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Biomedical subjects

S C Tam

Publications and source records attributed to S C Tam.

At least 37 records · Page 2Linked to original sources
PubMed1998

Acarbose in NIDDM patients with poor control on conventional oral agents. A 24-week placebo-controlled study.

OBJECTIVE: To determine the efficacy of acarbose, compared with placebo, on the metabolic control of NIDDM patients inadequately controlled on maximal doses of conventional oral agents. RESEARCH DESIGN AND METHODS: In this three-center double-blind study, 90 Chinese NIDDM patients with persistent poor glycemic control despite maximal doses of sulfonylurea and metformin were randomly assigned to receive additional treatment with acarbose 100 mg thrice daily or placebo for 24 weeks, after 6 weeks of dietary reinforcement. Efficacy was assessed by changes in HbA1c, fasting and 1-h postprandial plasma glucose and insulin levels, and fasting lipid levels. RESULTS: Acarbose treatment was associated with significantly greater reductions in HbA1c (-0.5 +/- 0.2% vs. placebo 0.1 +/- 0.2% [means +/- SEM], P = 0.038), 1-h postprandial glucose (-2.3 +/- 0.4 mmol/l vs. placebo 0.7 +/- 0.4 mmol/l, P < 0.001) and body weight (-0.54 +/- 0.32 kg vs. placebo 0.42 +/- 0.29 kg, P < 0.05). There was no significant difference between the two groups regarding changes in fasting plasma glucose and lipids or fasting and postprandial insulin levels. Flatulence was the most common side effect (acarbose vs. placebo: 28/45 vs. 11/44, P < 0.05). One patient on acarbose had asymptomatic elevations in serum transaminases that normalized in 4 weeks after acarbose withdrawal. Another patient on acarbose developed severe hypoglycemia; glycemic control was subsequently maintained on half the baseline dosage of sulfonylurea. CONCLUSIONS: In NIDDM patients inadequately controlled on conventional oral agents, acarbose in moderate doses resulted in beneficial effects on glycemic control, especially postprandial glycemia, and mean body weight. Additional use of acarbose can be considered as a useful alternative in such patients if they are reluctant to accept insulin therapy.

Acarbose↗
PubMed1997

Growth hormone therapy transiently increases apolipoprotein(a) in short beta-thalassaemia major children with normal growth hormone reserve.

Recombinant human growth hormone (rhGH) is now available for treatment of short stature due to growth hormone (GH) deficiency. It's potential use in other causes of short stature raises concerns about adverse effects of long term treatment on carbohydrate and lipoprotein metabolism. We describe the serial changes in lipids, lipoproteins and apolipoproteins, including apo(a) in 12 children with beta-thalassaemia major undergoing rhGH treatment for 24-36 months. All showed satisfactory increases in height and weight. A significantly higher mean plasma apo(a) was observed at 3 months (102.6 U/l) versus baseline (71.4 U/l, P < 0.01, geometric means). Subsequently apo(a) levels gradually decreased returning to pretreatment levels after 36 months of rhGH treatment. There were parallel rises and falls in the apo(a) isoforms of different sizes during treatment. There were only minimal changes in the other lipid related parameters. All children had markedly reduced cholesterol levels (3.0 +/- 0.49 mmol/l, mean +/- S.D.) characteristic of their underlying disease. In conclusion the elevation of apo(a) by GH is only transient, there is no differential effect of rhGH on the large and small isoforms of apo(a) and there are no clinically significant adverse effects of rhGH treatment on lipoprotein metabolism.

Adolescent↗
PubMed1997

Acute renal failure and proximal tubule lesions after trichosanthin injection in rats.

