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Biomedical subjects

B Ho

Publications and source records attributed to B Ho.

At least 19 recordsLinked to original sources
PubMed2006

Endotoxin levels in rural Thai and urban Singaporean homes.

BACKGROUND: Exposure to dust endotoxin and allergens in early childhood may influence the development of allergic diseases. AIMS: This study aimed to evaluate dust endotoxin and dust mite allergens in urban Singapore and rural Thai homes of young children and study potential environmental influences. METHODS: Mattress dust endotoxin and Der p 1, Der f 1, group 2 (Der f 2 and Der p 2) and Blo t 5 allergen levels were quantified in 101 infant mattress dust samples, 51 from urban Singapore and 50 from rural Thailand. Comprehensive questionnaires on the home environment and cleaning practices were completed. RESULTS: Endotoxin levels in rural Thailand were significantly higher than in urban Singapore (geometric mean 26,334.12 +/- 4.60 and 18,377.85 +/- 2.52 endotoxin units/g, respectively; p = 0.032). In contrast, higher levels of Der f 1 (p = 0.02), group 2 (p < 0.01) and Blo t 5 (p < 0.01) allergens were found in Singapore homes compared with rural Thai homes. Multiple logistic regression analysis showed that the use of detergents (p = 0.001) and disinfectants (p = 0.024) to clean floors and mattress protectors (p = 0.021) were independently associated with lower endotoxin levels. CONCLUSION: Endotoxin levels are higher in rural compared with urban homes in South East Asia. The reverse was true for dust mite allergen levels. Certain identifiable home environmental conditions and practices accounted for the differences in endotoxin levels.

Air Pollution, Indoor↗
PubMed2006

The specificity of Sushi peptides for endotoxin and anionic phospholipids: potential application of POPG as an adjuvant for anti-LPS strategies.

Sushi peptides [S1 (Sushi 1 peptide) and S3] are derived from the LPS (lipopolysaccharide; also known as endotoxin)-binding domains of an LPS-sensitive serine protease, Factor C, from the horseshoe crab (Carcinoscorpius rotundicauda). S1 and S3 interact at high affinity with LPS. The intermolecular disulphide bonding in the S3 dimer is indispensable for its LPS binding, disruption and consequent neutralization. Simultaneously, the specific interaction between the Sushi peptides and bacterial membrane phospholipids further explains the selective propensity of these peptides for the gram-negative bacteria. Our findings yield insights into a complex molecular paradigm in which the juxtaposition of LPS molecules and the anionic phospholipid POPG (1-palmitoyl-2-oleoyl phosphatidylglycerol) on the bacterial outer membrane confers such interfacial properties which create the optimal environment for the interaction between the peptides and bacterial membrane lipids.

Adjuvants, Pharmaceutic↗
PubMed2005

Spatial and temporal coordination of expression of immune response genes during Pseudomonas infection of horseshoe crab, Carcinoscorpius rotundicauda.

Knowledge on how genes are turned on/off during infection and immunity is lacking. Here, we report the co-regulation of diverse clusters of functionally related immune response genes in a horseshoe crab, Carcinoscorpius rotundicauda. Expressed sequence tag (EST) clusters for frontline immune defense, cell signalling, apoptosis and stress response genes were expressed or repressed spatio-temporally during the acute phase of Pseudomonas infection. An infection time course monitored by virtual Northern evaluation indicates upregulation of genes in blood cells (amebocytes) at 3-h postinfection, whereas most of the hepatopancreas genes remained down regulated over 72 h of infection. Thus, the two tissues orchestrate a coordinated and timely response to infection. The hepatopancreas probably immuno-modulates the expression of other genes and serves as a reservoir for later response, if/when chronic infection ensues. On the other hand, being the first to encounter pathogens, we reasoned that amebocytes would respond acutely to infection. Besides acute transactivation of the immune genes, the amebocytes maintained morphological integrity, indicating their ability to synthesise and store/secrete the immune proteins and effectors to sustain the frontline innate immune defense, while simultaneously elicit complement-mediated phagocytosis of the invading pathogen. Our results show that the immune response against Pseudomonas infection is spatially and temporally coordinated.

