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Biomedical subjects

S W Li

Publications and source records attributed to S W Li.

At least 19 recordsLinked to original sources

Controllable preparation of monodisperse O/W and W/O emulsions in the same microfluidic device.

This letter presents a simple way to prepare monodisperse O/W and W/O emulsions in the same T-junction microfluidic device just by changing the wetting properties of the microchannel wall with different surfactants. Highly uniform droplets ranging from 50 to 400 mum with a polydispersity index (sigma) value of less than 2% were successfully prepared. With the change in surfactants and surfactant concentrations, the interfacial tension and the wetting properties varied, and disordered or ordered two-phase flow patterns could be controllable. Monodisperse O/W and W/O emulsions were prepared under the action of a cross-flowing shear force or a perpendicular shear force by using an oil solution with 0.1-2.0 wt % Span 80 and an aqueous solution with 0.1-2.0 wt % Tween 20 as a continuous-phase flow, respectively. It gives a controllable method of preparing O/W and W/O emulsions in the same microfluidic device.

Emulsions↗

Audit of phlebotomy turnaround time in a private hospital setting.

An audit on the turnaround time (TAT) of a hospital phlebotomy service was undertaken to assess whether or not the existing service standards can satisfy the needs and expectations of both the external and internal customers. A job request survey form was designed and implemented in June 2005 to be used by the day shift to record the number of phlebotomy cases and the corresponding TAT. The success rate and complaints related to phlebotomy were also recorded. Phlebotomists provided the data for this study on an honor system basis. Out of 2,118 test requests received by the laboratory, 1,867 (88.1 percent) were phlebotomy requests. Approximately 62 phlebotomy requests were recorded, on average, per day shift. The average time, expressed in mean +/- standard deviation (SD) needed for response, arrival, and job completion was 7.4 +/- 1.5 minutes, 5.6 +/- 1.6 minutes, and 10.4 +/- 2.4 minutes respectively, with an average overall TAT of 23.4 +/- 4.1 minutes per phlebotomy request. The success rate at first phlebotomy attempt was 97 percent, and only one complaint was received during the audit period. This study may help hospital management identify possible bottlenecks that delay phlebotomy TAT, thus improving service standards in this area.

Hong Kong↗

Validation of the Chinese Challenging Behaviour Scale: clinical correlates of challenging behaviours in nursing home residents with dementia.

BACKGROUND: Behavioural and psychological symptoms of dementia (BPSD) are associated with considerable burden to patients with dementia and their caregivers. Formal caregivers in residential care settings face different challenges when delivering care. OBJECTIVE: This study aimed at assessing the clinical correlates of challenging BPSD using the Chinese version of the Challenging Behaviour Scale (CCBS) designed for residential care settings. METHODS: One hundred and twenty-five participants were recruited from three care-and-attention homes in Hong Kong. The CCBS was administered together with the Cantonese version of Mini-Mental State Examination (MMSE), Clinical Dementia Rating (CDR), Disability Assessment for Dementia (DAD) and Neuropsychiatric Inventory (NPI) to explore the relationships between challenging behaviour and important clinical correlates. RESULTS: The CCBS had good internal consistency (alpha = 0.86), inter-rater (ICC = 0.79) and test-retest reliability (ICC = 0.98). A four-factor structure is demonstrated by factor analysis: hyperactivity behaviours, hypoactivity behaviours, verbally aggressive and aberrant behaviours. Challenging behaviours were associated with male gender, cognitive impairment, functional disability, neuropsychiatric symptoms, and higher caregiver's workload. CONCLUSIONS: The CCBS is a valid and reliable measure to assess BPSD in residential care settings in local Chinese community. It is useful in evaluating the challenges faced by formal caregivers during daily care of the dementia patients.

Aged↗

Shear force induced monodisperse droplet formation in a microfluidic device by controlling wetting properties.

Perpendicular flow is used to induce oil droplet breakup by using a capillary as water phase flow channel. It is a new route to produce monodisperse emulsions. The wetting properties of the fluids on the walls are exceedingly important parameters. Depending on the oil and water flow rates, different spatial distributions of the two phases as laminar, plugs, cobbles and drops, are obtained. The effects of two-phase flow rates on plugs and drop size are studied, and the different droplet formation mechanisms of plug flow and drop flow are discussed. Two quantitative equations utilized to predict the droplet size are developed.

