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HPB : the Official Journal of the... 2008In patients with malignant hilar obstruction, liver resection is associated with an increased risk of postoperative liver failure attributed to the need for major liver...
AIM
In patients with malignant hilar obstruction, liver resection is associated with an increased risk of postoperative liver failure attributed to the need for major liver resection in a context of obstructive jaundice. To overcome this issue, most authors recommend preoperative biliary drainage (PBD). However, PBD carries risks of its own, including, primarily, sepsis and, more rarely, tumor seeding, bile peritonitis, and hemobilia. We, unlike most authors, have not used routine PBD before liver resection in jaundiced patients.
MATERIAL AND METHODS
Our series includes 62 patients who underwent major liver resection for cholangiocarcinoma; 33 of these had elevated bilirubin (60-470 micromol/l) and were operated without PBD. There were 43 extended right hepatectomies and 18 extended left hepatectomies.
RESULTS
Hospital deaths occurred in 5 patients (8%) including 3 of 33 jaundiced patients (9%, ns). All deaths occurred after extended right hepatectomy (12%), including 3 patients with a serum bilirubin level above 300 micromol/l and 2 with normal bilirubin. There were no deaths after left-sided resections, whatever the level of bilirubin.
CONCLUSIONS
PBD can be omitted in the following situations: recent onset jaundice (<2-3 weeks), total bilirubin <200 micromol/l, no previous endoscopic or transhepatic cholangiography, absence of sepsis, future liver remnant >40%. These criteria include most patients requiring left-sided resections and selected patients requiring right-sided resections. In other cases, PBD is required, associated with portal vein embolization in the event of a small future liver remnant.
PubMed: 18773089
DOI: 10.1080/13651820802007472 -
German Medical Science : GMS E-journal Jun 2007Low antioxidant system may contribute to the severity of neonatal hyperbilirubinemia. The aim of this research was to explore the relationship between plasma vitamin E...
OBJECTIVE
Low antioxidant system may contribute to the severity of neonatal hyperbilirubinemia. The aim of this research was to explore the relationship between plasma vitamin E and C levels and the severity of hyperbilirubinemia in full-term neonates with normal glucose 6-phosphate dehydrogenase (G6PD) activities.
METHODS
A total of 130 full-term healthy live birth neonates of healthy mothers with normal G6PD activity were included in this study. In addition to routine blood analysis, plasma total bilirubin, vitamin E and C levels and G6PD activity were measured on the first day of life. None of the neonates was ABO incompatible or anemic.
RESULTS
Neonates who did not develop hyperbilirubinemia (n=119) had a mean plasma bilirubin level of 65+/-24 micromol/l (median 58.1), while neonates who developed significant hyperbilirubinemia (n=11) had a mean plasma bilirubin level of 238+/-56 micromol/l (median 246.2) on the first day of life. Mean plasma vitamin C levels of neonates who developed hyperbilirubinemia were significantly lower than those who did not develop hyperbilirubinemia (87+/-22 micromol/l (median 89.4) vs. 132+/-36 micromol/l (median 127.7), respectively, P=0.0001). Similar results were observed for plasma vitamin E levels in neonates who did or did not develop hyperbilirubinemia (7.5+/-2 micromol/l (median 6.3) vs. 10.4+/-5 micromol/l (median 9.1), respectively, P=0.001). Hemoglobin and hematocrit were significantly lower in neonates who developed hyperbilirubinemia (P=0.0002 and P=0.0003, respectively), although gestational age and birth weight for the two groups showed no significant difference.
CONCLUSION
The results of the present work indicate that low level of plasma vitamins C and E are associated with significant hyperbilirubinemia in full-term neonates.
PubMed: 19675711
DOI: No ID Found -
Sheng Li Xue Bao : [Acta Physiologica... Aug 2008In the present study, we investigated the inhibitory action of ketanserin on wild-type (WT) and Y652 mutant human ether-a-go-go-related gene (HERG) potassium channels...
