bluuebunny/crossref_metadata_2025_split huggingface dataset:
Heme oxygenase‐1: a new therapeutic target for inflammatory bowel disease
Authors: Naito Y. , Takagi T. , Yoshikawa T. 
Published: December 2004

SummaryHeme oxygenase (HO) is the rate‐limiting enzyme in the catabolism of heme, followed by production of biliverdin, free iron and carbon monoxide (CO). Three mammalian HO isozymes have been identified, one of which, HO‐1, is a stress‐responsive protein induced by various oxidative agents. HO‐2 and HO‐3 genes are constitutively expressed. Recent studies demonstrate that the expression of HO‐1 in response to different inflammatory mediators may contribute to the resolution of inflammation and have protective effects in several organs against oxidative injury. Although the mechanism underlying the anti‐inflammatory actions of HO‐1 remains poorly defined, both CO and biliverdin/bilirubin have been implicated in this response. In the intestinal tract, HO‐1 is shown to be transcriptionally induced in response to oxidative stress, preconditioning and acute inflammation. Recent studies suggest that the induction of HO‐1 expression plays a critical protective role in intestinal damage models induced by trinitrobenzene sulphonic acid or dextran sulphate sodium, indicating that activation of HO‐1 may act as an endogenous defensive mechanism to reduce inflammation and tissue injury in the intestinal tract. These in vitro and in vivo data suggest that HO‐1 may be a novel therapeutic target in patients with inflammatory bowel disease.
The aetiopathogenesis of inflammatory bowel disease — immunology and repair mechanisms
Authors: Dignass A. U. , Baumgart D. C. , Sturm A. 
Published: December 2004

SummaryAlthough the aetiopathogenesis of Crohn's disease and ulcerative colitis, remains unsolved, current evidence indicates that defective T‐cell apoptosis and impairment of intestinal epithelial barrier function play important roles in the pathogenesis of both conditions. Without appropriate control of T‐cell proliferation and death during an immune response, an inappropriate accumulation of T cells and subsequent intestinal inflammation may occur. Differences in T‐cell responses between Crohn's disease and ulcerative colitis have been identified, with mucosal T‐cell apoptosis being defective in Crohn's disease, but not in ulcerative colitis. Furthermore, cell cycling is considerably faster, with a vigorous clonal expansion, in Crohn's disease, whereas, in ulcerative colitis, T cells cycle normally, but have a remarkably reduced capacity to divide and expand. The elimination of excessive T cells therefore seems to be a reasonable approach to restore the gut to a physiological state or, at least, a controlled state of inflammation. The tumour necrosis factor‐α blocker, infliximab, exerts its beneficial effects, at least in part, by the induction of apoptosis in lamina propria T cells and monocytes. In addition, repeated damage and injury of the intestinal surface is a hallmark of inflammatory bowel disease and may facilitate the entry of luminal antigens into the mammalian organism and the initiation and perpetuation of both nonspecific and specific immune responses. A better understanding of and enhancement of intestinal repair mechanisms may thus provide future approaches for the treatment of inflammatory bowel disease.
Problematic proctitis and distal colitis
Authors: Gionchetti P. , Rizzello F. , Morselli C. , Campieri M. 
Published: December 2004

SummaryAbout two‐thirds of patients with ulcerative colitis have an inflammatory involvement distal to the splenic flexure, and therefore may be effectively treated with topical treatment, allowing the delivery of the active drug directly to the site of inflammation and limiting systemic absorption and potential side‐effects. Topical aminosalicylate therapy is the most effective approach, and most patients will benefit hugely, provided that the formulation reaches the upper extent of the disease. Therefore, the choice of topical preparation should be based on the proximal extent of the disease and on patient preference. Oral aminosalicylates are less effective than topical therapies; however, a combination of oral and topical aminosalicylates can be successful in refractory patients. Alternatives to aminosalicylates are the new glucocorticoids, budesonide and beclometasone dipropionate, either as enemas or oral formulations (only beclometasone dipropionate). A combination of oral or rectal new glucocorticoids with rectal aminosalicylates should be considered in patients refractory to either approach. When these measures fail, treatment with oral glucocorticoids is necessary. An intensive intravenous steroid regimen is also helpful for patients refractory to oral steroids. Alternative treatments include short‐chain fatty acid enemas, nicotine enemas and patches, acetarsol suppositories, ciclosporin enemas and epidermal growth factor enemas. Several factors potentially having a negative impact on therapeutic response include concurrent enteric pathogens, coexistent irritable bowel syndrome, patient nonadherence to therapy, inadequate dosing and duration of therapy, and proximal progression of the disease. Surgical colectomy may be required in those rare patients refractory or intolerant to pharmacotherapy.
Anti‐tumour effects of nobiletin, a citrus flavonoid, on gastric cancer include: antiproliferative effects, induction of apoptosis and cell cycle deregulation
Authors: Yoshimizu N. , Otani Y. , Saikawa Y. , Kubota T. , Yoshida M. , Furukawa T. , Kumai K. , Kameyama K. , Fujii M. , Yano M. , Sato T. , Ito A. , Kitajima M. 
Published: December 2004