Emulsions↗

Abnormal response to physical activity in femurs after heterozygous inactivation of one allele of the Col2a1 gene for type II collagen in mice.

The objective of this study was to evaluate the influence of heterozygous inactivation of one allele of the type II collagen gene (Col2a1) on biomechanical properties and mineral density of bone under physical loading conditions. C57BL/6-TGN mice with heterozygous knockout (HZK) inactivation of Col2a1 gene and their nontransgenic littermate controls were housed in individual cages with running wheels for 9 and 15 months. The running activity of each mouse was monitored continuously throughout the experiment. Bone mineral density (BMD) of mice femora was measured using dual-energy X-ray absorptiometry (DXA) and peripheral quantitative computerized tomography (pQCT). Biomechanical properties were determined using three-point bending tests. Vertebral bone samples were prepared for quantitative polarized light microscopy and digital densitometry of proteoglycans. The concentration of total collagen and collagen cross-links were analyzed using high-performance liquid chromatograpy (HPLC). The average daily running distance was shorter for the HZK mice between the age of 4 and 15 months as compared with normal runners (P < 0.05). The ultimate breaking force was 14.8% and 23.6% (9 vs. 15 months) lower in HZK-runners than in wild-type runners. BMD of the femur was 6.1% lower in HZK-runners at the age of 9 months (P < 0.05). Physical activity increased cortical BMD in wild-type runners but not in the HZK runners at the age of 9 months. The collagen network of the HZK mice was less organized. There were only minor changes in BMD and mechanical and structural properties between sedentary HZK mice and their wild-type controls. Increased physical activity induced significantly lower bone density, mechanical properties, and organization of collagen fibers in male HZK mice. However, there were no major differences in biomechanical parameters between sedentary HZK and wild-type male mice. This suggests an important guiding role of collagen type II in bone remodelling and maturation.

Animals↗

Parent training: experience of the New Territories West School Health Promotion Project of Hong Kong.

Parents' participation in school life is an important element of a health-promoting school. To maximize the potential of parents as partners in health education and take on a leading role in promoting health in the school, family and community, a parental health education programme using the empowerment model had been launched in partnership between academic and health sectors. A total of 28 parents selected from eight schools in the New Territories West region of Hong Kong participated in the programme. Evaluation of the programme revealed that the programme had matched well with the expectation of most participants. All respondents had reported an increase in health awareness and knowledge, and confidence to promote health concepts in familiar environments, such as the home and school. They also showed interest to participate in further training in health related issues. Parental health education is recommended to enhance active involvement for building a greater sense of belonging and to put through individual empowerment to community empowerment. Parental involvement in school health promotion would be an effective way to facilitate the paradigm shift.

Adult↗

Premature vertebral endplate ossification and mild disc degeneration in mice after inactivation of one allele belonging to the Col2a1 gene for Type II collagen.

STUDY DESIGN: Skeletal tissues of mice with an inactivated allele of the Col2a1 gene for Type II collagen ("heterozygous knockout") were studied. OBJECTIVE: To determine whether a heterozygous inactivation of the Col2a1 gene has a role in the etiology of spine disorders such as disc degeneration. SUMMARY OF BACKGROUND DATA: Mutations in the COL2A1, COL11A1, COL11A2, and COL9A2 genes have been linked to spine disorders. However, the mechanism by which genetic factors lead to disc degeneration still are largely unknown. METHODS: Spine tissues were studied using radiograph analyses; conventional, quantitative, and polarized light microscopy; immunohistochemistry for the major extracellular components, and in situ hybridization for procollagens alpha1(I) and alpha1(II). Voluntary running activity also was monitored in half of the mice. RESULTS: As the findings showed, 1-month-old heterozygous knockout mice had shorter limb bones, skulls, and spines, as well as thicker and more irregular vertebral endplates, which calcified earlier than in the control mice. They also had a lower concentration of glycosaminoglycans in the anulus fibrosus, in the endplates, and in the vertebral bone than the controls. These features in the heterozygous knockout mice were compensated by the age of 15 months. However, the long bones and skulls of the mature heterozygous mice remained shorter than those of the controls. Gene-deficient mice used the running wheel less. However, physical exercise did not induce any marked structural changes in the skeleton. CONCLUSION: Mice with heterozygous knockout of Col2a1 show subtle early skeletal manifestations that bear some resemblance to those of human spine disorders.

