Biomedical subjects

C C Chen

Publications and source records attributed to C C Chen.

At least 199 records · Page 11Linked to original sources

PubMed1999

Spatial pattern summation is phase-insensitive in the fovea but not in the periphery.

We measured the effect of phase coherence on the detectability of a chain of Gabor patches. The stimuli were elongated patterns consisting of 1-8 vertical Gabor patches, aligned vertically and either in phase or 180 deg out of phase from their immediate neighbors. In the fovea, the phase configuration had no effect on detection threshold, suggesting a full-wave rectification operation mediating foveal spatial summation. At 5 deg in the periphery, detection thresholds for the in-phase configuration were lower than those for the alternating-phase configuration, to an extent compatible with a half-wave rectification operation mediating peripheral spatial summation.

Computer Simulation↗

PubMed1999

Signal transduction of arginine vasopressin-induced arachidonic acid release in H9c2 cardiac myoblasts: role of Ca2+ and the protein kinase C-dependent activation of p42 mitogen-activated protein kinase.

The mechanism of arginine vasopressin (AVP)-induced arachidonic acid (AA) release was examined in the cardiac myoblast cell line, H9c2. Stimulation of cells with AVP induced dose-dependent AA release, and this effect was completely inhibited by the V1 receptor antagonist, d(CH)5[Tyr(Me)2]AVP. AVP also produced dose-dependent stimulation of inositol phosphate formation; this was not affected by pertussis toxin, indicating the presence of the V1 receptor/Gq protein/PLCbeta pathway in H9c2 cells. The concentration-response curves for these two effects of AVP overlapped. AVP induced a rapid increase in [Ca2+]i, followed by a sustained increase. The Ca2+ ionophore, A23187 or ionomycin, mimicked the effect of AVP, whereas the protein kinase C (PKC) activator, TPA, only induced a slight increase in AA release. Both the AVP- or A23187-stimulated AA release and the AVP-induced sustained [Ca2+]i increase were completely blocked in the absence of external Ca2+. The receptor-operated Ca2+ channel blocker, SKF 96365, and the inorganic Ca2+ channel blockers, Ca2+ and Ni2+, also inhibited the AVP-induced AA release. Western blots demonstrated expression of PKCalpha, betaI, epsilon, delta, and zeta in H9c2 cells; PKC inhibitors (staurosporine or Ro 31-8220) or down-regulation of PKCalpha, betaI, epsilon, and delta by long-term (24 h) TPA treatment caused a partial blockade of the AVP-induced response, whereas the A23187-induced AA release was unaffected by down-regulation of these isoforms. AVP-induced, but not A23187-induced, AA release was partially blocked by the p42 MAPK cascade inhibitor, PD 98059. AVP and TPA, but not A23187, induced an increase in activity and tyrosine phosphorylation of p42 MAPK, together with a molecular weight shift, consistent with phosphorylation, of cytosolic PLA2. AVP- or TPA-induced activation and tyrosine phosphorylation of p42 MAPK were completely blocked by down-regulation of PKCalpha, betaI, epsilon, and delta, but still occurred, together with the cytosolic PLA2 mobility shift, in the absence of external Ca2+. These results show that AVP-induced AA release in H9c2 cells is secondary to activation of the V1 receptor/Gq protein/PLCP pathway, leading to an influx of extracellular Ca2+ and activation of PKCalpha, betaI, epsilon, and delta. The influx of extracellular Ca2- and DAG act, respectively, through PKC-/MAPK-independent or PKC-dependent MAPK pathways to mediate AA release.

Arachidonic Acid↗

PubMed1999

Lack of utility of (111)In-pentetreotide scintigraphy in localizing ectopic ACTH producing tumors: follow-up of 18 patients.

