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Biomedical subjects

Y C Lo

Publications and source records attributed to Y C Lo.

At least 55 records · Page 3Linked to original sources

Inactivated hepatitis A vaccine in healthy Chinese adults.

OBJECTIVES: To study the safety, tolerability of and immune response to an inactivated hepatitis A vaccine in healthy Chinese adults. DESIGN: Seronegative subjects were randomized to receive formalin-inactivated, alum-adjuvanted hepatitis A vaccine (25 units, MSD) at 0, 24 weeks (group I) or 0, 2, 24 weeks (group II). SUBJECTS: Healthy Chinese adults aged 18 years or above were recruited. All subjects were staff of a regional hospital and primary care clinic in Hong Kong. MAIN OUTCOME MEASURES: Side-effects, tolerance, seroconversion rate and geometric mean titre (GMT) of the two groups were noted and compared. RESULTS: Thirty-two and 28 people were recruited into group I and group II, respectively. Antibody against hepatitis A developed in 100% of the recipients 1 month after the last dose of either regimen, with a GMT of around 450 IU L-1. High antibody levels were maintained at the end of one year. There was no statistically significant difference in the seroconversion rates and GMTs between the two regimens of vaccination. All subjects in group I seroconverted at 24 weeks after one single dose of the vaccine. No adverse effects were reported except for complaints of some mild local and constitutional symptoms. CONCLUSIONS: The inactivated hepatitis A vaccine is highly immunogenic, safe and well-tolerated.

Adult↗

Vasomolol: an ultra short-acting and vasorelaxant vanilloid type beta 1-adrenoceptor antagonist.

The ultra-short-acting and vasorelaxant beta 1-adrenoceptor blocking activities of vasomolol, a guaiacoxypropanolamine derivative of vanillic acid ethyl ester, were studied. Vasomolol (0.5, 1.0, 3.0 mg/kg intravenously, i.v.) produced a dose-dependent bradycardia response and demonstrated particularly a hypotensive action with an ultra-short-acting property in pentobarbital-anesthetized normotensive rats. Vasomolol's steady state of beta-blockade was attained < or = 10 min after initial infusion, and a rapid recovery from blockade occurred after discontinuation of the infusion, although intravenous infusion of vasomolol (300 micrograms/kg/min) could not inhibit pressor responses induced by (-)phenylephrine (10 micrograms/kg i.v.). In isolated rat thoracic aorta, vasomolol (1-10 microM) inhibited vascular smooth muscle contractions induced by both (-)phenylephrine (10(-5) M) and high K+ (75 mM) concentration dependently. This inhibitory effect of vasomolol was more sensitive on K(+)-induced than on (-)phenylephrine-induced contractions, suggesting that the block of Ca2+ influx may involve the major mechanism of vasorelaxation. In isolated guinea pig tissues, vasomolol (0.01-10 microM) antagonized the (-)isoproterenol (ISO)-induced positive inotropic and chronotropic effects of the atria and tracheal relaxation responses in a concentration-dependent manner. The parallel shift to the right of the concentration-response curve of (-)ISO suggested that vasomolol was a beta-adrenoceptor competitive antagonist. The effect of vasomolol was more potent on atria than on tracheal tissues, indicating that it possesses beta 1-adrenoceptor selectivity. In addition, vasomolol did not show intrinsic sympathomimetic activity (ISA). Moreover, the binding characteristics of vasomolol were evaluated in [3H]dihydroalprenolol ([3H]DHA) binding to porcine ventricular membranes. Vasomolol was an ultra-short-acting and highly selective beta 1-adrenoceptor antagonist with vasorelaxant activity and is devoid of ISA.

Adrenergic beta-Antagonists↗

Capsinolol: the first beta-adrenoceptor blocker with an associated calcitonin gene-related peptide releasing activity in the heart.

