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Biomedical subjects

G Lu

Publications and source records attributed to G Lu.

At least 109 records · Page 6Linked to original sources
PubMed1997

Percutaneous absorption and disposition studies of methotrexate in rabbits and rats.

The absorption and disposition of methotrexate (MTX) in the plasma, synovial fluid (SF), skin, and muscle tissue were studied following administration of a topical MTX gel in rabbits and rats. In rabbits, MTX concentrations in the plasma increased steadily toward the peak (5.9 +/- 2.8 ng mL-1) which appeared at approximately 2 h postdose and declined with the elimination half-life of 4.48 +/- 1.74 h. At 1 h after the topical dose, the MTX concentrations in the skin (49.0 +/- 19.8 micrograms g-1), muscle (12.7 +/- 3.3 ng g-1), and SF (19.2 +/- 10.1 ng g-1) underneath the dosed stifle joint were significantly higher (p < 0.05) than those of the untreated stifle joint, indicating the potential therapeutic value of topical delivery of MTX for rheumatoid arthritis. A large fraction (approximately 59%) of MTX which was found in the skin at 1 h postdose was present in the stratum corneum, indicating its extensive binding capacity for MTX. The MTX concentrations in the muscle and SF of the dosed stifle joint at 1 h postdose were 1.8 and 2.6 times higher than those in the dosed elbow joint, respectively, reflecting the effect of dose site on the permeation of MTX. Using a new filter paper method, the amounts of SF obtained from the elbow and stifle joints of four rabbits were 26.3 +/- 8.3 and 48.8 +/- 5.2 mg, respectively. A significant enhancer effect of N,N-diethyl-n-toluamide (DEET) on the disposition of MTX in the stratum corneum of rabbit ear was observed (p < 0.05) by the tape-stripping method. In rats, the gel containing 4% DEET resulted in a twofold increase in the permeation of MTX into the muscle over the 4 h period postdose. A modified HPLC method with a linear calibration curve (r > 0.999) over the range of 2-50 ng mL-1. quantitation limit of 0.5 ng mL-1, and mean recovery of approximately 87% was used for the quantitation of MTX in the tissue and fluid samples.

Animals↗
PubMed1997

Hornet venom allergen antigen 5, Dol m 5: its T-cell epitopes in mice and its antigenic cross-reactivity with a mammalian testis protein.

BACKGROUND: A major venom allergen of white-faced hornet (Dolichovespula maculata) is antigen 5, Dol m 5. It is a 204-residue protein having 23% to 35% sequence identity with several proteins from diverse sources. The biologic function of antigen 5 and its sequence-related proteins is not known. OBJECTIVE: This study was done to delineate the T-cell epitopes of Dol m 5 and to test their cross-reactivity with a sequence-related mouse testis protein, tpx. METHODS: T-cell epitope mapping and cross-reactivity were studied with 15- or 20-residue peptides by their stimulation of spleen cells from mice immunized with recombinant Dol m 5 or tpx fragments. RESULTS: Three of 20 peptides studied were found to represent major T-cell epitopes of Dol m 5, being recognized by five or all of six mouse strains tested. One major epitope peptide, residue 176-195, showed cross-reactivity in BALB/c mice with the homologous antigen 5s from yellow jackets and wasps, as well as with mouse tpx. The cross-reactivity of Dol m 5 and mouse tpx is not reciprocal because spleen cells from tpx-immunized mice were stimulated by the hornet peptide, but cells from Dol m 5-immunized mice were not stimulated by the corresponding tpx peptides. CONCLUSION: Cross-reactivity of vespid antigen 5 and mouse tpx may be of importance in insect allergy because human and mouse testis proteins are highly homologous.

Allergens↗
PubMed1997

Effects of ethyl alcohol on canine jejunal circular smooth muscle.

