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Biomedical subjects

K S Leung

Publications and source records attributed to K S Leung.

At least 19 recordsLinked to original sources

Epimedium-derived phytoestrogen exert beneficial effect on preventing steroid-associated osteonecrosis in rabbits with inhibition of both thrombosis and lipid-deposition.

OBJECTIVES: This study tested the effect of Epimedium-derived phytoestrogen (PE) on preventing steroid-associated osteonecrosis (ON) in rabbit model. METHODS: Thirty 28-week-old male New-Zealand white rabbits were divided into control group (CON; n=14) and PE group (PE; n=16; 5 mg/kg body weight/day) after receiving an established inductive protocol for inducing steroid-associated ON. Before and after inductive protocol, Dynamic-MRI was employed on bilateral femora for local intra-osseous perfusion, blood samples were examined for coagulation, fibrinolysis and lipid-transportation, and marrow samples were quantified for adipogenesis-gene mRNA expression. Six weeks later, bilateral femora were dissected for Micro-CT-based micro-angiography, and then ON lesion, intravascular thrombosis and extravascular fat-cell-size were examined histopathologically. RESULTS: The incidence of ON in the PE group (31%) was significantly lower than that in the CON group (93%). Compared to the CON group, local intra-osseous perfusion was maintained in the PE group. Blocked trunk vessels were seldom found in micro-angiography of the PE-treated rabbits. Thrombosis incidence and fat-cell-size were both significantly lower in the PE group than those in the CON group. During the early period after induction, indicator of coagulation, fibrinolysis, lipid-transportation and adipogenesis-gene expression were found with significantly changing pattern in the PE group compared to the CON group. CONCLUSION: PE was able to exert beneficial effect on preventing steroid-associated ON in rabbits with inhibition of both thrombosis and lipid deposition.

Adrenal Cortex Hormones↗

Multiple bioimaging modalities in evaluation of an experimental osteonecrosis induced by a combination of lipopolysaccharide and methylprednisolone.

AIMS: The present study employed both static and dynamic imaging modalities to study both intra- and extravascular events attributing to steroid-associated osteonecrosis (ON) using an experimental protocol with a single low-dose lipopolysaccharide (LPS) injection and subsequently three injections of high-dose methylprednisolone (MPS). METHODS: Fourteen 28-week-old male New Zealand white rabbits received one intravenous injection of LPS (10 microg/kg). 24 h later, three injections of 20 mg/kg of MPS were given intramuscularly at a time interval of 24 h. Additional 6 rabbits were used as controls. Dynamic MRI was performed on bilateral femora for local intraosseous perfusion before and after LPS injection. Blood samples were collected for hematological examinations before and after LPS injection. Bilateral femora were dissected and decalcified for microCT-based microangiography. ON lesion, intravascular thrombus and extravascular marrow fat cell size were examined histopathologically. RESULTS: Intravascular thrombus was observed in all ON rabbits. Extravascular marrow fat cell size was significantly increased in ON rabbits than that of the controls (P<0.05). Compared to baseline, a significant decrease in ratio of tissue-type plasminogen activator/plasminogen activator inhibitor 1, activated partial thromboplatin time and a significant increase in ratio of low-density lipoprotein/high-density lipoprotein were only found in ON rabbits (P<0.05). Dynamic MRI showed a significant decrease in the perfusion index 'maximum enhancement' in the ON rabbits (P<0.05), and microCT-based microangiography showed blocked stem vessels in ON samples. Overall, 93% of the rabbits (13/14) developed ON, and no rabbits died throughout the experiment period. CONCLUSION: Both intra- and extravascular events were found attributing to the steroid-associated ON based on our experimental protocol with a single low-dose LPS injection and subsequent three injections of high-dose MPS. Both high ON incidence and no mortality in rabbits treated with this inductive protocol suggested its effectiveness for future studies on evaluation of therapeutic efficacy of interventions developed for prevention of steroid-associated ON.

Animals↗

In vivo measurements of macular and nerve fibre layer thickness in retinal arterial occlusion.

