Reduced expression of collagen type I and increased expression of matrix metalloproteinases 1 in patients with Crohn's disease.

Crohn's disease (CD) is a chronic inflammatory bowel disease of still unknown etiology. The aim of our study was to find out whether there are any changes in the colonic wall of CD patients that could give hints for a predisposing disorder concerning the extracellular matrix, especially the collagen metabolism. Eight samples of colonic tissue from patients with Crohn's disease were compared to 14 specimens from patients without Crohn's disease. We performed a sirius red test for the overall collagen content and immunohistochemical studies examining differentiation between" collagen type I and type III and the expression of MMP-1 and MMP-13. In the bowel sections of patients with Crohn's disease, decreased levels of mature collagen type I with a resulting lower ratio of collagen I/III compared to patients without Crohn's disease were found (1.12 +/- 0.29 vs. 1.59 i 0.31).The expression of MMP-1 was significantly increased in the CD group (9.21 i 6.02 vs.6.02 i 1.98), whereas expression of MMP-13 showed no difference in both groups. Our study gives the first indication that preexisting changes of the extracellular matrix in the colonic wall may play a role in the pathogenesis of CD. Further studies have to be done to elucidate these interesting aspect of the pathogenesis in Crohn's disease.     

Physiological levels of pro- and anti-inflammatory mediators in cerebrospinal fluid and plasma: a normative study

Numerous recent studies have reported a significant inflammatory reaction in the brain and the systemic circulation following traumatic brain injury (TBI), infection, or neoplasm of the brain with a sequential release of pro- and anti-inflammatory mediators. Although there is growing knowledge and understanding of the mechanisms leading to the often poor outcome of these patients, only a limited database exists on the physiological expression of pro- and anti-inflammatory cytokines and molecules in plasma and particularly in cerebrospinal fluid (CSF). Therefore, we analyzed paired plasma/CSF samples of healthy human volunteers for the physiological concentrations of Interleukin (IL)-6, IL-8, IL-10, soluble TNF-receptors (sTNF-R) p55 and p75, soluble ICAM (sICAM), and soluble E-selectin (sE-selectin). A physiological release of IL-6, IL-8, IL-10, and sTNF-R p55 and p75 was detected in plasma and CSF. In contrast, sICAM and sE-selectin were only detectable in plasma. Pro- and anti-inflammatory mediators exhibited different concentration patterns in plasma and CSF, suggesting a pro-inflammatory predisposition in the central nervous system.     

Margarine consumption, asthma, and allergy in young adults: results of the German National Health Survey 1998

PURPOSE: To examine whether frequent intake of margarine is associated with allergy prevalence in adults using data of a representative national health survey. METHODS: Data on 7124 subjects aged 18 to 79 years were obtained from the German National Health Survey 1998. Confounder-adjusted odds ratios (aOR) with 95% confidence intervals (CI) were calculated by multiple logistic regression, using the frequency of intake of low-fat butter, regular and low-fat margarine as explanatory variable in relation to frequent intake of regular butter as reference group. RESULTS: Frequent intake of margarine of any kind was positively associated with current asthma during the past 12 months in young adults aged 18 to 29 years (aOR, 2.33; 95% CI, 1.03-5.26). In subgroup analysis, the positive association was confined to frequent intake of low-fat margarine (4.51; 1.78-11.43) or the combination of low-fat margarine and low-fat butter (4.79; 1.84-12.44). Consumption of margarine of any kind was not related to hay fever, atopic dermatitis, and atopic sensitization to inhalant allergens. CONCLUSIONS: Frequent intake of margarine rich in n-6 PUFA is not consistently associated with allergic diseases in adults. Other constituents of low-fat margarine or certain dietary habits and lifestyle factors, characterized by use of low-fat margarine, may be related to current asthma.     

Nicotine and cotinine in adults' urine: The German Environmental Survey 1998

In 1998, the German Environmental Survey (GerES III) recruited approximately 5000 adults between the ages of 18 and 69 years. The study population for these analyses consisted of 1580 smokers (34% of the total population) and 3126 nonsmokers. Nicotine and cotinine concentrations in urine were determined by HPLC methods with UV-detection and corrected for creatinine. Nicotine and cotinine concentrations differed between smokers and nonsmokers by factors of 10-100. The multiple linear regression models used for the analyses of nicotine detection in the urine of smokers explained 43.2% and 42.3% of the total volume-specific and creatinine-specific variances, respectively. Cigarette smoking was the major factor responsible for 41% of the total variance. The explained variances of the cotinine results were larger, 51.0% and 49.3% of the total variance were volume-specific and creatinine-specific, respectively. More than 20% of nonsmokers in GerES III were exposed to environmental tobacco smoke at home, at work or in other places. The logistic regression analysis approach used for the group of nonsmokers showed the greatest effects for those exposed to tobacco smoke at home (adjusted OR varied between 4 and 6). These results were seen for nicotine as well as for cotinine excretion. Exposure to tobacco smoke in the workplace doubled the risk for the detection of nicotine and cotinine in urine. When other risk factors such as age, sex, social status, community size, season of urine collection, and the consumption of food containing nicotine such as potatoes, cabbage, tea were included, the effect estimates for tobacco smoke exposure remained unchanged. A new federal bill to diminish environmental tobacco smoke (ETS) exposure in the workplace was recently passed in Germany, but protection of nonsmokers from smoking family members at home needs more attention.     

