Biomedical subjects

P Liu

Publications and source records attributed to P Liu.

At least 145 records · Page 8Linked to original sources

PubMed1999

Multicenter randomized controlled trial of the effects of inhaled nitric oxide therapy on gas exchange in children with acute hypoxemic respiratory failure.

OBJECTIVES AND BACKGROUND: To determine whether inhaled nitric oxide (iNO) therapy can attenuate the progression of lung disease in acute hypoxemic respiratory failure, we performed a multicenter, randomized, masked, controlled study of the effects of prolonged iNO therapy on oxygenation. We hypothesized that iNO therapy would improve oxygenation in an acute manner, slow the rate of decline in gas exchange, and decrease the number of patients who meet pre-established oxygenation failure criteria. STUDY DESIGN: A total of 108 children (median age 2.5 years) with severe acute hypoxemic respiratory failure from 7 centers were enrolled. After consent was obtained, patients were randomized to treatment with iNO (10 ppm) or mechanical ventilation alone for at least 72 hours. Patients with an oxygenation index >/=40 for 3 hours or >/=25 for 6 hours were considered treatment failures and exited the study. RESULTS: Patient age, primary diagnosis, pediatric risk of mortality score, mode of ventilation, and median oxygenation index (35 +/- 22 vs 30 +/- 15; iNO vs control; mean +/- SEM) were not different between groups at study entry. Comparisons of oxygenation indexes during the first 12 hours demonstrated an acute improvement in oxygenation in the iNO group at 4 hours (-10.2 vs -2.7, mean values; P <.014) and at 12 hours (-9.2 vs -2.8; P <.007). At 12 hours 36% of the control group met failure criteria in contrast with 16% in the iNO group (P <.05). During prolonged therapy the failure rate was reduced in the iNO group in patients whose entry oxygenation index was >/=25 (P <.04) and in immunocompromised patients (P <.03). CONCLUSIONS: We conclude that iNO causes an acute improvement in oxygenation in children with severe AHRF. Two subgroups (immunocompromised and an entry oxygen index >/=25) appear to have a more sustained improvement in oxygenation, and we speculate that these subgroups may benefit from prolonged therapy.

Administration, Inhalation↗

PubMed1999

Absolute bioavailability of moxifloxacin.

Moxifloxacin (BAY 12-8039) is an investigational 8-methoxy-fluoroquinolone with broad-spectrum gram-positive and gram-negative activity. To determine the absolute bioavailability of moxifloxacin, this open-label, randomized, crossover study compared the pharmacokinetic characteristics of a single 100-mg dose administered either orally or intravenously as a 60-minute infusion in 10 healthy male volunteers (mean age [+/- SD], 29.3+/-7.1 years; mean weight [+/- SD], 77.7+/-8.7 kg). Geometric mean values for oral/IV moxifloxacin were as follows: peak serum concentration, 1.15/1.34 mg/L, and area under the concentration-time curve over 48 hours, 9.86/10.89 mg x h/L. The geometric mean absolute bioavailability of oral moxifloxacin was 91.8%. Mean renal clearance was approximately 2.3 L/h after administration of both the single oral and IV formulations, which suggests lack of active tubular secretion of moxifloxacin. Both the oral and IV formulations were well tolerated, with 5 reported possible or probable drug-related adverse events; they included headache, nausea, and localized urticaria. In summary, a single oral dose of moxifloxacin was extensively absorbed in healthy young men. Further studies are necessary in actual patients to confirm the viability of IV to oral conversion at the same dose of moxifloxacin.

Administration, Oral↗

PubMed1999

Evaluation of cytotoxicity and absorption enhancing effects of melittin - a novel absorption enhancer.

Melittin is the major active ingredient in bee venom and has been widely studied for its membrane-fusion property. We have explored the possibility of determining a concentration range of melittin where it is relatively safe to be used as an adsorption enhancer. Melittin's potential use as an adsorption enhancer for mannitol was determined using Caco-2 cells as the model epithelial membrane. The results indicated that at concentrations below 2.4 (M melittin is safe. Using a melittin concentration of 1.5 (M there was 3.5 times increased transepithelial transport of mannitol across Caco-2 cell monolayers.

Caco-2 Cells↗

PubMed1999

The effect of excitotoxic lesions centered on the perirhinal cortex in two versions of the radial arm maze task.

