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Basement Membrane Thickening (basement + membrane_thickening)
Selected AbstractsBasement membrane thickening and clinical features of children with asthmaALLERGY, Issue 6 2007E. S. Kim Background:, Asthma is a chronic inflammatory disease, characterized by airway inflammation, bronchial hyper-responsiveness, and airway obstruction. Although asthma induces partially reversible airway obstruction, obstruction can sometimes become irreversible. This may be a consequence of airway remodeling, which includes a number of structural changes, such as epithelial detachment, basement membrane (BM) thickening, smooth muscle hypertrophy, and new vessel formation. This study evaluated children with asthma for the presence of BM thickening. Methods:, Eighteen children with asthma and 24 control subjects underwent flexible bronchoscopy with endobronchial biopsy. Light microscopy was used to measure BM thickness in paraffin-embedded biopsy sections. The association between BM thickening and age, sex, duration of asthma, asthma severity, FEV1, FEV1/FVC, FEF25,75%, methacholine PC20, eosinophil count, and presence of atopy was examined. Results:, Basement membrane thickness was greater in subjects with asthma (8.3 ± 1.4 ,M) than in control subjects (6.8 ± 1.3 ,M, P = 0.0008). Multiple regression analysis revealed that sex, FEV1/FVC, total IgE, and atopy (IgE for Dermatophagoides pteronyssinus >0.34 kUA/l) were significant predictive factors for BM thickness. There was no significant association between BM thickness and age, duration of asthma, FEV1, FEF25,75%, methacholine PC20, eosinophil count, or asthma severity. Conclusions:, Basement membrane thickening has been known to be present in children with asthma. In addition, we report an association between BM thickness and sex, FEV1/FVC, total IgE, and the presence of IgE specific to D. pteronyssinus. [source] Protein kinase C and the development of diabetic vascular complicationsDIABETIC MEDICINE, Issue 12 2001K. J. Way Abstract Hyperglycemic control in diabetes is key to preventing the development and progression of vascular complications such as retinopathy, nephropathy and neuropathy. Increased activation of the diacylglycerol (DAG)-protein kinase C (PKC) signal transduction pathway has been identified in vascular tissues from diabetic animals, and in vascular cells exposed to elevated glucose. Vascular abnormalities associated with glucose-induced PKC activation leading to increased synthesis of DAG include altered vascular blood flow, extracellular matrix deposition, basement membrane thickening, increased permeability and neovascularization. Preferential activation of the PKC, isoform by elevated glucose is reported to occur in a variety of vascular tissues. This has lead to the development of LY333531, a PKC, isoform specific inhibitor, which has shown potential in animal models to be an orally effective and nontoxic therapy able to produce significant improvements in diabetic retinopathy, nephropathy, neuropathy and cardiac dysfunction. Additionally, the antioxidant vitamin E has been identified as an inhibitor of the DAG-PKC pathway, and shows promise in reducing vascular complications in animal models of diabetes. Given the overwhelming evidence indicating a role for PKC activation in contributing to the development of diabetic vascular complications, pharmacological therapies that can modulate this pathway, particularly with PKC isoform selectivity, show great promise for treatment of vascular complications, even in the presence of hyperglycemia. Diabet. Med. 18, 945,959 (2001) [source] Changes in oxidative balance in rat pericytes exposed to diabetic conditionsJOURNAL OF CELLULAR AND MOLECULAR MEDICINE, Issue 1 2004A. Manea Abstract Recent data indicate that the oxidative stress plays an important role in the pathogenesis of diabetes and its complications such as retinopathy, nephropathy and accelerated atherosclerosis. In diabetic retinopathy, it was demonstrated a selective loss of pericytes accompanied by capillary basement membrane thickening, increased permeability and neovascularization. This study was designed to investigate the role of diabetic conditions such as high glucose, AGE-Lysine, and angiotensin II in the modulation of antioxidant enzymes activities, glutathione level and reactive oxygen species (ROS) production in pericytes. The activity of antioxidant enzymes: superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and total glutathione (GSH) was measured spectrophotometrically. The production of ROS was detected by spectrofluorimetry and fluorescence microscopy after loading the cells with 2,-7, dichlorofluoresceine diacetate; as positive control H2O2 was used. Intracellular calcium was determined using Fura 2 