A20 is an early responding negative regulator of Toll-like receptor 5 signalling in intestinal epithelial cells during inflammation.

Several negative regulatory mechanisms control Toll-like receptor (TLR)-mediated inflammatory responses and restore immune system balance, including the zinc-finger protein A20, a negative regulator of TLR signalling that inhibits nuclear factor kappa B (NF-kappaB) activity. In the present study, we investigated TLR-5-mediated A20 expression and its role in intestinal epithelial cells (IECs) during inflammation. HCT-15 and HT-29 cells were stimulated with flagellin, then the expressions of A20, interleukin-1 receptor-associated kinase (IRAK-M) and Tollip were evaluated using RNase protection assay. Furthermore, experimental colitis was induced in tlr4-deficient CH3/HeJ mice by administration of dextran sodium sulphate (DSS), then flagellin was injected anally, and the colonic expression of A20 was examined by real-time polymerase chain reaction (PCR) and immunohistochemistry. To confirm flagellin-induced expression of A20, we employed an organ culture system. The role of A20 in flagellin-induced tolerance induction was evaluated in vitro, using a gene knock-down method targeting A20. A20 expression increased rapidly and peaked at 1 h after flagellin stimulation in cultured IECs, then declined gradually to the basal level. In vivo, anal injection of flagellin induced epithelial expression of A20 in injured colonic tissue, whereas flagellin did not cause a significant increase in A20 expression in non-injured normal tissue, which was also confirmed in vitro using the organ culture system. Gene knock-down using A20 siRNA did not influence tolerance induced by restimulation with flagellin. A20 is an early response negative regulator of TLR-5 signalling in IECs that functions during intestinal inflammation. Our results provide new insights into the negative feedback regulation of TLR-5 signalling that maintains the innate immune system in the gut.

Interobserver agreement on classifying endoscopic diagnoses of nonerosive esophagitis.

BACKGROUND AND STUDY AIMS: The majority of patients with gastroesophageal reflux disease in Japan have low-grade esophagitis, including minimal changes. A modified Los Angeles classification of esophagitis, consisting of erosive esophagitis (grades A - D) and nonerosive esophagitis (grades M and N) has been proposed and is in clinical use in Japan. However, it is unclear whether nonerosive esophagitis with only undemarcated mucosal discoloration (grade M) is clinically significant, since interobserver variations in classification have not been investigated. The aim of the present study was therefore to evaluate interobserver variance and diagnostic agreement in the diagnosis of nonerosive esophagitis (grades M and N). MATERIALS AND METHODS: A total of 84 endoscopists were enrolled to assess the grade of esophagitis in 30 patients by viewing endoscopic images of the gastroesophageal junction. The images were projected onto a screen, and all of the endoscopists reviewed them concurrently. The diagnosis was selected from the following three categories in the modified Los Angeles classification: grades N, M, or A. The endoscopists were grouped according to their experience, whether they had a board license, and whether they had received specialist training in esophagitis. The kappa coefficient of reliability was calculated. RESULTS: The kappa coefficient of reliability for all the endoscopists in the diagnosis of cases of grade M and N nonerosive esophagitis was unacceptably low at 0.22 (95 % CI, 0.21 - 0.24). Endoscopists with a board license and those who had completed a special esophagitis diagnostic course had slightly higher kappa values (0.26; 95 % CI, 0.23 - 0.30 and 0.29; 95 % CI, 0.26 - 0.32), respectively. CONCLUSIONS: Interobserver agreement on the endoscopic diagnosis of nonerosive esophagitis (grades M and N) is too low to be of clinical value.

Evaluation of modified crystal violet chromoendoscopy procedure using new mucosal pit pattern classification for detection of Barrett's dysplastic lesions.

