Vitreous levels of interleukine-8 and monocyte chemoattractant protein-1 in macular oedema with branch retinal vein occlusion.

PURPOSE: To investigate whether interleukine-8 (IL-8) and monocyte chemoattractant protein-1 (MCP-1) are related with macular oedema in patients with branch retinal vein occlusions (BRVOs). DESIGN: Retrospective case-control study. PARTICIPANTS: Nineteen patients who had macular oedema due to BRVO and nine patients with non-ischaemic ocular diseases (control group). METHODS: Macular oedema was examined by optical coherence tomography. Both venous blood and vitreous samples were obtained at the time of vitreoretinal surgery. IL-8 and MCP-1 levels in vitreous fluid and plasma were determined with enzyme-linked immunosorbent assay kits. Variables were compared with the Mann-Whitney U-test, Wilcoxon's signed-ranked test, and the chi2-test, when appropriate. To examine correlations, Spearman's rank-order correlation coefficients were calculated. Statistical significance was set at P<0.05. RESULTS: The vitreous fluid levels of IL-8 (median: 63.5 pg/ml) and MCP-1 (median: 1522.4 pg/ml) were significantly higher in the patients with BRVO than in the control group (median: 5.1 and 746.5 pg/ml respectively; P<0.001 and <0.001 respectively). Vitreous IL-8 and MCP-1 were significantly correlated in patients with BRVO (P=0.009). CONCLUSIONS: Both IL-8 and MCP-1 were elevated in the vitreous fluid of patients with BRVO and macular oedema. Both chemokines may contribute to the pathogenesis of macular oedema in patients with BRVO.

Interleukin-8, monocyte chemoattractant protein-1 and IL-10 in the vitreous fluid of patients with proliferative diabetic retinopathy.

AIMS: To determine the intra-vitreous levels of two pro-inflammatory cytokines [interleukin-8 (IL-8), monocyte chemoattractant protein-1 (MCP-1)] and the anti-inflammatory cytokine interleukin-10 (IL-10) in patients with proliferative diabetic retinopathy (PDR). In addition, the relationship between the profile of cytokines and PDR activity has also been evaluated. PATIENTS AND METHODS: The study included 22 consecutive diabetic patients with PDR (4 Type 1 and 18 Type 2) on whom a vitrectomy was performed. Sixteen age-matched non-diabetic patients with other conditions requiring vitrectomy, but in which the retina was not directly affected by neovascularization served as a control group. IL-8, MCP-1 and IL-10 were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: The vitreal levels of both IL-8 and MCP-1 were strikingly higher in diabetic patients with PDR in comparison with the control group [173.5 (64-1670) vs. 49 pg/ml (25-145), P < 0.001, and 2171 (388-6155) vs. 438 pg/ml (207-1344), P < 0.001, respectively]. In addition, the vitreous concentrations of IL-8 and MCP-1 were higher in patients with active PDR than in those patients with quiescent PDR [324.5 (80-1670) vs. 173.5 pg/ml (64-487), P = 0.06 and 3596 (1670-6155) vs. 1143 pg/ml (388-2500), P = 0.01, respectively]. However, vitreal levels of IL-10 in diabetic patients were similar to that obtained in the control group [2.89 (1.55-5.50) vs. 2.46 pg/ml (2.2-5.41), P = NS]. CONCLUSIONS: The pro-inflammatory cytokines IL-8 and MCP-1 are increased in the vitreous fluid of PDR patients without an increase in the anti-inflammatory cytokine IL-10. In addition, both IL-8 and MCP-1 intra-vitreous levels correlated with PDR activity, thus suggesting that these cytokines may be pathogenically important in PDR.

Metalloproteinases and tissue inhibitors of metalloproteinases in exudative pleural effusions.

