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C Y Hong

Publications and source records attributed to C Y Hong.

At least 73 records · Page 4Linked to original sources

Hemodynamic effects of eight-day octreotide and propranolol administration in portal hypertensive rats.

Octreotide and propranolol are both effective portal hypotensive drugs in the control or prevention of variceal bleeding. The present study was undertaken to investigate the hemodynamic effects of octreotide and propranolol, alone or in combination, in portal hypertensive rats. Portal hypertension was induced by partial portal vein ligation. Portal hypertensive rats were allocated into one of the four groups: vehicle group (saline, 0.5 ml/day), octreotide group (100 microg/kg/12 hr), propranolol group (30 mg/kg/day), and octreotide (100 microg/kg/12 hr) plus propranolol (30 mg/kg/day) group. Propranolol or saline was administered by gavage, octreotide by subcutaneous injection. Drug was given one day before ligation and continued for eight consecutive days. Systemic as well as splanchnic hemodynamic parameters were measured thereafter. The portal venous pressure, portal tributary blood flow, and cardiac index were significantly reduced by octreotide, propranolol, or octreotide plus propranolol in portal hypertensive rats. Portal territory, systemic, and renal vascular resistances were significantly enhanced, while hepatic arterial blood flow significantly reduced, in the octreotide and octreotide plus propranolol groups as compared to vehicle group. Our results showed that eight-day administration of octreotide, propranolol, or octreotide plus propranolol led to portal hypotensive and antihyperdynamic effects in portal hypertensive rats. Overall, octreotide treatment alone resulted in better antihyperdynamic profiles than propranolol treatment alone. The combination of octreotide and propranolol offered no therapeutic benefits and was slightly less effective than octreotide alone.

Adrenergic beta-Antagonists↗

Haemodynamic effects of 8-day octreotide and prazosin administration in portal hypertensive rats.

BACKGROUND: Octreotide and prazosin are both effective portal hypotensive drugs in the control or prevention of variceal bleeding. The present study was undertaken to investigate the haemodynamic effects of octreotide and prazosin, alone or in combination, in portal hypertensive rats. METHODS: Portal hypertension was induced by partial portal vein ligation. Portal hypertensive rats were allocated into one of the four groups-vehicle group (saline, 0.5 mL 12 h-1), octreotide group (30 micrograms kg-1 12 h-1), prazosin group (0.4 mg kg-1 12 h-1), and octreotide (30 micrograms kg-1 12 h-1) plus prazosin (0.4 mg kg-1 12 h-1) group-with eight rats in each group. Prazosin or saline was administered by gavage, whereas octreotide was administered by subcutaneous injection. The drug was given on the day of ligation and continued for 8 consecutive days. Systemic as well as splanchnic haemodynamic parameters were measured thereafter. RESULTS: Portal vein-ligated rats exhibited typical hyperdynamic state compared with sham-operated rats. The portal venous pressure, portal tributary blood flow and cardiac index were significantly reduced by treatment of octreotide, prazosin or octreotide plus prazosin in portal hypertensive rats. Hyperdynamic parameters of systemic, renal and portal territory vascular resistances, and renal as well as hepatic arterial blood flow were ameliorated by treatment of octreotide or octreotide plus prazosin in portal hypertensive rats. Overall, octreotide treatment exerted more beneficial haemodynamic effects than prazosin treatment. The combination of octreotide and prazosin exerted better haemodynamic effects in cardiac index but worse effects in systemic as well as portal territory vascular resistance than octreotide treatment alone.

Animals↗

Hemodynamic effects of 8-day DL-028 and octreotide administration in rats with portal hypertension.