BACKGROUND: Pit pattern diagnosis is important for endoscopic detection of dysplastic Barrett's lesions, though using magnification endoscopy can be difficult and laborious. We investigated the usefulness of a modified crystal violet chromoendoscopy procedure and utilised a new pit pattern classification for diagnosis of dysplastic Barrett's lesions. METHODS: A total of 1,030 patients suspected of having a columnar lined oesophagus were examined, of whom 816 demonstrated a crystal violet-stained columnar lined oesophagus. The early group of patients underwent 0.05% crystal violet chromoendoscopy, while the later group was examined using 0.03% crystal violet with 3.0% acetate. A targeted biopsy of the columnar lined oesophagus was performed using crystal violet staining after making a diagnosis of closed or open type pit pattern with a newly proposed system of classification. The relationship between type of pit pattern and histologically identified dysplastic Barrett's lesions was evaluated. RESULTS: Dysplastic Barrett's lesions were identified in biopsy samples with an open type pit pattern with a sensitivity of 96.0%. Further, Barrett's mucosa with the intestinal predominant mucin phenotype was closely associated with the open type pit pattern (sensitivity 81.9%, specificity 95.6%). CONCLUSIONS: The new pit pattern classification for diagnosis of Barrett's mucosa was found to be useful for identification of cases with dysplastic lesions and possible malignant potential using a crystal violet chromoendoscopic procedure.

Barrett's oesophagus with predominant intestinal metaplasia correlates with superficial cyclo-oxygenase-2 expression, increased proliferation and reduced apoptosis: changes that are partially reversed by non-steroidal anti-inflammatory drugs usage.

BACKGROUND: Cyclo-oxygenase-2 expression has been reported to play an important role in the metaplasia-dysplasia-carcinoma sequence in Barrett's oesophagus. However, the existence of cyclo-oxygenase-2 expressing cells in Barrett's epithelium is still uncertain. AIM: To identify the cells that express cyclo-oxygenase-2 protein and to investigate the relationship between cyclo-oxygenase-2 expression and mucin-phenotype of Barrett's epithelium. METHODS: Sections from 466 biopsy samples of Barrett's epithelium from 358 non-medicated patients were immunohistochemically examined for the cyclo-oxygenase-2 expression, mucin-phenotype, cell proliferation and apoptosis. RESULTS: Cyclo-oxygenase-2 expression was detected in 71.0% of Barrett's epithelium biopsy samples. In Barrett's epithelium with the gastric predominant mucin-phenotype, cyclo-oxygenase-2 expression was mainly found in stromal and deep epithelial cells, whereas in intestinal predominant mucin-phenotype, it was mostly in superficial epithelial cell. A significant elevation of proliferating cell nuclear antigen index and suppression of apoptotic index was observed in Barrett's epithelium with superficial epithelial cyclo-oxygenase-2 expression. Neither such elevation of proliferating cell nuclear antigen index nor the suppression of apoptotic index could be found in chronic non-steroidal anti-inflammatory drugs users. CONCLUSIONS: Barrett's epithelium with intestinal mucin and superficial epithelial cyclo-oxygenase-2 expression possess a higher proliferation potential, but this risk may be thwarted by non-steroidal anti-inflammatory drugs administration.

Which types of non-bleeding visible vessels in gastric peptic ulcers should be treated by endoscopic hemostasis?

BACKGROUND AND AIMS: Because non-bleeding visible vessels (NBVV) of gastric peptic ulcers have the potential to re-bleed, endoscopic hemostatic treatment may be necessary during the first emergency endoscopy. However, not all NBVV re-bleed, and endoscopic hemostasis sometimes causes fatal side-effects. Therefore, we have evaluated the risk of re-bleeding from various NBVV in gastric peptic ulcers to determine which types should be treated by endoscopy to prevent re-bleeding. METHODS: A total of 227 NBVV in 202 patients with gastric peptic ulcers that were endoscopically followed without endoscopic hemostatic procedures were classified by the following factors: vessel color, form, location of the NBVV in the ulcer crater, and location of the ulcer in the stomach. The re-bleeding rate was then analyzed for each type of NBVV. RESULTS: Significantly high rates of re-bleeding were observed in cases with white, protruded and peripheral NBVV. In particular, white NBVV located in the peripheral zone of the ulcer crater were frequent re-bleeding sources. The location of the ulcer in the stomach was not a statistically significant factor in determining re-bleeding rates. CONCLUSION: We found that white, protruded and peripherally located NBVV in gastric ulcers have a higher chance of re-bleeding if preventive endoscopic hemostatic procedures are not performed.