Rats with bilateral ibotenic acid lesions centered on the perirhinal cortex and sham-operated controls were tested in 2 versions of a spatially guided radial arm maze task. Lesioned rats made significantly more errors and required more sessions to reach criterion relative to controls in the standard radial maze task. When they were tested in a delayed nonmatch to sample version of this task, lesioned rats made more errors during the predelay phase and at both the 30-s and 10-min delays of the postdelay phase. These findings provide further support for the hypothesis that the role of the perirhinal cortex in object recognition memory may include reference to some spatial aspect of the environment.

Animals↗

PubMed1999

Requirement for Wnt3 in vertebrate axis formation.

Several studies have implicated Wnt signalling in primary axis formation during vertebrate embryogenesis, yet no Wnt protein has been shown to be essential for this process. In the mouse, primitive streak formation is the first overt morphological sign of the anterior-posterior axis. Here we show that Wnt3 is expressed before gastrulation in the proximal epiblast of the egg cylinder, then is restricted to the posterior proximal epiblast and its associated visceral endoderm and subsequently to the primitive streak and mesoderm. Wnt3-/- mice develop a normal egg cylinder but do not form a primitive streak, mesoderm or node. The epiblast continues to proliferate in an undifferentiated state that lacks anterior-posterior neural patterning, but anterior visceral endoderm markers are expressed and correctly positioned. Our results suggest that regional patterning of the visceral endoderm is independent of primitive streak formation, but the subsequent establishment of anterior-posterior neural pattern in the ectoderm is dependent on derivatives of the primitive streak. These studies provide genetic proof for the requirement of Wnt3 in primary axis formation in the mouse.

Animals↗

PubMed1999

Identification of caveolin-1 in lipoprotein particles secreted by exocrine cells.

Caveolin-1 is a protein component (of relative molecular mass 22, 000) of the striated coat that decorates the cytoplasmic surface of caveolae membranes. Previous biochemical and molecular tests have indicated that caveolin-1 is an integral membrane protein that is co-translationally inserted into endoplasmic-reticulum membranes of fibroblast and epithelial cells such that its carboxy- and amino-terminal ends are in the cytoplasm. Here we identify caveolin-1 in the secretory pathway of exocrine cells. Secretion of caveolin-1 from pancreatic acinar cells and a transfected exocrine cell line, but not from Chinese hamster ovary cells, is stimulated by the secretagogues secretin, cholecystokinin and dexamethasone. The secreted caveolin-1 co-fractionates with apolipoproteins, indicating that it may be secreted in a complex with lipids.

Animals↗

PubMed1999

Interferon-alpha protects myeloma cell lines from dexamethasone-induced apoptosis.

Because of the increasing use of IFN-alpha in both induction and maintenance therapy for multiple myeloma (MM), its effect on growth and apoptosis of myeloma cells is important to consider. To investigate the role of IFN-alpha on the growth of myeloma cells, we have studied its effects on the response of interleukin 6 (IL-6)-dependent myeloma cell line (ANBL6) and IL-6-independent myeloma cell line (C2E3) in the presence of IL-6 and dexamethasone (Dex). We found that although IFN-alpha is a potent inhibitor of proliferation, it has only a minimal effect on induction of apoptosis. Moreover, we found IFN-alpha as well as IL-6 can significantly suppress dexamethasone-induced apoptosis. The suppression of apoptosis is concurrent with the induction of both AP-1 and STAT binding activity. We also found that IL-6 but not IFN-alpha up-regulates Bcl-X(L) expression. However, IL-6-mediated Bcl-X(L) expression is suppressed in the presence of Dex. Therefore, the expression of Bcl-X(L) does not account for the protection of Dex-induced apoptosis by IFN-alpha and IL-6. Taken together, our results suggest that IFN-alpha may counteract the beneficial effects of corticosteroids or perhaps other apoptosis inducing agents in the treatment of myeloma.

Apoptosis↗

PubMed1999

Body weight and semen production of broiler breeder males as influenced by crude protein levels and feeding regimens during rearing.

