Impaired coronary endothelial function in a rat model of spontaneous albuminuria

BACKGROUND: Albuminuria is an independent risk factor of coronary artery disease and has been proposed to reflect a general endothelial disorder. The Munich Wistar Fr?mter (MWF) rat strain develops spontaneous albuminuria and, therefore, may be an interesting experimental model to study alterations of endothelial function under conditions of increased albuminuria. Our aim was to investigate if the MWF strain shows generalized endothelial dysfunction or endothelial dysfunction localized to the coronary vascular bed, and if so, determine which endothelial dilative mediators are involved. METHODS: Coronary and mesenteric arteries were investigated for endothelium-dependent relaxation and the contribution of prostacyclin, nitric oxide (NO) and endothelium-dependent hyperpolarization (EDH) in MWF rats compared to normal Wistar rats. In addition, as MWF rats show increased blood pressure, spontaneously hypertensive rats (SHR) with similar hypertension but without increased albuminuria also were studied. RESULTS: Maximal total endothelium-dependent relaxation of coronary arteries was strongly impaired in MWF rats (55 +/- 3%) compared to Wistar (89 +/- 5%) and SHR (89 +/- 2%) P < 0.05, respectively. The NO-mediated relaxation as well as the relaxation mediated by EDH were significantly lower in coronary arteries from MWF compared to Wistar. In mesenteric arteries of MWF the endothelium-dependent relaxation was intact. CONCLUSIONS: The strong impairment of coronary endothelium-dependent relaxation in the MWF model of spontaneous albuminuria may be due to defects in production or activity of NO and EDH. The intact mesenteric endothelium-dependent relaxation suggests that increased albuminuria may not be related to generalized endothelial vasodilator dysfunction in this model. Selective impairment of coronary endothelial function in a setting of spontaneous albuminuria may be a feature of the MWF that may be employed to further study cause-effect relations between albuminuria and coronary artery disease.     

Angiotensin receptors in the cardiovascular system

The angiotensin II receptors mediate the effects of the renin-angiotensin system, which has an important role in cardiovascular (patho)physiology. Four types of angiotensin receptors are known, of which the type 1 (AT1) and the type 2 (AT2) receptors are the most important. Stimulation of the AT1 receptor leads to a cascade of signalling pathways in several cell types, which finally leads to processes such as vasoconstriction, inflammation and proliferation. These processes are of great importance in various cardiovascular diseases, including hypertension, atherosclerosis and ventricular hypertrophy. The AT2 receptor is expressed mainly in the fetal stage. In adults, the AT2 receptor is minimally expressed under normal circumstances. Its role in the adult cardiovascular system is not well established, but its effects seem to oppose those of the AT1 receptor. This overview discusses the pathophysiological role of the angiotensin II receptors in various cardiovascular diseases with the emphasis on the signal transduction of the AT1 and the AT2 receptors.     

Effect of isovolaemic haemodilution on visual outcome in branch retinal vein occlusion

AIMS—To assess the efficacy of isovolaemic haemodilution therapy (IHT) in the treatment of patients with branch retinal vein occlusion (BRVO).
METHODS—Patients presenting with BRVO between 1 July 1991 and 31 August 1993 were eligible for inclusion and randomised into treatment and control groups. Patients randomised to receive IHT were treated for 6 weeks with venesection and volume replacement using hydroxyethylstarch, a plasma expander. The target haematocrit was 35%. Follow up was for 1 year.
RESULTS—The baseline visual acuity of the two groups was similar at 0.74 and 0.75 logMAR units (Snellen 6/36), for the IHT and control groups, respectively. At 6 weeks, visual acuity in the IHT group had improved by 0.20 logMAR units (2 lines on the Bailey-Lovie chart) (p=0.0001). Vision was unchanged in the control group. At 1 year, the IHT group exhibited an improvement of 0.43 logMAR units. By comparison, the improvement in the control group at 1 year was significantly less at 0.17 logMAR units (p=0.03). The final visual acuity in the IHT and control groups was 0.30 (Snellen 6/12) and 0.60 (Snellen 6/24) logMAR units, respectively.
CONCLUSIONS—The results support the theory that IHT has a positive effect on the visual outcome in patients with BRVO.

Keywords: branch retinal vein occlusion; haemodilution; laser treatment; macular oedema     

Deletion-type allele of the angiotensin-converting enzyme gene is associated with progressive ventricular dilation after anterior myocardial infarction

Objectives. This study sought to determine whether patients who are homozygous for the deletion (D)-type allele of the angiotensin-converting enzyme gene display augmented ventricular dilation after myocardial infarction.

