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ABSTRACT: Endoscopic ultrasonography (EUS) has now been accepted as the most sensitive method to localize insulinoma. However the data in Thai patients is lacking and the diagnostic performances of EUS comparing to computed tomography (CT) and magnetic resonance imaging (MRI) is unknown.
Retrospective analysis of 19 patients with recurrent hypoglycemia suggestive of insulinoma who underwent EUS, CT and MRI for tumor localization during 2007 to 2012. Surgical pathology or long-term follow-up was used as gold standard.
There were 14 patients with 15 insulinoma lesions and 5 patients without insulinoma (2 nesidioblastosis and 3 without lesion). EUS, CTand MRI were performed in 19, 11 and 10 patients, respectively. EUS could detect insulinoma with sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of 93%, 80%, 93% and 80%, respectively. The corresponding performances for CT were 78%, 100%, 100%, 50% and MRI were 71%, 33%, 71%, 33%, respectively. In patients with positive CT subsequent EUS did not change diagnosis. However, EUS was able to detect insulinoma in 50% of patients with negative CT On the other hand, in patients with positive MRI, EUS changed and corrected the diagnosis of MRI in 29% and was able to detect insulinoma in 67% of patients with negative MRI. EUS, CT and MRI correctly localized insulinoma in 87%, 67% and 57%, respectively. The most common incorrect localization was between pancreatic body and tail.
EUS has the best diagnostic performance in detection and localization of insulinoma. CT is less sensitive but very specific, therefore positive CT may preclude the need of EUS. MRI, however is less sensitive and specific than CT. Either positive or negative MRI may require further EUS.
Journal of the Medical Association of Thailand = Chotmaihet thangphaet 02/2013; 96 Suppl 2:S187-93.
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Gastrointestinal endoscopy 06/2012; 76(3):668-9. · 6.71 Impact Factor
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ABSTRACT: The present study was undertaken to evaluate the demographic data, endoscopic ultrasonography (EUS) characteristics of the sub-epithelial lesions, pathology results, complications and long-term follow-up of the patients whom referred for EUS evaluation at Siriraj Hospital.
From January 2008-June 2011, a total of 61 cases was referred for EUS evaluation due to subepithelial lesions. The endoscopic reports, pathology results and the patients' medical records were reviewed. The present study was approved by Siriraj Institutional Review Board.
A total of 61 patients were referred for evaluation of subepithelial lesions, 6 of them were excluded. Thus, 55 cases were analyzed. The mean age was 57.7 +/- 13.8 years (27-87 years). Sixty seven percent were female. Only one-third of the patients had symptoms. The provisional diagnosis of the sub-epithelial lesions, regarding only clinical and endosonographic characteristics were GIST neuroendocrine tumor (NET), pancreatic rest, lipoma, granular cell tumor and others (70.9%, 9.1%, 9.1%, 3.6%, 3.6% and 3.6% respectively). All the lesions were diagnosed as GIST originating from either the forth layer (97.4%) or the second layer (2.6%) of gastric or duodenal wall. Fine needle aspiration (FNA) was performed in 13 patients (23.6%). The positive predictive value, negative predictive value and accuracy of diagnosis of GIST made by endosonographers based on only endosonographic characteristics were 85, 100 and 86% (95% CI: 62.4%-94.4%) respectively.
Most of the subepithelial lesions which were referred for EUS evaluation at Siriraj Hospital were GISTs. The diagnosis of GISTcan be accurately made by using the EUS based on only endosonographic characteristics. FNA should be done for the large sized GIST. For small sized GIST (< 3 cm), FNA might not be beneficial but a 1year interval follow-up with EUS is recommended.
Journal of the Medical Association of Thailand = Chotmaihet thangphaet 02/2012; 95 Suppl 2:S61-7.
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ABSTRACT: Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) is considered as an effective technique to obtain cytology specimens for definite diagnosis of the patients who were suspected of having pancreatic cancer and unknown intra-abdominal lymphadenopathy. The value of repeated EUS-FNA in these patients who had inconclusive first EUS-FNA cytology is not well established.
To determine the yield of repeated EUS-FNA in obtaining a definite diagnosis in patients with clinically suspect for pancreatic cancer and unknown intra-abdominal lymphadenopathy including the reasons for which initial EUS-FNA failed.