SummaryAim:  To demonstrate the antitumour effects of nobiletin (5,6,7,8,3′,4′‐hexamethoxyflavone), a citrus flavonoid extracted from Citrus depressa Hayata, on human gastric cancer cell lines TMK‐1, MKN‐45, MKN‐74 and KATO‐III.Materials and methods:  3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT) assay, the TdT‐mediated dUTP biotin nick‐end labelling (TUNEL) method and cell‐cycle analysis revealed that nobiletin acted on these cells in several ways, namely by direct cytotoxicity, induction of apoptosis and modulation of cell cycle. The efficacy of combined treatment of nobiletin with a conventional anticancer drug, CDDP, was also examined. Treatment with nobiletin 24 h prior to CDDP administration showed a synergistic effect compared to the control.Conclusions:  Although the effective dose and administration route of nobiletin require further investigation, our study represents a potential successful linking of this compound with the treatment of gastric cancer.
Effect of cyclo‐oxygenase inhibitors on Helicobacter pylori susceptibility to metronidazole and clarithromycin
Authors: Gu Q. , Xia H. H.‐X. , Wang W. H. , Wang J. D. , Wong W. M. , Chan A. O. O. , Yuen M. F. , Lam S. K. , Cheung H. K.‐L. , Liu X. G. , Wong B. C.‐Y. 
Published: December 2004

SummaryBackground : We previously reported that aspirin inhibited Helicobacter pylori growth and suppressed the mutagenic effect of metronidazole.Aim : To determine the effects of a cyclo‐oxygenase (COX)‐2‐specific inhibitor, SC‐236, and a non‐selective COX inhibitor, indometacin, on the growth, urease activity and antimicrobial susceptibility of H. pylori.Methods : Three H. pylori reference strains, and 18 clinical isolates were treated with SC‐236 or indometacin for 24 and 48 h. Growth, urease activity and susceptibility to clarithromycin and metronidazole of the bacteria were assessed by viable colony counting, spectrophotometry and E‐test respectively.Results : SC‐236 and indometacin inhibited H. pylori growth in a dose‐dependent manner with the lowest inhibitory concentrations of 0.03 and 0.1 mm, and the lethal concentrations of 0.09 and 0.3 mm, respectively. The numbers of CFU/mL in Brucella broth containing 0.09 mm SC‐236 were 2 log lower at 24 h, and even 3 log lower at 48 h than that at 0 h (P = 0.035, compared with the vehicle control). Treatment of 0.3 mm indometacin reduced the number of CFU/mL by 1 log at 24 h compared with that at 0 h (P = 0.037 compared with the vehicle control). Helicobacter pylori urease activity began to decrease with 0.06 mm SC‐236 at 24 h (P = 0.016), and 0.3 mm indometacin at 48 h (P = 0.025). MICs of metronidazole and clarithromycin against H. pylori were decreased significantly in the presence of 0.03 mm SC‐236 or 0.1 mm indometacin (all P < 0.001).Conclusion : Both SC‐236 and indometacin suppressed the growth and urease activity of H. pylori in a dose‐dependent manner, and increased its susceptibility to the antibiotics.
Effects of effervescent ranitidine on gastric pH: comparison with almagate and placebo in fasting and postprandial conditions
Authors: Rey E. , Poves‐Francés C. , Sánchez G. , Fueyo A. , Badiola C. , Díaz‐Rubio M. 
Published: December 2004

