Tussilagone suppressed the production and gene expression of MUC5AC mucin via regulating nuclear factor-kappa B signaling pathway in airway epithelial cells

In the present study, we investigated whether tussilagone, a natural product derived from Tussilago farfara, significantly affects the production and gene expression of airway MUC5AC mucin. Confluent NCI-H292 cells were pretreated with tussilagone for 30 min and then stimulated with EGF (epidermal growth factor) or PMA (phorbol 12-myristate 13-acetate) for 24 h or the indicated periods. The MUC5AC mucin gene expression was measured by RT-PCR. Production of MUC5AC mucin protein was measured by ELISA. To elucidate the action mechanism of tussilagone, effect of tussilagone on PMA-induced NF-κB signaling pathway was investigated by western blot analysis. Tussilagone significantly inhibited the production of MUC5AC mucin protein and down-regulated the expression of MUC5AC mucin gene, induced by EGF or PMA. Tussilagone inhibited PMA-induced activation (phosphorylation) of inhibitory kappa B kinase (IKK), and thus phosphorylation and degradation of inhibitory kappa Ba (IκBα). Tussilagone inhibited PMA-induced phosphorylation and nuclear translocation of nuclear factor kappa B (NF-κB) p65. This, in turn, led to the down-regulation of MUC5AC protein production in NCI-H292 cells. These results suggest that tussilagone can regulate the production and gene expression of mucin by acting on airway epithelial cells through regulation of NF-κB signaling pathway.

A Winged-Helix Transcription Factor Foxg1 Induces Expression of Mss4 Gene in Rat Hippocampal Progenitor Cells

Foxg1 (previously named BF1) is a winged-helix transcription factor with restricted expression pattern in the telencephalic neuroepithelium of the neural tube and in the anterior half of the developing optic vesicle. Previous studies have shown that the targeted disruption of the Foxg1 gene leads to hypoplasia of the cerebral hemispheres with severe defect in the structures of the ventral telencephalon. To further investigate the molecular mechanisms by which Foxg1 plays essential roles during brain development, we have adopted a strategy to isolate genes whose expression changes immediately after introduction of Foxg1 in cultured neural precursor cell line, HiB5. Here, we report that seventeen genes were isolated by ordered differential displays that are up-regulated by over-expression of Foxg1, in cultured neuronal precursor cells. By nucleotide sequence comparison to known genes in the GeneBank database, we find that nine of these clones represent novel genes whose DNA sequences have not been reported. The results suggest that these genes are closely related to developmental regulation of Foxg1.

Effects of Intrarenal Arterial Infusion of Atrial Natriuretic Peptide Analogs on Renal Function in Unanesthetized Rabbits / 대한신장학회잡지

BACKGROUND: Atrial cardiomyocytes synthesize, store and release atrial natriuretic peptide(ANP) which has potent physiological effects, including natriuresis, diuresis, relaxation of vascular smooth muscle and inhibition of aldosterone and renin secretion. A family of atrial peptides are derived from a precursor proANP. However, the structure-activity relationship of several C-terminal ANPs are not yet well documented. METHODS: The effects of structural difference of ANP analogs on the renal function were studied with a sensitive and reproducible bioassay using intrarenal arterial infusion in unanesthetized rabbits. RESULTS: Rat ANP-(1-28)(rANP, 12-Ile), a-human ANP-(1-28)(hANP, 12-Met), atriopeptin III [APIII, rANP-(5-28)], atriopeptin II[APII, rANP-(5- 27)], atriopeptin I[API, rANP-(5-25)], a-human ANP- (7-28)[hANP-(7-28)], and ANP fragments(13-28) [ANP-(13-28)] and (17-28)[ANP-(17-28)] were infused into left renal artery. No significant differences were observed between rANP and hANP. Diuretic and natriuretic activities of APIII were significantly lower than those of rANP and hANP, but were similar to those of hANP-(7-28). Diuretic and natriuretic effects of APII were similar to rANP and hANP in terms of peak responses. Duration of the effects of APII were longer than those of rANP and hANP. No significant changes were observed by infusions of API, and ANP fragments, ANP-(13-28) and ANP-(17-28). rANP, hANP and APIII decreased active but increased inactive renin secretion. CONCLUSION: These data suggest that substitution of isoleucine to methionine at 12 position of ANP does not affect the renal effects of ANP and that disulfide bond and C-terminal segment of ANP are important for the possession of natriuretic and diuretic activities.

