Biomedical subjects

W K Seow

Publications and source records attributed to W K Seow.

At least 55 records · Page 3Linked to original sources

PubMed1991

Demonstration of the induction of apoptosis (programmed cell death) by tetrandrine, a novel anti-inflammatory agent.

Tetrandrine, a bisbenzylisoquinoline alkaloid, was found to cause death of malignant lymphoid and myeloid cells but not of Epstein-Barr virus-transformed lymphoblastoid cells. The death took the form of apoptosis (programmed cell death), the nature of the process being confirmed by DNA gel electrophoresis and electron microscopy. The induction of apoptosis by tetrandrine was much more rapid in CEM-C7 cells (4 h) than in the same cells treated with glucocorticoids (40 h), and did not require de novo protein synthesis. These results suggest that the anti-inflammatory and immunosuppressive properties of tetrandrine are mediated by novel mechanisms worthy of further investigation. They also indicate that tetrandrine may have value as an anti-neoplastic agent.

Alkaloids↗

PubMed1990

Inhibition of prostaglandin and leukotriene generation by the plant alkaloids tetrandrine and berbamine.

We compared the effects of two bisbenzylisoquinoline compounds on leukotriene and prostaglandin generation by human monocytes and neutrophils. The results show that tetrandrine had a much greater effect than berbamine on leukotriene generation. However, both compounds were equally potent in suppression of prostaglandin generation. This inhibitory effect on prostaglandin generation can be overcome by exogenous arachidonic acid (AA), suggesting that the site of inhibition is not on the cyclooxygenase enzyme complex, but more proximally on the phospholipase-mediated release of AA from the cell membrane, similar to the action of corticosteroids. These results, together with previous findings of inhibitory effects on other inflammatory mediators such as histamine, platelet-activating-factor (PAF) and interleukin 1 (IL-1) indicate that these plant alkaloids may be useful lead compounds for the development of a new class of anti-inflammatory drugs.

Alkaloids↗

PubMed1990

Suppression of neutrophil and lymphoproliferative responses in vitro by itraconazole but not fluconazole.

Itraconazole and fluconazole are triazole compounds recently licensed for the therapy of systemic fungal infections. At 10 micrograms/ml concentrations, itraconazole was found to suppress neutrophil chemotaxis, random movement, deoxyglucose uptake and hexose-monophosphate shunt activity to the same extent as ketoconazole, an older generation azole antifungal. Itraconazole was also found to suppress mitogen-induced lymphocyte transformation to the same extent as ketoconazole at concentrations as low as 1 microgram/ml. By contrast, significant inhibition of both neutrophil and lymphocyte functions was not observed with fluconazole at concentrations as high as 50 micrograms/ml. These results suggest that fluconazole may be less immunotoxic than itraconazole, and may be more suitable for use in immunocompromised patients.

Antifungal Agents↗

PubMed1990

Effects of the plant flavonoid baohuoside-1 on cancer cells in vitro.

The novel plant flavonoid 3,5,7,-trihydroxy-4'-methoxyl-8'-prenylflavone-3-O-alpha-L-rham nopranoxide (designated baohuoside-1) was shown to have cytotoxic and cytostatic effects on 6 cancer cell-lines, by means of microscopy, 51Cr-release and growth inhibition. The IC50 on the cells tested ranged from 2.8 to 7.5 micrograms/ml. At tumouricidal concentrations, inhibition of DNA and RNA synthesis, but not protein synthesis was observed.

Animals↗

PubMed1990

Tetrandrine, a plant alkaloid, inhibits the production of tumour necrosis factor-alpha (cachectin) hy human monocytes.

Human mononuclear leucocytes (MNL) or the adherent fraction (monocytes) produced tumour necrosis factor-alpha (TNF-alpha) (by ELISA) in culture when stimulated with killed Staphylococcus aureus. The bisbenzylisoquinoline alkaloid, tetrandrine inhibited the capacity of MNL and monocytes to produce TNF-alpha at a concentration range of 0.1 to 5 micrograms/ml. Tetrandrine may be potentially useful in the treatment of inflammatory diseases in which TNF-alpha plays a major role.

Alkaloids↗

PubMed1990

Fermentable simple sugars in self-administered medications as aetiologic agents in rampant caries. Case report.

Sucrose is recognized as the most cariogenic carbohydrate. However, other simple sugars may act as substrates for cariogenic micro-organisms. The clinical features of an adult patient suffering from rampant caries are described. It was considered that the predominant aetiologic factor was prolonged intake of mineral supplements which contained the disaccharide lactose. The principal caries risk factors included drug-induced xerostomia and prolonged contact time with the substrate in a retentive form. Chemical analysis of the products revealed the presence of lactose together with starch or glucose. A strategy for preventive management prior to restorative therapy based on chlorhexidine and fluoride-containing products was followed. Possible contributions of sugar-containing medications to caries risk status are discussed.

