Biomedical subjects

Wei Zhou

Publications and source records attributed to Wei Zhou.

At least 55 records · Page 3Linked to original sources

PubMed2006

Matrix metalloproteinase polymorphisms and survival in stage I non-small cell lung cancer.

PURPOSE: The matrix metalloproteinases (MMP) are a family of enzymes that can degrade extracellular matrix and facilitate invasion through the basement membrane. Several polymorphisms in MMP-1, MMP-2, MMP-3, and MMP-12 have been described, some of which lead to differential transcription. We hypothesized that polymorphisms in these MMP genes may be associated with survival outcomes in early-stage non-small cell lung cancer (NSCLC). EXPERIMENTAL DESIGN: We evaluated the relationship between MMP-1, MMP-2, MMP-3, and MMP-12 polymorphisms and both recurrence-free survival (RFS) and overall survival (OS) among 382 patients with stage I NSCLC. Analyses of genotype associations with survival outcomes were done using Cox proportional hazards models and Kaplan-Meier methods and the log-rank test. RESULTS: Patients carrying the variant G allele of the MMP-12 1082A/G polymorphism had significantly worse outcomes [crude hazard ratio (HR) for OS 1.74; 95% confidence interval (95% CI), 1.18-2.58, P=0.006; crude HR for RFS, 1.53; 95% CI, 1.05-2.23, P=0.03]. After adjusting for age, sex, stage, pack-years of smoking, and histologic subtype, the MMP-12 1082A/G polymorphism remained significantly associated with survival outcomes [adjusted HR (AHR) for OS, 1.94; 95% CI, 1.28-2.97, P=0.002; AHR for RFS, 1.61; 95% CI, 1.07-2.41, P=0.02]. None of the other MMP polymorphisms was significantly associated with survival. CONCLUSIONS: Our results show that patients with stage I NSCLC carrying the variant G allele of the MMP-12 1082A/G polymorphism have worse survival.

Adult↗

PubMed2006

Simultaneous determination of ribavirin and ribavirin base in monkey plasma by high performance liquid chromatography with tandem mass spectrometry.

For the first time, a liquid chromatographic method with tandem mass spectrometric detection (LC-MS/MS) for the simultaneous determination of ribavirin and rabavirin base was developed and validated over the concentration range of 10-5,000 ng/ml, respectively, using a 0.025 ml monkey plasma sample. Ribavirin, ribavirin base, and the internal standards were extracted from monkey plasma via protein precipitation. After evaporation of the supernatant, the extract was reconstituted with 5% methanol (containing 0.1% formic acid) and injected onto the LC-MS/MS system. Optimum chromatographic separation was achieved on a Waters Atlantis dc18 (150 mm x 2.1mm, 5 microm) column with mobile phase run in gradient with 100% water containing 0.5% formic acid (A) and 90% acetonitrile (containing 0.5% formic acid (B). The flow rate was 0.4-0.6 ml/min with total cycle time of approximately 7.0 min. Post-column addition of acetonitrile (containing 0.1% formic acid) at 0.3 ml/min was used to increase the ionization efficiency in the MS source. The method was validated for sensitivity, linearity, reproducibility, stability and recovery. Lack of adverse matrix effect and carry-over was also demonstrated. The intra-day and inter-day precision and accuracy of the quality control (QC) samples were <9.0% relative standard deviation (R.S.D.) and 10.8% bias for ribavirin, and 10.3% R.S.D. and 11.3% bias for ribavirin base. The current specific, accurate and precise assay is useful in support of the toxicokinetic and pharmacokinetic studies of these compounds.

Animals↗

PubMed2006

Short QT syndrome: a case report and review of literature.