AIM: To investigate the structure-function relationship in patients with retinal arterial occlusion by measuring the macular and the peripapillary retinal nerve fibre layer (RNFL) thickness and the visual sensitivity. METHODS: This is an observational case series with three patients with central retinal arterial occlusion (CRAO) and two patients with branch retinal arterial occlusion (BRAO). The macular/peripapillary RNFL thickness and the visual field were measured with Stratus optical coherence tomography (OCT) and Humphrey visual field analyzer, respectively, at least 1 year after the diagnosis of CRAO or BRAO. RESULTS: The macular thickness, in particular the inner retinal layer, and the peripapillary RNFL thickness were reduced in patients with retinal arterial occlusion. The decrease in the macular and the peripapillary RNFL thickness corresponded to the sites of retinal arterial occlusion with diffuse and segmental thinning found in CRAO and BRAO, respectively. Visual field defects were found in the corresponding locations of macular and RNFL thinning, and closely correlated with the degree of the structural damage. CONCLUSIONS: Structural damages in terms of reduction in the macular and peripapillary RNFL thickness were evident in patients with retinal arterial occlusion. A close structure-function correlation was found and a worse functional outcome is associated with a more extensive thinning of the macula and RNFL. OCT measurements of the macular/peripapillary RNFL thickness provide useful indicators to reflect the severity of the disease in retinal arterial occlusion and serve as a new paradigm to study and monitor the disease longitudinally.

Adult↗

Flavonoids derived from herbal Epimedium Brevicornum Maxim prevent OVX-induced osteoporosis in rats independent of its enhancement in intestinal calcium absorption.

AIM: Factorial design was used to test our hypothesis whether a group of flavonoids (FE) derived from herbal Epimedium Brevicornum Maxim exerted its preventive effects on estrogen-deficiency-induced osteoporosis mainly through an enhancement in intestinal calcium absorption. MATERIALS AND METHODS: Forty-five 12-month-old female Wistar rats were used and randomly assigned into sham-operated group and four ovariectomy (OVX) subgroups, i.e. OVX with vehicle (OVX group), OVX with FE (FE group), OVX with calcium supplement (CS group), and OVX with FE and CS (FE + CS group). Daily oral administration of FE (10 mg/kg/day) and/or CS (56 mg/kg/day) started on day 4 after OVX for 12 weeks. Before sacrificing the animals, urine and serum samples were collected for assaying indicators related to intestinal calcium absorption, regulator for calcium homeostasis, and markers of bone turnover. The left proximal femur was dissected for evaluation of the primary end-point (failure force), the second end-points (pQCT-quantified densitometry, geometry, and micro-CT-quantified 3-D trabecula micro-architecture), and pQCT-defined cross-sectional envelope. RESULTS: FE was found to be able to prevent OVX-induced reduction in failure force as well as the above second end-points, without resulting in an increased uterus weight. CS had no preventive effect on OVX-induced reduction in failure force. Two-way factorial interaction analysis between FE and CS showed that the un-enhanced suppression of parathyroid hormone for calcium homeostasis did not provide link between the enhanced intestinal calcium absorption and the enhanced inhibition of bone resorption in the present study. Furthermore, the discrepancies between the enhanced intestinal calcium absorption and the un-enhanced end-point measures as well as anabolic effect were also revealed by the interaction analysis. CONCLUSION: The present study suggested that FE inhibited bone resorption, stimulated bone formation, and accordingly prevented osteoporosis without hyperplastic effect on uterus in the OVX rat model, which was however independent of an enhancement in intestinal calcium absorption.

Animals↗

A prospective case-control study of ankle fracture in postmenopausal women.

OBJECTIVES: To compare bone mineral density of women with postmenopausal ankle fractures with controls and review patient characteristics, injury mechanisms, and outcomes. DESIGN: Prospective case-control study. SETTING: University teaching hospital, Hong Kong. PARTICIPANTS: Women older than 60 years, admitted with ankle fractures between 2002 and 2003 and controls (age-matched women with femoral neck fractures). MAIN OUTCOME MEASURES: Demographic data, bone mineral density, mechanism of injury, fracture pattern, treatment, and the functional outcome. RESULTS: The mean age of the study group (18 ankle fracture patients) was 74 years. The fractures usually resulted from a low-energy trauma; isolated lateral malleolar fracture was the most common (8/18), whilst six had bimalleolar fractures. Their mean T-score bone mineral density values at the spine and hip were -1.67 and -1.70, respectively; corresponding Z-scores were +0.73 and +0.99. The bone mineral density of the study group was significantly higher than in patients with fractured neck of femur (controls) and the general population (P<0.05). Nine of the study group had diabetes and one had impaired glucose tolerance. Treatment comprised casting in 10 patients and operative fixation in seven. Good functional recovery was achieved; most patients were able to resume their premorbid level of independent daily activities with a good motor functional independence score (85.18/91) 1 year post-injury. CONCLUSION: In this case-control study, postmenopausal ankle fractures were not associated with osteoporosis. Diabetic neuropathy may have been a risk factor for such injury. The functional outcome of such patients was generally satisfactory, provided appropriate treatment was given.

