Morphologic and biomechanical changes of rat oesophagus in experimental diabetes

AIM:To study morphologic and biomechanical changes ofoesophagus in diabetes rats.METHODS:Diabetes was induced by a single injection ofstreptozotocin(STZ).The type of diabetes mellitusinduced by parenteral STZ administration in rats wasinsulin-dependent(type I).The samples were excisedand studied in vitro using a self-developed biomaterialtest machine.RESULTS:The body mass was decreased after 4 d with STZtreatment.The length of esophagus shortened after 4,7,14 d.The opening angle increased after 14 d.The shear,longitudinal and circumferential stiffness were obviouslyraised after 28 d of STZ treatment.CONCLUSION:The changes of passive biomechanicalproperties reflect intra-structural alteration of tissue to acertain extent.This alteration will lead to some dysfunctionof movement.For example,tension of esophageal wallwill change due to some obstructive disease.     

Are changes in cognitive functioning in older adults related to changes in subjective complaints?

In many areas of intellectual functioning, age-related declines in older adults' performance and increases in subjective complaints about intellectual performance are observed. However, the literature mostly reports very low relations between functioning and respective complaints. This finding could be the consequence of examining the relation between subjective complaints and the perceived level of functioning. If, however, persons are sensitive to relative changes in performance, they might base their subjective judgment on changes in the level of cognitive functioning. With 202 subjects (mean age=63 years) and two measurements, the authors examine (a) the relation between functioning and complaints at each measurement point, and (b) the relation between changes in functioning and changes in complaints between the measurement points with latent difference variables. The results indicate that there is no relation between level of functioning and level of complaints, but that there is a substantial relation between changes in functioning and complaints.     

Dynamic changes of capillarization and peri-sinusoid fibrosis in alcoholic liver diseases

AIM:To investigate the dynamic changes of capillarizationand ped-sinusoid fibrosis in an alcoholic liver disease modelinduced by a new method.METHODS:Male SD rats were randomly divided into 6groups,namely normal,4 d,2 w,4 w,9 w and 11 w groups.The animals were fed with a mixture of alcohol for designateddays and then decollated,and their livers were harvestedto examine the pathological changes of hepatocytes,hepaticstellate cells,sinusoidal endothelial cells,sinusoid,peri-sinusoid.The generation of three kinds of extra cellular matrixwas also observed.RESULTS:The injury of hepatocytes became severer asmodeling going on.Under electronic microscope,fattyvesicles and swollen mitochondria in hepatocytes,activatedhepatic stellate cells with fibrils could been seen near oraround it.Fenestrae of sinusoidal endothelial cells weredecreased or disappeared,sinusoidal basement was formed.Under light microscopy typical peri-sinusoid fibrosis,gridding-like fibrosis,broaden portal areas,hepatocyte's fatty andballoon denaturation,iron sediment,dot necrosis,congregated lymphatic cells and leukocytes were observed.Type Ⅰ collagen showed an increasing trend as modelinggoing on,slightly recovered when modeling stopped for 2weeks.Meanwhile,type Ⅳ collagen decreased rapidly whenmodeling began and recovered after modeling stopped for2 weeks.Laminin increased as soon as modeling began anddid not recover when modeling stopped for 2 weeks.CONCLUSION:The pathological changes of the modelwere similar to that of human ALD,but mild in degree.Ithad typical peri-sinusoid fibrosis,however,capillarizationseemed to be instable.It may be related with the reductionof type Ⅳ collagen in the basement of sinusoid duringmodeling.     

Stress-related changes in oesophageal permeability: filling the gaps of GORD?

Albeit remaining a controversial issue, it has become increasingly recognised that psychological stress has a major impact on gut mucosal function and affects the course of gastrointestinal disorders. Research during the last decade has shown that stress causes barrier dysfunction of the gastrointestinal mucosa by mechanisms that mainly involve neuropeptides and mast cells. Moreover, accumulating evidence implicates increased permeability as a pathogenic factor in gastroesophageal reflux disease (GORD). Recent data demonstrating that psychological stress may induce a permeability defect in stratified epithelia, including the oesophagus, shed new light on the pathophysiological events leading to heartburn and GORD.     

Have rapid socioeconomic changes influenced awareness of blood pressure in Poland?