Postprandial glycaemic, lipaemic and haemostatic responses to ingestion of rapidly and slowly digested starches in healthy young women

The objective of the present study was to investigate the postprandial metabolism of two starches with contrasting rates of hydrolysis in vitro. Characterized using the Englyst method of in vitro starch classification, C*Set 06 598 contained predominantly rapidly digestible starch and C*Gel 04 201 contained predominantly slowly digestible starch. Each test starch, naturally enriched with 13C, was fed to ten healthy female volunteers as part of a moderate fat test meal (containing 75 g test starch and 21 g fat), in a double-blind randomized crossover design. The metabolic response to each starch was measured after an overnight fast, in an acute 6 h study, before and after 14 d of daily consumption of 75 g test starch. During each acute study, blood samples were taken at 15 min intervals for the first 2 h and at 30 min intervals for the remaining 4 h. Breath 13CO2 enrichment was measured at the same time points and indirect calorimetry was performed for 20 min every 40 min immediately before and throughout the study. Significantly more rapid, greater changes in postprandial plasma glucose, NEFA and serum insulin concentrations were observed after consumption of the rapidly digestible starch. Breath 13CO2 output over the first 3-4 h rose rapidly then began to decline following consumption of the rapidly digestible starch, but plateaued for the slowly digestible starch. The 14 d adaptation period did not affect any of the glycaemic or lipaemic variables but there was a reduction in postprandial plasminogen activator inhibitor-1 concentrations. These data confirm that starches characterized as predominantly rapidly digestible versus slowly digestible by the Englyst procedure provoke distinctly different patterns of metabolism postprandially.     

Hypocitraturia as a risk factor for nephrocalcinosis after kidney transplantation

Calcium-oxalate crystal deposition in kidney transplant biopsy specimen led us to investigate the impact of calcineurin inhibitor treatment on urinary excretion of lithogenic and stone inhibitory substances in 53 children after successful kidney transplantation (KTx) receiving cyclosporine A (CsA) or tacrolimus. We compared the values obtained with those of 12 patients with recurrent nephrotic syndrome under CsA and of 6 patients with Rasmussen encephalitis (RE) under tacrolimus therapy. Renal ultrasound examinations were repeatedly performed. Hypocitraturia was found in 69% of patients, with KTx patients having a significantly lower urinary citrate excretion than those receiving calcineurin inhibitors for other reasons. Secondly, we found hyperoxaluria in 35% of patients, again especially in those after KTx. No significant difference in urinary substances was seen comparing CsA with tacrolimus treatment. Urolithiasis was found in one and calcium-oxalate crystal deposition in biopsy specimen of three KTx patients. Calcineurin inhibitor treatment can lead to significant hypocitraturia, especially in patients after KTx receiving the highest dose of medication. Hyperoxaluria is primarily the result of a removal of significant body oxalate stores, deposited during dialysis, but may not be suspected as a specific side effect of calcineurin inhibitor therapy. Both findings can increase the risk for urolithiasis or nephrocalcinosis.     

Ultrasonographic evaluation at 6-month follow-up of plantar fasciitis after extracorporeal shock wave therapy

Introduction The aim of this study was to investigate the effect of extracorporeal shock wave therapy (ESWT) on the ultrasonographic appearance of chronically painful, proximal plantar fasciitis.Materials and methods Twenty-two patients with a unilateral proximal plantar fasciitis were prospectively enrolled after unsuccessful conservative treatment lasting 6 months. The contralateral plantar fascia was used as the control. ESWT (3×3000 shock waves/session of 0.2 mJ/mm²) was performed at weekly intervals. The thickness of the plantar fascia was measured ultrasonographically about 2 cm distal of the medial calcaneal tuberosity. Pain estimation on a visual analogue scale (VAS) and the comfortable walking time were recorded. No local anaesthesia was applied. Follow-up was done at 6, 12 and 24 weeks.Results Before ESWT, the plantar fasciitis side was ultrasonographically significantly thicker than the control side (p<0.05), whereas 6 months after ESWT, the thickness of the fascia was no longer significantly different. The decrease in thickness of the plantar fasciitis side was significant (p<0.05). Pain during activities of daily living decreased by 79% according to the VAS, and the comfortable walking time increased, both significantly (p<0.01). In patients with little pain (VAS<30), the thickness of the plantar fasciitis side was significantly less (p<0.01) compared with patients who still suffered more pain (VAS>30).Conclusion After ESWT, the thickness of the plantar fascia in patients with plantar fasciitis decreased, pain and walking time improved (all significantly).     

