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Y H Li

Publications and source records attributed to Y H Li.

At least 37 records · Page 2Linked to original sources
PubMed2002

Serum cholesterol changes from 1983-1984 to 1993-1994 in the People's Republic of China.

BACKGROUND AND AIM: Increasing cardiovascular disease (CVD) mortality in the People's Republic of China (PRC) led to the 1981 establishment of the PRC-USA Study of Cardiovascular and Cardiopulmonary Epidemiology which, among other objectives, is concerned with the correlates of CVD morbidity and mortality in Chinese populations among other objectives. This report describes changes in total cholesterol (TC) levels in four PRC populations from 1983 to 1993 and identifies factors related to the changes. METHODS AND RESULTS: Population screenings carried out in 1983-1984, 1987-1988 and 1993-1994 involved the collection of demographic data, specimens (including blood), medical history and physical examination data. The data from cohort and independent samples were used to assess TC changes in urban and rural men and women over the decade, with and without adjustment for age and body mass index (BMI) changes. For Guangzhou men and women, the cohort analyses (aged 35-54 at baseline) showed increases in TC of 10-20 mg/dL after adjustment for age and changes in BMI; the independent sample analyses (aged 35-44) also showed higher average TC levels in 1993-1994 than in 1983-1984. For the Beijing cohorts, the results showed decreases in TC during the decade in men, an increase in TC in urban women and no change in rural women; the independent sample analyses indicated declines in TC for Beijing men and women. Possible reasons for the Guangzhou TC increases are economic growth, and dietary and BMI changes. The mean age-adjusted BMI significantly increased (5-10%) over the 10-year period in all of the studied groups. CONCLUSIONS: TC increased 10-20 mg/dL in Guangzhou men and women, probably as a result of socioeconomic development during the decade. The inconsistent patterns of TC changes in Beijing require further study.

Adult↗
PubMed2001

Inhibition of vitronectin-mediated haptotaxis and haptoinvasion of MG-63 cells by domain 5 (D5(H)) of human high-molecular-weight kininogen and identification of a minimal amino acid sequence.

We found that human kinin-free high-molecular-weight kininogen (kf-HK) significantly inhibited vitronectin-mediated migration (haptotaxis) and invasive potentiation (haptoinvasion) of osteosarcoma (MG-63) cells but that HK, LK, the common heavy chain of HK and LK, and the light chain (D6(H)) of HK had no inhibitory effect. Recombinant GST-D5(H) (histidine-rich region of HK) obtained from Escherichia coli. (BL21) also inhibited both haptotaxis and haptoinvasion to about 30% of the control level in a dose-dependent manner. These findings suggest that a specific region of D5(H) is responsible for the inhibition of cell haptotaxis and haptoinvasion. Among the seven synthetic peptides covering D5(H), peptide H(479)KHGHGHGKHKNKGK(493) (P-5) inhibited both haptotaxis and haptoinvasion in a dose-dependent manner, suggesting that P-5 could possibly be utilized to prevent primary and secondary metastases of tumor cells.

Amino Acid Sequence↗
PubMed2001

Oral absorption of cephalosporins is quantitatively predicted from in vitro uptake into intestinal brush border membrane vesicles.

In order to establish a method to predict oral absorption of drugs, which are absorbed by the oligopeptide transporter (PepT1), fraction absorbed (F) of cephalosporin antibiotics was predicted from in vitro uptake into rat intestinal brush border membrane vesicles (BBMV). Using in vitro uptake data, F values of cephalosporins in humans were predicted using the equation derived from the complete radial mixing (CRM) model, which was proposed by Amidon et al. (Amidon et al., J. Pharm. Sci. 69 (1980) 1369). In the present study, uptake into BBMV was measured at 25 and 4 degrees C in the presence of an H+ -gradient, and the uptake clearance (CLuptake) was calculated. Clearance for the uptake mediated by PepT1 (DeltaCLuptake) was then calculated as CLuptake at 25 degrees C minus that at 4 degrees C. When DeltaCLuptake and F values were analyzed according to the present equation, fairly good correlation between DeltaCLuptake and F was observed. It was further demonstrated that the present method may be able to quantitatively predict F values of cephalosporins by using several cephalosporins as standards.

Absorption↗
PubMed2001

Antibodies against a truncated Staphylococcus aureus fibronectin-binding protein protect against dissemination of infection in the rat.