The short QT syndrome has been recently recognised as a genetic ion channel dysfunction. This new clinical entity is associated with an incidence of sudden cardiac death, syncope, and atrial fibrillation in otherwise healthy individuals. The distinctive ECG pattern consists of an abnormally short QT interval, a short or even absent ST segment and narrow T waves. A 30-year-old resuscitated woman with short QT syndrome is described together with an example of the classic ECG characteristics. A short-coupled variant of torsade de pointes was reveal on Holter recordings. The implantable cardioveter defibrillator seems to be the therapy of choice to prevent from sudden cardiac death. Quinidine proved to be efficient in prolonging the QT interval and rendering ventricular tachyarrhythmias non-inducible in patients with a mutation in KCNH2 (HERG). Our preliminary data suggest amiodarone combined with beta-blocker may be helpful in treating episodes of polymorphic ventricular tachycardia for patients with an unknown genotype. Because the short QT syndrome often involves young patients with an apparently normal heart, it is imperative for physicians to recognize the clinical features of the short QT syndrome in making a timely correct diagnosis.

Adrenergic beta-Antagonists↗

PubMed2006

Infrequent mutation of ATBF1 in human breast cancer.

Deletion at chromosome 16q is frequent in prostate and breast cancers, suggesting the existence of one or more tumor suppressor genes in 16q. Recently, the transcription factor ATBF1 at 16q22 was identified as a strong candidate tumor suppressor gene in prostate cancer, and loss of ATBF1 expression was associated with poorer prognosis in breast cancer. In the present study, we examined mutation, expression, and promoter methylation of ATBF1 in 32 breast cancer cell lines. Only 2 of the 32 cancer cell lines had mutations, although 18 nucleotide polymorphisms were detected. In addition, 24 of 32 (75%) cancer cell lines had reduced ATBF1 mRNA levels, yet promoter methylation was not involved in gene silencing. These findings suggest that ATBF1 plays a role in breast cancer through transcriptional downregulation rather than mutations.

Breast Neoplasms↗

PubMed2006

Hybrid approach to complex thoracic aortic aneurysms in high-risk patients: surgical challenges and clinical outcomes.

BACKGROUND: Endovascular therapy is a less invasive alternative treatment for high-risk patients with thoracic aortic aneurysms. However, this technology alone is often not applicable to complex aneurysmal morphology. The purpose of this study was to evaluate the utility of hybrid strategies in high-risk patients who are otherwise unsuitable for endovascular therapy alone. METHODS: During an 18-month period, 31 high-risk patients (mean age, 69 years; range, 52-89 years) underwent combined open and endovascular approaches for complex aneurysms, including 16 patients with ascending and arch aneurysms and 15 patients with aneurysms involving visceral vessels. Among them, 11 patients had histories of aneurysm repairs. To overcome the anatomic limitations of endovascular repairs, various adjunctive surgical maneuvers were used, including aortic arch reconstruction in 3 patients, supra-aortic trunk debranching in 13 patients (including 8 patients who required aortas as inflow sources), and visceral vessel bypasses in 15 patients (including 10 patients who required bypasses to all 3 visceral branches). Additionally, carotid artery access was obtained in 1 patient, and iliac artery conduits were created in 12 patients. RESULTS: Technical success was achieved in all patients. There was one perioperative death (3.2%) due to postoperative bleeding. Two patients (6.4%) had immediate type II endoleaks, which were resolved by the 1-month follow-up. Other procedure-related complications occurred in three patients (9.6%), including renal bypass thromboses in two patients and retroperitoneal hematoma, which was successfully managed conservatively, in one patient. During a mean follow-up of 16 months, two patients died of unrelated causes, whereas the remainder of patients were asymptomatic, without aneurysm enlargement. CONCLUSIONS: Our study highlights how hybrid strategies incorporating surgical and endovascular approaches can be used successfully in treating patients with complex thoracic aortic aneurysms. This combined approach potentially expands the field of endovascular stent grafting and is an attractive solution for patients with poor cardiopulmonary reserves.

Aged↗

PubMed2006

Mutation breeding of chitosanase-producing strain Bacillus sp. S65 by low-energy ion implantation.

In order to obtain an industrial strain with higher chitosanase yield, the wild strain Bacillus sp. S65 cells were mutated by a novel mutagen, nitrogen ion beam, with energy of 15 keV and dose ranging from 2.6 x 10(14 )to 5.2 x 10(15) ions/cm(2). One mutant, s65F5 with high yield of chitosanase was isolated. Results showed that the production of chitosanase of s65F5 was dramatically increased from 4.1 U/ml in s65 to 25 U/ml by ion beam implantation, while the fermentation time was shortened from 72 to 56 h, both of which greatly increased efficiency and reduced the cost of industrial production. Besides, the mutagenic effects of low-energy ion beam on survival rate showed characteristic down-up-down pattern, which was different from the traditional mutagens such as UV and gamma-ray and the possible mutation mechanism was discussed.

