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Biomedical subjects

H M Chen

Publications and source records attributed to H M Chen.

At least 55 records · Page 3Linked to original sources

Selective inhibition of inducible nitric oxide in ischemia-reperfusion of rat small intestine.

PURPOSE: We investigated the role of constitutive and inducible nitric oxide (NO) synthases in intestinal ischemia-reperfusion (I/R) injury by observing the alterations in hemodynamics and intestinal microcirculation in response to I/R in rats, with or without inhibitors of NO synthases. METHODS: Adult male Sprague-Dawley rats (n = 9/group) received a standard I/R procedure alone: I/R plus intravenous administration of aminoguanidine (an inhibitor of inducible NO synthase); I/R plus L-NAME (NG-nitro-L-arginine methyl ester, an inhibitor of constitutive and inducible NO synthase); IR + L-Arg (L-arginine, an NO precursor); or a sham operation plus the vehicle. The I/R procedure was performed by clamping the perfusion vessels of a segment of the terminal ileum, and medication was administered intravenously before and after intestinal ischemia. The intestinal perfusion and leukocyte-endothelial interactions were evaluated with in vivo microscopy and laser Doppler flowmetry. Surface expression of CD11b (an adhesion molecule) of circulating granulocytes was measured with flow cytometry. RESULTS: Intestinal I/R produced circulatory alterations, intestinal microcirculatory derangement, energy depletion, and lipid peroxidation. Aminoguanidine significantly attenuated the reperfusion-related depression of mean arterial pressure (MAP), the decrease in intestinal perfusion index, the decrease in tissue ATP preservation, the increase in tissue malondialdehyde (MDA) level, and the expression of CD11b of circulating granulocytes. Administration of L-NAME had only minor and transient effects on reperfusion-related changes of MAP, intestinal flux, numbers of adherent leukocytes, and CD11b expression, but had some protective effects on tissue MDA and adenosine triphosphate levels and flow velocity. L-Arg further decreased the MAP but did not affect reperfusion-related variables. CONCLUSIONS: Our results show that the selective inhibition of inducible NO synthase by aminoguanidine attenuates the hemodynamic and microcirculatory derangement that results from intestinal I/R.

Animals↗

A novel approach of intravenous electrocardiograph technique in correct position the long-term central venous catheter.

Intravenous electrocardiograph (IVECG) can correctly positioning the catheter tip by enlarging p wave as it is moved toward right atrium, and it is a safe, reliable and accurate technique. To evaluate the efficacy of wire-conducted IVECG signal and IVECG signal from the port with sodium bicarbonate (NaHCO3) flushed catheter and to compare those with conventional anatomy landmark method was the propose of this study. This prospective study was carried out in 216 patients who suffered from malignant diseases. The correct position of the catheter tip among these groups was confirmed as follows. In group 1 (n = 80), the anatomy landmark method and portable chest radiograph recognized the correct position. In group 2 (n = 72), IVECG signal was conducted from guide wire to identify the tip position. In group 3 (n = 64), IVECG signal was conducted from the port with NaHCO3 (0.8 mEq/mL) flushed catheter to ascertain the tip position. The patient characteristics did not differ significantly among the groups. The duration of operation was significantly (P < 0.001) longer in group 1 than in group 2 and group 3 (45.4 +/- 9.3 minutes vs 35.7 +/- 8.0 minutes and 35.2 +/- 9.7 minutes, respectively). Catheter tip placement times were shorter in group 2 and group 3 than in group 1 (5.3 +/- 2.9 minutes and 6.4 +/- 3.0 minutes vs 16.7 +/- 5.7 minutes, respectively); there was a statistically significant difference between the group 1 and group 2 and group 3 (p < 0.001). Nonetheless, the duration of operation and catheter tip placement time was similar in group 2 and group 3. Early and late complications within the subsequent 3 months showed no significant difference among groups. We concluded that IVECG signal conducted from guide wire obtained a similar efficiency to that signal from the port with NaHCO3 flushed catheter on positioning the catheter tip of the venous Port-A-Cath system. It is recommended to use these methods to facilitate implanting long-term central venous devices.