Aging↗

3,4-Dihydroxyphenylacetaldehyde and hydrogen peroxide generate a hydroxyl radical: possible role in Parkinson's disease pathogenesis.

3,4-Dihydroxyphenylacetaldehyde (DOPAL) and 3,4-dihydroxyphenylglycolaldehyde (DOPEGAL), the monoamine oxidase (MAO) metabolites of dopamine (DA) and norepinephrine (NE), respectively, are toxic to catecholamine (CA) neurons in vitro and in vivo. DOPEGAL generates a free radical and activates mitochondrial permeability transition, a mechanism implicated in neuron death. To determine if DOPAL and other DA metabolites generate the hydroxyl radical in the presence of H(2)O(2), we used HPLC-EC to detect salicylate hydroxylation products. To determine the relative reducing capacity of DOPAL and DOPEGAL we used cyclic voltammetry to measure their reduction potentials. Results indicate that DOPAL, but not DOPEGAL, DA or other DA metabolites, generates hydroxyl radicals. Atomic absorption spectroscopy and heavy metal screening indicate that this result is not due to contamination of DOPAL with iron or other heavy metals. DOPAL reduction potential (161 mV) is lower than that of DOPEGAL (235 mV). DOPAL is present in human substantia nigra. The implications of these findings to CA neuronal death in degenerative brain diseases are discussed.

3,4-Dihydroxyphenylacetic Acid↗

Selective dopaminergic vulnerability: 3,4-dihydroxyphenylacetaldehyde targets mitochondria.

Parkinson's disease (PD) is a major cause of age-related morbidity and mortality, present in nearly 1% of individuals at ages 70-79 and approximately 2.5% of individuals at age 85. L-DOPA (L-dihydroxyphenylalanine), which is metabolized to dopamine by dopa decarboxylase, is the primary therapy for PD, but may also contribute to disease progression. Association between mitochondrial dysfunction, monoamine oxidase (MAO) activity, and dopaminergic neurotoxicity has been repeatedly observed, but the mechanisms underlying selective dopaminergic neuron depletion in aging and neurodegenerative disorders remain unclear. We now report that 3,4-dihydroxyphenylacetaldehyde (DOPAL), the MAO metabolite of dopamine, is more cytotoxic in neuronally differentiated PC12 cells than dopamine and several of its metabolites. In isolated, energetically compromised mitochondria, physiological concentrations of DOPAL induced the permeability transition (PT), a trigger for cell death. Dopamine was > 1000-fold less potent. PT inhibitors protected both mitochondria and cells against DOPAL. Sensitivity to DOPAL was reduced > or = 30-fold in fully energized mitochondria, suggesting that mitochondrial respiration may increase resistance to PT induction by the endogenous DOPAL in the substantia nigra. These data provide a potential mechanism of action for L-DOPA-mediated neurotoxicity and suggest two potentially interactive mechanisms for the selective vulnerability of neurons exposed to dopamine.

3,4-Dihydroxyphenylacetic Acid↗

Transgenic mice with inactive alleles for procollagen N-proteinase (ADAMTS-2) develop fragile skin and male sterility.

Transgenic mice were prepared with inactive alleles for procollagen N-proteinase (ADAMTS-2; where ADAMTS stands for a disintegrin and metalloproteinase with thrombospondin repeats). Homozygous mice were grossly normal at birth, but after 1-2 months they developed thin skin that tore after gentle handling. Although the gene was inactivated, a large fraction of the N-propeptides of type I procollagen in skin and the N-propeptides of type II procollagen in cartilage were cleaved. Therefore the results suggested the tissues contained one or more additional enzymes that slowly process the proteins. Electron microscopy did not reveal any defects in the morphology of collagen fibrils in newborn mice. However, in two-month-old mice, the collagen fibrils in skin were seen as bizarre curls in cross-section and the mean diameters of the fibrils were approx. half of the controls. Although a portion of the N-propeptides of type II procollagen in cartilage were not cleaved, no defects in the morphology of the fibrils were seen by electron microscopy or by polarized-light microscopy. Female homozygous mice were fertile, but male mice were sterile with a marked decrease in testicular sperm. Therefore the results indicated that ADAMTS-2 plays an essential role in the maturation of spermatogonia.