BACKGROUND: DL-028 (chemical name: 3-[[4-(2-methoxyphenyl)piperazin-1-yl]methyl]-2,3-dihydroimidaz o[1,2-c]quinazolin-5(6H)-one (27b)) is a synthetic alpha1-adrenoceptor antagonist. The present study was undertaken to investigate the hemodynamic effects of chronic DL-028 administration, alone or in combination with octreotide, in rats with portal hypertension. METHODS: Portal hypertension was induced by partial portal-vein ligation. Portal-hypertensive rats were allocated to one of the four groups: vehicle group (saline, 0.5 ml/12 h), octreotide group (30 microg/kg/12 h), DL-028 group (0.4 mg/kg/12 h), and octreotide (30 mg/kg/l2 h) plus DL-028 (0.4 mg/kg/12 h) group, with eight rats in each group. DL-028 or saline was administered by gavage and octreotide by subcutaneous injection. Drugs were given immediately after ligation and for 8 consecutive days thereafter. Systemic and splanchnic hemodynamic variables were measured thereafter. RESULTS: Portal-vein-ligated rats showed a typical hyperdynamic state as compared with sham-operated rats. The portal venous pressure, portal tributary blood flow, and cardiac index were significantly reduced by treatment with octreotide, DL-028, or octreotide plus DL-028 in portal-hypertensive rats. Hyperdynamic variables of systemic, renal, hepatocollateral, and portal territory vascular resistances and renal and hepatic arterial blood flow were ameliorated by treatment with octreotide or octreotide plus DL-028 in portal-hypertensive rats. Octreotide plus DL-028 treatment exerted better hemodynamic effects on the cardiac index but worse effects on systemic and hepatocollateral vascular resistance than octreotide treatment alone. CONCLUSION: Although either DL-028 or octreotide ameliorated portal hypertension and splanchnic hyperemia in portal-hypertensive rats, octreotide treatment exerted more beneficial hemodynamic effects than DL-028 treatment. The combination of octreotide and DL-028 conferred no better hemodynamic benefits than octreotide alone, except on the cardiac index.

Adrenergic alpha-Antagonists↗

Neuropathy in non-insulin-dependent diabetes mellitus. The significance of symptoms.

OBJECTIVE: Clinical evaluation of significance of symptoms suggestive of neuropathy in non-insulin-dependent diabetics in general practice. DESIGN: Case control study. Interviewer-administered questionnaire. Physical examination by general practitioner researcher. SETTING: Government family practice clinic in Singapore. SUBJECTS: 55 patients with non-insulin-dependent diabetes (NIDDM) aged 35-84 years (51% males), and 53 non-diabetic controls matched for age (+/- 5 years) and gender. MAIN OUTCOME MEASURES: Proportions of subjects with presence of symptoms and physical signs. RESULTS: More patients than controls experienced symptoms suggestive of distal neuropathy (paraesthesiae: 13 vs. 4%), and lower extremity proximal myopathy (weakness climbing stairs: 42 vs. 19%, getting up from squatting position: 31 vs. 11%). No difference in proportions of patients and controls experiencing symptoms suggestive of autonomic neuropathy. More patients than controls had absent tendon reflexes (35 vs. 13%) and weaker hip muscles (24 vs. 6%). Of all who experienced symptoms indicating peripheral neuropathy, 36% of patients had absent tendon reflexes, compared with 8% of controls; and of those who experienced weakness of hip muscles, 31% of patients and 12% of controls had diminished power in the hip muscles. CONCLUSION: Symptoms suggestive of diabetic neuropathy are common and should be asked about in the routine follow-up of patients with diabetes. Up to a third of patients with symptoms will have clinical signs of diabetic neuropathy.

Adult↗

Trilinolein inhibits the adhesion of neutrophils to endothelial cells.

1. Trilinolein is a triacylglycerol with linoleic acid as the only type of fatty acid in all three esterified positions of glycerol. It was recently reported to have a myocardial protective effect in coronary ligated rats. We now study its effect on the adhesion of human neutrophils to cultured bovine endothelial cells. 2. Pretreatment of an endothelial monolayer with trilinolein at concentrations ranging from 10(-10) to 10(-6) mol/L significantly inhibited neutrophil adhesion to endothelial cells. Trilinolein was less potent than sodium nitroprusside in inhibiting neutrophil adhesion. 3. The inhibitory effect of trilinolein was antagonized by methylene blue and N(G)-nitro-L-arginine methyl ester. The inhibitory effect of trilinolein was not mediated through linoleic acid because linoleic acid did not inhibit neutrophil adhesion. 4. Pretreatment of neutrophils with trilinolein did not reduce neutrophil adhesion. However, in neutrophils activated with N-formyl-methionyl-leucyl-phenylalanine, trilinolein inhibited the neutrophil adhesion to endothelial cells. 5. We conclude that trilinolein inhibits neutrophil adhesion to the endothelial monolayer by stimulating the nitric oxide and cyclic GMP pathways in endothelial cells. It may also inhibit neutrophil adhesion by scavenging free radicals. The inhibitory effect of trilinolein on neutrophil adhesion may play a role in its myocardial protective activity.