Bacillus↗

PubMed2006

Inhibition of protein kinase Cbeta protects against diabetes-induced impairment in arachidonic acid dilation of small coronary arteries.

To test the hypothesis that protein kinase C (PKC)beta-induced reactive oxygen species (ROS) underlie the vascular dysfunction in diabetes, we examined the effects of (S)-13[(dimethylamino)-methyl]-10,11-14,15-tetrahydro-4,9:16,21-dimetheno-1H,13H-dibenzo[e,k]pyrrolo[3,4-h][1,4,13]oxadi-azacyclohexadecene-1,3(2H)-dione (LY333531; LY), a specific PKCbeta inhibitor, on arachidonic acid (AA)-mediated dilation in small coronary arteries from streptozotocin-induced diabetic rats. This study was designed to determine whether diabetes impairs AA-induced vasodilation of small coronary arteries and whether this defect could be blunted by dietary treatment with LY. Coronary diameter was measured using videomicroscopy in isolated pressurized vessels. In controls, AA dose dependently dilated coronary arteries, with 1 muM producing 54.7 +/- 3.1% and 30 microM producing 72.0 +/- 3.0% dilation (n = 9). In diabetic rats, 1 microM AA only produced 31.4 +/- 3.8% (n = 8; p < 0.01 versus control) and 30 microM 43.8 +/- 3.7% dilation (n = 8; p < 0.001 versus control). Nitroprusside-mediated vasodilations were similar in control and diabetic rats. In contrast, in diabetic rats receiving LY, AA-mediated coronary dilations were normal. In controls, AA-mediated vasodilation was inhibited by miconazole (an inhibitor of cytochrome P450 epoxygenase) and by iberiotoxin (IBTX, an inhibitor of the large conductance Ca(2+)-activated K(+) channel), but miconazole and IBTX had no effects in diabetic vessels. In diabetic rats receiving LY, the effects of miconazole and IBTX were similar to control. Superoxide dismutase restored responses to AA in diabetic vessels but had no effect in vessels from control or diabetic rats on LY. These results suggest that AA-mediated vasodilation in rat coronary arteries are impaired in diabetic rats due to increases in generation of ROS. LY protects against these defects in diabetes through inhibition of PKCbeta-mediated production of ROS.

Animals↗

PubMed2006

FOXO1A is a candidate for the 13q14 tumor suppressor gene inhibiting androgen receptor signaling in prostate cancer.

Chromosomal deletion is frequent at the region between BRCA2 and RB1 in the q14 band of chromosome 13 (13q14) in human cancers, including prostate cancer, suggesting the presence of a tumor suppressor gene. However, no reasonable candidate has been identified thus far. In this study, we did genetic and functional analyses to identify and evaluate the 13q14 tumor suppressor gene. Hemizygous and homozygous deletions in cell lines/xenografts of prostate cancer mapped the deletion locus to 919 kb, which harbors only one known gene, the FOXO1A transcription factor. Deletion at FOXO1A was detected in 31% to 34% in 6 cell lines, 27 xenografts, and 72 clinical specimens of prostate cancer, and was significantly more frequent than deletions at surrounding loci. In addition, FOXO1A was transcriptionally down-regulated in some prostate cancers. Functionally, ectopic expression of FOXO1A inhibited, and its knockdown promoted, cell proliferation or survival. Furthermore, FOXO1A inhibited androgen- and androgen receptor-mediated gene regulation and cell proliferation. Consistent with the understanding of FOXO1A biology, our findings suggest that FOXO1A is the 13q14 tumor suppressor gene, at least in prostate cancer. As a well-established negative effector in the phosphatidylinositol 3-kinase/AKT signaling pathway, FOXO1A inactivation in cancer would impair the therapeutic effect of phosphatidylinositol 3-kinase/AKT inhibitors in cancer treatment.