Aged↗

Scalable model-based clustering for large databases based on data summarization.

The scalability problem in data mining involves the development of methods for handling large databases with limited computational resources such as memory and computation time. In this paper, two scalable clustering algorithms, bEMADS and gEMADS, are presented based on the Gaussian mixture model. Both summarize data into subclusters and then generate Gaussian mixtures from their data summaries. Their core algorithm, EMADS, is defined on data summaries and approximates the aggregate behavior of each subcluster of data under the Gaussian mixture model. EMADS is provably convergent. Experimental results substantiate that both algorithms can run several orders of magnitude faster than expectation-maximization with little loss of accuracy.

Algorithms↗

Engineered allogeneic chondrocyte pellet for reconstruction of fibrocartilage zone at bone-tendon junction--a preliminary histological observation.

This study examined histologically the potential of using allogeneic cultured chondrocyte pellet (CCP) in enhancing bone-tendon junction (BTJ) healing using a rabbit partial patellectomy model. Chondrocytes isolated from the cartilaginous ribs of 6-week-old New Zealand white rabbits were cultured for 14 days to form CCP. Partial patellectomy was performed on 30 18-week-old rabbits. After removal of the distal third patella, the BTJ gap was repaired surgically with or without CCP interposition. Four samples of patella-patellar tendon complexes (PPTC) for each group were harvested each at 8, 12, and 16 weeks; and two additional PPTC for each group were harvested at 2, 4, and 6 weeks for early observation of fibrocartilage zone regeneration, histologically. Results showed that CCP interposition demonstrated earlier structural integration at the BTJ after 8, 12, and 16 weeks of healing, and formation of a fibrocartilage zone like structure, compared with control specimens. In addition, no immune rejection was observed in CCP experimental group. The results suggested that CCP had a stimulatory effect on BTJ healing. This bioengineering approach might have potential clinical application in treatment of difficult BTJ healing. However, systemic histomorphometric, immunological tests, and biomechanical evaluations are needed before any clinical trials.

Animals↗

A study of trabecular bones in ovariectomized goats with micro-computed tomography and peripheral quantitative computed tomography.

Osteoporotic fractures occur most frequently in trabeculae-rich skeletal sites. The purpose of this study was to use a high-resolution micro-computed tomography (micro-CT) to investigate the changes in trabecular bone microarchitecture and to use a peripheral quantitative computed tomography (pQCT) to study changes in volumetric bone mineral density (BMD) in a large animal model resulted from ovariectomy (OVX). Ten adult goats were used for this study. The first iliac crest biopsy was harvested before OVX and served as baseline; the second biopsy was collected 6 months later from the opposite side for both pQCT and micro-CT measurements. Results showed that after 6 months of OVX, the BMD of the iliac crest biopsies decreased significantly by 16.3% (P < 0.05). The bone volume density (BV/TV), trabecular number (Tb.N), and connectivity density (Conn.D) measured with micro-CT decrease significantly after OVX, with an average decrease of 8.34%, 8.51%, and 18.52% (P < 0.05 each), respectively. The trabecular plate separation (Tb.Sp) was 8.26% (P < 0.05) greater than baseline after OVX. Significant correlations were found between the reduction of BMD and the decreases of BV/TV and Tb.N (r = 0.839 and 0.719, respectively; P< 0.001 both), as well as the increase of Tb.Sp (r = -0.758, P< 0.001) and SMI (r = -0.697, P< 0.001). In conclusion, this was the first experimental study in goat model to show that OVX-induced bone loss in goats was attributed by deterioration of trabecular microarchitecture.

