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Biomedical subjects

Y H Thong

Publications and source records attributed to Y H Thong.

At least 19 recordsLinked to original sources

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

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

The quality of student-tutor interactions in the clinical learning environment.

We surveyed 403 students in their clinical years for their perceptions of the quality of clinical clerkships. Between 42.6 and 67.0% of tutorials were said to contain positive factors such as a relaxed teaching atmosphere, enthusiasm, a good selection of patients and adequate preparation. Negative features in 18.2-37.2% of tutorials included unreasonable expectations, conflicting information, late arrival, early departure, failure to show up and the display of anger, a patronizing attitude, favouritism or ridicule. While two-thirds of tutors were regarded as friendly and helpful, the remaining one-third were perceived as unconcerned, discouraging, derogatory or hostile. Overall, only half the clinical tutors were rated as effective teachers; more specifically in medicine and psychiatry, less than one-third of consultants were regarded as effective teachers, as compared with some two-thirds of consultants in obstetrics and gynaecology and paediatrics who were so regarded. Almost two-thirds of the students had predominantly positive reactions to interactions with their tutors, in terms of being motivated to learn, enthused about the subject and having their self-confidence increased. Some one-quarter had negative reactions such as indifference, depression, anger, embarrassment and fearfulness. However, the impact of student-tutor interactions was mainly confined to the students' academic well-being, with little effect on their personal-social lives. Finally, one-third of students had experienced at least some form of mistreatment by their tutors, including gender, appearance, religious and racial discrimination, unfair grading and public humiliation. These findings suggest that the clinical clerkship may not be providing an optimal learning environment for medical students.

Clinical Clerkship

A multicentre randomized placebo-controlled double-blind study on the efficacy of Ketotifen in infants with chronic cough or wheeze.

The efficacy of Ketotifen was examined in the treatment of 113 infants between 6 and 36 months of age presenting with a history of cough and/or wheeze in a multicentre randomized placebo-controlled double-blind study. A 4 week no-medication baseline phase preceded the 16 week treatment phase in which infants took 2.5 mL twice daily of either placebo or Ketotifen (0.5 mg) syrup; this was followed by a 4 week wash-out phase. Diary card evaluation was performed by the parent or guardian for the duration of the study and recorded wheeze and cough twice daily as well as medication used. The percentage of symptom-free days decreased significantly in both groups (P < 0.005) with placebo-treated infants experiencing significantly more symptom-free days compared with the Ketotifen group (P < 0.01), although this difference was never more than 10% in any 4 week treatment period. Symptom severity scores and use of beta-agonist medication were also less in the placebo-treated infants but did not reach statistical significance. This study was unable to show a therapeutic advantage of Ketotifen over placebo in this group of infants with chronic cough and/or wheeze and the apparent statistical advantage of placebo is not a clinically relevant finding.

Child, Preschool

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

The psychological profile of parents who volunteer their children for clinical research: a controlled study.

Three standard psychometric tests were administered to parents who volunteered their children for a randomised, double-blind placebo-controlled trial of a new asthma drug and to a control group of parents whose children were eligible for the trial but had declined the invitation. The trial took place at a children's hospital in Australia. The subjects comprised 68 parents who had volunteered their children and 42 who had not, a participation rate of 94 per cent and 70 per cent, respectively. The responses of these parents to the Gordon Survey of Interpersonal Values Questionnaire, the Coopersmith Self-Esteem Inventory and the Cattell Sixteen Personality Factor Questionnaire were analysed by computer. There was a marked difference between the psychological profiles of the two groups of parents. Volunteering parents put more value on benevolence while non-volunteering parents were more concerned with power and prestige. The self-esteem of volunteering parents was much lower than that of non-volunteering parents. Finally, volunteering parents were more introverted, exhibited greater anxiety and low supergo, while non-volunteering parents appeared to have greater social confidence and emotional stability. Since an individual's values, self-esteem and personality may be important antecedents of behaviour, these findings suggest that parents who volunteer their children for clinical research are not only socially disadvantaged and emotionally vulnerable, but may also be psychologically predisposed to volunteering. Furthermore, these findings provide evidence for the existence of a psychosocial 'filter' effect of the informed consent procedure, which may be discouraging the better educated, more privileged and psychologically resilient members of society from participation as research subjects.

Australia

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

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

Interaction of respiratory syncytial virus with human cord blood mononuclear cells.

