Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0432222 (SEM)
 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We investigated the vascular effects mediated by ETA and ETB receptors in human dorsal hand veins in vivo, using sarafotoxin S6c (SFTX6c) as a selective agonist of ETB receptors and endothelin-1 (ET-1) as a nonselective agonist of ETA and ETB receptors. The cyclo-oxygenase inhibitor aspirin and the nitric oxide synthase inhibitor L-NMMA were used to examine the modulating role of endothelial vasodilators on the response to SFTX6c. Drugs were all infused into the hand veins, at locally but not systemically active doses, via a 23 SWG butterfly cannula, with the exception of aspirin, which was administered orally. Hand vein size was measured by the Aellig technique. The study was performed in six healthy male subjects. Data (mean +/- SEM) were examined by ANOVA. Results are expressed as percent change from baseline at 60 min. ET-1 (5 pmol/min for 60 min) caused venoconstriction of 68 +/- 6% (p = 0.0001). SFTX6c at the same dose caused venoconstriction of 19 +/- 4% (p = 0.003). The response to SFTX6c was significantly less than to ET-1 (p = 0.002). Constriction to SFTX6c tended to increase when this agent was co-administered with aspirin (25 +/- 7%) or L-NMMA (24 +/- 10%) and was significantly potentiated when these agents were co-administered (45 +/- 4%; p = 0.01 vs. SFTX6c alone). We have demonstrated that the selective ETB agonist SFTX6c produces venoconstriction in human hand veins in vivo and that this venoconstriction is modulated by the generation of endothelium-derived vasodilators. In this vascular bed, venoconstriction rather than venodilatation appears to be the predominant effect of stimulation of ETB receptors with SFTX6c.
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PMID:Endothelium-dependent modulation of venoconstriction to sarafotoxin S6c in human veins in vivo. 858 56

The long-term maintenance of a rigid bone-implant interface (osseointegration) is the clinical goal of most dental implant systems, although the biological mechanism for retaining a foreign object in living bone is unclear. Little data are available on the physiological turnover (remodeling) of the supporting osseous tissue. The objective of this study was to histomorphometrically assess bone remodeling surrounding rigidly integrated titanium implants in multiple species. Implants, in place from 6 months to 5 years, were recovered from human, monkey, dog, and rabbit subjects. With the use of stereological point-hit and linear-intercept methods, indices of bone formation and resorption were determined. Remarkably similar patterns emerged among all investigated species. Repeated-measures ANOVA showed a 3 to 9 fold increase in remodeling within 1 mm of the bone-implant interface (P<0.001; data expressed as percent turnover / month, mean +/- SEM for n = 3-11). All morphometric indices (percent new bone, percent fluorochrome-labeled bone, percent resorption space) showed similar trends. These data suggest that the physiological mechanism for maintaining rigid osseous integration (osseointegration) is a sustained elevation of remodeling adjacent to the bone-implant interface.
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PMID:Remodeling dynamics of bone supporting rigidly fixed titanium implants: a histomorphometric comparison in four species including humans. 860 33

