Biomedical subjects

J Shen

Publications and source records attributed to J Shen.

At least 109 records · Page 6Linked to original sources

PubMed2001

EPR investigation of the free radicals generated during the photosensitization of TiO2 colloid by hypocrellin B.

The cation radical of dye produced from the interfacial electron transfer from a surface chelated dye to the conduction band of the colloidal TiO2 was studied by laser flash photolysis and electron paramagnetic resonance (EPR) techniques. The study employed hypocrellin B (HB), a natural photodynamic pigment with strong absorption over the visible light region, as a sensitizer and titanium dioxide as a colloid semiconductor. HB formed a chelate with this colloid semiconductor and exhibited a red-shifted and strongly enhanced absorption in the visible spectrum. Laser photolysis indicated that the electron excitation in the visible absorption band of the chelate resulted in extremely rapid and efficient electron injection from the excited triplet state of the dye into the conduction band of the semiconductor. A transient absorption of cation radical of HB at 570 nm was observed. The appearance of cation radical of HB was characterized by EPR spectrometry: the photoinduced EPR signal was not quenched by oxygen and its intensity decreased in the presence of NaI, a typical hole scavenger. The generation of conduction band electrons in HB-sensitized TiO2 system was also verified by the spin elimination of a stable cyclic nitroxide, 2,2, 6,6-tetramethylpiperidine-1-oxyl (TEMPO), and by the reduction of methyl viologen (MV2+) to its radical MV+.

Animals↗

PubMed2001

Chelation of hypocrellin B with zinc ions with electron paramagnetic resonance (EPR) evidence of the photodynamic activity of the resulting chelate.

Hypocrellin B (HB), a perylenequinone derivative, is an efficient phototherapeutic agent. The chelation of HB with Zinc ions (Zn2+) results in a metal chelate (Zn-HB) which exhibits considerable absorption (lambda max = 612 nm) in the phototherapeutic window. The structure of this chelate has been characterized by UV-Vis, IR and mass spectra. The redox potentials of the Zn-HB chelate were Eox = +1.1 V (vs. SCE) and Ere = -0.7 V (vs. SCE) as measured using the circle volt curve. The quantum yield of singlet oxygen generated by the Zn-HB chelate was 0.86, which both the electron spin trap (EPR) method and the chemical trap method show to be about 0.1 higher than that of its parent compound HB. In irradiated oxygen-saturated solutions of Zn-HB chelate, superoxide radical anions and hydroxyl radicals were detected by EPR spectroscopy using 5,5-dimethyl-1-pyrroline-N-oxide (DMPO) as the spin-trapping agent.

Chelating Agents↗

PubMed2001

Research on the neurophysiological mechanisms of acupuncture: review of selected studies and methodological issues.

This presentation reviews studies that contribute to an understanding of the neurophysiological mechanisms of acupuncture. A 1973 study, using volunteer medical students, looked into acupuncture's analgesic effect on experimentally induced pain and suggests that humoral factors may mediate acupuncture-induced analgesia. In a study of the possible role of the cerebrospinal fluid transmission of pain suppression effects of acupuncture, cerebrospinal fluid from acupuncture-treated rabbits was infused into recipient rabbits. The analgesic effect was observed in the recipient rabbits, suggesting that acupuncture-induced analgesia may be mediated by substances released in the cerebrospinal fluid. Studies of electroacupuncture in rats revealed that both low-frequency and high-frequency stimulation could induce analgesia, but that there are differential effects of low- and high-frequency acupuncture on the types of endorphins released. In another study, low-frequency electroacupuncture, given as median nerve stimulation in cats, was shown to protect the myocardium by inhibiting sympathetic pressor response and increasing myocardial oxygen demand. The development of neuroimaging tools, such as positron emission tomography (PET) and functional magnetic resonance imaging (fMRI), make noninvasive studies of acupuncture's effects on human brain activity possible. Studies using PET have shown that thalamic asymmetry present among patients suffering from chronic pain was reduced after the patients underwent acupuncture treatment. Other studies, using fMRI, have pointed to relationships between particular acupoints and visual-cortex activation. These powerful new tools open the possibility to new scientific studies of this ancient therapy.

