ABSTRACT
Depending on the intracellular buffering of calcium by chelation, zinc has the following two apparent effects on neuronal excitability: enhancement or reduction. Zinc increased tonic activity in the depolarized state when neurons were intracellularly dialyzed with EGTA but attenuated the neuronal activity when BAPTA was used as an intracellular calcium buffer. This suggests that neuronal excitability can be modulated by zinc, depending on the internal calcium buffering capacity. In this study, we elucidated the mechanisms of zinc-mediated alterations in neuronal excitability and determined the effect of calcium-related channels on zinc-mediated alterations in excitability. The zinc-induced augmentation of firing activity was mediated via the inhibition of small-conductance calcium-activated potassium (SK) channels with not only the contribution of voltage-gated L-type calcium channels (VGCCs) and ryanodine receptors (RyRs), but also through the activation of VGCCs via melastatin-like transient receptor potential channels. We suggest that zinc modulates the dopaminergic neuronal activity by regulating not only SK channels as calcium sensors, but also VGCCs or RyRs as calcium sources. Our results suggest that the cytosolic calcium-buffering capacity can tightly regulate zinc-induced neuronal firing patterns and that local calcium-signaling domains can determine the physiological and pathological state of synaptic activity in the dopaminergic system.
Subject(s)
Animals , Rats , Calcium , Calcium Channels, L-Type , Cytosol , Dopaminergic Neurons , Egtazic Acid , Electrophysiology , Fires , Neurons , Potassium , Ryanodine Receptor Calcium Release Channel , Transient Receptor Potential Channels , ZincABSTRACT
BACKGROUND/AIMS: Stomach cancer is the most common malignancy and one of the leading causes of cancer-related death in Korea. The early diagnosis and treatment of gastric cancer are very important because the prognosis of early gastric cancer is excellent. Gastric screening may provide an opportunity to detect asymptomatic early gastric cancer. We analyzed the characteristics of gastric cancer diagnosed with a health screening test to evaluate the usefulness of a screening program for gastric cancer. METHODS: We retrospectively reviewed the clinicopathological characteristics of 111 gastric cancer patients diagnosed using gastric endoscopy as a gastric screening test at the Health Promotion Center of Kyungpook National University Hospital from July 1997 through December 2005. RESULTS: The incidence of gastric cancer was 0.38% and the mean patient age was 58.5 years old. The proportion of early gastric cancer was 73% of all gastric cancer. In 55 cases, constituting 49.6% of all gastric cancer and 68% of early gastric cancer, the lesions were confined to the mucosa. The most common macroscopic types were type IIc in early gastric cancer and Borrmann type 3 in advanced gastric cancer. There were significant positive correlations between lymph node metastasis and both the depth of tumor invasion and size of the lesion. The 5-year survival rates are 82.7% in total gastric cancer and 97.2% in early gastric cancer. CONCLUSIONS: Gastric cancer detected during health screening has a favorable prognosis because gastric cancer confined to the mucosa predominates and early gastric cancer detected at screening has a lower incidence of metastasis to regional lymph nodes.
Subject(s)
Humans , Early Diagnosis , Endoscopy , Health Promotion , Incidence , Korea , Lymph Nodes , Mass Screening , Mucous Membrane , Neoplasm Metastasis , Prognosis , Retrospective Studies , Stomach Neoplasms , Survival RateABSTRACT
BACKGROUND/AIMS: Deoxycholic acid (DCA) has been appeared to be an endogenous colon tumor promoter. In this study, we investigated whether DCA induces nuclear factor-kappa B (NF-kappa B) activation and IL-8 expression, and tauroursodeoxycholic acid (TUDC) inhibits this signaling in HT-29 cells. METHODS: After DCA treatments, time courses of NF-kappa B binding activity were determined by electrophoretic mobility shift assay (EMSA). Also, we performed Western blotting of I kappa B alpha to confirm NF-kappa B activation. Time and concentration courses of DCA-induced secretion of IL-8 were measured with ELISA in supernatants of cultured media from the cells. To evaluate the role of NF-kappa B, IL-8 levels were assessed after pretreatment with using phosphorothioate-modified anti-sense oligonucleotides (ODN). Moreover, DCA-induced secretions of IL-8 were measured after pretreatment with TUDC. RESULTS: DCA dose-dependently induced prominent NF-kappa B binding complexes from 30 min to 8 hr and degradation of I kappa B alpha. The secretions of IL-8 were increased with DCA (50~200 micro M) treatment in a time and dose-dependent manner. Pre-incubation of the cells with TUDC (0.1~10 micro M) for 2 hours caused significant decreases in DCA induced IL-8 secretion. However, transient transfection using p50 or p65 AS-ODN showed no effect on IL-8 secretion. CONCLUSIONS: DCA may play as a colonic tumor promoter through anti-apoptotic effect of NF-kappa B activation and IL-8 expression, and DCA-induced NF-kappa B independent IL-8 expression is inhibited by TUDC.