The purpose of this study was to compare the shear bond strengths and enamel surface morphology after debonding a polycrystalline ceramic bracket (Transcend 2000) bonded with a light-cured resin cement (Transbond) without enamel etching or by etching for 15 seconds with 10% or 37% phosphoric acid and 10% maleic acid. Forty extracted noncarious human premolars were used. The buccal enamel surfaces were used and the teeth randomly divided in to four groups of 10 teeth each: Group 1: No enamel etching; Group 2: Enamel etching for 15 seconds with 10% phosphoric acid; Group 3: Enamel etching for 15 seconds with 37% phosphoric acid; and Group 4: Enamel etching for 15 seconds with 10% maleic acid. The brackets were bonded to the etched enamel surfaces according to manufacturers' instructions except the etching time variations. All specimens were stored in distilled water for 24 hours and then thermocycled for 300 cycles between 5 degrees C and 55 degrees C. The specimens were mounted in dental stone and placed in the Instron at a crosshead speed of 0.5 mm/min using a knife-edged blade. Immediately after debonding, the enamel surface and bracket-enamel interface were evaluated visually and with a stereomicroscope. Representative samples were then examined with the SEM. ANOVA and Student-Newman-Keuls tests were performed. The results (in MPa) were: Group 1:11.83 (+3.9); Group 2: 28.80 (+12.6); Group 3: 26.25 (+5.3); Group 4: 18.06 (+6.9). Groups 2 and 3 were statistically significantly different (p<0.0001) from Groups 1 and 4. Groups 2 vs. 3 or 1 vs. 4 were not statistically different. Debonding occurred mainly at the bracket-resin interface in all groups, except Group 2 which displayed two samples with enamel cohesive failures and two fracturing the bracket. The SEM evaluation revealed that after debonding, the group etched with the 37% phosphoric acid gel had the roughest enamel surface and was the only group to present enamel fractures. Bracket bonding with unetched enamel and enamel etched with 10% phosphoric acid gel should be clinically investigated using the products tested.
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PMID:Shear strength of ceramic brackets bonded to etched or unetched enamel. 861 86

Sinc DNA adducts of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) are formed at relatively high levels in the rat pancreas but not liver, we examined the uptake of PhIP and its N-hydroxy metabolite (N-OH-PhIP) into pancreatic acini and hepatocytes to determine if differential tissue uptake was a factor modulating the formation of PhIP-DNA adducts. In addition, since the precursors of PhIP formation are two amino acids and since various amino acid transporters have been identified in the pancreas, the possible involvement of these transporters in the uptake of PhIP and N-OH-PhIP was investigated. The uptake both heterocyclic compounds into both tissue preparations was rapid, with maximal uptake occurring with 1-2 min. However, PhIP uptake into pancreatic acini was significantly (2-way ANOVA, P < 0.05) greater than uptake of N-OH-PhIP into pancreatic acini and the uptake of both PhIP and N-OH-PhIP into hepatocytes. Although uptake was rapid, efflux of both compounds from both tissue preparations was also rapid. However, the efflux rate constant (1.86 +/- 0.6/min, mean +/- SEM) for PhIP) was significantly lower (Student's t-test, P < 0.05) than that for N-OH-PhIP (4.14 +/- 0.04/min) from pancreatic acini. This, combined with the increased uptake of PhIP into pancreatic acini , suggests that there is substantial but reversible binding of PhIP in the pancreas. The uptake of both PhIP and N-OH-PhIP into pancreatic acini and hepatocytes was not affected by the presence of various amino acids in the incubation buffer, indicating that amino acid transporters are not involved in uptake of these compounds. Furthermore, uptake of both compounds did not appear to be dependent on metabolic energy supply. The above data, together with the high octanol:buffer partition coefficients (logP = 1.322 and 1.301 for PhiP and N-OH-PhIP respectively) suggest that both uptake and efflux of PhIP and N-OH-PhIP are consistent with a process of passive diffusion. The tissue binding characteristics for PhIP in the pancreas may create conditions whereby pancreatic cytochrome P450 1A1 can catalyse the formation of N-OH-PhIP. While N-OH-PhIP is not the ultimate reactive DNA binding species, it has been shown to directly bind to and form DNA adducts. Therefore, it is possible that the apparent selective accumulation of PhIP may contribute to the high level of PhIP-DNA adducts formed in the rat pancreas.
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PMID:Uptake of the food-derived heterocyclic amine carcinogen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine and its N-hydroxy metabolite into rat pancreatic acini and hepatocytes in vitro. 862 7