Acupuncture Analgesia↗

PubMed2001

Apoptosis in endometrial glandular and stromal cells in women with and without endometriosis.

BACKGROUND: The aetiology of endometriosis is unknown. Ectopic dissemination of the endometrial cells gives origin to endometriotic lesions, but occurs in women with and without endometriosis. It has been suggested that increased ectopic cell survival facilitates their implantation. The objectives of this study were to evaluate endometrial apoptosis in women with endometriosis according to: (i) cyclic changes, (ii) glandular and stromal contribution, and (iii) stage of the disease. METHODS: The subjects were women undergoing diagnostic laparoscopy and endometrial biopsies for suspected endometriosis. Spontaneous apoptosis was evaluated using TdT-mediated dUTP-biotin nick end-labelling (TUNEL) assay. Apoptotic cells per 10 mm(2) (apoptotic index) in an area of 10-50 mm(2) in 5 microm endometrial tissue sections were counted and location of these cells was recorded. RESULTS: The apoptotic index in glandular epithelium was lower in endometriosis than controls (26.0 +/- 5.5 versus 51.2 +/- 9.7, P = 0.03) but not in the stroma (36.3 +/- 6.4 versus 48.4 +/- 11.3, NS). In controls, apoptosis was highest during the late secretory/menstrual and early proliferative phases and cyclic variability was apparent. In endometriosis, this cyclic variability was lost. There was a trend toward decreased apoptosis with increasing stage of the disease, but the differences lacked statistical significance. CONCLUSIONS: Spontaneous apoptosis is decreased in the endometrial glands in women with endometriosis, especially during late secretory/menstrual and early proliferative phases of the cycle. This may indicate increased viability of endometrial cells shed during menses, facilitating their ectopic survival and implantation.

Adult↗

PubMed2001

The ataxia-telangiectasia gene product may modulate DNA turnover and control cell fate by regulating cellular redox in lymphocytes.

The ATM kinase, when activated postnatally, exerts multiple functions to prevent the onset of ataxia-telangiectasia (AT). Using freshly isolated thymocytes from Atm-/- mice that were under stress during postnatal differentiation, we noted that thiol redox activity, as indicated by reduction of the tetrazolium MTS, and DNA turnover activity, as indicated by incorporation of [(3)H]thymidine into DNA, were both greatly increased compared with activities in thymocytes from Atm+/+ mice. This increased thymidine incorporation could be suppressed by the thiol N-acetylcysteine. In primary noncycling splenocytes, mitogens proportionally increased both the rate of [(3)H]thymidine incorporation and the rate of reduction of MTS. The mitogen-induced activities in splenocytes were not affected by ATM but were suppressed by the calcineurin-dependent inhibitor FK-506, which has no effect on these activities in thymocytes. These findings suggest that increased [(3)H]thymidine incorporation and reducing power indicate increased cell cycling in mitogenically stimulated splenocytes, whereas these two indicators represent increased FK-506-independent DNA turnover activities in thymocytes. Thus, a primary function of ATM is to activate the redox-sensitive checkpoint required for down-regulation of DNA turnover activities in developing lymphocytes. Cell-cycling checkpoints in undamaged quiescent lymphocytes are not activated by ATM with mitogenic stimulation. ATM may suppress abnormal DNA turnover and the resultant oncogenesis by regulating cellular thiol redox pathways.

Acetylcysteine↗

PubMed2001

Exposure rates of wrapped and unwrapped orbital implants following enucleation.