Octreotide scintigraphy has been advocated as the principal imaging modality for localizing ectopic ACTH-secreting tumors in Cushing's syndrome. To assess its usefulness we reviewed the course of 18 consecutive patients with ectopic ACTH-producing tumor. Imaging included (111)In-pentetreotide scintigraphy, computed tomography (CT), and/or magnetic resonance imaging (MRI). Tumor was detected initially in 7/18 patients, and in 3/18 during follow-up. No ACTH-secreting tumor was detected by octreotide scintigraphy when CT/ MRI were negative. Seventeen of forty octreotide scintigrams were abnormal. CT and/or MRI confirmed tumors in 10, but demonstrated nonendocrine lesions in association with 6 false positive octreotide scintigrams. Hepatic venous sampling for ACTH refuted one lesion detected by octreotide and CT scans. Twenty-three of forty octreotide scintigrams were normal. Of these, 8 were false negative, as CT and/or MRI detected tumor; 10 agreed with negative CT and MRI, and 5 correctly refuted false positive CT and/or MRI scans. Repeated CT/ MR, but not octreotide scintigraphy, led to tumor resection in 2 patients. We conclude that octreotide scintigraphy does not offer greater sensitivity than CT/MRI and that false positive scans are common. Although octreotide scintigraphy may be helpful in selected cases, it is not a significant advance over conventional imaging for ectopic ACTH-secreting tumors.

ACTH Syndrome, Ectopic↗

PubMed1999

Inhibition by magnolol of formylmethionyl-leucyl-phenyl alanine-induced respiratory burst in rat neutrophils.

The influence of the plant product magnolol on neutrophil superoxide anion (O2-*) generation has been investigated in the rat. Intraperitoneal injection of magnolol (30mg kg(-1)) significantly inhibited the formylmethionyl-leucyl-phenylalanine (fMLP)-induced respiratory burst in rat whole blood ex-vivo. Magnolol also inhibited the 02-* generation with an IC50 (concentration resulting in 50% inhibition) of 15.4+/-1.6 microM and O2 consumption in rat neutrophils in-vitro. Magnolol weakly inhibited the O2-* generation in the xanthine-xanthine oxidase system, decreased cellular cyclic AMP level and had no effect on cyclic GMP levels. It weakly inhibited neutrophil cytosolic protein kinase C activity but did not alter porcine heart protein kinase A activity. Magnolol attenuated fMLP-induced protein tyrosine phosphorylation with an IC50 of 24.0+/-1.9 microM and the phosphorylation of mitogen-activated protein kinase p42/44 with an IC50 of 28.5+/-4.5 microM. However, magnolol alone activated neutrophil phospholipase D activity as determined by the formation of phosphatidic acid and phosphatidyl-ethanol in the presence of ethanol. In the presence of NADPH, the arachidonate-activated NADPH oxidase activity in a cell-free system was weakly suppressed by magnolol. These results suggest that the inhibition of respiratory burst in fMLP-activated neutrophils by magnolol is probably attributable mainly to the attenuation of protein tyrosine phosphorylation and p42/44 mitogen-activated protein kinase activation, and partly to the suppression of protein kinase C and NADPH oxidase activities.

Animals↗

PubMed1999

Comprehensive evaluation of 35 patients with lymphangioleiomyomatosis.

OBJECTIVES: To evaluate comprehensively the characteristics of lymphangioleiomyomatosis (LAM), with emphasis on the application of imaging and immunohistochemical methods. DESIGN: Prospective study. PATIENTS: Thirty-five female subjects with LAM. SETTING: Clinical Center, National Institutes of Health. INTERVENTIONS: BAL, pulmonary function test, ventilation/perfusion lung scans, CT of the chest and abdomen, ultrasonography of abdomen, and immunohistochemical study of lung biopsy specimens. RESULTS: Most patients had exertional dyspnea (83%) and pneumothorax (69%). BAL did not show diagnostic changes. The most common abnormalities on pulmonary function tests were decreased diffusing capacity of carbon monoxide (83%), hypoxemia (57%), and airway obstruction (51%). Bronchodilator response was found in 26% of patients. CT, which is almost pathognomonic, showed numerous thin-walled cysts throughout both lungs in all patients. Thirty-four patients (97%) had abnormal ventilation and/or perfusion lung scans. An unusual "speckling" pattern was observed on ventilation scans of 74% of patients. Common extrapulmonary features were retroperitoneal adenopathy (77%) and renal angiomyolipomas (60%). The percentage of abnormal smooth muscle cells (LAM cells), reactive with HMB45, varied from 17 to 67% in 10 lung biopsy specimens. CONCLUSIONS: Improved diagnostic methods have defined the abnormalities in patients with pulmonary LAM and increased the potential for early recognition and treatment of this disorder. Patients with LAM should be evaluated for bronchodilator responsiveness and may benefit from a trial of bronchodilators.

