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B Balletshofer

Publications and source records attributed to B Balletshofer.

11 recordsLinked to original sources
PubMed2006

[Early systolic notched peripheral Doppler flow pattern as an indicator of functional obstruction of the common iliac artery after iatrogenic aortic dissection: a case report].

We report on a 57-year-old male patient with typical claudication localised in the right thigh, following aortic valve replacement. The ankle brachial index under resting conditions is within normal range on both sides. A conspicuous monomorphic double-humped peripheral Doppler flow pattern with an early systolic notch extending to the baseline can be registered in all the arteries of the right lower limb. The flow patterns of all other peripheral arteries are properly configured and of triphasic morphology. As the underlying cause of the pathologically altered Doppler flow morphology, aortic dissection Type A can be detected, extending from the former cannulation site of the ascending aorta into the right common iliac artery. Its dissection membrane functionally occludes the right common iliac artery in the early systole, the effect being brief and reversible. The pathogenesis of this morphologically altered Doppler flow pattern and potential differential diagnoses are discussed in this case report, also considering the current literature.

Aortic Dissection↗
PubMed2005

Insulin and its analogue glargine do not affect viability and proliferation of human coronary artery endothelial and smooth muscle cells.

AIMS/HYPOTHESIS: Present guidelines for the treatment of type 2 diabetes recommend HbA1c values of less than 7%. As beta cell function worsens during progress of the disease, insulin therapy is often necessary to achieve this ambitious goal. However, due to peripheral insulin resistance, many patients need rather high insulin dosages. In the light of the extremely high cardiovascular risk of diabetic patients, it is important to determine whether high concentrations of insulin or its frequently used analogues are harmful to the cardiovascular system. We therefore investigated the modulatory effects of regular human insulin and its analogue glargine on proliferation and apoptosis of human coronary artery endothelial cells (HCAECs) and human coronary artery smooth muscle cells (HCASMCs). METHODS: Cells were treated with regular human insulin or insulin glargine. Proliferation was determined by [3H]thymidine incorporation and by flow cytometric analysis of Ki-67 expression. Apoptosis was assessed by flow cytometry (cell cycle analysis and annexin V staining) and determination of caspase-3 activity. RESULTS: HCAECs and HCASMCs treated with regular human insulin or insulin glargine did not show significant increases in DNA synthesis or Ki-67 expression. Administration of regular human insulin or insulin glargine did not modulate the extent of apoptotic events. No influence of insulin on lipoapoptotic vascular cell death could be detected. CONCLUSIONS/INTERPRETATION: Taken together, neither regular human insulin nor insulin glargine influences growth and apoptosis of human coronary artery cells in vitro. Our data do not suggest that regular human insulin or insulin glargine promote atherosclerosis through mechanisms affecting the cellularity of human coronary arteries.

Apoptosis↗
PubMed2003

Glimepiride reduces mononuclear activation of the redox-sensitive transcription factor nuclear factor-kappa B.