Staphylococcus aureus bacteraemia (SAB) originating from local infections can lead to severe secondary infections such as endocarditis. The protective effect of antibodies against secondary infections was studied in a rat model, where a local joint infection leads to bacteraemia and endocarditis on damaged aortic valves. In this study, immunizations with a truncated D2-domain of the S. aureus fibronectin-binding protein displayed on a cow-pea mosaic virus (CPMV-D) carrier induced protection against endocarditis (P < 0.05). Opsonization of S. aureus with antibodies raised against CPMV-D stimulated both neutrophil activity and macrophage phagocytosis in vitro. Furthermore, intravenous administration of these antibodies protected mice from weight loss due to SAB.

Adhesins, Bacterial↗
PubMed2001

Functional mutation in the promoter region of thrombomodulin gene in relation to carotid atherosclerosis.

Thrombomodulin is an important endothelial anticoagulant protein that decreases thrombin activity and activates protein C. Our recent study has shown that the G-33A promoter mutation of thrombomodulin gene is associated with coronary artery disease. This study was conducted to determine whether the G-33A mutation in the promoter region of thrombomodulin gene is a genetic risk factor for ischemic stroke or carotid atherosclerosis. The functional significance of this mutation was also evaluated. We recruited 333 patients (mean age 64 years, 59% male) with ischemic stroke and 257 age- and sex-matched controls. In all study participants, carotid atherosclerosis was assessed by Duplex scanning, and thrombomodulin G-33A promoter mutation was detected by single-strand conformation polymorphism. Luciferase reporter gene assay was used to assess the influence of this mutation on thrombomodulin promoter activity. There was no significant difference in the thrombomodulin G-33A mutation frequency (GA+AA genotypes) between the stroke and the control groups (18.3 vs. 24. 1%, P=0.105). The G-33A mutation frequency was also similar between the study participants with and without carotid atherosclerosis (22.2 vs. 19.8%, P=0.550). When only younger subjects (age </=60 years) were included in the analysis, however, we found the mutation occurred more frequently in participants with carotid atherosclerosis (33.3 vs. 17.3%, odds ratio [OR]=2.38, 95% confidence interval [CI]=1.16-4.90, P=0.027). Multiple logistic regression analyses showed that only diabetes mellitus (OR=3.11, 95% CI=1.33-7.30, P=0.009) and G-33A mutation (OR=2.46, 95% CI=1.14-5.29, P=0.021) were associated independently with carotid atherosclerosis in younger subjects. As assessed by luciferase reporter gene assays, the contructs bearing the G-33A mutation showed a significant decrease (36+/-12%) in transcriptional activity in comparison with the wild type constructs. Our findings suggest that G-33A mutation reduces the thrombomodulin promoter activity and is associated with carotid atherosclerosis in younger subjects.

Aged↗
PubMed2001

1,2,5-Thiadiazolidin-3-one 1,1 dioxide: a powerful scaffold for probing the S' subsites of (chymo)trypsin-like serine proteases.

The 1,2,5-thiadiazolidin-3-one 1,1 dioxide scaffold (I) embodies a motif that allows it to dock to the active site of (chymo)trypsin-like proteases in a predictable and substrate-like fashion. Consequently, inhibitors derived from this heterocyclic scaffold interact with both the S and S' subsites of an enzyme. Exploitation of binding interactions with both the S and S' subsites of a target enzyme may lead to compounds with greatly enhanced enzyme selectivity and inhibitory potency. This preliminary report describes the use of a series of compounds having the heterocyclic scaffold linked to various amino acids to probe the S' subsites of human leukocyte elastase (HLE), proteinase 3 (PR 3), and cathepsin G (Cat G). For comparative purposes, a series of compounds derived from a related scaffold, isothiazolidin-3-one 1,1 dioxide (II), was also generated. Several of the compounds were found to be highly potent and selective time-dependent inhibitors of HLE, PR 3, and Cat G.

Cathepsin G↗
PubMed2001

Heterogeneity of hippocampal GABA(A) receptors: regulation by corticosterone.