Catheterization, Central Venous↗

Malignant phyllodes tumor of the breast metastasizing to the pancreas: case report.

Phyllodes tumor of the breast, or cystosarcoma phyllodes, is an unusual breast tumor. It is usually considered a benign lesion but may have malignant potential. Only a small proportion of malignant phyllodes tumors will metastasize. A phyllodes tumor of the breast metastasizing to the pancreas is rare. This 39-year-old female patient initially presented to us with a 5 x 4 x 2 cm tumor of a right breast. After excision of the tumor, she received another wise excision for a local recurrence of the tumor. Three years had passed when she started having hematemesis and tarry stools intermittently over a period of about one month. Clinical evaluation disclosed a huge mass with an ulcerated and bloody base over the second portion of the duodenum. A pancreatoduodenectomy was then performed. During the postoperative recovery period, a rapidly enlarging tumor of the right breast was noted. She subsequently underwent a total mastectomy of the right breast. Both the duodenal tumor and the breast tumor were found to be malignant phyllodes tumors. The rarity of this kind of patient and presentation is discussed.

Adult↗

[cDNA cloning, sequence analysis of trehalose-6-phosphate synthase gene from Saccharomyces cerevisiae AS2.1416].

The trehalose-6-phosphate synthase gene tps1 was amplified from yeast S. cerevisiae AS2.1416 cDNA library by polymerase chain reaction. This 1.5 kb fragment was cloned into PstI and BamHI sites of pGEM-T easy vector and the sequence of the gene indicated the cloned tps1 gene contained 1485 nucleotides encoding for 495 amino acid and shared a sequence homology of 99.6% with that from S. cerevisiae S288C.

Cloning, Molecular↗

Partial anomalous pulmonary venous connection draining into superior vena cava--two cases reports.

Anomalous pulmonary venous connection is a relatively common associated anomaly in patients with atrial septal defect (ASD), particularly among those with the sinus venosus type. The incidence of partial anomalous pulmonary venous connection (PAPVC) is higher than 0.7% in the general population and 10% in patients with ASD. In this study, we present two cases with initial impression of ASD, the sinus venosus type in one and the secundum type in the other. The one with the sinus venosus type was found to have a PAPVC that drained into SVC, and the other was suspected of having the same problem because an abnormal shunt was found during cardiac catheterization. This speculation could not be proved, however, due to transesophageal echocardiogram failure. Because we feared the possibility of cardiac defects other than ASD, we performed a minimally invasive operation using a small midline incision instead of the submammary incision and did a full median sternotomy on the patient to look for other complicating coexistent cardiac defects. This patient and the former one were both proven intraoperatively to have a PAPVC that drained into SVC with sinus venosus ASD. The operation to correct an ASD is a rudimentary procedure, and it often becomes a common type of minimally invasive operation among young cardiac surgeons with limited experience. A submammary incision under the impression of simple ASD may meet with certain complications. Therefore, after our experience with the latter case, we do the minimally invasive operation using a small midline incision, which can be easily extended if need be.

Adult↗

Knee isokinetic strength and body fat analysis in university students.