1. The beta-adrenoceptor blocking and calcitonin gene-related peptide (CGRP)-releasing properties of capsinolol (N-[4-(2-hydroxy-3 (isopropylamino) propoxy)-3-methoxybenzyl]-nonanamide), derived from nonivamide, were investigated under in vivo and in vitro conditions. 2. Capsinolol (0.1, 0.5, 1.0 mg kg-1, i.v.), as well as (+/-)-propranolol, produced a dose-dependent bradycardia response and a temporary pressor action in urethane-anaesthetized normotensive Wistar rats. These cardiovascular effects were different from the vagus reflex and parasympathetic efferent effects shown by capsaicin (0.1 mg kg-1, i.v.) in the rat. 3. Capsinolol (1.0 mg kg-1) inhibited the tachycardia effects induced by (-)-isoprenaline, but had no blocking effect on the arterial pressor responses induced by (-)-phenylephrine. The findings suggest that capsinolol possesses beta-adrenoceptor blocking activity, but it has no alpha-adrenoceptor blocking activity. 4. In guinea-pig isolated tissues, capsinolol (10(-8) to 10(-6) M) antagonized (-)-isoprenaline-induced positive chronotropic and inotropic effects of the atria and tracheal relaxation responses in a concentration-dependent manner. The parallel shift to the right of the concentration-response curve of (-)-isoprenaline suggests capsinolol is a beta-adrenoceptor competitive antagonist. 5. Capsinolol (10(-5) to 10(-4) M) exhibited a positive cardiotonic effect that was not inhibited by (+/-)-propranolol and reserpine, but was inhibited by capsazepine (10(-6) M) and CGRP8-37 (10(-6) M). This effect was independent of intrinsic sympathomimetic effects. 6. An immunoassay of released CGRP from guinea-pig isolated perfused heart indicated that capsinolol increases the release of CGRP and thus produces positive cardiotonic effects. 7. In conclusion, capsinolol is a non-selective beta-adrenoceptor antagonist with capsaicin-like cardiotonic properties unrelated to traditional intrinsic sympathomimetic effects. It is suggested that capsinolol causes CGRP release from cardiac sensory neurones via a non-adrenergic mechanism and then activates CGRP receptors on cardiac muscle.

Adrenergic beta-1 Receptor Antagonists↗

The first one hundred AIDS cases in Hong Kong.

OBJECTIVE: To study the clinical and epidemiological characteristics of the first 100 reported AIDS cases in Hong Kong. PATIENTS AND METHODS: The case records of the first 100 AIDS cases reported to the Department of Health were retrieved. An analysis was made on their demographic data, clinical and immunologic profile, treatment received as well as mortality. RESULTS: The AIDS patients were reported over a ten-year period, from February 1985 to March 1994. The majority of them were male, Chinese and between the age of 20 and 49. More than 80% acquired HIV via sexual contact. The most common primary AIDS- defining illness was Pneumocystis carinii pneumonia (PCP), which occurred in 46 patients. Eight episodes of Penicillium marneffei infection have been recorded. Fifty-nine patients have received antiretroviral therapy whereas PCP prophylaxis was given to 47 patients. The mean CD4 count at HIV and AIDS diagnosis was 394/microliters and 121 /microliters respectively. Sixty-seven patients were known to have died at the time of the analysis. PCP was the most common cause of death, accounting for over one-fifth of the cases. The median survival after AIDS diagnosis was less than 2 months for cases reported in 1985-1987 and over 15 months for those of 1990-1991. CONCLUSION: Pneumocystis carinii pneumonia was the most common initial AIDS-defining disease and cause of death in Hong Kong. Survival of the patients has gradually improved over the past few years.

Acquired Immunodeficiency Syndrome↗

Effect of capsaicin on membrane currents in cultured vascular smooth muscle cells of rat aorta.