The purpose of this study was to evaluate the effects of mannitol (Man), dexamethasone (DM), dichloroacetic acid (DCA) and 1,3-butanediol (BD) in reduction of posttraumatic cortical edema following brain deformation injury to rats. Ten minutes prior to fluid percussion injury, each animal received one of four pretreatments or placebo: Man, 1 g/kg intravenously, DM 3.0 mg/kg intravenously, DCA 25 mg/kg intraperitoneally BD 0.5 mg/kg intraperitoneally (n = 12 per treatment group), or equivolume saline (n = 8 per corresponding trauma group). Six hours after trauma, cortical tissue was harvested. Using a benzene-kerosene gradient column calibrated with potassium sulfate standards, the specific gravity (SpG) of cortical tissue from each group was measured and compared (ANOVA, P < .05). The measured cortical SpG from traumatized animals receiving Man (mean 1.037 +/- SEM .001), DCA (1.038 +/- .001), and BD (1.039 +/- .001) were equal to SpG from untraumitized cortex (1.041 +/- .001), and were significantly greater than SpG from traumatized cortex for animals receiving DM (1.035 +/- .001) or placebo (1.033 +/- .002). Pretreatment with DCA, Man, and BD appears to protect against development of posttraumatic cortical edema when measured 6 hours after blunt head trauma in the rat. Each of these chemical treatments appears effective in preventing or reducing posttraumatic cortical edema.
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PMID:Effects of chemical pretreatment on posttraumatic cortical edema in the rat. 863 Jan 50

To explore whether lipoprotein(a), Lp(a), may accumulate preferentially to LDL in the arterial wall at sites of injury, cholesterol-fed rabbits were injected intravenously with radiolabeled Lp(a) and/or LDL 3.1 +/- 0.1 days (mean +/- SEM, n = 30) after a balloon injury of the thoracic aorta. After 5 to 10 minutes' exposure to labeled lipoproteins, more labeled LDL than labeled Lp(a) was recovered in the intima-inner media of the balloon-injured segment (n = 9; paired t test, P < .0001); however, the amount of tightly bound labeled lipoprotein was similar for the two lipoprotein fractions. In the second set of experiments, 131I-Lp(a) (or 131I-LDL) was injected 26 hours before and 125I-Lp(a) (or 125I-LDL) 3 hours before the aorta was removed. Permeability and fractional loss of labeled Lp(a) (n = 8) versus LDL (n = 7) in the balloon-injured aortic intima-inner media were: permeability, 0.46 +/- 0.10 microL/cm2 per hour versus 1.41 +/- 0.32 microL/cm2 per hour (nonpaired t test, P < .0001); and fractional loss, 0.12 +/- 0.02 h-1 versus 0.44 +/- 0.05 h-1 (nonpaired t test, P = .0001), respectively. Finally, after 23 hours' exposure to labeled lipoproteins, the total accumulation and the amount of tightly bound labeled Lp(a) in the balloon-injured intima-inner media were, respectively, 174% (n = 6; ANOVA, P = .03) and 256% ANOVA, P = .005) of the values for labeled LDL. For labeled Lp(a) in the balloon-injured compared with the normal aortic intima-inner media, the recovery after 5 to 10 minutes, the permeability, and the accumulation after 23 hours were all increased, whereas the fractional loss was unchanged. These data suggest that the accumulation of Lp(a) is much larger in injured vessels than in normal vessels. Moreover, the data support the idea of a specific accumulation of Lp(a) compared with LDL in injured vessels.
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PMID:Specific accumulation of lipoprotein(a) in balloon-injured rabbit aorta in vivo. 863 19