Ethyl alcohol has many symptomatic effects on the gastrointestinal tract. Our aim was to determine the effects of ethyl alcohol on circular smooth muscle contractility of the canine small bowel. Mechanical and intracellular electrical recordings were made in vitro from the circular muscle of full-thickness strips of muscularis externa from canine jejunum. Ethyl alcohol (20-120 mM) dose-dependently decreased spontaneous contractile amplitude, hyperpolarized the resting membrane potential, and decreased the amplitude of the slow wave. Ethyl alcohol also decreased the amplitude of the inhibitory junction potential (during electrical field stimulation-EFS) but did not alter the maximum absolute cell-polarized potential reached during EFS. An increase in extracellular calcium (15 mM) partially restored spontaneous contractile amplitude, resting membrane potential, and slow-wave amplitude. Ethyl alcohol decreased the amplitude of contractions evoked by acetylcholine, CCK, and substance P. These data suggest that ethyl alcohol has direct effects on jejunal smooth muscle contractility. These effects can be partially reversed by increasing the availability of extracellular calcium.

Animals↗
PubMed1997

Effect of extrinsic denervation in a canine model of jejunoileal autotransplantation on mechanical and electrical activity of jejunal circular smooth muscle.

Little is known about the acute and chronic effects of the intestinal transplantation on smooth muscle contractile physiology. Our aim was to determine the effects of the denervation necessitated by jejunoileal autotransplantation on membrane potential and contractile activity. Six dogs underwent a model of jejunoileal autotransplantation that specifically avoids ischemia/reperfusion injury (by maintaining blood flow to the gut during the "transplantation" procedure). Strips of jejunal circular muscle were studied sequentially before and 2 and 8 weeks after denervation by recording mechanical and intracellular electrical activities in vitro. The amplitude of spontaneous contractions (X +/- SD) was increased (P < 0.05) at 2 compared to 0 weeks (126 +/- 19 vs 77 +/- 32 g/g; P < 0.05) but markedly decreased at 8 weeks (7 +/- 2 g/g). Contraction frequency, resting membrane potential, and amplitude of slow waves were unchanged across these time points. Bethanechol (10(-7)-10(-4) M) and substance P (10(-8)-10(-6) M) dose-dependently increased contractile activity at all time points, but the absolute change in amplitude was decreased at 8 weeks. The amplitude of inhibitory junction potentials (IJPs) and duration of inhibition of contractile activity in the presence of cholinergic and adrenergic blockade increased at 2 and 8 weeks; off-contraction amplitude was decreased at 8 weeks (P < 0.05). These effects may occur via changes in neurotransmitter release, changes in regulation of membrane receptors, or alteration of characteristics of the membrane threshold potential.

Animals↗
PubMed1997

Influence of n-3 fatty acid supplementation on the endogenous activities of plasma lipases.

The aim of these studies was to explore the possibility that enhanced triacylglycerol clearance may contribute to the hypotriacylglycerolemic effect of n-3 fatty acids in humans. Healthy subjects (n = 20) and hypertriacylglycerolemic patients (n = 6) were given a placebo (olive oil, OO) or a fish-oil concentrate (FOC; 41% eicosapentaenoic acid and 23% docosahexaenoic acid) in two, independent, randomized, blind trials. For the healthy subjects, the FOC treatment period was 3 wk long and FOC intakes were 5 g/d. For the patients, treatment periods were 4 wk long and dosages were 5 g.70 kg body wt-1.d-1. Washout periods were 2-4 wk for both groups. Blood samples were drawn at the end of each phase and analyzed for plasma lipids, lipoproteins, and endogenous (nonheparin-stimulated) activities of lipoprotein lipase (LPL) and hepatic lipase (HL). In the healthy subjects the FOC decreased plasma triacylglycerol concentrations by 18% (P < 0.01), whereas in the patients concentrations were reduced by 35% (P < 0.05). Low-density-lipoprotein-cholesterol concentrations increased by 25% in the latter group (P = 0.06). FOC increased the endogenous activities of LPL and HL by 62% and 68%, respectively (P < 0.0001), in the healthy subjects, but only LPL in the patients (65%, P < 0.005). These data suggest that endogenous lipase activities may be altered by nutritional interventions, and further, that accelerated lipolysis could contribute, at least in part, to the observed effects of n-3 fatty acids on human lipoprotein metabolism.