AM assay. The results showed that the cells cultured in high glucose alone, do not exhibit major changes in the antioxidant enzyme activities. The presence of AGE-Lys or Ang II induced the increase of SOD activity. Their combination decreased significantly GPx activity and GSH level. Athree times increase in ROS production and a significant impairment of intracellular calcium homeostasis was detected in cells cultured in the presence of the three pro-diabetic agents used. In conclusion, our data indicate that diabetic conditions induce in pericytes: (i) an increase of ROS and SOD activity, (ii) a decrease in GPx activity and GSH level, (iii) a major perturbation of the intracellular calcium homeostasis. The data may explain the structural and functional abnormalities of pericytes characteristic for diabetic retinopathy. [source] Sural Nerve Pathology In Asymptomatic Minimally Neuropathic Diabetic PatientsJOURNAL OF THE PERIPHERAL NERVOUS SYSTEM, Issue 3 2000Ra Malik 12 diabetic patients aged 47.5 ± 9.4 yr., duration of diabetes (14.6 ± 10.3 yr.) and 15 control subjects were studied. In diabetic patients neuropathy symptom score =0, neuropathy deficit score = 4.5 + 0.7/30, vibration = 12.0 + 1.8 V, thermal perception (2.0 + 0.8°C), heart rate variation during deep breathing (17.8 + 2.3), 30:15 ratio (1.31 + 0.07) was normal. Baseline (n=12) and repeat neurophysiology (n=10) performed 8.7 + 0.6 years after sural nerve biopsy demonstrated normal values at baseline, with progression of neuropathy (peroneal motor nerve conduction velocity (ms,1) (42.3 + 2.9 v 39.4 +2.0), sural nerve conduction velocity (45.4 + 3.7 v 43.6 + 1.7). Myelinated fibre density, fibre and axonal area and g-ratio were not significantly reduced. Teased fibre studies showed paranodal abnormalities (p < 0.001), segmental demyelination (P < 0.01) with remyelination (P < 0.01) without axonal degeneration. Unassociated Schwann cell profile density (p < 0.04) and axon density (P < 0.001) were increased and axon diameter was decreased (P < 0.007) with a shift of the size frequency distribution to the left (skewness- 0.89 v 0.64, P < 0.03) suggestive of unmyelinated axonal atrophy/regeneration. Endoneurial capillary basement membrane thickening (P < 0.006), endothelial cell hyperplasia (P < 0.004) and luminal narrowing (P < 0.007) occurred. Current measures of neuropathy are too insensitive to detect significant nerve fibre pathology. The presence of microangiopathy provides support for a microvascular basis of diabetic neuropathy. [source] Allograft diabetic nephropathy may progress to end-stage renal diseasePEDIATRIC TRANSPLANTATION, Issue 4 2004Moro O. Salifu Abstract:, Mesangial expansion and glomerular basement membrane thickening characteristic of diabetic nephropathy recur in diabetic recipients of renal allografts from non-diabetic donors but progression to renal failure is minimally documented. Three female renal allograft recipients (aged 40, 62 and 73 yr), who developed end-stage renal disease (ESRD) due to recurrent diabetic nephropathy (two patients) and de novo diabetes (one patient) are reported. Onset of proteinuria, uncontrolled hypertension, azotemia, renal allograft pathologic findings and the need for hemodialysis were analyzed. None of the kidney donors (one cadaver, two living related) had known diabetes or perturbed glucose metabolism pre-transplantation. The three patients presented had different varieties of diabetes; type 1, type 2 and new onset diabetes after transplantation (NODAT). In each subject, proteinuria was detected by dipstick at a mean of 8.3 yr (range 8,9) post-transplantation and increased to the nephrotic range (3.7,4.8 g/day) inducing hypoalbuminemia and azotemia. A histopathologic diagnosis of allograft diabetic nephropathy was made in a mean of 11.7 yr (range 10,14), based on glomerular basement membrane thickening, nodular and diffuse intercapillary glomerulosclerosis, arteriolosclerosis, and tubular atrophy with marked tubular basement membrane thickening characteristic of advanced diabetic nephropathy. All three patients manifested uremia and resumed hemodialysis. Two patients died from sepsis within 2 months and one patient died 2.5 yr later after resumption of maintenance hemodialysis. We infer that recurrent or de novo diabetic nephropathy in renal allografts follows a clinical decade-long course irrespective of diabetes. Reports of ESRD due to allograft diabetic nephropathy (ADN) have been limited because of shorter survival of diabetic transplant recipients and few kidney biopsies performed in patients with chronic allograft dysfunction. The occurrence of allograft diabetic nephropathy in some, but not all patients, however, suggests that individual genetic variability modulates disease expression. [source] | ||||||||||