Propofol has free radical scavenging properties similar to those of recognized phenol-based antioxidants. We have examined these properties in an in vitro model of radical-induced cellular injury, comparing its activity with that of thiopentone (which has also been shown to have radical scavenging activity). Haemolysis of human erythrocytes was induced using the azo compound 2,2'-azo-bis(2-amidinopropane) dihydrochloride (ABAP). This was achieved by incubating a 10% suspension of erythrocytes with ABAP 100 mmol litre-1 at 37 degrees C. For propofol, at concentrations of 12.5, 25 and 50 mumol litre-1, the times to achieve 50% haemolysis were mean 126 (SEM 7) min (95% confidence interval 108-144 min), 150 (8) (129-170) min and 182 (12) (160-180) min, respectively (Intralipid control 107 (7) (90-125) min, ANOVA P < 0.0001). For thiopentone, at concentrations of 62.5, 125 and 250 mumol litre-1, the values were 117 (2) (112-121) min, 126 (3) (119-133) min and 138 (2) (132-144) min, respectively (saline control 109 (2) (104-113) min, ANOVA P < 0.0001). Spectroscopic analysis in the visible and ultraviolet spectra demonstrated a steady increase in the proportion of methaemoglobin during haemolysis, with the highest concentrations in the propofol-containing flasks. The formation of methaemoglobin was preceded by the generation of ferrylhaemoglobin (a Fe4+ haemoglobin species). Further experiments examining oxidation of purified methaemoglobin to ferrylhaemoglobin by hydrogen peroxide suggested that propofol, but not Intralipid or thiopentone, reduced ferrylhaemoglobin back to the met- state, and thereby explained the higher concentrations of methaemoglobin in the propofol-containing erythrocyte suspensions. We conclude that propofol is a more potent free radical scavenger in this model of oxidant stress than thiopentone, and that reduction of high oxidation states of haemoglobin may contribute to such activity.
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PMID:Effect of propofol and thiopentone on free radical mediated oxidative stress of the erythrocyte. 865 27

The role of human growth hormone (hGH) as a nutritional adjunct for cancer patients is controversial because of its potential mitogenic effects on tumor growth. No studies to date have examined the effect of hGH on human tumor response in vivo. In Vitro: Athymic mice were injected (s.c.) daily with hGH (GH, n=14) or saline (CTL, n=14). On Day 10, serum was collected and added to human pancreatic carcinoma cells in culture. In Vivo: Athymic mice were inoculated (s.c.) with human pancreatic carcinoma cells. On Day 14, mice were randomized to receive daily either hGH (GH, n=14) or saline (CTL, n=12). On Day 29, animals received [3H]phenylalanine for tissue protein fractional synthetic rate (FSR) measurement. Tumors were excised and cell cycle kinetics analyzed. Data are expressed as mean +/- SEM. Statistical analysis was performed by unpaired t test and/or ANOVA where appropriate. In Vitro: Serum from GH-treated animals had elevated IGF-1 levels (287 +/- 34 ng/ml vs 157 +/- 53 ng/ml, P<0.001) and significantly stimulated cell growth (No. cells x 10(3)/well) compared with CTL serum (925 +/- 31 vs 747 +/- 38, P<0.001). In Vivo: Serum for GH-treated animals had elevated IGF-1 levels (287 +/- 34 ng/ml vs 157 +/- 53 ng/ml, P<0.001) and significantly stimulated cell growth (No. cells x 10(3)/well) compared with CTL serum (925 +/- 31 vs 747 +/- 38, P<0.001). In Vivo: Growth hormone had no significant effect on tumor growth rate (mm3/day) (1.45 +/- 0.47 CTL vs 1.57 +/- 0.66 GH), final tumor weight (mg) (0.19 +/- 0.15 CTL vs 0.17+/- 0.06 GH), DNA Index (1.5 +/- 0.1 CTL vs 1.5 +/- 0.1 GH), percent S phase (20.3 +/- 3.3 CTL vs 22.1 +/- 3.0 GH), or tumor FSR (%/day) (51.1 +/- 17.8 CTL vs 70.2 +/- 61.1 GH). Growth hormone significantly elevated serum IGF-1 levels (ng/ml) (176 +/- 48 CTL vs 222 +/- 53 GH, P<0.005) and liver FSR (%/day) (62.8 +/- 17.8 CTL vs 79.7 +/- 12.7 GH, P<0.005). Serum of GH-treated mice increased human pancreatic cell growth in vitro. In vivo, GH administration raised serum IGF-1 levels and increased liver protein FSR, without tumor growth, cell cycle kinetics, or protein FSR.
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PMID:Effect of human growth hormone on human pancreatic carcinoma growth, protein, and cell cycle kinetics. 865 2