An appropriate dietary CP level and feeding regimen during rearing is considered important for controlling BW and improving semen production in broiler breeder males. A total of 640 day-old broiler breeder male chicks of two commercial strains (A and B) received treatments of a factorial arrangement of two CP levels (12 and 16%) of corn-soybean grower diets and two feeding regimens [changing feed to a grower diet from the standard broiler starter at 0.45 and 0.68 kg BW and then skip-a-day feeding]. Four- to 28-wk BW differed between CP levels during rearing, with heavier BW on the 16% CP diet than on the 12% CP diet in spite of isocaloric feed intake. Strains did not show a significant difference in BW prior to 40 wk of age. Feed restriction initiated at 0.45 or 0.68 kg BW had no effect in controlling BW after 4 wk of age. Uniformity of BW did not differ between CP levels. Semen volume was greater on the 12% than on the 16% CP diet from 28 to 36 wk of age. Semen concentration was not affected by CP levels, feeding regimens, or strains. Spermatozoa per ejaculate from 28 to 52 wk of age was correlated negatively with 8- to 20-wk BW. This negative relationship was attenuated with age, until at Week 46 or later spermatozoa per ejaculate was associated positively with BW after sexual maturity. No difference in percentage of males in semen production was noted between strains, CP levels, or feeding regimens. In brief, diet changes at 0.45 or 0.68 kg BW were not important in improving semen production, whereas the low CP diet (12%) had advantages in semen production over the high CP diet (16%). A negative relationship existed between semen production and BW during rearing; however, continued BW gain after sexual maturity was necessary to optimize semen production, especially during the late breeding period.

Animal Feed↗

PubMed1999

Vasopressin-evoked [Ca2+]i responses in neonatal rat cardiomyocytes.

The presence of arginine vasopressin (AVP) V1 receptors on neonatal rat cardiomyocytes (NRCs) linked to processes capable of elevating intracellular free calcium ([Ca2+]i) is now firmly established. This study examined the sources and signaling involved in [Ca2+]i elevations evoked by AVP in NRCs. AVP promoted increases in both [Ca2+]i and 1,4,5-inositoltrisphosphate (IP3) levels in NRCs. The degree of [Ca2+]i elevation was less than that of angiotensin II, but greater than that of endothelin-1. Extracellular Mg2+ depletion led to diminution of the maximal [Ca2+]i response, with a rightward shift in the concentration-response curves to AVP. The phospholipase C inhibitors, D-609, NCDC, or U73122, and the IP3 receptor blocker, heparin, abolished the [Ca2+]i response to AVP. Neither cyclooxygenase inhibition with indomethacin nor PKC inhibition with staurosporine had any effect. Neither ryanodine nor caffeine, which deplete sarcoplasmic reticulum (SR) Ca2+ stores, nor ruthenium red, which inhibits both SR and mitochondrial Ca2+ stores, affected [Ca2+]i responses to AVP. The SR Ca2+ pump inhibitor, cyclopiazonic acid, abolished, and removal of extracellular Ca2+ attenuated, the response to AVP. These data indicate that activation of cardiac V1 receptors by AVP results in mobilization of Ca2+ from a distinct, non-SR, nonmitochondrial, intracellular Ca2+ pool that is Ca2+ pump replenished and IP3 sensitive. This process occurs secondary to phospholipase C (PLC)-mediated generation of IP3, requires the presence of Mg2+ and extracellular Ca2+, and occurs in a manner independent of PKC and cyclooxygenase activation. Such mechanisms of Ca2+ mobilization might indicate a distinct role for AVP in cardiac physiology and disease.

Angiotensin II↗

PubMed1999

Pretransitional behavior above the nematic-isotropic phase transition of an auxetic trimer liquid crystal.

Static light scattering and electric field-induced Kerr measurements were performed above the nematic-isotropic phase transition of a terminal-lateral-lateral-terminal negative Poisson ratio trimer. For both measurements the inverse susceptibility was observed to be nearly linear with temperature, a result inconsistent with our previously reported Kerr data [Phys. Rev. E 58, 2041 (1998)].

Journal Article↗

PubMed1999

Forskolin inhibits cyclin D1 expression in cultured airway smooth-muscle cells.