Animals↗
PubMed2004

De novo design of potent antimicrobial peptides.

Lipopolysaccharide (LPS), shed by gram-negative bacteria during infection and antimicrobial therapy, may lead to lethal endotoxic shock syndrome. A rational design strategy based on the presumed mechanism of antibacterial effect was adopted to design cationic antimicrobial peptides capable of binding to LPS through tandemly repeated sequences of alternating cationic and nonpolar residues. The peptides were designed to achieve enhanced antimicrobial potency due to initial bacterial membrane binding with a reduced risk of endotoxic shock. The peptides designed displayed binding affinities to LPS and lipid A (LA) in the low micromolar range and by molecular modeling were predicted to form amphipathic beta-hairpin-like structures when they bind to LPS or LA. They also exhibited strong effects against gram-negative bacteria, with MICs in the nanomolar range, and low cytotoxic and hemolytic activities at concentrations significantly exceeding their MICs. Quantitative structure-activity relationship (QSAR) analysis of peptide sequences and their antimicrobial, cytotoxic, and hemolytic activities revealed that site-directed substitutions of residues in the hydrophobic face of the amphipathic peptides with less lipophilic residues selectively decrease the hemolytic effect without significantly affecting the antimicrobial or cytotoxic activity. On the other hand, the antimicrobial effect can be enhanced by substitutions in the polar face with more polar residues, which increase the amphipathicity of the peptide. On the basis of the QSARs, new analogs that have strong antimicrobial effects but that lack hemolytic activity can be proposed. The findings highlight the importance of peptide amphipathicity and allow a rational method that can be used to dissociate the antimicrobial and hemolytic effects of cationic peptides, which have potent antimicrobial properties, to be proposed.

Anti-Bacterial Agents↗
PubMed2002

Unwanted effects of morphine-6-glucoronide and morphine.

The active metabolite of morphine, morphine-6-glucuronide (M6G), may have fewer unwanted effects than morphine. We randomly allocated 144 women to receive either M6G or morphine as part of general anaesthesia for day case gynaecological laparoscopy. The incidence of nausea, vomiting, pain, sedation and skin rash, and severity of nausea, pain and sedation after surgery were recorded by direct observation in hospital, and by questionnaire until the next morning. Compared with the M6G group, patients who received morphine were more likely to report nausea in the first 2 h after surgery (odds ratio 2.9, CI 1.31-6.21) and to suffer it with greater severity. During the same time period, they were more likely to vomit and feel sleepy, but the intensity of pain and use of rescue analgesics were similar in both groups. The incidences of nausea, vomiting and the feeling of sleepiness continued to be greater in the morphine group during and after the journey home. The next morning, patients in the morphine group remained sleepier, but the incidence of nausea was similar for the two groups. M6G appears to have a better toxicity profile than morphine. More efficacy studies are needed to define accurately the analgesic potency of systemically administered M6G.

Adolescent↗
PubMed2002

Acute pain services in Hong Kong: facilities, volume, and quality.

Acute pain services in public hospitals in Hong Kong were studied. Audit data on the volume and quality of acute pain services were collected prospectively from 1997 to 1999, and data on related facilities were collected in 2000. About 20% of patients undergoing a major operation received an acute pain service; of these, 78.6% were satisfied with the treatment provided. In 2000, 86% (18/21) of hospitals providing anaesthetic services were running an acute pain service. Staffing was better in hospitals providing a high volume of acute pain services, ranging from a full-time specialist anaesthesiologist assisted by a half-time trainee to a half-time specialist assisted by a full- or half-time trainee. However, only four hospitals were staffed with pain nurses. In total, 57% of patients received intravenous patient-controlled analgesia and 32% epidural analgesia. The mean duration of acute pain service treatment was 3.1 days. Currently anaesthesiologist-based acute pain services take care of a limited number of patients. To expand the coverage, there should be a move towards an anaesthesiologist-led, pain nurse-based, acute pain service. The present shortage of pain nurses should be addressed.