Abdomen↗

PubMed1999

p38 but not p44/42 mitogen-activated protein kinase is required for nitric oxide synthase induction mediated by lipopolysaccharide in RAW 264.7 macrophages.

Protein kinase C (PKC)-alpha, -betaI, and -delta are known to be involved in the lipopolysaccharide (LPS)-induced nitric oxide (NO) production in RAW 264.7 macrophages. The role of mitogen-activated protein kinases (MAPK) p44/42 and p38 in the LPS effect was studied further. LPS-mediated NO release and the inducible form of NO synthase expression were inhibited by the p38 inhibitor, SB 203580, but not by the MAPK kinase inhibitor, PD 98059. Ten-minute treatment of cells with LPS resulted in the activation of p44/42 MAPK, p38, and c-Jun NH2-terminal kinase. Marked or slight activation, respectively, of p44/42 MAPK or p38 was also seen after 10-min treatment with 12-O-tetradecanoylphorbol-13-acetate, but c-Jun NH2-terminal kinase activation did not occur. Tyrosine kinase inhibitor, genestein, attenuated the LPS-induced activation of both p44/42 MAPK and p38, whereas the PKC inhibitors, Ro 31-8220 and calphostin C, or long-term treatment with 12-O-tetradecanoylphorbol-13-acetate resulted in inhibition of p44/42 MAPK activation, but had only a slight effect on p38 activation, indicating that LPS-mediated PKC activation resulted in the activation of p44/42 MAPK. Nuclear factor-kappaB (NF-kappaB)-specific DNA-protein-binding activity in the nuclear extracts was enhanced by 10-min, 1-h, or 24-h treatment with LPS. Analysis of the proteins involved in NF-kappaB binding showed translocation of p65 from the cytosol to the nucleus after 10-min treatment with LPS. The onset of NF-kappaB activation correlated with the cytosolic degradation of both inhibitory proteins of NF-kappaB, IkappaB-alpha and IkappaB-beta. IkappaB-alpha was resynthesized rapidly after loss (1-h LPS treatment), whereas IkappaB-beta levels were not restored until after 24-h treatment. SB 203580 but not PD 98059 inhibited the LPS-induced stimulation of NF-kappaB DNA-protein binding. Thus, activation of p38 but not p44/42 MAPK by LPS resulted in the stimulation of NF-kappaB-specific DNA-protein binding and the subsequent expression of inducible form of NO synthase and NO release in RAW 264.7 macrophages.

Animals↗

PubMed1999

Type 1 GM1 gangliosidosis with basal ganglia calcification: a case report.

This report concerns a 10-month-old boy, admitted to the Veterans General Hospital-Kaohsiung with generalized tonic convulsion and aspiration pneumonia. He was found to have had developmental regression, progressive hypotonia and hepatosplenomegaly since four months of age. Physical examination revealed a large head circumference (97th percentile), frontal bossing, depressed nasal bridge, hepatosplenomegaly, broad hands and short fingers. Neurologic examination showed poor control of eye movement, profound hypotonia, muscle weakness, brisk deep tendon reflexes and Babinski's sign. Hypoplasia of the vertebral bodies with anterior beaking, wedge-shaped metacarpals, spatulated ribs and a J-shaped sella turcica were displayed on bone radiographs. Cranial computerized tomography scans showed diffuse brain atrophy, dilated ventricles and calcification of the bilateral basal ganglia. Vacuolated lymphocytes were noted in a peripheral blood smear. Type 1 GM1 gangliosidosis was diagnosed based on a deficiency of beta-galactosidase activity. To our knowledge, basal ganglia calcification in type 1 GM1 gangliosidosis has never been reported in the literature. We suggest that type 1 GM1 gangliosidosis be considered in the differential diagnosis of patients with an early onset of neurologic decline, organomegaly and basal ganglia calcification.

Basal Ganglia Diseases↗

PubMed1999

Specificity of somatostatin receptor scintigraphy: a prospective study and effects of false-positive localizations on management in patients with gastrinomas.