A prospective study of the interrelationship between subjective and objective measures of disability before and 2 months after lumbar decompression surgery for disc herniation

The value of range of motion (ROM) as an indicator of impairment associated with spinal problems, and in monitoring changes in response to treatment, is a controversial issue. The aim of this study was to examine the interrelationship between subjective disability (Roland-Morris scores) and objectively measured impairment (ROM), both before and in response to spinal decompression surgery, in an older group of patients with herniated lumbar disc (DH). Seventy-six individuals took part in the study: 33 patients (mean age 57 years, SD 9 years) presenting with DH and for whom decompression surgery was planned, and 43 controls (mean age 57 years, SD 7 years), with no history of back pain requiring medical treatment. In the patient group, pain intensity (leg and back; visual analog score), self-rated disability (Roland-Morris score), certain psychological attributes, and ROM of the spine (Spinal Mouse) were measured before and 2 months after decompression surgery. In addition, the patients rated the success of surgery on a 1–5 Likert scale. The pain-free control group performed only the tests of spinal mobility. Before surgery, compared with matched controls, significantly lower values were observed in the DH patients for standing lumbar lordosis (p=0.01), and for range of flexion of the lumbar spine (ROF_lumbar) (p=0.0006), but not of the hips (ROF_hip) (p=0.14). Roland-Morris Disability scores correlated significantly with ROF_lumbar (r=0.61, p=0.0002), but less well with ROF_hip(r=0.43, p=0.01). Two months after surgery, there were significant reductions in back pain and leg pain (p=0.0001) and in Roland-Morris Disability scores (p=0.019). There was also a significant decrease in the group mean values for lumbar lordosis angle (i.e., a flatter spine after surgery, p=0.002) and ROF_lumbar (p=0.038). ROF_hip showed a (nonsignificant) tendency to increase (p=0.08) towards normal control values. As a result of these two opposing changes, the range of total trunk flexion showed no significant changes from pre-surgery to 2 months post-surgery (p=0.60). On an individual basis, there was a highly significant relationship between the change in self-rated disability scores and the change in ROF_lumbar, pre-surgery- to 2 months post-surgery (r= –0.82; p<0.0001). Changes in ROF_hip showed no such relationship (r= –0.30, p=0.10). The patients in the poor outcome group (surgery didnt help; 9%) had a significantly greater reduction in ROF_lumbar post-surgery compared with the good outcome group (surgery helped; 91%) (p=0.04). In stepwise linear regression, the change in ROF_lumbar was the only variable accounting for the change in self-rated disability pre-surgery to post-surgery (variables not included: pain intensity, psychological factors). The pivotal role of lumbar mobility in explaining disability emphasizes the importance of measuring lumbar and hip ranges of motion separately, as opposed to global trunk motion. In the patient group examined, the determination of lumbar spinal mobility provides a valid, objective measure of function, that shows differences from normal matched controls, that correlates well with self-rated disability, and the changes in which correlate extremely well with subjective changes in disability following surgery.     

Adrenomedullin reduces mesangial cell number and glomerular inflammation in experimental mesangioproliferative glomerulonephritis

BACKGROUND: Adrenomedullin (ADM) is a vasodilator peptide that is abundantly expressed in the kidney. ADM has antiproliferative effects on glomerular mesangial cells (MC) in vitro. Whether or not treatment with ADM can reduce MC proliferation in vivo [i.e., in mesangioproliferative glomerulonephritis (GN)] is unknown. We tested the hypothesis that ADM substitution reduces MC proliferation in GN. METHODS: GN in rats was induced by injection of an anti-Thy-1.1 antibody. Rats received osmotic minipumps, which continuously delivered rat ADM (500 ng/hour, N = 11), or vehicle (N = 13) from day 3 to day 6 after GN induction. Rats were sacrificed 6 days after induction of GN. On kidney sections, cells staining positive for proliferating cell nuclear antigen, mesangial cells, monocytes, and apoptotic cells were counted. Parameters of inflammation and fibrosis were measured in renal cortex and sieved glomeruli by real-time polymerase chain reaction (PCR). RESULTS: Systolic blood pressure, diuresis, albuminuria, creatinine clearance, microaneurysm formation, and mesangial matrix expansion were not influenced by ADM infusion. However, ADM treatment significantly reduced the number of MC, showed a tendency to reduce total glomerular cell proliferation, and significantly increased apoptosis. ADM-treated GN animals showed significantly less glomerular monocyte infiltration. ADM treatment normalized transforming growth factor (TGF)-beta1 mRNA expression and reduced monocyte chemoattractant protein-1 (MCP-1), osteopontin, plasminogen activator inhibitor-1 (PAI-1), collagen I, and collagen III mRNA expression significantly. CONCLUSION: Exogenous ADM infusion reduces MC number and glomerular monocyte infiltration in the state of mesangial proliferation during acute experimental mesangioproliferative GN. These findings indicate that ADM can influence the course of mesangioproliferative GN.