Dental Caries↗

PubMed1990

In vitro immunosuppressive and anti-phagocytic properties of the exopolysaccharide of mucoid strains of Pseudomonas aeruginosa.

The exopolysaccharide (EPS) of Pseudomonas aeruginosa was found to significantly inhibit neutrophil random movement, chemotaxis and degranulation at concentrations as low as 0.3 microgram/ml. Neutrophil adherence, respiratory burst and bactericidal capacity were inhibited by EPS concentrations of greater than or equal to 3 micrograms/ml. Similarly, mitogen-induced lymphocyte transformation was more sensitive to the inhibitory effects of EPS than natural-killer cell cytotoxicity. These results cannot be explained by simple mechanical blockade, as additions of EPS as late as 48 h after the initiation of lymphocyte cultures still resulted in a significant inhibition of lymphocyte transformation. However, the inhibitory effects of EPS can be reversed by extensive washing of treated lymphocytes. These results suggest that the propensity of mucoid P. aeruginosa to persist in cystic fibrosis may be explained in part by the ability of EPS to interfere with host immunity.

Blood Bactericidal Activity↗

PubMed1990

Enamel hypoplasia in prematurely-born children: a scanning electron microscopic study.

Although the enamel defects of low birthweight prematurely-born children have been well investigated clinically the ultrastructure has not been studied in detail. Using scanning electron microscopy this investigation examined the enamel surface of 4 representative teeth from a group of exofoliated teeth from prematurely-born, very-low birthweight children compared to an equal number of control teeth from normal birthweight children. The results showed that all 4 teeth from the prematurely-born group had enamel defects at the ultrastructural level even though the defects were evident only macroscopically in 2 teeth. By contrast all the control teeth from normal children did not show abnormalities of surface structure. Thus this investigation further confirms that birth prematurity and low birthweight adversely affect the activities of ameloblasts. Previous clinical investigations have reported that prematurely-born children show high prevalences of enamel hypoplasia of around 20-100%. The etiological factors involved in the pathogenesis of enamel defects are unclear, but are likely to be related to many systemic illnesses occurring during the neonatal period. These include respiratory distress syndrome, hyperbilirubinemia, maternal diabetes as well as neonatal rickets. Furthermore, Seow et al. (1989) showed recently that deficiency of calcium and phosphate mineral in the neonatal period is related directly to enamel hypoplasia in very-low birthweight, prematurely born children. In addition to systemic factors, local factors such as laryngoscopy and endotracheal intubation have also been implicated in the etiology of enamel hypoplasia in these children. While the enamel defects have been well studied at the clinical level, there is a paucity of information on the ultrastructural nature.(ABSTRACT TRUNCATED AT 250 WORDS)

Dental Enamel Hypoplasia↗

PubMed1990

PH of endodontic medicaments used in pediatric dentistry: effects of dyadic combinations.

The optimum pH of an endodontic medicament is close as possible to that of body fluids, i.e., around 7.2 as higher and lower pH's are likely to cause cellular necrosis of tissues in direct contact with the medicament. This study investigated the pH of various endodontic medicaments commonly used in pediatric dentistry, both singly and in the various combinations available for clinical use. The results showed that the pH ranged from a low of 2.90 +/- 0.02 for iodoform paste (Kri) to a high of 12.45 +/- 0.02 for calcium hydroxide (Calyxl). Eugenol showed a pH of 4.34 +/- 0.05, formocresol 2.79 +/- 0.02, and a commercially-available antibiotic-corticosteroid paste (Ledermix) 8.13 +/- 0.01. Addition of up to 50 percent (v/v) of Ledermix or 25 percent Kri respectively did not affect the pH of Calyxl significantly. Although the addition of up to 75 percent Kri to Ledermix caused a fall in pH, the changes are probably not significant clinically. Furthermore, the addition of 50 percent eugenol to formocresol increased its pH significantly. The optimum pH of an endodontic medicament is as close as possible to that of body fluids, i.e., around 7.2. Higher and lower pH's are likely to cause cellular necrosis of tissues in direct contact with the medicament. However with the exception of calcium hydroxide there has been very little information available on the pH of endodontic medicaments commonly used in pediatric dentistry. Medicaments such as formocresol, eugenol and iodoform pastes have been extensively used for endodontic therapy yet very little attention has been given to their pH values.(ABSTRACT TRUNCATED AT 250 WORDS)

Calcium Hydroxide↗

PubMed1989

Anti-inflammatory and immunosuppressive properties of the bis-benzylisoquinolines: in vitro comparisons of tetrandrine and berbamine.

