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Biomedical subjects

Z X Lu

Publications and source records attributed to Z X Lu.

At least 19 recordsLinked to original sources
PubMed2006

Optimization of a medium for enhancing nicotine biodegradation by Ochrobactrum intermedium DN2.

AIMS: To optimize a medium for nicotine degradation by Ochrobactrum intermedium DN2 in presence of yeast extract, glucose and Tween 80 using response surface methodology (RSM). METHODS AND RESULTS: In this study, the effects of yeast extract, glucose and Tween 80 on nicotine degradation were investigated in flasks using a novel nicotine-degrading bacterium, O. intermedium DN2. A full factorial central composite design was applied in the design of experiments and in the analysis of the experimental data. The results showed that the most significant variable influencing nicotine degradation was yeast extract, followed by glucose, and then Tween 80. Moreover these three factors interacted with each other and combined to produce positive effects on nicotine degradation. The experimental data also allowed the development of an empirical model (P < 0.0001) describing the inter-relationship between independent and dependent variables. By solving the regression equation, the optimal values of the variables were determined as: yeast extracts 0.094%, glucose 0.101% and Tween 80 0.080%. Using the medium obtained, about 1,220 mg l(-1) of nicotine was degraded (95.55%) within 10 h at the specific biodegradation of 116.59 mg l(-1) h(-1) in 30-l bioreactor containing 25-l tobacco extract. CONCLUSIONS: An optimal medium of nicotine degradation by the strain DN2 was obtained. SIGNIFICANCE AND IMPACT OF THE STUDY: RSM proved to be reliable in developing the model, optimizing factors and analysing interaction effects. The results provide better understanding on the interactions between yeast extract, glucose and Tween 80 for nicotine biodegradation.

Biodegradation, Environmental↗
PubMed2004

Arabinoxylan fibre improves metabolic control in people with Type II diabetes.

OBJECTIVE: To determine whether diet supplementation with arabinoxylan-rich (AX)-fibre from wheat improves glycaemic control in Type II diabetes. DESIGN: Randomized, crossover intervention trial. SETTING: Monash Medical Centre. SUBJECTS: A total of 15 subjects with Type II diabetes. INTERVENTIONS: Over two 5-week periods, subjects supplemented their usual diet with control bread and muffins (50% whole wheat, 50% white flour) (control diet) or with AX-bread and muffins (50% whole wheat, 36% white flour, 14% AX fibre) (AX diet). Subjects completed a 7-day food diary. At 0 and 5 weeks, venous blood was collected for determination of fasting and 2 h glucose, insulin, fructosamine and blood lipids. Blood pressure, body weight and body fat were also determined. A 24 h faecal sample, from 12 subjects, was weighed and analysed for faecal polysaccharide as a marker for dietary compliance. RESULTS: Control and AX diets were similar except the AX diet supplied an additional 15.1 (12.0-18.5) (mean (95% confidence intervals)) g/day dietary fibre (P=0.000). Consumption of the AX diet increased faecal output by 61.5 (0.2-122.8) g/day (P=0.05) on a wet weight basis and significantly lowered fasting and 2 h plasma glucose, 2 h insulin and serum fructosamine (P=0.002, 0.000, 0.015, and 0.02, respectively). Blood lipids, body weight, fat mass and blood pressure remained unchanged. CONCLUSION: A supplement of 15 g/day of AX-rich fibre can significantly improve glycaemic control in people with Type II diabetes.

Blood Glucose↗
PubMed2001

Discovery of a series of nonpeptide small molecules that inhibit the binding of insulin-like growth factor (IGF) to IGF-binding proteins.