The application of capsaicin (1 microM) produced a minor relaxant effect in endothelium-denuded rat aortae. However, capsaicin caused a greater relaxation of blood vessels precontracted with high K+ or phenylephrine. The effects of capsaicin on the ionic currents were also examined in A7r5 vascular smooth muscle cells. The tight-seal whole-cell voltage clamp technique was used. Capsaicin inhibited the Ba2+ inward current (IBa) through the voltage-dependent L-type Ca2+ channel in a concentration-dependent fashion, whereas calcitonin gene-related peptide and phenylephrine produced a minor increase in IBa. Capsaicin did not alter the overall shape of current-voltage relationship of IBa. However, capsaicin (3 microM) shifted the quasi-steady-state inactivation curve of IBa to more negative membrane potential by about 5 mV. These effects of capsaicin on IBa were reversible. In addition, capsaicin had inhibitory effects on voltage dependent K+ currents. These results suggest that inhibition of the voltage-dependent L-type Ca2+ channel is involved in the capsaicin-induced relaxation of the vascular smooth muscle, whereas capsaicin-induced inhibition of voltage-dependent K+ channels might produce an increase in cell excitability.

Animals↗

A reduced dose approach to hepatitis B vaccination for low-risk newborns and preschool children.

The effectiveness of a 2.5 micrograms dose of the hepatitis B vaccine (B-Hepavac II) was compared with that of 5 micrograms in 587 low-risk neonates and 777 preschool children of age 3-8 years. The vaccines were administered at months 0, 1 and 3, with postvaccination serology tested at months 4 and 12. The seroconversion rates of the 2.5 microgram recipients (newborn: 93.5%; preschool children: 97.4%) are comparable with the 5 micrograms group (newborn: 95.7%; preschool children: 98.7%). The seroconversion rates of the newborns are, however, significantly lower in the 2.5 micrograms group if positive response is taken as a titre > 10 IU l-1, instead of > 0 IU l-1. The older children, on the other hand, achieved a higher seroconversion rate and geometric mean titre (GMT) when compared with the newborns. irrespective of the dose received.

Child, Preschool↗

C-fiber-evoked autonomic cardiovascular effects after injection of Piper betle inflorescence extracts.

Piper betle inflorescence extracts contain eugenol (6.2%) and safrole (78.9%). Intravenous injections of water extracts of P. betle inflorescence (PBE), eugenol, and safrole in rats induced hypotensive and bradycardiac effects, whereas both intraarterial and intrathecal injections of PBE, eugenol and safrole resulted in hypotensive and tachycardiac effects. Moreover, the effects of intravenous injections of PBE were reversed or inhibited by the pretreatment with bilateral vagotomy, atropine (1 mg/kg, i.p.) and capsaicin (100 mg/kg, s.c.). Effects of intraarterial injections of PBE on blood pressure were inhibited by the pretreatment with substance P (SP) antagonist (1 nmol, i.t.) and clonidine (2.5 micrograms, i.t.), while heart rate was only inhibited by the pretreatment with SP antagonist (1 nmol, i.t.). In addition, the tachycardia resulting from intrathecal injections of PBE was inhibited by pretreatment with propranolol (0.3 mg/kg, i.v.). Eugenol and safrole induced the same pattern on blood pressure and heart rate changes as PBE in rats after various treatments. This report suggests that acute administration of betel inflorescence extracts by different routes may activate C-fiber-evoked parasympathetic and sympathetic cardiovascular reflexes in rats.

Animals↗

Practice of drug abuse among inmates of a drug rehabilitation centre in Hong Kong.