In the present study, we investigated the inhibitory action of ketanserin on wild-type (WT) and Y652 mutant human ether-a-go-go-related gene (HERG) potassium channels expressed in Xenopus oocytes and the effects of changing the channel molecular determinants characteristics on the blockade with and without ketanserin intervention using standard two-microelectrode voltage-clamp techniques. Point mutations were introduced into HERG gene (Y652A and Y652R) and subcloned into the pSP64 plasmid expression vector. Complementary RNAs for injection into oocytes were prepared with SP6 Cap-Scribe after linearization of the expression construct with EcoR I. Clampfit 9.2 software was employed for data collection and analysis. Origin 6.0 software was used to fit the data, calculate time constants and plot histograms. The results showed that ketanserin blocked WT HERG currents in voltage- and concentration-dependent manner and showed minimal tonic blockade of HERG current evaluated by the envelope of tails test. The IC50 value was (0.38+/-0.04) micromol/L for WT HERG potassium channel. The peaks of the I-V relationship for HERG channel suggested a negative shift in the voltage-dependence of activation after using ketanserin, whose midpoint of activation values (V1/2) were (-16.59+/-1.01) mV (control) vs (-20.59+/-0.87) mV (ketanserin) at 0.1 micromol/L, (-22.39+/-0.94) mV at 1 micromol/L, (-23.51+/-0.91) mV at 10 micromol/L, respectively (P<0.05, n=6). Characteristics of blockade were consistent with an open-state channel blockade, because the extent and rate of onset of blockade was voltage-dependent, increasing at more potentials even in the condition of leftward shift of activation curve. Meanwhile, in the different depolarization duration, the fractional blockade of end-pulse step current and peak tail current at 100 ms duration was significantly lower than that at 400 ms and 700 ms, which indicated that following the channel activation fractional blockade was enhanced by the activated channels. Ketanserin could also modulate the inactivation of HERG channel, which shifted the voltage-dependence of WT HERG channel inactivation curve from (-51.71+/-2.15) mV to (-80.76+/-14.98) mV (P<0.05, n=4). The S6 mutation, Y652A and Y652R, significantly attenuated the blockade by ketanserin. The IC50 value were (27.13+/-9.40) micromol/L and (20.20+/-2.80) micromol/L, respectively, increased by approximately 72-fold for Y652A and 53-fold for Y652R compared to that of WT HERG channel blockade [(0.38+/-0.04) micromol/L]. However, between the inhibitory effects of Y652A and Y652R, there was no significant difference. In conclusion, ketanserin blocks WT HERG currents in voltage- and concentration-dependent manner and preferentially blocks open-state HERG channels. Tyr-652 is one of the critical residues in the ketanserin-binding sites.
Topics: Animals; Ether-A-Go-Go Potassium Channels; Humans; Ketanserin; Mutation; Oocytes; Patch-Clamp Techniques; Potassium Channel Blockers; Xenopus
PubMed: 18690396
DOI: No ID Found -
Acta Pharmacologica Sinica May 2002To investigate the metabolic characteristics of cytochrome P-450 C YP2A6 in human liver microsomes.
AIM
To investigate the metabolic characteristics of cytochrome P-450 C YP2A6 in human liver microsomes.
METHODS
Cytochrome P-450 enzyme activities were measured by biochemical assays. Xenobiotics were employed to observe their effects on CYP2A6 in vitro. The kinetics of coumarin 7-hydroxylase was determined, and the correlation between CYP2A6 and UDP-glucuronosyltransferase (UGT) was analyzed.