PURPOSE: To compare the complication rate of porous polyethylene orbital motility implants with solid acrylic implants following enucleation and identify possible risk factors. METHODS: The authors retrospectively reviewed the charts of a total of 117 consecutive enucleations performed at the University of Illinois at Chicago between March 28, 1994, and May 28, 1999. Data obtained included patient demographics, surgical indication, implant type, attending surgeon, surgical technique, and any reported complications. The primary outcome was presence or absence of implant exposure at the final recorded visit. RESULTS: Of the 117 identified cases, 29 were eliminated due to insufficient follow-up data. Of the 88 remaining cases, 48 patients received porous implants and 40 received solid acrylic implants. Implant exposure developed in four cases. All exposures occurred in unwrapped porous polyethylene implants (n=2) or porous polyethylene implants wrapped in absorbable material (n=2). All exposures occurred in patients younger than 18 years of age, and 75% occurred early after trauma-associated enucleation surgery. CONCLUSIONS: The exposure rate of porous polyethylene implants in this study (9%) was found to be comparable to published rates for hydroxyapatite implants. There were no exposures of unwrapped solid acrylic spheres. Unwrapped porous implants in pediatric patients or following trauma-related enucleation may represent an increased risk for postoperative implant exposure. Absorbable wrapping of porous implants may carry the same risk for exposure as no wrapping. Porous implants wrapped in durable material appear to be as safe as solid acrylic spheres.

Adolescent↗

PubMed2001

Ex vivo adenovirus mediated gene transfection of human conjunctival epithelium.

AIM: To investigate the efficacy of "ex vivo" adenoviral vector mediated gene transfection of human conjunctival epithelial cell as a possible route for gene therapy for the distribution of anti-inflammatory agents for the potential treatment of immune mediated ocular inflammatory disorders. METHODS: Human conjunctival cells (HCs) were cultured with various concentrations of recombinant adenoviral vectors carrying a reporter gene LacZ, GFP, or an immunomodulating cytokine vIL-10. vIL-10 in culture supernatant was detected by sandwich ELISA and biological activity was assessed by suppression of ConA stimulated splenocyte proliferation. X-gal and GFP expression was assessed by histochemistry. RESULTS: The extent of adenoviral vector mediated transfer of both reporter genes and vIL-10 was dose dependent. LacZ expression could be detected for at least 50 day after infection with multiple of infection (MOI) 200. Following AdCMVvIL-10 transduction, vIL-10 protein expression occurred between 4-6 days post-transduction, and was maintained at a detectable level for at least 1 month. Secreted vIL-10 showed biological activity, significantly inhibiting Con A induced splenocyte proliferation. Additionally, transfection of HCs with two Adv vectors, one carrying LacZ and the other carrying GFP, resulted in co-expression within a single cell. CONCLUSION: These results confirm previous successful adenoviral vector mediated gene transfer to HCs and further show that expression can be maintained. Furthermore the data show HCs can secrete biologically active vIL-10 that could be developed as a strategy to suppress immune mediated disorders. The successful co-transduction of HCs as described for other tissues, opens avenues to develop a multiple target gene therapy locally.

Adenoviridae↗

PubMed2001

Increased L-arginine uptake and inducible nitric oxide synthase activity in aortas of rats with heart failure.

L-Arginine crosses the cell membrane primarily through the system y(+) transporter. The aim of this study was to investigate the role of L-arginine transport in nitric oxide (NO) production in aortas of rats with heart failure induced by myocardial infarction. Tumor necrosis factor-alpha levels in aortas of rats with heart failure were six times higher than in sham rats (P < 0.01). L-Arginine uptake was increased in aortas of rats with heart failure compared with sham rats (P < 0.01). Cationic amino acid transporter-2B and inducible (i) nitric oxide synthase (NOS) expression were increased in aortas of rats with heart failure compared with sham rats (P < 0.05). Aortic strips from rats with heart failure treated with L-arginine but not D-arginine increased NO production (P < 0.05). The effect of L-arginine on NO production was blocked by L-lysine, a basic amino acid that shares the same system y(+) transporter with L-arginine, and by the NOS inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME). Treatment with L-lysine and L-NAME in vivo decreased plasma nitrate and nitrite levels in rats with heart failure (P < 0.05). Our data demonstrate that NO production is dependent on iNOS activity and L-arginine uptake and suggest that L-arginine transport plays an important role in enhanced NO production in heart failure.

Animals↗

PubMed2001

Galanin-like peptide mRNA in neural lobe of rat pituitary. Increased expression after osmotic stimulation suggests a role for galanin-like peptide in neuron-glial interactions and/or neurosecretion.

