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Biomedical subjects

E Ritz

Publications and source records attributed to E Ritz.

At least 1,117 records · Page 62Linked to original sources
PubMedDate not supplied

Rational drug treatment of the hypertensive diabetic with nephropathy.

Development of hypertension in Type I diabetics parallels evolution of nephropathy. In Type II diabetics, excessive prevalence of hypertension prior to the appearance of proteinuria suggests that factors other than nephropathy are operative in its pathogenesis. On the other hand, the risk of nephropathy in Type II diabetics is higher than previously appreciated. Recent evidence suggests that angiotensin II plays an important role in the induction and progression of diabetic nephropathy. This provides a rationale for antihypertensive therapy with converting enzyme inhibitors in nephropathic diabetics in whom they have been shown to lower blood pressure and diminish proteinuria. Furthermore, in a retrospective study of patients with various renal diseases (including diabetic nephropathy), the authors found suggestive evidence that converting enzyme inhibitors may also attenuate progression of renal failure to a greater extent than other antihypertensive drugs.

Antihypertensive Agents↗
PubMedDate not supplied

Ultrastructure of the rat testis in experimental uremia.

The ultrastructure of the testis was studied in chronically uremic rats with and without administration of hCG. Concomitantly, sham operated pair fed control rats were examined. In uremic rats the seminiferous tubules contained a certain number of necrotic spermatocytes and spermatids with defective acrosome formation. The Sertoli cells showed evidence of reduced function: they had only scarce endoplasmic reticulum and lipid droplets. Leydig cells were rather heterogeneous with respect to ultrastructure. Some cells had poorly developed endoplasmic reticulum, a small Golgi apparatus and no lipid droplets, while others appeared normal. Administration of hCG had marked effects on Leydig cells: such cells acquired numerous mitochondria and rough endoplasmic reticulum, while smooth endoplasmic reticulum, lipid droplets, lysosomes and Golgi apparatus were inconspicuous. In contrast, administration of hCH failed to reverse premature germ cell loss.

Animals↗
PubMedDate not supplied

Hypertension and cardiovascular risk factors in hemodialyzed diabetic patients.

In a retrospective study, the cause of death and the cardiovascular risk conferred by hypertension and other risk factors were analyzed in 200 diabetic and 200 nondiabetic patients who were matched for age, sex, year of admission, and center of treatment. Total and cardiovascular mortality were considerably higher in diabetics, cardiovascular mortality being 4.8 times higher in patients with type I and 3.0 times higher in those with type II diabetes compared to matched controls. Cardiovascular mortality progressively increased with age and had not improved in recent years. In both types I and II diabetes, the rate (58%) and proportion (38%) of deaths from cardiovascular causes were significantly higher in diabetics than in matched controls. Myocardial infarction (13%) and stroke (7%) accounted only for a minority of cardiovascular mortality, the majority (80%) being due to "sudden death of unknown cause." Autopsy was carried out in 33% of patients with sudden death. A documented history of long-standing hypertension increased cardiovascular death in diabetic more than in nondiabetic patients. Diabetic retinopathy (an index of microangiopathy) and absence of peripheral pulses, amputation, or history of myocardial infarction, stroke, or transient ischemic attacks (as evidence of macroangiopathy) caused surprisingly little increase in relative risk for cardiovascular death. In diabetics but not in nondiabetics, cardiomegaly, particularly in association with electrocardiographic abnormalities, was a strong predictor of cardiovascular death.

Adult↗
PubMedDate not supplied

Natural history of nephropathy in type I diabetes. Relationship to metabolic control and blood pressure.

In recent years, the respective roles of metabolic control and blood pressure on the development of nephropathy in patients with type I diabetes have been studied intensively. Based on our own retrospective analysis, we conclude that metabolic control, but not blood pressure, determines the onset of proteinuria in these patients. Once proteinuria has developed, concurrent metabolic control has little effect on the time interval to onset of renal failure. In contrast, blood pressure has great predictive value for the time interval to onset of both renal failure and proliferative retinopathy.

Adolescent↗
PubMedDate not supplied

Diabetic nephropathy--what have we learned in the last three decades?

The past three decades have seen enormous conceptual advances in understanding the pathogenesis of diabetic nephropathy. Increasing evidence points to important genetic determination of the renal risk, i.e. the propensity to develop diabetic nephropathy, in type 1 and type 2 diabetic patients. We are also further along the path to understanding the abnormalities of renal hemodynamics that underly these patients' propensity to develop diabetic glomerulosclerosis, i.e. afferent arterial vasodilation and increased glomerular pressure, identified in elegant experimental studies. Another important advance is the recognition that increased urinary albumin excretion is not only an extremely sensitive marker, but also an important player in the pathogenesis of diabetic nephropathy. Finally, the concept of the toxicity of hyperglycemia ("glucotoxicity") has been carried to the molecular level, so that pathomechanisms such as activation of protein kinase C and cellular damage by advanced glycation endproducts (AGE), to name only two, have been elucidated. Diabetic nephropathy has become the leading cause of endstage renal failure (ESRF) in Western countries, particularly in patients with type 2 diabetes. Three treatment modalities are available: (i) hemodialysis,(ii) CAPD and (iii) transplantation, meaning kidney transplantation, combined pancreas and kidney transplantation or - still in a very preliminary stage - islet cell transplantation. The ideal is to have all three modalities available to meet each patient's individual needs. Treatment outcome continues to be considerably worse, however, in diabetic than non-diabetic patients. This highlights the importance of prevention. Progression to ESRF in diabetic nephropathy is preventable, at least to a large extent.

