Biomedical subjects

Y S Chang

Publications and source records attributed to Y S Chang.

At least 55 records · Page 3Linked to original sources

PubMed2000

Transcription of Epstein-Barr virus-encoded nuclear antigen 1 promoter Qp is repressed by transforming growth factor-beta via Smad4 binding element in human BL cells.

In Epstein-Barr virus (EBV)-infected BL cells, the oncogenic EBV-encoded nuclear antigen 1 (EBNA 1) gene is directed from the latent promoter Qp. Yeast one-hybrid screen analysis using the -50 to -37 sequence of Qp as the bait was carried out to identify transcriptional factors that may control Qp activity. Results showed that Smad4 binds the -50 to -37 sequence of Qp, indicating that this promoter is potentially regulated by TGF-beta. The association of Smad4 with Qp was further confirmed by supershift of EMSA complexes using Smad4-specific antibody. The transfection of a Qp reporter construct in two EBV(+) BL cell lines, Rael and WW2, showed that Qp activity is repressed in response to the TGF-beta treatment. This repression involves the interaction of a Smad3/Smad4 complex and the transcriptional repressor TGIF, as determined by cotransfection assay and coimmunoprecipitation analysis. Results suggest that TGF-beta may transcriptionally repress Qp through the Smad4-binding site in human BL cells.

Burkitt Lymphoma↗

PubMed2000

Gastric dysplasia and gastric cancer: Helicobacter pylori, serum vitamin C, and other risk factors.

BACKGROUND: Gastric cancer is generally thought to arise through a series of gastric mucosal changes, but the determinants of the precancerous lesions are not well understood. To identify such determinants, we launched a follow-up study in 1989-1990 among 3433 adults in Linqu County, China, a region with very high rates of gastric cancer. METHODS: Data on cigarette smoking, alcohol consumption, and other characteristics of the participants were obtained by interview in 1989-1990, when an initial endoscopy was taken. At study entry, antibodies to Helicobacter pylori were assayed in 2646 adults (77% of people screened), and levels of serum micronutrients were measured in approximately 450 adults. Follow-up endoscopic and histopathologic examinations were conducted in 1994. Antibodies to H. pylori, levels of serum micronutrients, and other baseline characteristics were compared between subjects whose condition showed progression to dysplasia or gastric cancer from study entry to 1994 and subjects with no change or with regression of their lesions over the same time frame. All P: values are two-sided. RESULTS: The presence of H. pylori at baseline was associated with an increased risk of progression to dysplasia or gastric cancer (odds ratio [OR] = 1.8; 95% confidence interval [CI] = 1.2-2.6). The risk of progression to dysplasia or gastric cancer also was moderately increased with the number of years of cigarette smoking. In contrast, the risk of progression was decreased by 80% (OR = 0.2; 95% CI = 0.1-0.7) among subjects with baseline ascorbic acid levels in the highest tertile compared with those in the lowest tertile, and there was a slightly elevated risk in those individuals with higher levels of alpha-tocopherol. CONCLUSIONS: H. pylori infection, cigarette smoking, and low levels of dietary vitamin C may contribute to the progression of precancerous lesions to gastric cancer in this high-risk population.

Adult↗

PubMed2000

Second malignant tumors in patients with nasopharyngeal carcinoma and their association with Epstein-Barr virus.