Galanin-like peptide (GALP) was recently identified in the porcine hypothalamus, pituitary gland and gut, and has reported selectivity for the GalR2, c.f. the GalR1 receptor. GALP cDNAs have been cloned from pig, rat and human, and GALP mRNA expression is restricted to the arcuate nucleus in normal rat brain. This study examined the regional and cellular distribution of GALP mRNA in the rat pituitary gland, and subsequently determined the effect of osmotic stimulation on GALP transcript levels. GALP mRNA was not detected in the anterior or intermediate lobes, but moderate levels of GALP mRNA were present in the neural (posterior) lobe, in presumed pituicytes, of normal male and female rats. Osmotic stimulation by dehydration or salt loading produced a time-dependent increase in GALP mRNA levels in the neural lobe. Thus, dehydration for 4 days increased GALP mRNA 40-fold, while salt loading for 4, 7 or 10 days increased GALP levels 14-, 21- and 25-fold, respectively (p < or = 0.001). Levels of vasopressin (VP) mRNA in the neural lobe were also increased by these treatments, consistent with previous reports. Galanin (GAL) and GalR2 receptor mRNAs were not detected in the neural lobe, under normal or osmotic stimulation conditions. In addition, GALP mRNA levels in the arcuate nucleus were not altered in dehydrated or salt-loaded rats; and GALP mRNA was not detected in magnocellular neurons of the supraoptic or paraventricular nucleus, despite the characteristic up-regulation of VP and GAL mRNA in these cells. In view of the established anatomy and function of VP/oxytocin neurons in the hypothalamo-neurohypophysial system and the role played by pituicytes in their regulation, the likely synthesis/release of GALP by these specialized astrocytes strongly suggests a role for this novel peptide in regulation of pituicyte morphology/function and/or neurohormone release.

Animals↗

PubMed2001

Tissue-specific expression and splicing of the rat polycystic kidney disease 1 gene.

Autosomal dominant polycystic kidney disease (ADPKD) is the most common genetic potentially lethal human disorder and the polycystic kidney disease 1 (Pkd1) gene is accounted for 85-90% of these cases. We have obtained rat Pkdl cDNA sequence and characterized splicing of Pkdl RNA transcripts in normal rat tissues. Our sequence data revealed a high conservation of the Pkdl gene between rat and other species and mapped rat Pkdl to chromosome 10 in "tail-to-tail" orientation to the tuberous sclerosis 2 (Tsc2) gene. Pkdl was found ubiquitously expressed in the normal rat tissues and the brain had a complex pattern of exon 12 splicing. A novel splicing variant lacking entire exon 31, which occurs in rat and mouse but not in humans, was also identified. As the rat appears to be a valuable model for investigating polycystic kidney disease, the characterization of the rat Pkdl gene will help facilitate future studies to elucidate the molecular mechanisms of cystogenesis in this animal model.

3' Untranslated Regions↗

PubMed2001

Visual search asymmetry: the influence of stimulus familiarity and low-level features.

Wang, Cavanagh, and Green (1994) demonstrated a pop-out effect in searching for an unfamiliar target among familiar distractors (U-F search) and argued for the importance of a familiarity difference between the target and the distractors in determining search efficiency. In four experiments, we explored the generality of that finding. Experiment 1 compared search efficiency across a variety of target-distractor pairs. In Experiments 2, 3, and 4, we used Chinese characters and their transforms as targets and distractors and compared search performance between Chinese and non-Chinese participants. We demonstrated that search asymmetry and search efficiency in the U-F condition are influenced by the presence of low-level feature differences between the familiar and the unfamiliar stimuli. Our findings suggest that the familiarity of the distractors, rather than the familiarity difference between the target and the distractors, determines search efficiency. We also documented a counterintuitive familiarity-inferiority effect, suggesting that knowledge of search stimuli may, sometimes, be detrimental to search performance.

Attention↗

PubMed2001

The genetic events of HPV-immortalized esophageal epithelium cells.