Many factors such as anthropometric variables influence strength performance. This study is to determine the relationship between knee isokinetic strength and body composition, and to compare the gender differences. Test-retest reliability had been performed within one week for all measurement methods before the formal study. Fifty-eight 20-25 year-old university students, 32 females and 26 males, participated in this study. Isokinetic strength of the knee flexion and extension was measured at two angular velocities of 60 degrees/sec and 120 degrees/sec. Body composition was measured by bioelectrical impedance analysis (BIA) and skinfold caliper. The others variables including height, body weight, body mass index (BMI), and waist to hip ratio were measured or calculated. The results showed that the intra-class correlation coefficients for isokinetic knee strength were between 0.83 and 0.93, and body composition and anthropometric variables were between 0.83 and 0.98. Isokinetic knee strength was significantly correlated with body height, body weight, BMI, waist and hip ratio and percent of body fat estimated by skinfold caliper (r = -0.56 to 0.64). The correlation between isokinetic strength with percent of body fat estimated by BIA (r = -0.60 to -0.74; p < 0.001) and with fat free mass (r = 0.64 to 0.78; p < 0.001) was even higher. Although male subjects had significantly greater mean values in body height, body weight, waist to hip ratio and isokinetic strength than female subjects, the MANCOVA showed that the effect of gender on knee isokinetic strength would be eliminated when the covariant variable, the percent of body fat measured by BIA and BMI was controlled in the analysis model. In conclusion, knee isokinetic strength was significantly negatively correlated with proportion of fat and positively correlated with fat free mass. The magnitude of strength difference between males and females could be explained by differences in body fat proportion and BMI in this study. Therapist would take the body fat composition, fat free mass, and BMI into consideration in knee muscle strength measurement. Less body fat and higher BMI will contain more fat free mass that produces more muscle strength.

Adipose Tissue↗

Discrete subaortic membranous stenosis--a case report.

Isolated subaortic stenosis is a rare type of cardiac anomaly which has been characterized as having two types: the discrete type, including membranous or fibromuscular, and the tunnel type. In the discrete type, a crescent-shaped, fibrous curtain is attached to the ventricular septum or completely encircles the left ventricular outflow tract and can be located anywhere from immediately below the aortic valve to 10 mm or more into the body of ventricle. A 22-year-old female presented at our hospital with a divided PDA, a murmur that was found by incident and progressive exertional dyspnea. Echocardiography revealed left ventricular hypertrophy, moderate aortic insufficiency, and severe aortic stenosis characterized by a thickened aortic valve and membranous type subaortic stenosis with a transmembranous high pressure gradient, 121 mmHg. An operation to replace the aortic valve and excise the membranous collar was performed with cardiopulmonary bypass support. The patient did well during the postoperative follow-up period. If the preoperative LVOT pressure gradient had been higher than 45 mmHg, the incidence of recurrent stenosis, progression of aortic regurgitation and the need for reoperation would have been higher. In order to prevent this from happening, we chose to replace the defective valve with a mechanical valve and enucleate the discrete lesion.

Adult↗

The effect of pH on the structure, binding and model membrane lysis by cecropin B and analogs.

Cecropins are a group of anti-bacterial, cationic peptides that have an amphipathic N-terminal segment, and a largely hydrophobic C-terminal segment and normally form a helix-hinge-helix structure. In this study, the ability of cecropin B (CB) and two analogs to lyse phospholipid bilayers, which have two levels of anionic content, has been examined by dye-leakage measurements over the pH range 2. 0-12.0. The two analogs differ from the natural peptide by having either two amphipathic segments (CB1) or two hydrophobic segments (CB3). All these peptides (except CB3 on low anionic content bilayers where it is not active) have maximal lytic activity on both types of bilayers at high pH. However, the pattern of secondary structure formation on these bilayers by the peptides, as measured by circular dichroism (CD), and the pattern of their ability to bind lipid monolayers, as measured using a biosensor, do not directly correlate with the pattern of their lytic ability. CB and CB1 with low anionic content bilayers have secondary structures as measured by CD with a similar pattern to membrane lysis, but binding is maximal near neutral, not high, pH. CB3 has some secondary structures on low anionic content bilayers at low pH and this becomes maximal over the basic range, but CB3 neither binds to nor lyses with these lipid layers. On high anionic content lipid layers, all peptides show high levels of secondary structures over most of the pH range and maximal binding at neutral pH (except for CB3, which does not bind). All three peptides lyse with high anionic content bilayers, but show no activity at neutral pH and reach maximal activity at very high pH. This work shows that pH is a major factor in the capability of antibacterial peptides to lyse with liposomes and that secondary structure and binding ability may not be the main determinants.

