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Biomedical subjects

T L Hwang

Publications and source records attributed to T L Hwang.

At least 37 records · Page 2Linked to original sources
PubMed1999

Neutrophil elastase inhibitor (ONO-5046) attenuates reperfusion-induced hepatic microcirculatory derangement, energy depletion and lipid peroxidation in rats.

UNLABELLED: Microcirculatory derangement, energy depletion, and lipid peroxidation are associated with the development of ischemia-reperfusion injury in the liver. This study investigated the effects of a neutrophil elastase inhibitor (ONO-5046) on hepatic ischemia-reperfusion injury. Adult, male Sprague-Dawley rats were divided into four treatment groups: 1) sham-operated control (laparotomy only, no ischemia) and saline injection (1 mL/kg), n = 6; 2) ischemia control (1-h ischemia, 2-h reperfusion) and saline injection (1 mL/kg), n = 6; 3) intravenous injection with ONO-5046 at a dose of 1 mg/kg 5 min before ischemia and immediately after reperfusion plus 1-h ischemia and 2-h reperfusion, n = 6; and 4) intravenous injection with ONO-5046 at a dose of 10 mg/kg 5 min before ischemia and immediately after reperfusion plus 1-h ischemia and 2-h reperfusion, n = 6. A laser-Doppler flowmeter and in vivo microscopy were used to investigate hepatic microcirculation. Tissue malondialdehyde (MDA) and adenosine triphosphate (ATP) levels were determined at the end of the experiment. RESULTS: Compared with ischemia alone, ONO-5046 significantly reduced the extent of microcirculatory and hemodynamic derangement after ischemia-reperfusion. ONO-5046 at both doses significantly attenuated decreases in mean arterial pressure. ONO-5046 lessened adherent leukocyte count and improved flow velocity in the sinusoids and postsinusoidal venules. ONO-5046 at the dose of 10m/kg reduced MDA (1.97 +/- 0.54 micromol/g protein vs. 3.58 +/- 1.21 micromol/g protein in the ischemia and reperfusion group) and increased ATP levels (2.62 +/- 0.19 micromol/g wet wt vs. 0.57 +/- 0.37 pmol/g wet wt in the ischemia and reperfusion group), whereas ONO-5046 at a smaller dose (1 mg/kg) had lesser but significant effects on MDA and ATP alterations. This study demonstrates that treatment with ONO-5046, a neutrophil elastase inhibitor, can ameliorate ischemia-reperfusion injury of the rat liver.

Adenosine Triphosphate↗
PubMed1998

Cell proliferation in human prostatic smooth muscle cells involves the modulation of protein kinase C isozymes.

We have examined the role of protein kinase C in the regulation of foetal-calf serum-stimulated cell proliferation in human prostatic smooth muscle cells. The data showed that the proliferative effect to foetal-calf serum (10%, v/v) was partially inhibited by 12-(2-cyanoethyl)-6,7,12,13-tetrahydro-13-methyl-5-oxo-5H-indolo (2,3-a) pyrrolo (3,4-c)-carbazole (Go-6976), a selective Ca2+-dependent protein kinase C inhibitor, suggesting that Ca2+-dependent protein kinase C isozymes might play roles in this proliferative regulation. Additionally, foetal-calf serum caused a significant translocation of protein kinase C-betaII and -epsilon from a cytosolic to a membrane distribution. These findings combined with the aforementioned functional experiments suggest that foetal-calf serum-stimulated cell proliferation might involve the activation of protein kinase C-betaII in human prostatic smooth muscle cells; however, the role of protein kinase C-epsilon in mediating cellular functions other than cell proliferation remains further investigation in these cells.

Carbazoles↗
PubMed1998

Pyogenic liver abscesses in patients with malignant disease: a report of 52 cases treated at a single institution.