Animals↗

Haemodynamic effects of chronic octreotide and tetrandrine administration in portal hypertensive rats.

Octreotide is an effective portal hypotensive drug in the control of variceal bleeding. Tetrandrine is a type of calcium channel blocker recently reported to reduce portal hypertension. The present study was undertaken to investigate the haemodynamic effects of octreotide and tetrandrine, alone and in combination, in portal hypertensive rats. Portal hypertension was induced by partial portal vein ligation. Portal hypertensive rats were allocated into one of the four groups: vehicle group (saline, 0.5 mL/day), octreotide group (100 microg/kg per 12 h), tetrandrine group (20 mg/kg per 12 h), and octreotide (100 microg/kg per 12 h) plus tetrandrine (20mg/kg per 12 h) group. Tetrandrine or saline was administered by gavage, and octreotide by subcutaneous injection. The drug was given for 8 consecutive days, starting 1 day before ligation and continuing onwards. Haemodynamic parameters were measured thereafter, using the radioactive microsphere method. The portal venous pressure and portal tributary blood flow were significantly reduced, while portal territory and renal vascular resistances were significantly enhanced, by octreotide, tetrandrine, or octreotide plus tetrandrine in portal hypertensive rats, compared with the vehicle group. Our results showed that long-term administration of octreotide, tetrandrine, or octreotide plus tetrandrine led to portal hypotensive effects in portal hypertensive rats, but octreotide alone exerted better anti-hyperdynamic effects compared with tetrandrine alone. A combination of octreotide and tetrandrine offered no major beneficial anti-hyperdynamic effects compared with octreotide alone.

Alkaloids↗

Effects of tetramethylpyrazine on portal hypertensive rats.

The effects of tetramethylpyrazine, an alkaloid isolated from a Chinese herb Ligusticum wallichii Franch have been assessed in portal hypertensive rats. Portal hypertension was induced by partial portal vein ligation in Sprague-Dawley rats. Two weeks after ligation, when the hyperdynamic state had stabilized, rats were anaesthetized after an overnight fast and cannulated for measurement of mean arterial pressure, portal venous pressure, cardiac index and heart rate. Tetramethylpyrazine (3.0, 9.9 and 30mgkg(-1)) induced dose-dependent reductions of portal venous pressure and mean arterial pressure after intravenous infusion. The maximum percentage reduction of portal venous pressure after tetramethylpyrazine was 6.0+/-0.8, 9.3+/-1.6 and 20+/-2% of baseline for doses of 3.0, 9.9 and 30.0mgkg(-1), respectively. Also, total peripheral resistance was significantly reduced by tetramethylpyrazine and cardiac index was slightly increased. Our results showed that tetramethylpyrazine induced portal pressure reduction in portal hypertensive rats.

Animals↗

Cordyceps sinensis increases the expression of major histocompatibility complex class II antigens on human hepatoma cell line HA22T/VGH cells.