Since previous published studies about second malignant tumors (SMTs) in nasopharyngeal carcinoma (NPC) patients usually included a limited sample size and did not attain consistent results, we conducted a large retrospective study in a cohort of 1,549 patients to assess the risk of SMT in NPC patients following radiotherapy (RT) in Taiwan. The follow-up period ranged from 2 to 16 years, with a median of 7 years. Thirty-nine patients developed SMTs during the 7,145 person-year follow-up [standardized incidence ratio (SIR): 2. 8; 95% confidence interval (CI): 2.0 to 3.9]. Increased risks of developing SMTs were observed for head and neck (H/N) cancer (SIR: 16.5; 95% CI: 10.0 to 26.8), gastric cancer (SIR: 5.5; 95% CI: 2.2 to 11.4) and leukemia (SIR: 9; 95% CI: 1.9 to 26.3). Paraffin-embedded specimens of secondary H/N cancer (11), secondary gastric cancer (6) and their corresponding NPC specimens were examined by EBER in situ hybridization to assess the association between Epstein-Barr virus (EBV) and these SMTs. Twenty-six primary H/N and 5 gastric cancer specimens were chosen as the control groups. In H/N cancer, EBV was detected in 3.8% of the primary cancers and 9.1% of the secondary cancers. All the positive specimens resulted from hypopharyngeal cancer. Of the secondary gastric cancers, only 1 case (16.6%) was associated with EBV. None of the primary gastric cancers was associated with EBV. Our results indicate an increased risk of developing SMTs, with a preference for head and neck cancer, gastric cancer and leukemia, in NPC patients after RT in Taiwan. Only a small proportion of the secondary H/N and gastric cancers was associated with EBV.

Adolescent↗

PubMed2000

X-ray structure of MalY from Escherichia coli: a pyridoxal 5'-phosphate-dependent enzyme acting as a modulator in mal gene expression.

MalY represents a bifunctional pyridoxal 5'-phosphate-dependent enzyme acting as a beta-cystathionase and as a repressor of the maltose regulon. Here we present the crystal structures of wild-type and A221V mutant protein. Each subunit of the MalY dimer is composed of a large pyridoxal 5'-phosphate-binding domain and a small domain similar to aminotransferases. The structural alignment with related enzymes identifies residues that are generally responsible for beta-lyase activity and depicts a unique binding mode of the pyridoxal 5'-phosphate correlated with a larger, more flexible substrate-binding pocket. In a screen for MalY mutants with reduced mal repressor properties, mutations occurred in three clusters: I, 83-84; II, 181-189 and III, 215-221, which constitute a clearly distinguished region in the MalY crystal structure far away from the cofactor. The tertiary structure of one of these mutants (A221V) demonstrates that positional rearrangements are indeed restricted to regions I, II and III. Therefore, we propose that a direct protein-protein interaction with MalT, the central transcriptional activator of the maltose system, underlies MalY-dependent repression of the maltose system.

Bacterial Proteins↗

PubMed2000

Sonographic detection of delayed small bowel perforations after blunt abdominal trauma.

Isolated perforations of the small bowel resulting from blunt abdominal trauma are rare and difficult to diagnose because of their variable presentation, especially when their appearance is delayed. We report 2 such cases that were diagnosed by sonography and emphasize the usefulness of sonography in detecting bowel injuries after blunt abdominal trauma.

Abdominal Injuries↗

PubMed2000

Effect of vascular endothelial growth factor on cultured endothelial cell monolayer transport properties.

