Biomedical subjects

W K Seow

Publications and source records attributed to W K Seow.

At least 37 records · Page 2Linked to original sources

PubMed1994

Nicotine-induced release of elastase and eicosanoids by human neutrophils.

We examined the direct effects of nicotine on a variety of neutrophil functions at concentrations achievable in lung and oral tissues from cigarette smoking. The results show dose-dependent suppression of chemotaxis and phagocytosis, and enhancement of degranulation and eicosanoid generation, but not superoxide production. Cell viability was not affected by the concentrations of nicotine used in these experiments, as shown by trypan blue dye exclusion and MTT assays. These results implicate nicotine as the ingredient in cigarette smoke responsible for inflammatory damage to lungs and oral tissues observed in cigarette smokers.

Cell Degranulation↗

PubMed1994

Immunopharmacology and toxicology of the plant flavonoid baohuoside-1 in mice.

The plant flavonoid baohuoside-1 (B-1), isolated from Epimedium davidii, was shown to suppress antibody and delayed-type hypersensitivity responses in mice in a dose-dependent fashion. By contrast, similar dosage schedules of B-1 did not significantly prolong survival of cardiac grafts. Furthermore, B-1 did not potentiate the effects of the standard anti-rejection drug cyclosporine. Assessment of the mice for appearance, behaviour, biochemistry, haematology and histology revealed no toxic effects at the dosages used in the experiments. These results indicate that the immunosuppressive properties of B-1 are confined to the antibody-mediated system, and suggest that B-1 may be of value in the treatment of chronic inflammatory and autoimmune diseases in which autoantibodies have a major role in pathogenesis.

Animals↗

PubMed1994

Effect of berbamine on blood and bone-marrow stem cells of cyclophosphamide-treated mice.

The bisbenzylisoquinoline alkaloid berbamine has been used in China and Japan for the therapy of leukopaenic complications of cancer. Mice treated with non-toxic doses showed significant enhancement of neutrophil and lymphocyte counts in the circulation, but a decrease in the numbers of bone marrow stem cells in a dose-dependent manner after two weeks. Similar findings were observed in cyclophosphamide-treated mice. These results indicate that berbamine acts by stimulating the maturation and release of leukocyte progenitors, and may have value in leukopaenic patients.

Alkaloids↗

PubMed1993

Synergy between tetrandrine and FK506 in prevention of diabetes in BB rats.

Delayed administration of tetrandrine, a novel broad-spectrum anti-inflammatory agent, to BB rats at a dosage schedule of 20 mg kg-1 day-1 from 79 days of age reduced the cumulative incidence of diabetes from 73.1 to 41.7% (p < 0.01). Brief treatment with the potent immunosuppressive agent FK506 at a dosage schedule of 0.5 mg kg-1 day-1 from 79 days of age for 5 days had no significant effect on the cumulative incidence of diabetes (66.7%, p > 0.1). However, the combination of tetrandrine and FK506 in the afore-mentioned dosage schedules reduced the incidence of diabetes to only 3.6% (p < 0.001). These results suggest that the strong synergy between tetrandrine and FK506 may offer a safe and effective therapeutic strategy for the treatment of patients with recent onset or imminent IDDM.

Alkaloids↗

PubMed1993

Comparative effects of tetrandrine and berbamine on guineapig airway microvascular leakage induced by platelet-activating factor and other allergic mediators.

The bisbenzylisoquinoline analogues, tetrandrine and berbamine, were investigated for their effects on guineapig airway microvascular leakage, an animal model of asthma and allergic inflammation. Significant inhibition of microvascular leakage by tetrandrine was observed with all four allergic mediators used in these experiments. By contrast, berbamine was able to suppress microvascular leakage induced by platelet-activating factor and bradykinin, but not by leukotriene D4 or histamine. These results indicate that tetrandrine has broad-spectrum inhibitory activity on allergic mediators, and may have value for the therapy of diseases in which these mediators have a role in pathogenesis.

Alkaloids↗

PubMed1993

Palatal measurements of prematurely born, very low birth weight infants: comparison of three methods.