The aim of this study was to assess the expression of several metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) in exudative pleural effusions, and their relationship with inflammatory and fibrinolytic mediators in parapneumonic effusions. The study included 51 parapneumonic effusions (30 empyema or complicated parapneumonic, 21 noncomplicated parapneumonic), 28 tuberculous, 30 malignant and 30 transudates. Inflammatory markers (tumour necrosis factor-alpha, interleukin-8, polymorphonuclear elastase), fibrinolytic system variables (tissue plasminogen activator (PA), urokinase PA (u-PA), plasminogen activation inhibitor (PAI)-1, PAI-2), and several MMPs (MMP-1, MMP-2, MMP-8, MMP-9) and TIMPs (TIMP-1, TIMP-2) were determined by ELISA in plasma and pleural fluid. Elevated MMP-2 and TIMP-1 concentrations were observed in all the pleural fluid samples studied. The group of empyema or complicated parapneumonic effusions showed higher MMP-1, MMP-8 and MMP-9 concentrations than the remaining exudates. There was no correlation between MMP and TIMP levels in plasma and pleural fluid in this group of effusions. In parapneumonic effusions, MMP-1, MMP-8 and MMP-9 showed a positive correlation with the inflammatory markers and with u-PA and PAI-1. Moreover, there was a relationship between MMP-8 concentration in pleural fluid and pleural thickening at the end of treatment. In conclusion, elevated metalloproteinase-1, -8 and -9 expression was found in parapneumonic pleural effusions. These metalloproteinases could be implicated in the local inflammatory response existing in this group of effusions.

Analysis of bone alkaline phosphatase as a marker for the diagnosis of osteoporosis in men under androgen ablation.

The objective of this study was to evaluate the usefulness of serum determination of bone alkaline phosphatase (BAP) in the diagnosis of osteoporosis in men with prostate cancer under androgen ablation. Serum levels of BAP and bone mineral density (BMD) were assessed in 110 patients with non-metastatic, treated prostate cancer. Fifty-eight patients were under androgen deprivation during a period between two and 96 months and 52 had been submitted only to radical prostatectomy. Mean serum BAP was 11.8 ng/mL in patients with normal BMD, 16.7 ng/mL in patients with osteopenia (p. 0.058), and 19.3 ng/mL in patients with osteoporosis (p = 0.044). The correlation between serum BAP and BMD was significant (p. 0.006) but with an index of only 0.26. Receiver operating characteristic analysis for the diagnosis of osteoporosis showed an area under the curve of 0.608. None of the cutoff points that provided specificities of 75%, 90% and 95% gave significant distributions. The positive and negative predictive values as well as the odds ratios were not of any clinical usefulness. We conclude that serum BAP should not be considered a good marker for the diagnosis of osteoporosis in men with prostate cancer. Therefore, BAP serum determination cannot replace bone densitometry as a diagnostic tool.

Nitric oxide and vascular endothelial growth factor concentrations are increased but not related in vitreous fluid of patients with proliferative diabetic retinopathy.

AIMS: Several reports have implicated nitric oxide (NO) in the angiogenic process. The assessment of NO stable end products, nitrite and nitrate (NOx), is commonly used as a measure of NO production in biological fluids. The aims of the study were to investigate NOx concentrations in the vitreous fluid of patients with proliferative diabetic retinopathy (PDR) and to evaluate the relationship between NOx and vascular endothelial growth factor (VEGF). PATIENTS AND METHODS: Serum and vitreous fluid samples were obtained simultaneously at the time of vitreoretinal surgery from 23 patients with PDR, and 17 control non-diabetic patients with non-proliferative ocular disease. NOx was determined by using the Griess reaction and VEGF levels were assessed by ELISA. RESULTS: The intravitreous concentration of NOx was significantly elevated in patients with PDR in comparison with the control group (31.6 +/- 2.96 micromol/l vs. 18 +/- 2.46 micromol/l; P = 0.01). However, we did not detect any differences between NOx serum concentrations. We observed a correlation between serum and vitreous levels of NOx in diabetic patients (r = 0.79; P < 0.001), but not in the control group. Intravitreous levels of VEGF in patients with PDR were higher than those obtained in serum (1.42 ng/ml (0.12-7.62) vs. 0.12 ng/ml (0.03-0.42); P < 0.01). Vitreal levels of VEGF were strikingly higher in patients with PDR than in the control subjects (1.42 ng/ml (0.12-7.62) vs. 0.009 ng/ml (0.009-0.04); P < 0.001). No correlation between vitreal concentrations of NOx and VEGF was observed, either in diabetic patients or in the control group. CONCLUSIONS: NOx and VEGF are increased but not related in the vitreous fluid of diabetic patients with PDR. Our results suggest that serum diffusion could play a significant role in explaining the increase of NOx. By contrast, intraocular production seems to be the main factor responsible for the intravitreous enhancement of VEGF.