Vascular endothelial growth factor (VEGF) is a potent enhancer of microvascular permeability in vivo. To date, its effects on hydraulic conductivity (L(p)) and diffusive albumin permeability (P(e)) of endothelial monolayers have not been thoroughly assessed in vitro. We hypothesized that VEGF affects endothelial transport properties differently depending on vessel location and endothelial phenotype. Using three well-established endothelial cell culture models-human umbilical vein endothelial cells (HUVECs), bovine aortic endothelial cells (BAECs), and bovine retinal microvascular cells (BRECs)-grown on porous, polycarbonate filters we were able to produce baseline transport properties characteristic of restrictive barriers. Our results show 3.1-fold and 5.7-fold increases in endothelial L(p) for BAEC and BREC monolayers, respectively, at the end of 3 h of VEGF (100 ng/ml) exposure. HUVECs, however, showed no significant alteration in L(p) after 3 h (100 ng/ml) or 24 h (25 ng/ml) of incubation with VEGF even though they were responsive to the inflammatory mediators, thrombin (1 U/ml; 27-fold increase in L(p) in 25 min) and bradykinin (10 microM; 4-fold increase in L(p) in 20 min). Protein kinase C (PKC) and nitric oxide (NO) are downstream effectors of VEGF signaling. BAEC L(p) was responsive to activation of NO (SNAP) and PKC (PMA), whereas these agents had no effect in altering HUVEC L(p). Moreover, BAECs exposed to the PKC inhibitor, staurosporine (50 ng/ml), exhibited significant attenuation of VEGF-induced increase in L(p), but inhibition of nitric oxide synthase (NOS) with L-NMMA (100 microM) had no effect in altering the VEGF-induced increase in L(p). These data provide strong evidence that in BAECs, the VEGF-induced increase in L(p) is mediated by a PKC-dependent mechanism. Regarding diffusive albumin P(e), at the end of 3 h, BAECs and BRECs showed 6.0-fold and 9. 9-fold increases in P(e) in response to VEGF (100 ng/ml), whereas VEGF had no significant effect after 3 h (100 ng/ml) or 24 h (25 ng/ml) in changing HUVEC P(e). In summary, these data indicate that VEGF affects endothelial transport properties differently depending on the vessel type and that differences in cell signaling pathways underlie the differences in VEGF responsiveness.

Animals↗

PubMed2000

Modifier effects on supercritical CO2 extraction efficiency of cephalotaxine from Cephalotaxus wilsoniana leaves.

The effects of modifiers such as methanol, water, diethylamine in methanol (10 v/v %), and diethylamine in water (10 v/v %) were investigated at three different concentrations (1, 5, and 10 v/v %) of the modifiers in supercritical CO2 (SC-CO2) in order to enhance the supercritical fluid extraction (SFE) efficiency of cephalotaxine from Cephalotaxus wilsoniana leaves. Among the modifiers employed, methanol basified with diethylamine was found to greatly enhance the extraction efficiency relative to any other modifiers employed. The results suggest that cephalotaxine in plant matrices may be readily changed from SC-CO2-insoluble salt to SC-CO2-soluble free base by basified modifiers. In addition, SC-CO2 modified with basified methanol could enhance the extraction efficiency of cephalotaxine more than 30% when compared to the conventional organic solvent extraction.

Antineoplastic Agents, Phytogenic↗

PubMed2000

High glucose-induced intercellular adhesion molecule-1 (ICAM-1) expression through an osmotic effect in rat mesangial cells is PKC-NF-kappa B-dependent.