To enable investigation of palatal changes in infants who are prematurely born, it is necessary to first establish a reliable method of measurement of these tiny edentulous palates. This study compared the Olivetti-Inspector machine, Vernier calipers, and stereophotogrammetry for this purpose. Measurements were taken of 12 palatal casts of four infants at prescribed time intervals during the neonatal period. In each of the three methods, measurements were recorded as variables generated in the X and Z axes of the Cartesian scale in relation to three specified points along the Y axis. The results revealed that all methods were comparable, but the Vernier calipers differed significantly from the other two methods in height measurements, (p < 0.001). It was also found that both the Olivetti-Inspector machine and the Vernier calipers consistently underestimated the width, compared with Olivetti-Inspector machine, (p < 0.05). Stereophotogrammetry was found to be the most consistent method of measuring the configuration of preterm infant palates.

Calibration↗

PubMed1993

Taurodontism of the mandibular first permanent molar distinguishes between the tricho-dento-osseous (TDO) syndrome and amelogenesis imperfecta.

The diagnosis of tricho-dento-osseous (TDO) syndrome is often confused with that of a variant of amelogenesis imperfecta (AI) which shows similar dental features of hypomaturation-hypoplastic enamel defects and putative taurodontism. In this controlled study, an objective, biometric measurement technique was used to determine the prevalence and severity of taurodontism of the mandibular first permanent molar in 23 patients with AI and one patient with TDO syndrome compared with age- and sex-matched controls. The published radiographs of previous cases of TDO and hypomaturation-hypoplastic AI were also reviewed with regard to the presence and severity of taurodontism. The results indicate that in all cases of TDO, taurodontism of the molars including mandibular first permanent molars was consistently present and in a severe form. By contrast, the taurodontic defects present in all cases of AI, including the hypomaturation-hypoplastic variant were not significantly different from matched, healthy controls. Of significance is the fact that in all the AI cases, none of the taurodontic defects were present on the mandibular first permanent molars. The results indicate that true taurodontism as indicated by a change in the mandibular first permanent molars occurs only in the TDO syndrome. This feature may be used to differentiate clearly between TDO and AI.

Abnormalities, Multiple↗

PubMed1993

Inhibition of adherence of mucoid Pseudomonas aeruginosa by alginase, specific monoclonal antibodies, and antibiotics.

The adherence of pseudomonal species was investigated by using a newly developed radiometric dacron fiber microcolumn assay. Pseudomonas aeruginosa, P. stutzeri, and Xanthomonas maltophilia were more adherent (approximately 20%) than P. pseudomallei, P. fluorescens, and P. cepacia (approximately 10%). Mucoid strains of P. aeruginosa were consistently more adherent than nonmucoid strains (30% versus 20%). Alginase was shown to inhibit the adherence of mucoid but not nonmucoid P. aeruginosa. Monoclonal antibodies to alginate were also shown to inhibit the adherence of mucoid but not nonmucoid P. aeruginosa. In addition, antibiotics active against P. aeruginosa were shown to inhibit the adherence of both mucoid and nonmucoid strains. Furthermore, synergism between dyadic combinations of monoclonal antibodies and antibiotic (ciprofloxacin), as well as alginase and antibiotic, was also observed. These results indicate that bacterial alginate has an intrinsic role in the adherence of mucoid P. aeruginosa and may have evolved not only for protection against dehydration in the water and soil ecosystem of this bacterium, but also as a means of attaching to soil substrates in the same ecosystem to enhance survival. They also suggest that synergistic combinations of antibiotics with alginase or monoclonal antibodies to alginate may be of value in the therapy of some pseudomonal infections.

Alginates↗

PubMed1993

Suppression of lymphocyte and neutrophil functions by Pseudomonas aeruginosa mucoid exopolysaccharide (alginate): reversal by physicochemical, alginase, and specific monoclonal antibody treatments.

The mucoid exopolysaccharide (MEP or alginate) of Pseudomonas aeruginosa is thought to be a virulence factor for this organism by virtue of its ability to suppress local host defense mechanisms. We purified MEP from clinical isolates of mucoid P. aeruginosa, subjected it to degradation by ultrasonication, heat, alkali, and alginase, and reacted it with monoclonal antibodies specific for MEP epitopes. Partial reversal or complete abrogation of the inhibitory effects of alginate on human neutrophil random migration, chemotaxis, and hexose monophosphate shunt activity and lymphocyte transformation were observed following most of these treatments. Physicochemical analysis of degraded MEP revealed a positive correlation between changes in molecular size and viscosity and loss of biological properties. The biological properties of MEP were also shown to be dependent on the structural integrity of the O-acetyl groups substituted for the mannuronic acid residues. The results show that the capacity of MEP to suppress neutrophil and lymphocyte functions is dependent on its acetyl content and the physical properties of large size and viscosity and may provide part of the explanation for the propensity of mucoid P. aeruginosa to persist in the airways of patients with cystic fibrosis. These findings highlight the important role of MEP as one of the virulence factors in the pathogenesis of inflammatory damage and subsequent pulmonary destruction in cystic fibrosis.