Vitreous levels of vascular cell adhesion molecule and vascular endothelial growth factor in patients with proliferative diabetic retinopathy: a case-control study.

OBJECTIVE: To evaluate the intravitreous concentration of vascular cell adhesion molecule (VCAM)-1 in diabetic patients with proliferative diabetic retinopathy (PDR) and the relationship of VCAM-1 with vascular endothelial growth factor (VEGF). RESEARCH DESIGN AND METHODS: Serum and vitreous fluid samples were obtained simultaneously at the onset of vitrectomy from 20 diabetic patients with PDR and 20 nondiabetic control subjects with nonproliferative ocular disease. Both groups were matched by serum levels of VCGM-1 and VEGF. VCAM-1 and VEGF were determined by enzyme-linked immunosorbent assay. Statistics were determined using the Mann-Whitney U test and Spearman's rank correlation test. RESULTS: The intravitreous concentration of VCAM-1 was signifcantly elevated in diabetic patients with PDR compared with control subjects (26 ng/ml [19-118] vs. 22 ng/ml [20-47], P < 0.05). A direct correlation between VCAM-1 and total vitreous proteins was detected in diabetic patients (r = 0.64, P = 0.003), but not in control subjects. After adjusting for total intravitreous proteins, VCAM-1 was significantly lower in diabetic patients with PDR than in control subjects (8.2 ng/ml [4-31.4] vs. 43.1 ng/ml [9.7-100], P < 0.001). Intravitreous VEGF concentrations were higher in patients with PDR than in control subjects in absolute terms (1.34 ng/ml [0.16-6.22] vs. 0.009 ng/ml [0.009-0.044], P < 0.0001) and after correcting for total vitreal proteins (0.33 ng/ml [0.01-2.3] vs. 0.013 ng/ml [0.003-0.035], P = 0.0001). Finally, the vitreous ratio of VCAM-1 to proteins correlated with the vitreous ratio of VEGF to proteins in both diabetic patients (r = 0.74, P = 0.001) and control subjects (r = 0.84, P = 0.005). CONCLUSIONS: The low proportion of VCAM-1 in relation to total vitreal proteins observed in diabetic patients with PDR suggests that VCAM-1 is quenched by diabetic retina. In addition, the direct correlation detected between VCAM-1 and VEGF suggests that cellular adhesion and neovascularization may be linked processes.

Determination of xanthine oxidoreductase forms: influence of reaction conditions.

Xanthine oxidoreductase (XOR) has been implicated in ischaemia-reperfusion injury, and increases in this enzyme have been found in plasma of patients with different illnesses. The catalytic concentrations of the XOR forms found in plasma, using various reaction conditions, greatly differ in the related literature. We studied the effect of the assay conditions on the xanthine oxidation rate catalysed by the XOR forms. Our results demonstrate inhibition of XOR by the reaction products and a time-dependent decrease in the reaction rates of XOR forms. Substrate consumption and inhibition by the products did not account for this decrease. Determination at 60 min incubation leads to catalytic concentrations up to 80% lower for the XOR forms than those obtained at 10 min. We conclude that elimination of the reaction products (NADH, H(2)O(2) and O(2)) from the reaction mixture, and short incubation times, are necessary for accurate measurement of the XOR activities.

[Residual pleural thickening in tuberculous pleuritis. Associated factors]]. / Engrosamiento pleural residual en la pleuritis tuberculosa. Factores asociados.

BACKGROUND: To study the factors related to the development of residual pleural thickening in pleural tuberculosis. PATIENTS AND METHODS: We studied 39 patients with tuberculous pleural effusion. A chest X-ray was taken of each patient at the end of treatment. The patients' medical histories, pleural fluid findings and diagnostic chest films were evaluated. Residual pleural thickening was defined as thickening that was visibly greater than 2 mm in the lower side portion of the chest film. RESULTS: Residual pleural thickening developed in 26% of patients and was found mainly in men (RR = 3.86). In no patients with Löwenstein-Jensen cultures positive for Mycobacterium tuberculosis did pleural complications develop. CONCLUSION: Residual pleural thickening is a common complication of tuberculous pleural effusion. Residual pleural thickening in tuberculous pleurisy occurs more often in men and older patients, and in cases in which pleural liquid culture is negative for M. tuberculosis.