AIMS/HYPOTHESIS: Infiltration of mononuclear cells and glomerular enlargement accompanied by glomerular cell proliferation are very early characteristics of the pathophysiology of diabetes. To clarify the mechanism of early diabetic nephropathy, we measured [3H]-thymidine incorporation and cell numbers to show the influence of a high ambient glucose concentration and the osmotic effect on rat mesangial cell proliferation. We also measured the effect of high glucose on the expression of intercellular adhesion molecule-1 and vascular adhesion molecule-1 by flow cytometry and semiquantitative RT-PCR in mesangial cells and the adhesion of leukocytes to mesangial cells. METHODS/RESULTS: Cells exposed to high D-glucose (30 mmol/l) caused an increase in [3H]-thymidine incorporation and cell numbers at 24 and 48 h and normalized at 72 h (p < 0.05), whereas these changes were not found in high mannitol (30 mmol/l), IL-1 beta, or TNF alpha-stimulated mesangial cells. Cells exposed to high-glucose (15, 30, or 60 mmol/l) or osmotic agents (L-glucose, raffinose and mannitol) showed that intercellular adhesion molecule-1 expression began to increase after 24 h, reached its maximum at 24 and 48 h and gradually decreased afterwards. The stimulatory effects of high glucose and high mannitol on mRNA expression were observed as early as 6 h and reached its maximum at 12 h. Up-regulation of ICAM-1 protein and mRNA was also found in IL-1-beta and TNF-alpha-stimulated mesangial cells. Neither vascular adhesion molecule-1 protein nor mRNA expression was, however, affected by high glucose and high mannitol. Notably, the protein kinase C inhibitors calphostin C and staurosporine reduced high glucose- or high mannitol-induced intercellular adhesion molecule-1 mRNA expression and high glucose-induced proliferation. Furthermore, the NF-kappa B inhibitor N-tosyl-L-phenylalanine chloromethyl ketone reduced high glucose- or high mannitol-induced intercellular adhesion molecule-1 mRNA expression and high glucose-induced proliferation. Results showed that high glucose (15, 30 mmol/l) or high concentrations of osmotic agents remarkably increased the number of adherent leukocytes to mesangial cells (p < 0.01) compared with control cells (5 mmol/l D-glucose). Functional blocking of intercellular adhesion molecule-1 on mesangial cells with rat intercellular adhesion molecule-1 monoclonal antibody, calphostin C, staurosporine, or N-tosyl-L-phenylalanine chloromethyl ketone significantly inhibited high glucose- or high mannitol-induced increase in leukocyte adhesion (p << 0.05). CONCLUSION/INTERPRETATION: These results suggest that high glucose can upregulate intercellular adhesion molecule-1 protein and mRNA expression but not vascular adhesion molecule-1 expression in mesangial cells and promote leukocyte adhesion through up-regulation of intercellular adhesion molecule-1 through osmotic effect, possibly depending on the protein kinase C nuclear factor-kappa B (PKC-NF-kappa B) pathway. High glucose itself can also promote mesangial cell proliferation through the PKC-NF-kappa B pathways. We conclude that hyperglycaemia in itself seems to be an important factor in the development of early diabetic nephropathy.

Animals↗

PubMed2000

Preparation of rhenium-188-tin colloid as a radiation synovectomy agent and comparison with rhenium-188-sulfur colloid.

As a generator-produced beta-emitting radionuclide, the importance of 188Re for radionuclide therapy is increasing rapidly. We prepared 188Re-tin colloid and compared its properties with 188Re-sulfur colloid. Labeling efficiencies reached >98% for tin colloid at 2 h and 89-94% for sulfur colloid at 3 h. All the preparations were stable for 72 h in water, serum, and synovial fluid. If labeled at higher temperature, the particle size of tin colloid increased. The residual radioactivity of 188Re-sulfur colloid in disposable polypropylene syringes after injecting mice was high (62.0+/-7.0%) due to its hydrophobic nature, while that of 188Re-tin colloid was low (2.9+/-1.6%). Although both 188Re-tin colloid and 188Re-sulfur colloid might be useful for radionuclide therapy, we conclude that 188Re tin colloid is more advantageous over 188Re sulfur colloid, due to higher labeling efficiency, control of the particle size, and lower residual activity in the injection syringes.

Animals↗

PubMed2000

Inhibition of phospholipase cgamma1 and cancer cell proliferation by triterpene esters from Uncaria rhynchophylla.

Investigation of the hooks of Uncaria rhynchophylla resulted in isolation of six phospholipase Cgamma1 (PLCgamma1) inhibitors (1-6). The structures of these compounds were elucidated as pentacyclic triterpene esters by spectroscopic and chemical analysis. Three of them, namely uncarinic acids C (1), D (2), and E (3), are newly reported as natural products. All the compounds showed dose-dependent inhibitory activities against PLCgamma1 in vitro with IC(50) values of 9.5-44.6 microM and inhibited the proliferation of human cancer cells with IC(50) values of 0.5-6.5 microg/mL.

3T3 Cells↗

PubMed2000

Minimal toxicity to myeloid progenitor cells of weekly 24-hr infusion of high-dose 5-fluorouracil: direct evidence from colony forming unit-granulocyte and monocyte (CFU-GM) clonogenic assay.