AIMS: Glimepiride has the lowest ratio of insulin release to glucose decrease compared with other sulphonylureas. This prompted us to study in vitro and in vivo in a placebo-controlled study the effect of glimepiride on the redox-sensitive transcription factor nuclear factor-kappa B (NF-kappaB). METHODS: Fifteen patients with type 2 diabetes on glibenclamide with a stable HbA1c over the last 6 months were included. After sampling for determination of baseline values, 10 patients were changed to an equivalent dose of glimepiride, while the placebo group was maintained at glibenclamide plus placebo. The glimepiride dose in these patients was adjusted so that no change in glucose control occurred, allowing for direct comparison. The others were kept on glibenclamide and received additional placebo. After 4 weeks of glimepiride or glibenclamide plus placebo, a second blood sample was taken. Mononuclear cells were isolated and assayed in a tissue-culture-independent electrophoretic mobility shift assay (EMSA)-based detection system for NF-kappaB binding activity, and by Western Blot for nuclear localization of NF-kappaB-p65, the cytoplasmic content of IkappaBalpha and the NF-kappaB-controlled haemoxygenase-1. Glimepiride dose-dependent inhibition of carboxymethyllysin (CML) albumin or tumour necrosis factor alpha (TNFalpha)- and H2O2-induced activation of NF-kappaB binding were determined, using isolated peripheral blood mononuclear cells from healthy volunteers, and transcriptional activity of bovine aortic endothelial cells either left untreated or induced with CML albumin incubated with or without glimepiride. Furthermore, in-vitro studies were implemented to demonstrate radical quenching properties of glimepiride in the cell-free 2,2'-azo-bis(2-aminopropane)-dihydrochloride system. RESULTS: Baseline glucose and HbA1c remained stable in the patients switched from glibenclamide to a corresponding dose of glimepiride or kept on glibenclamide plus placebo. While in the group of patients only taking glibenclamide plus placebo the NF-kappaB binding activity did not change significantly (p = 0.58), the NF-kappaB binding activity in the group of patients taking glimepiride was reduced from 19.3 relative NF-kappaB-p65-equivalents to 15.5 relative NF-kappaB-p65-equivalents (p = 0.04). The nuclear translocation of NF-kappaB-p65 was reduced from 100% at baseline to 58% after 4 weeks (p = 0.04); the cytoplasmic localization of NF-kappaB-p65 increased from 100% to 129% (p = 0.03) and the cytoplasmic content of IkappaBalpha increased from 100% to 109% (p = 0.06). The redox-sensitive haemoxygenase-1 antigen was reduced from 100% to 82% (p = 0.04). To prove directly that glimepiride reduces NF-kappaB activation, we isolated peripheral blood mononuclear cells (PBMC) from healthy volunteers. In vitro, glimepiride reduced TNFalpha-(1 nmol/l) and CML albumin (800 nmol/l)-induced NF-kappaB activation dose dependently, being half maximal at 120 micromol/l. H2O2-mediated NF-kappaB activation was only partially reduced. In addition, glimepiride reduced NF-kappaB-dependent gene expression using a NF-kappaB-driven luciferase reporter system. Finally, a cell-free detection system showed that glimepiride has radical quenching properties. CONCLUSION: Glimepiride can affect the activation of the redox-sensitive transcription factor NF-kappaB in vitro and in vivo.

Aged↗
PubMed2001

Acute adrenocortical insufficiency due to heparin-induced thrombocytopenia with subsequent bilateral haemorrhagic infarction of the adrenal glands.

A 56 year old male developed bilateral massive adrenal haemorrhage (BMAH) resulting in chronic adrenal insufficiency in the course of heparin-induced thrombocytopenia (HIT)-syndrome. Thrombosis of the central adrenal vein (CAV) with subsequent adrenal haemorrhagic infarction is the most probable cause of the rare association of HIT and BMAH. The exorbitantly high catecholamine plasma levels within the CAV in addition to immunogenic platelet activation are discussed as possible underlying pathophysiological mechanisms.

Adrenal Gland Diseases↗
PubMed2000

Endothelial dysfunction in diabetes mellitus.

Diabetes mellitus and impaired glucose tolerance are linked to increased cardiovascular morbidity and mortality. Vascular disease is directly associated with plasma glucose levels, and reduction of these levels forestalls to a certain extent the vascular complications of diabetes, such as myocardial infarction, nephropathies, and retinopathies. In addition to hyperglycemia, there are other risk factors that play a prominent role, such as hypertension, hyperlipidemia, and genetic factors. Endothelial dysfunction is one of the major factors in the development of cardiovascular disease. The vascular endothelium regulates the blood flow by tightly controlling the coagulation system, cell-cell interaction, and vascular tone. These functions are disturbed in diabetic patients. In diabetics, endothelin-1 levels are increased, leading to vasoconstriction. Endothelin levels are directly related to plasma glucose levels. In addition, the endothelial cell-NO axis is disturbed. NO release and function are impaired. This seems to be dependent upon hyperglycemia and genetic factors. Impaired NO function also results in vasoconstriction. Furthermore, enhanced vascular permeability is seen in diabetics. This appears to be related to impaired endothelial cell relaxation and reactive oxygen species as well as advanced glycosylated end products (AGEs). The complex changes seen in diabetes and even prediabetes are therefore related to numerous derailments related to endothelial dysfunction, and no single therapeutic approach is likely to solve the problem of vascular complications.

Diabetes Mellitus↗
PubMed2000

Acute improvement of peripheral endothelial function in postmenopausal women with coronary artery disease after single oral intake of 17beta-estradiol valerate.