BACKGROUND: Prognosis of pyogenic liver abscesses in patients with malignant disease is generally considered poor. The discrepancy between the outcomes of liver abscesses caused by hepatopancreatobiliary malignant disease and those caused by other malignant diseases, however, to our knowledge has never been investigated. OBJECTIVES: To clarify the clinical course of pyogenic liver abscess in patients with different types of cancer, and to compare outcomes in abscesses caused by hepatopancreatobiliary malignant disease and other malignant disease. DESIGN: Retrospective review of case series in our experience from 1980 through 1993. SETTING: Tertiary care university teaching hospital. PATIENTS: Fifty-two patients with pyogenic liver abscess related to the underlying cancer were divided into 2 groups. Group 1 (n=32) was composed of patients with cancer originating from the hepatic parenchyma, bile duct, and pancreas; group 2 (n=20) was composed of patients with cancer originating from other sites. INTERVENTIONS: Parenteral antibiotics, percutaneous drainage, surgical drainage, or hepatectomy, in combinations, were employed. MAIN OUTCOME MEASURES: Patient characteristics, symptoms, laboratory data, abscess characteristics, microbiological study, management, and outcome of the 2 groups were analyzed. RESULTS: Thirteen patients (41%) in group 1 and 16 patients (80%) in group 2 had undergone prior anticancer treatment. Jaundice was encountered more often in group 1 than in group 2 (29 patients [91%] vs 6 patients [30%], respectively, P=.001), whereas nausea and vomiting were more frequently seen in group 2 than in group 1 (17 patients [52%] vs 6 patients[31%], respectively, P=.04). Leukocytosis, hypoalbuminemia, hyperbilirubinemia, and reversed albumin-globulin ratio were more pronounced in group 1 than in group 2 (P=.001, .02, .003, and .03, respectively). Abscesses communicating with the intrahepatic biliary tree were more frequently encountered in group 1 than in group 2 (11 patients [34%] vs 2 patients [10%], respectively, P=.03). Escherichia coli and Klebsiella pneumoniae predominated in group 1, while the bacteria species in group 2 were more diverse. The hospital mortality rates of group 1 and group 2 were 28% (9 of 32 patients) vs 10% (2 of 20 patients) (P=.04), respectively. Twenty-three patients (72%) of group 1 died of uncontrolled biliary sepsis or progressive cancer or both within 6 months after the diagnosis, while 17 patients (85%) of group 2 survived longer than 1 year without relapse of the abscess and continued with anticancer treatment. CONCLUSIONS: Pyogenic liver abscess could be a presentation of hepatopancreatobiliary malignant disease at the preterminal stage, and carries a grave prognosis. Pyogenic liver abscess in patients with nonhepatopancreatobiliary malignant disease has a better chance of favorable outcome.

Adult↗
PubMed1998

Fast broadband inversion by adiabatic pulses.

Despite the advantages of compensation for resonance offset and B1 inhomogeneity, adiabatic pulses are not yet in general use in high-resolution NMR, often because of the conception that these pulses require longer time or increased power to perform. We show that adiabatic pulses with tangential frequency sweeps and other frequency-modulation functions can be optimized to accomplish 13C and 1H broadband inversion using pulse lengths of 192 and 64 micro(s), respectively, at B1 strengths available with modern high-resolution probes.

Algorithms↗
PubMed1998

Multiple-pulse mixing sequences that selectively enhance chemical exchange or cross-relaxation peaks in high-resolution NMR spectra.

Rotating-frame NMR experiments which either emphasize or suppress cross relaxation, and which simultaneously suppress TOCSY, COSY, and zero-quantum peaks in NMR spectra, are presented and analyzed. The new experiments rely on mixing sequences which follow naturally from the transverse-ROESY (Tr-ROESY) sequence of Hwang and Shaka, and which are applicable to larger molecules in solution (spin diffusion limit). In the first variant a modified Tr-ROESY sequence, called multiple-pulse ROESY (MP-ROESY), is used to enhance cross-relaxation peak intensity compared to Tr-ROESY; in the second, called phase-modulated CLEAN chemical exchange (CLEANEX-PM), cross-relaxation peaks are greatly attenuated. The two methods are thus complementary: MP-ROESY is used to observe Overhauser peaks, and CLEANEX-PM is used to eliminate them, permitting clear observation of chemical exchange peaks alone. The new techniques are examined by theory and experiment. Practical guidelines that will result in high-quality spectra are given, including the judicious use of continuous weak static magnetic field gradients.

Magnetic Resonance Spectroscopy↗
PubMed1998

Accurate quantitation of water-amide proton exchange rates using the phase-modulated CLEAN chemical EXchange (CLEANEX-PM) approach with a Fast-HSQC (FHSQC) detection scheme.