Analgesia, Patient-Controlled↗
PubMed2001

High-performance affinity capture-removal of bacterial pyrogen from solutions.

Synthetic peptide S3delta has high affinity for bacterial endotoxin or lipopolysaccharide (LPS). Under tested conditions of pH 5-9 and 0-0.4 M NaCl, the affinity constant, KD ranged from 2.10(-6) to 2 x 10(-9) M(-1). A novel affinity matrix based on peptide S3delta was developed for removal of LPS from solutions such as: water; buffers with a wide range of ionic strength and pH; medium for cell culture; and protein solutions under optimized conditions. At a starting LPS of approximately 100 EU/ml, a post-purification level below 0.005 EU/ml was achieved.

Amino Acid Sequence↗
PubMed2001

Synthesis and structure-activity relationships of potential anticonvulsants based on 2-piperidinecarboxylic acid and related pharmacophores.

Using N-(2,6-dimethyl)phenyl-2-piperidinecarboxamide (1) and N-(alpha-methylbenzyl)-2-piperidinecarboxamide (2) as structural leads, a variety of analogues were synthesised and evaluated for anticonvulsant activity in the MES test in mice. In the N-benzyl series, introduction of 3-Cl, 4-Cl, 3,4-Cl2, or 3-CF3 groups on the aromatic ring led to an increase in MES activity. Replacement of the alpha-methyl group by either i-Pr or benzyl groups enhanced MES activity with no increase in neurotoxicity. Substitution on the piperidine ring nitrogen led to a decrease in MES activity and neurotoxicity, while reduction of the amide carbonyl led to a complete loss of activity. Movement of the carboxamide group to either the 3- or 4-positions of the piperidine ring decreased MES activity and neurotoxicity. Incorporation of the piperidine ring into a tetrahydroisoquinoline or diazahydrinone nucleus led to increased neurotoxicity. In the N-(2,6-dimethyl)phenyl series, opening of the piperidine ring between the 1- and 6-positions gave the active norleucine derivative 75 (ED50=5.8 mgkg(-1), TD50 =36.4 mgkg(-1), PI=6.3). Replacement of the piperidine ring of 1 by cycloalkane (cyclohexane, cyclopentane, and cyclobutane) resulted in compounds with decreased MES activity and neurotoxicity, whereas replacement of the piperidine ring by a 4-pyridyl group led to a retention of MES activity with a comparable PI. Simplification of the 2-piperidinecarboxamide nucleus of 1 into a glycinecarboxamide nucleus led to about a six-fold decrease in MES activity. The 2,6-dimethylanilides were the most potent compounds in the MES test in each group of compounds evaluated, and compounds 50 and 75 should be useful leads in the development of agents for the treatment of tonic-clonic and partial seizures in man.

Animals↗
PubMed2001

Helicobacter pylori in familial clusters based on antibody profile.

Studies have shown a high prevalence of Helicobacter pylori infection in close communities and that intrafamilial spread during early childhood may be a route of transmission. A total of 72 household members from 21 families were enrolled in this study. Sera from individuals showed 50/72 (69.4%) seropositive for IgG against H. pylori by ELISA. Western blots showed diversity in the protein profiles with molecular masses ranging from approximately 8 to 130 kDa. Cohen's kappa statistical analysis of the blot patterns showed that nine families demonstrated similar profiles (100%), while 4 other families showed varying similarities (17-50%). The results support the hypothesis of intrafamilial transmission of H. pylori. Furthermore, serological studies can be used as an effective approach to determine the familial status in relation to H. pylori infection.

Adolescent↗
PubMed2001

High therapeutic index of factor C Sushi peptides: potent antimicrobials against Pseudomonas aeruginosa.

