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ABSTRACT: Distinct connective tissue diseases (CTD's) such as systemic lupus erythematosus (SLE), systemic sclerosis, mixed connective tissue disease as well as dermato- and polymyositis comprise a group of diseases, where autoantibodies are not merely indicators of autoimmune disease, but also play an relevant role in the underlying pathogenicity. This knowledge led to the development of antibody targeting therapies using rituximab or belimumab. Upon this, therapeutic plasma exchange, and more recently immunoadsorption (IAS) have been successfully applied to remove pathogenic autoantibodies under various conditions in some of these CTD's. While the technique of IAS is superior to plasma exchange in regard to specificity and efficacy, the clinical use of IAS in CTD's is currently restricted to a small proportion of clinical situations with either refractory disease or the necessity to avoid aggressive immunosuppressive regimens. Despite the presence of a large number of case series and few controlled trials using IAS, there is a need for further prospective randomized trials to clearly define the role of IAS in these CTD's.
Atherosclerosis. Supplements 01/2013; 14(1):185-9. · 4.94 Impact Factor
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ABSTRACT: There is evidence of iron deficiency (ID) in patients treated with lipoprotein apheresis. Aim of this study was to assess ID in apheresis patients and to study its management comparing safety and efficacy of two approved intravenous (i.v.) iron formulations.
Inclusion criteria were defined as a) serum ferritin < 300 μg/l and transferrin saturation < 20%, b) ferritin < 100 μg/l. Both iron deficient alone and ID anemic (IDA) patients were included. Other causes for anemia were ruled out by thorough history-taking and examination/blood tests. Patients were treated with six different lipoprotein apheresis methods: DALI, Liposorber D, TheraSorb LDL, HELP, MONET and Lipidfiltration. 50 patients were randomized to either ferric carboxymaltose (FCM, 500-1000 mg as single shot infusion over 20 min) or ferric gluconate (FG, 62.5 mg once weekly).
50 of 67 patients of our Lipoprotein Apheresis Center showed iron deficiency. Both i.v. iron formulations studied were equally safe (no serious adverse events (SAEs), 6 patients/group showed adverse events (AEs)) and both effective (clinically and with respect to laboratory data) in lipoprotein apheresis patients, however FCM led to a more rapid and steeper rise of iron parameters.
ID and IDA are common findings in lipoprotein apheresis patients. The pathogenesis remains yet poorly understood and is probably multifactorial. Differential diagnosis of ID/IDA is as essential as differential therapy. Handled with care, older i.v. iron preparations like FG appear to be safe and effective in lipoprotein apheresis patients. However, novel formulations like FCM can be administered rapidly at higher doses due to high complex stability, allowing faster filling of iron stores. Newer laboratory parameters (Reticulocyte-He, low/medium/high fluorescence reticulocytes (LFR/MFR/HFR)) assessing iron status may be helpful in early detection of ID and in monitoring iron replacement therapy.
Atherosclerosis. Supplements 01/2013; 14(1):115-22. · 4.94 Impact Factor
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ABSTRACT: Acute modification of plasma lipidomic profile was assessed by top-down shotgun profiling on a LTQ Orbitrap hybrid mass spectrometer in 14 patients treated with two different apheresis techniques: plasma lipidfiltration (LF) and whole blood dextran sulfate adsorption (DSA).
Patients treated with DSA revealed a significantly more pronounced reduction of LDL-cholesterol (LDL-C), a diminished decrease of HDL-cholesterol (HDL-C) and triglycerides (TG), and a similar reduction in lipoprotein (a) (Lp(a)) level. Against the overall tendency of reduction of lipid metabolites of all lipid classes in post-apheresis plasma, independent of apheresis technology applied, a highly significant increase of phosphatidylethanolamines (PE) in response to DSA was observed.
These data indicate that DSA technology may be associated with an activation or damage of blood cells at contact surface which subsequently leads to a massive liberation of cellular and membrane PE's. Pathophysiological consequences, especially with respect to coagulation system and oxidative stress, have to be further elucidated.