SummaryAim : To compare the effect of effervescent ranitidine, almagate (magnesium carbonate‐aluminium hydroxide) and placebo on gastric pH, in fasting and postprandial conditions.Methods : Twelve healthy volunteers underwent a gastro‐oesophageal pH monitoring on three different occasions after the administration of each of the following randomly allocated treatments: almagate, effervescent ranitidine and placebo. Treatment effects were assessed in fasting and postprandial conditions. Onset and duration of alkalinization, percentage of time with pH >4 and median gastric pH after treatments were calculated in both periods.Results : Onset of action of effervescent ranitidine was similar to almagate in fasting [median 1.2 min (IQR: 0.6–12.7) vs. 2.9 min (0.4–227.6)] and postprandial conditions [1.4 min (0.5–4.9) vs. 4.1 min (1.3–63.8)] and both were significantly faster than placebo [fasting 211.1 min (2.7–240); postprandial 240 min (175.6–240)]. The duration of action of effervescent ranitidine was statistically significant longer than almagate in fasting [235 min (105.2–239.4) vs. 19.4 min (6.7–38.8)] and postprandial conditions [171.8 min (133.2–239.5) vs. 61.3 min (44.7–91.9)]. Effervescent ranitidine was more effective than almagate in increasing the percentage of time with a pH >4 both in fasting (73.9% vs. 7.3%) and postprandial (59.1% vs. 21.3%).Conclusions : Effervescent ranitidine shows an effect on gastric pH as fast as almagate but provides a duration of alkalinization longer than almagate, in both fasting and postprandial conditions.
Review article: tegaserod for chronic constipation
Authors: Johanson J. F. 
Published: December 2004

SummaryConstipation is one of the most common gastrointestinal conditions with limited effective treatment options. Tegaserod, a 5‐HT4 receptor agonist has demonstrated efficacy in relieving constipation‐related symptoms in patients suffering from irritable bowel syndrome with constipation. This paper reviews two recent reports that have evaluated the efficacy and safety of tegaserod in pateints with chronic constipation. Two double‐blind, randomized, placebo‐controlled trials have been reported; one in Europe and Asia (E2301) the other in North and South America (E2302). After a 2‐week baseline period, patients were randomized to treatment with tegaserod 2 mg b.d., tegaserod 6 mg b.d. or placebo for 12 weeks. Two thousand, six hundred and twelve patients were randomized, the majority were white females. In both studies, responder rates during weeks 1–4 were significantly greater in the tegaserod groups compared with placebo. A similar trend was seen over weeks 1–12. Statistically significant improvements over placebo were seen across the majority of secondary efficacy variables. Tegaserod was safe with no consistent differences in the frequency of adverse events among the various groups. In conclusion, treatment of chronic constipation with tegaserod was associated with significant improvement in bowel frequency as well as other constipation symptoms. Tegaserod was also well tolerated in this patient population.
Spatial heterogeneity of ecosystem carbon fluxes in a broadleaved forest in Northern Germany
Authors: Kutsch Werner L. , Liu Chunjiang , Hörmann Georg , Herbst Mathias 
Published: December 2004

AbstractCarbon fluxes were investigated in a mature deciduous forest, located in Northern Germany (53°47′N–10°36′E), by means of eddy‐covariance technique, stand survey and models. This forest has been managed following a concept of nature‐oriented forestry since the 1980s. One of the goals of the study was to test whether changed management led to increased carbon sequestration. The forest contains several broadleaved tree species. Depending on wind direction, the fetch‐area of the eddy‐covariance data was dominated by different tree species. Three subplots dominated by Oak, Beech or Alder/Ash could be distinguished from the tower data. In each of these subplots, 30 × 30 m2 areas were defined to analyse leaf area index, litterfall and the increase of the wood biomass.Eddy‐covariance analysis showed that the gross primary productivity (GPP′) was higher in the Oak subplot (−1794 g C m−2 yr−1) in comparison with the Beech plot and the Alder/Ash plot (−1470 and −1595 g C m−2 yr−1, respectively). The total ecosystem respiration (TER) was the highest in the Alder/Ash‐dominated subplot (1401 g  C m−2 yr−1) followed by the Oak plot and the Beech plot (1235 and 1174 g C m−2 yr−1, respectively). The resulting net ecosystem productivity (NEP) was −559 g C m−2 yr−1 for the Oak‐dominated subplot, −295 g C m−2 yr−1 for the Beech plot and −193 g C m−2 yr−1 for the Alder/Ash plot.From Stand survey and modelling, the net primary productivity was estimated as 1103, 702 and 671 g C m−2 yr−1 in the Oak, Beech and Alder/Ash plot, respectively. Also carbon flux with litterfall was the highest in the Oak plot 343 g C m−2 yr−1 and lowest in Alder/Ash plot (197 g m−2 yr−1) with the Beech plot in between (228 g m−2 yr−1). The observations indicate an increase of the proportion of litterfall with increasing GPP′ and a different ability of carbon sequestration of the three stands in medium temporary scale. Only in the Oak stand that comprised the oldest trees and the most structured canopy the carbon sequestration was increased compared with conventionally managed forests.
The effects of chronic smoking on the ocular surface and tear characteristics: a clinical, histological and biochemical study
Authors: Satici Ahmet , Bitiren Muharrem , Ozardali Ilyas , Vural Huseyin , Kilic Adil , Guzey Mustafa 
Published: December 2004