The structural basis of the recently recognized renal impairment after infusion of trichosanthin (TCS), a type I ribosome inactivating protein, is uncertain, but functionally it appears to be related to a lesion in the renal tubules. In this study, renal dysfunction in experimental rats was induced by a single dose of TCS. Creatinine clearance and tubular proteinuria were used to assess renal function. Light microscopy and ultrastructure of the kidneys were examined and apoptosis in proximal tubules was evaluated by the in situ TdT-mediated nick end labeling technique. TCS-treated rats demonstrated a significant dose-dependent decrease in creatinine clearance together with a mild degree of low-molecular-weight proteinuria. The proximal convoluted tubule was the site of lesions showing individual tubular cell death, which was more abundant in rats receiving high doses of TCS. Apoptotic cell death, together with heterophagosomes and large residual bodies, was observed. DNA fragmentation was confirmed by the in situ technique. There was also a dose-dependent density of apoptotic cells. Other portions of the nephron were spared, and it was not accompanied by any inflammatory infiltrate. In conclusion, these findings are consistent with TCS-induced proximal tubular toxicity resulting in reduction of glomerular filtration rate and tubular proteinuria. The extent of injury is dosage dependent. Both necrotic cell death and apoptosis participated in the loss of cells from the proximal tubules. Such toxicity may be mediated through intracellular events induced by trichosanthin.

Acute Kidney Injury↗
PubMed1997

Prolactin profile in a cohort of Chinese systemic lupus erythematosus patients.

Prolactin (PRL) is an important immunoregulatory hormone secreted by the anterior pituitary gland. Hyperprolactinaemia has been implicated in the pathogenesis of systemic lupus erythematosus (SLE). However, clinical studies regarding the PRL level and lupus disease activity have yielded contradictory results. The aim of our present study was, therefore, to re-evaluate the association of PRL level and disease activity in SLE by analysing a larger patient cohort and following them up serially. Seventy-two consecutive SLE patients were recruited and the serum PRL level was measured at each visit. Our results showed that hyperprolactinaemia (> 500 mIU/l) occurred in 35% (25/72) of the patients. A total of 72% (18/25) of the hyperprolactinaemic patients had mild elevation (arbitrarily defined as 500-800 mIU/l) of the level only. No correlation could be found between the PRL level and various clinical and serological parameters of lupus disease activity. On serial follow-up of 44 patients, again no correlation between PRL and disease activity could be demonstrated. We conclude that hyperprolactinaemia occurs in some patients with SLE, but the serum level of PRL does not correlate with clinical or serological disease activity and is not a reliable marker for disease monitoring. The mechanism and pathoaetiological and clinical significance of hyperprolactinaemia in a small subset of SLE patients remain unclear and a longer follow-up is necessary.

Adolescent↗
PubMed1996

Research communication copper-1,10-phenanthroline induces internucleosomal DNA fragmentation in HepG2 cells, resulting from direct oxidation by the hydroxyl radical.

In view of the current speculation regarding the possible role of reactive oxygen species (ROS) in apoptosis, both under physiological conditions and in response to chemicals that promote their intracellular formation, the present investigation was undertaken to examine whether DNA fragmentation during oxidative stress results from endonuclease activity (apoptosis) or from direct attack by ROS. We report that the incubation of HepG2 cells (a human-derived hepatoma cell line) with the copper(II) complex of 1,10-phenanthroline, CuII(OP)2, results in internucleosomal DNA fragmentation, which is widely recognized as being a hallmark of apoptosis. DNA fragmentation did not occur at low temperature, but activity was restored by the addition of ascorbic acid. It is proposed that DNA fragmentation results from the direct attack of hydroxyl radicals upon DNA. Hydroxyl radicals are produced from oxygen by the redox-cycling of CuII(OP)2, which is supported by metabolic processes at normal temperature. At low temperature ascorbic acid provides an artificial cellular reducing environment, thereby restoring hydroxyl radical formation. These findings were confirmed by the detection of internucleosomal DNA fragmentation following the exposure of isolated chromatin to a biomimetic CuII(OP)2 redox-cycling system. We conclude that DNA laddering, the widely employed hallmark of apoptosis, is not unique to endonuclease activity and may also result from direct attack upon DNA by the hydroxyl radical.