The authors retrospectively reviewed the EUS database of Siriraj endoscopy center from January 2007 to May 2011, to identify all patients who underwent repeated EUS-FNA for high index suspicion of pancreatic cancer and unknown intra-abdominal lymphadenopathy. The inconclusive results of the first EUS-FNA, the factors associated with non-diagnosed versus diagnosed cytology results were compared.
A total of 478 EUS- FNA were performed in our institution. Fifteen patients (6M, 9F), mean age of 57 +/- 11.8 years (30-72 years) had repeated EUS-FNA done for the evaluation of possible malignant diseases. Eight of these patients presented with pancreatic masses and the other seven patients had unknown intra-abdominal lymphadenopathy. The second EUS-FNA diagnosed and was truly benign in 4 patients. Repeated EUS-FNA facilitated determination of the true status of the disease in 13 of 15 patients which 9 of whom were malignancy. Sensitivity, specificity, positive predictive value, negative predictive value and accuracy of repeated EUS-FNA for both inconclusive pancreatic masses and unknown intra-abdominal lymphadenopathy were 90%, 100%, 100%, 80% and 92.8% respectively.
Repeated EUS-FNA for inconclusive initial cytology of patients with suspected pancreatic cancer and unknown intra-abdominal lymphadenopathy provided a very high yield for definite tissue diagnosis and should be recommended.
Journal of the Medical Association of Thailand = Chotmaihet thangphaet 02/2012; 95 Suppl 2:S68-74.
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ABSTRACT: To characterize the effects of age on clinical presentations and endoscopic diagnoses and to determine outcomes after endoscopic therapy among patients aged ≥ 65 years admitted for acute upper gastrointestinal bleeding (UGIB) compared with those aged < 65 years.
Medical records and an endoscopy data-base of 526 consecutive patients with overt UGIB ad-mitted during 2007-2009 were reviewed. The initial presentations and clinical course within 30 d after endoscopy were obtained.
A total of 235 patients aged ≥ 65 years constituted the elderly population (mean age of 74.2 ± 6.7 years, 63% male). Compared to young patients, the elderly patients were more likely to present with melena (53% vs 30%, respectively; P < 0.001), have comorbidities (69% vs 54%, respectively; P < 0.001), and receive antiplatelet agents (39% vs 10%, respectively; P < 0.001). Interestingly, hemodynamic instability was observed less in this group (49% vs 68%, respectively; P < 0.001). Peptic ulcer was the leading cause of UGIB in the elderly patients, followed by varices and gastropathy. The elderly and young patients had a similar clinical course with regard to the utilization of endoscopic therapy, requirement for transfusion, duration of hospital stay, need for surgery [relative risk (RR), 0.31; 95% confidence interval (CI), 0.03-2.75; P = 0.26], rebleeding (RR, 1.44; 95% CI, 0.92-2.25; P = 0.11), and mortality (RR, 1.10; 95% CI, 0.57-2.11; P = 0.77). In Cox's regression analysis, hemodynamic instability at presentation, background of liver cirrhosis or disseminated malignancy, transfusion requirement, and development of rebleeding were significantly associated with 30-d mortality.
Despite multiple comorbidities and the concomitant use of antiplatelets in the elderly patients, advanced age does not appear to influence adverse outcomes of acute UGIB after therapeutic endoscopy.
World Journal of Gastroenterology 08/2011; 17(32):3724-32. · 2.47 Impact Factor
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ABSTRACT: Unlike endoscopic retrograde cholangiopancreatography (ERCP) service, endoscopic ultrasonography (EUS) service in Thailand is at its elementary state. Currently, there are only 11 hospitals in Thailand carrying out EUS whereas there are more than 50 hospitals carrying out ERCP. This is a multicenter questionnaire survey that obtained information on EUS practice for pancreatic cysts. Of those 11 hospitals, only three hospitals provided enough number of patients with pancreatic cysts undergoing EUS. There were many differences in endosonographers opinions regarding specific information in the pancreatic cyst. In addition, the threshold to carry out and not to carry out fine needle aspiration are varies.