Tetrandrine and berbamine are two naturally occurring analogues with a bis-benzylisoquinoline structure. Comparative in vitro studies show that tetrandrine has significantly greater suppressive effects on adherence, locomotion and 3H-deoxyglucose uptake of neutrophils, as well as the mitogen-induced lymphocyte responses and mixed lymphocyte reactions. Also, tetrandrine displayed anti-oxidant activity while berbamine did not. By contrast, berbamine demonstrated a significantly greater capacity for inhibition of NK cell cytotoxicity. These results show that tetrandrine is superior to berbamine in most aspects of anti-inflammatory and immunosuppressive activity. Since these two alkaloids differ by only one substitution in the side chain of one of the benzene rings, these findings may provide further insight into structure-activity relationships and clues to the synthesis and development of active analogues of this promising class of drugs for the treatment of chronic inflammatory diseases.

Alkaloids↗

PubMed1989

Inhibition of neutrophil locomotion, natural killer cell cytotoxicity and lymphocyte transformation by 1-methyl-3-phenyl-1,2,4-triazinium-5-olate, a novel triazinium zwitterion.

We studied a novel triazinium zwitterion compound for its effects on neutrophil locomotion and deoxyglucose uptake, Natural Killer (NK) cell cytotoxicity and mitogen-induced lymphocyte transformation. The results show significant inhibition of neutrophil locomotion at concentrations of 10 micrograms/ml or greater; by contrast, there was no significant effect on neutrophil deoxyglucose uptake. Significant suppression of NK cell cytotoxicity occurred at similar concentrations in a dose-dependent fashion. Marked suppression of mitogen-induced lymphocyte transformation was also observed for all three mitogens used in the assays. This effect was dose-dependent, reversible by washing and still evident even when it was added 37 h after the initiation of cultures. These results suggest that 1-methyl-3-phenyl-1,2,4-triazinium-5-olate may have application as an anti-inflammatory and immunosuppressive agent.

Anti-Inflammatory Agents, Non-Steroidal↗

PubMed1989

Effects of the newer antifungal agents (bifonazole, ICI 195, 739 and amorolfin) on in vitro phagocytic, lymphocytic and natural-killer cell responses.

Amphotericin B and some of the imidazole drugs have been shown to suppress certain neutrophil and lymphocyte functions both in vitro and in vivo. We present here the in vitro effects of: amorolfin, a morpholine derivative; the imidazoles clotrimazole and ketoconazole; the N-substituted imidazole bifonazole and a triazole (ICE 195, 739), on neutrophil and lymphocyte function. All of these drugs inhibited neutrophil random migration, chemotaxis and hexose monophosphate shunt activity. The effects of the drugs on neutrophil adherence, deoxyglucose transport and beta-glucuronidase release were variable while lysozyme release was unaffected. Natural Killer cell cytoxicity was depressed by all drugs tested except for amorolfin. Mitogen-induced lymphocyte blastogenesis was suppressed by all the antifungal drugs tested. Similar results were obtained using the mitogens phytohaemagglutinin, concanavalin A and pokeweed mitogen. The mechanism of action of these drugs on these cell functions remains unknown, there may be a correlation between their effects on fungi and their effects on leukocytes. Clearance of systemic fungal infection is heavily dependent on integrity of the cellular immune system and it is clearly undesirable that antifungal drugs have immunosuppressive properties. Further studies are required to determine the in vivo and clinical relevance of our observations.

Antifungal Agents↗

PubMed1989

Inhibitory effects of human neutrophil granules and oxygen radicals on adherence of Candida albicans.

The adherence of Candida albicans to dacron fibre microcolumns was significantly suppressed after interaction with human neutrophils. The adherence-inhibiting properties of neutrophils were shown to reside in their cytoplasmic granules and granular enzymes. Oxygen-derived free radicals produced by the respiratory burst may also be responsible, as shown by experiments in which oxygen radicals were generated by the cell-free hypoxanthine-xanthine oxidase system. Dose-response studies with H2O2 and beta-glucoronidase demonstrated that lower concentrations of these agents inhibited adherence without affecting viability of C. albicans. These results suggest that interference with adherence mechanisms may be an effective means of host defence by neutrophils against the colonisation of mucosal surfaces by C. albicans.

Candida albicans↗

PubMed1989

Suppression by tetrandrine of human platelet aggregation induced by platelet-activating factor and other stimulants.