RESULTS
CYP2A6 activities of human liver microsomes were from 0.47 to 4.14 micromol . min-1 . g-1, with a 8.8-fold variation. The Km and Vmax of CYP2A6 ranged from 0.25 to 1.56 micromol/L and 1.41 to 8.70 micromol . min-1 . g-1, respectively. CYP2A6 activity was markedly inhibited (> 50 %) by pilocarpine, diethyldithio carbamic (DDC), and rifampicin, the IC50 was 5.31 micromol/L, 156.35 micromol/L, and 38.81 micromol/L, respectively. alpha-Naphthoflavone, sulfaphenazole, troleandomycin (TAO), ketoconazole, phenobarbital, prednisolone, and azithromycin had little or no effects on coumarin 7-hydroxylation. A significant correlation was observed between CYP2A6 and UGT2 (r = 0.9453, P < 0.05).
CONCLUSION
CYP2A6 activity and kinetics exhibited a considerable variation in human liver microsomes in vitro, and a significant correlation was existed between CYP2A6 and phase II enzyme UGT2. Not only pilocarpine, CYP2A6 specific inhibitor, but also rifampicin and DDC inhibited CYP2A6 activity selectively.
Topics: Adult; Aryl Hydrocarbon Hydroxylases; Asian People; Cytochrome P-450 CYP2A6; Enzyme Inhibitors; Glucuronosyltransferase; Humans; Male; Microsomes, Liver; Middle Aged; Mixed Function Oxygenases; Pilocarpine; Rifampin
PubMed: 11978200
DOI: No ID Found -
Acta Pharmacologica Sinica Jul 2004The present study deals with the investigation of mechanisms involved in the synergistic interaction between epinephrine and arachidonic acid (AA).
AIM
The present study deals with the investigation of mechanisms involved in the synergistic interaction between epinephrine and arachidonic acid (AA).
METHODS
Venous blood was taken from healthy human volunteers reported to be free of medications for one week. Platelet aggregation was monitored at 37 degree using Dual-channel Lumi-aggregometer. The resulting aggregation was recorded for 5 min by the measurement of light transmission as a function of time.
RESULTS
The data show that a synergism in platelet aggregation mediated by subthreshold concentrations of epinephrine (1 micromol/L) and AA (0.2 micromol/L) was inhibited by the alpha2-receptor antagonist (yohimbine, IC50)=0.6 micromol/L) and an inhibitor of AA-cyclooxygenase (COX), indomethacin (IC50=0.25 micromol/L). In examining receptor influence on intraplatelet signalling pathways, it was found that the synergistic effect was inhibited by calcium channel blockers, verapamil (IC50=0.4 micromol/L) and diltiazem (IC50=2.5 micromol/L), as well as by low concentrations of inhibitors of phospholipase C (PLC) (U73122; IC50=0.2 micromol/L) and mitogens activated protein kinase (MAPK) (PD 98059; IC50=3.8 micromol/L). Herbimycin A, a specific inhibitor of tyrosine light chain kinase (TLCK), showed inhibition at IC50 value of 15 micromol/L, whereas chelerythrine, a protein kinase C (PKC) inhibitor, had no effect up to 20 micromol/L.
CONCLUSION
These data suggest that synergism between epinephrine and AA in platelet aggregation is triggered through receptors coupled to G-protein, which in turn, activate PLC, COX, and MAP kinase-signaling pathways.
Topics: Adrenergic Agonists; Adrenergic alpha-2 Receptor Antagonists; Adult; Arachidonic Acid; Calcium Channel Blockers; Cyclooxygenase Inhibitors; Drug Synergism; Epinephrine; Female; Flavonoids; Humans; Indomethacin; Male; Platelet Aggregation; Receptors, G-Protein-Coupled; Signal Transduction; Type C Phospholipases; Verapamil; Yohimbine
PubMed: 15210061
DOI: No ID Found -
World Journal of Gastroenterology Jul 2006To evaluate the levels of serum carnitine in patients with cancer in digestive organs and to compare them with other cancers in order to provide new insights into the... (Comparative Study)
Comparative Study
AIM
To evaluate the levels of serum carnitine in patients with cancer in digestive organs and to compare them with other cancers in order to provide new insights into the mechanisms of cachexia.