Insulin-like growth factors (IGF-I and II) play an important role in metabolic and mitogenic activities through stimulation of the IGF-I receptor on the cell surface. Although the concentration of IGF in blood and cerebrospinal fluid is quite high (>100 nM), this large pool of IGF is biologically inactive because of its association with six distinct binding proteins, which form high-affinity complexes with IGF. Thus, inhibitors of IGF-binding proteins (IGFBPs), especially IGFBP-3, could potentially alter the distribution between the "free" and "bound" forms of IGF and thereby elevate biologically active IGF-I to exert a beneficial effect on those patients with diseases that respond to the application of exogenous IGF-I. Whereas IGF-I peptide variants, which bind to IGFBPs but not the IGF-I receptor, have been shown to be potent IGF/IGFBP inhibitors, small molecule nonpeptide IGF/IGFBP inhibitors have the potential advantages of oral bioavailability and flexible dosing regimen. Here we report the discovery of several isoquinoline analogues, exemplified by 1 and 2, which bind IGFBP-3 as well as other IGFBPs at low nanomolar concentrations. More importantly, both compounds were shown to be able to release biologically active IGF-I from the IGF-I/IGFBP-3 complex. These results point to the feasibility of developing orally active therapeutics to treat IGF-responsive diseases by optimization of the lead molecules 1 and 2.

3T3 Cells↗
PubMed2000

Arabinoxylan fiber, a byproduct of wheat flour processing, reduces the postprandial glucose response in normoglycemic subjects.

BACKGROUND: Arabinoxylan (AX) is the major component of dietary fiber in the cereal grains that make up a large proportion of our diet. However, the physiologic effect of AX is unknown. OBJECTIVE: The objective of this study was to determine whether AX improves postprandial glucose and insulin responses in healthy humans. DESIGN: AX-rich fiber was extracted from the byproduct of wheat-flour processing. Three isoenergic breakfasts, comprising bread, margarine, and jam, had 75 g available carbohydrate, 10 g protein, and 14 g fat and contained 0, 6, and 12 g AX-rich fiber, respectively. Fourteen healthy subjects consumed the 3 breakfast meals in random order on 3 mornings >/=3 d apart after an overnight fast. Blood was taken from the subjects at regular intervals over 2 h and was analyzed for glucose and insulin. The palatability of bread containing AX-rich fiber was compared with that of a control bread. RESULTS: Compared with the control meal containing 0 g AX-rich fiber, the peak postprandial glucose concentration after meals containing 6 and 12 g AX-rich fiber was significantly lower (6. 3 +/- 1.3 compared with 7.2 +/- 1.0 mmol/L, P < 0.01; 5.9 +/- 0.9 compared with 7.2 +/- 1.0 mmol/L, P < 0.001, respectively). The incremental area under the curve (IAUC) for glucose was 20.2% (95% CI: 5.8%, 34.7%; P < 0.01) and 41.4% (25.9%, 56.8%; P < 0.001) lower, whereas IAUC for insulin was 17.0% (2.0%, 32.1%; P < 0.05) and 32. 7% (18.8%, 46.6%; P < 0.001) lower, respectively. Bread containing AX-rich fiber was as pala as 50% whole-wheat bread when evaluated with sensory analysis by 30 volunteers. CONCLUSIONS: Postprandial glucose and insulin responses were improved by ingestion of AX-rich fiber. Further research is required to determine whether AX-rich fiber is of benefit to people with type 2 diabetes.

Adult↗
PubMed2000

Arabinoxylan fiber from a by-product of wheat flour processing behaves physiologically like a soluble, fermentable fiber in the large bowel of rats.

Arabinoxylan is a major dietary fiber component of many cereals. Its physiological effects in the colon are largely unknown. This study examined the effects of an arabinoxylan-rich fiber (AX) extracted from a by-product of wheat flour processing in the rat colon compared with well-characterized soluble/rapidly fermentable and insoluble/slowly fermentable fibers. Rats were fed diets containing no fiber (NF) or 100 g/kg of total dietary fiber from AX, guar gum (GG) or wheat bran (WB) for 4 wk. Cecal mass and short-chain fatty acid (SCFA) pool were significantly higher while pH was significantly lower in the fiber-supplemented groups, particularly in the AX and GG groups. The pattern of SCFA production in the cecum was altered; AX fiber was a good source for acetate while GG and WB favored propionate and butyrate production, respectively. Fecal output was 7-, 6- and 5-fold higher, respectively, in the AX, GG and WB than in the NF groups (P < 0.01). All epithelial proliferation indices (crypt column height, number of mitotic cells/crypt column and mitotic index) differed significantly across the groups in a descending order of AX > GG > WB > NF. Distal mucosal dipeptidyl peptidase IV activities, which indicate cell differentiation status, were significantly lower in fiber-supplemented groups than in the NF groups. Distal mucosal alkaline phosphatase activities, induced as a response to injury or stress, were significantly higher for the AX and GG groups than for the NF or WB groups (P < 0.001). These results indicate that AX fiber behaves like a rapidly fermentable, soluble fiber in the rat colon.