Atherosclerosis. Supplements 01/2013; 14(1):151-5. · 4.94 Impact Factor
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ABSTRACT: Lipoprotein apheresis is indicated in patients at high risk for cardiovascular disease due to severe hyperlipoproteinemia, which is not adequately controlled by diet and medication. This extracorporeal therapy reduces the event rate, although it does not completely abolish new events. We compared atherogenic risk factors in patients who were treated in 2009 and 2010 with lipoprotein apheresis and who suffered events (n 20) with patients who did not (n 44). Among the 45 cardiovascular events that occurred four were strokes, one was myocardial infarction, and two were bypass operations (one coronary and one peripheral). The following risk factors were found to be associated with events: male gender, coexisting diabetes/glucose intolerance and elevation of Lp(a) concentrations. In addition, the history of previous cardiovascular events, the efficiency of the lipoprotein apheresis therapy as judged by the reduction rates of LDL-C and of Lp(a), and the duration of the extracorporeal treatment (patients with events had started treatment with lipoprotein apheresis more recently) may play a role. We did not observe any influence of family history, of the underlying lipid disorder or lipid levels, of arterial hypertension or of smoking habits. Evidently, apheresis therapy of longer duration (more than two years) stabilizes the cardiovascular situation of the patients. Patients on apheresis therapy should be regularly assessed with respect to their risk factor and vascular situation. Lipoprotein apheresis therapy is important for the reduction of cardiovascular events, but optimization of additional modifiable risk factors should also be undertaken.
Atherosclerosis. Supplements 01/2013; 14(1):45-50. · 4.94 Impact Factor
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ABSTRACT: The acute changes of circulating oxidative stress parameters were compared in 16 patients undergoing two different apheresis techniques: plasma lipidfiltration (LF) or whole blood dextran sulfate adsorption (DSA).
Immediately after apheresis LF was associated with an increase in systemic phagocyte count, enhanced formation of reactive oxygen species and decreased activity of the antioxidant enzyme paraoxonase. After DSA, circulating phagocyte oxidant generating activity was significantly lower. Compared to LF, the systemic level of oxidized LDL and antioxLDL antibodies showed a larger decrease in DSA. All measured oxidative stress parameters returned to nearly pre-apheresis level at day three after apheresis,
The data show a more pronounced leukocyte activation immediately after LF in contrast to DSA, possibly as a consequence of necessity of prior separation of blood plasma. The pathophysiological importance of the short-term oxidative burden after a single apheresis session remains to be determined.
Atherosclerosis. Supplements 01/2013; 14(1):157-60. · 4.94 Impact Factor
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ABSTRACT: To determine whether previously demonstrated beneficial short-term effects on cardiovascular function in regular users of lipoprotein apheresis would be sustainable over time.
Regular users of lipoprotein apheresis (n = 17) were studied between February 2009 and July 2010. All patients were examined for endothelial and autonomic function at baseline and at one year of regular treatment. Microvascular function was determined by flicker-induced vasodilation of retinal vessels using the Dynamic Vessel Analyzer. Autonomic regulation of blood pressure and heart rate upon cardiovascular perturbation by deep breathing at 0.1 Hz and orthostatic challenge was evaluated by trigonometric regressive spectral analysis.
The acute improvement of cardiovagal function and venular endothelial function seen after a single lipoprotein apheresis was not evident at one year of regular treatment. However, baroreflex sensitivity showed an improved recovery after orthostatic challenge as compared to baseline measurements. Initially compromised autonomic and microvascular function had not further deteriorated at one year of regular lipoprotein apheresis treatment.
In patients with advanced atherosclerotic disease regular lipoprotein apheresis treatment maintains residual cardiovascular functioning over time.
Atherosclerosis. Supplements 01/2013; 14(1):135-41. · 4.94 Impact Factor
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ABSTRACT: In high-risk patients who are already on a maximal lipid-lowering therapy, a lipoprotein apheresis is an important therapeutic option in preventing further progress of vascular complications as it may decrease both LDL-cholesterol (LDL-C) and lipoprotein(a) (Lp(a)) levels. We looked at the occurrence of cardiovascular events before apheresis and during apheresis in three groups defined by their lipid patterns at the start of an apheresis treatment: Group 1 (LDL-C ≥ 3.4 mmol/l and Lp(a) ≤ 600 mg/l; n = 35), Group 2 (LDL-C ≤ 3.4 mmol/l and Lp(a) ≥ 600 mg/l n = 37) and Group 3 (LDL-C ≥ 3.4 mmol/l and Lp(a) ≥ 600 mg/l; n = 15). Group 2 shows a time period of about 10 years from the first event until the start of apheresis treatment (compared to 2-6 years in the other two groups). Before the start of apheresis treatment 2.1 events per patient had occurred in Group 1, 3.4 events per patient in Group 2 and 1.8 events per patient in Group 3. Under apheresis therapy just 0.9 events per patient occurred in Group 1, 0.5 in Group 2 and 0.5 in Group 3. When comparing the two years before the start of apheresis treatment with the first two years under apheresis we saw the following reduction rates of cardiovascular events: Group 1-54%; Group 2-83%; Group 3-83.5%. Our results show that the reduction of cardiovascular events due to lipoprotein apheresis is especially high in patients with elevated levels of Lp(a) compared to patients with elevated LDL-C only indicating that physicians should be more focused on the risk factor elevated Lp(a).