METHODS
Fifty-five cachectic patients with or without gastrointestinal cancer were enrolled in the present study. They underwent routine laboratory investigations, including examination of the levels of various forms of carnitine present in serum (i.e., long-chain acylcarnitine, short-chain acylcarnitine, free carnitine, and total carnitine). These values were compared with those found in 60 cancer patients in good nutritional status as well as with those of 30 healthy control subjects.
RESULTS
When the cachectic patients with gastro-intestinal cancer were compared with the cachectic patients without gastrointestinal cancer, the difference was -6.8 micromol/L in free carnitine (P < 0.005), 0.04 micromol/L in long chain acylcarnitine (P < 0.05), 8.7 micromol/L in total carnitine (P < 0.001). In the cachectic patients with or without gastrointestinal cancer, the difference was 12.2 micromol/L in free carnitine (P < 0.001), 4.60 micromol/L in short chain acylcarnitine (P < 0.001), and 0.60 micromol /L in long-chain acylcarnitine (P < 0.005) and 17.4 micromol/L in total carnitine (P < 0.001). In the cachectic patients with gastrointestinal cancer and the healthy control subjects, the difference was 15.5 micromol/L in free carnitine (P < 0.001), 5.2 micromol /L in short-chain acylcarnitine (P < 0.001), 1.0 micromol/L in long chain acylcarnitine (P < 0.001), and 21.8 micromol/L in total carnitine (P < 0.001).
CONCLUSION
Low serum levels of carnitine in terminal neoplastic patients are decreased greatly due to the decreased dietary intake and impaired endogenous synthesis of this substance. These low serum carnitine levels also contribute to the progression of cachexia in cancer patients.
Topics: Adult; Breast Neoplasms; Cachexia; Carnitine; Case-Control Studies; Diet; Disease Progression; Female; Gastrointestinal Neoplasms; Humans; Kidney Neoplasms; Lung Neoplasms; Male; Middle Aged; Prostatic Neoplasms; Skin Neoplasms
PubMed: 16874868
DOI: 10.3748/wjg.v12.i28.4541 -
American Journal of Physiology. Heart... Oct 2009Diastolic depolarization (DD) of atrial myocytes can lead to spontaneous action potentials (APs) and, potentially, atrial tachyarrhythmias. This study examined the...
Diastolic depolarization (DD) of atrial myocytes can lead to spontaneous action potentials (APs) and, potentially, atrial tachyarrhythmias. This study examined the hypotheses that 1) a slowly inactivating component of the Na(+) current (referred to as late I(Na)) may contribute to DD and initiate AP firing and that 2) blocking late I(Na) will reduce spontaneous and induced firing of APs by atrial myocytes. Guinea pig atrial myocytes without or with DD and spontaneous AP firing were studied using the whole cell patch-clamp technique. In experiments using cells with a stable resting membrane potential (no spontaneous DD or firing), hydrogen peroxide (H(2)O(2), 50 micromol/l) caused DD and AP firing. The H(2)O(2)-induced activity was suppressed by the late I(Na) inhibitors tetrodotoxin (TTX, 1 micromol/l) and ranolazine (5 micromol/l). In cells with DD but no spontaneous APs, the late I(Na) enhancer anemone toxin II (ATX-II, 10 nmol/l) accelerated DD and induced APs. In cells with DD and spontaneous AP firing, TTX and ranolazine (both, 1 micromol/l) significantly reduced the slope of DD by 81 +/- 12% and 75 +/- 11% and the frequency of spontaneous firing by 70 +/- 15% and 74 +/- 9%, respectively. Ramp voltage-clamp simulating DD elicited a slow inward current. TTX at 1, 3, and 10 micromol/l inhibited this current by 41 +/- 4%, 73 +/- 2%, and 91 +/- 1%, respectively, suggesting that a slowly inactivating I(Na) underlies the DD. ATX-II and H(2)O(2) increased the amplitude of this current, and the effects of ATX-II and H(2)O(2) were attenuated by ranolazine or TTX. In conclusion, late I(Na) can contribute to the DD of atrial myocytes and the inhibition of this current suppresses atrial DD and spontaneous APs.