Androgen Receptor Antagonists↗

PubMed2006

Long-term recording on multi-electrode array reveals degraded inhibitory connection in neuronal network development.

Spontaneous neuronal activity plays an important role in development. However, the mechanism that underlies the long-term spontaneous developmental change of cultured neuronal networks in vitro is not well understood. To investigate the contribution of inhibitory and excitatory connections to the development of neuronal networks, dissociated neurons from an embryonic rat hippocampal formation were cultured on a multi-electrode array plate and spontaneous activities were recorded by multi-channel system. These spontaneous activities were compared to bicuculline-induced firings, which were recorded by 60 electrodes simultaneously from 1 to 14 weeks in vitro (WIV). The phenomena showed that the spontaneous firing activities changed from an initial pattern of synchronized bursts to a later pattern of high frequency random spikes. The bicuculline-induced firing activities transformed from a pattern of synchronized bursts throughout all active sites in 3 WIV, to a pattern of local synchronized or random spikes appearing in the intervals of synchronized bursts after 11 WIV, while the firing rate hardly changed. Kynurenic acid, a broad-spectrum glutamate receptor antagonist, blocked all activities while CNQX inhibited only the local synchronized or random spikes. These suggest that the inhibitory connection was age-dependent degraded in vitro and the developmental spontaneous firing pattern was built by the homeostatic balance of the excitatory-inhibitory connection networks. Long-term cultures on MEA provided a useful tool to measure the relationship between spontaneous developmental change and pharmacological influence in vitro.

Animals↗

PubMed2006

LKB1 mutation in large cell carcinoma of the lung.

Germline inactivation of LKB1 is responsible for Peutz-Jeghers syndrome, an autosomal dominant disorder characterized by benign hamartomas of the GI tract and an increased predisposition to certain cancers, including lung. Acquired mutations in LKB1 are rarely observed in most sporadic tumor types except for adenocarcinomas of the lung where up to 50% harbor inactivating mutations. In this study, we focused on LKB1 mutations in lung cancer cell lines originating from large cell carcinomas. We identified a novel 1.5kb interstitial deletion within LKB1 gene in H157 cancer cells. Homozygosity mapping-of-deletion analysis (HOMOD) analysis showed that the deletion is accompanied by LOH of one parental allele, indicating biallelic inactivation of LKB1. This deletion results in an LKB1 transcript lacking exons 2 and 3 and a predicted in-frame deletion of 58 amino acids within the kinase domain of the LKB1 protein. The truncated transcript was expressed at relatively low levels, and the truncated LKB1 protein was virtually undetectable in this cell line. To determine the impact of LKB1 protein truncation on its function, we examined AMPK-alpha, a downstream target of LKB1 kinase activity triggered by low energy stress conditions. Phosphorylation of AMPK-alpha was attenuated in H157 cells treated with 2-deoxyglucose, and could be rescued by expression of an exogenous GFP-LKB1 fusion protein. Therefore, our data suggest that LKB1 function is compromised in H157. Of the four cell lines and six primary tumors of large cell lung carcinoma origin that have been evaluated in this and other studies, LKB1 mutations have been found in three cases. These results suggest that, in addition to adenocarcinomas, acquired loss of function mutations in LKB1 may also be frequently involved in the pathogenesis of large cell lung carcinomas.

AMP-Activated Protein Kinase Kinases↗

PubMed2006

[C1 lateral mass-C2 pedicle screws and crosslink compression fixation for instable atlas fracture].