A Prospective Randomized Trial of Open and Closed Hemorrhoidectomies

BACKGROUND: Open and closed hemorrhoidectomies are the most common surgical treatment methods for hemorrhoids. However, the advantages and the disadvantages of each procedure have not yet delineated. PURPOSE: To compare open and close hemorrhoidectomies. METHODS: A prospective randomized trial of open and closed hemorrhoidectomies was performed between January 1997 and July 1997. All patients who underwent consecutive, surgery by a single surgeon (JSJ) for grade III or IV homorrhoids were classified into two groups : Open (GI) and closed (GII) hemorrhoidectomies. For the comparison of each procedure, the duration of the hospital stay, the patients' complaints, the pain score (Grade 1-10), and the complications after surgery were assessed.. Followup data were also obtained by telephone interviews. For the physiologic comparison, the preoperative and the postoperative anorectal manometry results were evaluated. RESULTS: Fortyone (41) patients were underwent hemorrhoidectomies : GI (n=18) and GII (n=23). There were no differences between the two groups in terms of duration of symptoms, degree of hemorrhoid, age, and gender. There were no differences respect to parameters related with postoperative complaints during the hospital stay, such as pain on defecation, skin edema, and anal itching. However, bleeding on defecation (83% in GI vs. 43.5% in GII, p<0.05), and anal soiling (61% in GI vs. 13% in GII, p<0.05) were significantly higher in GI patients. The pain score on postoperative day 1 was significantly higher in GI (6.6 vs. 4.9, p<0.05). Other parameters of complications (stricture, 5.7% in GI. vs. 4.3% in GII; defecation difficulty; 5.7% in GI vs. 4.3% in GII; and fecal incontinence; 0% in GI vs. 4.3% in GII) showed no significant differance during the mean followup period of 4.7 months. Neither the mean hospital stay (7 days in GI, 6.2 days in GII) nor the period of complete wound healing (32.7 vs 28.3 days in GI, GII, respectively) was different between the two groups. The preoperative and the postoperative anorectal manometric findings were not different in the two groups. CONCLUSIONS: The closed hemorrhoidectomy was superior to the open procedures in terms of some parameters such as the pain score on postoperative day 1, bleeding on defecation, and postoperative soiling during the hospital stay. However, the intermediate postoperative outcomes were not different for the two procedures.

Risk Factors of Recurrent Hemorrhoid after Primary Management

Before surgery for hemorrhoid, patients always have a worry of postoperative recurrence. The exact incidence and risk factors of recurrent hemorrhoid have not yet been delineated up to now. Therefore, the aim of this study was to assess the etiology of the recurrence after surgery. MATERIAL AND METHODS: Between March, 1997 and Feburary 1998, all patients who visited the Dept. of Surgery, Korea Veteran Hosipital, due to the recurrent hemorroid after surgical managememt including sclerotherapy(Group II: GII, n=60) were compared to the age and sex mathed(1:2) with primary hemorroid patients(group I: GI, n=120). The risk factors which might be related with the recurrence such as 1) hemorroidal factor(duration of symtom, symtom, associated perinial disease) 2) patient factor (constipation, incontience, cardiovascular disease, pulmonary and hepatic disease) 3) anorectal physiologic factors 4) surgical factors were evaluated. Stastical analysis were performed by a chi-square-test or Mann-Whitney U test and set the significance at p<0.05. RESULTS: There were no differences between the two groups in terms of age(GI 58.1+/-8.5, GII 60.9+/-3.3 years), gender(M:F, GI; 97:23, GII; 56:4 ). The ratio of having a contipation before surgery was 41% in GI, 55% in GII. It was not statistically significant. However, the other factors related with constipation such as duration of constipation(GI; 9.85+/-7.73 years, GII; 14.62+/-7.38 years: p<0.05), duration of straining during defecation(GI; 5.82+/-2.34, GII; 7.32+/-5.6 minutes, p<0.05) number of laxative use(GI; 29, GII; 28) were significantly different between the two groups. The fecal incontince are 5% in group Iand 13% in group II. There were no differences in patient's subject symtoms related with hemorrhoid, and comorbid perianal disease between the two groups. In anorectal manometric findings, rectal complince was significantly lower in GII than that of GI(25.1+/-50.04 cc/cmH20 vs 16.0+/-25.2 cc/cmH20 p<0.05). GII has a significant number of preopertive hypertension than GI(6.7% vs. 21.6%, p<0.05). CONCLUSION: When a patient with hemorrhoid has a constipation or hypertension, and lower compliance in manometric findings, it would be related with the postoperative recurrence after treatment. Therefore, we surgeons should correct these comorbid conditions before surgery, otherwise give an information to the patient of high chance of postoperative recurrence after management.

Management of Small Bowel Obstruction after Previous Abdominal Operation

There is a continuing debate among surgeons about whether postoperative adhesive small bowel obstruction is best managed operatively or nonoperatively. This retrospective study was designed to determine the factors influencing the treatment modality of postoperative small bowel obstruction. A clinical analysis was conducted on 112 cases of small bowel obstruction after previous abdominal operation, who were admitted to the department of general surgery of Korea Veterans Hospital from January, 1984 to December, 1994. The patients were divided into two groups according to the modality of treatment: operatively(N=35) and nonoperatively(N=77) treated groups. Clinical parameters such as age, sex, symptoms and signs, type of previous operation, interval between previous operation and admission due to obstructive symptoms, time period from onset of symptoms to admission, and interval from admission to operation, were compared between two groups. Among 112 cases, the conservative treatment was performed in 77 cases and operative management was performed in 35 cases. There was no significant difference in the distribution of age and sex between two groups. The previous operations leading to adhesive intestinal obstruction were appendectomy(18.8%), gastroduodenal operation(17.0%), operation for multiple organ injury(16.1%), and Obsetric & Gynecologic surgery(9.8%) in that orders. The interval between previous abdominal operation and admission was under 1 month in 20 cases, 1 to 6 months in 10 cases, 7 to 12 months in 16 cases, and 1 to 2 years in 16 cases. The major symptoms and signs were abdominal pain, abdominal tenderness, vomiting, abdominal distension, hyperperistalsis, and leukocytosis. Among the above signs and symptoms, continuous abdominal pain, leukocytosis, and tachycardia were significantly higher in the operative group compared to those of the nonoperative group. The most common procedures of operative management were adhesiolysis, small bowel resection, bypass surgery, and colon resection in that orders. The incidence of postoperative complications was 31.4% and the most common complication was wound infection. In conclusion, at admission, the presence of strangulating signs such as continuous abdominal pain, leukocytosis, and tachycardia in patients with small bowel obstruction after previous abdominal operation mandates early operative intervention rather than conservative treatment.