Background. Recent evidence suggests that the deletion-type allele of the angiotensin-converting enzyme gene (DD genotype) is associated with an increased prevalence of myocardial infarction and myocardial hypertrophy. However, it is unknown whether the DD genotype is associated with adverse cardiac remodeling. To address this question we determined the genotype in patients enrolled in the Captopril and Thrombolysis Study (CATS), a prospective trial in which patients received either captopril or placebo during and after thrombolysis for a first anterior myocardial infarction.

Methods. Cardiac volume was determined by echocardiography immediately after thrombolysis and at 1-year follow-up. The genotype for the angiotensin-converting enzyme was determined in 96 patients. Norepinephrine levels were assessed during and immediately after thrombolysis.

Results. Immediately after thrombolysis, cardiac volume did not differ between genotype groups. However, at 1-year follow-up, both end-systolic and end-diastolic left ventricular volumes were significantly greater in the DD-genotype group. Norepinephrine increased to higher levels in the DD-genotype group that received placebo therapy. Captopril treatment effectively blunted both the norepinephrine increase and cardiac dilation in the DD-genotype group.

Conclusions. This exploratory study suggests that homozygosity for the angiotensin-converting enzyme deletion-type allele is associated with augmented neurohumoral activation as well as augmented cardiac dilation after an acute anterior myocardial infarction, an effect that may be susceptible to angiotensin-converting enzyme inhibition.     

Absence of association between cyclin D1 (CCND1) G870A polymorphism and age of onset in hereditary nonpolyposis colorectal cancer

CCND1 encodes cyclin D1, which plays an important role in the G₁ to S phase transition of the cell cycle. A common polymorphism (c.G870A) increases alternate splicing. Hereditary nonpolyposis colorectal cancer (HNPCC) is caused by mutations in mismatch repair (MMR) genes, mainly MSH2 and MLH1, and shows a wide range in the age of its onset (AO), suggesting the existence of other modifying genetic factors. To date, two studies have investigated the association between CCND1 G/A variation and AO in HNPCC with contradictory results in 86 and 146 MMR mutation carriers, respectively. To clarify the role of the CCND1 G/A variation in HNPCC, we performed a study in 406 individuals carrying exclusively clear cut pathogenic mutations in MSH2 or MLH1. We did not observe a significant difference in genotype frequencies of affected and unaffected mutation carriers and healthy controls. A significant association between CCND1 genotypes and AO was found neither in the global comparison (log-rank, P=0.2981; Wilcoxon, P=0.2567) nor in a multivariate Cox regression analysis (hazard ratios 1.111, 95%CI 0.950–1.299, P=0.188 and 1.090, 95%CI 0.868–1.369, P=0.459 for the additive and dominant effect, respectively). We conclude, that the CCND1 G870A sequence variation is not a genetic modifier of the phenotype of HNPCC.     

Survival of cephalosporin-resistant enterobacteriaceae on fingers.

Five strains of Enterobacter species (n=4) and Pantoea species (n=1) resistant to third-generation cephalosporins and isolated from clusters of 3-25 premature infants and small children and 5 strains (4 Enterobacter strains and 1 Pantoea strain) with the same resistance pattern that were isolated from 1 premature infant or small child each were inoculated on the fingertips of 10 volunteer study participants to test whether survival on fingertips is correlated with horizontal transmission. Although there was no significant difference in survival between the groups of transmitted and sporadic strains, there were significant differences in bacterial survival between the participants.     

Early onset of type I diabetes mellitus, Hashimoto's thyroiditis and celiac disease in a 7-yr-old boy with Down's syndrome

Abstract:  Patients with Down's syndrome are at higher risk for developing autoimmune diseases than those of the general population. Autoimmune diseases like Hashimoto's thyroiditis, Graves' disease, diabetes mellitus type I, celiac disease, autoimmune chronic active hepatitis, alopecia, vitiligo and hypoparathyroidism are recognized associations with Down's syndrome. We describe the case of a very young boy with Down's syndrome who was diagnosed with diabetes mellitus type I, Hashimoto's thyroiditis and celiac disease before 8 yr of age. Unspecific symptoms like weight loss, unstable blood sugar with high amplitudes, behavioural problems and dry skin were suspicious for other endocrine disorders or celiac disease in our case. The boy was showing the typical human leukocyte antigen profile for these autoimmune diseases. The prevalence of these autoimmune diseases is higher in Down's syndrome than in general population. Therefore, we advice to follow children with Down's syndrome who develop more than two autoimmune diseases very carefully.