Subject(s)
Humans , Blotting, Western , Colonic Neoplasms , Deoxycholic Acid/pharmacology , Dose-Response Relationship, Drug , Electrophoretic Mobility Shift Assay , English Abstract , HT29 Cells , Interleukin-8/metabolism , NF-kappa B/metabolism , Oligonucleotides, Antisense/pharmacology , Signal Transduction/drug effects , Taurochenodeoxycholic Acid/pharmacology , Transcriptional Activation/drug effectsABSTRACT
Esophageal tuberculosis is a rare form of adult tuberculosis, even in countries with a high incidence of tuberculosis. Secondary esophageal tuberculosis is more common than primary tuberculosis and may result from direct extension from adjacent mediastinal or hilar lymph nodes with tuberculosis or from extension from the pharynx or larynx. Clinical symptoms related to esophageal tuberculosis are dysphagia, mild fever, hematemesis and melena. Because esophageal tuberculosis has clinical symptoms and radiological appearance similar to that of esophageal malignancy, esophageal tuberculosis should be considered in the differential diagnosis of esophageal malignancy. In this report, we describe three patients with esophageal tuberculosis, diagnosed by endoscopy with biopsy and responed well to antituberculosis chemotherapy.
Subject(s)
Adult , Humans , Biopsy , Deglutition Disorders , Diagnosis, Differential , Drug Therapy , Endoscopy , Esophagus , Fever , Hematemesis , Incidence , Larynx , Lymph Nodes , Melena , Pharynx , Tuberculosis , UlcerABSTRACT
BACKGROUNDS/AIMS: The therapeutic requirements of patients with non-erosive reflux disease (NERD) are similar to those with erosive esophagitis. The pharmacological action mechanism of prokinetics is quite different; domperidone is a peripheral dopamine D2-antagonist and cisapride is a HT4-agonist. This study was performed to evaluate the therapeutic effect of these two different prokinetics in patients with NERD. METHODS: 178 patients, with heartburn and/or regurgitation, without reflux esophagitis were enrolled and divided into 2 groups by randomization code. In this prospective multicenter trial, 178 patients (93 patients in cisapride group, 85 patients in domperidone group) received 10 mg of cisapride three times a day or 10 mg of domperidone three time a day for 2 or 4 weeks. Symptom assessment was performed in each patients before treatments, 2 and 4 weeks after treatment. RESULTS: Of the 133 patients available for final analysis, 65 were allocated to the cisapride group and 68 to the domperidone group. After 2 weeks treatment, heartburn was reduced in 81.1% of cisapride group, 56.7% of domperidone group (p < 0.05) and regurgitation was reduced in 89.7% of cisapride group, 77.7% of domperidone group. After 4 weeks treatment, heartburn was reduced in 94.3% of cisapride group, 88.7% of domperidone group and this difference was not significant. The proportion of adverse events in cisapride group was 9.4% and was 5.5% in domperidone group. CONCLUSIONS: Cisapride tartrate was more effective in relieving heartburn in NERD patients than domperidone maleate after 2 week treatment. However, this superior effect dose not persist longer than 2 weeks.
Subject(s)
Humans , Cisapride , Domperidone , Dopamine , Esophagitis , Esophagitis, Peptic , Heartburn , Prospective Studies , Random Allocation , Symptom AssessmentABSTRACT
BACKGROUND/AIMS: Portal hypertension in cirrhosis is associated with a hyperdynamic circulation, which is characterized by hypervolemia, high cardiac output, arterial hypotension and low peripheral vascular resistance. These circulatory abnormalities are thought to be secondary to a splanchnic arteriolar vasodilation related to the increase in portal pressure. Studies assessing regional hemodynamics in patients of cirrhosis with ascites have shown vasoconstriction in the renal circulation and in peripheral vascular territory. This study was designed to assess the cerebral vascular resistance in cirrhotic patients with ascites. METHODS: The resistive index in the middle cerebral artery and in a renal interlobar artery were measured by Doppler ultrasonography in 12 cirrhotic subjects without ascites, 23 cirrhotic subjects with ascites, and 8 healthy subjects. The arterial blood pressure and plasma renin and norepinephrine concentration, which reflect the activity of the renin-ngiotensin and sympathetic nervous systems respectively, were also measured. RESULTS: The resistive index in the middle cerebral artery were significantly higher in cirrhotic patients with ascites (0.58 +/- 0.04, mean +/- standard deviation) than in cirrhotic patients without ascites (0.53 +/- 0.02, p<0.01) and in control subjects (0.50 +/- 0.05, p<0.01). The resistive index in the middle cerebral artery showed direct correlation with renal resistive index (r = 0.52, p<0.01), plasma renin activity (r = 0.44, p<0.01) and norepinephrine (r = 0.33, p<0.05). The resistive index in the middle cerebral artery showed an inverse correlation with mean arterial pressure (r = -.59, p<0.01). CONCLUSION: The results suggest that in patients of cirrhosis with ascites, independent of the amount of ascites, there is a cerebral vasoconstriction which is related with the arterial hypotension and the overactivity of vasoconstrictor systems.
Subject(s)
Humans , Arterial Pressure , Arteries , Ascites , Cardiac Output, High , Fibrosis , Hemodynamics , Hypertension, Portal , Hypotension , Liver Cirrhosis , Liver , Middle Cerebral Artery , Norepinephrine , Plasma , Portal Pressure , Renal Circulation , Renin , Sympathetic Nervous System , Ultrasonography, Doppler , Vascular Resistance , Vasoconstriction , VasodilationABSTRACT
Carcinoid-type tumorlets of the lung are nodular microscopic proliferation of round and spindle-shaped small cells which originated from bronchial or bronchiolar Kulchitsky-type neuroendocrine cells, which are usually encountered as an incidental finding during microscopic examination of the lungs at autopsy or surgically removed for bronchiectasis or other reasons. We report one case of carcinoid-type tumorlets in the lung which was surgically removed from a patient who had bronchiectasis, and the cells of tumorlets showed immunohistochemical reactivities for markers of epithelial and neuroendocrine differentiation.