This study on the interaction between respiratory syncytial virus (RSV) and human cord blood mononuclear cells shows that RSV replication can occur in neonatal macrophages. Although neonatal lymphocytes were not supportive of RSV replication, exposure to RSV resulted in significant inhibition of mitogen-induced transformation. Both adult and neonatal NK cell cytotoxicity were unaffected by exposure to RSV. These results suggest that RSV has preferential effects on human cord blood mononuclear cell subpopulations.

Antigens, Viral

Effects of exercise stress on various immune functions in horses.

Chemotactic locomotion and luminol-dependent chemiluminescence of neutrophils, mitogen-induced lymphocyte blastogenesis, serum cortisol concentration, immunoglobulin quantification, and leukocyte counts were determined to evaluate the effect of a single strenuous exercise in horses. Increased serum cortisol concentration (P less than 0.01) and an increased neutrophil-to-lymphocyte ratio (P less than 0.05) indicated that horses had been stressed. The chemotactic index and peak chemiluminescence production decreased significantly (P less than 0.05 and P less than 0.01, respectively) 1 day after exercise. Mitogen-induced blastogenesis of lymphocytes and serum immunoglobulin values remained unchanged in response to exercise. Results of this study indicated that a single bout of exercise may transiently impair neutrophil antimicrobial functions and nonspecific defense mechanisms, but not specific immunity in horses.

Animals

Reactions to argasid tick bites by island residents on the Great Barrier Reef.

OBJECTIVE: To attribute a cause and quantify allergic-like symptoms observed among island residents. DESIGN: Skin prick tests and intradermal injections with ultraviolet-irradiated, filtered (0.22 microns) whole-body homogenates of the soft tick, Ornithodoros capensis, were used to reproduce experimentally the symptoms observed. SETTING: Heron Island, Great Barrier Reef, Australia. PARTICIPANTS: Island residents were designated as such after having spent more than 1 month on the island during the summer seabird breeding season. INTERVENTIONS: Control measures were instigated using a residual insecticide, delta-methrin, sprayed inside sleeping quarters. MAIN OUTCOME MEASURES: Acaricide spraying reduced (X2 = 4.42; P less than 0.05) the number of island residents complaining of having been bitten by ticks, yet was considered an inefficient control measure as 67% reported being attacked by ticks after spraying. RESULTS: Among 97 island residents, elevated total IgE levels were associated with reaction to tick bite in 11 cases (X2 = 27.17; P less than 0.001), but were not of reliable diagnostic value. Symptoms included intense pruritus, blistering (a major feature), erythema, weeping lesions, lymphangitis, dull ache, rheumatic pain and general lassitude, and intense discomfort. Sera from two of four volunteers with known reactions to O. capensis and one of four others with reactions to the Australian paralysis tick, Ixodes holocyclus, cross-reacted with antigens from a total of four of six biting/stinging and non-biting arthropods (radioallergosorbent tests). CONCLUSIONS: Symptoms associated with reactions to tick bite peaked in severity at 35-40 hours and thus the response was most likely delayed type IV hypersensitivity.

Animals

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

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

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

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

Sociodemographic and motivational characteristics of parents who volunteer their children for clinical research: a controlled study.

OBJECTIVE: To determine the sociodemographic and motivational characteristics of parents who volunteer their children for clinical research. DESIGN: A questionnaire was administered to parents who volunteered their children for a randomised, double blind, placebo controlled trial of a drug to treat asthma and to a control group of parents whose children were eligible for the trial but had refused the invitation. SETTING: A children's hospital in Australia. SUBJECTS: 68 Parents who had volunteered their children and 42 who had not; a response rate of 94% and 70%, respectively. MAIN OUTCOME MEASURES: Responses of parents to questionnaire designed to assess their perceptions, attitudes, and health seeking behaviour as well as sociodemographic data. RESULTS: Volunteering parents were less well educated with only 15% (10/68) of mothers and 16% (11/68) and of fathers having had a tertiary or university education compared with 26% (11/42) of mothers and 45% (19/42) in the non-volunteering group. Fewer volunteering parents had professional or administrative jobs than did non-volunteering parents (mothers 6% (4/68); fathers 9% (6/68) v mothers 14% (6/42); fathers 31% (13/42)). Volunteering parents had less social support, and they displayed greater health seeking behaviour and consumed more habit forming substances. They were motivated by a desire to help others and to contribute to medical research, but they were also searching for more information and better ways to help their own children. CONCLUSION: Parents who volunteer their children for medical research are significantly more socially disadvantaged and emotionally vulnerable.

Adult