Topics: Acetanilides; Action Potentials; Animals; Atrial Function; Cnidarian Venoms; Diastole; Female; Guinea Pigs; Heart Atria; Hydrogen Peroxide; Kinetics; Male; Myocytes, Cardiac; Patch-Clamp Techniques; Piperazines; Ranolazine; Sodium; Sodium Channel Blockers; Sodium Channels; Tachycardia, Supraventricular; Tetrodotoxin
PubMed: 19700626
DOI: 10.1152/ajpheart.00444.2009 -
World Journal of Gastroenterology Feb 2006To characterize H+ and HCO3- transporters in polarized CFPAC-1 human pancreatic duct cells, which were derived from a cystic fibrosis patient with the DeltaF508 CFTR...
AIM
To characterize H+ and HCO3- transporters in polarized CFPAC-1 human pancreatic duct cells, which were derived from a cystic fibrosis patient with the DeltaF508 CFTR mutation.
METHODS
CFPAC-1 cells were seeded at high density onto permeable supports and grown to confluence. The cells were loaded with the pH-sensitive fluorescent dye BCECF, and mounted into a perfusion chamber, which allowed the simultaneous perfusion of the basolateral and apical membranes. Transmembrane base flux was calculated from the changes in intracellular pH and the buffering capacity of the cells.
RESULTS
Our results showed differential permeability to HCO3-/CO2 at the apical and basolateral membranes of CFPAC-1 cells. Na+/ HCO3- co-transporters (NBCs) and Cl-/ HCO3- exchangers (AEs) were present on the basolateral membrane, and Na+/H+ exchangers (NHEs) on both the apical and basolateral membranes of the cells. Basolateral HCO3- uptake was sensitive to variations of extracellular K+ concentration, the membrane permeable carbonic anhydrase (CA) inhibitors acetazolamide (100 micromol/L) and ethoxyzolamide (100 micromol/L), and was partially inhibited by H2-DIDS (600 micromol/L). The membrane-impermeable CA inhibitor 1-N-(4-sulfamoylphenylethyl)-2,4,6-trimethylpyridine perchlorate did not have any effect on HCO3- uptake. The basolateral AE had a much higher activity than that in the apical membrane, whereas there was no such difference with the NHE under resting conditions. Also, 10 micromol/L forskolin did not significantly influence Cl-/ HCO3- exchange on the apical and basolateral membranes. The administration of 250 micromol/L H2-DIDS significantly inhibited the basolateral AE. Amiloride (300 micromol/L) completely inhibited NHEs on both membranes of the cells. RT-PCR revealed the expression of pNBC1, AE2, and NHE1 mRNA.
CONCLUSION
These data suggest that apart from the lack of CFTR and apical Cl-/ HCO3- exchanger activity, CFPAC-1 cells express similar H+ and HCO3- transporters to those observed in native animal tissue.
Topics: 4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid; Acetazolamide; Anion Transport Proteins; Bicarbonates; Cell Line; Cell Membrane Permeability; Ethoxzolamide; Humans; Hydrogen-Ion Concentration; Pancreatic Ducts; Potassium
PubMed: 16521216
DOI: 10.3748/wjg.v12.i6.885 -
Scandinavian Journal of Work,... Aug 2004The aim of this study was to evaluate different biomarkers of exposure to N-methyl-2-pyrrolidone (NMP), a widely used industrial chemical. For this purpose, differences...