Safety and efficacy of glucagon as a premedication for upper gastrointestinal endoscopy--a comparative study with butyl scopolamine bromide.

BACKGROUND: Glucagon inhibits digestive motility and is used for endoscopic premedication; however, its effect on cardiopulmonary function during endoscopy has not yet been fully investigated. AIM: To clarify the efficacy and safety of glucagon compared with butyl scopolamine bromide as upper gastrointestinal endoscopy premedication. METHODS: Two hundred and forty consecutive patients over 40 years of age, referred for upper gastrointestinal endoscopy, without any complications, were studied. These patients were randomly premedicated with butyl scopolamine bromide (SC group) or glucagon (G group). Time course changes in blood pressure, arterial oxygen saturation, heart rate and the number of retching episodes during endoscopy were examined. The efficacy of glucose tablets after upper gastrointestinal endoscopy to prevent hypoglycaemia caused by glucagon was evaluated. Cardiopulmonary parameters were also examined in 77 complicated patients with glucagon premedication (GC group). RESULTS: A continuous increase in heart rate during upper gastrointestinal endoscopy was observed in the SC group, but not in the G and GC groups. Blood pressure, arterial oxygen saturation and number of retching episodes were not different between the groups. Hypoglycaemia-related symptoms were frequent in the G group without glucose tablets, but were prevented by the administration of glucose. CONCLUSIONS: Glucagon has a weaker effect on cardiopulmonary function during upper gastrointestinal endoscopy than butyl scopolamine bromide. Glucose administration prevents hypoglycaemia-related symptoms caused by glucagon.

Clinical relevance of precore and basal core promoter variants of hepatitis B virus during natural hepatitis B e antigen seroconversion may be overstated.

BACKGROUND: Clinical relevance of nucleotide changes in precore and basal core promoters in the hepatitis B virus genome during hepatitis B e antigen seroconversion may be overstated. The authors investigated the existence and changes in the relative proportion of variants to wild virus that occur with seroconversion. METHODS: Sera from 30 school-aged long-term hepatitis B virus carriers, including 11 tested before and after seroconversion during 1 to 8 years of follow-up, were evaluated for variations in nucleotide sequences of the basal core promoter (T1762 and A1764), precore region (A1869), and carboxyl-terminus of the X region of the hepatitis B virus genome using an amplification refractory mutation detection system with mutant-specific primers. RESULTS: All variants were found to already exist before seroconversion at various wild-type/mutant ratios. The positive rates of these variants were not changed with loss of hepatitis B e antigen. Although there was a relative increase in the concentration of these mutants in wild-type/mutant mixed populations, most patients with only a wild-type population maintained the same pattern after loss of hepatitis B e antigen. CONCLUSIONS: Our results indicate that hepatitis B virus exists as a quasi species, and correlations of nucleotide sequences with clinical and serologic findings must be done with caution.

Intragastric distribution of Helicobacter pylori during short-term omeprazole therapy: study using Carnoy's fixation and immunohistochemistry for detection of bacteria.