Chronic stressors produce changes in hippocampal neurochemistry, neuronal morphology, and hippocampal-dependent learning and memory processes. In rats, stress-induced changes in CA3 apical dendritic structure are mediated by corticosterone (CORT) acting, in part, on excitatory amino acid neurotransmission. CORT also alters GABA-mediated inhibitory neurotransmission, so the GABA(A) receptor system may also contribute to dendritic remodeling and other stress-related changes in hippocampal function. A previous study indicated that chronic CORT treatment produces complex changes in GABA(A) receptor subunit mRNA levels, so we hypothesized that CORT alters the pharmacological properties of hippocampal GABA(A) receptors. To test this, adult male rats were treated with CORT or vehicle pellets for 10 d, after which we quantified [(35)S]t-butylbicyclophosphorothionate ([(35)S]TBPS) and [(3)H]flunitrazepam binding to GABA(A) receptors using in vitro receptor autoradiography. Pharmacological properties of receptors were assessed by examining the allosteric regulation of binding at both sites by GABA and 5alpha-pregnane-3alpha,21-diol-20-one (THDOC), an endogenous anxiolytic steroid. We found striking regional differences in the modulation of [(35)S]TBPS binding, particularly between strata radiatum and strata oriens, suggesting a functional heterogeneity among hippocampal GABA(A) receptors even within the apical versus basal dendrites of pyramidal neurons. Furthermore, we found that CORT treatment decreased the negative modulation of hippocampal [(35)S]TBPS binding by both GABA and THDOC and increased the enhancement of [(3)H]flunitrazepam binding by GABA and THDOC in the dentate gyrus. Together, these data suggest that prolonged exposure to stress levels of corticosteroids may alter hippocampal inhibitory tone by regulating the pharmacological properties of GABA(A) receptors in discrete dendritic subfields.

Allosteric Regulation↗
PubMed2001

Long-term implantation test and tumorigenicity of polyvinyl alcohol hydrogel plates.

Two types of flat plates made from a polyvinyl alcohol (PVA) hydrogel with a water content of 80 and 20 (PVA-H80, PVA-H20), 20 x 10 x 1 mm in size, were subcutaneously implanted into each of 50 young, male Wistar rats. As a control, a sham operation was done on another set of 50 rats (Sham Op group). The shape and transparency of the PVA hydrogel were unchanged for up to 24 months. Tumors arose in 14 rats from the PVA-H80 group. In the PVA-H20 group, tumors appeared in 15 rats. The average tumor latency was 598 +/- 109 days in the PVA-H80 and 637 +/- 94 days in the PVA-H20. There was no difference in tumor incidence between the PVA-H20 and PVA-H80 groups (p < 0.05). In the Sham Op group, no malignant tumors appeared. Histopathologically, the tumors induced by hydrogel plates were malignant tumors resembling fibrosarcoma or malignant fibrous histiocytoma. This indicates that PVA hydrogel implants also induce solid state carcinogenesis at a similarly high rate to medical grade hydrophobic material reported in a previous study.

Absorbable Implants↗
PubMed2001

Stereoselectivity of the folate transporter in rabbit small intestine: studies with amethopterin enantiomers.

Stereoselectivity of the folate transporter was examined using rabbit intestinal brush border membrane vesicles (BBMV). Methotrexate (MTX) and the antipode (D-amethopterin) were used as model substrates of the transporter. Folic acid (FA) and MTX were actively taken up into BBMV in the presence of an H+ gradient. Initial uptake of FA and MTX was concentration-dependent with Km values of 1.5 and 1.6 microM for FA and MTX, respectively. FA and MTX mutually inhibited uptake in a competitive manner, with Ki values being similar to the corresponding Km values, demonstrating that FA and MTX share the folate transporter. D-Amethopterin also inhibited FA uptake competitively, with a Ki value approximately 60-fold greater than that of MTX, showing that the affinity of the D-isomer (D-amethopterin) to the folate transporter is much less than that of the L-isomer (MTX). The extent of stereoselectivity observed in the present study is consistent with the previously reported differences in plasma concentration between amethopterin enantiomers following oral administration in humans.

Animals↗
PubMed2001

Synergistic induction of IL-10 by hypertonic saline solution and lipopolysaccharides in murine peritoneal macrophages.