UNLABELLED: Somatostatin receptor scintigraphy (SRS) is being increasingly used both for localization and, in some cases, diagnosis of various diseases. There are no prospective studies of its specificity or occurrence of false-positive results and their effects on management. This study was designed to address both of these issues. METHODS: Over a 40-mo period, 146 consecutive patients with Zollinger-Ellison syndrome (ZES) undergoing 480 SRS examinations were studied prospectively. Patients were admitted at least yearly and underwent SRS as well as conventional imaging studies (ultrasonography, CT, MRI) and angiography, if necessary. All admissions were assigned to one of five different clinical categories in which imaging studies had different purposes. SRS localizations were classified as true-positive or false-positive based on preset criteria. A false-positive result was determined to change clinical management based on five preset criteria. RESULTS: Of all SRS examinations, 12% resulted in a false-positive localization for a neuroendocrine tumor or its metastases, resulting in a sensitivity of 71%, specificity of 86% and positive and negative predictive values of 85% and 52%, respectively. Extra-abdominal false-positive localizations (2/3) were more common than intra-abdominal (1/3). Thyroid disease, breast disease and granulomatosis lung disease were the most frequent causes of extra-abdominal false-positive localizations. Accessory spleens, localization to previous operative sites, renal parapelvic cysts and various procedural aspects were the most frequent causes of intra-abdominal false-positive localizations. Of all SRS studies, 2.7% resulted in a false-positive result that altered management. CONCLUSION: False-positive SRS localization occurs in 1 of 10 patients with ZES. By having a thorough understanding of diseases or circumstances that result in false-positive localization and comparing the SRS result with the clinical context, the percentage of patients in whom false-positive localization results in altered management can be reduced to below 3% and the correct diagnosis made in almost every case.

False Positive Reactions↗

PubMed1999

Subtype-selective antagonism of N-methyl-D-aspartate receptors by felbamate: insights into the mechanism of action.

Felbamate is an anticonvulsant used in the treatment of seizures associated with Lennox-Gastaut syndrome and complex partial seizures that are refractory to other medications. Its unique clinical profile is thought to be due to an interaction with N-methyl-D-aspartate (NMDA) receptors, resulting in decreased excitatory amino acid neurotransmission. To further characterize the interaction between felbamate and NMDA receptors, recombinant receptors expressed in Xenopus oocytes were used to investigate the subtype specificity and mechanism of action. Felbamate reduced NMDA- and glycine-induced currents most effectively at NMDA receptors composed of NR1 and NR2B subunits (IC50 = 0.93 mM), followed by NR1-2C (2.02 mM) and NR1-2A (8.56 mM) receptors. The NR1-2B-selective interaction was noncompetitive with respect to the coagonists NMDA and glycine and was not dependent on voltage. Felbamate enhanced the affinity of the NR1-2B receptor for the agonist NMDA by 3.5-fold, suggesting a similarity in mechanism to other noncompetitive antagonists such as ifenprodil. However, a point mutation at position 201 (E201R) of the epsilon2 (mouse NR2B) subunit that affects receptor sensitivity to ifenprodil, haloperidol, and protons reduced the affinity of NR1-epsilon2 receptors for felbamate by only 2-fold. Furthermore, pH had no effect on the affinity of NR1-2B receptors for felbamate. We suggest that felbamate interacts with a unique site on the NR2B subunit (or one formed by NR1 plus NR2B) that interacts allosterically with the NMDA/glutamate binding site. These results suggest that the unique clinical profile of felbamate is due in part to an interaction with the NR1-2B subtype of NMDA receptor.

Algorithms↗

PubMed1999

Botulism: heart rate variation, sympathetic skin responses, and plasma norepinephrine.