Alleles↗

Catecholamine monoamine oxidase a metabolite in adrenergic neurons is cytotoxic in vivo.

3,4-Dihydroxyphenylglycolaldehyde is the monoamine oxidase-A metabolite of two catecholamine neurotransmitters, epinephrine and norepinephrine. This aldehyde metabolite and its synthesizing enzymes increase in cell bodies of catecholamine neurons in Alzheimer's disease. To test the hypothesis that 3,4-dihydroxyphenylglycolaldehyde, but not epinephrine or its major metabolite 4-hydroxy-3-methoxyphenylglycol, is a neurotoxin, we injected 3,4-dihydroxyphenylglycolaldehyde onto adrenergic neurons in the rostral ventrolateral medulla. Injections of epinephrine or 4-hydroxy-3-methoxyphenylglycol were made into the same area of controls. A dose response and time study were performed. Adrenergic neurons were identified by their content of the epinephrine synthesizing enzyme, phenylethanolamine N-methyltransferase, immunohistochemically. Apoptosis was evaluated by in situ terminal deoxynucleotidyl-transferase mediated dUTP nick end label staining. Injection of 3,4-dihydroxyphenylglycolaldehyde in amounts as low as 50 ng results in loss of adrenergic neurons and apoptosis after 18 h. The degree of neurotoxicity is dose and time dependent. Doses of 3,4-dihydroxyphenylglycolaldehyde 10-fold higher produce necrosis. Neither epinephrine nor 4-hydroxy-3-methoxyphenylglycol are toxic. A 2.5 microg injection of 3,4-dihydroxyphenylglycolaldehyde is toxic to cortical neurons but not glia. Active uptake of the catecholamine-derived aldehyde into differentiated PC-12 cells is demonstrated. Implications of these findings for catecholamine neuron death in neurodegenerative diseases are discussed.

Aldehydes↗

Targeted disruption of Col11a2 produces a mild cartilage phenotype in transgenic mice: comparison with the human disorder otospondylomegaepiphyseal dysplasia (OSMED).

Transgenic mice were prepared by homologous recombination with a Col11a2 targeting gene in which an inverted neomycin-resistant gene was inserted between restriction sites in exons 27 and 28. The targeted allele was transcribed in shortened mRNAs, which could be detected by Northern blotting. However, translation of the full-length Col11a2 chain was unable to occur because of the presence of premature termination codons within the inverted neomycin-resistant gene. Analysis of pepsin-resistant collagen chains from rib cartilage of homozygous mice demonstrated the lack of synthesis of intact alpha2(XI) chains. However, pepsin-resistant collagen chains of either alpha1(XI) or alpha1(V) were still detected on sodium dodecyl sulfate polyacrylamide gel electrophoresis. Therefore, alpha2(XI) chains are not essential for the assembly of some molecular forms of triple-helical type V/XI collagen. The phenotype was milder than in the cho/cho mouse in which, as the result of mutation, translation of the full-length alpha1(XI) chain fails to occur and the mice die at birth (Li et al., 1995). Homozygous mice without expression of an alpha2(XI) chain had a smaller body size, receding snouts, and deafness. Nasal bones in the homozygous transgenic mice were specifically shorter and dimpled on their external surfaces. Chondrocytes in growth plates of all long bones were markedly disorganized and failed to align in columns. Analysis of growth plates from transgenic mice by in situ hybridization showed expression of alpha1(II) and alpha1(XI) but not of alpha1(I) or alpha1(V) which, in contrast, were expressed in the developing bone and in the bone collar. Expression of alpha1(X) specifically in the hypertrophic cartilage was observed in normal and transgenic mice. No obvious osteoarthritis was observed throughout the life of homozygous mice up to 1 year of age, although minor morphologic anomalies in the articular cartilages were discernible. The mild phenotype is consistent with similar mutations in the COL11A2 gene seen in patients with nonocular Stickler syndrome and some patients with otospondylomegaepiphyseal dysplasia (OSMED), as well as in patients with a nonsyndromic form of deafness called DFNA13.