Hepatocyte growth factor in vitreous and serum from patients with proliferative diabetic retinopathy.

BACKGROUND: Hepatocyte growth factor (HGF) is an endothelium specific growth factor that has been implicated in angiogenesis, a crucial event for the development of proliferative diabetic retinopathy (PDR). The aim of the study is to determine the intravitreous concentrations of HGF in diabetic patients with PDR, and to investigate whether its serum levels could contribute to its intravitreous concentration. METHODS: 17 diabetic patients and seven non-diabetic patients in whom a vitrectomy was performed were studied. Both groups were matched by serum levels of HGF. Venous blood and vitreous samples were collected simultaneously at the time of vitreoretinal surgery. Vitreous and serum HGF were determined by ELISA. RESULTS: Intravitreous concentrations of HGF (median and range) were higher in diabetic patients (17.04 ng/ml (9.98-80)) in comparison with non-diabetic patients (5.88 ng/ml (2.57-14.20); p=0. 003). Intravitreous HGF concentrations were strikingly higher than serum HGF concentrations both in diabetic patients (17.04 ng/ml (9. 98-80) v 0.66 ng/ml (0.26-1.26); p<0.001) and in the control group (5.88 ng/ml (2.57-14.20) v 0.68 ng/ml (0.49-0.96); p=0.003). No correlation was found between serum and vitreous levels of HGF in both groups (diabetic patients, r= -0.31; p=0.5 and control subjects r= -0.15; p=0.5). CONCLUSION: The high vitreous levels of HGF observed in diabetic patients with PDR cannot be attributed to serum diffusion across the blood-retinal barrier. Therefore, intraocular synthesis appears to be the main contributing factor for the high vitreous HGF concentrations in diabetic patients, a cytokine that seems to be directly involved in the pathogenesis of PDR.

Serum laminin as a marker of diabetic retinopathy development: a 4-year follow-up study.

PURPOSE: The usefulness of laminin as a serum marker of diabetic retinopathy is a topic that generates conflicting views. The aim of the present study was to investigate the effect of diabetic retinopathy on serum laminin-P1, the larger pepsin resistant fragment of laminin, and to elucidate whether serum laminin-P1 could be an indicator of the risk for development of diabetic retinopathy. METHODS: In a prospective study, 97 consecutive diabetic patients (35 type 1 and 62 type 2) without diabetic retinopathy and a urinary albumin excretion rate lower than 20 microg per minute were enrolled in a 4-year follow-up study. Patients who developed microalbuminuria during the study were excluded in order to avoid the influence of diabetic nephropathy on serum laminin-P1. At the end of follow-up, data from ophthalmologic studies and serum laminin-P1 were evaluated in the 66 normoalbuminuric diabetic patients who completed the study. RESULTS: No statistical differences were observed in baseline laminin-P1 serum concentrations between patients who developed diabetic retinopathy (n = 15) and patients who remained without it during follow-up (n = 51). However, serum laminin-P1 levels obtained at the end of the study were significantly higher in patients who developed diabetic retinopathy (1.75 +/- 0.33 U/ml versus 1.47 +/- 0. 27 U/ml; P =.002). Furthermore, statistical difference was observed when initial and final values of serum laminin-P1 were compared in patients who developed diabetic retinopathy (1.56 +/- 0.27 U/ml versus 1.75 +/- 0.33 U/ml; P =.001). Remarkably, an increase in serum laminin-P1 concentration was detected in all but two of the patients who developed diabetic retinopathy. The relative risk of development of diabetic retinopathy in patients who showed an increase in serum laminin-P1 during follow-up was 5.4 (95% confidence interval, 1.32 to 22.13). CONCLUSIONS: Serum laminin-P1 is a marker and a risk indicator of diabetic retinopathy but is not an early predictor of its development.

Effect of panretinal photocoagulation on serum levels of laminin in patients with diabetes: a prospective study.