Previous studies suggest that down-regulation of the major histocompatibility complex (MHC) antigens on the cell surface of certain tumors results in an escape of immune surveillance. Cordyceps sinensis is well known for its modulatory effect on host immune system. To investigate the modulatory effect of Cordyceps sinensis on MHC class II antigen expression on hepatoma cells, immunostaining with monoclonal antibody (MAb) L243, against the HLA DR region of MHC class II antigens on human hepatoma cell line HA22T/VGH was analyzed by using flow cytofluorimetry. The degree of fluorescence intensity on L243(+) cells was expressed as relative mean fluorescence intensity (RMFI). The extract of Cordyceps sinensis (VGH-CS-ME-82, 40 micrograms/ml) was found to increase the MHC class II antigen expression on HA22T/VGH cells with the percentage of L243(+) cells 40.2 +/- 2.5 and RMFI 6.6 +/- 0.4; whereas cells without treatment disclosed the percentage of L243(+) cells 17.2 +/- 1.4 and RMFI 5.4 +/- 0.3, respectively (p < 0.05). There was a dose-related increase in the degree of fluorescence intensity in terms of RMFI on VGH-CS-ME-82 induced cells. The RMFI in cells treated with IFN-gamma 0, 0.2 and 5 ng/ml were 5.4 +/- 0.3, 8.2 +/- 0.4, and 24.9 +/- 1.5, respectively; whereas the RMFI in cells co-incubated with VGH-CS-ME-82 (40 micrograms/ml) and IFN-gamma 0, 0.2 ng/ml and 5 ng/ml were 6.7 +/- 0.2 (p < 0.05), 9.2 +/- 0.9 (p < 0.1) and 29.5 +/- 1.2 (p < 0.005), respectively. We conclude that VGH-CS-ME-82, either alone or with IFN-gamma induction, increases the MHC class II antigen expression on hepatoma cell line HA22T/VGH, which will shed light into the present immunotherapy, and make the host immune surveillance more effective against tumor cells with down-regulated MHC class II antigen expression.

Carcinoma, Hepatocellular↗

Portal hypotensive effects of DL-028 and prazosin on portal hypertensive rats.

The portal hypotensive effects of prazosin and DL-028 (chem- ical name: 3-[[4-(2-methoxyphenyl)piperazin-1-yl]methyl]- 2, 3-dihydroimidazo[1,2-c]quinazolin-5(6H)-one(27b)), a synthetic alpha1-adrenoceptor antagonist, were assessed in portal hypertensive rats. Portal hypertension was induced by partial portal vein ligation in Sprague-Dawley rats. Two weeks after ligation, when the hyperdynamic state was stabilized the rats were anesthetized after an overnight fast and cannulated for measuring mean arterial pressure (MAP), portal venous pressure (PVP), cardiac index (CI) and heart rate (HR). Both DL-028 and prazosin (1, 3.3 and 10 microgram/kg) induced dose-dependent decreases of PVP and MAP after intravenous infusion, with effects lasting for longer than 30 min. The maximum percentage reduction of PVP after DL-028 was 10, 10 and 15%, respectively, for the dosages given (1, 3.3 and 10 microgram/kg), and 5, 12 and 25%, respectively, after prazosin. CI was not changed by either drug. HR was not changed by either drug except DL-028 at 10.0 microgram/kg with a bradycardiac effect. Our results showed that both DL-028 and prazosin reduced PVP in portal hypertensive rats.

Adrenergic alpha-1 Receptor Antagonists↗

Increase of vitamin E content in LDL and reduction of atherosclerosis in cholesterol-fed rabbits by a water-soluble antioxidant-rich fraction of Salvia miltiorrhiza.

Antioxidants that prevent LDL from oxidation may reduce atherosclerosis. Salvia miltiorrhiza Bunge is a Chinese herb widely used for the treatment of atherosclerosis-related disorders. Salvianolic acid B (Sal B), a water-soluble polyphenolic antioxidant isolated from the roots of this plant, was found to scavenge 1,1-diphenyl-2-picrylhydrazyl radicals and inhibit LDL oxidation more effectively than probucol. In order to evaluate the antiatherogenic potential, New Zealand White rabbits were fed for 12 weeks a normal diet, a high cholesterol diet, a high cholesterol diet containing 1% probucol, or a high cholesterol diet containing a 5% water-soluble extract of S miltiorrhiza (SM). Both SM and probucol feeding reduced plasma cholesterol. LDLs from the SM-treated group were more resistant to Cu2+-induced oxidation and contained more vitamin E (21.7+/-2.1 mmol/micromol LDL cholesterol) than did LDLs from the high cholesterol diet group (9.6+/-1.8 nmnol/micromol LDL cholesterol) (P<.005). Endothelial damage, determined at week 6, was reduced by 53% in the SM group (P<.01). SM treatment reduced the atherosclerotic area in the abdominal aorta by 56% (P<.005) and cholesterol deposition in the thoracic aorta by 50% (P<.005). The severity of atherosclerosis in the SM group was significantly reduced after adjustment by using cholesterol exposure as an index of the cholesterol-lowering effect. This study concludes that the reduction of atherosclerosis by SM relies not only on its cholesterol-lowering effect but more heavily on its antioxidant potential to prevent endothelial damage and inhibit LDL oxidative modification in hypercholesterolemic animals.