OBJECTIVES: To evaluate the feasibility and reliability of C(1) lateral-mass screw-C(2) pedicle screw and crosslink compression fixation for Jefferson fracture. METHODS: Seventeen patients with atlas fracture, 12 males and 5 females, aged 42.5 (25 - 67), 4 of which with unstable atlas fracture, were treated. 11 cases underwent C(1) lateral mass and C(2) pedicle screws and crosslink fixation, 6 of which had axial instability and rupture of atlas transverse ligament, 1 had C(2) luminal fracture, and the other 4 had axial instability. With the assistant of regional anatomy study and fluoroscopy the C(1) lateral mass screw and C(2) pedicle screw were inserted properly. Connecting rods were applied into the two screws on each side. Crosslink between the two rods were applied, compressing to achieve the realignment of the C(1) lateral mass fracture and C(0)-C(1)-C(2) into anatomical position. C(1)-C(2) fusions with posterior bone graft were performed in the patients with axial instability or transverse ligament discontinuity. RESULTS: The operative time ranged from 90 to 176 min with an average of 124 min. The intra-operative blood loss ranged from 270 to 1200 ml with an average of 432 ml. Fluoroscopic examination was used for 18 seconds on average. There were no neurological deficits, vertebral artery related complications or other complications in all the patients. No neurological deficit was aggravated after the patient's mobilization with brace 5 days after operation. One case of vertebral artery rupture happened because of the use of electrocautery. The bleeding was stopped by the use of hemostatic sponge and bone cement without causing cerebral hemodynamic deficit. X-ray examination showed bone fusion and stability in all the patients three months after the operation. The restoration of the C(2) fracture was confirmed by CT scan. CONCLUSION: Osteosynthesis of the atlas by C(1) lateral-mass screw-C(2) pedicle screw and crosslink compression fixation is an ideal option for C(1) burst fracture with or without rupture of transverse ligament. The procedure allows a physiological reconstruction of the C(0)-C(1)-C(2) joint and short segmental solid fusion for Jefferson fracture.

Adult↗

PubMed2006

Smoking cessation before diagnosis and survival in early stage non-small cell lung cancer patients.

Smoking cessation decreases the risk of lung cancer. However, little is known about how smoking cessation affects lung cancer survival. We examined the association between smoking cessation and overall survival (OS) and recurrence-free survival (RFS) in 543 early stage non-small cell lung cancer (NSCLC) patients. The data were analyzed using log-rank test and Cox proportional hazard models, adjusting for age, gender, stage, and smoking intensity. The median follow-up time was 57 months (range 0.2-140 months). There were 191 recurrences and 285 deaths. The 5-year OS rates were 50% (95% confidence interval (CI), 43-58%) for current smokers, 54% (44-65%) for ex-smokers who quit 1-8 years, 59% (49-70%) for ex-smokers who quit 9-17 years, 58% (47-69%) for ex-smokers who quit > or =18 years prior to diagnosis, and 76% (63-90%) for never smokers (P=0.09, log-rank test). The adjusted hazard ratios for ex-smokers who quit 1-8, 9-17, > or =18 years, and never smokers were 0.82 (95% CI, 0.59-1.13), 0.69 (0.49-0.97), 0.66 (0.45-0.95), and 0.54 (0.29-0.996), respectively, when compared with current smokers (P(trend)=0.004). Similar associations were found among ever smokers-only, when smoking cessation time was treated as a continuous variable, and for RFS. The significantly beneficial effects of smoking cessation on OS and RFS were observed among women only, while not among men (P=0.01 for interactions between gender and smoking cessation). In conclusion, smoking cessation is associated with improved survival in early stage NSCLC patients. The longer the time since cessation of smoking, the better the survival outcome.

Adult↗

PubMed2006

Homozygous deletion of SMAD4 in breast cancer cell lines and invasive ductal carcinomas.

Inactivation of TGF-beta/SMAD4 signaling was postulated to play an important role in breast cancer development. Even though SMAD4 is located on 18q21, a region frequently lost in breast cancers, point mutations of SMAD4 were rarely observed, implying that biallelic inactivation of SMAD4 was not necessary in the process. In this study, a novel homozygous deletion of SMAD4 was identified in breast cancer cell line SW527 during a screening of 31 breast cancer cell lines. As several breast cancer cell lines were shown to contain SMAD4 homozygous deletion, we sought to develop a reliable method to access such lesions in archived primary tumor specimens. First, a DNA quantification method was developed to measure as few as 5 copies of DNA templates so that the amount of genomic DNA isolated by laser-capture microdissection can be accurately determined. Next, accurate DNA quantitation allowed sufficient DNA templates to be included in the homozygous deletion assay for the robust amplification of SMAD4 genetic markers. Two out of 24 primary infiltrative ductal carcinomas (IDC) with 18q allelic imbalance were determined to contain SMAD4 homozygous deletions, and these samples are also negative for Smad4 protein expression by immunohistochemistry. Our data suggest that biallelic inactivation of SMAD4 through homozygous deletion does occur in a small percentage of IDCs, and support the hypothesis that inactivation of TGF-beta/SMAD4 signaling plays in a role in the development of a subset of IDC.