BACKGROUND/AIM: Laminin, a major specific non-collagenous glycoprotein of basement membrane, has been proposed as an index of diabetic retinopathy and high serum concentrations have been reported in patients with proliferative diabetic retinopathy. On the other hand, panretinal photocoagulation (PRP) prevents the progression of severe diabetic retinopathy and reverses preretinal neovascularisation. The aim of the study was to investigate the effect of PRP on serum levels of laminin in patients with diabetes. METHODS: 20 patients with diabetes undergoing PRP and 15 patients with mild or moderate non-proliferative diabetic retinopathy in whom a PRP was not performed were included in the study. Serum laminin-P1 (Lam-P1), the largest pepsin resistant fragment of laminin, was determined by radioimmunoassay in each patient before starting PRP and 3 months after it was accomplished. Similarly, a baseline and a 4 month sample were analysed in the non-photocoagulated controls. RESULTS: Serum Lam-P1 concentrations obtained 3 months after PRP were significantly lower when compared with the initial values (1.62 (SD 0.36) U/ml v 1.91 (0.37) U/ml; p <0.001). A decrease of serum levels of Lam-P1 could be seen in all patients. By contrast, in those patients with mild or moderate non-proliferative diabetic retinopathy in whom a PRP was not performed, no significant changes were detected in serum Lam-P1 concentrations (1.72 (0.20) U/ml v 1. 74 (0.17); p=0.250). CONCLUSION: PRP decreases serum Lam-P1 levels in patients with severe diabetic retinopathy. Thus, the studies addressed to evaluate the usefulness of Lam-P1 as a marker of diabetic retinopathy should consider previous PRP as an influencing factor. Finally, our results suggest that retinal source of Lam-P1 strongly contributes to serum Lam-P1 in patients with severe diabetic retinopathy.

Susceptibility of "et," the spontaneously mutating CD1-derived nude mouse, to infection of M. lepraemurium.

We have studied the susceptibility to infection by Mycobacterium lepraemurium (MLM) of a nude, hypothymic, CD1-derived, spontaneous mouse mutant called "et" because of its extraterrestrial appearance. We found that despite their hypothymia, et/et mice were not more susceptible to infection by MLM than their euthymic et/+ counterparts. Infection of both et/et and et/+ mice with 50 x 10(6) bacilli by the intraperitoneal route led only to a mild infection with low levels of antimycobacterial antibodies and a small number of lesions. These lesions were indicative of reactive hepatitis and hyaline perisplenitis with lymphoid hyperplasia. Some small bacilliferous granulomas were also observed at the end of the experiment (5 months of infection). CD1 mice behave in a rather "resistant" manner to the infection by MLM. It is clear that the nu gene is not necessarily linked to the thymus defect, and it is also clear that the hypothymia of et/et mice does not obviously affect their general cell-mediated immune competence.

[Fibronectin and diabetes mellitus: the factors that influence its plasma concentrations and its usefulness as a marker of late complications]. / Fibronectina y diabetes mellitus: factores que influyen en las concentraciones plasmáticas y utilidad como marcador de complicaciones tardías.

BACKGROUND: The usefulness of plasma fibronectin (FNp) as a marker of late diabetic complications is controversial. The aim of the study was to assess the influence of several variables on FNp in diabetic patients and to determine its usefulness as a marker of late diabetic complications. PATIENTS AND METHODS: 79 diabetic patients randomly selected were included in the study. The clinical variables considered were: age, gender, body mass index (BMI), tobacco and alcohol consumption, type, duration and treatment of diabetes, hypertension, and diabetic late complications (macroangiopathy, retinopathy, nephropathy and neuropathy). The laboratory variables analyzed were: blood glucose, glycated hemoglobin, total cholesterol, HDL-cholesterol, LDL-cholesterol, tryglicerides, apolipoprotein AI, apolipoprotein B, microalbuminuria, creatinin and FNp. Statistical study included a multiple regression analysis taking FNp as the dependent variable. RESULTS: A direct correlation between FNp and BMI and also with tryglicerides was observed (r = 0.362; p = 0.002, and r = 0.234; p = 0.038, respectively). Higher levels of FNp were found in type 2 diabetic patients in comparison with type 1 (464 [SD, 127] versus 395 [SD, 96] mg/dl; p = 0.014). This difference was due to the higher BMI and tryglicerides concentrations observed in type 2 diabetic patients in comparison with type 1 (28.61 [SD, 4.67] versus 22.56 [SD, 2,.19] kg/m2; p < 0.001, and 4.24 [SD, 2.36] versus 2.52 [SD, 1.40] mmol/l, respectively). Multiple regression analysis showed that only BMI significantly influenced on FNp concentrations (r = 0.330; p = 0.004). No relation among FNp and late diabetic complications and other variables considered in the study was observed. CONCLUSIONS: FNp is not a useful marker of diabetic late complications and its concentrations are direct and independently influenced by BMI.