BACKGROUND: Botulism may involve the autonomic nervous system. METHODS: We assessed the autonomic function of 6 botulism patients with heart rate variations, sympathetic skin responses, and plasma norepinephrine. RESULTS: Two weeks after onset, all the patients had absent sympathetic skin response in the palm and sole. Compared with controls, the heart rate variation of botulism patients was significantly decreased at rest (3.1 +/- 1.2% vs. 20.9 +/- 2.0%, p = 0.0018) and during deep breathing (4.3 +/- 2.3% vs. 29.7 +/- 2.6%, p = 0.0018). The botulism patients had significantly lower plasma norepinephrine levels (supine 29.2 +/- 10.1 pg/ml vs. 257.5 +/- 65.8 pg/ml, p = 0.0018; standing 40.3 +/- 13.1 pg/ml vs. 498.5 +/- 85.6 pg/ml, p = 0.0018). The heart rate variation and sympathetic skin response was greatly improved 6 months after onset. CONCLUSIONS: Heart rate variation, absence of sympathetic skin response, and low plasma norepinephrine are all manifestations of autonomic dysfunction in botulism patients.

Adult↗

PubMed1999

[TGF-beta 1 in the experimentally induced inflammatory periodontal tissues in miniature swines].

TGF-beta 1 is a multifunctional molecule which has unique and potent effects on many target cells and tissues. TGF-beta 1 may promote inflammatory reaction by certain intercellular interaction. TGF-beta 1 at extremely low concentrations shows strong chemotatic activity for mononuclear phagocytes and stimulates bone resorption by enhancing production of PGE2. On the other hand, TGF-beta 1 plays a very important role in the regulation of extracellular matrix turnover presumably by modulating the action of other growth factors on matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinases (TIMPs) expression. TGF-beta 1 was identified intra- and extracellularly in the inflamed gingival tissues and the distribution was associated with areas of inflammation. Sixteen miniature swines were used in this experimental gingivitis/periodontitis study. The ligatures were placed in situ for periods of 3, 5, 8 and 13 weeks and peroral innoculations of Porphyromonas gingivalis/Actinomyces viscosus into the ligatures were carried out only in the experimental group. ELISA was used to measure the levels of TGF-beta 1 in gingival tissues from the experimental and control groups. Recording of the clinical periodontal parameters was performed and the proportion of black-pigmented Bacteroides in the ligature (plaques) removed immediately prior to the biopsies was recorded. The results revealed that the concentration of TGF-beta 1 of the experimental group was higher and significantly different in statistics on the period of third week than that of the control group. The concentration of TGF-beta 1 was significantly different between the third week and the thirteenth week in the experimental group, and was negatively related to the time-length of ligatures. Furthermore, the concentration of TGF-beta 1 was negatively related to the changes of the calculus index and gingival index. These data indicated that the concentration of TGF-beta 1 of gingival tissue exhibited dynamic changes associated with the progression of experimental periodontal inflammation. The levels of TGF-beta 1 in gingival tissue may be valuable in detecting the inflammatory reaction of periodontal tissues.

Animals↗

PubMed1999

Clinical and manometric evaluation of postoperative fecal soiling in patients with Hirschsprung's disease.

We examined the usefulness of manometry as an indicator of fecal soiling after surgical correction of Hirschsprung's disease, and attempted to identify measures to alleviate this complication. Sequential clinical and manometric evaluations of postoperative fecal soiling were performed in 35 patients (30 males, 5 females) with Hirschsprung's disease. The resting anal pressure (RAP), resting rectal pressure, and anorectal pressure gradient (ARPG) all decreased significantly from the preoperative values after corrective pull-through surgery. This correlated well with the clinical change from preoperative obstipation to frequent stool passage or soiling postoperatively. A total of 80% of the patients had mild or severe fecal soiling within 4 years after surgery, but only 40% had persistent symptoms thereafter. The manometric profile showed significant elevations in RAP and ARPG 4 years after surgery. Only five patients had positive conversion of rectoanal sphincteric inhibitory reflex (RASIR) after surgery, and the presence of RASIR was not related to continence. Also, there was no difference in the manometric profile between patients with and without RASIR. However, patients without RASIR were prone to suffer from severe diarrhea or soiling on consuming specific foods or catching cold. In conclusion, anorectal manometry can be an objective tool for the evaluation of postoperative fecal soiling in patients with Hirschsprung's disease. The low conversion rate of RASIR combined with hypersensitivity of the bowel in patients with Hirschsprung's disease suggests that some kind of enteric nervous system disorder might exist other than aganglionosis.