Animals↗

A double-blind randomised comparison of risperidone and haloperidol in the treatment of behavioural and psychological symptoms in Chinese dementia patients.

BACKGROUND: Behavioural and psychological symptoms (BPSD) are common during the course of dementia and present severe problems to patients and their caregivers. OBJECTIVES: To assess the therapeutic efficacy and safety of haloperidol and risperidone in treating BPSD in Chinese dementia patients. METHODS: A 12-week double-blind randomised comparison of haloperidol and risperidone treatments was conducted in 58 patients with DSM-IV diagnosis of dementia of Alzheimer's type or vascular dementia. They were randomly assigned to receive flexible doses (0.5 to 2 mg/day) of haloperidol or risperidone. Clinical response was evaluated using the Cohen-Mansfield Agitation Inventory (CMAI), the Behavioral Pathology in Alzheimer's Disease Rating Scale (BEHAVE-AD), Simpson-Angus Scale, Functional Assessment Staging and Cantonese version of the Mini-Mental State Examination. RESULTS: The mean doses at the last week were 0.90 mg/day of haloperidol and 0.85 mg/day of risperidone. Both haloperidol and risperidone significantly reduced the severity of BPSD (scores on CMAI and BEHAVE-AD), with no significant between-group differences. Haloperidol-treated patients showed a worsening on Simpson-Angus scale while there was no significant change in this measure in risperidone-treated patients. CONCLUSIONS: Low-dose haloperidol and risperidone were well tolerated and associated with reductions in the severity and frequency of behavioural symptoms in subjects with dementia. Risperidone may have a more favourable risk-benefit profile in view of its lower propensity to induce extrapyramidal symptoms.

Aged↗

Agitation in Chinese elderly: validation of the Chinese version of the Cohen-Mansfield Agitation Inventory.

The reliability and validity of the Chinese version of the Cohen-Mansfield Agitation Inventory (CCMAI) were studied in 164 demented patients. The agitation pattern in Chinese elderly was also examined in this study. The CCMAI demonstrated high validity, test-retest reliability, and interrater reliability. Eighty-five percent of demented patients manifested one or more agitated behaviors at least once a week. Factor analysis yielded three subtypes of agitation: physically aggressive behaviors, physically nonaggressive behaviors, and verbally agitated behaviors. There was a linear upward trend in physical aggression as one progressed from one Global Deterioration Scale stage to the next. Community-living patients showed higher physically nonaggressive and verbally agitated behaviors, whereas institution residents exhibited a significantly higher level of physical aggression. The differences between residential and institutionalized patients need further research. Future study should focus not only on the behavioral disturbances; medical, psychological, and environmental factors should be taken into account to provide a more accurate profile.

Aged↗

More knee joint osteoarthritis (OA) in mice after inactivation of one allele of type II procollagen gene but less OA after lifelong voluntary wheel running exercise.

OBJECTIVE: To investigate the incidence and severity of osteoarthritis (OA) and the effects of voluntary wheel running in normal mice and mice carrying either a targeted inactivation of one allele, heterozygous 'knockout', of Col2a1 gene or both alleles, homozygous 'knockout', of Col11a2 gene. METHODS: Mice lived until 15 months of age in individual cages. Running activity was recorded around the clock. OA changes were evaluated from serial knee joint sections by light microscopy. RESULTS: Heterozygous inactivation of Col2a1 gene coding for type II procollagen made the cartilage more susceptible to OA. At 15 months of age, OA prevalence was 60-90% in knockouts and 20-45% in normal controls (P < 0.01-0.001). Unexpectedly, a reduction of OA due to wheel running was observed in both knockout strains (P< 0.05-0.01). This effect was most evident in the femoral condyles. Incidence of OA in runners was approximately 50-85% of that in sedentary littermates. OA prevalence was higher in normal control and runner mice with high body weight. Running did not affect OA development in normal mice. CONCLUSION: Heterozygous knockout of Col2a1 gene increased the OA prevalence in mice. Lifelong voluntary wheel running had a protective effect against OA in both knockout mice lines. The reason for this remains unknown. Reduction of OA may result from the reorganization and strengthening of the articular cartilage collagen network and/or adjacent muscles due to running, or lower body weight. Increased compliance of the articular cartilage and bones of the knockout mice may also contribute to the reduction of OA in exercised animals.