The aim of our study was to evaluate changes in awareness of blood pressure during transition into a market economy in Poland. Thus, in 1994, we conducted a cross-sectional survey based on a questionnaire interview on a sample of 2080 men (M) and women (F) aged 18 years and over. The subjects were selected from a Polish population by stratified and cluster random sampling with quotas by the Center for Social Research in Sopot. They were asked if they were aware of blood pressure. The results were analysed according to age, sex, education level, income and place of living. In September 1997 we carried out the same investigation on a new group of 1664 adults. In addition to the questionnaire, the blood pressure (three recordings at home) measurements were completed. The interviewers were well-trained medical students. Awareness of blood pressure has declined (P < 0.001) from 71% in 1994 to 65.5% in 1997. The highest decrease in awareness of blood pressure was observed among less educated people, as well as among people living in smaller cities and villages. The overall prevalence of hypertension was 25.9% by 'older' WHO criteria (BP > or =160/95 mm Hg or taking antihypertensive medication) and 44.5% by JNC VI criteria (BP > or =140/90 mm Hg or taking antihypertensive medication). Forty-six percent of hypertensive subjects classified by JNC VI criteria were previously known to be hypertensives and 54% were newly detected (F: 39%, M: 69%). Low awareness of blood pressure in Poland is the crucial factor of insufficient detectability of hypertension. Decline of awareness of blood pressure being the most significant among people representing lower social status, emphasises the need for urgent preventive measures.     

TNF-α induces changes in LDH isotype profile following triggering of apoptosis in PBL of non-Hodgkin’s lymphomas

Based on the possibility of tumor necrosis factor (TNF)- to perform multiple and opposite biologic effects, we simultaneously investigated in vitro its effects on intracellular lactate dehydrogenase (LDH)-H and LDH-M isoenzyme activity and morphological characteristics following induction of apoptosis in peripheral blood mononuclear cells (PBMC) of non-Hodgkins lymphoma patients (NHL) prior to and after the end of applied chemotherapy. TNF- showed a significant increase (p<0.05) of LDH–H and LDH-M activity in sonified PBMC of healthy controls after 18 h cultures accompanied with an increase of apoptotic index (AI) from 2.3 to 16.2%. Contrary to this, in PBMC of NHL patients prior to therapy TNF- induced a significant decrease (p<0.05) of LDH-H isotype activity. In patients after administration of chemotherapy, TNF- in a dose of 100 U/ml induced a significant increase (p<0.05) of LDH-M isotype activity, but not of LDH-H. In the PBMC of NHL patients prior to chemotherapy, TNF- in vitro induced an increase of AI from 2.8 up to 6.8%, while in PBMC of NHL patients after applied chemotherapy AI changed from 7.2 to 14.4%. However, there was no significant difference in the increase of apoptosis in PBMC of NHL patients with high-grade malignancy and high rate response among patients who received first-line therapy, high-dose therapy, or third-line therapy regimens after in vitro TNF- treatment. These results indicated different susceptibilities of PBMC of NHL to TNF- when effects were analyzed by determination of intracellular LDH isotype profile and induction of apoptosis prior to and after administration of therapy in comparison to effects on healthy controls PBMC.     

Impact of Helicobacter pylori infection on histological changes in non-erosive reflux disease

AIM:The evidence for an association between Helicobacterpylori (H pylori) and gastroesophageal reflux disease,eitherin non-erosive (NERD) or erosive esophagitis (ERD) remainsuncertain.The available data on the histological changes inNERD and the effect on Hpyloriinfection on them are elusive.The aim of this study therefore was to prospectively evaluatethe histological findings and the impact of Hpyloriinfectionon a group of symptomatic patients with NERD.METHODS:Fifty consecutive patients were prospectivelyevaluated for symptoms compatible with GORD.In all cases,routine endoscopy and lugol directed biopsies were performedand assessed histologically in a blinded manner.RESULTS:The overall prevalence of Hpyloriinfection was70%.Twenty-nine patients out of 50 (58%) were NERDpatients.No statistical significance was observed betweenthe H pyloristatus and NERD.The remaining 21 (42%)were diagnosed as follows:13 (26%),6 (12%),2(4%) withesophagitis grade A,B and C respectively.A statisticallysignificant correlation was observed between the Hpylori and esophagitis grade A,as well as between Hpylori-andgrade B.Biopsies from 2 patients were not included becauseof insufficient materials.Histologically,a basal zone hyperplasiawas found in 47 (97.91%) patients,alterations of glycogencontent in 47 (97.91%),papillae elongation in 33 (68.75%),blood vessels dilatation in 35(72.91%),chronic inflammationin 21 (43.75%),infiltration with eosinophils,neutophils andT-lymphocytes in 4 (8.33%),6 (12.5%) and 39 (81.25%)respectively.No correlation was observed between theHpyloristatus and the histological parameters studied eitherin NERD or GERD.CONCLUSION:Histological assessment can not differentiatesymptomatic patients with erosive versus non-erosive refluxdisease.Moreover,Hpyloriinfection may not act as animportant factor in patients with NERD.     