To compare the effects of sub-anaesthetic concentrations of propofol and halothane on the respiratory control system, we have studied the acute ventilatory response to isocapnic hypoxia (AHVR) in 12 adults with and without three different concentrations of propofol and halothane. Target doses for propofol were 0, 0.05, 0.1 and 0.2 of the effective plasma concentration (EC50 = 8.1 micrograms ml-1). Target doses for halothane were 0, 0.05, 0.1 and 0.2 minimum alveolar concentration (MAC = 0.77%). The doses achieved experimentally were 0.01, 0.06, 0.13 and 0.26 of the EC50 for propofol and 0, 0.05, 0.11 and 0.20 MAC for halothane. During the experiment subjects breathed via a mouthpiece from an end-tidal forcing system. End-tidal PO2 (PE'O2) was held at 13.3 kPa for 5 min, and then at 6.7 kPa for 5 min. End-tidal PCO2 (PE'CO2) was held constant at 0.13-0.27 kPa greater than the subject's natural level throughout. The mean values for AHVR with propofol were: 12.8 (SEM 2.4) litre min-1 (0.01 EC50), 10.0 (1.9) litre min-1 (0.06 EC50), 9.8 (2.3) litre min-1 (0.13 EC50) and 4.9 (1.2) litre min-1 (0.26 EC50). The values for AHVR with halothane were: 11.9 (2.4) litre min-1 (0 MAC), 7.8 (1.6) litre min-1 (0.05 MAC), 5.9 (1.2) litre min-1 (0.11 MAC) and 3.2 (1.6) litre min-1 (0.2 MAC). The decline in AHVR with increasing dose for both drugs was statistically significant (ANOVA, P < 0.001); there was no significant difference between the two drugs with respect to this decline. Normoxic ventilation with propofol declined from 13.2 (1.6) litre min-1 (0.01 EC50) to 8.3 (0.9 litre min-1 (0.26 EC50), and with halothane declined from 13.5 (2.0) litre min-1 (0 MAC) to 11.8 (1.6) litre min-1 (0.2 MAC). This was significant for both drugs (ANOVA, P < 0.001).
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PMID:Comparison of the effects of sub-hypnotic concentrations of propofol and halothane on the acute ventilatory response to hypoxia. 867 19

We have developed a human tissue preparation suitable for measurement of cilia beat frequency derived from nasal turbinates. Cilia beat frequency of turbinate explants from 11 patients did not change significantly over a 10-day observation period while maintained in an incubator, with mean cilia beat frequency of 13.1 (SEM 0.3) Hz to 14.4 (0.2) Hz (ANOVA for repeated measures, P = 0.168). We have used this preparation to investigate recovery of ciliary function after depression by inhalation anaesthetic agents. Eight or nine turbinate explants were exposed to three times the minimum alveolar concentration (MAC) of halothane, enflurane or isoflurane for a period of 1 h and thereafter to a period of air washout. After exposure to the inhalation agent there was a significant reduction in cilia beat frequency with all three agents: halothane 14.3 (0.4) Hz to 9.5 (0.3) Hz; enflurane 13.7 (0.6) Hz to 10.5 (0.5) Hz;isoflurane 15.9 (0.6) Hz to 10.6 (0.3) Hz. Cilia beat frequency returned to values after air washout that were not significantly different from baseline after 90 min of washout of halothane and 60 min of washout of enflurane and isoflurane (repeated measures ANOVA, unpaired t test; P = 0.01 at 60 min and P = 0.31 at 90 min washout for halothane; P = 0.83 at 60 min washout for enflurane; P = 0.26 at 60 min washout for isoflurane).
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PMID:Recovery of respiratory ciliary function after depression by inhalation anaesthetic agents: an in vitro study using nasal turbinate explants. 867 62


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