Aging↗

Inactivation of one allele of the type II collagen gene alters the collagen network in murine articular cartilage and makes cartilage softer.

OBJECTIVE: To evaluate the influence of inactivation of one allele ("heterozygous knockout" or "heterozygous inactivation") of the type II procollagen gene (Col2a1) on the biomechanical properties and structure of the articular cartilage and subchondral bone in 15 month old mice. METHODS: Indentation stiffness of the humerus head articular cartilage was measured by a microindentation method. Cartilage and subchondral bone were prepared for digital densitometry of proteoglycans (PGs), polarised light microscopy (PLM) of collagen, and osteoarthrosis (OA) grading. RESULTS: Heterozygous inactivation of the Col2a1 gene softened articular cartilage (p=0.002) as measured by indentation stiffness ((mean (SEM) 0.50 (0.07) MPa v 0.94 (0.13) MPa in controls). Fibrillar collagen network exhibited lower birefringence in the intermediate (p=0.04) and deep zones (p=0.01) of cartilage by PLM, indicating either decreased collagen content or a lower degree of fibril parallelism in the knockout mice. The total and zonal thicknesses of articular cartilage were unchanged. Zonal PG contents did not differ significantly. In knockout mice, the prevalence of superficial fibrillation-that is, a sign of OA, was higher than in controls (73% v 21%, p=0.002). The collagen induced birefringence of the superficial zone was not reduced. The subchondral bone volume fraction was lower in knockout mice than in controls, 31% v 43% (p=0.01), and optical retardation values in PLM of bone collagen were slightly but significantly lower (p=0.01). CONCLUSION: Heterozygous inactivation of the Col2a1 gene made articular cartilage softer, altered the collagenous network, reduced subchondral bone volume, and altered its microstructure. Changes in the cartilage collagen network probably contributed to increased susceptibility to OA.

Animals↗

Expression of lipopolysaccharide binding protein and its receptor CD14 in experimental alcoholic liver disease.

AIM: To evaluate the relationship between the expression of lipopolysaccharides (LPS) binding protein (LBP) and CD14 mRNA and the severity of liver injury in alcohol-fed rats. METHODS: Twenty Wistar rats were divided into two groups:ethanol-fed group (group E) and control group (group C). Group E was fed with ethanol(5-12 g x kg(-1) x d(-1)) and group C received dextrose instead of ethanol. Rats of the two groups were sacrificed at 4 weeks and 8 weeks. Levels of endotoxin and alanine transaminase (ALT) in blood were measured, and liver pathology was observed under light and electronic microscopy. Expressions of LBP and CD14 mRNA in liver tissues were determined by RT-PCR analysis. RESULTS: Plasma endotoxin levels were increased more significantly in group E(129+/-21) ng x L(-1) and (187+/-35) ng x L(-1) at 4 and 8 wk than in control rats(48+/-9) ng x L(-1) and (53+/-11) ng x L(-1), respectively (P<0.05). Mean values of plasma ALT levels were (1867+/-250) nkat x L(-1) and (2450+/-367) nkat x L(-1) in Group E. The values were increased more dramatically in ethanol-fed rats than in Group C after 4 and 8 weeks. In liver section from ethanol-fed rats, there were marked pathological changes (steatosis, cell infiltration and necrosis). In ethanol-fed rats, ethanol administration led to a significant increase in LBP and CD14 mRNA levels compared with the control group (P<0.05). CONCLUSION: Ethanol administration led to a significant increase in endotoxin levels in serum and LBP and CD14 mRNA expressions in liver tissues. The increase of LBP and CD14 mRNA expression might wake the liver more sensitive to endotoxin and liver injury.

Acute-Phase Proteins↗