Sharing of contaminated injection equipment accounts for the rapid spread of the human immunodeficiency virus (HIV) among injecting drug users (IDUs). The profile of drug addiction practice among inmates of the Shek Kwu Chau Drug Rehabilitation Centre in Hong Kong was studied. Registers on all the new admissions to the Centre during a two-year period between 1990 and 1992 were reviewed. Of the 3129 drug users studied, 68.7% were aged between 21 and 40; 84.8% were IDUs and heroin was the commonest drug of addition. Nearly 70% of the IDUs had never shared injection equipment with others. There were significantly more young addicts (< or = 30 years old) who had shared needles compared with the older ones (31.2% vs 26.8%, P < 0.05). Those with addiction time > 6 months were more likely to have shared needles than the new ones. Only 19% of the drug users accepted HIV testing at their first admission. Factors speculated for the low needle-sharing rates among IDUs in Hong Kong and the low HIV prevalence in the IDU population are discussed. It is of utmost importance to monitor continuously such a high-risk behaviour pattern so as to design appropriate intervention strategies to stop the transmission of HIV.

Acquired Immunodeficiency Syndrome↗

Profile of opportunistic infections among HIV-1 infected people in Hong Kong.

BACKGROUND: To determine the spectrum of opportunistic infections in patients with human immunodeficiency virus (HIV-1) infection in Hong Kong. METHODS: A retrospective study of 214 HIV-1-infected patients, seen between December 1984 and December 1993 in a specialist clinic for HIV/AIDS: RESULTS: A majority (94%) of the patients in the cohort were male; 84% had acquired HIV via sexual contacts. Two-thirds were ethnic Chinese. Ninety-two (43%) had developed AIDS, and 54(25%) had presented with other non AIDS-defining opportunistic infections during the study period. The primary AIDS defining illnesses of 80 patients were infections: Pneumocystis carinii pneumonia (50%), extrapulmonary tuberculosis (10%) and cytomegalovirus (CMV) disease (8%). Opportunistic infections among Chinese and non-Chinese were similar in spectrum, though higher frequencies of infection with CMV, Mycobacterium avium intracellulare and tuberculosis were seen among Chinese, whereas the opposite was true for Pneumocystis carinii pneumonia, toxoplasmosis and cryptosporidiosis. Disseminated Penicillium marneffei infection was another significant disease for HIV-positive patients. Common non AIDS-defining opportunistic infections included herpes zoster, oral candidiasis, herpes simplex infection and genital/anal wart. The median CD4 count at HIV diagnosis for AIDS patients was much lower than non-AIDS patients (147 vs 546/ul). Survival of deceased AIDS patients was poor, with a median of only five months. Survival has however, apparently, improved over the recent years. CONCLUSIONS: In Hong Kong, Pneumocystis carinii pneumonia remained the most common primary AIDS event, while Penicillium marneffei was emerging as another significant cause of major infection. Herpes zoster and oral candidiasis were the two most frequently encountered minor opportunistic infections.

AIDS-Related Opportunistic Infections↗

Magnolol and honokiol isolated from Magnolia officinalis protect rat heart mitochondria against lipid peroxidation.

In isolated rat heart mitochondria lipid peroxidation was induced with ADP and ferrous sulfate (FeSO4). Oxygen consumption and malondialdehyde (MDA) production were measured to quantitate lipid peroxidation. The antioxidant effects of magnolol and honokiol purified from Magnolia officinalis were 1000 times higher than that of alpha-tocopherol. The IC50 values of magnolol and honokiol for inhibition of oxygen consumption were 8.0 x 10(-8) M and 1.0 x 10(-7) M, respectively, while that of alpha-tocopherol was 1.0 x 10(-4) M. Magnolol at 0.5 microM inhibited 71.4 +/- 9.4% of oxygen consumption and 59.3 +/- 4.6% MDA production. At the same concentration, honokiol inhibited 78.1 +/- 4.7% of oxygen consumption and 86.9 +/- 4.0% of MDA production. Of conjugated diene formation 48.4 +/- 4.6% and 53.1 +/- 3.4% were inhibited by 0.5 microM magnolol and honokiol, respectively. Also both magnolol and honokiol exhibited free radical scavenging activities as shown by the diphenyl-p-picrylhydrazyl assay, but they were less potent than alpha-tocopherol.

Animals↗

Three-dimensional conformal radiation therapy in locally advanced carcinoma of the prostate: preliminary results of a phase I dose-escalation study.