BACKGROUND: There is controversy about the effect of acid-suppressive therapy on Helicobacter pylori density and the severity of histological gastritis in the corpus. AIM: To evaluate the precise distribution of H. pylori, both on the surface mucus cells and in the surface mucus gel layer, by using Carnoy's fixation and immunostaining for the detection of bacteria. METHODS: A total of 19 peptic ulcer patients with H. pylori infection were studied. All patients received a 6-week course of treatment with omeprazole (20 mg/day). Before and after the therapy, H. pylori density in Carnoy-fixed tissue sections was examined immunohistochemically. The effect of omeprazole therapy on the severity of gastritis was also evaluated. RESULTS: H. pylori density and the grade of gastritis significantly decreased in the antrum after omeprazole therapy. In the corpus, however, there were no significant changes in H. pylori density or the severity of gastritis after omeprazole therapy. CONCLUSION: Carnoy's fixation and immunostaining was found to be useful for the detection of H. pylori in the surface mucus gel layer as well as on the surface mucus cells in biopsy tissue sections. By using this method, H. pylori density decreased in the antrum, but remained unchanged in the corpus after a 6-week course of omeprazole therapy.

Efficacy of ecabet sodium for Helicobacter pylori eradication triple therapy in comparison with a lansoprazole-based regimen.

BACKGROUND: The cytoprotective agent, ecabet sodium, inhibits urease activity and growth of Helicobacter pylori. AIM: To evaluate the efficacy and safety of ecabet sodium-based eradication of H. pylori infection, compared with a lansoprazole-based regimen, in a randomized multicentre study. SUBJECTS AND METHODS: A total of 120 H. pylori-positive patients were assigned to one of two treatment regimens for 2 weeks: ecabet sodium 1 g b.d., amoxicillin 500 mg t.d.s. and clarithromycin 400 mg b.d. (EAC: 60 patients); or lansoprazole 30 mg (o.m.) with the same antimicrobial agents (LAC: 60 patients). Cure of infection was assessed by a 13C-urea breath test 1 month after completion of treatment. RESULTS: One patient in the EAC group and two in the LAC group did not complete therapy because of an adverse event, and three did not undergo the 13C-urea breath test. Cure rates for the intention-to-treat, all-patients-treated and per protocol analysis in the EAC group were 85%, 86% and 88%, respectively, whereas those in the LAC group were 85%, 88% and 91%. There were no significant differences in cure rate or adverse events between the two regimens. CONCLUSIONS: Ecabet sodium in combination with amoxicillin and clarithromycin is as effective as lansoprazole-based eradication therapy for H. pylori.

Co-infection by serologically-silent hepatitis B virus may contribute to poor interferon response in patients with chronic hepatitis C by down-regulation of type-I interferon receptor gene expression in the liver.

Intrahepatic mRNA levels of type-I interferon (IFN) receptor genes have been shown to correlate with the clinical efficacy of IFN therapy in patients with chronic hepatitis C. Recently, co-infection by serologically-silent hepatitis B virus (HBV) has been assumed to be associated with the poor IFN response in patients with chronic hepatitis C. The aim of this study was to investigate the relationship between the co-infection of serologically-silent HBV and type-I IFN receptor gene expression in the liver of patients with chronic hepatitis C. The intrahepatic mRNA levels of IFNAR2, one of the two subunits of the type-I IFN receptor, were quantified and compared with both the prevalence of HBV DNA and the hepatitis C virus (HCV) genotype in 45 patients with chronic hepatitis C, who were negative for hepatitis B surface antigen. Co-infection, as evaluated by a nested polymerase chain reaction, was present in 22 patients (48.9%), with dominance of the HCV genotype 1b (65.2%) over genotype 2a (31.8%). Co-infection was associated with lower IFNAR2 mRNA levels, higher levels of serum HCV RNA, and a poor IFN response, regardless of the HCV genotype. The findings suggest the possibility that co-infection by serologically-silent HBV is one of the factors that can lead to an unfavorable IFN response in chronic hepatitis C by down-regulation of IFN receptor gene expression in the liver.

T cell-mediated cytotoxicity via Fas/Fas ligand signaling in Helicobacter pylori-infected gastric corpus.