Base Sequence↗

PubMed2006

Enhancement of periodontal tissue regeneration by locally controlled delivery of insulin-like growth factor-I from dextran-co-gelatin microspheres.

The present work focused on the design of novel hydrogel microspheres based on both dextran- and gelatin-derived biomaterials, and discussed whether locally controlled delivery of IGF-I from dextran-co-gelatin hydrogel microspheres (DG-MP) was useful for periodontal regeneration enhancement. Microspheres were synthesized when gelatin was cooperating with glycidyl methacrylate (GMA) derivatized dextrans (Dex-GMA) and the resultant DG-MP with a hydrogel character of which the cross-linking density could be controlled by the degree of substitution (DS, the number of methacrylates per 100 glucopyranose residues) of Dex-GMA. In this study, three types of DG-MP (DG-MP4.7, DG-MP6.3 and DG-MP7.8) obtained from gelatin and Dex-GMA (differing in DS: 4.7, 6.3 and 7.8 respectively) were prepared and characterized by swelling and degradation properties, drug release kinetics and biological capability in promoting tissue regeneration. By swelling in aqueous positively charged IGF-I solutions, the protein could be encapsulated in DG-MP by polyionic complexation with negatively charged acidic gelatin. No obvious influence of Dex-GMA's DS on DG-MP's configuration and size was observed, and the release and degraded properties showed no significant difference between three types of DG-MP in PBS buffer either. However, high DS of Dex-GMA could lower microsphere's swelling, prolong its degraded time and minimize IGF-I burst release markedly in dextranase-containing PBS, where IGF-I release from a slow release type of microspheres (DG-MP7.8) could be maintained more than 28 days, and an effective protein release kinetics without a significant burst but a relevantly constant release after the initial burst was achieved. IGF-I in DG-MP resulted in more new bone formation in the periodontal defects within 4 or 8 weeks than IGF-I in blood clot directly did (P < 0.01). The observed newly formation of periodontal tissues including the height and percentage of new bone and new cementum on the denuded root surfaces of the furcation area in DG-MP7.8 group were more than that in other groups (P < 0.05). The adequate width of regenerative periodontal ligament (PDL), regular Sharpey's fibers and alveolar bone reconstruction could be observed only in DG-MP7.8 group. These combined results demonstrate that effective release kinetics can be realized by adjusting the DS of Dex-GMA and followed cross-linking density of DG-MP, and that locally controlled delivery of IGF-I from slow release type of DG-MP may serve as a novel therapeutic strategy for periodontal tissue regeneration.

Animals↗

PubMed2006

The Sjogren's syndrome-associated autoantigen Ro52 is an E3 ligase that regulates proliferation and cell death.

Patients affected by Sjögren's syndrome and systemic lupus erythematosus (SLE) carry autoantibodies to an intracellular protein denoted Ro52. Although the serologic presence of Ro52 autoantibodies is used clinically for diagnostic purposes, the function of the protein or why it is targeted as an autoantigen in several rheumatic conditions has not been elucidated. In this study, we show that the expression of Ro52 is significantly increased in PBMC of patients with Sjögren's syndrome and SLE, and demonstrate that Ro52 is a RING-dependent E3 ligase involved in ubiquitination. Overexpression of Ro52, but not of Ro52 lacking the RING domain, in a mouse B cell line lead to decreased growth in steady state and increased cell death after activation via the CD40 pathway. The role of Ro52 in activation-mediated cell death was further confirmed as a reduction in Ro52 expression restored cell viability. These findings suggest that the increased expression of the Ro52 autoantigen in patients may be directly involved in the reduced cellular proliferation and increased apoptotic cell death observed in Sjögren's syndrome and SLE, and may thus contribute to the autoantigenic load and induction of autoimmune B and T cell responses observed in rheumatic patients.