Factor C protein isolated from the horseshoe crab, Carcinoscorpius rotundicauda, has endotoxin binding capability. Synthetic peptides of 34 amino acids based on the sequence of two regions of factor C (Sushi 1 and Sushi 3) as well as their corresponding mutants exhibited activities against 30 clinical isolates of Pseudomonas aeruginosa. Collectively, all four peptides demonstrated exceptionally effective bactericidal activity against P. aeruginosa with 90% minimal bactericidal concentrations (MBC(90)s) in the range of 0.06 to 0.25 microg/ml (16 to 63 nM). Viable bacteria were reduced by 90% after 7 min and were totally eradicated within 40 to 50 min. These peptides are minimally hemolytic against both rabbit and human erythrocytes even at concentrations up to 1,600-fold their MBC(90)s. Both in vitro and in vivo studies indicate that cytotoxic effects are small even at 1,000-fold their MBC(90)s. Furthermore, the Sushi peptides are tolerant of high-salt and adverse pH conditions. These findings demonstrate the promising therapeutic potential of the Sushi peptides.

Arthropod Proteins↗
PubMed2001

Anaesthetic clinical indicators in public hospitals providing anaesthetic care in Hong Kong: prospective study.

OBJECTIVES: To assess the quality of anaesthetic services as defined in the six anaesthetic clinical indicators against preset standards and to identify risk factors for adverse events in the recovery room. DESIGN: Prospective study. SETTING: All public hospitals providing anaesthetic care in Hong Kong. PATIENTS: Eighteen thousand, seven hundred and fifty-nine patients receiving elective or emergency anaesthesia administered by anaesthetists from June 1998 to July 1998. MAIN OUTCOME MEASURES: Patient demographics, American Society of Anesthesiologists status, category and nature of operation, presence of preoperative anaesthetic visit in ward, type of anaesthesia, reasons for a recovery room stay of more than a 2-hour duration, intubation to relieve respiratory distress in the recovery room, presence of hypothermia in the recovery room for operations lasting more than 2 hours, and dental or ocular injuries attributable to anaesthesia. RESULTS: There are two major findings from this study. Firstly, a high incidence of hypothermia in the recovery room was reported. Secondly, a greater risk of prolonged stay in the recovery room was identified for patients older than 65 years, major operations, and anaesthetic techniques using combined general and regional anaesthesia. CONCLUSION: The six anaesthetic clinical indicators reflected the provision of anaesthetic care in public hospitals in Hong Kong. Good compliance to the preset standard of the anaesthetic clinical indicators was achieved during the study period.

Adolescent↗
PubMed2001

Efficacy of a nitroimidazole containing tripletherapy regime in Singapore.

BACKGROUND: There has been a gradual increase in the proportion of Singapore patients with metronidazole resistant strains of Helicobacter pylori. We studied the efficacy of a nitroimidazole containing regime in eradicating H. pylori. METHODS: Consecutive treatment naive patients with peptic ulcer disease and culture proven H. pylori were recruited. From each patient, two antral biopsies were taken for rapid urease test and two for histology. Two biopsies each from the gastric antrum and corpus were taken for H. pylori culture. Antibiotic sensitivity to amoxycillin, metronidazole, clarithromycin and tetracycline were tested using the disc diffusion method. Patients were treated with lansoprazole 30 mg bd, tinidazole 500 mg bd and clarithromycin 500 mg bd for seven days. Successful eradication was defined as either negative urea breath tests 4 and 12 weeks after treatment, or negative histology and culture at least four weeks after the end of treatment. RESULTS: A total of 64 patients were culture positive (51 males, 13 females). Forty-two patients had duodenal ulcers (DU), 17 gastric ulcers (GU), and 5 DU and GU. Metronidazole resistance was detected in 16 patients (25%). Three of the 16 patients (19%) had a mixed population of resistant and sensitive strains of H. pylori. None of the H. pylori isolates were resistant to amoxycillin, tetracycline or clarithromycin. Overall, eradication was achieved in 51/64 patients (80%). Eradication rate was 88% (42/48) among those with metronidazole sensitive strains, and 56% (9/16) among those with metronidazole resistant strains (p < 0.02). CONCLUSION: A high proportion of our patients with metronidazole resistant strains of H. pylori failed eradication therapy when a nitroimidazole containing regime was used. It may not be appropriate to use a nitroimidazole containing without prior knowledge of the antibiotic sensitivity pattern of the H. pylori isolate.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed2000

Molecular dynamics study on lipid A from Escherichia coli: insights into its mechanism of biological action.