BACKGROUND: Liver injury after ischemia/reperfusion is an important cause of morbidity in surgical patients. We have shown that the preconditioning of animals that were subjected to liver ischemia/reperfusion with hypertonic saline solution (HTS) prevented injury by inhibiting Kupffer cell tumor necrosis factor (TNF) production. We postulated that the induction of anti-inflammatory interleukin-10 (IL-10) by HTS might contribute to protection. METHODS: Murine thioglycolate--elicited peritoneal exudative macrophages (PEMs) were used to model the effects of HTS on IL-10 release from Kupffer cells. Cells were preconditioned with 500 mOsm HTS (or isotonic saline medium) for 2 hours and then stimulated with lipopolysaccharide (LPS; 1 microg/mL) or vehicle for 4 hours under isotonic conditions. TNF-alpha and IL-10 were measured in the culture supernatant by enzyme-linked immunosorbent assay; TNF, IL-10, and SOCS-3 messenger RNA expression were assessed by Northern blot. NF-kappa B activation was examined by electrophoretic mobility shift assay and Western blot for I kappa B degradation. RESULTS: In the absence of LPS, isotonic medium--and HTS-pretreated PEMs produced little IL-10 (24.9 +/- 66.0 and 0 pg/mL, respectively); however, stimulation of PEMs with LPS increased IL-10 (134.9 +/- 72.2 pg/mL). Preconditioning with HTS significantly augmented LPS-induced IL-10 production, resulting in a 2-fold increase in IL-10 compared with the isotonic solution LPS group (270.7 +/- 106.8 pg/mL; P <.01). HTS alone increased IL-10 mRNA levels and markedly augmented levels induced by LPS alone. To determine whether IL-10 accounted for HTS-induced TNF inhibition, cells from IL-10 knockout animals were studied. A lack of IL-10 did not reverse the inhibitory effect of HTS on LPS-induced TNF. NF-kappa B activation was the same in HTS-and isotonic solution--pretreated groups after LPS. CONCLUSIONS: HTS augments IL-10 induction by LPS at the gene level. Although TNF is reduced, it is not causally related to increased IL-10 or altered NF-kappa B signaling. HTS might exert its beneficial effects by independently modulating pro- and anti-inflammatory molecules, accounting for the potent immunomodulation exerted by HTS in vivo.

Animals↗
PubMed2001

uvrA is an acid-inducible gene involved in the adaptive response to low pH in Streptococcus mutans.

The pH-inducible acid tolerance response (ATR) is believed to play a major role in acid adaptation and virulence of Streptococcus mutans. To study this phenomenon in S. mutans JH1005, differential display PCR was used to identify and clone 13 cDNA products that had increased expression in response to pH 5.0 compared to that of pH 7.5-grown cells. One of these products, confirmed to be pH inducible by RNA dot blot and reverse transcription-PCR analyses, had 67% identity to a uvrA-UV repair excinuclease gene in Bacillus subtilis. Further sequence analysis of the uvrA homologue using the S. mutans genome database revealed that the complete gene was encoded in an open reading frame (ORF) of 2,829 bp (944 amino acids; 104.67 kDa). Immediately 3' of uvrA was an ORF encoding a putative aminopeptidase gene (pepP). uvrA knockouts were constructed in S. mutans strains JH1005, NG8, and UA159 using allelic-exchange mutagenesis, replacing the entire gene with an erythromycin resistance cassette. As with uvrA mutants in other bacteria, the S. mutans uvrA mutants were extremely sensitive to UV irradiation. The uvrA mutant of S. mutans JH1005 was also more sensitive than the wild type to growth at pH 5.0, showing a 15% reduction in growth rate and a 14% reduction in final resting culture density. Acid-adapted S. mutans JH1005 uvrA mutants were shown to be more resistant to UV irradiation than was the parent but were unable to survive exposure to a killing pH of 3.0. Moreover, agarose gel electrophoretic analysis of chromosomal DNA isolated from uvrA-deficient cells exposed to low pH demonstrated more DNA damage than that for the wild-type strain. Here we suggest that uvrA and the nucleotide excision repair pathway are involved in the repair of acid-induced DNA damage and are associated with successful adaptation of S. mutans to low pH.

Acids↗
PubMed2001

Cell density modulates acid adaptation in Streptococcus mutans: implications for survival in biofilms.