Animals↗

Novel fluoroquinolone antibacterial agents containing oxime-substituted (aminomethyl)pyrrolidines: synthesis and antibacterial activity of 7-(4-(aminomethyl)-3-(methoxyimino)pyrrolidin-1-yl)-1-cyclopropyl-6- fluoro-4-oxo-1,4-dihydro[1,8]naphthyridine-3-carboxylic acid (LB20304).

New pyrrolidine derivatives, which bear an alkyloxime substituent in the 4-position and an aminomethyl substituent in the 3-position of the pyrrolidine ring, have been synthesized and coupled with various quinolinecarboxylic acids to produce a series of new fluoroquinolone antibacterials. These fluoroquinolones were found to possess potent antimicrobial activity against both Gram-negative and Gram-positive organisms, including methicillin resistant Staphylococcus aureus (MRSA). Variations at the C-8 position of the quinolone nucleus included fluorine, chlorine, nitrogen, methoxy, and hydrogen atom substitution. The activity imparted to the substituted quinolone nucleus by the C-8 substituent was in the order F (C5-NH2) > F (C5-H) > naphthyridine > Cl = OMe = H against Gram-positive organisms. In the case of Gram-negative strains, activity was in the order F (C5-NH2) > naphthyridine = F (C5-H) > H > Cl > OMe. The advantages provided by the newly introduced oxime group of the quinolones were clearly demonstrated by their comparison to a desoximino compound 30. In addition, the oxime moiety greatly improved the pharmacokinetic parameters of the novel quinolones. Among these compounds, compound 20 (LB20304) showed the best in vivo efficacy and pharmacokinetic profile in animals, as well as good physical properties. The MICs (microgram/mL) of LB20304, compound 30, and ciprofloxacin against several test organisms are as follows: S. aureus 6538p (0.008, 0.031, and 0.13), methicillin resistant S. aureus 241 (4, 16, and 128), Streptococcus epidermidis 887E (0.008, 0.016, and 0.13), methicillin resistant S. epidermidis 178 (4, 32, and 128), Enterococcus faecalis 29212 (0.063, 0.13, and 1), Pseudomonas aeruginosa 1912E (0.25, 0.5, and 0.13), Escherichia coli 3190Y (0.008, 0.016, and 0.008), Enterobacter cloacae P99 (0.008, 0.031, and 0.008), Actinobacter calcoaceticus 15473 (0.063, 0.13, and 0.25). On the basis of these promising results, LB20304 was selected as a candidate for further evaluation.

Animals↗

Hemodynamic effects of chronic tetrandrine treatment in Sprague-Dawley rats.

Tetrandrine is a calcium channel antagonist with reported anti-hypertensive effect. The present study aimed to investigate the hemodynamic effects of chronic tetrandrine treatment on normotensive Sprague-Dawley rats. Animals were allocated into one of the two groups: tetrandrine group and vehicle group. Tetrandrine (20 mg/kg) or vehicle was administered by gavage every 12 hours for consecutive 8 days. After 8 days of tetrandrine treatment, systemic hemodynamics and organ blood flows were measured on the next morning after an overnight fast, using radioactive microsphere method. Mean arterial pressure (96 +/- 2 vs. 118 +/- 4 mmHg) and systemic vascular resistance (254 +/- 35 vs. 369 +/- 5 dyn.sec.cm5 x 10(3)/100 g body wt) were significantly decreased in the tetrandine group as compared to the vehicle group. The cardiac-index (35.2 +/- 2.7 vs. 25.5 +/- 0.8 mL/min/100 g body wt) was increased in the tetrandrine group. The portal venous pressure, portal tributary blood flow, portal territory vascular resistance, renal blood flow, renal vascular resistance, heart rate and body weight were similar between the two groups. In conclusion, long-term treatment of tetrandrine reduced mean arterial pressure and systemic vascular resistance but did not change splanchnic or renal hemodynamics in normal rats.

Alkaloids↗

In vitro and in vivo protective effect of honokiol on rat liver from peroxidative injury.