Alginates↗

PubMed1992

Comparative effects of tetrandrine and berbamine on subcutaneous air pouch inflammation induced by interleukin-1, tumour necrosis factor and platelet-activating factor.

The effects of the bisbenzylisoquinoline alkaloids tetrandrine and berbamine on the action of IL-1, TNF and PAF were investigated in the rat subcutaneous air pouch model of inflammation. Both compounds were equipotent in the suppression of leukocyte infiltration into air pouches induced by IL-1 and TNF, with ED50 values in the range 20-30 mg/kg/3 days. Both were also equipotent in suppression of PMN infiltration induced by PAF with ED50 values in the same range as that for IL-1 and TNF. However, tetrandrine was more potent than berbamine as a suppressant of PAF-induced MNC infiltration, but much less potent than berbamine in carageenen-induced PMN infiltration. These results suggest that these bisbenzylisoquinolines may have value in the therapy of chronic inflammatory diseases where IL-1, TNF and PAF have a role in pathogenesis.

Alkaloids↗

PubMed1992

Comparative effects of tetrandrine and berbamine on production of the inflammatory cytokines interleukin-1 and tumor necrosis factor.

Tetrandrine and berbamine are bisbenzylisoquinoline compounds which differ from each other in a minor way in terms of chemical structure, yet tetrandrine is 6-18 times more potent than berbamine in terms of inhibitory effects on production of interleukin-1 and tumor necrosis factor (TNF alpha) by monocytes and macrophages, and TNF beta production by lymphocytes. Moreover, tetrandrine significantly suppressed phosphoinositide turnover while berbamine did not. These findings may provide important insights into structure-activity relationships and the design of novel analogues and congeners useful in the therapy of chronic inflammatory and auto-immune diseases.

Alkaloids↗

PubMed1992

Modulation of human neutrophil adherence by oral bacteria.

Polymorphonuclear neutrophils (PMNs) comprise over 90 per cent of leukocytes in the oral cavity. Although these phagocytic cells have primary defence roles in the gingiva, their stimulation by micro-organisms may also cause substantial tissue damage due to the release of lysosomal enzymes and oxygen radicals. Adherence of PMNs to the endothelium and their subsequent diapedesis and egress to areas of infection are considered early vital events in the inflammatory process. In this study, oral bacteria were screened to determine their direct effects on PMN activation using an in vitro method of measuring PMN adherence to Dacron fibres. Most of the bacteria investigated increased PMN adherence, indicating their potential to cause tissue damage through the release of PMN lysosomal enzymes and other products. In contrast, Bacteroides species suppressed PMNs, indicating their ability to circumvent the phagocytic cells, thus gaining a potential advantage in dental colonization. The modulatory effects of oral bacteria on PMN activation may have significant roles in the immunopathogenesis of oral disease.

Aggregatibacter actinomycetemcomitans↗

PubMed1992

Comparative effects of tetrandrine and berbamine on acute and relapsing experimental allergic encephalitis in Lewis rats.

The effects of the bisbenzylisoquinoline alkaloids tetrandrine and berbamine on experimental allergic encephalitis (EAE) in Lewis rats was investigated. Amelioration of the acute-phase EAE was only minimal. However, the incidence of relapsing EAE was reduced by 41 and 65% for tetrandrine and berbamine, respectively, at the non-toxic treatment schedule of 60 mg/kg administered on alternate days. These results suggest that bisbenzylisoquinoline compounds may have a potential role in the therapy of progressive multiple sclerosis.

Alkaloids↗

PubMed1992

Prevention by tetrandrine of spontaneous development of diabetes mellitus in BB rats.