Animals↗
PubMed2000

[The regulating mechanism of anti-fungicides on mouse oocyte development].

AIM: To study the mechanism of the effect of gonadotropin-induced oocyte maturation. METHODS: Mouse oocytes were cultured in HX-medium, and the effects of amphotericin B and ketoconazole on resumption of meiosis of mouse oocyte were examined. RESULTS: 1. FSH(10-200 IU/L) induced a dose-dependent manner of oocytes maturation in CEO. A maximum increase in GVBD was observed with 25-50 IU/L FSH. 2. Amphotericin tericim B (0.025-2.5 micrograms/L) caused significant increases in GVBD in CEO, which mimicked the function of FSH. 3. Ketoconazole (10(-7)-10(-3) mol/L) inhibited the effect of FSH on resumption of meiosis, but no effect on oocyte spontaneous maturation. CONCLUSION: Amphotericin B and ketoconazole are able to affect mouse oocyte maturation, and indicates that they have a regulation on FSH-induced synthesis of meiosis-activating sterol.

Amphotericin B↗
PubMed1998

Inhibition of eukaryote protein kinases and of a cyclic nucleotide-binding phosphatase by prenylated xanthones.

A series of prenylated xanthones are variously potent inhibitors of the catalytic subunit (cAK) of rat liver cyclic AMP-dependent protein kinase (PKA), rat brain Ca2+ and phospholipid-dependent protein kinase C (PKC), chicken gizzard myosin light chain kinase (MLCK), wheat embryo Ca2+-dependent protein kinase (CDPK) and potato tuber cyclic nucleotide-binding phosphatase (Pase). The prenylated xanthones examined are mostly derivatives of alpha-mangostin in which the 3-hydroxyl and 6-hydroxyl are variously substituted with groups R or R', respectively, or derivatives of 3-isomangostin (mangostanol) in which the 9-hydroxyl is substituted with groups R' or the prenyl side chain is modified. The most potent inhibitors of cAK have non-protonatable and relatively small R' and R groups. Conversely, the most potent inhibitors of PKC and MLCK have bulkier and basic R' groups. Some prenylated xanthones are also potent inhibitors of CDPK. PKC and cAK are competitively inhibited by particular prenylated xanthones whereas the compounds that are the most potent inhibitors of MLCK and CDPK are non-competitive inhibitors. Prenylated xanthones having relatively small and non-protonatable R' and R groups inhibit a high-affinity cyclic nucleotide binding Pase in a non-competitive fashion.

Animals↗
PubMed1998

Displacement of insulin-like growth factors from their binding proteins as a potential treatment for stroke.

Insulin-like growth factors I and II (IGF-I and IGF-II) play an important role in normal growth and brain development and protect brain cells from several forms of injury. The effects of IGFs are mediated by type-I and type-II receptors and modulated by potentially six specific binding proteins that form high-affinity complexes with IGFs in blood and cerebrospinal fluid (CSF) and under most circumstances inactivate them. Because brain injury is commonly associated with increases in IGFs and their associated binding proteins, we hypothesized that displacement of this large "pool" of endogenous IGF from the binding proteins would elevate "free" IGF levels to elicit neuroprotective effects comparable to those produced by administration of exogenous IGF. A human IGF-I analog [(Leu24, 59, 60, Ala31)hIGF-I] with high affinity to IGF-binding proteins (Ki = 0.3-3.9 nM) and no biological activity at the IGF receptors (Ki = >10,000 nM) increased the levels of "free, bioavailable" IGF-I in the CSF. Intracerebroventricular administration of this analog up to 1h after an ischemic insult to the rat brain had a potent neuroprotective action comparable to IGF-I. This novel strategy for increasing "free" IGF levels in the brain may be useful for the treatment of stroke and other neurodegenerative diseases.