Anti-Infective Agents↗

Affinity purification of Schistosoma japonicum glutathione-S-transferase and its site-directed mutants with glutathione affinity chromatography and immobilized metal affinity chromatography.

A C-terminally polyhistidine-tagged protein of Schistosoma japonicum glutathione-S-transferase, named as SjGST/His, and its Cys85-->Ser, Cys138-->Ser, and Cys178-->Ser site-directed mutants were prepared and highly expressed in Escherichia coli. Both immobilized metal affinity chromatography (IMAC) and glutathione (GSH) affinity chromatography were used to purify these four enzymes. All of them were purified with equal efficiency by Ni2+-chelated nitrilotriacetic acid agarose gel, but not by GSH Sepharose 4B gel. The protein amounts of wild-type and Cys85-->Ser enzymes purified by the latter gel were three to seven-fold greater than those of the other two enzymes purified by the same gel, while their specific activities were two-fold lower, presumably because of the occurrence of noncovalent aggregation. Both purification methods yielded highly pure enzymes, while there were minor amounts of inter- and intra-disulfide forms in the IMAC purified enzymes except for the Cys85-->Ser mutant. Addition of dithiothreitol to GSH-affinity purified enzymes shifted all of their mass spectra of matrix-assisted laser desorption/ionization-time of flight mass spectrometry toward low molecular-mass regions, while addition of GSH to IMAC purified enzymes shifted the spectra toward high molecular-mass regions. The shift values of wild-type enzyme were larger than those of the three mutants, indicating that the Cys85, Cys138, and Cys178 residues were S-thiolated by GSH during the GSH-affinity purification. This result was confirmed by isoelectric focusing. These findings suggest that IMAC is more efficient than the conventional GSH-affinity system for the purification of SjGST/His enzyme, especially for its mutants and fusion proteins.

Animals↗

Secondary structure formation is the earliest structural event in the refolding of an all beta-sheet protein.

The refolding kinetics of cobrotoxin (CBTX), a small-molecular-weight ( approximately 7 kDa) all beta-sheet protein, has been monitored using a variety of biophysical techniques. The secondary structure formation and hydrophobic collapse occur as distinct events during the refolding of the protein. Complete secondary structure formation occurs prior to the clustering of the hydrophobic residues. The late stage(s) of the refolding pathway of CBTX is characterized by change(s) in the local environment and optical asymmetry of the indole ring of the sole tryptophan residue. The results obtained in the present study, to our knowledge, represent the first unambiguous experimental support for the framework model of protein folding.

Cobra Neurotoxin Proteins↗

Study on binding of REEs with water-soluble polysaccharides in fern.

The binding of rare earth elements (REEs) with water-soluble polysaccharides of nondeproteinization and deproteinization in the leaves of the fern Dicranopteris dichotoma was studied by molecular activation analysis (MAA). Two cold-water-soluble polysaccharides (extracted by 75% ethanol and 90% ethanol, respectively) and one hot-water-soluble polysaccharide (extracted by 90% ethanol) were separated using biochemical separation techniques. The eight rare earth elements (La, Ce, Nd, Sm, Eu, Tb, Yb, and Lu) in these polysaccharides were determined by instrumental neutron activation analysis. Our new results showed that the REEs were bound firmly with the water-soluble polysaccharides in the plant, regardless of whether nondeproteinization or deproteinization was used. The molecular-weight (MW) measurement demonstrated that REEs were mainly bound with low-MW (10,000-20,000) polysaccharides.

Chromatography, Ion Exchange↗

Intrahepatic cholangiocarcinoma in Taiwan.