Animals↗

Low intensity pulsed ultrasound stimulates osteogenic activity of human periosteal cells.

The effect of low intensity pulsed ultrasound on human periosteal cells was investigated. Normal human periosteum was obtained to culture the periosteal cells. After characterization, cultures of periosteal cells at Days 2 and 4 were treated with ultrasound for 5, 10, and 20 minutes respectively. Assessments were done to assess total number of viable cells, cell proliferation, alkaline phosphatase activity, osteocalcin secretion, vascular endothelial growth factor expression, and calcium nodule formation. With the cells not treated with ultrasound as the control, the results showed that ultrasound did not affect the total number of viable cells. It stimulated cell proliferation at the early phase of cell culture. The activity of alkaline phosphatase was increased significantly in the culture at Day 4. A similar effect was seen with osteocalcin secretion and the responses were dose-dependent. The vascular endothelial growth factor secretion increased in Day 2 and Day 4 cultures with the dose-dependent effect. Formation of calcium nodules was significantly higher with ultrasound treatment. We think that low intensity pulsed ultrasound stimulated periosteal cell proliferation and differentiation toward osteogenic lineage. The dose-dependent effect on osteogenic activities may modify the existing treatment regimen. Ultrasound treatment should be started from the beginning of fracture healing.

Adult↗

Early magnetic resonance imaging of radiographically occult osteoporotic fractures of the femoral neck.

Osteoporosis is associated with thinning of cortical and trabecular bone, which reduces bone strength and predisposes individuals to fracture development. Femoral neck fractures in patients with osteoporosis may not be apparent on radiographs. Magnetic resonance imaging is useful at detecting these radiographically occult fractures; yet, the practice has not been widely adopted in Hong Kong. In this article, we review our experience of early magnetic resonance imaging in this clinical context--that is, imaging performed within 48 hours of presentation to hospital. Twenty-eight patients (age range, 69-93 years) over a 3-year period were studied. Magnetic resonance imaging revealed radiographically occult neck fractures in 14 (50%) cases (equivalent to 4% of all femoral neck fractures). These fractures were treated surgically (64%) or conservatively (36%) with good bone healing and clinical outcome. When no femoral neck fracture was present, magnetic resonance imaging revealed an alternative cause for symptoms in all 14 cases. We strongly endorse the use of early magnetic resonance imaging for patients with osteoporosis who have a clinically suspected femoral neck fracture that is not visible radiographically.

Aged↗

Acrylamide in Asian foods in Hong Kong.

About 400 food samples, mainly Asian foods available in Hong Kong, were tested for acrylamide by an LC-MS/MS method using [1, 2, 3-(13)C(3)]-acrylamide as surrogate. The acrylamide levels in the more commonly consumed food items in the food groups such as rice and rice products, noodles, bakery and batter-based products, were generally less than 60 microg kg(-1). Higher levels were found in the food groups such as biscuit-related products and crisps. The highest levels were detected in potato crisps (1500-1700 microg kg(-1)). Lower levels were found in rye flour-based crisps (440 microg kg(-1)), followed by corn-based (65 to 230 microg kg(-1)) and wheat flour-based crisps (61-200 microg kg(-1)), and then rice flour-based crisps (15-42 microg kg(-1)). The acrylamide formation during deep frying of a wheat flour-based product, Chinese fried fritter, was studied. Deep-frying at 170 degrees C resulted in gentle but steady rise in acrylamide content. A steep rise for frying at 210 degrees C was recorded. The moisture content of the product decreased with frying time, but the fat content increased. It is proposed that the reaction for the formation of acrylamide was initiated on the surface and then penetrated into the interior of the food matrix by heat transfer via radiation/conduction and diffusion of hot oil.

Acrylamide↗

Interactions between modern and Chinese medicinal drugs: a general review.

While the use of health food and over-the-counter drugs for health promotion and adjuvant therapy is becoming increasingly popular, the concern about adverse effects is mounting. The possible adverse effects that may arise from drug interactions between these herbal preparations and standard modem therapy are equally worrying. Herbal toxicity and adverse effects are well documented in classical Chinese medicinal volumes. Interactions between herbal preparations and standard modem therapy are known. Extensive work needs to be done before useful guidelines can be established. However, based on available reports and clinical observations, some commonly used herbs and Chinese medicines have already demonstrated the need for special attention when used together with modern therapy. This paper analyzes the important material already available, and would serve as a preliminary checklist for patients who are taking herbal preparations, while at the same time receiving treatment from modern medicine.