Atherosclerosis. Supplements 01/2013; 14(1):39-44. · 4.94 Impact Factor
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ABSTRACT: Adipocyte fatty acid-binding protein (FABP4) is a member of the intracellular lipid-binding protein family highly expressed in adipocytes and macrophages. Recent studies indicate a key role for circulating FABP4 in the pathogenesis of atherosclerosis and type 2 diabetes. We described an additional role for FABP4 in the development of cardiac dysfunction in obesity. Therefore, FABP4 seems to be a target in the prevention and treatment of metabolic and cardiovascular disorders in obesity with high potential for future therapeutic applications. However, a safe pharmacological therapy is not yet available. Lipoprotein apheresis is an established therapy for severe and otherwise untreatable hypercholesterolemia which increases life expectancy in patients at high-risk for cardiovascular events. We therefore investigated the acute effect of lipoprotein apheresis on FABP4 serum levels in 64 high-risk patients (25 women, 39 men) under regular apheresis treatment.
FABP4 levels were significantly reduced by 23.2 ± 1.8% by apheresis treatment. Although women had higher FABP4 levels than men (53.5 ± 8.3 ng/ml vs. 30.7 ± 4.3 ng/ml), reduction rate after lipoprotein apheresis was similar in both genders. Among the apheresis methods investigated, immunoadsorption of lipoproteins was most effective in lowering circulating FABP4.
These data suggest that the reduction of FABP4 serum levels may contribute to the preventive effect of lipoprotein apheresis on cardiovascular events.
Atherosclerosis. Supplements 01/2013; 14(1):129-34. · 4.94 Impact Factor
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ABSTRACT: The mental health status of persons with Jewish background living in Germany is discussed with special regard to social exclusion like anti-Semitism and overprotective parental rearing behavior, as a transmissional factor of the KZ-Syndrome. These stressors are considered in the context of a higher risk for depression/fear and psychosomatic disorders and also abnormal cortisol levels. The present sample (N=89) is derived from the Jewish population currently living in the German region of Saxony aged between 17-36 years that emigrated from the post-Soviet-Union areas. The mean age was 22.9 years. Two questionnaires to detect psychosomatic symptoms (Giessen complaint list (GBB)-24, hospital anxiety and depression scale) and one questionnaire addressing parental rearing behavior (FEE) were employed. Comparisons were drawn with normative data from the literature about the German residential population. In addition, questions were asked concerning the experience of anti-Semitism in Germany and in the post-Soviet-Union areas. A higher prevalence of depression/fear (10.3% versus 18.2%) and psychosomatic symptoms (M=14.03 versus 17.8; t=2.42; P<0.05) was observed in Jewish migrants to Germany as compared with non-Jewish German residents. Furthermore, anti-Semitic experiences in Germany correlated positively with depression (r=0.293; P<0.01) and fear (r=0.254; P<0.05). The anti-Semitic experiences in the post-Soviet-Union areas also correlated positively with limb pain (r=0.41, P<0.01), fatigue symptoms (r=0.296, P<0.01) and psychocardial symptoms (r=0.219, P<0.05). It was also confirmed that the male respondents recalled a controlling and overprotecting maternal rearing behavior more frequently than the German standard random sample (M=15.39 versus 18.6; t=2.68; P<0.01). The latter also correlated significantly positive with epigastric pain (r=0.349; P<0.01). The present results show that depression, fear and psychosomatic problems are common in Jewish residents with a background of migration from the post-Soviet-Union areas to Germany. Apart from the transgenerational passing of psychological traumata and the Holocaust experiences, other stressors like anti-Semitism, control and overprotection as parental rearing measures appear to be important factors specifically contributing to the pathogenesis of the attributed symptoms.