Animals↗
PubMed1998

Inhibition of eukaryote serine/threonine-specific protein kinases by piceatannol.

The protein tyrosine kinase (PTK) inhibitor piceatannol is also an inhibitor of the rat liver cyclic AMP-dependent protein kinase (PKA) catalytic subunit (cAK), rat brain Ca(2+)- and phospholipid-dependent protein kinase C (PKC), avian gizzard Ca(2+)-calmodulin-dependent myosin light chain kinae (MLCK), and of wheat embryo Ca(2+)-dependent protein kinase (CDPK) (IC50 values 3, 8, 12, and 19 microM, respectively). However, a number of piceatannol-related compounds with fewer or no phenolic hydroxy substituents are inactive or very poor inhibitors of these serine/threonine protein kinases. Similarly, the PTK inhibitor ellagic acid is a potent inhibitor of cAK and of PKC (IC50 values 2 and 8 microM, respectively), whereas the non-phenolic perylene is ineffective as a protein kinase inhibitor. Ellagic acid is a competitive inhibitor of both cAK and of PKC but piceatannol inhibits these enzymes in a fashion that is competitive and non-competitive, respectively. Interaction with calmodulin may contribute to the inhibition of MLCK and CDPK by piceatannol.

Animals↗
PubMed1998

Modulation of fecal markers relevant to colon cancer risk: a high-starch Chinese diet did not generate expected beneficial changes relative to a Western-type diet.

In a randomized, crossover dietary intervention study, 12 Australians (of white descent) consumed a diet typical of low-income communities in China and an average Australian diet so that effects on fecal markers thought to be relevant to colon cancer risk could be compared. The Chinese diet contained 35.3 g starch/MJ daily [including 2 g resistant starch (RS)/MJ and 1.5 g nonstarch polysaccharides (NSPs)/MJ]; the Australian diet contained 12 g starch/MJ daily (including 0.8 g RS and 2.7 g NSPs/MJ). Subjects followed each diet for 3 wk. Serum cholesterol concentrations were significantly lower after the low-fat, high-starch Chinese diet than after the Australian diet (mean +/- SEM: 4.17 +/- 0.30 compared with 5.04 +/- 0.28 mmol/L, respectively, P < 0.05), a difference indicative of dietary compliance. Fecal pH was lower after the Chinese diet (6.51 +/- 0.04) than after the Australian diet (6.63 +/- 0.05; P < 0.05). For all other fecal markers examined, however, the Chinese diet produced less favorable changes, including lower fecal bulk (86 +/- 11 compared with 141 +/- 20 g wet wt/d, P < 0.01), slower transit through the gut (69 +/- 6 compared with 56 +/- 7 h, P = 0.06), lower fecal concentrations of short-chain fatty acids [72.8 +/- 7.3 compared with 98 +/- 7.6 mmol/L (including butyrate: 12.2 +/- 1.3 compared with 18.4 +/- 2.3 mmol/L), P < 0.05], and higher fecal concentrations of potentially damaging ammonia (540 +/- 50 compared with 450 +/- 40 mg/L, P < 0.01) and phenols (109.2 +/- 13.2 compared with 68.5 +/- 12.9 mg/L, P < 0.01). These results suggest that consumption of a high-starch diet alone is insufficient to reduce the risk of developing colon cancer.

Adult↗
PubMed1997

Inhibition of eukaryote protein kinases by isoquinoline and oxazine alkaloids.