Chronic estrogen supplementation is known to improve endothelial function in postmenopausal women. We studied the acute effect of a single dose of orally administered 17beta-estradiol valerate (E2) on the peripheral endothelial dependent and independent vasodilatation in postmenopausal women with coronary artery disease (CAD). 20 postmenopausal women (age: 64.9 (7.2) y, height: 1.61 (0.04) m. weight: 68.6 (10.6) kg) with angiographically confirmed CAD were randomly examined for flow-associated vasodilatation (= FAD%, a marker for endothelial dependent vasodilatation) and for glyceryltrinitrate (400 microg, p.o.) induced vasodilatation (= GTN%, representing endothelial independent vasodilatation) two hours after placebo controlled, randomized crossover intake of 4 mg E2 p.o. After placebo FAD% was impaired (3.5 (1.7)%) compared to historic controls. After the oral intake of 4 mg E2, FAD% improved to 5.0 (2.8)% (P=0.02). GTN% was not significantly influenced by the oral E2 (E2: 12.6 (5.7) v placebo: 11.2 (6.9)%, P=0.14). Endothelial dysfunction can partially be restored by a single oral dose of 4 mg E2. This indicates an acute vasoprotective effect of E2 beyond its genomic and lipid modifying actions. It remains to be investigated if estrogen might play a beneficial role in the acute treatment of symptomatic coronary artery disease such as angina pectoris or preinfarct syndrome.

Aged↗
PubMed2000

The PPARgamma2 polymorphism pro12Ala is associated with better insulin sensitivity in the offspring of type 2 diabetic patients.

Recently, a highly prevalent polymorphism of the PPARgamma2-receptor (Pro12Ala) was described and found to be associated with reduced transcriptional activity. Both human and animal studies suggested that this polymorphism may be associated with increased insulin sensitivity. However, an effect independent of other factors known to influence insulin sensitivity has yet to be demonstrated. Therefore, we compared insulin sensitivity using the hyperinsulinemic-euglycemic clamp technique in 37 subjects heterozygous for the PPARgamma2-Pro12Ala mutation and 37 control subjects negative for the PPARgamma2-Pro12Ala. The control group was selected from 190 subjects by pair-matching for sex, BMI, fat distribution and body composition. In the group heterozygous for the polymorphism steady-state plasma insulin during the clamp was significantly lower (63.3 microU/ml +/- 2.8) than in the control group (74.9 microU/ml +/- 4.0, p = 0.02). While MCR of glucose was similar in the PPARgamma2-Pro12Ala group (8.1 ml/kg x min x 100 +/- 0.5) and the control group (7.6 ml/kg x min x 100 +/- 3.0, p = 0.7), the insulin sensitivity index was significantly higher in the PPARgamma2-Pro12Ala group (12.5 mg/kg x min x microU/ml +/- 0.9 vs. 9.7 mg/kg x min x microU/ml +/- 0.8, p = 0.039). In addition, an arbitrary lipolysis index (decrease in FFA divided by increase in insulin) was also found to be marginally higher in the PPARgamma2-Pro12Ala group (8.0 +/- 0.9) compared to the control group (6.1 +/- 0.7, p = 0.097). In conclusion, these data suggest that the PPARgamma2-Pro12Ala mutation is associated with better insulin sensitivity of glucose disposal and possibly, also of antilipolysis.

Adult↗
PubMed1999

Insulin action and secretion in healthy, glucose tolerant first degree relatives of patients with type 2 diabetes mellitus. Influence of body weight.

It is a matter of controversy, whether insulin action or secretion - or both - are disturbed in first degree relatives of patients with type 2 diabetes. We intended to assess both the compensatory and the obesity-related part of insulin secretion. In order to dissect out the latter, matching for insulin sensitivity was mandatory to normalize for the compensatory part of hyperinsulinemia. In 154 healthy, glucose tolerant first degree relatives of patients with type 2 diabetes we directly quantified both insulin sensitivity (by euglycemic-glucose-clamp technique) and insulin secretion (oral glucose load; stimulated serum c-peptide). Insulin sensitivity was scattered over a wide range with a considerable overlap of both first degree relatives of patients with type 2 diabetes and 97 controls without a family history of diabetes. Average insulin sensitivity was higher in controls (8.0+/-0.3 vs. 7.1 + 0.2 ml x kg-l x min-1, p < 0.05). Prevalence of insulin resistance (defined as controls, lowest tertile for insulin sensitivity) was 40% in first degree relatives of patients with type 2 diabetes. Insulin secretion after oral glucose was significantly increased in insulin resistant first degree relatives of patients with type 2 diabetes compared to insulin sensitive first degree relatives of patients with type 2 diabetes. Early phase relative insulin secretion (30 min) expressed as x-fold increase above basal was smaller in insulin resistant first degree relatives of patients with type 2 diabetes than in insulin sensitive counterparts (5.3+/-0.4 vs. 7.3+/-0.5; p < 0.01). Body mass index was distributed over the whole range in insulin resistant first degree relatives of patients with type 2 diabetes. In the insulin sensitive subgroup absolute and relative secretion did not differ in obese (Body mass index >25 kg/m2) and insulin sensitivity-matched lean. In obese insulin resistant first degree relatives of patients with type 2 diabetes absolute hyperinsulinemia was combined with reduced and delayed relative early insulin release. In summary, degree and prevalence of insulin resistance is higher in first degree relatives of patients with type 2 diabetes than in controls. However, both groups are of heterogenous metabolic composition and family history as major discriminator should not be overestimated. Our data suggest, that hyperinsulinemia cannot simply be explained as a compensatory event to balance insulin resistance. Hypersecretion is associated with insulin resistance predominantly in combination with obesity. It might be speculated that adipose tissue derived signals to the beta-cell might lead to hypersecretion only in the genetic background that also leads to insulin resistance.