Immunohistologic markers of immune activation and changes of glycosylation of serum proteins in primary Sjögren's syndrome

OBIECTIVE: To assess the possible correlations between the immune activation of certain surface antigens at the lip salivary gland (LSG) level, and changes in glycosylation of serum proteins in primary Sj?gren's syndrome (SS). METHODS: LSG biopsy samples were obtained from 22 SS patients (mean age 56.3 years; mean disease duration 70.8 months) and prepared for immunohistochemical analysis using murine monoclonal antibodies for interleukin-2 receptor (IL-2R) (CD25) and for the class II major histocompatibility antigen HLA-DR. The glycosylation of serum proteins was evaluated in all patients by an enzyme-linked lectin assay (ELLA) using concanavalin A (Con A). RESULTS: In LSG specimens the presence of IL-2R was observed at the infiltrating level, mainly periductally, in 13 (59%) cases and on the epithelial cells of 14 (64%) patients. In 13 out of 22 SS patients (59%) a marked positivity both of the infiltrates and of the epithelium was found for anti-HLA-DR monoclonal antibody. The degree of expression of different antigens on LSG samples was correlated with their histologic class according to Tarpley evaluation. The positivity for IL-2R and HLA-DR molecules on glandular tissues was correlated. A significant increase in the total Con A reactivity of serum proteins was found in those patients expressing IL-2R and HLA-DR antigens on LSG specimens. CONCLUSIONS: The co-expression of IL-2R and HLA-DR antigens on both the epithelium and infiltrates of LSG is consistent with a participation of these cells in the immune process of SS. Moreover, changes in the glycosylation of serum proteins seem to be related to the presence of these immunoactivation markers of the disease at the LSG level, suggesting that the control of protein glycosylation could be mediated by the same mechanisms involved in the tissue damage of SS.     

Temporal changes in the frequencies of HLA genotypes in patients with Type 1 diabetes--indication of an increased environmental pressure?

AIMS/HYPOTHESIS: The incidence of Type 1 diabetes has increased 2.5 times during the time period from 1966 to 2000 in Finland-a general trend seen in almost all developed countries that can only be explained by environmental factors. The aim of this study was to test the possible effect of a changing environment on distribution of genotypes associated with disease susceptibility. METHODS: HLA DRB1-DQA1-DQB1 genes and two diabetes-associated polymorphisms at IDDM2 and IDDM12 were analyzed. The frequencies of genotypes were compared between cases diagnosed with childhood-onset Type 1 diabetes during the period of 1939-1965 (n=367) and those diagnosed between 1990 and 2001 (n=736). Chi-square statistics or the Fisher's Exact test were used for the comparison of frequencies of analyzed haplotypes and genotypes in the two groups. RESULTS: The frequencies of (DR3) -DQA1*05-DQB1*02 and (DR4) -DQB1*0302 risk haplotypes and the high risk (DR3) -DQA1*05-DQB1*02/DRB1*0401-DQB1*0302 genotype were higher while proportion of patients carrying protective haplotypes-(DR15) -DQB1*0602 and (DR1301) -DQB1*0603-or protective genotypes was lower in patients diagnosed before 1965 as compared to those who developed disease after 1990. No temporal variation was found in the frequencies of genotypes at IDDM2 and IDDM12. CONCLUSION/INTERPRETATION: Our data suggest that the need for genetic susceptibility to develop Type 1 diabetes has decreased over time due to an increasing environmental pressure and this results in a higher disease progression rate especially in subjects with protective HLA genotypes.     