Honokiol, a compound extracted from the Chinese medicinal herb Magnolia officinalis, has a strong antioxidant effect on the inhibition of lipid peroxidation in rat heart mitochondria. To investigate the protective effect of honokiol on hepatocytes from peroxidative injury, oxygen consumption and malondialdehyde formation for in vitro iron-induced lipid peroxidation were assayed, and the mitochondrial respiratory function for in vivo ischemia-reperfusion injury were evaluated in rat liver, respectively. The inhibitory effect of honokiol on oxygen consumption and malondialdehyde formation during iron-induced lipid peroxidation in liver mitochondria showed obvious dose-dependent responses with a concentration of 50% inhibition being 2.3 x 10(-7) M and 4.96 x 10(-7) M, respectively, that is, 550 times and 680 times more potent than alpha-tocopherol, respectively. When rat livers were introduced with ischemia 60 min followed by reperfusion for 60 min, and then pretreated with honokiol (10 micrograms/kg BW), the mitochondrial respiratory control ratio (the quotient of the respiration rate of State 3 to that of State 4) and ADP/O ratio from the honokiol-treated livers were significantly higher than those of non-treated livers during reperfusion. The dose-dependent protective effect of honokiol on ischemia-reperfusion injury was 10 microgram-100 micrograms/Kg body weight. We conclude that honokiol is a strong antioxidant and shed insight into clinical implications for protection of hepatocytes from ischemia-reperfusion injury.

Animals↗

Myocardial protective effect of trilinolein: an antioxidant isolated from the medicinal plant Panax pseudoginseng.

In a previous study we demonstrated that trilinolein, a natural plant triacylglycerol, is a novel myocardial protective agent in vivo. The mechanism probably involves an antioxidant effect. This work investigated the mechanism of myocardial protection of trilinolein to determine if inhibition of calcium influx and alteration of activity of superoxide dismutase are involved. In isolated cardiomyocytes, pretreatment with trilinolein at a low concentration of 10(-9) M effectively reduced 45Ca2+ influx stimulated by hypoxia/normoxia by 34%. In isolated perfused rat heart subjected to 60 min global hypoxemia without reperfusion, pretreatment with 10(-7) M trilinolein for 15 min reduced infarct size by 37%. Assay of superoxide dismutase-mRNA by Northern blot analysis in in vivo rat heart subjected to 30 min ischaemia and 10 min reperfusion showed pretreatment with 10(-7) M trilinolein had a synergistic action with antioxidant systems preventing the rise in superoxide dismutase-mRNA. These results reconfirm the myocardial protection of trilinolein and suggest it may be related to antioxidant activity and inhibition of 45Ca2+ influx.

Animals↗

Inositol phosphate responses in portal veins from portal hypertensive rats: receptor- and nonreceptor-mediated responses.

BACKGROUND/AIMS: Venous hyporesponsiveness in portal hypertension has been reported previously by us. The present study was undertaken to investigate possible changes of phosphoinositide signal transduction pathway in the portal veins from portal hypertensive rats METHODS: Portal hypertension was induced by partial portal vein ligation. Fourteen days after surgery, portal veins were removed for measurement of [3H]inositol phosphate responses to both receptor- and nonreceptor-mediated stimuli. RESULTS: Basal [3H]inositol phosphate formation was similar between the two groups. Both phenylephrine and angiotensin II stimulated [3H]inositol phosphate formation in portal veins, but the responses were attenuated in the portal hypertensive group. In contrast, the [3H]inositol phosphate formation by nonreceptor-mediated stimuli (GTP gamma S, NaF/AlCl3, and phospholipase C) was similar between the two groups. CONCLUSION: Our results showed that the receptor-mediated [3H]inositol phosphate formation was attenuated, while the non-receptor-mediated formation was unaltered, in the portal vein from portal hypertensive rats.

Angiotensin II↗

Chronic administration of propranolol improves vascular contractile responsiveness in portal hypertensive rats.