We report our experience of the surgical treatment of intrahepatic cholangiocarcinoma (ICC) in Taiwanese patients. A total of 162 patients with histologically proven ICC were treated of whom 106 (65. 4%) had associated hepatolithiasis. Patients with hepatolithiasis were in earlier stages than those without hepatolithiasis. Two-thirds of the patients with hepatolithiasis presented with acute cholangitis, and two-thirds of those without hepatolithiasis presented with hepatomegaly. The rate of hepatic resection was 29.6% (48 of 162), and these rates were 31.1% and 26.8% for the patients with and without hepatolithiasis, respectively. Ninety-three percent of the patients with hepatolithiasis underwent common bile duct exploration, compared with 18% of those without hepatolithiasis. The surgical mortality rates were 3.7% (6/162), for all patients, and 3. 8% and 3.6% for patients with and without hepatolithiasis, respectively. The morbidity rate was much higher in the patients with hepatolithiasis (37.7% vs 16.1%). The 1-, 3-, and 5-year survival rates were 35.5%, 20.5%, and 16.5% in the patients with hepatolithiasis and 27.2%, 8.8%, and 7.8% in those without hepatolithiasis. Concomitant hepatolithiasis prevented precise diagnosis preoperatively and precipitated biliary sepsis, which affected resectability and increased postoperative morbidity. Hepatolithiasis per se did not influence long-term survival.

Adult↗

Carcinogenesis in the biliary system associated with APDJ.

Anomalous pancreaticobiliary ductal junction (APDJ) is a rare congenital anomaly which is considered to be an etiological factor in the development of carcinoma of the biliary tract. It is generally accepted that pancreatic juice reflux into the biliary tract due to APDJ is one of the etiologies of biliary tract cancers. Refluxing pancreatic juice results in changes of bile and induces chronic inflammation and increased cellular proliferation, leading to epithelial hyperplasia, metaplasia, and carcinoma of the biliary tract. K-ras mutations are more prevalent in the carcinomas of biliary tract associated with APDJ compared with those without APDJ. There is no difference in the overexpression of p53 between biliary tract carcinomas associated with APDJ and those unassociated with APDJ. Further studies are needed to evaluate the role of cytokines and growth factors in carcinogenesis of the biliary system associated with APDJ.

Adenocarcinoma↗

Membrane lysis by the antibacterial peptides cecropins B1 and B3: A spin-label electron spin resonance study on phospholipid bilayers.

Custom antibacterial peptides, cecropins B1 (CB1) and B3 (CB3), were synthesized. These peptides have particular sequence characteristics, with CB1 having two amphipathic alpha-helical segments and CB3 having two hydrophobic alpha-helical segments. These differences were exploited for a study of their efficacy in breaking up liposomes, which had different combinations of phosphatidic acid (PA) and phosphatidylcholine (PC), and a study of their lipid binding ability. Binding and nonbinding lysis actions of CB1 and CB3 on liposomes were examined further by electron spin resonance (ESR). The spin-labeled lipids 5'SL-PC, 7'SL-PC, 10'SL-PC, 12'SL-PC, and 16'SL-PC were used as probes. The ESR spectra revealed larger outer hyperfine splittings (2A(max)) for CB1 when the interactions of CB1 and CB3 with liposomes were compared. These observations indicate a larger restriction of the motion of the spin-labeled chains in the presence of CB1. Plots of the effective order parameter at the various probe positions (chain flexibility gradient) versus the peptide-lipid ratio further suggested that the lysis action of CB1 is related to its capacity to bind to the lipid bilayers. In contrast, there is no evidence of binding for CB3. To augment these findings, four spin-labeled peptides, C8SL-CB1, C32SL-CB1, C5SL-CB3, and C30SL-CB3, were also examined for their binding to and their state of aggregation within the lipid bilayers. Association isotherms of the peptides were measured for liposomes containing two molar fractions of PA (0.25 and 0.75). The membrane binding of the CB1 peptides exhibited a cooperative behavior, whereas the association isotherm of CB3 revealed binding to the lipid only for beta = 0.75 liposomes. To further identify the location of CB1 in the lipid bilayers, measurements of the collision rate with chromium oxalate in solution were conducted. Results from ESR power saturation measurements suggested that the NH(2)-terminal alpha-helix of CB1 is located on the surface of the lipid bilayers, whereas the COOH-terminal alpha-helix of CB1 is embedded below the surface of the lipid bilayers. These conclusions were further supported by the observed relationship between the partition distribution of peptides bound to liposomes at different PA/PC ratios and the amounts of free peptides. Based on the above observations, possible mechanisms of the bilayer lysis induced by CB1 and CB3 on liposomes of different composition are discussed.