Digestive Endoscopy 05/2011; 23 Suppl 1:54-7. · 1.19 Impact Factor
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Tawesak Tanwandee,
Manop Pithukpakorn,
Noppawan Vipatakul,
Phunchai Charatcharoenwitthaya,
Siwaporn Chainuvati,
Supot Nimanong,
Varayu Prachayakul,
Supot Pongprasobchai,
Sathaporn Manatsathit,
Somchai Leelakusolvong, Nonthalee Pausawasdi,
Udom Kachintorn,
Chanin Limwongse,
Suthipol Udompunturak
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ABSTRACT: The low-density lipoprotein receptor (LDL-R) has been proposed to function as a receptor for the hepatitis C virus (HCV) entry. Polymorphism of LDL-R gene may influence the clearance of virus and response to treatment. This study was conducted to evaluate the association of LDL-R gene polymorphism and the response to antiviral treatment in patients with chronic HCV infection.
A total of 112 naïve patients with HCV genotype 3 were enrolled in the study. All patients were treated with a combination of pegylated interferon and ribavirin for 24 weeks. Polymerase chain reaction combined with restriction fragment length polymorphism was used to detect the polymorphism at the LDL-R gene intron 11 loci, including intron1, intron 3.1, intron 3.2, intron 4, intron 6, exon 8, intron 11, intron 13, intron 14 and 3'UTR-2 SNPs in intron 16 region. Comparisons of genotype and allele frequency between responders and nonresponders were analyzed.
Patients had a mean age of 54 years and 43% were male. Mean HCVRNA viral load and alanine aminotransferase level were 6.3 log, IU/mL and 100 IU/L, respectively. Sustained virological response, relapse and no response were documented in 68.7%, 17.9% and 13.4%, respectively. Baseline characteristics including age, sex, body weight, aminotransferase levels and HCV RNA viral load were similar between responders and nonresponders. No statistical difference was found for either genotype distribution or allele frequency among responders and nonresponders.
This study did not provide the evidence for a role of LDL-R polymorphism the response to antiviral treatment in patients with HCV genotype 3. This indicates that a genetic component via the LDL-R may not control HCV treatment outcome in HCV genotype 3
Journal of the Medical Association of Thailand = Chotmaihet thangphaet 02/2011; 94 Suppl 1:S147-53.
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Supot Pongprasobchai,
Voravut Jianjaroonwong,
Phunchai Charatcharoenwitthaya,
Chulaluk Komoltri,
Tawesak Tanwandee,
Somchai Leelakusolvong, Nonthalee Pausawasdi,
Wichit Srikureja,
Siwaporn Chainuvati,
Varayu Prachayakul,
Sathaporn Manatsathit,
Udom Kachintorn
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ABSTRACT: To investigate the performance of erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) for predicting severe acute pancreatitis (AP).
Fifty patients with AP were prospectively enrolled. Erythrocyte sedimentation rate and CRP were measured at admission and every 12 hours for 48 hours after admission.
The patients' mean age was 50 ± 2.2 years, 64% were male, and 30% developed severe AP. Patients with severe AP had higher levels of ESR (77 ± 4.7 vs 50 ± 4.8 mm/h; P = 0.002) and CRP (218 ± 30.7 vs 97 ± 12.1 mg/L; P <0.001) at 36 hours after admission compared with those with mild AP. Erythrocyte sedimentation rates of 60 mm/h or greater predict severe AP at 36 hours with a sensitivity, specificity, and positive and negative predictive values of 86%, 57%, and 48% and 90%, whereas CRP of 150 mg/L or greater provided the results of 86%, 87%, and 75% and 93%, respectively. Elevation of either ESR or CRP at 24 hours increased the sensitivity and negative predictive value to 100%, and elevation of both ESR and CRP increased the specificity and PPV to 100%.
Erythrocyte sedimentation rate can predict severe AP with a slightly inferior performance to CRP. Combined ESR and CRP at 24 hours can predict severe AP accurately.
Pancreas 11/2010; 39(8):1226-30. · 2.39 Impact Factor
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ABSTRACT: Pancreatic cystic neoplasms are increasingly identified and their management remains uncertain. Recent studies demonstrate an evolving clinical approach.
The vast majority of asymptomatic pancreatic cysts without concerning clinical or imaging features can be observed without surgery. Clinical predictors for malignancy at surgery include male sex, age above 50 years, weight loss, and high cyst fluid carcinoembryonic antigen (CEA), but these factors are insufficient for patient selection. Endoscopic ultrasound (EUS)-guided fine needle aspiration with cyst fluid analysis for risk stratification and selective resection appears the most cost-effective approach. In addition to CEA, DNA analysis, differential protein expression, and proteomic studies of cyst fluid may be helpful in differentiating cystic lesions in selected patients. EUS-guided ethanol lavage of cysts resulted in regression; this method may have a role in treatment in the future. More future research investigating the safety of this procedure, technique modifications, and choice of agent is needed.