Accumulation of intracellular cyclic adenosine monophosphate (cAMP) has been shown to inhibit the growth of cultured airway smooth-muscle cells, but the precise mechanism underlying the antimitogenic action of cAMP in these cells is unknown. We examined the effects of forskolin, an activator of adenylate cyclase, on DNA synthesis, cyclin D1 expression, and cAMP response element-binding protein (CREB) phosphorylation and DNA binding in bovine tracheal myocytes. DNA synthesis was assessed by measurement of [3H]thymidine incorporation. Cyclin D1 protein abundance and CREB phosphorylation were assessed by immunoblotting. Cyclin D1 promoter transcriptional activation was determined by measurement of luciferase activity in cells transiently cotransfected with complementary DNAs encoding the full-length cyclin D1 promoter subcloned into a luciferase reporter and beta-galactosidase (to normalize for transfection efficiency). The binding of nuclear proteins to the cyclin D1 promoter cAMP response element (CRE) was determined by electrophoretic mobility shift assay. We found that forskolin attenuated platelet-derived growth factor-induced DNA synthesis in a concentration-dependent manner. In addition, forskolin pretreatment decreased both cyclin D1 promoter activity and protein levels. Forskolin treatment induced the phosphorylation of CREB and increased the binding of nuclear protein to the cyclin D1 promoter CRE. Finally, addition of an antibody against CREB1 induced supershift of at least one protein-DNA complex. Together, these data suggest that cAMP suppresses cyclin D1 gene expression via phosphorylation and transactivation of CREB. Further studies are needed to determine whether this is the primary mechanism of cAMP-induced growth inhibition, or whether additional pathways are also involved.

Animals↗

PubMed1999

Morphological and functional characteristics of acinar atrophy and recovery in the duct-ligated parotid gland of the rat.

Although acinar atrophy occurs frequently in salivary diseases, the relationship between structural changes and functional decrements is not well-established, and the potential for recovery of histological and functional integrity has not been wholly quantified. We aimed, therefore, to develop further our understanding of pathological acinar atrophy. Stensen's duct was ligated for periods up to six weeks and, in separate experiments, was de-ligated after two weeks and allowed to recover for up to two weeks. Qualitative and quantitative histological analyses were carried out. Additionally, the ability of enzymatically dispersed cells from ligated and de-ligated glands to respond to neurohormonal stimuli was also measured. The results confirmed that totally obstructed glands undergo a rapid, progressive severe atrophy amounting to absolute losses of over 85% of acinar tissue by two weeks. Acinar shrinkage and cell losses through apoptosis accounted for the glandular atrophy. Remaining intralobular epithelia consisted of extremely atrophic acini and numerous duct-like structures with intermediate forms. Dispersed cells from atrophic glands exhibited agonist-induced release of chloride similar to normal. Together, these structural-functional results confirm the persistent viability of acinar-like cells in the obstructed gland and suggest that the duct-like structures are derived from surviving atrophic acini. De-ligated glands exhibited a near-normal recovery of structure by two weeks. Their enzymatically dispersed cells responded normally to agonist stimulation. The results support the view that pathological atrophy is largely similar to physiological atrophy, providing a mechanism for acinar cell survival under adverse conditions, with the possibility of eventual recovery.

Animals↗

PubMed1999

Alginate-pectin-poly-L-lysine particulate as a potential controlled release formulation.

Drug delivery particulates were prepared using alginate, polylysine and pectin. Theophylline, chlorothiazide and indomethacin were used as the model drugs for in-vitro assessments, and mannitol was the model for assessing paracellular drug absorption across Caco-2 cell monolayers. Alginate and pectin served as the core polymers and polylysine helped to strengthen the particulates. Use of pectin specially helped in forming a more robust particulate that was more resistant in acidic pH and modulated the release profiles of the encapsulated model drugs in the alkaline pH. Alginate and pectin were also found to enhance the paracellular absorption of mannitol across Caco-2 cell monolayers by about three times. The release rate could be described as a first-order or square-root time process depending on the drug load. Use of alginate-polylysine-pectin particulates is expected to combine the advantages of bioadhesion, absorption enhancement, and sustained release. This particulate system may have potential use as a carrier for drugs that are poorly absorbed after oral administration.

Adhesiveness↗

PubMed1999

Repetitive coxsackievirus infection induces cardiac dilatation in post-myocarditic mice.