The aporphine isoquinoline alkaloid apomorphine is a potent inhibitor of the catalytic subunit (cAK) of rat liver cyclic AMP-dependent protein kinase (PKA), myosin light chain kinase (MLCK), and Ca(2+)- and phospholipid-dependent protein kinase C (PKC) (IC50 values 1, 11, and 8 microM, respectively). However, a number of O-methylated analogues of apomorphine are inactive or poor inhibitors of cAK. The benzophenanthridine isoquinoline alkaloid sanguinarine is a potent inhibitor of cAK but is a relatively poor inhibitor of PKC (IC50 values 6 and 217 microM respectively). However a number of methylated analogues of sanguinarine are inactive as cAK inhibitors. The aporphine isoquinoline alkaloids (+)-boldine and bulbocapnine are non-competitive inhibitors of MLCK with respect to both peptide substrate and ATP. The inhibition of cAK, MLCK, and PKC by apomorphine and sanguinarine is competitive with respect to ATP as substrate. The oxazine alkaloids darrow red, nile blue A, and oxazine 170 are variously effective as inhibitors of cAK, MLCK, PKC, and CDPK (IC50 values 4-65 microM). Ca2+ binds to apomorphine and (+)-boldine which, together with nile blue A and oxazine 170, are potent inhibitors of calmodulin (CaM)-dependent MLCK (IC50 values 11, 12, 4, and 7 microM, respectively), and interact with dansyl-CaM.

Alkaloids↗
PubMed1997

Solution conformation of N-terminal fragments of trichosanthin small domain (TCS 182-200). Circular dichroic studies.

Three peptides, T14, T18 and TDK, derived from the N-terminus of trichosanthin small domain (TCS 182-200) have been investigated by circular dichroism. Secondary structure and structural transitions of the above peptides under different conditions were studied. Alcohol prompts a transition of the T18 peptide from a beta-sheet to an alpha-helical structure. It also increases the alpha-helicities of T14 and TDK. The beta-sheet of T18 peptide appears more hydrophobic than the alpha-helix of T14 or TDK. The effects of polypeptide sequence and solvent on secondary structure formation of these model peptides are discussed.

Amino Acid Sequence↗
PubMed1996

Selective inhibition of cyclic AMP-dependent protein kinase by isoquinoline derivatives.

A large series of isoquinoline derivatives was synthesised including derivatives of isoquinoline, isoquinolino[3,4-c]furazan, 1,2-dihydro-1-oxoisoquinoline, 6-oxopyrimido[1,2-d]isoquinoline, benzo[c][1,8]-naphthyridine, pyrazino[2,3-c]isoquinoline and benzimidazo[2,1-a]isoquinoline as well as further structurally related isoquinoline derivatives and pyrido-2,3-furazans. Representatives of all of these classes of isoquinolines are potent and selective inhibitors of the cyclic AMP-dependent protein kinase (PKA) catalytic subunit (cAK) from rat liver. The most effective cAK inhibitors are a series of 1,3-di-substituted and 1,3,4-tri-substituted isoquinolines (IC50 values 30-50 nM) (compounds A1, A2, A3, A4 and A5) and 2-ethylcarboxy-3-amino-5,6-dihydro-6-oxobenzo[c] [1,8]naphthyridine (E1) (IC50 0.08 microM). Compounds A1-A5 inhibit cAK in a fashion that is competitive with respect to ATP as substrate. The isoquinoline inhibitors A1-A5 are ineffective or very poor inhibitors of wheat embryo Ca(2+)-dependent protein kinase (CDPK) and rat brain Ca(2+)-dependent protein kinase C (PKC), chicken gizzard myosin light chain kinase (MLCK) and potato tuber cyclic nucleotide-binding phosphatase (Pase). E1 is a moderately effective inhibitor of CDPK and PKC (IC50 values 30 and 61 microM, respectively). The bisisoquinoline-1(2H)-one compound B7 inhibits cAK, CDPK, PKC and MLCK (IC50 values 8, 95, 24 and 7 microM, respectively) as does J1 [2-(p-bromophenyl)pyrrolo-[2,3-c]isoquinoline-5(4H)-one] (IC50 values 2, 50, 44 and 7 microM, respectively). The very potent isoquinoline-derived cAK inhibitors found here involve substitution of the N-containing isoquinoline ring system and these inhibitors show high specificity for cAK.