Animals↗

Baseline BMD and bone loss at distal radius measured by peripheral quantitative computed tomography in peri- and postmenopausal Hong Kong Chinese women.

The current study was designed to investigate the rate of bone loss in distal radius and its association with baseline volumetric bone mineral density (BMD) and years since menopause (YSM) in peri- and postmenopausal women using precise and multislice peripheral quantitative computed tomography (pQCT; Densiscan 2000). Two hundred and five healthy Hong Kong Chinese perimenopausal ( n = 26) and postmenopausal ( n = 179) women within 10 years of the onset of menopause were recruited. Anthropometric parameters and menstrual status were also measured. The linear regression model derived from the baseline volumetric BMD revealed a significant and slightly better correlation with YSM than age, with a YSM-related annual decline of 2.56%, 1.82% and 0.65% in trabecular BMD (tBMD), integral BMD (iBMD) and cortical BMD (cBMD), respectively. Follow-up measurements after a time interval of 12 months showed that the rate of bone loss was higher than the annual decline in BMD calculated from the baseline BMD, with decreases of 2.89%, 2.16% 0.91% in tBMD, iBMD and cBMD, respectively. Baseline BMD was associated with age or YSM ( r ranges from -0.283 to -0.502; p<0.001 in all cases), but no relationship was found between annual rate of bone loss and age or YSM. The rate of bone loss did not correlate with baseline volumetric BMD values or YSM after dividing the subjects into fast bone losers (with annual tBMD loss > or =3%), normal bone losers (with annual tBMD loss > or = 1% but <3%) or slow bone losers (with annual tBMD loss <1%). The rate of bone loss was greater in both trabecular and cortical bone of postmenopausal women within the first 3 menopausal years but was only significant in the iBMD as compared with perimenopausal and postmenopausal women over 7 years after onset of menopause. The percentage distribution of slow and fast bone losers was not found to be associated with YSM. As a total of only 4 fracture cases were documented, the study could not provide conclusive information on whether perimenopausal and early postmenopausal baseline volumetric BMD or rate of bone loss determines the development of osteoporosis or fracture occurrence.

Adult↗

In situ model for studying potassium currents in various growth plate chondrocyte subpopulations.

A new in situ model of partially digested growth plate cartilage suitable for patch clamp study of membrane currents of chondrocytes from various differentiation stages was developed. Thin sections of growth plate were enzyme digested to expose intact membranes of chondrocytes previously covered by extracellular matrix. This treatment dramatically increased the success rate of tight-seal formation from virtually 0% up to 40%. Whole-cell patch clamp recording revealed a delayed outward rectifying current as the major macroscopic current in chondrocytes of all differentiation stages. This current was sensitive to tetraethylammonium chloride and reversed polarity at a membrane potential close to the equilibrium potential of K+. Chondrocytes at resting stage expressed a much smaller K+ current than the proliferative and hypertrophic chondrocytes. When the current amplitudes were normalized for the cell membrane area, proliferative cells expressed a significantly higher outward current density.

Animals↗

Growth plate chondrocytes inhibit neo-angiogenesis -- a possible mechanism for tumor control.

Clinically, tumors seldom grow across the articular cartilage and physeal plate. It is believed that avascular cartilage may inhibit the neo-vascularization of tumor spread. The conditioned medium of growth plate chondrocytes resisted the migration of ECV304 by approximately 41% in invasion assay. Growth plate chondrocytes were shown by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay to have an insignificant effect on the viability of human endothelial cells and fibroblasts. However, the proliferation of human endothelial cells was significantly inhibited by growth plate chondrocytes. The inhibitory activity was up to 35% and specific to endothelial cells. Inhibition of blood vessel formation was also demonstrated in the chick chorioallantoic membrane (CAM) assay. These findings demonstrated that growth plate chondrocytes secrete anti-angiogenesis factor(s) which specifically inhibit both the migration and proliferation of endothelial cells.