Albuminuria↗
PubMedDate not supplied

Plasma parathyroid hormone, phosphatemia and vitamin D receptor genotype: are they interrelated?

It is not clear how the rate of bone mineral loss and vitamin D receptor (VDR) Bsml polymorphism in hemodialysed patients are related. We therefore analysed the relationships between indices of calcium-phosphate metabolism in respect to VDR genotype in 180 hemodialysed patients. We measured plasma concentrations of calcium, phosphate, iPTH, 1,25(OH)2D3 and activity of the bone fraction of alkaline phosphatase on the day before dialysis. VDR genotype BB, Bb and bb were found in 39, 84 and 57 patients, respectively. The allele frequency was B 0.45 and b 0.55. Subjects with BB genotype had insignificantly higher plasma levels of phosphate, iPTH and activity of the bone fraction of alkaline phosphatase, but significantly lower (p<0.02) concentrations of 1,25(OH)2D3 [iP (mmol/l): 2.05+/-0.09, 1.98+/-0.06, 1.93+/-0.06; iPTH (pg/ml): 257+/-50, 229+/-24, 219+/-30; AP(BF) (nmol/l/s): 515+/-45, 477+/-27, 457+/-34; 1,25(OH)2D3 (pg/ml): 23.4+/-1.5, 26.2+/-1.0, 29.3+/-1.3, for BB, Bb and bb respectively]. The strongest significant correlation between phosphatemia and iPTH was in the BB subgroup (r=0.343). Moreover, only in this subgroup did phosphatemia significantly contribute to the increase in iPTH, assessed by multiple regression analysis. In conclusion, it seems likely that BB VDR genotype in HD patients contributes to the severity of secondary hyperparathyroidism by a mechanism involving phosphatemia.

Aged↗
PubMedDate not supplied

[Neoangiogenesis: from molecular biology to clinical medicine].

Cardiovascular disease is the most common cause of premature death in patients with end-stage renal disease, probably due to a specific "uraemic cardiomyopathy" This article reviews the pathogenesis of cardiac changes in uraemia and particularly the role of an impaired vessel formation. Experimental and autoptic data showed remarkable changes in heart capillarization in renal failure, i.e. a decrease in myocardial capillary supply and a concomitant increase in intercapillary distance. Promoting the formation of new collateral vessels in ischemic tissues using angiogenic growth factors (therapeutic angiogenesis), such as VEGF, constitutes a promising approach for the treatment of uraemic cardiomyopathy.

Humans↗
PubMedDate not supplied

Angiotensin II induces hypertrophy and hyperplasia in adult human mesangial cells.

Several experimental studies point to a potential role of angiotensin II (Ang II) in the progression of glomerulosclerosis even in the absence of glomerular hypertension. We tested the hypothesis that Ang II acts as a growth factor for adult human mesangial cells (AHMC). AHMC were isolated from noninvolved parts of tumor nephrectomy specimens and grown in RPMI medium with the addition of fetal calf serum (FCS). All studies were performed with growth-arrested cells. Proliferation studies were done in serum-free standard growth medium (SF) with the addition of either various concentrations of insulin, plasma-derived serum, or FCS. Ang II (10(-10) to 10(-6) M) dose dependently increased the 3H-thymidine uptake of AHMC up to 57 +/- 13% over solvent controls (p < 0.01). In parallel, the DNA content was 36 +/- 10% higher (p < 0.05) than in solvent controls after 2 days of culture. The cell numbers were higher up to 47 +/- 8% in Ang II (10(-6) M) stimulated cultures after 4 days of incubation (p < 0.01). The effect of Ang II was specific, since it was almost completely obliterated by the AT1 receptor antagonist DuP753. The effect of Ang II was particularly marked when cultures were incubated with SF plus high concentrations (1.7 x 10(-6) M) of insulin or SF plus 10% plasma-derived serum. In contrast, the effect was not significant when cultures were incubated with SF plus 10% FCS. Ang II, when added to platelet-derived growth factor at various concentrations, did not further increase the proliferation. The effect on protein synthesis was assessed in growth-arrested AHMC by 3H-methionine uptake and protein/DNA ratio in cell lysates. Ang II (10(-10) to 10(-6) M) dose dependently increased the 3H-methionine uptake of AHMC up to 47 +/- 10% over solvent controls (p < 0.01). In parallel Ang II (10(-8) to 10(-6) M) dose dependently increased the 3H-methionine uptake of the protein/DNA ratio by 24 +/- 6% after 48 h of incubation. DuP753 obliterated the stimulatory effect of Ang II. Ang II (10(-6) M) also increased the mRNA of the immediate-early growth-related gene Egr-1. We conclude that Ang II induces hypertrophy and proliferation in adult human mesangial cells. This result is of interest with respect to a potential role of Ang II in the pathogenesis of glomerulosclerosis in humans.

Adult↗