Amino Acid Sequence↗

The effect of Glu75 of staphylococcal nuclease on enzyme activity, protein stability and protein unfolding.

Staphylococcal nuclease mutants, E57G and E75G, were generated. A comparison of the kinetic parameters both for mutants and wild-type protein shows that the Michaelis constants (Km) were almost identical for the wild-type protein and E57G mutant. An approximately 30-fold decrease in Km compared with the wild-type protein was observed for the E75G mutant. The turnover numbers for the enzyme (kcat) were higher with both the wild-type protein and the E57G mutant (3.88 +/- 0.21 x 103 s-1 and 3.71 +/- 0.28 x 103 s-1) than with the E75G mutant (3.04 +/- 0.02 x 102 s-1). The results of thermal denaturation with differential scanning microcalorimetry indicate that the excess calorimetric enthalpy of denaturations, DeltaHcal, was almost identical for the wild-type protein and E57G mutant (84.1 +/- 6.2 kcal.mol-1 and 79.3 +/- 7.1 kcal.mol-1, respectively). An approximately twofold decrease in DeltaHcal compared with the wild-type protein was observed for the E75G mutant (42.7 +/- 5.5 kcal.mol-1). These outcomes imply that Glu at position 75 plays a significant role in maintaining enzyme activity and protein stability. Further study of the unfolding of the wild-type protein and E75G mutant was conducted by using time-resolved fluorescence with a picosecond laser pulse. Two fluorescent lifetimes were found in the subnanosecond time range. The faster lifetime (tau2) did not generally vary with either pH or the concentration of guanidinium hydrochloride (GdmHCl) in the wild-type protein and the E75G mutant. The slow lifetime (tau1), however, did vary with these parameters and was faster as the protein is unfolded by either pH or GdmHCl denaturation. The midpoints of the transition for tau1 are pH 3.5 and 5.8 for the wild-type protein and E75G mutant, respectively, and the GdmHCl concentrations are 1.1 m and 0.6 m for the wild-type protein and E75G mutant, respectively. Parallel steady-state fluorescence measurements have also been carried out and the results are in general agreement with the time-resolved fluorescence experiments, indicating that Glu at position 75 plays an important role in protein unfolding.

Calorimetry, Differential Scanning↗

An efficient, short synthesis and potent anti-hepatitis B viral activity of a novel ring-expanded purine nucleoside analogue containing a 5:7-fused, planar, aromatic, imidazo[4,5-e][1,3]diazepine ring system.

An efficient, short synthesis of a ring-expanded nucleoside analogue containing a novel 5:7-fused, planar, and potentially aromatic imidazo[4,5-e][1,3]diazepine heterocyclic ring system is reported. The target compound, 6-amino-8-hydroxy-4H-1-beta-D- ribofuranosylimidazo[4,5-e][1,3]diazepin-4-one (2) was synthesized in a single step in > or = 90% yield by condensation of guanidine with either methyl 1-beta-D-ribofuranosylimidazole-4,5- dicarboxylate(1a) or its 2',3',5'-tri-O-benzoyl derivative (1b). Compound 2 showed potent anti-hepatitis B virus (anti-HBV) activity with an EC50 value of 0.17 microM in the transfected hepatoma cell line 2.2.15, and a low cellular toxicity with a CC50 value of 2.4 mM (TI > 14,000).

Antiviral Agents↗

Aminoguanidine attenuates hemodynamic and microcirculatory derangement in rat intestinal ischemia and reperfusion.