BACKGROUND: Helicobacter pylori infection induces T helper-1 immune responses in inflamed mucosa. However, the role of T cell-mediated cytotoxicity in the induction of epithelial apoptosis is still unclear. The aim of this study was to investigate the involvement of the Fas/Fas ligand (Fas/Fas-L) system in the H. pylori-infected gastric corpus. MATERIALS AND METHODS: Gastric fundic biopsy specimens were taken from patients with and without H. pylori infection. The expression of Fas and Fas-L was examined by immunohistochemistry and RT-PCR. Subsets of gastric infiltrating T cells in the biopsy specimens were studied by immunohistochemistry and flow cytometry. In histological sections, apoptosis was detected by the TUNEL method. We studied the in vitro expression of Fas-L in peripheral T cells after stimulation with H. pylori antigen and interferon-gamma (IFN-gamma). The Fas-mediated in vitro cytotoxicity of activated T cells was assessed by flow cytometry. RESULTS: The numbers of CD4+ and CD8+ T cells were greater in H. pylori-infected subjects. Fas expression was abundantly increased on fundic gland epithelium, and Fas-L was detected on lamina propria mononuclear cells in H. pylori-infected mucosa. TUNEL-positive epithelial cells were also increased in H. pylori-infected subjects. H. pylori antigen and IFN-gamma induced Fas-L mRNA expression in both CD4+ and CD8+ T cells. In cytotoxic assay, activated T cells induced apoptosis in AGS cells, which could be significantly inhibited by neutralizing Fas-L antibody. CONCLUSIONS: T cell-mediated cytotoxicity via Fas/Fas-L signaling may contribute to the induction of apoptosis in gastric epithelial cells during H. pylori infection.

Comparison between short-term food restriction and exercise on whole body glucose disposal in high-fat rats.

High-fat diets induce whole-body insulin resistance. The aim of this study was to compare effect of two interventions: 3-day food restriction (66% of ad libitum fed) and 3-day exercise training (voluntary running wheels), on decreased insulin-mediated whole body glucose uptake in high-fat fed rats (5 mo old) using the hyperinsulinemic euglycemic clamp procedure. The control group was maintained on rat chow alone. After high-fat feeding for 2 wk, insulin-stimulated whole body glucose utilization was significantly decreased by 26%. The exercise training was more effective than food restriction in lowering plasma concentrations of insulin and triacylglycerol and tissue concentrations of triacylglycerol in soleus muscles. Diminished whole-body glucose uptake resulting from high-fat feeding was reversed completely by exercise training, but only partially by food restriction. The time course of starvation on insulin-stimulated glucose uptake was also observed in high-fat fed rats. Although the extension of starvation time to 48 h resulted in decreased plasma glucose, insulin and triacylglycerol concentrations, whole body glucose uptake did not increase further. These findings suggest that short-term exercise has a higher restorative effect on insulin sensitivity in high-fat fed rats than food restriction, in spite of the same loss in body weight, presumably due in part to improved local lipid availability.

Role of hepatitis B virus in non-B, non-C chronic liver disease: in vitro proliferation and interferon-gamma production of peripheral blood mononuclear cells in response to hepatitis B core antigen and its relation to hepatitis activity.

OBJECTIVE: Although hepatitis B virus (HBV) DNA has been detected in the sera of patients with chronic liver disease with neither hepatitis B surface antigen nor antihepatitis C virus antibody (non-B, non-C [NBNC] CLD), whether HBV has some pathogenic role in NBNC CLD has not been made clear. METHODS: To investigate the significance of HBV DNA in NBNC CLD, we performed in vitro stimulation assays of peripheral blood mononuclear cells (PBMCs) in response to hepatitis B core antigen (HBcAg) in 17 NBNC CLD patients. RESULTS: HBV DNA with an 8-nucleotide deletion in the core promoter region was detected in 13 (76%) of the 17 patients by nested polymerase chain reaction. Interferon-gamma (IFN-gamma) production and proliferation of PBMCs of HBV DNA-positive patients showed a significant increase in response to HBcAg. The histological activity of hepatitis was also found to be significantly associated with the magnitude of IFN-gamma production and proliferation of PBMCs in response to HBcAg. Although five (38%) of the 13 HBV DNA-positive NBNC CLD patients had anti-HBs and/or anti-HBc, there was no difference in response of PBMCs to HBcAg between the HBV DNA-positive and -negative groups. CONCLUSION: Our observation suggests that HBV may have a pathogenic role in HBV DNA-positive NBNC CLD, even in those patients without any serological markers of HBV.