Measurement of exchange rates between water and NH protons by magnetization transfer methods is often complicated by artifacts, such as intramolecular NOEs, and/or TOCSY transfer from C alpha protons coincident with the water frequency, or exchange-relayed NOEs from fast exchanging hydroxyl or amine protons. By applying the Phase-Modulated CLEAN chemical EXchange (CLEANEX-PM) spin-locking sequence, 135 degrees (x) 120 degrees (-x) 110 degrees (x) 110 degrees (-x) 120 degrees (x) 135 degrees (-x) during the mixing period, these artifacts can be eliminated, revealing an unambiguous water-NH exchange spectrum. In this paper, the CLEANEX-PM mixing scheme is combined with Fast-HSQC (FHSQC) detection and used to obtain accurate chemical exchange rates from the initial slope analysis for a sample of 15N labeled staphylococcal nuclease. The results are compared to rates obtained using Water EXchange filter (WEX) II-FHSQC, and spin-echo-filtered WEX II-FHSQC measurements, and clearly identify the spurious NOE contributions in the exchange system.

Magnetic Resonance Spectroscopy↗
PubMed1998

Hepatocellular carcinoma complicated with coexisting hepatolithiasis: pitfalls in diagnosis and management.

Nineteen patients with hepatocellular carcinoma associated with hepatolithiasis were retrospectively analyzed. Eleven of the 19 patients presented with hepatolithiasis-related biliary infection. Diagnosis was erroneously assumed to be hepatolithiasis alone, liver abscess, or cholangiocarcinoma in five of 11 patients before surgery was attempted. Middle-age, male sex, liver cirrhosis, hepatitis B or C infection, abnormal alpha-fetoprotein, and negative carcinoembryonic antigen raised the suspicion of associated hepatocellular carcinoma rather than cholangiocarcinoma in patients with hepatolithiasis. Antibiotics and nonoperative methods to resolve biliary infection first, followed by hepatectomy, in selected cases, to eradicate hepatocellular carcinoma and hepatolithiasis simultaneously provides the best chance for long-term survival. Otherwise, patients often died of hepatolithiasis-related biliary sepsis rather than hepatocellular carcinoma per se in the long run.

Adult↗
PubMed1998

Comparison of two soluble guanylyl cyclase inhibitors, methylene blue and ODQ, on sodium nitroprusside-induced relaxation in guinea-pig trachea.

To clarify further the role of cyclic GMP in mediating the relaxant response in guinea-pig trachea induced by sodium nitroprusside (SNP), the effects of soluble guanylyl cyclase inhibitors, methylene blue and 1H-[1,2,4]oxadiazolo[4,3,-a]quinoxalin-1-one (ODQ) on SNP-induced muscle relaxation and cyclic GMP accumulation were determined. SNP (0.3-100 microM) evoked a concentration-dependent relaxation of guinea-pig isolated tracheas precontracted with 0.3 microM carbachol. Preincubation of the preparations with methylene blue (10, 30 and 100 microM) resulted in a slight but concentration-dependent prevention of the relaxant response to SNP. In contrast, the relaxation to SNP was extensively prevented by 3 microM ODQ and almost abolished by 10 microM ODQ. SNP (30 microM) induced a significant elevation of cyclic GMP accumulation (from 1.34+/-0.14 to 5.39+/-0.28 pmol mg(-1) protein, n= 5; P<0.001), which was partially attenuated by 100 microM methylene blue (3.11+/-0.51 pmol mg(-1) protein, n=5; P<0.05), whereas completely abolished by 10 microM ODQ (1.31+/-0.28 pmol mg(-1) protein, n = 5; P<0.001). Methylene blue, but not ODQ and Nomega-nitro-L-arginine methyl ester (L-NAME), caused a concentration-dependent contraction in the tracheal preparation. The tension produced by 100 microM methylene blue was 41.8+/-4.3% (0.3 microM carbachol as 100%; n = 12). Moreover, the non-selective muscarinic receptor antagonist atropine and the M3-selective antagonist 4-diphenylacetoxy-N-methylpiperidine methiodine greatly inhibited the contractile effect evoked by methylene blue (100 microM). In conclusion, this study provides substantial evidence that SNP-induced muscle relaxation in guinea-pig trachea is completely via a cyclic GMP-dependent mechanism. Furthermore, ODQ, but not methylene blue, will likely become an important tool in differentiating between cyclic GMP-dependent and -independent effects of nitric oxide.

Animals↗
PubMed1998

Hepatocellular carcinoma presenting as pyogenic liver abscess: characteristics, diagnosis, and management.