Fatty Acids, Omega-3↗
PubMed1997

Characterization of two genes encoding the Mycobacterium tuberculosis ribonucleotide reductase small subunit.

Two nrdF genes, nrdF1 and nrdF2, encoding the small subunit (R2) of ribonucleotide reductase (RR) from Mycobacterium tuberculosis have 71% identity at the amino acid level and are both highly homologous with Salmonella typhimurium R2F. The calculated molecular masses of R2-1 and R2-2 are 36,588 (322 amino acids [aa]) and 36,957 (324 aa) Da, respectively. Western blot analysis of crude M. tuberculosis extracts indicates that both R2s are expressed in vivo. Recombinant R2-2 is enzymatically active when assayed with pure recombinant M. tuberculosis R1 subunit. Both ATP and dATP are activators for CDP reduction up to 2 and 1 mM, respectively. The gene encoding M. tuberculosis R2-1, nrdF1, is not linked to nrdF2, nor is either gene linked to the gene encoding the large subunit, M. tuberculosis nrdE. The gene encoding MTP64 was found downstream from nrdF1, and the gene encoding alcohol dehydrogenase was found downstream from nrdF2. A nrdA(Ts) strain of E. coli (E101) could be complemented by simultaneous transformation with M. tuberculosis nrdE and nrdF2. An M. tuberculosis nrdF2 variant in which the codon for the catalytically necessary tyrosine was replaced by the phenylalanine codon did not complement E101 when cotransformed with M. tuberculosis nrdE. Similarly, M. tuberculosis nrdF1 and nrdE did not complement E101. Activity of recombinant M. tuberculosis RR was inhibited by incubating the enzyme with a peptide corresponding to the 7 C-terminal amino acid residues of the R2-2 subunit. M. tuberculosis is a species in which a nrdEF system appears to encode the biologically active species of RR and also the only bacterial species identified so far in which class I RR subunits are not arranged on an operon.

Adenosine Triphosphate↗
PubMed1997

Inflammation modulates in vitro colonic myoelectric and contractile activity and interstitial cells of Cajal.

Inflammation suppresses phasic contractile activity in vivo. We investigated whether inflammation also suppresses in vitro phasic contractile activity and, if so, whether this could in part be due to the alteration of specific slow wave characteristics and morphology of the interstitial cells of Cajal (ICC). Circular muscle strips were obtained from normal and inflamed distal canine colon. Inflammation was induced by mucosal exposure to ethanol and acetic acid. The amplitudes of spontaneous, methacholine-induced, substance P-induced, and electrical field stimulation-induced contractions were smaller in inflamed muscle strips than in normal muscle strips. Inflammation reduced the resting membrane potential and the amplitude and duration of slow waves in circular muscle cells. Inflammation did not affect the amplitude of inhibitory junction potentials but did decrease their duration. Ultrastructural studies showed expansion of the extracellular space between circular muscle cells, reduction in the density of ICC and associated neural structures, damage to ICC processes, vacuolization of their cytoplasm, and blebbings of the plasma membrane. We conclude that inflammation-induced alterations of slow wave characteristics contribute to the suppression of phasic contractions. These alterations may, in part, be due to the damage to ICC. Inflammation impairs both the myogenic and neural regulation of phasic contractions.

Acetic Acid↗
PubMed1997

Fatty acids, not insulin, modulate alpha1-adrenergic reactivity in dorsal hand veins.