The approach to incidentally discover pancreatic cystic lesions is challenging due to the difficulty in preoperative definitive lesion characterization. Recently developed diagnostic and treatment strategies show promise for improved patient outcomes.
Current opinion in gastroenterology 09/2010; 26(5):506-12. · 4.33 Impact Factor
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ABSTRACT: The management of incidental pancreatic cysts is not well established because of lack of information on their natural history. International Consensus Guidelines advocate observation of asymptomatic patients with small lesions, despite limited data to support this approach.
To characterize clinical outcomes in a cohort of asymptomatic patients with incidental pancreatic cysts who underwent endoscopic ultrasound (EUS) evaluation+/-fine needle aspiration (FNA).
Overall, 317 patients underwent EUS for evaluation of pancreatic cysts from 1995 to 2005. A total of 97/317 (31%) had asymptomatic, incidentally discovered pancreatic cysts; of 97 asymptomatic patients, 93 were contacted. Of these patients, 71/93 (76%) had lesions<3 cm and benign EUS features. All were followed without operative therapy. The mean follow-up was 44 months (range, 6-123). A total of 69/71 (97%) were alive and free of symptoms of pancreatic disease; 2 patients died of unrelated causes. Among these 71 patients with lesions<3 cm, FNA was performed in 33 patients and cytology was negative for malignant cells in all. Overall, 45/71 patients had either follow-up cross-sectional imaging or EUS. All of them had stable lesions. Surveillance studies were performed with a mean follow-up of 28 months (range, 4-120). The 22 patients with lesions >3 cm and/or concerning EUS features underwent resection. Pathologic analysis revealed that 2/22 patients had adenocarcinoma and that 60% had premalignant lesions.
Endoscopic ultrasound is helpful in evaluation of patients with small incidental pancreatic cystic lesions. Asymptomatic cysts with benign radiographic and/or endosonographic features may safely be followed clinically and with serial imaging.
Surgery 09/2009; 147(1):13-20. · 3.10 Impact Factor
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Tawesak Tanwandee,
Supatsri Setthasin,
Phunchai Charatcharoenwitthaya,
Siwaporn Chainuvati,
Somchai Leelakusolvong, Nonthalee Pausawasdi,
Wichit Srikureja,
Supot Pongprasobchai,
Sathaporn Manatsathit,
Udom Kachintorn,
Patama Ekpo,
Sunsanee Senawong
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ABSTRACT: There is no established clinical role for the lens culinaris agglutinin-reactive fraction of alpha-fetoprotein (AFP-L3%) in the management of the Thai hepatocellular carcinoma (HCC) patient population. The aim of this prospective study was to evaluate clinical utility and performance characteristics of AFP-L3% for the diagnosis of HCC in Thai referral patients.
Sixty-one histologically proven HCC patients and 35 patients with other liver cancers were included for analysis.
The HCC population was comprised of 50 males and 11 females, with a mean age of 48.8 years. According to the Okuda system, three were classed as stage I, thirty-five belonged to stages II, and six were classified in stage III. An AFP-L3% a cut-off value of > 15% yielded a sensitivity of 82% (95% confidence interval [CI], 74-88%), specificity of 71% (95% CI, 58-82%), positive predictive value of 83% (95% CI, 75-90), and negative predictive value of 69% (95% CI, 56-80) for the diagnosis of HCC. In HCC patients with AFP of < 200 ng/ml, an AFP-L3% at a cut-off value of > 15% not only maintained high sensitivity of 83% and good specificity of 71% but also increased negative predictive value to 86% for the diagnosis of HCC.
AFP-L3% provides high sensitivity but with lower sensitivity in the diagnosis of HCC than total AFP in individuals with symptomatic liver mass. However, considering its high negative predictive value in patients with AFP < 200 ng/ml, AFP-L3% might be useful as an adjunctive marker, in combination with AFP, to exclude the presence of HCC.
Journal of the Medical Association of Thailand = Chotmaihet thangphaet 03/2009; 92 Suppl 2:S49-56.
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ABSTRACT: To analyze the role of endoscopy in the diagnosis and treatment of pancreatic adenocarcinoma. New developments, including molecular analysis of endoscopic tissue samples and injection of antitumor agents, are discussed.