Streptococcus mutans normally colonizes dental biofilms and is regularly exposed to continual cycles of acidic pH during ingestion of fermentable dietary carbohydrates. The ability of S. mutans to survive at low pH is an important virulence factor in the pathogenesis of dental caries. Despite a few studies of the acid adaptation mechanism of this organism, little work has focused on the acid tolerance of S. mutans growing in high-cell-density biofilms. It is unknown whether biofilm growth mode or high cell density affects acid adaptation by S. mutans. This study was initiated to examine the acid tolerance response (ATR) of S. mutans biofilm cells and to determine the effect of cell density on the induction of acid adaptation. S. mutans BM71 cells were first grown in broth cultures to examine acid adaptation associated with growth phase, cell density, carbon starvation, and induction by culture filtrates. The cells were also grown in a chemostat-based biofilm fermentor for biofilm formation. Adaptation of biofilm cells to low pH was established in the chemostat by the acid generated from excess glucose metabolism, followed by a pH 3.5 acid shock for 3 h. Both biofilm and planktonic cells were removed to assay percentages of survival. The results showed that S. mutans BM71 exhibited a log-phase ATR induced by low pH and a stationary-phase acid resistance induced by carbon starvation. Cell density was found to modulate acid adaptation in S. mutans log-phase cells, since pre-adapted cells at a higher cell density or from a dense biofilm displayed significantly higher resistance to the killing pH than the cells at a lower cell density. The log-phase ATR could also be induced by a neutralized culture filtrate collected from a low-pH culture, suggesting that the culture filtrate contained an extracellular induction component(s) involved in acid adaptation in S. mutans. Heat or proteinase treatment abolished the induction by the culture filtrate. The results also showed that mutants defective in the comC, -D, or -E genes, which encode a quorum sensing system essential for cell density-dependent induction of genetic competence, had a diminished log-phase ATR. Addition of synthetic competence stimulating peptide (CSP) to the comC mutant restored the ATR. This study demonstrated that cell density and biofilm growth mode modulated acid adaptation in S. mutans, suggesting that optimal development of acid adaptation in this organism involves both low pH induction and cell-cell communication.

Amino Acid Sequence↗
PubMed2001

Natural genetic transformation of Streptococcus mutans growing in biofilms.

Streptococcus mutans is a bacterium that has evolved to be dependent upon a biofilm "lifestyle" for survival and persistence in its natural ecosystem, dental plaque. We initiated this study to identify the genes involved in the development of genetic competence in S. mutans and to assay the natural genetic transformability of biofilm-grown cells. Using genomic analyses, we identified a quorum-sensing peptide pheromone signaling system similar to those previously found in other streptococci. The genetic locus of this system comprises three genes, comC, comD, and comE, that encode a precursor to the peptide competence factor, a histidine kinase, and a response regulator, respectively. We deduced the sequence of comC and its active pheromone product and chemically synthesized the corresponding 21-amino-acid competence-stimulating peptide (CSP). Addition of CSP to noncompetent cells facilitated increased transformation frequencies, with typically 1% of the total cell population transformed. To further confirm the roles of these genes in genetic competence, we inactivated them by insertion-duplication mutagenesis or allelic replacement followed by assays of transformation efficiency. We also demonstrated that biofilm-grown S. mutans cells were transformed at a rate 10- to 600-fold higher than planktonic S. mutans cells. Donor DNA included a suicide plasmid, S. mutans chromosomal DNA harboring a heterologous erythromycin resistance gene, and a replicative plasmid. The cells were optimally transformed during the formation of 8- to 16-h-old biofilms primarily consisting of microcolonies on solid surfaces. We also found that dead cells in the biofilms could act as donors of a chromosomally encoded antibiotic resistance determinant. This work demonstrated that a peptide pheromone system controls genetic competence in S. mutans and that the system functions optimally when the cells are living in actively growing biofilms.

Amino Acid Sequence↗
PubMed2001

Inhibition of macrophage proinflammatory cytokine expression by steroids and recombinant IL-10.

Chronic lung disease (CLD) of prematurity is a prolonged respiratory failure in very-low-birth-weight neonates. Proinflammatory cytokines have been implicated in the development of CLD. Steroids have been shown to produce some improvement in neonates with this disease. The purpose of this study was to evaluate the downregulation of these proinflammatory cytokines by dexamethasone, budesonide and recombinant IL-10 (rIL-10) in order to elucidate the mechanism of the clinical benefit of steroids in babies. Our results showed that dexamethasone, budesonide and rIL-10 significantly inhibited both IL-6 and TNF-alpha production in the THP-1 cell line stimulated by lipopolysaccharide and Ureaplasma urealyticum antigen. Similar effects were found in macrophages from tracheobronchial aspirate fluid from newborn infants. In the rat alveolar macrophage cell line, steroids inhibited IL-6 and TNF-alpha production, while rat rIL-10 did not significantly decrease production. In conclusion, steroids and human rIL-10 were able to downregulate proinflammatory cytokine production, which may explain the beneficial effect of steroids and suggests that rIL-10 could be tried as an anti-inflammatory agent in neonates with a high risk of CLD.