Resistance to the vasodilator action of insulin and its capacity to antagonize vascular alpha-adrenergic reactivity may contribute to the increased neurovascular tone and blood pressure in obese hypertensive subjects. We showed that nonesterified fatty acids (NEFAs) were elevated in obese hypertensive subjects and that raising NEFAs locally in dorsal hand veins of healthy normotensive subjects enhances alpha1adrenoceptor reactivity. Research by others suggests that insulin antagonizes alpha1-adrenoceptor tone in dorsal hand veins. Taken together with evidence that NEFAs antagonize several of the metabolic actions of insulin, these observations raise the possibility that NEFAs participate in resistance to the vascular effects of insulin and suggest that dorsal hand veins represent a good model for studying these interactions. Thus, we produced local hyperinsulinemia in the dorsal hand veins of six lean normal volunteers and quantified changes of venous distensibility in response to phenylephrine in the presence and absence of a local elevation of NEFAs. We confirmed that raising NEFAs locally decreased by twofold to threefold the phenylephrine ED50 (P<.01), but this alpha1-sensitizing action of NEFAs was not antagonized by insulin concentrations up to approximately 1000 microU/mL. Moreover, local hyperinsulinemia alone did not affect vascular alpha1-adrenergic sensitivity as measured by the phenylephrine ED50. To address the possibility that the absence of an insulin effect reflected a lack of nitric oxide-mediated, endothelium-dependent dilation in hand veins, responses to acetylcholine were obtained. Acetylcholine relaxed preconstricted hand veins by 60% to 80% (P<.01) in the presence and absence of indomethacin, which suggests substantial endothelium-dependent, cyclooxygenase-independent vasodilation. The results confirm that raising NEFAs locally enhances vascular alpha1-adrenoceptor sensitivity. Despite the presence of significant endothelium-dependent dilation in dorsal hand veins, insulin does not antagonize vascular alpha1-adrenoceptor sensitivity in the presence of either ambient or locally elevated fatty acids.

Acetylcholine↗
PubMed1997

Fatty acids augment endothelium-dependent dilation in hand veins by a cyclooxygenase-dependent mechanism.

Evidence supports the hypothesis that elevated nonesterified fatty acids (NEFAs) in patients with insulin resistance, eg, obese hypertensive subjects, contribute to increased vascular alpha-adrenergic reactivity and tone by impairing endothelium-dependent vasodilation. To generate further support for this notion, we studied responses to endothelium-dependent and independent dilators under control (0.9% NaCl/heparin) conditions in one hand and with elevated NEFAs in the contralateral hand (10% intralipid/heparin). To observe venodilator responses, the dorsal hand vein diameter was first reduced by approximately 60% with phenylephrine. Studies were repeated with indomethacin to block the generation of cyclooxygenase products. In contrast to previous in vitro data, elevating NEFAs locally in vivo augmented rather than suppressed venodilator responses to the two endothelium-dependent dilators acetylcholine and methacholine (P<.05). Responses to the endothelium-independent dilator nitroglycerin were unaffected. Indomethacin attenuated the capacity of intralipid/heparin to enhance endothelium-dependent dilator responses to acetylcholine and methacholine. Indomethacin did not affect venodilator responses to nitroglycerin. The effect of intralipid/heparin to significantly reduce the phenylephrine infusion rate required to reduce hand vein diameter by approximately 60% was reversed by indomethacin. These data indicate that raising fatty acids locally augments endothelium-dependent dilation by a cyclooxygenase-dependent mechanism. The findings also suggest that NEFAs augment alpha-adrenoceptor-mediated constriction in hand veins by a cyclooxygenase-dependent mechanism. These hand vein studies do not support the notion that the elevated NEFAs in obese hypertensive patients augment alpha1-adrenoceptor-mediated reactivity by reducing nitric oxide synthesis.

Acetylcholine↗
PubMed1997

[Effects of acute repeated hypoxia on levels of adenosine and its A1 receptor in mouse brain].