PURPOSE: The acute morbidity of doses of 64.8-75.6 Gy and preliminary observations of late complications and tumor response using 3-dimensional conformal radiation therapy in carcinoma of the prostate are assessed. METHODS AND MATERIALS: 123 patients (Stage A2-12, B1-17, B2-43, C-51) were irradiated to the prostate and seminal vesicles using a 3-dimensional conformal radiation therapy technique. The median follow-up time was 15.2 months. The minimum tumor dose was 64.8-66.6 Gy in 49 patients, 70.2 Gy in 46, and 75.6 Gy in 28. Toxicity was scored according to the Radiation Therapy Oncology Group morbidity grading system. RESULTS: This technique of 3-dimensional conformal radiation therapy was well-tolerated with minimal acute morbidity. Only 32% of patients had grade 2 or 3 acute morbidity requiring short-term medication for relief of urinary symptoms or diarrhea. Only one patient (0.8%) has so far developed a severe (grade 4) late complication. Serum prostate specific antigen concentrations normalized in 67% of patients (64/96) within 1-14 months (median 4.5 months) after treatment and were progressively decreasing at last measurement in an additional 22% (21/96). Abnormal rising prostate specific antigen levels were observed in 15 patients, 11 of whom have already developed other evidence of relapsing disease. CONCLUSION: Acute toxicity for the doses tested with this 3-dimensional conformal radiation therapy technique is reduced compared to traditional treatment techniques, and the initial tumor response as assessed by prostate specific antigen measurement is highly encouraging with prostate specific antigen levels returning to normal in the majority of patients. Based on these results, a further increase of the dose to 81 Gy has been implemented in accordance with the schema of an ongoing Phase I dose-escalation study.

Adenocarcinoma↗

Autonomic and sensory cardiovascular activities of nonivamide: intrathecal administration of clonidine.

The effects of nonivamide on the cardiovascular system were examined and compared with the effects of substance P (SP) in rats. Intravenous (i.v.) injection (10 micrograms/kg) of nonivamide produced triphasic pressure responses (A; depressor, B; pressor, and C; depressor) and biphasic bradycardia responses (f; fast bradycardia and s; slow bradycardia). IA injection (10 micrograms/kg) into the epigastric artery caused hypotension and mild tachycardia. The effects of atropine, vagotomy, SP antagonist, propranolol, and clonidine on these responses were examined and mechanisms responsible for the nonivamide-induced responses are postulated as follows. A and f are due to vagal reflex resulting from the excitation of afferent sensory neurons in the heart and are parasympathetic efferent effects from the nucleus solitarius. B is involved in sympathetic activation, partly caused by the release of SP in the spinal cord. C is due to the vasodilatory effect of SP released from perivascular stores. s was diminished by vagotomy and is due to the bradycardiac effect of acetylcholine, released by SP, from cardiac stores. The activation of the autonomic system is inhibited by clonidine and involved in the wide spectrum of nonivamide-induced cardiovascular effects.

Animals↗

Astragalus membranaceus and Polygonum multiflorum protect rat heart mitochondria against lipid peroxidation.

We isolated rat heart mitochondria and induced lipid peroxidation with ADP and FeSO4. Oxygen consumption and MDA formation were measured for quantitating the amount of lipid peroxidation. Using these methods, we screened the water extracts of 14 Chinese medicinal herbs for their effect on lipid peroxidation. It was found that Astragalus membranaceus inhibited 42.1 +/- 3.4% of oxygen consumption and 39.8 +/- 3.2% of MDA production at concentration of 2 mg dried herb/ml mitochondrial suspension. At the same concentration, Polygonum multiflorum inhibited 52.1 +/- 7.3% of oxygen consumption and 50.9 +/- 5.3% of MDA production. Other herbs did not inhibit lipid peroxidation to 50% of control at concentration up to 6 mg dried herb/ml mitochondrial suspension. Purification and identification of the active component(s) in Astragalus membranaceus and Polygonum multiflorum as well as their clinical application await further studies.