Although very high doses of 5-fluorouracil was used in the weekly 24-h infusion, high-dose 5-fluorouracil (2600 mg/m2/week) and leucovorin (500 mg/m2/week) protocol, myelosuppression was surprisingly low. The current study was conducted to investigate the possible mechanism underlying the low myelosuppression. To mimic the clinical situation, peripheral blood progenitor cells collected from 12 patients were used for colony forming unit-granulocyte and monocyte clonogenic assay; and 2 representative modes of 5-fluorouracil exposure (30 min. versus 24 hr) were examined for cytotoxic effects on human myeloid progenitor cells. Previous pharmacokinetic studies have estimated the concentrations of 5-fluorouracil in the bone marrow to be 200-400 microM and 1-2 microM for the 30 min. infusion (600-900 mg/m2) and the 24 hr-infusion (1000-2000 mg/m2) regimens, respectively. The results of our colony-forming unit-granulocyte and monocyte clonogenic assay showed that 24-hr exposure to 5-fluorouracil (2 microM) and 30 min. exposure to 5-fluorouracil (100 microM) resulted in 27.2% and 78.2% inhibition of the colony formation, respectively. Our data provided direct evidence which may explain why myelotoxicity is significantly less in weekly 24 hr infusion of fluorouracil than in the conventional bolus regimens.

Adolescent↗

PubMed2000

Effect of alpha-phenyl-N-tert-butylnitrone on brain cell membrane function and energy metabolism in experimental Escherichia coli meningitis in the newborn piglet.

We evaluated the efficacy of alpha-phenyl-N-tertbutylnitrone as an adjunctive therapy in experimental bacterial meningitis in the newborn piglet. Meningitis was induced by intracisternal injection of 10(8) colony-forming units of Escherichia coli in 100 microl of saline. Alpha-Phenyl-N-tert-butylnitrone 100 mg/kg was given as a bolus intravenous injection 30 min before induction of meningitis. Although it completely abolished the elevated CSF tumor necrosis factor-a level observed in the meningitis group, alpha-phenyl-N-tert-butylnitrone did not down-modulate parameters of inflammatory responses such as increased intracranial pressure, hypoglycorrhachia, elevated CSF lactate level, and CSF leukocytosis observed in this group. However, alpha-phenyl-N-tert-butylnitrone treatment mitigated alterations in brain cell membrane structure and function during meningitis, evidenced by amelioration of increased brain cell membrane lipid peroxidation products (conjugated dienes) and decreased Na+, K+-ATPase activity. Reduced mean arterial blood pressure, cerebral perfusion pressure, brain glucose concentration, and cerebral energy stores and marginally increased brain lactate level observed in the meningitis group were also ameliorated. These results suggest that although it failed to attenuate the inflammatory responses, alpha-phenyl-N-tert-butylnitrone was effective in ameliorating brain injury in neonatal bacterial meningitis.

Animals↗

PubMed2000

Urgent endoscopic nasobiliary drainage without fluoroscopic guidance: A useful treatment for critically ill patients with biliary obstruction.

BACKGROUND: Endoscopic nasobiliary drainage (ENBD) is routinely performed under fluoroscopic control. This is a report of our experience with urgent ENBD without fluoroscopic guidance in critically ill patients. METHODS: Twenty-six critically ill patients who underwent urgent ENBD for biliary obstruction were analyzed. ENBD was performed without fluoroscopic control because of high risk of transportation or inaccessibility of the x-ray facilities. A pig-tailed nasobiliary catheter was inserted into the bile duct with the help of a guidewire under endoscopic control to bypass the site of obstruction. Successful placement was confirmed by free flow of bile on aspiration via the nasobiliary catheter. RESULTS: A nasobiliary catheter was successfully placed in 23 patients (88%). Adequate bile drainage was achieved in 20 patients with an overall success rate of 77%. There were no procedure-related complications. The mortality rate for patients with successful biliary drainage was 10% (2 of 20), in contrast to 83% (5 of 6) for the group in which drainage was unsuccessful. CONCLUSIONS: Urgent ENBD is effective for patients with biliary obstruction. With experience, this procedure may be successfully performed in critically ill patients without fluoroscopic guidance at primary care hospitals or intensive care units where fluoroscopic facilities are not readily available.