Serologically silent hepatitis B virus coinfection in patients with hepatitis C virus-associated chronic liver disease: clinical and virological significance.

Frequent coinfection of surface antigen-negative hepatitis B virus (silent HBV) in hepatitis C virus (HCV)-associated chronic liver disease (CLD) has been reported. The clinical and virological significance of silent HBV infection was investigated in 65 patients with HCV-associated CLD who subsequently received interferon (IFN) therapy. HBV DNA was detected in 34 (52.3%) patients by a nested polymerase chain reaction (PCR). Virologically, all of the 34 patients were found to have HBV with an eight-nucleotide deletion in the core promoter. Coinfection of silent HBV was more frequent with HCV genotype 1b than in 2a (64.3% vs. 28.6%, P<.01). With HCV genotype 1b, the serum RNA level was significantly higher (> or =10(6) copies per milliliter vs. < or =10(5) copies per milliliter) in patients with silent HBV than those without coinfection (P<.01). Clinically, silent HBV was associated with a higher level of serum alanine aminotransferase (158.5+/-104.8 vs. 121.8+/-78.6 IU/I; mean +/- SD) and a greater histological activity of hepatitis as evaluated by histological activity index score (9.4+/-3.8 vs. 8.6+/-4.5; mean +/- SD), although it was not statistically significant. Silent HBV was also associated with poor efficacy of IFN therapy (P<.01). The results suggest that silent HBV has some promoting effect for HCV replication, at least for HCV genotype 1b, and may affect the histological activity of hepatitis and IFN response in HCV-associated CLD.

Mild hypothermia can attenuate nitroglycerin-induced vasodilation of pial arterioles in the cat.

UNLABELLED: The purpose of the present study was to investigate the effect of mild hypothermia on nitroglycerin-induced vasodilation of cerebral vessels. The cranial window technique, combined with microscopic video recording, was used in an experiment involving 26 cats anesthetized with isoflurane. Animals were randomly assigned to either a normothermic or a mildly hypothermic group (33 degrees C). We administered three different concentrations of nitroglycerin (10[-6], 10[-5], 10[-4] M) under the window and measured the diameter of small (< 100 microm) and large (100-200 microm) pial arterioles. In the normothermic group (n = 13), nitroglycerin produced a significant dilation of both small and large arterioles in a dose-dependent manner. In the hypothermic group (n = 13), a significant dilation of arterioles was observed only after topical application of nitroglycerin at a concentration of 10(-4) M. The percent increase in diameter of small and large arterioles was less in the hypothermic group than the normothermic group. Our in vivo study demonstrates that topically applied nitroglycerin produces a dose-dependent dilation of pial arterioles in normothermic cats anesthetized with isoflurane, but the reduction of temperature to 33 degrees C significantly attenuates nitroglycerin-induced vasodilation of pial arterioles. IMPLICATIONS: Although nitroglycerin may be used in hypothermic patients, the effect of mild hypothermia on nitroglycerin-induced vasodilation of cerebral vessels is unknown. In this study, we investigated the effects of nitroglycerin on pial arteriolar diameter in normothermic and hyperthermic cats. Hypothermia was found to attenuate nitroglycerin-induced vasodilation.

[Anesthesia for a patient with heparin-induced thrombocytopenia: a case report].

A 68 year-old man underwent a femoral-popliteal bypass surgery. He was diagnosed as heparin-induced thrombocytopenia (HIT) by platelet aggregation test when he underwent CABG 4 years ago. For the present surgery we administered nafamostat mesilate and urokinase for anticoagulation during surgery instead of heparin. After the operation, laboratory studies showed no thrombocytopenia.