Endoscopic ultrasound is superior to multidetector computed tomography for detection of smaller than 3-cm pancreatic tumors, and for T staging, while they are equivalent for nodal staging and assessment of resectability. Molecular analysis of endoscopic ultrasound-guided fine-needle aspiration samples has the potential to improve cancer detection. Placement of biliary self-expanding metal stents prior to Whipple resection appears to be an option to reduce stent obstruction and allow neo-adjuvant therapy. Endoscopic ultrasound-guided biliary drainage is a new approach to patients who failed to have a biliary stent placed by endoscopic retrograde cholangiopancreatography. Contrast-enhanced endoscopic ultrasound may be useful to differentiate focal inflammation from pancreatic carcinoma. Optical coherence tomography was shown to distinguish nonneoplastic from neoplastic main pancreatic duct tissue. Finally, endoscopic ultrasound-guided interstitial brachytherapy and injection of therapeutic agents into tumors have shown exciting preliminary results.
Endoscopic approaches for diagnosis and palliation of pancreatic adenocarcinoma are rapidly expanding. These new techniques show promise in the diagnosis, staging, and treatment of pancreatic malignancy.
Current Opinion in Gastroenterology 10/2007; 23(5):515-21. · 4.19 Impact Factor
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ABSTRACT: Bone morphogenetic protein (BMP)-4 is an important regulator of cellular growth and differentiation. Expression of BMP-4 has been documented in the gastric mucosa. We reported that incubation of canine parietal cells with EGF for 72 h induced both parietal cell morphological transformation and inhibition of H(+)/K(+)-ATPase gene expression through MAPK-dependent mechanisms. We explored the role of BMP-4 in parietal cell maturation and differentiation. Moreover, we investigated if BMP-4 modulates the actions of EGF in parietal cells. H(+)/K(+)-ATPase gene expression was examined by Northern blots and quantitative RT-PCR. Acid production was assessed by measuring the uptake of [(14)C]aminopyrine. Parietal cell apoptosis was quantitated by Western blots with anti-cleaved caspase 3 antibodies and by counting the numbers of fragmented, propidium iodide-stained nuclei. MAPK activation and Smad1 phosphorylation were measured by Western blots with anti-phospho-MAPK and anti-phospho-Smad1 antibodies. Parietal cell morphology was examined by immunohistochemical staining of cells with anti-H(+)/K(+)-ATPase alpha-subunit antibodies. BMP-4 stimulated Smad1 phosphorylation and induced H(+)/K(+)-ATPase gene expression. BMP-4 attenuated EGF-mediated inhibition of H(+)/K(+)-ATPase gene expression and blocked EGF induction of both parietal cell morphological transformation and MAPK activation. Incubation of cells with BMP-4 enhanced histamine-stimulated [(14)C]aminopyrine uptake. BMP-4 had no effect on parietal cell apoptosis, whereas TGF-beta stimulated caspase-3 activation and nuclear fragmentation. In conclusion, BMP-4 promotes the induction and maintenance of a differentiated parietal cell phenotype. These findings may provide new clues for a better understanding of the mechanisms that regulate gastric epithelial cell growth and differentiation.
AJP Gastrointestinal and Liver Physiology 10/2007; 293(3):G607-14. · 3.43 Impact Factor
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ABSTRACT: Incubation of purified (>95%) canine parietal cells in primary culture with epidermal growth factor for 7-16 hours stimulates H(+)K(+)-adenosine triphosphatase gene expression. In this study, we examined the effect of prolonged stimulation (72 hours) of the parietal cells with epidermal growth factor.
H(+)K(+)-adenosine triphosphatase protein and gene expression were assessed by immunohistochemistry and Northern blots. Mitogen-activated protein kinase and Akt activation were quantitated by kinase assays and Western blots with specific antiphospho antibodies. Akt overexpression was achieved by adenovirus-mediated gene transfer of a constitutively active Akt gene.