We studied cytogenesis, telomere and telomerase, and c-myc, ras, bcl-2, and p53 genes of cells in the progressive process of immortal epithelial cells from embryonic esophagus induced by human papillomavirus (HPV). The SHEE cell line, established by us, consist of immortalized epithelial cells from the embryonic esophagus induced by genes E6E7 of HPV type 18. It was in initial malignant transformation when cultivated over 60 passages without co-carcinogens. Cells of the 10th, 31st, and 60th passages were represented in the progressive process within the immortal period. In these three stages of the cell line, the modal number of chromosome and karyotypes were analyzed. The telomere length was assayed by Southern blot methods, and the telomerase activity was analyzed by hTR and hTERT assay. C-myc, p53, bcl-2, ras genes were assayed by the multi-PCR method. The morphology of the 10th passage cells exhibited good differentiation, the 60th passage cells were relatively poorly differentiated, and the 31st passage cells differentiated in two distinct ways. The growth characteristics of the 31st and 60th passage cells were weakened at contact-inhibition and anchorage-dependent growth. Karyotypes of three cell passages belonged to hyperdiploid and hypotriploid with abnormal chromosomes +1, +3, +7, +9, +17, +18; del(1)(p32); der(4), t(4;?)(q31;?); der(5),t(5;?)(q31;?); der(13),t(13;13)(p11;q11) and others. Bimodal distribution of chromosomes with more aberrant chromosomes appeared in the 31st and 60th passage cells. Telomere length sharply shortened from normal fetal esophagus to the 10th and 31st passage step by step, but was stable from the 31st to the 60th passage and the telomerase activities measured were expressed at late two passages. p53 mutant was positive in three passages, c-myc was positive in the 31st and the 60th passage K-ras only in the last. The results reveal that changes of chromosomes, telomere length, telomerase activity and certain gene expressions are important events of HPV-immortalized esophageal epithelium cells. All of these changes occurred in dynamic progressive process. This cell line may be useful for the elucidation of the genetic mechanism of cellular immortalization.

Cell Line, Transformed↗

PubMed2001

A comparative study of telomerase activity and malignant phenotype in multistage carcinogenesis of esophageal epithelial cells induced by human papillomavirus.

To examine certain characteristics of multistep carcinogenesis, we studied telomerase activity and malignant phenotypes in the immortal, premalignant and malignant stages of esophageal epithelial cells induced by HPV. An immortalized human fetal esophageal epithelial cell line (SHEE) was induced by E6E7 genes of human papillomavirus (HPV) type 18. Cells in the 10th passage, (SHEE10), 31st passage (SHEE31), 61st passage (SHEE61) and SHEE61A which were selected and expanded from anchorage-independent growth colonies of SHEE61, were examined as follows: cell morphology by electron-microscopy; the cell cycle by flow cytometry, telomerase activity by TRAP assay, tumorigenic detection including anchorage-independent growth by soft agar culture and tumor formation by inoculating cells into SCID and nude mice, and detection of HPV18 E6E7 oncoprotein by Western blot. The morphology of the SHEE10 cells exhibited good differentiation, the SHEE60 and SHEE61A cells were relatively poorly differentiated, and the SHEE31 cells were differentiated in two distinct ways. The telomerase was activated in SHEE31, SHEE61 and SHEE61A, but not in SHEE10 cells. SHEE61 and SHEE61A cells were weakened in contact-inhibition and increased in anchorage-independent growth. Inoculated into SCID and nude mice, the cells of the earlier two passages could not develop tumors; the SHEE61 developed one tumor in four SCID mice, but not in nude mice, and the SHEE61A cells developed tumors in both strains of immunodeficient mice. HPV18 E6E7 DNA detection by Western blotting was positive in all cell passages. In the process of carcinogenesis by HPV, the cells of SHEE31 are in an immortalized state with telomerase activity. The fact that SHEE61 cells remained immortalized and also demonstrated anchorage-independent growth, reveals premalignant character; the cells of SHEE61A exhibited malignant transformation with tumor formation in mice. The results revealed that the telomerase activity, anchorage-independent growth and tumor formation in nude mice are the indicators for immortalization, premalignancy and malignancy, respectively.