Allantois↗

Expression of basic fibroblast growth factor during distraction osteogenesis.

Distraction osteogenesis is a process of tissue regeneration under an external mechanical stimulation. In the study, the spatial and temporal expression patterns of basic fibroblast growth factor in the newly formed osseous tissue during distraction osteogenesis in goats were studied using immunohistochemistry. During the distraction period, the expression of basic fibroblast growth factor was observed in the osteoblasts on the newly formed trabecular bone and the bone formation front. The cells of osteoblastic lineage and the mesenchymal cells in the distraction callus also expressed basic fibroblast growth factor. The expression of basic fibroblast growth factor in the distraction period was stronger than that during the latency and consolidation periods. However, some osteoblasts still were expressing basic fibroblast growth factor in the consolidation periods. According to these results, basic fibroblast growth factor may have a local regulatory role during distraction osteogenesis. The tensile force may stimulate the expression of basic fibroblast growth factor in osteoblasts and other cell types.

Animals↗

Goats as an osteopenic animal model.

A large osteopenic animal model that resembles human osteoporotic changes is essential for osteoporosis research. This study aimed at establishing a large osteopenic animal model in goats. Twenty-five Chinese mountain goats were used in which they were either ovariectomized (OVX) and fed with a low-calcium diet (n = 16) or sham-operated (SHAM; n = 9). Monthly photodensitometric analysis on proximal tibial metaphysis and calcaneus was performed. Two iliac crest biopsy specimens obtained before and 6 months after OVX were used for bone mineral density (BMD) measurement with peripheral quantitative computed tomography (pQCT). Lumbar vertebrae (L2 and L7), humeral heads, and calcanei were collected for BMD measurement after euthanasia. The humeral heads and calcanei were used in biomechanical indentation test. BMD measurement showed a significant 25.0% (p = 0.006) decrease in BMD of the iliac crest biopsy specimens 6 months after OVX. It also was statistically significant when compared with the SHAM (p = 0.028). BMD at L2, L7, calcaneus, and humeral head reduced by 24-33% (p ranged from 0.001 to 0.011) when compared with the SHAM. Photodensitometry showed a continuous decrease in bone density after OVX. There were significant decreases of 18.9% in proximal tibial metaphysis (p = 0.003) and 21.8% in calcaneus (p = 0.023) in the OVX group 6 months postoperatively. Indentation test on the humeral head and calcaneus showed a significant decrease 52% (p = 0.006) and 54% (p = 0.001), respectively, in energy required for displacement of 3 mm in the OVX group compared with the SHAM group. The decreases correlated significantly to the decrease in BMD of the corresponding specimens (r2 = 0.439 and 0.581; p < 0.001 for both). In conclusion, this study showed that OVX plus a low-calcium diet could induce significant osteopenia and deterioration of mechanical properties of the cancellous bone in goats.

Animals↗

TGF-beta1 is the factor secreted by proliferative chondrocytes to inhibit neo-angiogenesis.

Growth plate is an avascular tissue, which has been reported to be capable of retarding tumor spread. It is believed that angiogenic inhibitor(s) exist to inhibit the neo-vascularization of tumor, thus impeding the tumor growth. In this study, growth plate chondrocyte-derived TGFbeta1 was identified to be anti-angiogenic. It was found that growth plate chondrocytes (GPC) secreted TGFbeta1 mostly in latent form as demonstrated by gel filtration and immunoblotting. Enzyme-linked immunosorbent assay (ELISA) was followed to quantify TGFbeta1 in GPC conditioned medium (CM), in which 866 pg/ml of TGFbeta1 was found. Besides, the angiogenesis inhibitory effect of GPC CM was abolished by the addition of anti-TGFbeta1 antibody in the in vitro culture system and the in vivo chick chorioallantoic membrane (CAM) assay. This confirmed the anti-angiogenic properties of chondrocyte-derived TGFbeta1. TGFbeta1 was expressed predominantly in the proliferative zone of porcine growth plate. This explains the low incidence of tumor invasion across the entire growth plate. Also, this helps to explain the observation that tumor invasion across the physis increases with age as the proliferative zone gradually disappears. J. Cell. Biochem. Suppl. 36: 79-88, 2001.

Allantois↗