Adolescent↗

PubMed1999

Effects of excitatory amino acids and nimodipine on calcium currents in cultured rat cortical neurons.

AIM: To study the effect of excitatory amino acid (EAA) and calcium channel blocker on neuronal calcium channels. METHODS: With path-clamp technique (whole-cell recording), the effects of Bay-K-8644, cesium glutamate, potassium aspartate, and nimodipine (Nim) on calcium currents (ICa) in cultured cortical neurons of neonatal rats were studied. RESULTS: ICa was raised obviously by Bay-K-8644 and glutamate. ICa was raised concentration-dependently by aspartate (0.5, 5, 50 mmol.L-1), with increasing rates 15% +/- 3%, 37% +/- 3%, and 53% +/- 6%, respectively. The inhibition of ICa was obvious while adding Nim in the bath solution. With Nim 10 mumol.L-1, the inhibitory rate was 46% +/- 4%. CONCLUSION: EAA had increasing effects on neuronal calcium currents and Nim inhibited Ca2+ influx in neurons.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗

PubMed1999

Interleukin-1 beta in oral submucous fibrosis, verrucous hyperplasia and squamous cell carcinoma tissues.

Interleukin-1 beta (IL-1 beta) has been proven to be a multi-effect mediator of inflammation including in the promotion of inflammatory cells to move from blood to inflamed tissues, the regulation of the synthesis and decomposition of extra-cellular matrix, and indirectly in causing bone resorption and inhibition of bone growth. In this study, the amounts of IL-1 beta in the biopsied specimens of normal oral mucosa, oral submucous fibrosis (OSF), oral squamous cell carcinoma (OSCC), and verrucous hyperplasia (VerH) were quantified by ELISA. The results showed that the amounts of IL-1 beta (pg per mg tissue, mean +/- SD) in normal oral mucosa, OSF, OSCC, and VerH were 1.07 +/- 0.53, 0.76 +/- 0.56, 4.37 +/- 0.87 and 3.97 +/- 1.93 respectively. There were no significant differences (p > 0.05, Mann-Whitney U Test) between the amounts of IL-1 beta in normal oral mucosa and OSF, and between VerH and OSCC. However, a significant difference in IL-1 beta level was found (p < 0.001) between normal oral mucosa and OSCC or VerH. Immunohistochemistry staining technique using antibody against IL-1 beta showed positive staining in hyperplastic epithelium (VerH) and tumor cells of OSCC. These results might suggest a correlation between the amounts of IL-1 beta in oral precancerous and cancerous lesions and cell transformation. On the other hand, the amount of IL-1 beta did not change significantly as OSF progressed. Thus, IL-1 beta levels may not be useful to gauge the seriousness of fibrosis, but the gradual increase in IL-1 beta level from normal oral mucosa through VerH to OSCC suggests that IL-1 beta may play an important role in oral carcinogenesis.

Adult↗

PubMed1999

Acute respiratory distress syndrome due to tuberculosis in a child after allogeneic bone marrow transplantation for acute lymphoblastic leukemia.

We report the occurrence of tuberculosis in a 10-year-old Taiwanese boy, approximately 4 months after he received a matched-related bone marrow transplantation from his sister for acute T-cell lymphoblastic leukemia. After transplantation, grade III acute graft-versus-host disease developed and the patient was treated with prednisolone and cyclosporine. Marrow failure was noted on day 77 post-transplantation, however, after an episode of herpes zoster infection. Interstitial pneumonia, diagnosed on the basis of chest x-ray and computed tomography findings, occurred on day 120. Histologic examination of an open-lung biopsy specimen showed caseating granulomas and a few acid-fast bacilli. The patient died of acute respiratory distress syndrome, despite immediate implementation of antituberculosis therapy. Sputum cultures grew Mycobacterium tuberculosis 5 weeks later. This report demonstrates that the possibility of tuberculosis needs to be considered in immunocompromised patients, and that appropriate prophylaxis should be instituted in areas where tuberculosis is endemic.

Bone Marrow Transplantation↗

PubMed1999

What is new in nuclear medicine imaging?