Treatment of BB rats with the plant alkaloid tetrandrine (20 mg.kg-1.day-1), a novel anti-inflammatory compound, from 35 to 120 days of age reduced the cumulative incidence of spontaneous diabetes from 75.5 to 10.9% (P less than 0.001). Dose-response studies with 0, 5, 10, and 20 mg.kg-1.day-1 of tetrandrine from 35 to 130 days resulted in spontaneous diabetes in 84.2, 63.1, 31.6, and 5.3% of the rats, respectively. When the start of treatment with 20 mg.kg-1.day-1 tetrandrine was delayed until 70 days of age, there was a significant reduction of the incidence of diabetes from 63.1 to 28.6% (P less than 0.01). Histological examination of the pancreases from tetrandrine-treated rats showed a lesser degree of insulitis than controls (P less than 0.01). Drug toxicity was not seen in the rats, as assessed by appearance, behavioral change, organ histology, and blood chemistry. These results provide some hope that tetrandrine may be of value in preventing diabetes and treating newly diagnosed diabetic subjects, either by itself or in combination with a more potent immunosuppressive agent.

Alkaloids↗

PubMed1992

Preventive dental health practices of non-institutionalized Down syndrome children: a controlled study.

Although Down syndrome children are known to be greatly predisposed to periodontal disease when compared with normal children, the preventive dental health practices of non-institutionalized Down syndrome children have not been well reported. This questionnaire study of 25 Down syndrome children aged 1-14 years compared with 25 normal control children showed that Down syndrome children have poorer dental health practices compared with normal children. Significantly greater numbers of Down syndrome children were weaned from the bottle at greater than 18 months of age (56% vs 24%, p less than 0.05) or had taken a bottle to bed (40% vs 12%, p less than 0.05), indicating their increased risk for the development of nursing bottle caries. In addition, Down syndrome children were receiving less help during tooth brushing (60% vs 84%, p less than 0.05), were older when they first visited the dentist, and less likely to be taking regular fluoride supplements. These results indicate that Down syndrome children are further disadvantaged by poor preventive dental health practices and should be targeted for increased preventive dental care.

Adolescent↗

PubMed1991

Comparative immunopharmacology and toxicology of the bisbenzylisoquinoline alkaloids tetrandrine and berbamine.

Comparison of the bisbenzylisoquinolines tetrandrine and berbamine shows that both drugs are equipotent in terms of enhancement of antibody responses and suppression of delayed-type hypersensitivity (DTH) responses to sheep red blood cell antigens. Both compounds are also equally active when given to mice during the induction and expression phases of DTH. Using a model of experimental brucellosis in mice, it was found that both compounds did not affect antibody responses, while they caused equipotent suppression of DTH. By contrast, berbamine but not tetrandrine caused significant suppression of spleen weight. Also, berbamine caused a significantly greater enhancement of spleen colony counts of Brucella abortus than tetrandrine. Short-term toxicology studies showed no toxic effects at bioactive doses.

Alkaloids↗

PubMed1991

In vitro immunopharmacological profile of the plant flavonoid baohuoside-1.

A novel flavonoid compound baohuoside-1 (3,5,7-trihydroxy-4'-methoxyl-8-prenylflavone-3-O-alpha-L-rhamnopy ranoside) was investigated for immunopharmacological properties in vitro. The results show that baohuoside-1 has significant suppressive effects on neutrophil chemotaxis, mitogen-induced lymphocyte transformation, mixed-lymphocyte culture, NK-cell cytotoxicity and IL-2 production. These dose-dependent inhibitory effects were found to be significant at concentrations of less than 1 microgram/ml, compared with greater than 94% cell viability at concentrations of 10 micrograms/ml. These results suggest that baohuoside-1 may have potential as an anti-inflammatory/immunosuppressive agent.

Anti-Inflammatory Agents, Non-Steroidal↗

PubMed1991

Effect of the novel triazinium zwitterion 1-methyl-3-phenyl-1,2,4-triazinium-5-olate on immunological responses and experimental brucellosis in mice.

The immunopharmacology of a novel triazinium zwitterion, designated JR-6, was studied in mice. Experiments show dose-response inhibition of antibody and delayed-type hypersensitivity (DTH) responses to sheep red blood cell antigens. Suppression of DTH was confirmed using trinitrochlorobenzene as a contact-sensitizing antigen. Using a model of experimental brucellosis in mice, it was found that JR-6 caused suppression of specific antibody and DTH reaction, as well as spleen weight, but a statistically significant increase in viable counts of Brucella abortus was not observed. Extensive short-term toxicology studies showed reduction in lymphocyte and neutrophil counts, and slow weight gain of treated mice. However, organ histology, liver function tests and biochemical profiles were normal.

Animals↗