Interleukin-8 and markers of neutrophil degranulation in pleural effusions.

In order to know the degree of interleukin-8 (IL-8) production in the pleural space and its relationship to neutrophil activation, IL-8, neutrophil elastase (NE), and myeloperoxidase (MPO) were assessed in blood and pleural fluid (PF) of 219 patients with pleural effusions. Correlations between blood and PF IL-8, NE, and MPO were either absent or weak, except for IL-8 in transudates (r = 0.6745, p < 0.001). PF IL-8, NE, and MPO concentrations in cases of empyema were higher than in cases of effusion of other causes (p < 0.001). No significant differences in inflammatory markers were observed between parapneumonic and tuberculous fluids. IL-8, NE, and MPO levels in malignant, nonspecific, and transudative effusions were lower than in those due to infection, the lowest levels corresponding to transudates. No significant correlation was observed between PF IL-8 and neutrophil count in any group; in contrast, IL-8 was associated with NE and MPO in empyema (r = 0.7545, and r = 0.7283; p < 0.001), tuberculosis (r = 0.4016, p = 0.008 and r = 0.6545, p < 0.001), and nonspecific effusions (r = 0.3748, p = 0.007 and r = 0.3085, p = 0.028). Our results indicate that local production of markers of the nonspecific inflammatory response is high in both chronic and acute pleural infection, and suggest a role for IL-8 in the release of NE and MPO.

Determination of D-lactate by enzymatic methods in biological fluids: study of interferences.

Analysis of nondeproteinized samples with an enzymatic method to determine D-lactate indicated interferences. The presence of L-lactate dehydrogenase (LD) and L-lactate in the sample led to underestimation of D-lactate content when a sample blank was processed and overestimation when it was omitted. We proved that this interference is not due to lack of D-LD stereospecificity. Moreover, assessment of D-LD and L-LD KM for NAD+ allowed us to rule out the different affinities for this coenzyme as a cause of the interference. Our results underline the importance of deproteinizing samples for D-lactate analysis when enzymatic methods are used. The ultrafiltration procedure we propose is convenient and shows acceptable mean recovery (108%) and good imprecision (within-run CV = 4.2% and 3.0% for D-lactate at 31 and 107 mumol/L, respectively; between-run CVs were 7.3% at 49 mumol/L D-lactate and 3.1% at 115 mumol/L D-lactate).

Serum concentrations of laminin-P1 in diabetes mellitus: usefulness as an index of diabetic microangiopathy.

OBJECTIVE: To assess the influence of several variables on serum laminin-P1 (Lam-P1) and to evaluate its usefulness as a serum marker of diabetic microangiopathy. MATERIAL AND METHODS: We determined Lam-P1 by serum radioimmunoassay in 121 controls and 176 diabetic patients, 58 type 1 (insulin dependent) and 118 type (non-insulin dependent), grouped according to retinal status and urinary albumin excretion. The variables evaluated were: age, gender, body mass index, blood pressure, consumption of tobacco and alcohol, type of diabetes, duration of disease, fasting blood glucose, HbA1, cholesterol, HDL-cholesterol, LDL-cholesterol, triglycerides and apolipoproteins (A1, B). Imprecision for laminin determination was: 3.6% intrassay; 5.8% interassay. STATISTICS: Student's t-test, ANOVA, ANCOVA, and multiple regression analysis. RESULTS: In diabetic patients Lam-P1 was higher than in controls (X = 1.63 +/- S.D. 0.36 vs. X = 1.40 +/- S.D. 0.18 U ml-1; P < 0.001) and only correlated with age (P = 0.002). Lam-P1 was higher in diabetics with proliferative retinopathy than in patients with non-proliferative retinopathy and without retinopathy (X = 2.17 +/- S.D. 0.49 U ml-1 vs. X = 1.71 +/- S.D. 0.22 U ml-1 vs. X = 1.47 +/- S.D. 0.26 U ml-1; P < 0.001). Patients with macroalbuminuria presented higher serum Lam-P1 than patients with micro or normoalbuminuria (X = 2.39 +/- S.D. 0.53 U ml-1 vs. X = 1.78 +/- S.D. 0.23 U ml-1 vs. X = 1.51 +/- S.D. 0.29 U ml-1; P < 0.001). These differences remained significative when patients were age-adjusted. CONCLUSIONS: Lam-P1 could be useful as an index of diabetic microangiopathy but patient's age should be considered.