Cell Death↗
PubMed1996

Evidence for differences in the post-transcriptional regulation of rat metallothionein isoforms.

The expression of metallothionein (MT)-1 and -2 mRNAs in rat liver following administration of Cd or Cu was investigated using specific oligonucleotides. The specificity was confirmed using a competitive prehybridization assay. Cd injection caused a biphasic induction of both isoform mRNAs, whereas Cu induced a sustained, monophasic response. Analysis of polyribosomal RNA showed that, after both Cd and Cu treatments, the recruitment of MT-1 mRNA into polyribosomes paralleled the increase in transcription, but the increase of polyribosomal MT-2 mRNA was less than that of total MT-2 mRNA. This indicates that not all the MT-2 mRNA induced was translated, suggesting that there is translational control of MT-2 mRNA expression, but not of MT-1 mRNA. This hypothesis was supported by the observation that, after Cu treatment, the induction of MT-1 protein was induced to the same extent as MT-1 mRNA, whereas the total MT protein (MT-1 + MT-2) was increased far less (7-fold) than MT-2 mRNA (30-fold).

Animals↗
PubMed1996

Pulsed laser treatment of plasma-sprayed hydroxyapatite coatings.

Plasma-sprayed hydroxyapatite (HA) coatings have complex microstructures. There are often variations in phase, structure and chemical composition among the starting material and coating. Some of these changes may not be acceptable for biomedical applications. Attaining all the requirements for a functional coating in a single spraying process is not easily achieved. Additional post-treatment may be necessary. This study examines the use of a pulsed laser to enhance the coating characteristics of plasma-sprayed HA coatings. Preliminary results show the laser-treated coatings having a modified microstructure with crack networks and pores in the size range 5-30 microns. The pores and cracks were quantified by an image analyser. The crack network is less significant in coatings that are treated at lower energy intensity and this could be interesting in that the laser can be used to alter the surface phase composition as well as the morphology. However, repetitive passes with the pulsed laser did not help to seal the cracks that formed.

Biocompatible Materials↗
PubMed1995

Generation of 5,5-dimethyl-1-pyrroline N-oxide hydroxyl and scavenger radical adducts from copper/H2O2 mixtures: effects of metal ion chelation and the search for high-valent metal-oxygen intermediates.

A metal-catalyzed nucleophilic addition mechanism for the formation of radical adducts of the spin trap 5,5-dimethyl-1-pyrroline N-oxide (DMPO) has been described recently (K. Makino, T. Hagiwara, A. Hagi, M. Nishi, and A. Murakami, 1990, Biochem. Biophys. Res. Commun. 172, 1073-1080; P. M. Hanna, W. Chamulitrat, and R. P. Mason, 1992, Arch. Biochem. Biophys. 296, 640-644). In the present investigation, we have demonstrated that the recently reported inhibition of copper-dependent hydroxyl radical formation by the complexing agent 1,10-phenanthroline (OP), which appears to contradict the well-known chemical nuclease properties of CuI(OP)2, is an artifact resulting from an inhibition of the nucleophilic addition of water to DMPO by OP (A. C. Mello-Filho and R. Meneghini, 1991, Mutat. Res. 251, 109-113). Copper bound to OP was found to be a good catalyst of hydroxyl radical formation: the CuII(OP)2 complex can be reduced by H2O2 and the CuI(OP)2 generated reacts with the peroxide to form .OH. In contrast, no evidence could be obtained for oxidant formation from the CuII(aq)/H2O2 reaction system, despite the detection of a prominent signal from the DMPO hydroxyl radical adduct (DMPO/.OH) (the formation of which was due solely to the nucleophilic addition of water to DMPO). The failure to generate an oxidant in this reaction mixture was attributed to the failure of hydrogen peroxide to reduce CuII(aq), as hydroxyl radical formation did occur when CuI(aq) was added directly to H2O2. However, in order to account for the high concentration of alpha-hydroxyethanol radicals detected when ethanol was included in the CuI(aq)/H2O2 reaction, the possibility that an oxidant in addition to .OH (e.g., CuO+) is generated is discussed.