Abstract.Purpose:  To investigate the effects of chronic smoking on the ocular surface and tear characteristics. Methods:  The Schirmer I‐test, tear film break‐up time, rose Bengal staining scores, impression cytology, tear lysozyme concentration, eye irritation symptoms, and eye irritation indices were determined for 44 eyes in 44 healthy, chronic smokers who had smoked six or more cigarettes per day for the previous year. Thirty‐seven eyes in 37 healthy, non‐smokers were assessed in the same masked manner for comparison. Cytological specimens were obtained from the temporal interpalpebral bulbar conjunctiva by ‘impression’ technique. Goblet cells were counted in the specimens obtained and squamous metaplasia was graded following epithelial cell morphology assessment. Results:  In chronic smokers, we found decreased tear film break‐up time (p = 0.022) and tear lysozyme concentration (p = 0.013), and increased Schirmer I‐test values (p = 0.047), squamous metaplasia scores (p = 0.016), eye irritation scores (p < 0.001) and eye irritation indices (p = 0.013), as compared with the control group. There were no statistically significant differences in goblet cell counts (p = 0.710) or rose Bengal staining scores (p = 0.827). Conclusion:  These findings suggest that chronic smoking has a negative effect on the ocular surface and affects some tear characteristics. The chronic ocular irritative effects of cigarette smoking may lead to defects in ocular surface defence.
The influence of sex hormones on ocular blood flow in women
Authors: Toker Ebru , Yenice Özlem , Akpinar Ihsan , Aribal Erkin , Kazokoglu Haluk 
Published: December 2004

Abstract.Purpose:  To investigate the influence of sex hormones on ocular haemodynamics, blood flow velocities in the ophthalmic and central retinal arteries and serum levels of sex hormones were measured in pre‐ and postmenopausal women. Methods:  Colour Doppler imaging (CDI) was used to determine the flow velocities (peak systolic velocity [PSV] and end‐diastolic velocity [EDV]) and the resistive index (RI) in the ophthalmic and central retinal arteries in 22 premenopausal and 32 postmenopausal women, who had never received hormone replacement therapy. Serum levels were measured for oestradiol, free testosterone and follicle‐stimulating hormone. The CDI parameters were compared between the two groups and the influence of serum levels of oestradiol and testosterone on blood flow velocities and the resistive indices were analysed. Results:  After correcting for age and mean arterial blood pressure, an analysis of covariance disclosed a significantly lower EDV (p = 0.02) and a significantly higher RI (p = 0.01) in the central retinal artery of postmenopausal women compared with premenopausal women. Partial correlation analysis, controlling for age, revealed significant correlations between the CDI parameters and serum levels of oestradiol and testosterone. For premenopausal women, PSV (r = 0.58, p = 0.04) and EDV (r = 0.73, p = 0.006) in the ophthalmic artery correlated positively with serum oestradiol levels. The RI in the central retinal artery decreased with increasing oestradiol levels in both groups (premenopausal r = − 0.40, p = 0.04; postmenopausal r = − 0.32, p = 0.05). Peak systolic velocity in the central retinal artery correlated negatively (r = − 0.49, p = 0.04), whereas the RI correlated positively (r = 0.53, p = 0.02) with testosterone levels in the premenopausal group. Postmenopausal women with higher testosterone levels had lower EDV (r = − 0.53, p = 0.007) in the central retinal artery and higher RI in both vessels (ophthalmic artery r = 0.48, p = 0.01; central retinal artery r = 0.61, p = 0.002). Conclusion:  Our data provide evidence of a relationship between serum sex hormone levels and blood flow velocities and resistive indices in retrobulbar arteries. Oestradiol appears to have beneficial effects on ocular haemodynamics, whereas testosterone may act as an antagonistic to the effects of oestrogen.
Regulation mechanisms of retinal pigment epithelial cell migration by the TGF‐β superfamily
Authors: Mitsuhiro Marcia Regina Kimie Higashi , Eguchi Shuichiro , Yamashita Hidetoshi 
Published: December 2004