Animals↗
PubMed2001

Stereotactic radiosurgery for primary trigeminal neuralgia using the Leksell Gamma unit.

OBJECTIVE: Previous papers have reported Gamma Knife radiosurgery to be a safe, effective method for primary trigeminal neuralgia. Since November 1996, we have treated primary trigeminal neuralgia using the Leksell Gamma Knife at the Tianjin Medical University. The present study reports clinical results of Gamma Knife radiosurgery in the treatment of trigeminal neuralgia in 80 cases. METHODS: The mean patient age was 67 years (range 32-92), the mean duration of facial pain was 7.6 years (range 1.5-29). The male:female ratio was 31:49. The right side of the face was involved in 45 patients (56.25%) and the left side in 30 cases (37.5%), with bilateral involvement in 5 cases (6.25%). Under local anesthesia, all patients underwent stereotactic MRI to identify the trigeminal nerve. A single isocenter, using a 4-mm collimator, was positioned at the sensory root of the trigeminal nerve entry zone of the pons, 4-6 mm from the brainstem surface, so that no more than the 20% isodose was administered to the brainstem. The maximum dose was between 70 and 90 Gy, with a mean of 75.6 Gy. For bilateral trigeminal neuralgia, two separate matrices were employed, and bilateral Gamma Knife radiosurgery was performed on the same day. RESULTS: Follow-up ranged from 12 to 43 months (mean 23.7 months). Neurological evaluation indicated excellent response in 42 cases (52.5%), good response in 25 cases (31.25%), effective response in 8 cases (10%), so the total pain control rate was 93.75%. The latency from Gamma Knife surgery to pain relief ranged from 1 to 120 days (mean 22 days). Among the 75 patients 7 with pain control experienced pain recurrence 5-26 months after being completely free from pain. A second Gamma Knife radiosurgery was performed in 7 recurrent cases and 5 patients with treatment failure. A maximal dose ranging from 70 to 80 Gy was given (mean 74.2 Gy). After a mean follow-up of 18 months (8-33 months), 9 patients achieved excellent results, and 2 had good results. The latency interval to pain relief ranged from 1 to 120 days (mean 15 days). Nine patients developed new facial numbness, while no other complication appeared in the remainder of the patients. CONCLUSIONS: Gamma Knife radiosurgery is a safe and effective method in the treatment of trigeminal neuralgia once diagnosis is established.

Adult↗
PubMed2001

Meconium induces expression of inducible NO synthase and activation of NF-kappaB in rat alveolar macrophages.

Meconium aspiration causes intensive inflammatory reactions in the lungs, and may lead to neonatal respiratory disorder. Infiltrated inflammatory cells, particularly macrophages, play an important role in such an inflammation. A rat alveolar macrophage cell line (ATCC8383) was exposed to meconium alone or in combination with dexamethasone, budesonide, or interferon-gamma. Nitric oxide (NO) accumulation in the supernatant of the cell culture was detected by Griess reaction, and mRNA of inducible NO synthase (iNOS) expression was detected by reverse transcriptase-PCR. Nuclear factor-kappa B was analyzed by electrophoretic mobility shift assay, and iNOS location and nuclear factor-kappa B transactivation were determined by immunostaining. Our results showed that meconium was capable of inducing production of NO and expression of iNOS in alveolar macrophages in a dose- (1-25 mg/mL, p < 0.05) and time- (4-48 h, p < 0.05) dependent manner. This capability of meconium could be further enhanced in the presence of interferon-gamma (100 IU/mL, p < 0.05). Budesonide (10(-4)-10(-10) M) or dexamethasone (10(-4)-10(-6) M) effectively inhibited the meconium-induced NO production (p < 0.05). Using the protein synthesis inhibitor cycloheximide, we demonstrated that meconium directly induced iNOS in macrophages. Furthermore, meconium also triggered nuclear factor-kappa B activation, a mechanism possibly responsible for the iNOS expression. Our findings suggest that meconium is a potent inflammatory stimulus, resulting in iNOS expression, leading to overproduction of NO from the macrophages, which may be of pathogenic importance in meconium aspiration syndrome. In vitro steroids down-regulated the iNOS expression, thus suggesting a potential to down-regulate NO-mediated inflammation in neonates with meconium aspiration syndrome.

Animals↗