Adult↗

PubMed2000

Intestinal protein loss in patients with haemorrhagic fever with renal syndrome.

BACKGROUND: In haemorrhagic fever with renal syndrome (HFRS) vascular dysfunction has been observed in various organs, but the involvement of the intestine has not yet been reported. This study was performed to evaluate the association of intestinal protein loss in this disease with other clinical parameters reflecting vascular permeability or disease severity. METHODS: Twenty patients with HFRS were included in this study. Intestinal protein loss was measured by (99m)Tc-human serum albumin ((99m)Tc-HSA) scintigraphy in the acute stage, and quantitative analysis of protein loss was measured by the faecal clearance of alpha 1-antitrypsin (C(AT)) in the acute and the recovery stages. C(AT) was then compared with clinical parameters reflecting disease activity and vascular permeability. RESULTS: (99m)Tc-HSA scintigraphy was positive in 13 (65%) patients, and C(AT) in the acute stage was significantly increased as compared with C(AT) in the recovery stage (40.5+/-24.1 vs 9.2+/-4.2 ml/day, P<0.001). C(AT) was associated with serum albumin levels, frequency of hypotensive episodes, severity of acute renal failure, and degree of thrombocytopenia. CONCLUSIONS: Our data suggest that the increased vascular permeability of HFRS is associated with the increased intestinal loss of plasma proteins, which might represent one of the parameters of disease severity in HFRS.

Adult↗

PubMed2000

Clinical usefulness of basal FSH as a prognostic factor in patients undergoing intracytoplasmic sperm injection.

OBJECTIVE: To determine if basal serum follicle stimulating hormone (FSH) level could be a prognostic factor of the clinical outcome in intracytoplasmic sperm injection (ICSI) cycles in the couples with male factor infertility. MATERIALS AND METHODS: From December 1995 to March 1998, total 118 patients underwent in vitro fertilization and embryo transfer (IVF-ET) with ICSI due to male factor infertility were included in this study. Patients were allocated to the low basal FSH group (< 8.5 mIU/ml) and the high basal FSH group (> or = 8.5 mIU/ml). The basal levels of FSH were measured in the 3rd day of menstrual cycle preceding ovarian stimulation cycle in total IVF cycles by immunoradiometric assay (IRMA). Statistical analysis was performed using Student's t-test, Fisher's exact test, and chi 2 test as appropriate. Statistical significance was defined as p < 0.05. RESULTS: The total dose of exogeneous gonadotropin required in the high basal FSH group was significantly higher than that in the low basal FSH group. The numbers of retrieved oocytes and oocytes with grade I, II were significantly higher in the low basal FSH group. The clinical pregnancy rate per cycle in the low basal FSH group (16.2%) was significantly higher than that in the high basal FSH group (4.0%). CONCLUSION: These results suggested that the basal serum FSH levels could be predictive of pregnancy outcome and the results of controlled ovarian hyperstimulation (COH) in ICSI cycles.

Adult↗

PubMed2000

Relationship between endometrial estrogen and progesterone receptors, and sonographic endometrial appearance in the preovulatory phase.