Structural changes in the airways: cause or effect of chronic cough?

Patients with a chronic cough have asthma or "asthma-related" diagnoses such as cough variant asthma or non-asthmatic eosinophilic bronchitis usually responsive to inhaled corticosteroid therapy, or non-asthma-related diagnoses including "idiopathic" or "unexplained" cases. Both of these conditions involve airway inflammation. More recently, structural changes or remodeling of the lower airways, which have been considered characteristic of classic asthma with wheezing, have also been demonstrated in patients with chronic cough, irrespective of its cause. In this article, the presence, pathogenesis, and possible consequences of such structural changes in patients with chronic cough are reviewed. Although whether chronic cough leads to structural changes or structural changes is a cause of chronic cough is difficult to determine, the concomitance of both mechanisms may lead to a positive feedback mechanism or a vicious cycle of cough persistence.     

Can the changes in dietary fat intake reduce the risk of onset and development of atherosclerosis and of ischemic cardiopathy in particular?

In this review we have collected data from epidemiologic studies and clinical trials published from 1968 to 1989 on the relationship between dietary fat and risk of coronary heart disease. Although the reported observational studies of diet and coronary heart disease provide general support for the classic diet-heart hypothesis, evidence of specific dietary lipids is weak. A positive association with saturated fat intake was seen in two prospective studies. A positive association with cholesterol intake was found in only two cohort studies, and an inverse relationship with polyunsaturated fat intake in only one. Clear evidence from dietary trials in the prevention of coronary heart disease has not been found. The analysis of trends in coronary heart disease and stroke mortality of developed countries has shown a discrepancy between fat intakes, cholesterol levels and mortality. The reduction in intake of certain foods "at high risk" such as meat, eggs, milk and cheese, as a preventive intervention, is based on weak scientific evidence. A strategy program has to emphasize the maintenance of ideal body weight by caloric control, an adequate level of physical activity, and the control of other risk factors such as hypertension, hypercholesterolemia, and diabetes.     

Possibility of non-invasive diagnosis of gastric mucosal precancerous changes

AIM:To assess the possibility of non-invasive screening ofatrophic chronic gastritis for preventing further developmentof gastric cancer.METHODS:One hundred and seventy-eight consecutiveHelicobacter pylori(H pylori)-positive dyspeptic patientsafter detection of serum levels of pepsinogen-1(PG-1)andgastrin-17(G-17)by enzyme immunoassay were proposedfor endoscopy and histology.The serologic and morphologicresults were compared with estimating the sensitivity,specificity and prognostic values of the tests.RESULTS:There was statistically significant reversedependence between the grade of stomach mucosal antralor corpus atrophy and the proper decreasing of serum G17or PG1 levels.The serologic method was quite sensitive inthe diagnosis of non-atrophic and severe antral and corpusgastritis.Also,it was characterized by the high positive andnegative prognostic values.CONCLUSION:Detection of serum G-17 and PG1 levels canbe offered as the screening tool for atrophic gastritis.Thepositive serologic results require further chromoendoscopywith mucosal biopsy,for revealing probable progressing ofatrophic process with development of intestinal metaplasia,dysplasia or gastric cancer.Pasechnikov VD,Chukov SZ,Kotelevets SM,Mostovov AN,Mernova VP,Polyakova MB.Possibility of non-invasive diagnosisof gastric mucosal precancerous changes.World J Gastroenterol2004;10(21):3146-3150http://www.wjgnet.com/1007-9327/10/3146.asp     

Renal carcinogenesis in models of diabetes in rats—metabolic changes are closely related to neoplastic development