We performed a 17-year retrospective analysis of 10 cases of hepatocellular carcinoma presenting as pyogenic liver abscess. Spontaneous tumor necrosis and biliary obstruction caused by tumor thrombi, superimposed with bacterial infection, were the two major pathogeneses. Exact diagnosis of the underlying hepatocellular carcinoma was made for five of the 10 patients before management was attempted. Main clinical manifestations included fever, chills, right-upper-quadrant pain, malaise, anorexia, jaundice, and hepatomegaly. Characteristics such as middle age and male sex, seropositivity for hepatitis B and/or hepatitis C, chronic liver disease, unexplained anemia, marked weight loss, and a severely inversed albumin/globulin ratio raise suspicions about the underlying hepatocellular carcinoma. Management strategies included percutaneous drainage (n = 3), surgical drainage (n = 4), and hepatectomy (n = 3) in addition to administration of parenteral antibiotics in all cases. The prognosis was dismal, with a mean survival of 3.5 months (range, 8 days to 6 months).

Adult↗
PubMed1998

Activation of muscarinic K+ channels by extracellular ATP and UTP in rat atrial myocytes.

The effects of extracellular adenine and pyrimidine nucleotides on the acetylcholine-activated K+ channels (KACh) in rat cardiac myocytes were compared and examined by using the patch-clamp technique. In perforated-patch whole-cell recording experiments, extracellular adenosine triphosphate (ATP) reversibly caused an increase in K+ current. 8-Cyclopentyl-1,3-dipropylxanthine (CPX; 1 microM), a potent A1-adenosine-receptor antagonist, only partially antagonized the ATP-induced increase in K+ current, whereas glibenclamide (30 microM) had no effect. In cell-attached mode, adenosine and ATP activated single channels that had nearly identical conductance (29 pS) and open time (1.53 ms). These results suggest that adenosine and ATP can activate the same population of K+ channels. Uridine triphosphate (UTP; 100 microM) also caused an increase in steady-state K+ current. In cell-attached mode, the addition of UTP to the recording pipette solution (not in the bath solution) activated the channel current. The single-channel conductance and open time for UTP-induced channel current were 27 pS and 1.57 ms, respectively. These values were similar to those for the K+ channels activated by adenosine or ATP. The rank order of potency for the activation of KACh channels was adenosine = ATP > UTP. The addition of CPX (1 microM) to the pipette solution attenuated the ATP-induced channel activity by approximately 70% and fully prevented activation by AMPCPP, a less hydrolyzable ATP analog but did not cause any effect on UTP-induced channel activity. In pertussis toxin-treated cardiac myocytes, no any activity of UTP-induced KACh-channel current was observed. Our results demonstrate that extracellular ATP and UTP can directly activate KACh-channel current. This activation also was linked to pertussis toxin-sensitive G protein. The effect of extracellular ATP is mainly caused by the action on binding to A1-adenosine receptor, whereas the effect of extracellular UTP may be mediated possibly by P2u-purinergic (or 5'-nucleotide) receptor.

Acetylcholine↗
PubMed1998

Leukocyte-endothelial adherence correlates with pancreatic nitric oxide production in early cerulein-induced pancreatitis in rats.

The role of nitric oxide (NO) in microcirculation during the development of acute pancreatitis was not clear. An in vivo microscopic technique was used for evaluating leukocyte-endothelial adherence in the pancreatic microcirculation after induction (cerulein) of acute pancreatitis. Microdialysis was performed to detect pancreatic nitrate concentration (NO level) by high-performance liquid chromatography. Cerulein caused significantly reduced flow velocity in 1 h (31 %) and increased the number of sticking leukocytes in 2 h; both persisted for at least 3 h. Pancreatic NO level was found to be significantly elevated (2.5-fold) in 1 h and also persisted for 3 h. Both microcirculatory changes and NO elevation were significantly alleviated in cerulein-induced animals pretreated with NO synthase inhibitor (NG-nitro-L-arginine), indicating that elevation of NO could precede and account for a major portion of the observed microcirculatory changes. Furthermore, there was a strong positive correlation between numbers of adherent leukocytes and pancreatic NO level, suggesting that during the development of acute pancreatitis, NO could play an adverse role in microcirculation.

Animals↗
PubMed1998

Antiproliferative effect in human prostatic smooth muscle cells by nitric oxide donor.