Epidermal growth factor changed the morphology of the cultured cells, which acquired the appearance of fusiform cells, and it inhibited H(+)K(+)-adenosine triphosphatase gene expression. Staining of the cells both with anti-H(+)K(+)-adenosine triphosphatase antibodies and with Texas Red-labeled Dolichos biflorus lectin confirmed that the fusiform cells expressed markers of parietal cell differentiation. Epidermal growth factor stimulated mitogen-activated protein kinase with 2 peaks of activation, observed after 5 minutes and 72 hours, whereas it activated Akt after 5 minutes but not 72 hours of incubation. Overexpression of Akt blocked both epidermal growth factor-induced morphological transformation and inhibition of H + K + -adenosine triphosphatase gene expression. Identical results were observed in the presence of the mitogen-activated protein kinase inhibitor PD98059.
Activation of the Akt signal-transduction pathway seems to be a crucial event for the induction of parietal cell maturation and differentiation.
Gastroenterology 11/2004; 127(4):1150-61. · 11.68 Impact Factor
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ABSTRACT: G17 has growth promoting and antiapoptotic effects on the AR4-2J pancreatic acinar cell line. We previously reported that whereas MAPK regulates G17-stimulation of AR4-2J cell proliferation, Akt mediates the antiapoptotic action of G17. We examined the signal-transduction pathways mediating G17 stimulation of AR4-2J cell growth and survival. G17 activated the small GTP binding proteins Ras, Rac, Rho, and Cdc42. Transduction of the cells with adenoviral vectors expressing dominant negative Akt, Ras, Rho, and Cdc42 but not dominant negative Rac inhibited AR4-2J cell proliferation and survival. Both exoenzyme C3 from Clostridium botulinum (C3), a toxin known to inactivate Rho, and PD98059, a MAPK inhibitor, reversed G17 inhibition of AR4-2J cell apoptosis. G17 induction of Akt activation was reduced by >60% by both dominant negative Ras and Rho and by 30% by dominant negative Cdc42. In contrast, G17-stimulated MAPK activation was blocked by >80% by dominant negative Ras but not by dominant negative Rho and Cdc42. Similar results were observed in the presence of C3. Dominant negative Rac failed to affect G17 induction of both Akt and MAPK, whereas it inhibited sorbitol by almost 50% but not G17-stimulated activation of p38 kinase. Thus G17 promotes AR4-2J cell growth and survival through the activation of multiple GTP binding proteins, which, in turn, regulate different protein kinase cascades. Whereas Ras activates Akt and MAPK, Rho and Cdc42 appear to regulate Akt and possibly other as yet unidentified kinases mediating the growth-stimulatory actions of G17.
AJP Gastrointestinal and Liver Physiology 09/2004; 287(3):G715-25. · 3.43 Impact Factor
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ABSTRACT: We examined expression, function, and regulation of the cyclooxygenase (COX)-2 gene in gastric parietal cells. COX-2-specific mRNA was isolated from purified (>95%) canine gastric parietal cells in primary culture and measured by Northern blots using a human COX-2 cDNA probe. Carbachol was the most potent inducer of COX-2 gene expression. Gastrin and histamine exhibited minor stimulatory effects. Carbachol-stimulated expression was inhibited by intracellular Ca(2+) chelator 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid-AM (90%), protein kinase C (PKC) inhibitor GF-109203X (48%), and p38 kinase inhibitor SB-203580 (48%). Nuclear factor (NF)-kappaB inhibitor 1-pyrrolidinecarbodithioic acid inhibited carbachol-stimulated expression by 80%. Similar results were observed in the presence of adenoviral vector Ad.dom.neg.IkappaB, which expresses a repressor of NF-kappaB. Addition of SB-203580 with Ad.dom.neg.IkappaB almost completely blocked carbachol stimulation of COX-2 gene expression. We examined the effect of carbachol on PGE(2) release by enzyme-linked immunoassay. Carbachol induced PGE(2) release. Ad.dom.neg.IkappaB, alone or with SB-203580, produced, respectively, partial (70%) and almost complete (>80%) inhibition of carbachol-stimulated PGE(2) production. Selective COX-2 inhibitor NS-398 blocked carbachol-stimulated PGE(2) release without affecting basal PGE(2) production. In contrast, indomethacin inhibited both basal and carbachol-stimulated PGE(2) release. Carbachol induces COX-2 gene expression in the parietal cells through signaling pathways that involve intracellular Ca(2+), PKC, p38 kinase, and activation of NF-kappaB. The functional significance of these effects seems to be stimulation of PGE(2) release.
AJP Gastrointestinal and Liver Physiology 06/2002; 282(6):G1069-78. · 3.43 Impact Factor