Animals↗

PubMed2001

[Evaluation of dynamic enhanced fast multiplanar spoiling gradient recalled(FMPSPGR) in the diagnosis of small hepatocellular carcinoma].

OBJECTIVE: To analyze the features of small hepotocellular carcinoma (SHCC) by spin echo (SE) sequence and dynamic enhanced FMPSPGR, and to compare the sensitivity for detecting and the accuracy for characterization, further to discuss the value of FMPSPGR in the diagnosis of SHCC. METHODS: SE T(1)WI, T(2)WI and FMPSPGR dynamic imaging of the liver were performed for 58 patients with SHCC. The sensitivity for detecting and accuracy for characterization were statistically compared. RESULTS: Seventy-two lesions were found in 58 patients. In the detection of SHCC, the order of the sensitivity was dynamic enhanced FMPSPGR>SE T(2)WI>no-enhanced FMPSPGR>SE T(1)WI. Dynamic enhanced FMPSPGR was significantly higher than any of the others. There was significant difference between no-enhanced FMPSPGR and SE T(2)WI, but not significant difference between T(2)WI and no-enhanced FMPSPGR. In the characterization of SHCC, the accuracy of pre- and post-contrast FMPSPGR was significantly higher than that of SE (T(1)WI+T(2)WI) with remarkable statistical difference. CONCLUSIONS: FMPSPGR dynamic imaging is superior to SE in the detection and characterization of SHCC. The sensitivity for detecting and the accuracy for characterization will be improved when both FMPSPGR and SE are used.

Adult↗

PubMed2001

[Inhibitory effect of aminoglycoside antibiotics on rabbit carotid baroreceptor activity in vitro].

The present study was to investigate the effects of aminoglycoside antibiotics, changes in extracellular Ca2+ concentration and antagonists of L-type Ca-channels on the activity of rabbit carotid sinus baroreceptors (CS-BRA) in isolated and superperfused carotid sinus-carotid sinus nerve (CS-CNS) preparations, using extracellular recording technique. The results are as follows. (1) Streptomycin (0.25-0.75 mmol/L) and gentamycin (0.43-1.29 mmol/L) inhibited CS-BRA in a dose-dependent manner, which recovered after the drugs were washed out. (2) Perfusion with high Ca2+ (3.3 mmol/L) solution inhibited CS-BRA, while perfusate with trace Ca2+ (in the order of 10(-5) mol/L) increased it. (3) Verapamil and diltiazem had no effect on CS-BRA at a concentration of 10(-7) mol/L, but inhibited it at higher concentrations (> 10(-6) mol/L). These results suggest: (1) aminoglycoside antibiotics can inhibit CS-BRA specifically, thus providing a new tool for the study of baroreceptors; (2) calcium ions are not necessary for producing generator potentials of baroreceptors, and the L-type calcium channel does not seem to be involved in CS-BRA per se; and (3) the inhibitory effects of aminoglycoside antibiotics on CS-BRA may not be related to the blocking of L-type calcium channels.

Aminoglycosides↗

PubMed2001

A tool model for predicting atmospheric chemical kinetics with sensitivity analysis.

A package(a tool model) for program of predicting atmospheric chemical kinetics with sensitivity analysis is presented. The new direct method of calculating the first order sensitivity coefficients using sparse matrix technology to chemical kinetics is included in the tool model, it is only necessary to triangularize the matrix related to the Jacobian matrix of the model equation. The Gear type procedure is used to integrate a model equation and its coupled auxiliary sensitivity coefficient equations. The FORTRAN subroutines of the model equation, the sensitivity coefficient equations, and their Jacobian analytical expressions are generated automatically from a chemical mechanism. The kinetic representation for the model equation and its sensitivity coefficient equations, and their Jacobian matrix is presented. Various FORTRAN subroutines in packages, such as SLODE, modified MA28, Gear package, with which the program runs in conjunction are recommended. The photo-oxidation of dimethyl disulfide is used for illustration.