We obtained a primary culture of prostatic cells through explantation from patients with benign prostatic hyperplasia. Structural morphology, immunohistochemical staining, and growth characteristics of these cells demonstrate that they are consistent with the population of smooth muscle cells (SMCs). We examined the influence of a nitric oxide donor, sodium nitroprusside (SNP), on the regulation of human prostatic SMC proliferation. SNP exhibited a concentration-dependent (0.1-10 microM) inhibition of fetal calf serum-induced proliferation in human prostatic SMCs. In addition, growth-inhibitory responses to 8-bromo-cGMP (1-30 muM) were observed. However, the responses to SNP were significantly diminished by the presence of 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (3 microM; a selective guanylate cyclase inhibitor). Furthermore, SNP induced an increased concentration-dependent accumulation of intracellular cGMP in human prostatic SMCs. After 48-hr period of deprivation of serum, cells were restimulated with serum to permit cell cycle progression. The addition of SNP (10 microM) at various times after the addition of serum to serum-deprived cells showed maximal inhibition of cell proliferation even when added 6 hr after the serum. This blocking effect of cell cycle progression was lost gradually as the delay from serum to SNP application increased from 6 to 18 hr. The membrane-associated protein kinase C (PKC) activity was studied in human prostatic SMCs; results showed that fetal calf serum (10%, v/v) significantly increased membrane-associated PKC activity. SNP (10 muM), which had little effect on basal kinase activity, completely abolished serum-induced augmentation of PKC activity. Therefore, we suggest that SNP mediates its antiproliferative effect by the inhibition of PKC activity on human prostatic SMCs; furthermore, its antiproliferative effect occurs at the early G1 phase of the cell cycle.

Apoptosis↗
PubMed1998

Prognostic factors in node-negative breast cancer patients: the experience in Taiwan.

BACKGROUND: Adjuvant chemotherapy has improved the length of disease-free survival and overall survival in node-negative breast cancer patients. It has been a common practice to select only the patients with higher rates of recurrence for adjuvant therapy. Therefore, it is essential to define the risk factors in node-negative breast cancer patients. MATERIALS AND METHODS: Two hundred fifty-five patients with axillary node-negative breast cancers without adjuvant chemotherapy or hormonal therapy at Chang Gung Memorial Hospital between 1981 and 1986 were included in this study. Tissue blocks for DNA flow cytometry study was available in the tumors of 145 patients. RESULTS: The median follow-up period was 121 months and the percentages of patients with 10 years of disease-free survival (DFS) and overall survival (OS) were 75.1% and 82.2%, respectively. The significant poor prognostic factors for 10 years of OS were a tumor size larger than 3 cm, negative estrogen and progesterone receptor status, and having a non-diploid tumor (p value = 0.0176, 0.048 and 0.016, respectively). The patients with frozen section, high mitotic rate, and Scarff-Blood-Richardson (SBR) grade II and III tumors had a worse prognosis than the others, but this trend did not reach statistical significance. The patients with positive estrogen receptor status had a 10-year disease-free rate (DFR) of 94%, and these with tumors less than 2 cm plus SBR grade I had a 10-year DFR of 92%. CONCLUSION: The node-negative breast cancer patients with a low risk of recurrence were those who had estrogen receptor positive, tumor less than 2 cm with SBR grade I, and intraductal carcinomas. Adjuvant chemotherapy would be no benefit for these patients.

Adult↗
PubMed1998

Helicobacter pylori in surgical specimens from patients with resectable gastric adenocarcinoma.

BACKGROUND: To investigate the prevalence of Helicobacter pylori (H. pylori) in surgical specimens from patients with respectable gastric adenocarcinoma using a histological method, and to study the specific biology of H. pylori-associated gastric cancer. MATERIALS AND METHODS: The presence of H. pylori in resected specimens from 276 patients treated between October 1994 and October 1996 was evaluated histologically using hematoxylin-eosin stain. Clinicopathologic data, including age, gender, cancer location, invasion depth, histologic type (intestinal or diffuse), stage (early or advanced), and the histology of the noncancerous gastric mucosa, were compared between patients testing positive and those testing negative for H. pylori. RESULTS: The overall positive rate of H. pylori was 27.5%. H. pylori-positive gastric cancer was frequently associated with atrophic gastritis or intestinal metaplasia in the noncancerous tissue, but was not associated with other variables. CONCLUSION: The results contradict the prevailing concept that H. pylori rarely colonizes in the metaplastic mucosa. To determine whether patients who have normal mucosa with superficial gastritis have a lower seroprevalence of H. pylori, further serologic study of the IgG antibody against H. pylori is mandatory. Our histologically positive rate is relatively lower than the seropositive one. More tissue samplings and special stains may provide more precise results.

Adenocarcinoma↗
PubMed1997

Ionic mechanisms of tetrandrine in cultured rat aortic smooth muscle cells.