OBJECTIVES: The purpose of the present study is to evaluate the relationship between endometrial concentrations of estrogen receptor (ER) and progesterone receptor (PR), and sonographic endometrial findings in the preovulatory phase of menstrual cycle. STUDY DESIGN: In 45 cycles of 45 infertile women with tubal factor only, transvaginal sonographic assessments and biopsy for immunohistochemical staining of the endometrium were made in the preovulatory phase of unstimulated, normal menstrual cycle. Immunohistochemical localization of ER and PR was scored according to intensity of staining and proportion of cells specifically stained in glandular epithelium and stroma, and the results were analysed according to the sonographic endometrial thickness (< 6 mm, 6-10 mm, or > 10 mm) and patterns. Endometrial patterns were classified as A, centrally hyperechogenic triple-line pattern or non-A, not triple-line. RESULTS: There were no significant differences in the endometrial thickness, serum estradiol level and serum progesterone level between A and non-A groups. The receptor scores of epithelial and stromal ER and epithelial PR were comparable in A and non-A groups. However, the receptor score of stromal PR was significantly higher in A group, with 4.8 +/- 1.4 compared with 2.7 +/- 1.7 in non-A group (p < 0.001). There were no differences in the receptor scores of epithelial ER, epithelial PR, stromal ER and stromal PR among the 3 groups according to the endometrial thickness. CONCLUSIONS: This study suggests that high PR expression in endometrial stroma could be related to the sonographic triple-line or multilayered pattern of endometrium in the preovulatory period.

Adult↗

PubMed2000

The evaluation of the therapeutic effect of tao-shang-tsao on alpha-naphthylisothiocyanate and carbon tetrachloride-induced acute liver damage in rats.

The hepatoprotective effects of Tao-shang-tsao, Ixeris laevigata Sch.-Bip. var. oldhami Kitam., were studied on cholestatic hepatitis induced by alpha-naphthylisothiocyanate (ANIT, 100 mg/10 ml/kg, in olive oil, i.p.) and acute hepatitis induced by carbon tetrachloride (20% CCl4/olive oil, 1.5 ml/kg, i.p.) in rats by post-treatment with the crude methanolic extracts of I. laevigata (0.3, 1.0, and 2.0 g/kg) orally in the therapeutic model. Hepatoprotective activity was monitored by estimating the serum transaminases concentrations and histopathological changes in the livers of experimental rats. It was found that the I. laevigata extract significantly decreased the acute elevation of serum transaminases by biochemical examination. According to pathohistological studies in the liver of experimental rats, the crude I. laevigata extract ameliorates the central necrosis, fatty change or proliferation of bile duct epithelium focal necrosis caused by ANIT or CCl4-induced hepatitis rats.

1-Naphthylisothiocyanate↗

PubMed2000

The efficacy of pentoxifylline as an anti-inflammatory agent in experimental Escherichia coli meningitis in the newborn piglet.

This study was done to evaluate the anti-inflammatory effect and the ensuing neuroprotective effect of pentoxifylline in neonatal experimental bacterial meningitis. Newborn piglets were divided into three groups: 10 in the control group (CG), 13 in the meningitis group (MG), and 13 in the meningitis with pentoxifylline group (PG). Meningitis was induced by intracisternal injection of 10(8) colony-forming units of Escherichia coli in 100 microl of saline. In PG, 20 mg/kg of pentoxifylline was given as a bolus intravenous injection 30 min before induction of meningitis and 6 mg/kg/h was given continuously throughout the experiment. In PG, the increase of CSF TNF-alpha level observed in MG was abolished. Reduced brain glucose and ATP concentrations observed in MG were significantly increased in PG. However, other parameters of inflammatory responses such as increased intracranial pressure, reduced glucose and increased lactate concentrations in the CSF observed in MG were not significantly down-modulated. The extent of CSF leukocytosis was even higher in PG than in MG. Increased cerebral cortical cell membrane lipid peroxidation products and decreased Na(+),K(+)-ATPase activity observed in MG, indicative of meningitis-induced brain cell membrane dysfunction, tended to improve without statistical significance in PG. In summary, although some anti-inflammatory effects have been observed, the overall anti-inflammatory effects of pentoxifylline was very weak, and it failed to significantly reduce the brain damage in experimental neonatal bacterial meningitis.

Animals↗