Air Pollutants↗

PubMed2001

Relationship between gene polymorphism of the PAI-1 promoter and myocardial infarction.

OBJECTIVE: To investigate the association between gene polymorphism of the plasminogen activator inhibitor-1 (PAI-1) and myocardial infarction (MI) in Chinese. METHODS: PAI-1 genotyping with polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and allele specific polymerase chain reaction (ASPCR) was performed in 87 myocardial infarction patients and 92 unrelated healthy controls. All subjects' clinical features and PAI-1 activity were tested. RESULTS: There were two polymorphisms within the promoter, a G/A single base substitution polymorphism upstream at -844 bp, and a single guanosine deletion/insertion 4G/5G polymorphism -675 bp upstream from the start of transcription. Significant differences between the patients and the controls were observed neither for the frequencies of the GG, GA and AA genotypes nor for the PAI-1 activities of these three types. But for the 4G/5G polymorphism, there were significant differences between patients and controls for the frequencies of the 4G/4G, 4G/5G and 5G/5G genotypes (P < 0.05). In the MI group, the PAI-1 activity of the 4G/4G type was significantly higher than that of the 5G/5G type (P < 0.05). Further more, a positive correlation between the glucose level and PAI-1 activity was found (r = 0.34, P = 0.02). CONCLUSION: This study indicates that the 4G/5G gene polymorphism of PAI-1 is associated with myocardial infarction, that 4G/4G type is probably an important hereditary risk factor, and that glucose has functional importance in regulating PAI-1 activity.

Adult↗

PubMed2001

All-trans retinoic acid in pulmonary vascular structural remodeling in rats with pulmonary hypertension induced by monocrotaline.

OBJECTIVE: To determine whether all-trans retinoic acid (atRA) exerts an inhibitory effect on rats with pulmonary hypertension induced by monocrotaline. METHODS: All rats were given a single subcutaneous injection of either monocrotaline (60 mg/kg) or saline. Monocrotaline-injected rats received either atRA (30 mg.kg-1.day-1) or saline through oral-gastro intubation. On Days 7, 14, 21, and 28 respectively after monocrotaline injection, cardiovascular catheters were inserted to examine the mean pulmonary artery pressure of rats in each group. Meanwhile, the matrix metalloproteinase-1 (MMP-1) mRNA expression and hydroxyproline content in the main pulmonary artery were determined by RT-PCR and chromometry, respectively. RESULTS: The mean pulmonary artery pressure of rats in the model group increased significantly on day 21 and reached a peak on Day 28 compared with the control group (25.7 +/- 4.3 mm Hg vs 15.1 +/- 1.5 mm Hg and 38.5 +/- 6.4 mm Hg vs 16.4 +/- 2.0 mm Hg, P < 0.01). MMP-1 mRNA overexpression was present on Day 14 (0.72 +/- 0.15 vs 0.39 +/- 0.08, P < 0.01) and was rapidly down-regulated on Day 21 and 28 compared with Day 14, but was still higher than that in the control. The hydroxyoroline content of the main pulmonary artery dropped significantly on Day 14 (4.01 +/- 1.13 micrograms/mg vs 5.10 +/- 0.91 micrograms/mg, P < 0.05) and increased significantly on Days 21 and 28 compared with the control. atRA inhibited the MMP-1 mRNA overexpression from Day 14 to Day 28 and reduced the hydroxyproline content (5.59 +/- 0.70 micrograms/mg vs 7.96 +/- 1.13 micrograms/mg and 7.77 +/- 0.96 micrograms/mg vs 9.93 +/- 1.27 micrograms/mg, P < 0.01) and the mean pulmonary artery pressure compared with the model group (19.6 +/- 3.2 mm Hg vs 25.7 +/- 4.3 mm Hg and 26.3 +/- 4.6 mm Hg vs 38.5 +/- 6.4 mm Hg, P < 0.01). CONCLUSION: atRA inhibits MMP-1 overexpression and the accumulation of collagen, which might elicit favorable geometric remodeling in rat pulmonary hypertension induced by monocrotaline.

Animals↗