Adolescent↗
PubMed1999

Beta-blocking agents in patients with insulin resistance: effects of vasodilating beta-blockers.

Essential hypertension is--at least in many subjects--associated with a decrease in insulin sensitivity, while glycaemic control is (still) normal. It seems that in hypertensive patients, two major functions of insulin are impaired: there is insulin resistance of peripheral glucose uptake (primarily skeletal muscle) and insulin resistance of insulin-stimulated vasodilation. In view of some retrospective data and meta-analyses, which showed a less than expected reduction in coronary events (coronary paradox), the metabolic side effects of the antihypertensive treatment have received more attention. Many groups have shown that conventional antihypertensive treatment, both with beta-blockers and/or diuretics, decreases insulin sensitivity by various mechanisms. While low-dose diuretics seem to be free of these metabolic effects, there is no evidence for this in the beta-adrenergic blockers. However, recent metabolic studies evaluated the effects of vasodilating beta-blockers, such as dilevalol, carvedilol and celiprolol, on insulin sensitivity and the atherogenic risk factors. None of them decreased insulin sensitivity, as has been described for the beta-blockers with and without beta1 selectivity. This supports the idea that peripheral vascular resistance and peripheral blood flow play a central role in mediating the metabolic side effects of the beta-blocking agents, as the vasodilating action (either via beta2 stimulation or alpha1-blockade) seems to more than offset the detrimental effects of the blockade of beta (or beta1) receptors. Further studies are needed to elucidate the relevance of the radical scavenging properties of these agents and their connection to their metabolic effects. Therefore, the beneficial characteristics of these newer beta-adrenoreceptor blockers suggest that the vasodilating beta-blocking agents could be advantageous for hypertensive patients with insulin resistance or type 2 diabetes.

Adrenergic beta-Antagonists↗
PubMed1996

Predictors of 10-year macrovascular and overall mortality in patients with NIDDM: the Munich General Practitioner Project.

The 10-year follow-up of the Munich General Practitioner Project was designed as a long-term prospective study to evaluate factors predicting macrovascular and overall mortality in a random cohort of non-insulin-dependent diabetic (NIDDM) patients. Of the original 290 patients (103 males, 187 females, median age 65 years) 92.5% could be assessed, 103 subjects had died, 58 from macrovascular causes. In an univariate analysis of baseline data, deceased patients, and especially those who died from macrovascular causes had significantly higher fasting blood glucose, HbA1c, von Willebrand-factor protein, urine albumin excretion, and serum beta 2-microglobulin, were significantly older, exhibited significantly more ischaemic heart disease (abnormal ECG Minnesota codes), carotid artery and peripheral vascular disease (both determined by ultrasound-Doppler), and had significantly inferior knowledge about diabetes and its treatment. No significant differences were seen for gender, blood pressure, smoking, total cholesterol, triglycerides, HDL-cholesterol, or the use of antidiabetic, antihypertensive or coronary drugs. In a multiple logistic regression analysis, the risk factors for macrovascular death were age, HbA1c and von Willebrand-factor protein. When baseline macrovascular disease was taken into account, carotid artery disease was also a determinant. The main variables from the metabolic syndrome (blood pressure, dyslipidaemia, body mass index) did not enter a multiple logistic regression analysis. The data suggest that age and haemoglobin A1c are major determinants, and that in addition von Willebrand-factor associated endothelial damage is a risk factor for macrovascular mortality in NIDDM patients.

Age Factors↗