Copper↗
PubMed1995

A cross-sectional study of growth, puberty and endocrine function in patients with thalassaemia major in Hong Kong.

METHODOLOGY: A cross-sectional study of growth, puberty and endocrine function was performed on 35 girls and 33 boys with thalassaemia major. RESULTS: Despite regular transfusion and chelation therapy, 75% of the girls and 62% of the boys over the age of 12 years were below the third percentile for height. Hypogonadotropic hypogonadism was found in a similar percentage of patients. Moderate to marked zinc deficiency secondary to chelation therapy was considered unlikely because normal serum zinc levels were found in all but three of our patients, but we could not exclude the possibility of a marginal status of zinc nutrition causing growth failure. Growth hormone deficiency and diabetes mellitus were sometimes encountered but hypothyroidism, hypoparathyroidism and adrenal insufficiency were rare among our patients. Most of the patients with growth failure had normal growth hormone (GH) response to insulin induced hypoglycaemia. The serum insulin-like growth factor-1 (IGF-1) levels were low in our patients and no significant difference in the serum IGF-1 levels was found between prepubertal children with or without growth failure (0.4 +/- 0.1 mU/mL vs 0.37 +/- 0.11 mU/mL, P = 0.39). Similarly, no difference in the serum IGF-1 levels was found between pubertal children with or without growth failure (0.48 +/- 0.2 U/mL vs 0.56 +/- 0.14 U/mL, P = 0.26). CONCLUSIONS: Delayed sexual maturation and a possible defect in growth unrelated to the GH-IGF-1 axis may be responsible for the growth failure in adolescent children with thalassaemia major.

Adolescent↗
PubMed1994

Calcium indicator dye Quin2 inhibits hydrogen peroxide-induced DNA strand break formation via chelation of iron.

Exposure of HeLa cells to H2O2 at 4 degrees C caused DNA strand breakage which was prevented by the metal chelator 1,10-phenanthroline, but not by neocuproine. This is believed to indicate the participation of iron, rather than copper, in the formation of reactive hydroxyl radicals (.OH) from H2O2. The calcium indicator dye Quin2 also prevented H2O2-induced DNA fragmentation. The inhibition of oxidant-induced DNA fragmentation at 37 degrees C by Quin2 is often presented as evidence for the involvement of Ca(2+)-dependent endonucleases in damage. However, our finding that Quin2 inhibits DNA fragmentation at 4 degrees C led us to investigate the possibility that Quin2 may also inhibit DNA damage via its effects on metal-dependent .OH formation. Using ESR spin trapping techniques and in vitro DNA oxidation measurements, we found that the binding of Fe by Quin2 does not prevent .OH formation, but inhibits DNA damage. This is believed to reflect the prevention of iron ion binding to DNA by Quin2, directing .OH generation to the bulk solution, thereby preventing damage. The Cu-Quin2 complex was found to be a poor catalyst of both .OH formation and in vitro DNA damage. These findings suggest that the frequently reported protective effect of Quin2 toward DNA in cells exposed to oxidants may be due to the chelation of metal ions rather than the prevention of Ca(2+)-dependent endonuclease activation.

Aminoquinolines↗
PubMed1994

Serum lipid and apolipoprotein distributions in Hong Kong Chinese.