OBJECTIVES
The aim of this study was to evaluate different biomarkers of exposure to N-methyl-2-pyrrolidone (NMP), a widely used industrial chemical. For this purpose, differences in toxicokinetics between men and women and between pure and water-mixed NMP were evaluated after dermal absorption.
METHODS
Six female and six male volunteers (groups 1 and 2) were topically exposed for 6 hours to 300 mg of NMP. An additional group of six male volunteers (group 3) was exposed to 300 mg of NMP in a 50% water solution. Blood and urine were sampled before, during, and up to 9 days after the exposure. Plasma and urine were analyzed using mass spectrometry.
RESULTS
For groups 1 and 2, 16% and 18% of the applied dose were recovered in the urine as the sum of NMP and its metabolites. For group 3, 4% was recovered. The maximal concentration of 5-hydroxy-N-methyl-2-pyrrolidone (5-HNMP) was 10, 8.1, and 2.1 micromol/l for groups 1, 2 and 3, respectively, in plasma and 420, 360 and 62 micromol/l in urine adjusted for density. For 2-hydroxy-N-methylsuccinimide (2-HMSI), the maximal concentration was 5.4, 4.5, and 1.3 micromol/l for groups 1, 2 and 3, in plasma, respectively, and 110, 82 and 19 micromol/l in urine adjusted for density. For 5-HNMP there was a difference in time to reach the maximal concentration depending on whether pure NMP or 50% NMP in water was used. No such difference was seen for 2-HMSI. The differences in kinetics between male and female volunteers were small.
CONCLUSIONS
Preferably 2-HMSI should be used as the biomarker of exposure to NMP.
Topics: Adult; Biomarkers; Female; Humans; Male; Middle Aged; Occupational Exposure; Pyrrolidinones; Sweden
PubMed: 15458014
DOI: 10.5271/sjweh.799 -
The Journal of Nutrition Mar 2006The purpose of this study was to determine whether the plasma response to dietary cholesterol from eggs is associated with the plasma carotenoid response and whether... (Comparative Study)
Comparative Study
The purpose of this study was to determine whether the plasma response to dietary cholesterol from eggs is associated with the plasma carotenoid response and whether gender influences the carotenoid response. Using a crossover design, 40 subjects classified as either hyper- (10 men and 10 women) or hyporesponders (10 men and 10 women) to dietary cholesterol consumed an egg (EGG, 640 mg/d additional dietary cholesterol and 600 microg lutein + zeaxanthin) or placebo (SUB, 0 mg/d cholesterol, 0 microg lutein + zeaxanthin and 568 microg beta-carotene) diet for 30 d, followed by a 3-wk washout period and the alternate diet. Plasma concentrations of lutein and beta-carotene after each dietary period were then examined to determine whether the response to carotenoid intake was similar to that seen for dietary cholesterol. After the EGG period, the increase in plasma lutein in female hyperresponders (mean increase +/- SD; 0.32 +/- 0.19 micromol/L) and male hyperresponders (0.26 +/- 0.11 micromol/L) was significantly greater than that of their hyporesponsive counterparts (0.16 +/- 0.18 micromol/L for women and 0.14 +/- 0.11 micromol/L men). Gender was not a significant factor influencing lutein response. Both men and women classified as hyperresponders significantly increased plasma beta-carotene after the SUB period, whereas their hyporesponsive counterparts were not affected. The increase in plasma beta-carotene in female hyperresponders (0.29 +/- 0.48 micromol/L) was significantly greater than that in male hyperresponders (0.07 +/- 0.07 micromol/L). We conclude that plasma responses to cholesterol and carotenoids are related and that gender influences the beta-carotene response to a greater degree than the lutein response.
Topics: Analysis of Variance; Cholesterol; Cholesterol, Dietary; Cholesterol, HDL; Cholesterol, LDL; Eggs; Female; Humans; Lutein; Male; Placebos; Sex Characteristics; Triglycerides; beta Carotene
PubMed: 16484531
DOI: 10.1093/jn/136.3.601