Animals↗
PubMed1995

Resistant starch in the diet increases breath hydrogen and serum acetate in human subjects.

The colonic fermentation of two diets differing in amounts of resistant starch (RS) was studied. High- and low-RS diets were fed to eight healthy subjects in three meals for 1 d. Breath hydrogen and two blood samples were collected over a 28-h period. The high-RS diet provided 59.1 +/- 4.7 g (mean +/- SE) RS and the low-RS diet provided 5.2 +/- 0.4 g RS. Breath hydrogen and the average total serum acetate were significantly higher during the high-RS diet than during the low-RS diet: 34.1 +/- 4.7 and 23.9 +/- 3.9 ppm (P < 0.001) and 169.1 +/- 12.8 and 118 +/- 6.6 mumol/L (P < 0.01), respectively. Butyrate and propionate were also detected in serum samples. Although not statistically significant, there was a trend (P = 0.087) for butyrate to increase with the high-RS diet. Subjects reported greater gastrointestinal symptoms during the high-RS diet. These results suggest that RS may have effects comparable with those of some fermentable dietary fibers.

Acetates↗
PubMed1995

Effect of resistant starch on fecal bulk and fermentation-dependent events in humans.

This study investigated the effect of two diets, which differed in resistant starch (RS) concentration, on fecal bulk and fermentation-dependent events in 11 humans. Amounts of RS consumed were 5.0 +/- 0.4 and 39.0 +/- 3.0 g/d (mean +/- SEM) for the low- and high-RS diets, respectively. The two diets were fed for 3 wk each in a randomized crossover design. Fecal collections were made in the third week of each study period. The high-RS diet produced an increase (P < 0.01) in total fecal output (from 138 +/- 22 to 197 +/- 37 g/d) and lowered fecal pH (6.9 +/- 0.1 to 6.3 +/- 0.1). There were significant increases (P < 0.05) in the fecal concentrations and daily excretion of butyrate (+38% and +100%, respectively) and acetate (+26% and +72%, respectively) during the high-RS period. The fecal excretion (g/d) of nonstarch polysaccharides (NSP) also rose by 50% during the high-RS diet, suggesting that the presence of starch in the colon may affect the fermentation of NSP. Subjects reported an increase in flatulence and easier defecation. These results demonstrate that RS has a significant impact on putative markers of colonic health in humans.

Acetates↗
PubMed1994

Percutaneous balloon mitral valvuloplasty. An observation of 50 patients.

Percutaneous balloon mitral valvuloplasty (PBMV) was successfully performed in 50 selected patients with mitral stenosis by using Inoue pillow-shaped balloon and Inoue technique. The average diameter of balloon used was 26.9 +/- 0.9 mm. 90% (45/50) of cases had either double or single mitral commissura split. Of the rest 5 cases, 1 had a mitral score 13 and 4 had a history of mitral valve commissurotomy. Totally they had a mean mitral valve area increase from 1.13 +/- 0.32 to 2.21 +/- 0.43 cm2, left atrial pressure decrease from 31.8 +/- 9.3 to 14.7 +/- 5.6 mmHg, left atrial diameter reduction from 44.9 +/- 7.7 to 37.4 +/- 4.9 mm, and transmitral gradient decrease from 21.7 +/- 9.8 to 4.0 +/- 5.2 mmHg. Most patients had a obvious cardiac function improvement, especially in patients with mitral score of 8 or less. 30% patients (15/50) had a mild mitral regurgitation, but relieved 3-6 months after procedure. During one year of follow up, the majority of patients (16/20) were found in a good cardiac function, mitral area and the left atrial diameter, except in 4 patients with a high mitral score of more than 10. It is suggested that for patient with lower mitral morphological score and good general health, a larger diameter balloon might be suitable for effectively improving patient's symptom, but for patients with a previous surgical mitral commissurotomy, PBMV should not be selected.

Adult↗