STUDY OBJECTIVE: The aim was to describe the distribution of lipids and apolipoproteins in the Chinese population in Hong Kong. DESIGN: This was a prospective, cross sectional, population based survey. SETTINGS: The study was conducted in a single, self referred, out patient screening centre. PARTICIPANTS: Altogether 825 Chinese adults aged > or = 20 years were screened. One hundred subjects who had previously had lipid measurement and 29 who were taking lipid modifying drugs were excluded but 289 men and 407 women remained for further analysis. MAIN RESULTS: Age standardised mean (SEM) lipids concentrations for Hong Kong Chinese were total cholesterol: men, 5.48 (0.05) mmol/l and women, 5.46 (0.06) mmol/l; triglycerides: men, 1.22 (1.03) mmol/l and women, 1.00 (1.03) mmol/l; high density lipoprotein (HDL) cholesterol: men, 1.25 (0.02) mmol/l and women, 1.42 (0.02) mmol/l; low density lipoprotein (LDL) cholesterol: men, 3.56 (0.05) mmol/l and women, 3.50 (0.06) mmol/l; apolipoprotein A-I (apo A-I): men, 1.34 (0.01) g/l and women, 1.46 (0.01) g/l; and apolipoprotein B (apo B): men, 1.15 (0.02) g/l and women, 1.06 (0.02) g/l. The total to HDL cholesterol ratios were men, 4.62 (0.07) and women, 4.10 (0.08); and apo B to apo A-I ratios (apo B/A) were men, 0.88 (0.02) and women, 0.75 (0.02). While levels of total cholesterol, LDL cholesterol, apo B, triglycerides, total/HDL cholesterol, and apo B/A were positively associated with age in both sexes and were higher in men before the age 50-59 years, they rose steeply thereafter in women to cross over the levels in men. In contrast, HDL cholesterol decreased with age while apo A-I remained constant, and both were consistently higher in women than in men in all age groups. CONCLUSIONS: Hong Kong Chinese have attained lipid profiles similar to those in other developed western populations. Environmental factors seem influential in this regard. Faced with the increasing coronary mortality of recent years, there should be a major effort to reduce the cholesterol concentrations in this population.

Adult↗
PubMed1994

Hyperlipidemia after renal transplantation: treatment with gemfibrozil.

Thirty-eight renal allograft recipients who had persistent hyperlipidemia and stable renal function 27.8 +/- 18.2 months after renal transplantation were treated with gemfibrozil. Gemfibrozil therapy resulted in a decrease in the levels of total cholesterol (TC; 297.6 +/- 41.0 mg/dl to 249.2 +/- 43.7 mg/dl, -16.3%; p < 0.0001), triglyceride (TG; 231.9 +/- 116.8 to 125.7 +/- 58.4 mg/dl, -45.8%, p < 0.0005), and LDL-cholesterol (LDL-C; 203.8 +/- 37.4 to 174.5 +/- 42.5 mg/dl, -14.4%; p = 0.001), which were sustained for 29.1 +/- 16.0 months. Comparison of sequential lipid profiles between gemfibrozil-treated individuals and untreated hyperlipidemic controls matched for age, sex, time after transplantation, and the degree of hyperlipidemia, showed that gemfibrozil-treated patients had lower levels of TC (239.9 +/- 39.5 vs. 272.8 +/- 34.1 mg/dl; p < 0.005), TG (125.7 +/- 26.6 vs. 167.3 +/- 69.0 mg/dl; p < 0.05), and LDL-C (160.2 +/- 41.3 vs. 185.3 +/- 26.6 mg/dl; p < 0.05) on serial follow-up. No significant side-effect was observed with gemfibrozil therapy. Our data showed that gemfibrozil was a safe and effective drug for the treatment of hyperlipidemia in renal allograft recipients, which could reduce these patients's long-term cardiovascular risks.

Adult↗
PubMed1994

Renal reabsorption of trichosanthin and the effect on GFR.