Modern nuclear medicine tests can be of great help to today's surgical oncologists. The new techniques of positron emission tomography (PET) and single photon emission computed tomography (SPECT), and the availability of new radiopharmaceuticals for localization of tumors and assessment of organ function provide information vital to the management of oncology patients.

Fluorodeoxyglucose F18↗

PubMed1999

Prophylactic octreotide reduces the severity of histopathologic changes and hemodynamic shock in early taurodeoxycholate-induced experimental pancreatitis.

The findings related to the effects of somatostain and octreotide in experimental and clinical acute pancreatitis are so far inconclusive. In this study, we examined the early effects of prophylactic octreotide in acute experimental pancreatitis. Serum levels of amylase and lipase, pancreatic histopathology and systemic hemodynamic profiles, including mean arterial pressure, cardiac index, systemic vascular resistance and heart rate, were evaluated 5 hours after glycodeoxycholic acid (GDOC) or sodium taurodeoxycholate (TDC)-induced pancreatitis with or without prophylactic octreotide (10 micrograms/Kg) in rats, GDOC and TDC induced mild and severe pancreatitis, respectively. Octreotide significantly reduced serum levels of amylase and lipase at 5 hours in GDOC and TDC-induced pancreatitis. Octreotide significantly reduced the severity of pancreatic edema, necrosis and hemorrhage in TDC-induced pancreatitis. In addition, hemodynamic shock in TDC-induced pancreatitis was improved significantly by the administration of octreotide (mean arterial pressure 70.3 +/- 7.7 vs. 95.0 +/- 3.5 mmHg, p < 0.05; cardiac index 16.7 +/- 2.5 vs. 24.0 +/- 5.1 ml.min-1. 100 g-1, p < 0.05). However, octreotide did not show significant beneficial effect in pancreatic histopathology and hemodynamics in GDOC-induced pancreatitis. Thus we conclude that prophylactic octreotide improves pancreatic histopathology and hemodynamic shock in TDC-induced pancreatitis.

Acute Disease↗

PubMed1998

Antisense oligonucleotides targeting protein kinase C-alpha, -beta I, or -delta but not -eta inhibit lipopolysaccharide-induced nitric oxide synthase expression in RAW 264.7 macrophages: involvement of a nuclear factor kappa B-dependent mechanism.

The signaling pathway for protein kinase C (PKC) activation and the role of PKC isoforms in LPS-induced nitric oxide (NO) release were studied in RAW 264.7 macrophages. The tyrosine kinase inhibitor genestein attenuated LPS-induced NO release and inducible nitric oxide synthase (iNOS) expression, as did the phosphoinositide-specific phospholipase C (PI-PLC) inhibitor U73122 and the phosphatidylcholine-specific phospholipase C (PC-PLC) inhibitor D609. LPS stimulated phosphatidylinositol (PI) hydrolysis and PKC activity in RAW cells; both were inhibited by genestein. The PKC inhibitors (staurosporine, calphostin C, Ro 31-8220, or Go 6976) or long-term 12-O-tetradecanoylphorbol 13-acetate (TPA) treatment also resulted in inhibition of LPS-induced NO release and iNOS expression. Western blot analysis showed expression of PKC-alpha, -betaI, -delta, -eta, and -zeta in RAW cells; down-regulation of PKC-alpha, -betaI, and -delta, but not -eta, was seen after long-term TPA treatment, indicating the possible involvement of one or all of PKC-alpha, -betaI, and -delta, but not -eta, in LPS-mediated effects. Treatment with antisense oligonucleotides for these isoforms further demonstrated the involvement of PKC-alpha, -betaI, and delta, but not -eta, in LPS responses. Stimulation of cells with LPS for 1 h caused activation of NF-kappaB in the nuclei by detection of NF-kappaB-specific DNA-protein binding; this was inhibited by genestein, U73122, D609, calphostin C, or antisense oligonucleotides for PKC-alpha, -betaI, and -delta, but not -eta. These data suggest that LPS activates PI-PLC and PC-PLC via an upstream tyrosine kinase to induce PKC activation, resulting in the stimulation of NF-kappaB DNA-protein binding, then initiated the expression of iNOS and NO release. PKC isoforms alpha, betaI, and delta were shown to be involved in the regulation of these LPS-induced events.

Animals↗