Translational psychiatry. 01/2013; 3:e241.
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ABSTRACT: Background: Measurements of plasma free metanephrines provide a sensitive test for the diagnosis of pheochromocytoma/paraganglioma (P/PGL), with highly elevated levels diagnostic of the disease. However, there is less diagnostic certainty in patients with mild elevations of these catecholamine metabolites.Patients and methods: Here we report use of the clonidine suppression test (CST) as a second-tier diagnostic test in 24 patients with mild elevations of plasma free metanephrines and/or catecholamines. Blood samples before and 3 hours after clonidine were analyzed for plasma concentrations of metanephrines and catecholamines with a negative test result defined as either a clonidine-induced fall in normetanephrine or noradrenaline by more than 40 % and 50 % respectively or to below the upper cut-offs of reference intervals.Results: P/PGLs were confirmed in 9 patients and excluded in 15 by independent criteria. More than half of the patients without P/PGL showed normalized plasma concentrations of normetanephrine at baseline before clonidine compared to initial screening; all showed appropriate clonidine-induced falls in normetanephrine and noradrenaline or levels after the drug below upper cut-offs, indicating a diagnostic specificity of 100 % (CI 78-100 %). However, similar responses for noradrenaline were noted in 7 patients with P/PGL, indicating a diagnostic sensitivity of only 22 % (CI 2,8-60 %) compared to 100 % (CI 66-100 %) for normetanephrine.Conclusion: These results support use of the CST in combination with measurements of normetanephrine for confirming or excluding P/PGL in patients with borderline elevated test results, which should, however, first be confirmed by sampling blood under standardized resting conditions.
DMW - Deutsche Medizinische Wochenschrift 01/2013; 138(3):76-81. · 0.53 Impact Factor
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C G Ziegler,
M Ullrich,
A V Schally,
R Bergmann,
J Pietzsch,
L Gebauer,
K Gondek,
N Qin,
K Pacak,
M Ehrhart-Bornstein,
G Eisenhofer, S R Bornstein
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ABSTRACT: Pheochromocytoma is a rare but potentially lethal chromaffin cell tumor with currently no effective treatment. Peptide hormone receptors are frequently overexpressed on endocrine tumor cells and can be specifically targeted by various anti-tumor peptide analogs. The present study carried out on mouse pheochromocytoma cells (MPC) and a more aggressive mouse tumor tissue-derived (MTT) cell line revealed that these cells are characterized by pronounced expression of the somatostatin receptor 2 (sst2), growth hormone-releasing hormone (GHRH) receptor and the luteinizing hormone-releasing hormone (LHRH) receptor. We further demonstrated significant anti-tumor effects mediated by cytotoxic somatostatin analogs, AN-162 and AN-238, by LHRH antagonist, Cetrorelix, by the cytotoxic LHRH analog, AN-152, and by recently developed GHRH antagonist, MIA-602, on MPC and for AN-152 and MIA-602 on MTT cells. Studies of novel anti-tumor compounds on these mouse cell lines serve as an important basis for mouse models of metastatic pheochromocytoma, which we are currently establishing.
Molecular and Cellular Endocrinology 12/2012; · 4.19 Impact Factor
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ABSTRACT: Stem cell - based therapies for central nervous system disorders are intensely pursued. Such approaches can be divided into two categories: Transplantation-based, and those that aim to pharmacologically target the endogenous stem cell population in the tissue. Endogenous stem cell - based strategies avoid the problem of immune incompatibility between the host and the grafted cells. They also avoid the placement of a large amount of cells in confined areas, a manipulation which alters the characteristics of the neurovascular microenvironment. We show here that massive pharmacological activation (increase in cell numbers) of the endogenous neural stem cell population in the adult rodent brain maintains the cytoarchitecture of the neurovascular niche. Distances between adjacent stem cells (identified by expression of Hes3) are maintained above a minimum. Hes3+ cells maintain their physical association with blood vessels. These results also suggest a mechanism by which the activation signal from the lateral ventricle can be propagated to areas a long distance away from the lateral ventricles, through autocrine/paracrine actions between adjacent Hes3+ cells, along blood vessels. Finally, powerful effects of angiopoietin 2 on Hes3+ cells help explain the prevalence of proliferating endogenous neural stem cells close to the subventricular zone (an area of high angiopoietin 2 concentration) and the quiescent state of stem cells away from the ventricles and their tight physical association with blood vessels (which express high levels of angiopoietin 1, a cytokine that opposes angiopoietin 2 functions).