Experiments were conducted on Kunming mice. Content of adenosine (ADO) and its metabolites in the brain was measured by specific enzymatic method, and radioligand binding method was used to study ADO A1, receptor. ADO content of the hippocampus in group C (hypoxia exposure for four runs) was markedly higher than that in groups A (control, without hypoxia exposure) and B (hypoxia exposure for one run), showing that ADO content can be cumulatively increased in the hippocampus, which is more sensitive to ischemia and hypoxia, during acute repeated hypoxia exposures. A1 receptor density, but of group C was significantly lower than that of group A and no difference was seen between groups B and C, but A1 receptor affinity in the hippocampus, pons and medula oblongata in group C was significantly higher than that in group A, implying that during acute repeated hypoxia there may be some mechanisms preventing A1 receptor density from decreasing further and making A1 receptor affinity increase in some brain regions. These results indicate that cumulatively increased ADO in the hippocampus via A1 receptor may play a neuroprotective role in CNS as an inhibitory neuromodulator and thus contribute to the formation and development of acute hypoxia adaptation or tolerance.

Adenosine↗
PubMed1997

[Corneal topographic analysis of small incision in cataract surgery].

OBJECTIVE: The study was designed to investigate the corneal topographical and corneal curvature changes of small incision in cataract surgery. METHODS: 38 eyes of 36 patients who had undergone small incision cataract surgery were followed up at one week and one, three, six and twelve months postoperatively by corneal topography and keratometer. RESULTS: At one week postoperatively, there was slight steeping or flattening at the center and peripheral cornea, but the change was recovered to the preoperative state after one month. No significant changes had been observed after a long-term observation. The result of keratometer was different from that of topography. CONCLUSIONS: It is clearly demonstrated that smaller wound incision produces less astigmatism, faster postoperative recovery and more stable refraction. The results of corneal topography reflect curvature changes more reliably and precisely than that of keratometer, and topography is of great value in cataractous surgical evaluation.

Adolescent↗
PubMed1997

[Immuno-enhancing effect of gebie oral liquid on mice].

Gebie Oral Liquid can increase the weight of thymus and spleen of the mouse, damaged by prednisone and cytoxan, enhance the phagocytosis of monocytes and DHT, and promote the blastogenesis of splenic lymphocytes as well as the activity of NK cells.

Animals↗
PubMed1997

[The plant regeneration of Salvia miltiorrhiza Bge. transformed by Agrobacterium].

The hairy roots and crown galls of Salvia miltiorrhiza were obtained by infecting plant with A. rhizogenes (strain 15834, LBA 9402) and A. tumefaciens (strain C58). The transformed plants were regenerated light and transplanted form cultural medium into soil successfully. The plants transformed by A. rhizogenes have characteristics of short stems and develop hairy roots, those and trans formed by A. tumefaciens grow vigorously featuring, longer stems and well developed roots. Both biomass production and tanshenone content are higher than the original plant.

Agrobacterium tumefaciens↗
PubMed1997

N-3 fatty acids and chylomicron metabolism in the rat.

Dietary n-3 fatty acids (FAs) reduce postprandial triacylglycerol concentrations in humans by unknown mechanisms. Our goals were to reproduce this phenomenon in the rat, and then to determine the mechanism. In an oral fat tolerance study two groups of rats were fed diets containing 2.1% ethyl esters of n-3 FA or olive oil for 2 weeks. After gavaging with emulsified soybean oil, the postprandial chylomicron triacylglycerol levels in the n-3 FA group were reduced by 40% (P < 0.05). The hypothesis that n-3 FA feeding reduced chylomicron production/secretion from the gut was tested by blocking chylomicron removal with Triton WR1339 before gavaging the rats with the fat load. This completely eliminated the hypochylomicronemic effect suggesting that chylomicron input was not inhibited by n-3 FAs. Chylomicron clearance was studied by injecting chylomicrons containing radioactive retinyl esters and triacylglycerol into rats from both groups. Pre-feeding with n-3 FAs accelerated the removal of chylomicron triacylglycerol and retinyl esters from the plasma with significantly lower fractions of dose remaining at 2, 4, and 8 min post-injection for both tracers. These findings suggest than n-3 FAs reduce postprandial chylomicronemia in the rat by accelerating chylomicron lipid clearance.

Animals↗