 53), normal postmenopausal women (group II, n= 198), and osteoporotic women without (group III, n= 141) and with vertebral fractures (group IV, n= 53). The osteoporotic subjects had a T-score of the spine or hip neck bone mineral density (BMD) <−2.5 based on the local Chinese peak young mean values. When compared with postmenopausal controls, mean broadband ultrasound attenuation (BUA), speed of sound (SOS), and quantitative ultrasound index (QUI) were 26%, 2.1% and 25% lower in women with vertebral fractures (p all <0.005). The correlation coefficients between QUS parameters and BMD of the spine and hip ranged between 0.4 and 0.5. The ability of the QUS to discriminate between patients groups was determined based on the mean value of normal premenopausal women in group I. The mean T-score for women with fractures was −2.87 ± 1.02 for BUA, −2.54 ± 0.79 for SOS, −3.17 ± 0.70 for QUI, −2.65 ± 0.86 for L2–4 BMD and −2.53 ± 0.66 for hip neck BMD. After adjustment for age and body mass index, the odds ratio of vertebral fracture was 1.71 (95% CI 1.2–2.6) for each 1 SD reduction in BUA, 2.72 (1.3–5.3) for SOS, 2.58 (1.4–4.6) for QUI, 2.33 (1.6–3.3) for L2–4 BMD, 2.09 (1.37–3.20) for femoral neck BMD and 1.88 (1.34–2.92) for total hip BMD. The association between the QUS parameters and vertebral fracture risk persisted even adjustment for BMD. The area under the receiver operating characteristic curve for BUA for vertebral fracture was 0.92, for SOS, QUI, L2–4 BMD and femoral neck BMD was 0.95, and for total hip was 0.91. Received: 7 January 1999 / Accepted: 18 May 1999     

Technetium-99m-sestamibi/pertechnetate subtraction scintigraphy vs ultrasonography for preoperative localization in primary hyperparathyroidism

A prospective study was performed to evaluate the efficacy of technetium-99m-sestamibi and technetium-99m-pertechnetate subtraction scanning and US for imaging parathyroid glands in primary hyperparathyroidism. Sixty-three patients were surgically treated for primary hyperparathyroidism (HPT). Preoperative scintigraphy and US were performed in all cases. Bilateral neck exploration was carried out on each patient. Results of radionuclide studies and US were compared with surgical and histological findings. In 57 patients with primary HPT the radionuclide scanning gave true-positive results. Four false-negative and two false-positive scintigrams were obtained. The sensitivity and the positive predictive value (PPV) of scintigraphy were 93 and 97%, respectively. Forty-one cases were correctly localized by the US. Seventeen US results were false negative and five were false positive. The sensitivity and the PPV for US were 71 and 89%, respectively. There was a statistically significant difference between the sensitivity of the scintigraphy compared with the US ( p=0.001). Sensitivities of radionuclide scans and US were higher for adenomas (100 and 83%) than for hyperplastic glands (75 and 40%). The sensitivity of technetium-99m-sestamibi and technetium-99m-pertechnetate subtraction scintigraphy was significantly higher compared with US. This sensitive method could help surgeons in performing a rapid and directed parathyroidectomy.     

Liver X receptors orchestrate osteoblast/osteoclast crosstalk and counteract pathologic bone loss

Osteoporosis is characterized by enhanced differentiation of bone‐resorbing osteoclasts, resulting in a rapid loss of functional trabecular bone. Bone‐forming osteoblasts and osteoblast‐derived osteocytes perform a key role in the regulation of osteoclast development by providing both the pro‐osteoclastogenic cytokine receptor activator of NF‐κB ligand (RANKL) and its natural decoy receptor osteoprotegerin (OPG). By regulating the RANKL/OPG ratio, osteoblasts hence determine the rate of both osteoclast differentiation and bone turnover. Here, we describe a novel role for liver X receptors (LXRs) during the crosstalk of bone‐forming osteoblasts and bone‐resorbing osteoclasts. By using a system of osteoblast/osteoclast cocultures, we identify LXRs as regulator of RANKL expression and the RANKL/OPG ratio in osteoblasts. Activation of LXRs drastically reduced the RANKL/OPG ratio and interfered with osteoblast‐mediated osteoclast differentiation in vitro. During an ovariectomy (OVX)‐induced model of postmenopausal osteoporosis, the application of an LXR agonist shifted the RANKL/OPG ratio in vivo, ameliorated the enhanced osteoclast differentiation, and provided complete protection from OVX‐induced bone loss. These results reveal an unexpected involvement of LXRs in the regulation of bone turnover and highlight a potential role for LXRs as novel targets in the treatment of osteoporosis and related diseases. © 2012 American Society for Bone and Mineral Research.     

Estrogen receptor α CA dinucleotide repeat polymorphism is associated with rate of bone loss in perimenopausal women and bone mineral density and risk of osteoporotic fractures in postmenopausal women

Summary The association between a newly identified CA repeat polymorphism of the estrogen receptor alpha gene (ESR1) with osteoporosis was investigated. Postmenopausal women with <18 CA repeats had low BMD, increased rate of bone loss and increased fracture risk. Introduction Studies have shown that intronic dinucleotide repeat polymorphisms in some genes are associated with disease risk by modulating mRNA splicing efficiency. D6S440 is a newly identified intronic CA repeat polymorphism located downstream of the 5’-splicing site of exon 5 of ESR1. Methods The associations of D6S440 with bone mineral density (BMD), rate of bone loss and fracture risk were evaluated in 452 pre-, 110 peri- and 622 postmenopausal southern Chinese women using regression models. Results Post- but not premenopausal women with less CA repeats had lower spine and hip BMD. The number of CA repeats was linearly related to hip BMD in postmenopausal women (β = 0.008; p = 0.004). Postmenopausal women with CA repeats <18 had higher risks of having osteoporosis (BMD T-score<−2.5 at the spine: OR 2.46, 95% CI 1.30–4.65; at the hip: OR 3.79(1.64–8.74)) and low trauma fractures (OR 2.31(1.29–4.14)) than those with ≥18 repeats. Perimenopausal women with <18 CA repeats had significantly greater bone loss in 18 months at the hip than those with ≥18 repeats (−1.96% vs. −1.61%, p = 0.029). Conclusions ESR1 CA repeat polymorphism is associated with BMD variation, rate of bone loss and fracture risk, and this may be a useful genetic marker for fracture risk assessment. Funding Source: This project is supported by CRCG Grant, Bone Health Fund, Matching Grant and Osteoporosis and Endocrine Research Fund of the University of Hong Kong.     

Early results after minimal lobectomy for benign nodular goiter

Following traditional operations (enucleation and subtotal resection) for benign nodular goiters recurrences may develop. Reoperations for this condition can cause complications, such as hypoparathyroidism and damage of the recurrent laryngeal nerve. That is why total thyroidectomy is recommended by many specialists in benign thyroid disease. We performed lobectomy on one side, and, if necessary, partial resection on the other side. Lobectomy was performed on one side in 31 cases, with partial resections on the other side in 73 patients. We tried to identify the parathyroid glands and both recurrent laryngeal nerves. Postoperative complications were evaluated. Temporary dysfunction of the recurrent laryngeal nerve was detected in 2.3%, permanent damage in 1.1%. Temporary hypocalcaemia developed in 16.4%, permanent hypocalcemia in 1.9%. Two reoperations were necessary for bleeding. Because of the low postoperative complication rate we recommend this method as an alternative to thyroidectomy for benign nodular goiters. We know that our favourable results can be compared with traditional subtotal resection and thyroidectomy when long term results of thyroid function and data about nodular recurrences will be collected.