Trichosanthin (TCS) is a ribosome-inactivating protein that has a wide range of biological and pharmacological activities. Due to its small molecular size, TCS is filtered by the glomerulus and can be recovered from urine. A previous experiment showed that the kidney is an important organ for its elimination. However, urine TCS recovery was unexpectedly small, suggesting renal reabsorption of this compound. To substantiate renal TCS reabsorption, different doses of TCS were injected intravenously into rats. Increasing the dose from 0.375 mg/kg to 12 mg/kg enhanced the percentage urine recovery from less than 0.29 +/- 0.06% to 39.07 +/- 2.46%. This demonstrated that TCS is reabsorbed by a saturable mechanism. Reabsorption of most small molecular weight filterable proteins shares a common endocytotic process. It is very likely that TCS utilizes the same process for reabsorption. When a filterable protein such as hemoglobin was infused with TCS, it competed with TCS for reabsorption and therefore increased the percentage urine TCS recovery to 35 +/- 2%. Infusion of another filterable protein, lysozyme, increased recovery to 3.2 +/- 0.8%. This supports the proposal that renal TCS uptake utilizes the common endocytotic mechanism. It was also found in this study that injection of TCS depressed the glomerular filtration rate (GFR), implying renal toxicity. This effect can be attributed to ribosome inactivation which takes place inside the cells. Should reabsorption of TCS be reduced, renal toxicity will disappear. For this purpose, dextran-trichosanthin (DXTCS) conjugate was synthesized to increase its effective molecular size.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Hypopituitarism after tuberculous meningitis in childhood.

OBJECTIVE: To study the prevalence and pathogenesis of hypopituitarism following tuberculous meningitis in childhood. DESIGN: A retrospective cross-sectional study. SETTING: A university teaching hospital and a tuberculosis referral center. PATIENTS: Forty-nine patients, aged 23.4 +/- 6.0 years (mean +/- SD), who had tuberculous meningitis in childhood (age at diagnosis, 5.9 +/- 5.0 years) were studied. MEASUREMENTS: A detailed assessment of hypothalamic-pituitary function, including conventional stimulation tests and responses to four hypothalamic releasing hormones, was done. Magnetic resonance imaging of the hypothalamic-pituitary region was performed in patients with abnormal endocrine function. RESULTS: Ten patients were found to have abnormal pituitary function: Seven had growth hormone deficiency, four of whom also had gonadotropin deficiency; the other three had gonadotropin deficiency, corticotropin deficiency, and mild hyperprolactinemia, respectively; none had diabetes insipidus. Among those with growth hormone deficiency, a significant correlation (r = 0.749, P < 0.05) was found between the height standard deviation score and the age at diagnosis of tuberculous meningitis. Growth hormone, corticotropin, and gonadotropin responses to growth hormone releasing hormone, corticotropin releasing hormone, and gonadotropin releasing hormone, respectively, suggested a hypothalamic defect in five patients. Magnetic resonance imaging scans of the hypothalamic-pituitary region were abnormal in five patients. CONCLUSIONS: Hypopituitarism was documented in 20% of a small subset of patients years after recovery from tuberculous meningitis in childhood. The cause appears to be tuberculous lesions affecting the hypothalamus, pituitary stalk and, directly or indirectly, the pituitary itself. Early recognition and treatment can be beneficial.

Adolescent↗
PubMed1993

The biological activities of trichosanthin after coupling to dextran.

1. The major biological and pharmacological activities of trichosanthin (TCS) were retained after its covalent coupling to dextran T40. The potency and toxicity was generally reduced. 2. A dose of TCS as low as 0.02 mg/25 g induced 100% mid-term abortion whereas 20 times as much dextran-trichosanthin (DX-TCS) is required to produce the same effect. 3. A third of the mice died at a TCS dose of 0.1 mg/25 g but 4 times as much DX-TCS did not cause any death. 4. DX-TCS suppressed Con A or PHA induced lymphocyte transformation in a dose dependent manner. The potency was decreased as compared to TCS. 5. Both TCS and DX-TCS exhibited a cytostatic effect on cultured tumour cells (PU5 and hepatoma), the former being more potent.

Abortifacient Agents↗