Adenosine Diphosphate↗

Effect of flavan-3-ol tannins purified from Camellia sinensis on lipid peroxidation of rat heart mitochondria.

We induced lipid peroxidation in rat heart mitochondria with FeSO4 and compared the inhibitory effect of various flavan-3-ol tannins on it. These tannins were purified from Chinese tea (Camellia sinensis). Oxygen consumption and malondialdehyde formation were used to quantitate the amount of lipid peroxidation. The free radical scavenger activity of tannins was then measured with a diphenyl-p-picrylhydrazyl method. These tannins significantly inhibited lipid peroxidation at micromolar concentration. Their potencies were higher than that of Trolox, a water soluble analogue of vitamin E. Since epicatechin-3-O-gallate, epigallocatechin-3-O-gallate and gallocatechin-3-O-gallate were more potent than other flavan-3-ol tannins in these assays, we considered that a galloyl group in 3-O-position increased the scavenger activity of flavan-3-ol tannins as well as their potency in inhibiting lipid peroxidation.

Animals↗

Cardiovascular interactions of nonivamide, glyceryl nonivamide, capsaicin analogues, and substance P antagonist in rats.

Nonanoyl vanillylamide-4-o-glycerol (glyceryl nonivamide, GLNVA) a nonpungent ether-linked derivative of nonanoyl vanillylamide (nonivamide, NVA) was compared to capsaicin (CAP) and NVA with regard to its depressor response in rats. IV injection of CAP and NVA (10(-1) to 10(-4) mg/kg) in Wistar rats elicit a triphasic blood pressure response, bradycardia, and aponea. However, IV injection of GLNVA results in a monophasic reduction in blood pressure, with little effect on heart rate and respiration. The depressor response to GLNVA was not diminished by bilateral vagotomy or by systemic pretreatment with atropine. Following the CAP pretreatment, the delayed hypotension induced by CAP, NVA, and the hypotension of GLNVA was almost abolished. Injection of CAP, NVA (10 micrograms/kg), or GLNVA (100 micrograms/kg) into one femoral artery elicited a fall in blood pressure in the rat. This effect was abolished following intrathecal injection of substance P antagonist [D-Pro2,D-Trp7,9]-SP. Microejections of CAP, NVA, or GLNVA into the nucleus tractus solitarii (NTS) evoked hypotension, the bradycardia following microejection of CAP and NVA into the NTS occurred only at higher doses of GLNVA. From these results it is suggested that GLNVA appears to act more exclusively than CAP by stimulating peripheral perivascular small diameter C-fiber sensory nerves.

Animals↗

The effect of single doses of radiation on mouse spinal cord.

We have used a mouse model to study spinal cord injury following single doses (12 to 75 Gy) of radiation. The spinal cord (T9,10-L4,5) of C3Hf/Sed//Kam mice was irradiated and response graded using four levels of neurological change. Findings were: (a) the doses required to paralyze 50% of animals (ED50) were 19.79, 20.77, and 21.85 Gy for mild, partial, and complete paralysis, respectively, as measured 200-360 days after radiation. (b) Most damage was progressive but it was not necessarily so; after doses up to 28 Gy recovery was occasionally seen. (c) Latency depended on the dose and the level of damage. Following doses around the ED50, paralysis occurred between 180 to 300 days. (d) There were significant fluctuations in the dose-latency relationship at doses less than 35 Gy. Latency may be not a reliable endpoint to compare biological effects of radiation in this dose range. (e) The radiosensitivity of mouse spinal cord was similar to that reported for rats. (f) Histologically, demyelination was the dominant lesion in the paralyzed animals. We conclude that the mouse is a good animal model to study radiation damage to the spinal cord, at least when a 2.2 cm length is irradiated.

Animals↗