Amino Acid Sequence↗

PubMed2006

Inhibition of PGI2 signaling by miconazole in vascular smooth muscle cells.

Miconazole is widely used clinically as an anti-fungal agent and experimentally as a cytochrome P450 (CYP) inhibitor. In rat coronary arteries that produce PGI(2) as the major arachidonic acid (AA) metabolite, activation of the large-conductance K(+) (BK) channels in coronary arterial smooth muscle cells by AA was inhibited by miconazole but not by the CYP inhibitor SKF525A. Activation of BK currents in coronary smooth muscle cells by carbacyclin or iloprost also was inhibited by miconazole but not by SKF525A, suggesting that miconazole might have properties other than those of CYP inhibition. In addition, carbacyclin-induced dilation of isolated mesenteric arteries was inhibited by treatment with miconazole (51.9+/-4.2% dilation in control, n=7 versus 30.1+/-4.0% with miconazole, n=4, p<0.005) but not SKF525A (52.8+/-3.6%, n=8). In contrast, miconazole did not affect BK channel activation and vasodilation produced by the phosphodiesterase inhibitor RO-201724. In cultured coronary smooth muscle cells, carbacyclin (1microM) stimulated cAMP production by 22-fold (183+/-29pmol/mg at baseline, 4062+/-212pmol/mg with carbacyclin, n=3, p<0.001). The carbacyclin effect was significantly attenuated by treatment with miconazole (1542+/-201pmol/mg, n=3, p<0.001 versus carbacyclin alone), but not by SKF525A (3460+/-406pmol/mg, n=3, p=NS versus carbacyclin alone). These results indicate that in addition to its CYP inhibition properties, miconazole inhibits PGI(2) signaling. Hence, experiments using miconazole as a CYP inhibitor should be interpreted with caution.

4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone↗

PubMed2006

Role of glutamate in a visceral sympathoexcitatory reflex in rostral ventrolateral medulla of cats.

The rostral ventrolateral medulla (rVLM) is involved in processing visceral sympathetic reflexes. However, there is little information on specific neurotransmitters in this brain stem region involved in this reflex. The present study investigated the importance of glutamate and glutamatergic receptors in the rVLM during gallbladder stimulation with bradykinin (BK), because glutamate is thought to function as an excitatory neurotransmitter in this region. Stimulation of visceral afferents activated glutamatergic neurons in the rVLM, as noted by double-labeling with c-Fos and the cellular vesicular glutamate transporter 3 (VGLUT3). Visceral reflex activation significantly increased arterial blood pressure as well as extracellular glutamate concentrations in the rVLM as determined by microdialysis. Barodenervation did not alter the release of glutamate in the rVLM evoked by visceral reflex stimulation. Iontophoresis of glutamate into the rVLM enhanced the activity of sympathetic premotor cardiovascular rVLM neurons. Also, the responses of these neurons to visceral afferent stimulation with BK were attenuated significantly (70%) by blockade of glutamatergic receptors with kynurenic acid. Microinjection of either an N-methyl-D-aspartate (NMDA) receptor antagonist 2-amino-5-phosphonopentanate (25 mM, 30 nl) or an dl-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (2 mM, 30 nl) into the rVLM significantly attenuated the visceral sympathoexcitatory reflex responses. These results suggest that glutamate in the rVLM serves as an excitatory neurotransmitter through a baroreflex-independent mechanism and that both NMDA and AMPA receptors mediate the visceral sympathoexcitatory reflex responses.

Animals↗

PubMed2006

A tutorial on information retrieval: basic terms and concepts.

This informal tutorial is intended for investigators and students who would like to understand the workings of information retrieval systems, including the most frequently used search engines: PubMed and Google. Having a basic knowledge of the terms and concepts of information retrieval should improve the efficiency and productivity of searches. As well, this knowledge is needed in order to follow current research efforts in biomedical information retrieval and text mining that are developing new systems not only for finding documents on a given topic, but extracting and integrating knowledge across documents.

Journal Article↗