BACKGROUND: Nitric oxide (NO) participates in the regulation of hemodynamic and microcirculatory changes in intestinal ischemia and reperfusion (I/R). However, the nature of the involvement of an inducible NO release has been controversial. This study evaluates the impact of an inducible NO synthase inhibitor, aminoguanidine, used as a treatment in a rat intestinal I/R model. METHODS: We investigated the hemodynamics by measuring the mean arterial pressure (MAP), and the microcirculatory responses of the intestine and liver to systemically administered aminoguanidine by use of laser-Doppler flowmetry (LDF), in vivo microscopy, and flow cytometry. RESULTS: During the 30-min ischemia of the selected 20-cm ileal segment, no MAP change was noted. At reperfusion, a marked decrease of MAP was noted and the lowest levels were noted 3 hours after reperfusion (67 +/- 4% vs. 99 +/- 5% in sham-operated control animals). A marked decrease in liver perfusion as measured by LDF was noted 1 hour after reperfusion and remained low at 5 hours (72 +/- 4% vs. 97 +/- 3% in sham-operated control animals). A marked decrease in intestine perfusion was noted by using LDF 1 hour after reperfusion and remained low at 5 hours (43 +/- 3% vs. 92 +/- 4% in sham-operated control animals). The flow velocity of the postcapillary venules of the intestine was markedly decreased (1.01 +/- 0.62 vs. 2.67 +/- 0.34 mm/s in sham-operated control animals) at 5 hours after reperfusion. The flow velocity of the postsinusoidal venules of the liver was also markedly decreased (1.01 +/- 0.62% vs. 2.67 +/- 0.34% in sham-operated control animals). Leukocyte-endothelial interaction (adhesion) was increased in the postcapillary venules of the intestine (54 +/- 12 vs. 6 +/- 4/microm2 in sham-operated control animals) and in the postsinusoidal venules of the liver (32 +/- 8 vs. 2 +/- 2/microm2 in sham-operated control animals). Concomitantly, the granulocyte count was increased (9.1 +/- 0.6 vs. 2.1 +/- 0.3% of total circulating leukocytes in sham-operated control animals), with an increase of CD 11b expression. Aminoguanidine administration (1 mg/kg) 0.5 hour before ischemia and 1 hour after reperfusion significantly increased MAP, increased intestine and liver perfusion, decreased adhesion, and decreased circulating granulocytes and CD 11b expression. CONCLUSION: Inhibition of an inducible NO release by aminoguanidine in intestinal I/R can attenuate hemodynamic and microcirculatory derangement.

Animals↗

Spinal nitric oxide participates in the control of the blood pressure during graded hemorrhage in the conscious rat.

We sought to evaluate the role of spinal nitric oxide (NO) in the control of blood pressure in the conscious animal and determine its possible participation in the progression of hemorrhagic shock. Adult, male Sprague-Dawley rats were chronically prepared with intrathecal, intravenous, and intra-arterial catheters. We first investigated the role of spinal NO on blood pressure control by intrathecal administration of N(G)-nitro-L-arginine methyl ester hydrochloride (L-NAME) at 0.37 micromol, 0.74 micromol. or 1.48 micromol. A dose-related increase in blood pressure was observed. We next pretreated animals with intrathecal or intravenous L-NAME at 0.37 micromol and induced the animal to shock by graded hemorrhage. Animals that received vehicle control or intravenous L-NAME had a decrease in blood pressure after 12% of the total circulatory blood volume (TBV) had been removed and developed severe hypotension after 24% TBV was bled. On the other hand, intrathecal pretreatment of L-NAME significantly attenuated the decrease in blood pressure. The blood pressure was maintained until 40% TBV had been withdrawn. We concluded that inhibition of NO synthase, in the spinal cord, increased blood pressure in a dose-dependent manner, and hemorrhagic shock induced by graded hemorrhage may involve an upregulation mechanism of spinal NO synthase in producing severe hypotension in conscious rats.

Animals↗