The relation between mycarditis and dilated cardiomyopathy (DCM) is controversial. To clarify the pathogenic mechanism of these diseases, the present study examined the effect of repetitive inoculation with coxsackievirus B3 (CVB3) in post-myocarditic mice. Inbred 3-week-old A/J mice were inoculated intraperitoneally with CVB3 (Nancy strain; 2x10(4) plaque-forming units) and reinfected in the same manner with CVB3 at 40 weeks (3W+/40W+). All mice were killed at 42 weeks old. The weight of the hearts of the 3W+/40W+ group were significantly increased compared with those of the 3W-/40W+ group, and both the heart weight/body weight and lung weight/body weight ratios of the 3W+/40W+ group were also significantly increased over those of the 3W-/40W- group, although the levels of serum neutralizing antibody titers were significantly increased in the 3W+/40W+ group over the level of the other groups. No increase in inflammatory cell infiltration or fibrosis progression was observed in the 3W+/40W+ group relative to the 3W+/40W- group, but the second inoculation resulted in a significant left ventricular dilatation and in left and right ventricular free wall thinning (3.31+/-0.20 mm vs 2.61+/-0.19 mm, p<0.05; 0.54+/-0.09 mm vs 0.72+/-0.16 mm, p<0.05, respectively). The sarcomere length was also significantly increased in the 3W+/40W+ group compared with that of the other groups, as determined by electron microscopy. Degenerative or necrotic areas in the infected hearts were not stained with anti-mouse IgG antibody, but were stained, only in 3W+/40W+ mice, with anti-mouse IgM antibody. The concentrations of TNF-alpha in the hearts of the 3W+/40W+ group were increased significantly over those of the 3W+/40W- group. Repetitive CVB3 infection produced cardiac dilatation without inflammatory cell infiltration in post- myocarditic mice. Autoimmunity mediated by the circulation of certain antibodies (eg, antibodies against the CVB3 genome or a CVB3-related protein) may be part of the pathogenic mechanism for this phenomenon. Thus, repetitive virus infection might contribute to the pathogenesis of cardiac dilatation.

Animals↗

PubMed1999

Long-term renal sodium handling in patients with cirrhosis treated with transjugular intrahepatic portosystemic shunts for refractory ascites.

PURPOSE: The long-term effects of transjugular intrahepatic portosystemic shunts on renal sodium excretion are not known. We sought to determine these long-term effects, as well as to measure the effects of a sodium load in patients who are free of ascites. SUBJECTS AND METHODS: Ten patients with cirrhosis who had been successfully treated with transjugular intrahepatic portosystemic stent shunt for refractory ascites were studied before the shunt and again at 6 and 14 months after the shunt while on a 22 mmol sodium/day diet. At 14 months they were also studied on a 200 mmol sodium/day diet for 7 days without diuretics. Renal sodium handling, central blood volume, neurohumoral factors, and hepatic function were measured. RESULTS: Sodium balance was negative at 6 months (urinary sodium excretion [mean +/- SD] 51 +/- 11 mmol/day versus 7 +/- 2 mmol/day pre-shunt; P < 0.05), was maintained at 14 months (22 +/- 4 mmol/day; P < 0.05 versus pre-shunt), and was associated with normalization of renin activity and aldosterone levels, but not norepinephrine levels, as well as significantly improved renal hemodynamic measurements. Sodium loading with 200 mmol/day resulted in weight gain associated with increased central blood volume and appropriate renal sodium handling in most but not all patients (urinary sodium excretion 188 +/- 14 mmol/day), despite persistent nonsuppressibility of sympathetic hyperactivity. CONCLUSIONS: In cirrhotic patients with refractory ascites treated with a transjugular intrahepatic portosystemic stent shunt, long-term renal sodium handling is improved. Adequate intravascular filling in ascites-free cirrhotic patients with normal portal pressure permits an improved but not normalized renal response to a sodium load, possibly due to persistently elevated sympathetic activity. Therefore, these patients should increase their sodium intake cautiously.

Adult↗

PubMed1999

Effects of ursodeoxycholic acid on systemic, renal and forearm haemodynamics and sodium homoeostasis in cirrhotic patients with refractory ascites.

