High glucose increases inducible NO production in cultured rat mesangial cells. Possible role in fibronectin production.

BACKGROUND/AIM: Increased nitric oxide (NO) generation and action have been suggested to be associated with glomerular hyperfiltration and increased vascular permeability early in diabetes. However, previous studies have primarily focused on the constitutive nitric oxide synthase (cNOS) pathway present in endothelial cells, and the role of the inducible NOS (iNOS) pathway in diabetic nephropathy has remained unclear. This study examined whether high glucose modulates NO synthesis by the iNOS pathway in rat mesangial cells. In addition, the effect of inhibition of the iNOS pathway on fibronectin production was determined to examine the role of the iNOS pathway in high glucose-induced extracellular expansion by mesangial cells. METHODS: NO synthesis by the iNOS pathway was evaluated by nitrite and iNOS mRNA and protein productions. The effects of protein kinase C (PKC) inhibitor and aldose reductase inhibitor on the iNOS mRNA expression and aminoguanidine, a relatively specific inhibitor of the iNOS on fibronectin protein production were examined. RESULTS: High 30 mM glucose concentration led to significant increases in nitrite production of rat mesangial cells upon stimulation with lipopolysaccharide (LPS) plus interferon-gamma (IFN-gamma) compared with control 5.6 mM glucose concentration. Mesangial iNOS mRNA expression and protein production also increased significantly in response to high glucose. The addition of calphostin C, a PKC inhibitor, and 6-bromo-1,3-dioxo-1H-benz[d,e]isoquinoline-2(3H)-acetic acid, an aldose reductase inhibitor, significantly suppressed the enhancement of iNOS mRNA expression in high glucose concentration. High glucose also significantly increased fibronectin protein production of mesangial cells upon stimulation with LPS plus IFN-gamma compared to control glucose. Aminoguanidine reversed this high glucose-induced fibronectin production at dose inhibiting iNOS mRNA expression. CONCLUSIONS: These results indicate that high glucose enhances cytokine-induced NO production by rat mesangial cells, and that the activation of PKC and aldose reductase pathway may play a role in this enhancement. In addition, high glucose-induced NO production by the iNOS pathway may promote extracellular matrix accumulation by mesangial cells under certain condition.     

Acute effects of serotonin on rat bladder contractility.

INTRODUCTION: The purpose of this study is to investigate in vitro the effects of serotonin on the rat detrusor. In particular, it examines which drugs inhibit the serotonin-induced detrusor contractions. MATERIALS AND METHODS: Isometric tension changes of isolated rat bladder muscle strips were recorded in an organ bath using a force transducer. Acute effects of serotonin (0.0001-0.01 mM) on resting tension were assessed. Electrical field stimulation (EFS); bethanechol (0.0001-0.01 mM); ATP (1-3 mM)- or KCl (63.5-254 mM)-induced contractions using an application in an organ bath were compared with serotonin-induced contractions. In order to examine the action mechanism of serotonin-induced stimulation, EFS-, bethanechol-, ATP- or KCl-induced contraction on serotonin treatment (0.001 mM) was assessed and serotonin (0.001-0.1 mM) was cumulatively added to the organ bath following preincubation with propranolol, ketanserin, tropisetron, propiverine, sodium nitroprusside or doxazosin. RESULTS: The serotonin-induced response has two phases: an initial transient contraction and a prolonged tonic phase. Serotonin produced a reversible and dose-dependent contraction of the detrusor strips. Responses to bethanechol significantly increased with a concentration of 0.001 mM serotonin (p < 0.05). There was no effect on the responses to ATP, KCl, or EFS on 0.001 mM serotonin. The 5-HT(2) receptor is mainly responsible for serotonin-induced contractions of the detrusor (p < 0.05), while the 5-HT(1) receptor is partially responsible. Doxazosin and propiverine each significantly suppressed the response to serotonin, while sodium nitroprusside and tropisetron each had no effect (p < 0.05). CONCLUSIONS: Because the 5-HT(2) antagonist blocked the effect of serotonin-induced bladder contractions and the stimulation of the adrenoreceptors, the 5-HT(2) antagonist seems to improve lower urinary tract symptoms.     

Cellular basis of diabetic nephropathy: 1. Study design and renal structural-functional relationships in patients with long-standing type 1 diabetes.

This study was designed to elucidate the cellular basis of risk of or protection from nephropathy in patients with type 1 diabetes. Entry criteria included diabetes duration of > or =8 years (mean duration, 22.5 years) and glomerular filtration rate (GFR) >30 ml x min(-1) x 1.73 m(-2). Patients were classified, on the basis of the estimated rate of mesangial expansion, as "fast-track" (upper quintile) or "slow-track" (lower quintile). A total of 88 patients were normoalbuminuric, 17 were microalbuminuric, and 19 were proteinuric. All three groups had increased glomerular basement membrane (GBM) width and mesangial fractional volume [Vv(Mes/glom)], with increasing severity from normoalbuminuria to microalbuminuria to proteinuria but with considerable overlap among groups. Vv(Mes/glom) (r = 0.75, P < 0.001) and GBM width (r = 0.63, P < 0.001) correlated with albumin excretion rate (AER), whereas surface density of peripheral GBM per glomerulus [Sv(PGBM/glom)] (r = 0.50, P < 0.001) and Vv(Mes/glom) (r = -0.48, P < 0.001) correlated with GFR. Vv(Mes/glom) and GBM width together explained 59% of AER variability. GFR was predicted by Sv(PGBM/glom), AER, and sex. Fast-track patients had worse glycemic control, higher AER, lower GFR, more hypertension and retinopathy, and, as expected, worse glomerular lesions than slow-track patients. Thus, there are strong relationships between glomerular structure and renal function across the spectrum of AER, but there is considerable structural overlap among AER categories. Given that normoalbuminuric patients may have advanced glomerulopathy, the selection of slow-track patients based on glomerular structure may better identify protected patients than AER alone.     