Propranolol is used clinically as a prophylactic drug to prevent oesophageal variceal bleeding in cirrhotic patients with portal hypertension. Vascular hyporesponsiveness is a common characteristic of the portal hypertensive state. The present study aimed to investigate whether chronic administration of propranolol could improve vascular responsiveness in portal hypertensive rats. Portal hypertension was induced by partial portal vein ligation (PVL). Sham-operated rats served as controls. There were four study groups: PVL-propranolol group (portal hypertensive rats receiving propranolol), PVL-vehicle group (portal hypertensive rats receiving saline), sham-propranolol group (sham-operated rats receiving propranolol) and sham-vehicle group (sham-operated rats receiving saline). Propranolol (30 mg kg-1 day-1) or saline was given for 9 days via gastric gavage starting 1 day before ligation and thereafter. Then, the superior mesenteric artery was removed from each group for contractile study after haemodynamic measurement. In portal hypertensive rats, propranolol significantly alleviated the hyperdynamic state, including portal pressure, cardiac index and total peripheral resistance in the treated group compared with the vehicle group. The maximal contractile responses to KCl and vasopressin in mesenteric artery were significantly greater in the sham-vehicle group than in the PVL-vehicle group. Long-term propranolol treatment enhanced the contractile reactivity of mesenteric artery to KCl and vasopressin in PVL rats, and the contractile profiles were corrected towards those in sham-treated animals. In contrast, propranolol treatment decreased heart rate, mean arterial pressure and cardiac index but did not alter the contractile responsiveness of sham-operated rats. These results showed that, in portal vein stenosed rats, long-term treatment with propranolol improved arterial contractile reactivity together with portal pressure reduction. The propranolol effect on vascular reactivity is probably related to haemodynamic improvement, instead of a direct contractile effect on the vasculature.

Animals↗

Haemodynamic effects of chronic tetrandrine treatment in portal hypertensive rats.

Tetrandrine is a calcium channel antagonist with reported antihypertensive effect. However, the potential role of tetrandrine as a therapeutic agent in portal hypertension has yet to be explored. The present study aimed to investigate the haemodynamic effects of chronic tetrandrine treatment on portal hypertensive rats. Portal hypertension was induced by partial portal vein ligation in Sprague-Dawley rats. Animals were allocated into one of two groups: a tetrandrine group and a vehicle group. Tetrandrine (20 mg/kg) or vehicle was administered by gavage every 12 h for 8 consecutive days, starting 1 day before ligation and continuing thereafter. After 8 days of tetrandrine treatment, systemic haemodynamics, organ blood flow and the degree of portal-systemic shunting were measured after an overnight fast. The portal venous pressure and protal tributary blood flow were significantly decreased, while portal territory as well as hepto-collateral vascular resistance significantly increased in the tetrandrine group compared with the vehicle group. The cardiac index was increased, while systemic vascular resistance was decreased, the the tetrandrine group. Mean arterial pressure, heart rate, portal-systemic shunting and bodyweight were similar between the two groups. Renal blood flow was decreased in the tetrandrine group. In conclusion, long-term treatment of tetrandrine reduced portal venous pressure and alleviated splanchnic hyperaemina in portal hypertensive rats without affecting the portal-systemic shunting.

Alkaloids↗

Immunolocalization of interstitial collagenase (MMP-1) and tissue inhibitor of metalloproteinases-1 (TIMP-1) in radicular cysts.

To investigate the mechanisms involved in expansion of radicular cysts, monoclonal antibodies against interstitial collagenase (MMP-1) and tissue inhibitor of metalloproteinases-1 (TIMP-1) were used to localize the sites of MMP-1 and TIMP-1 expression in 30 radicular cysts. Positive MMP-1 staining was detected in the lining epithelium and subepithelial fibroblasts, macrophages, endothelial cells and osteoblasts/osteocytes in all specimens. Positive TIMP-1 staining was identified in osteoblasts/osteocytes and endothelial cells of all specimens, and in the lining epithelium and subepithelial fibrous connective tissue wall of five radicular cysts with an intense inflammatory cell infiltrate. The number and distribution of positive cells for MMP-1 or TIMP-1 varied widely among individual specimens, but strong immunostaining was constantly detected at sites with prominent subepithelial inflammation. Results here support the hypothesis that MMP-1 may play an important role in the expansion of radicular cysts. The absence of TIMP-1 expression in lining epithelium and subepithelial fibroblasts and macrophages in most cases studied indicated that an imbalance between MMP-1 and TIMP-1 production may lead to radicular cyst expansion.

Antibodies, Monoclonal↗