Systemic arterial vasodilatation has been implicated in the pathogenesis of sodium retention in cirrhosis. Hydrophobic bile acids, which have vasodilatory actions, may be involved. Ursodeoxycholic acid, a hydrophilic bile acid, could potentially decrease systemic arterial vasodilatation, possibly due to its antioxidant effects, and improve sodium handling in cirrhosis. The effects of ursodeoxycholic acid on systemic, renal and forearm haemodynamics, liver function and renal sodium handling were assessed in vasodilated cirrhotic patients with refractory ascites treated with a transjugular intrahepatic porto-systemic shunt (TIPS). Eight cirrhotic patients with refractory ascites without TIPS placement served as controls for the sodium handling effects of ursodeoxycholic acid. From 1 month post TIPS, seven patients were studied before, after 1 month of treatment with ursodeoxycholic acid (15 mg.day-1.kg-1) and at 1 month follow-up. Lipid peroxidation products were used as indices of its antioxidant effects. Ursodeoxycholic acid caused a significant reduction in sodium excretion in both groups (P<0.05). This, in the post-TIPS patients (urinary sodium excretion: 35+/-8 mmol/day at 1 month versus 93+/-21 mmol/day at baseline, P<0.05), was due to a significant increase in sodium reabsorption proximal to the distal tubule (P<0.05), without any significant changes in systemic, renal or forearm haemodynamics, or in liver function. No significant change in lipid peroxidation products was observed. We conclude that: (i) in cirrhotic patients with refractory ascites, ursodeoxycholic acid causes sodium retention, (ii) the abnormality in sodium handling in the post-TIPS cirrhotic patients appears to be the result of a direct effect on the proximal nephron, suggesting that factors other than systemic vasodilatation also contribute to sodium retention in cirrhosis, (iii) caution should be exercised in administering ursodeoxycholic acid in cirrhotic patients with ascites.

Adult↗

PubMed1999

What is the relevance of apoptosis to the myocardium?

Direct and indirect evidence from a number of studies demonstrates that apoptosis is an important process in heart failure in humans. It is thought that a proapoptotic shift in conditions occurs during heart failure, involving the entire population of cardiac myocytes. A complex mechanism of programmed cell death has been postulated, involving such factors as Fas, Bax and Bcl-2; tumour necrosis may also play a role. Given the myriad apoptotic pathways, a number of opportunities for treatment have been identified.

Apoptosis↗

PubMed1999

Role of cardiac structural and functional abnormalities in the pathogenesis of hyperdynamic circulation and renal sodium retention in cirrhosis.

The aim of this study was to assess the relationship between subtle cardiovascular abnormalities and abnormal sodium handling in cirrhosis. A total of 35 biopsy-proven patients with cirrhosis with or without ascites and 14 age-matched controls underwent two-dimensional echocardiography and radionuclide angiography for assessment of cardiac volumes, structural changes and systolic and diastolic functions under strict metabolic conditions of a sodium intake of 22 mmol/day. Cardiac output, systemic vascular resistance and pressure/volume relationship (an index of cardiac contractility) were calculated. Eight controls and 14 patients with non-ascitic cirrhosis underwent repeat volume measurements and the pressure/volume relationship was re-evaluated after consuming a diet containing 200 mmol of sodium/day for 7 days. Ascitic cirrhotic patients had significant reductions in (i) cardiac pre-load (end diastolic volume 106+/-9 ml; P<0.05 compared with controls), due to relatively thicker left ventricular wall and septum (P<0.05); (ii) afterload (systemic vascular resistance 992+/-84 dyn.s.cm(-5); P<0. 05 compared with controls) due to systemic arterial vasodilatation; and (iii) reversal of the pressure/volume relationship, indicating contractility dysfunction. Increased cardiac output (6.12+/-0.45 litres/min; P<0.05 compared with controls) was due to a significantly increased heart rate. Pre-ascitic cirrhotic patients had contractile dysfunction, which was accentuated when challenged with a dietary sodium load, associated with renal sodium retention (urinary sodium excretion 162+/-12 mmol/day, compared with 197+/-12 mmol/day in controls; P<0.05). Cardiac output was maintained, since the pre-load was normal or increased, despite a mild degree of ventricular thickening, indicating some diastolic dysfunction. We conclude that: (i) contractile dysfunction is present in cirrhosis and is aggravated by a sodium load; (ii) an increased pre-load in the pre-ascitic patients compensates for the cardiac dysfunction; and (iii) in ascitic patients, a reduced afterload, manifested as systemic arterial vasodilatation, compensates for a reduced pre-load and contractile dysfunction. Cirrhotic cardiomyopathy may well play a pathogenic role in the complications of cirrhosis.

Adult↗