Relationship between Stress Urinary Incontinence and Pelvic Organ Prolapse

We investigated the objective coexisting rate of stress urinary incontinence and pelvic organ prolapse, and also compared the treatment outcomes in patients who had both conditions, treated by a corrective operation on the basis of a precise preoperative evaluation. We reviewed 97 cases who underwent urodynamic studies and evaluation of the prolapse according to the Pelvic Organ Prolapse Quantification (POP-Q) system from among patients who were admitted for treatment of either stress urinary incontinence or pelvic organ prolapse. A Burch urethropexy, either alone or with a parvaginal repair, was done to correct the stress urinary incontinence, as well as additional operations to correct prolapse of stage II or more. The patients were evaluated postoperatively for the stress urinary incontinence and the degree of prolapse at every visit. Nineteen of 30 (63.3%) patients who were admitted with stress urinary incontinence had a coexisting pelvic organ prolapse, most often of the anterior wall. In 42 of 67 (62.7%) cases admitted with pelvic organ prolapse there was a coexisting stress urinary incontinence. A total of 61 patients who had both conditions were followed for 12 months postoperatively. The recurrence rate of stress urinary incontinence and prolapse (all of which were stage II) was 3.3% and 18.0%, respectively. It was noted that the greater the preoperative stage, the higher the recurrence rate (stage II 4.35%; stage III 25.0%; stage IV 33.6%). The coexisting rates of pelvic organ prolapse in patients having stress urinary incontinence, and stress urinary incontinence in patients having a pelvic organ prolapse, were both high. Therefore, when a preoperative evaluation that simultaneously considers both conditions and the correcting surgery is based on this evaluation, the recurrence rates of both conditions could be lowered.     

Brachiocephalic Vein Thrombus of Papillary Thyroid Cancer: Report of a Case

Differentiated thyroid cancer sometimes shows microscopic vascular invasion but rarely causes a tumor thrombus in a great vein. A preoperative diagnosis of the latter condition is difficult if a patient does not have any overt symptoms, but it is important for operative planning. We encountered a 26-year-old woman with papillary thyroid cancer and a tumor thrombus extending from the brachiocephalic vein to the superior vena cava. The tumor was successfully treated by surgical resection. To our knowledge only 19 such cases have so far been reported. We herein report our case, review the literature, and discuss the associated diagnostic problems and treatments including such areas as age, gender, symptoms, pathology, extension, and outcome. Received: October 20, 2000 / Accepted: July 17, 2001     

Endovascular stent grafting of the descending thoracic aorta after arch repair in acute type A dissection

An endovascular stent graft was successfully deployed to the primary entry site in the proximal descending thoracic aorta after total aortic arch replacement using the "elephant trunk" technique in acute type A aortic dissection. The residual false lumen of the descending aorta was thrombosed completely after stent grafting. The elephant trunk was feasible for a proximal landing zone for stent grafting of the descending aorta. Stent grafting in combination with aortic arch replacement was a safe and effective procedure, and may be an alternative choice in carefully selected patients with type A aortic dissection.     

Mechanical consequence of trabecular bone loss and its treatment: a three-dimensional model simulation

Age-related changes in the microstructure of trabecular bone, such as decreases in trabecular number and trabecular thickness, lead to reductions in mechanical properties, such as Young's modulus and strength. Current drug therapy, such as bisphosphonate or parathyroid hormone, improves the mechanical properties of bone mainly by increasing the trabecular thickness, but not increasing the trabecular number. However, the mechanical efficacy of these treatments has not been fully quantified using trabecular bone models. In this study, we used an idealized three-dimensional (3D) microstructural model of trabecular bone to create bone loss either through trabeculae thinning or random removal of trabeculae, and simulated treatment by increasing the trabeculae thickness of the remaining trabeculae. The reduction in either the Young's modulus or the strength due to trabeculae loss was proportional to a much higher power of reduction in bone volume fraction than due to trabeculae thinning. This indicates that bone loss due to trabeculae loss is much more detrimental to Young's modulus and strength of trabecular bone than due to trabeculae thinning, indicating the importance of trabecular number and connectivity in the mechanical integrity of trabecular bone. In general, treatments by increasing the trabecular thickness of remaining trabeculae after trabeculae loss cannot fully recover the initial mechanical properties of intact bone, even if bone loss is fully recovered, whereas trabecular thickening can fully restore the mechanical properties after bone loss by trabeculae thinning. The results also show that the residual loss in mechanical properties is dependent on the extent of trabeculae loss.     

The Effect of Hypercholesterolemia on Rotator Cuff Disease

Background  

The causes of rotator cuff tendon rupture are multifactorial and still unclear. Intrinsic and extrinsic factors have been implicated as predisposing risk factors for rotator cuff rupture. Previous studies have suggested a relationship between elevated serum lipid profiles and tendon ruptures, although not rotator cuff tears specifically.     

Increased Intratumoral Lymphatic Vessel Density Correlates with Lymph Node Metastasis in Early Gastric Carcinoma

Background  

Prediction of lymph node metastasis in early gastric carcinoma (EGC) is important for management and follow-up of EGC patients. Increased lymphangiogenesis has been suggested to correlate with lymphatic invasion and lymph node metastasis in various tumors.