Helicobacter pylori infection accelerates gene expression of glicentin in the gastric mucosa. Its association with intestinal metaplasia of the stomach.

BACKGROUND: Glicentin is an intestinal polypeptide hormone which seems to promote intestinal metaplasia (IM) in the gastric mucosa. The aim of this study was to clarify whether Helicobacter pylori infection accelerates glicentin gene expression. METHOD: Glicentin mRNA was investigated by reverse-transcription polymerase chain reaction using gastric biopsies from 47 patients examined endoscopically and denying IM. RESULTS: IM was observed in 18 (38.3%) cases histologically, but not in the other 29 (62.7%). Glicentin mRNA was significantly correlated with histological IM (P < 0.01) and was positively correlated with H. pylori infection (P < 0.05). CONCLUSION: Our results indicate that H. pylori infection is associated with the induction of glicentin in the gastric mucosa, thus supporting the hypothesis that H. pylori infection accelerates IM of the stomach.

Effectiveness of interferon-alpha therapy in chronic hepatitis C is associated with the amount of interferon-alpha receptor mRNA in the liver.

BACKGROUND/AIMS: This study aimed to investigate the relationship between interferon-alpha receptor mRNA in the liver and the response to interferon therapy in chronic hepatitis C. METHODS: Interferon-alpha receptor mRNA was quantified by reverse transcription polymerase chain reaction using liver biopsies from 40 patients, comprising 20 responders and 20 non-responders to subsequent interferon therapy. RESULTS: The amount of interferon-alpha receptor mRNA was significantly larger in interferon-responders (0.72+/-0.12) than non-responders (0.26+/-0.08) (p<0.01). Regardless of the response to interferon, histological activity index scores and the amount of HCV-RNA showed significant inverse correlation to the amount of interferon-alpha receptor mRNA, whereas the HCV-RNA genotype was not associated with the amount of interferon-alpha receptor mRNA. Logistic analysis and multiple regression analysis showed that the amount of interferon-alpha receptor mRNA was significantly associated with the efficacy of interferon (p=0.0275), but not with fibrosis of the liver (p= 0.2726). CONCLUSIONS: Our results suggest that the amount of interferon-alpha receptor mRNA is an important factor determining the response to interferon, and may be a new predictor of interferon response in chronic hepatitis C.

Nitric oxide involvement in hypoxic dilation of pial arteries in the cat.

BACKGROUND: The reactivity of cerebral arteries to different stimuli varies according to vessel size. Whether nitric oxide mediates hypoxic vasodilation is controversial. The authors considered this question by measuring the diameter of pial arteries and arterioles with or without exposure to the nitric oxide synthase inhibitor, N omega-nitro-L-arginine methyl ester (L-NAME). METHODS: The cranial window technique, combined with microscopic video recording, was used in an experiment involving 20 cats anesthetized with fentanyl and midazolam. The diameters of pial arteries and arterioles were measured under the following conditions: (1) normoxia (PaO2 > 100 mmHg); (2) hypoxia (PaO2 < 45 mmHg); (3) normoxia with L-NAME infusion; and (4) hypoxia with L-NAME infusion. Changes in vessel diameter were analyzed with respect to artery size. RESULTS: Under hypoxic conditions, arteries and arterioles smaller than 200 microns were dilated significantly (P < 0.05). In arterioles smaller than 200 microns, L-NAME attenuated this hypoxic vasodilation (P < 0.05). In contrast, under normoxic conditions, L-NAME caused significant vasoconstriction in arteries larger than 100 microns but not in arteries smaller than 100 microns. CONCLUSIONS: Arteries and arterioles smaller than 200 microns are dilated by hypoxia, and nitric oxide contributes to this process. Nitric oxide synthesis may also be related to the regulation of resting vascular tone in arteries larger than 100 microns.