Abstract.Purpose:  To investigate the expression of specific receptors, signal transducers and the effect of transforming growth factor‐β(TGF‐β) on retinal pigment epithelium (RPE) migration and proliferation. Methods:  Human RPE cell line D407 was used in all experiments. The effect of TGF‐β on migration and proliferation were studied using a wound healing model and [3H]‐thymidine incorporation, respectively. The expression of RNA related to the TGF‐β superfamily receptors and SMAD1−4 were assayed by reverse transcriptase‐polymerase chain reaction (RT‐CPR). The effects of TGF‐β on the intracellular position of SMAD were studied by immunoperoxidase and immunofluorescence. Results:  Transforming growth factor‐β 4 nm and activin A 0.36 nm stimulated RPE migration. There was no effect on proliferation. RNA for TGF‐β receptors types 1 and 2, and SMAD1−4 were detected in RPE culture. Transforming growth factor‐β signal transducer SMAD2 but not SMAD1 moved from the cytoplasm to the nucleus after TGF‐β stimulation. Conclusion:  Transforming growth factor‐β can regulate RPE cell migration through specific signal transduction pathways.
Exfoliative glaucoma and primary open‐angle glaucoma: associations with death causes and comorbidity
Authors: Ritland J. S. , Egge K. , Lydersen S. , Juul R. , Semb S. O. 
Published: December 2004

Abstract.Purpose:  To investigate whether type of glaucoma or use of acetazolamide are associated with main cause of death and comorbidity. Material and Methods:  The survival data, including date and cause of death, for 1147 patients with capsular or simple glaucoma who were ultimately hospitalized at the Eye Department, National Hospital, Oslo, between 1961 and 1970, were analysed. Binary logistic regression was carried out to investigate the patterns of death causes and comorbidity in subgroup analyses. Results:  Patients with exfoliative glaucoma (XFG) and those with primary open‐angle glaucoma (POAG) showed no significant differences in rates of death caused by acute cerebrovascular diseases, cardiac diseases and cancer. Interestingly, we found that chronic cerebral diseases such as senile dementia, cerebral atrophy and chronic cerebral ischaemia (n = 81) were more common in patients with XFG than in those with POAG (p = 0.01) and in the group of acetazolamide users (p = 0.03). Patients with XFG had a higher probability of developing an acute cerebrovascular disease than patients with POAG (n = 228, p = 0.03). Conclusion:  In this retrospective study, we found that comorbidity with acute cerebrovascular disease and chronic cerebral diseases (senile dementia, cerebral atrophy and chronic cerebral ischaemia) were more common in patients with XFG than in patients with POAG. Prospective data are needed in order to conclude upon the associations found in this study.
Visual acuity and refractive errors in a suburban Danish population: Inter99 Eye Study
Authors: Kessel Line , Hougaard Jesper Leth , Mortensen Claus , Jørgensen Torben , Lund‐Andersen Henrik , Larsen Michael 
Published: December 2004

Abstract.Purpose: The present study was performed as part of an epidemiological study, the Inter99 Eye Study. The aim of the study was to describe refractive errors and visual acuity (VA) in a suburban Danish population.Methods: The Inter99 Eye Study comprised 970 subjects aged 30–60 years and included a random control group as well as groups at high risk for ischaemic heart disease and diabetes mellitus. The present study presents VAs and refractive data from the control group (n = 502). All subjects completed a detailed questionnaire and underwent a standardized general physical and ophthalmic examination including determination of best corrected VA and subjective refractioning.Results: Visual acuity ≤ 0.05 was found in one eye of one subject and VA ≤ 0.3 in 11 eyes of 11 subjects. The main cause of reduced visual function was strabismic amblyopia. Myopia (≤ − 0.5 D, spherical equivalent refraction) was present in 33.1% of right eyes of the total population but in 56.8% of subjects with a university degree.Conclusions: Strabismic amblyopia was a significant cause of unilateral visual impairment. Myopia was approximately twice as frequent in subjects with a university degree as in the remaining study population.