Aims/hypothesis There is an increased risk of renal cell carcinoma (RCC) in human diabetes mellitus. We therefore examined the influence of hyperglycaemia and glucose-lowering treatment on nephrocarcinogenesis in rats. Methods Rats (n = 850), which were either spontaneously diabetic, streptozotocin-diabetic or normoglycaemic, were examined with special reference to Armanni–Ebstein lesions (AEL). Results Irrespective of the cause of diabetes, diabetic but not normoglycaemic rats developed typical glycogenotic clear-cell AEL. AEL showed strong proliferative activity, which was nearly completely inhibited by EGF receptor blockade (Gefitinib treatment). Many findings suggested a stepwise development of RCCs from AEL. Whereas the number and size of RCCs gradually increased in all diabetic groups, beginning at 6 months after onset of diabetes, normoglycaemic controls did not developed RCC. After 28 months, up to 82% of diabetic animals had at least one RCC. In contrast to the proximal tubules, the distal tubular system, including glycogenotic AEL, had the same levels of enzyme activities as RCC (e.g. high glycogen phosphorylase and synthase activity, lack of glucose 6-phosphatase activity) and the same expression patterns of cytokeratin 7 and several growth factors, along with their receptors and signal transduction proteins (TGF-α, EGF receptor, IGF-I, IGF-I receptor, IGF-II receptor, insulin receptor substrate 1, v-raf-1 murine leukemia viral oncogene homologue 1 and mitogen activated protein kinase kinase 1). In addition, direct morphological transitions between distal tubules, AEL and RCCs were frequently observed. All these findings indicate a common origin and a precursor–product relationship of AEL and RCCs. Conclusions/interpretation Nephrocarcinogenesis in diabetic rats results from sustained hyperglycaemia, resulting in an adaptive metabolic response, altered growth factor signalling and subsequent neoplastic transformation of the tubular epithelial cells. Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorised users.     

Chronological changes in the systemic manifestations of intestinal Behcet’s disease and their significance in diagnosis

Purpose

Intestinal Behçet's disease (BD) is challenging to diagnose, especially if the patient presents with typical colonoscopic findings of intestinal BD without systemic manifestations of BD. We performed this study to evaluate the systemic manifestations of BD in patients with typical colonoscopic findings of intestinal BD at the time of initial presentation and to identity the chronologic changes of these features during an extended follow-up period.

Methods

One hundred twenty-six consecutive patients who showed typical colonoscopic findings of intestinal BD at a single institution in Korea were enrolled. Clinical and endoscopic data were collected from a medical database and using a written questionnaire. Parameters including demographic characteristics and the subset type of BD at the initial and endpoints of the follow-up were analyzed.

Results

The mean follow-up period was 63.9?±?50.9 months. The number of cases that satisfied the International Study Group for Behçet’s Disease criteria at initial diagnosis, 19.0%, increased to 53.2% by the end of follow-up. When the Japanese criteria were used for classification, the proportion of complete and incomplete type BD increased (2.4% and 26.2% to 18.3% and 49.2%, respectively), while that of suspected and not-satisfied subtype BD decreased (22.2% and 49.2% to 19.0% and 13.5%, respectively) during the follow-up period.

Conclusions

Our data suggest that patients who lack the systemic manifestations of BD could be included in the category of intestinal BD when typical intestinal lesion is identified, indicating that close examination and early treatment should be considered in such patients.     

Glucose-dependent changes in SNARE protein levels in pancreatic β-cells

Prolonged exposure to high glucose concentration alters the expression of a set of proteins in pancreatic β-cells and impairs their capacity to secrete insulin. The cellular and molecular mechanisms that lie behind this effect are poorly understood. In this study, three either in vitro or in vivo models (cultured rat pancreatic islets incubated in high glucose media, partially pancreatectomized rats, and islets transplanted to streptozotozin-induced diabetic mice) were used to evaluate the dependence of the biological model and the treatment, together with the cell location (insulin granule or plasma membrane) of the affected proteins and the possible effect of sustained insulin secretion, on the glucose-induced changes in protein expression. In all three models, islets exposed to high glucose concentrations showed a reduced expression of secretory granule-associated vesicle-soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins synaptobrevin/vesicle-associated membrane protein 2 and cellubrevin but minor or no significant changes in the expression of the membrane-associated target-SNARE proteins syntaxin1 and synaptosomal-associated protein-25 and a marked increase in the expression of synaptosomal-associated protein-23 protein. The inhibition of insulin secretion by the L-type voltage-dependent calcium channel nifedipine or the potassium channel activator diazoxide prevented the glucose-induced reduction in islet insulin content but not in vesicle-SNARE proteins, indicating that the granule depletion due to sustained exocytosis was not involved in the changes of protein expression induced by high glucose concentration. Altogether, the results suggest that high glucose has a direct toxic effect on the secretory pathway by decreasing the expression of insulin granule SNARE-associated proteins.