Intracolonic release in vivo of interleukin-1 beta in chronic ulcerative colitis.

1. To investigate the role of interleukin-1 beta in chronic ulcerative colitis, we quantified interleukin-1 beta steady-state release into the colonic lumen. 2. We studied 26 patients with untreated chronic ulcerative colitis and seven patients with irritable bowel syndrome who served as disease controls. In seven ulcerative colitis patients, the disease was inactive and in 19 it was mild to moderately active, according to clinical and colonoscopic criteria. Seven patients with active colitis were studied before and after 4 weeks of treatment with oral 5-aminosalicylic acid. 3. Colonic perfusions were performed using a double-lumen technique. An isotonic solution was continuously infused 50 cm from the anal verge at 5 ml/min, and was recovered 30 cm distally by siphonage. Interleukin-1 beta was measured by ELISA, polymorphonuclear elastase by immunoactivation and leukotriene B4 by specific RIA. 4. All control patients and five out of seven patients with inactive colitis had undetectable interleukin-1 beta release. In active colitis, the release of interleukin-1 beta was detected in 17 out of 19 patients (median 500 pg/min, interquartiles 270-1582 pg/min, P < 0.01 compared with control subjects and patients with inactive colitis). Elastase and leukotriene B4 release were also significantly increased in active colitis compared with inactive colitis and controls. Leukotriene B4 release was similar in inactive colitis and controls, whereas elastase release was higher in inactive colitis than in controls. Five out of seven patients with colitis improved after treatment with 5-aminosalicylic acid. In all responder patients, interleukin-1 beta became undetectable or declined. 5. Our results demonstrate under conditions in vivo that active colitis is associated with enhanced interleukin-1 beta release into the colonic lumen whereas such release does not occur in remission, supporting the concept that ulcerative colitis flare-ups involve increased interleukin-1 beta production.

Effects of thromboxane synthase inhibition on in vivo release of inflammatory mediators in chronic ulcerative colitis.

OBJECTIVE: To evaluate the effects of a thromboxane inhibitor on the production of eicosanoids by the colonic mucosa of patients with chronic ulcerative colitis. PATIENTS AND METHODS: Fourteen patients with active left-sided ulcerative colitis were divided into in two treatment groups. Seven patients received oral ridogrel (300 mg twice daily) and seven 5-aminosalicylic acid (5-ASA; 1 g twice daily) for 4 weeks. Intracolonic eicosanoid and elastase release were measured using a colonic double-lumen perfusion technique. An isotonic solution was infused 50 cm from the anal verge at the rate of 5 ml/min, and recovered by siphonage 30 cm distally. Effluents were assayed for thromboxane B2 (TXB2), prostaglandin E2 (PGE2), and leukotriene B4 (LTB4) by radioimmunoassay (RIA), and for polymorphonuclear elastase by immunoactivation. Clinical and colonoscopic criteria were used to determine activity before and after treatment. RESULTS: Four of the seven patients in the ridogrel group and five of the seven in the 5-ASA group showed clinical and colonoscopic improvement. Intraluminal elastase release decreased in every responding patient in the 5-ASA group (P < 0.05) and in three out of seven responders in the ridogrel group. Basal eicosanoid release was similar in both groups. In the responders, 5-ASA significantly reduced the release of the three eicosanoids (P < 0.05). Ridogrel reduced the release of TXB2 to 31% of basal levels (P < 0.01) but the release of PGE2 and LTB4 was not affected. CONCLUSIONS: These results suggest that ridogrel is an oral active selective inhibitor of thromboxane synthetase, which modifies the pattern of colonic eicosanoid generation in patients with chronic ulcerative colitis. Oral ridogrel may be a useful treatment for patients with non-severe ulcerative colitis, although specific indications require further studies.