The ionic mechanism of tetrandrine, an alkaloid extracted from the Chinese medicinal herb Radix stephania tetrandrae, was investigated in A7r5 vascular smooth muscle cells. The nystatin-perforated whole-cell voltage-clamp technique was performed to examine the effects of tetrandrine on ionic currents. Tetrandrine (1-100 microM) reversibly caused an inhibition of L-type voltage-dependent Ca2+ current (I(Ca,L)) in a concentration-dependent manner. Tetrandrine did not cause any change in the overall shape of the current-voltage relationship of I(Ca,L). The IC50 value of tetrandrine-induced inhibition of I(Ca,L) was 5 microM. In the presence of Bay K 8644 (3 microM) or cyclopiazonic acid (30 microM), tetrandrine still produced a significant inhibition of I(Ca,L). The inhibitory effects of tetrandrine on I(Ca,L) exhibited tonic and use-dependent characteristics. Moreover. tetrandrine (3 microM) shifted the steady-state inactivation curve of I(Ca,L) to more negative membrane potentials by approximately -15 mV. These results indicate that tetrandrine directly inhibits the voltage-dependent L-type Ca2+ current in vascular smooth muscle cells, which may predominantly contribute to the vasodilatory actions of tetrandrine.

Alkaloids↗
PubMed1997

Pancreaticojejunal anastomotic leak after pancreaticoduodenectomy--multivariate analysis of perioperative risk factors.

The records of 131 consecutive patients with periampullary carcinoma who underwent pancreaticoduodenectomy within a 12-year period were reviewed to determine the perioperative risk factors of pancreaticojejunal (PJ) anastomotic leak. Twenty-one PJ leaks were identified, for a frequency of 16% (21 of 131); 19% (4 of 21) of these patients eventually died of PJ leak-related complications. A total of 23 items of perioperative data, presumed as risk factors predisposing to PJ leak, were examined. By univariate analysis, advanced age, prolonged duration of untreated jaundice, deep jaundice, decreased creatinine clearance, increased intraoperative blood loss, and shock during operation were statistically significant. However, by multivariate analysis, only duration of jaundice, creatinine clearance, and intraoperative blood loss turned out to be independent risk factors. Noteworthily, jaundiced patients with impaired creatinine clearance not only had a higher incidence of PJ leak, but were also more liable to experience sepsis and intraabdominal bleeding, which uniformly elicited a grave clinical course. Routine preoperative biliary drainage failed to enhance the security of PJ. Completion pancreatectomy continued to carry a poor prognosis, and should be avoided when possible and replaced by early, aggressive radiologic intervention.

Adult↗
PubMed1997

Changes of adenosine triphosphate-dependent calcium uptake in microsomal fractions of rat liver during sepsis.

BACKGROUND: Intracellular calcium concentration is an important regulator of cellular metabolism. Endoplasmic reticulum membranes play an important role in the regulation of cytoplasmic calcium in the mammalian liver. The characterization of the changes of calcium uptake in endoplasmic reticulum may contribute to the potential intracellular mechanisms for cellular dysfunction during sepsis. METHODS: The effects of sepsis on the calcium uptake in rough endoplasmic reticulum of rat liver were studied. Sepsis was induced by means of cecal ligation and puncture (CLP). The control rats underwent sham operation. Microsomal fractions were isolated from the liver with differential centrifugation. RESULTS: The calcium uptake by liver endoplasmic reticulum was decreased by 30% to 35% (p < 0.05) during early sepsis (9 hours after CLP) and by 38% to 43% (p < 0.05) during late sepsis (18 hours after CLP), respectively. The maximum velocity values for adenosine triphosphate (ATP) and for Ca2+ were also decreased by 25% to 37% (p < 0.05) during early sepsis and by 35% to 42% (p < 0.05) during late sepsis. The Michaelis-Menten constant for ATP and Ca2+ transport had no difference among three groups. The magnesium stimulation and vanadate inhibitory activity were also decreased by 17% to 38% (p < 0.05) during early sepsis and by 34% to 50% (p < 0.05) during late sepsis. CONCLUSIONS: These data demonstrate that ATP-dependent calcium uptake in rough endoplasmic reticulum of rat liver was impaired during early and late sepsis. Because the low intracellular calcium concentration plays an important role in the regulation of cellular function, an impairment in the ATP-dependent calcium uptake by endoplasmic reticulum during early and late sepsis may have a pathophysiologic significance in contributing to the development of altered hepatic metabolism during sepsis.

Adenosine Triphosphate↗