Tetrandrine was found to have inhibitory effects on platelet-activating factor induced platelet aggregation in a dose-dependent manner. There was preferential inhibition of platelet aggregation induced by agents such as collagen, thrombin, adrenaline, and adenosine diphosphate. No inhibitory effect of tetrandrine was observed on platelet aggregation induced by adenosine diphosphate, arachidonic acid, and the calcium ionophore A23187. These results support our previous findings of interference with the phosphatidylinositol second-messenger system as one of the sites of action of tetrandrine. Since platelets may have an important role in the pathogenesis of asthma and other allergic diseases, these findings suggest that tetrandrine may have clinical application as a non-steroidal broad-spectrum anti-allergic drug.

Adenosine Diphosphate↗

PubMed1989

Tetrandrine and transmembrane signal transduction: effect on phosphoinositide metabolism, calcium flux and protein kinase C translocation in human lymphocytes.

Time-course and dose-dependent studies showed consistent suppression of phosphoinositide turnover in Con A-stimulated human lymphocytes in the presence of the plant alkaloid, tetrandrine. Significant inhibition of Con A-stimulated calcium flux was also observed. Furthermore, protein kinase C activity was also significantly inhibited by tetrandrine irrespective of whether Con A or phorbol myristate acetate was the stimulant. These results suggest that the immunosuppressive properties of tetrandrine are in part mediated by the capacity of tetrandrine to interfere with transmembrane signalling.

Alkaloids↗

PubMed1989

Modulation of human neutrophil adherence by periodontopathic bacteria: reversal by specific monoclonal antibodies.

Previous investigations by us have shown that direct interaction of Fusobacterium nucleatum with polymorphonuclear neutrophils (PMNs) results in the stimulation of PMN adherence whereas direct interaction with Bacteroides gingivalis results in PMN suppression. In the present study, panels of monoclonal antibodies (MAbs) raised against cell wall antigens of F. nucleatum and B. gingivalis were tested to determine their ability to block the modulatory effects of the bacteria in their interactions with PMNs. While no activity was demonstrated for any of the 9 MAbs raised against F. nucleatum, it was found that 2 of 16 MAbs raised against B. gingivalis were able to reverse the suppression of PMN adherence induced by the bacteria. Further studies on these 2 reactive MAbs showed that the effect of MAbs were abrogated by heat treatment as well as by trypsin proteolysis. Investigations into the nature of the reactive epitopes on the bacterial surface showed that they probably contain protein components susceptible to proteolytic attack by subtilisin. In addition, beta-galactose may be a component of the reactive epitopes for one of the MAbs, but sialic acid residues on the bacterial surface are probably not involved as their elimination by neuraminidase did not affect the binding of both MAbs. The results of the present study strongly validate our previous observations that direct specific interaction of B. gingivalis with human PMNs occurs, resulting in the suppression of PMNs.

Antibodies, Bacterial↗

PubMed1989

Effect of tetrandrine on immunological responses and cardiac transplant rejection in mice.

Mice treated with the plant alkaloid tetrandrine have a reduced capacity to mount delayed-type hypersensitivity (DTH) responses. This suppressive effect on DTH was more pronounced when treatment was begun 2 days prior to immunization with sheep erythrocytes. Similar dosage regimens significantly delayed the rejection of cardiac transplants. By contrast, there was significant enhancement of antibody production. These immunomodulatory properties of tetrandrine may account for some of its potential in the treatment of chronic inflammatory diseases, where immunological mechanisms are known to play a major role in pathogenesis.

Alkaloids↗

PubMed1989

Direct modulation of human neutrophil behaviour by Candida albicans.

We examined the direct effect of unopsonized yeast particles of Candida albicans on two aspects of neutrophil behaviour, namely adherence and 3H-deoxyglucose uptake. The data show that brief exposure of C. albicans to human neutrophils resulted in decreased ability of the neutrophils to adhere to Dacron fibre and take up deoxyglucose. This inhibitory effect was further shown to be dependent on yeast concentration and on the integrity of the yeast cell wall. Additional experiments indicate that this effect was direct rather than indirect through soluble mediators in the supernatant. Interference experiments with glucan and mannan, the two major polysaccharide components of the yeast cell wall, suggest that the ligand in direct interaction between C. albicans and neutrophil contains glucan. Finally, it was shown that nonpathogenic species of Candida such as C. krusei, C. parapsilosis and C. guilliermondii did not display neutrophil-modulatory properties while the occasionally pathogenic C. tropicalis did. These results indicate that C. albicans has the ability to circumvent neutrophil defence mechanisms, and may in part explain the propensity of this fungus to cause infection.

Biological Transport↗