Structural properties of the Escherichia coli lipid A moiety were analysed by means of molecular mechanics and molecular dynamics simulations and compared to synthetic monophospho and dephospho analogues with different biological activities in the Limulus assay. The conformation of glucosamine disaccharide headgroup, order and packing of fatty acid chains, solvation of phosphate groups, coordination by water molecules, sodium counterions and models of cationic amino acid side chains were described in terms of mean values, mean residence times, radial distribution functions, coordination numbers, solvation and interaction energies. Solvation and polar interactions of the phosphate groups were correlated to known biological activities the lipid A variants. The observed relationship between the biological effect and the number and position of the phosphate groups were explained with the help of simple mechanistic models of lipid A action. The possible mechanism of action involving specific binding of lipid A disaccharide headgroup to cationic residues of a receptor model was compared with an alternative mechanism, which assumes a relationship between the ability to adopt non-lamellar supramolecular structures and the biological activity. Conclusions are drawn about the probable mode of lipid A action. Implications for rational drug design of endotoxin-neutralising agents are discussed.

Carbohydrate Conformation↗
PubMed2000

Inhaled mannitol identifies methacholine-responsive children with active asthma.

Inhaled mannitol has been developed for bronchial challenge testing in adults. This study determined if mannitol could identify children with active asthma and responsive to methacholine, and whether mannitol challenge was faster to complete than methacholine challenge. Twenty-five children (aged 6-13 years) responsive to methacholine and 10 nonasthmatic children unresponsive to methacholine were studied. The methacholine challenge (Cockcroft protocol) was followed by a mannitol challenge on separate days. Twenty-one asthmatic children were positive to mannitol. Three taking inhaled corticosteroids with borderline methacholine responsiveness did not respond to mannitol, and one could not complete the mannitol challenge due to cough. The geometric mean (GM) and 95% confidence interval (CI) for PD(15) for mannitol was 39 mg (19, 78), and PC(20) for methacholine was 0.6 mg/mL (0.35-1.02) (r(p) = 0.75, p < 0.001, n = 21). Responses to mannitol were repeatable: GM PD(15) for the first challenge was 29 mg (CI: 17,50), and for the second challenge, 33 mg (CI: 20, 55) (P = 0.44, n = 9). Mannitol was faster to administer than methacholine (median (range)) 14 min (5-32) vs. 29 min (19-49), respectively (P < 0.001). Time to recover to baseline FEV(1) spontaneously and after bronchodilator administration was similar for both challenges. There were no significant falls in arterial oxygen saturations. During mannitol challenge, the mean (SD) fall in FEV(1) in nonasthmatic children was 3.1% (2.9). We conclude that mannitol identifies children with airway hyperresponsiveness and is faster to perform than the methacholine challenge.

Asthma↗
PubMed2000

Accurate diagnosis of Helicobacter pylori. Serologic testing.

Serologic testing is a useful noninvasive testing strategy for H. pylori. It is particularly useful in areas where the prevalence of H. pylori is high and inexpensive point-of-contact fingerprick tests are used. Sensitive tests are valuable ways of excluding H. pylori infection and can be used in conjunction with a direct test (urease histology culture or breath test) to confirm absence of H. pylori if the two methods are concordant. Serologic testing is more definitive and differentiating if the antigenic epitopes of H. pylori can be differentiated based on the antigenic epitopes that specifically associate with gastric cancer, peptic ulcer, and nonulcer dyspepsia. A study by Kawahara's group reported that Hsp 60 may be involved in the development of mucosa-associated lymphoid tissue based on ELISA. The idea of differentiating antigens for H. pylori may open a new area for use of serologic testing in the diagnostic approach of H. pylori infections.

Antibodies, Bacterial↗