CNS & neurological disorders drug targets 11/2012; · 3.57 Impact Factor
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ABSTRACT: Apart from their role in cardiovascular homeostasis and immunomodulation, aldosterone and cortisol are also implicated in the pathogenesis of insulin resistance and type 2 diabetes mellitus (T2DM). Furthermore, glycoxidative modifications of lipoproteins are increasingly recognized as an etiological factor for increased cardiovascular morbidity and mortality in prediabetic individuals. The causative relationship between in vivo lipoprotein modifications and steroidogenesis in subjects with impaired glucose tolerance (IGT), however, is not well defined. Therefore, we aimed to investigate the impact of in vivo modified lipoproteins on aldosterone and cortisol release from human adrenocortical H295R cells. Following an oral glucose tolerance test, 20 individuals with normal glucose tolerance (NGT) and 20 IGT subjects were randomly selected from the ongoing PRAEDIAS prevention study in our department. Cells were incubated for 24 h with lipoproteins isolated from NGT and IGT individuals and aldosterone and cortisol release was measured in the supernatants. VLDL induced a greater stimulating effect on adrenocortical aldosterone and cortisol release compared to HDL and LDL. Moreover, IGT-VLDL evoked a significantly higher effect (p<0.05) on hormone release than NGT-VLDL. Incubation of cells with in vitro modified lipoproteins and specific pharmacological inhibitors suggests that VLDL presumably recruits ERK1/2 as one of the downstream effectors of Jak-2. In summary, in vivo modified VLDL are able to promote prediabetic hormonal dysregulation by modulating adrenocortical steroidogenesis via Jak-2-ERK dependent pathway.
Hormone and Metabolic Research 10/2012; · 2.19 Impact Factor
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J Graessler,
Y Qin,
H Zhong,
J Zhang,
J Licinio,
M-L Wong,
A Xu,
T Chavakis,
A B Bornstein,
M Ehrhart-Bornstein,
V Lamounier-Zepter,
T Lohmann,
T Wolf, S R Bornstein
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ABSTRACT: Roux-en-Y gastric bypass (RYGB) has become a prominent therapeutic option for long-term treatment of morbid obesity and type 2 diabetes mellitus (T2D). Cross talk and pathogenetic consequences of RYGB-induced profound effects on metabolism and gut microbiome are poorly understood. The aim of the present study therefore was to characterize intra-individual changes of gut microbial composition before and 3 months after RYGB by metagenomic sequencing in morbidly obese patients (body mass index (BMI)>40 kg m(-)(2)) with T2D. Subsequently, metagenomic data were correlated with clinical indices. Based on gene relative abundance profile, 1061 species, 729 genera, 44 phyla and 5127 KO (KEGG Orthology) were identified. Despite high diversity, bacteria could mostly be assigned to seven bacterial divisions. The overall metagenomic RYGB-induced shift was characterized by a reduction of Firmicutes and Bacteroidetes and an increase of Proteobacteria. Twenty-two microbial species and 11 genera were significantly altered by RYGB. Using principal component analysis, highly correlated species were assembled into two common components. Component 1 consisted of species that were mainly associated with BMI and C-reactive protein. This component was characterized by increased numbers of Proteobacterium Enterobacter cancerogenus and decreased Firmicutes Faecalibacterium prausnitzii and Coprococcus comes. Functional analysis of carbohydrate metabolism by KO revealed significant effects in 13 KOs assigned to phosphotransferase system. Spearmen's Rank correlation indicated an association of 10 species with plasma total- or low-density lipoprotein cholesterol, and 5 species with triglycerides. F. prausnitzii was directly correlated to fasting blood glucose. This is the first clinical demonstration of a profound and specific intra-individual modification of gut microbial composition by full metagenomic sequencing. A clear correlation exists of microbiome composition and gene function with an improvement in metabolic and inflammatory parameters. This will allow to develop new diagnostic and therapeutic strategies based on metagenomic sequencing of the human gut microbiome.The Pharmacogenomics Journal advance online publication, 2 October 2012; doi:10.1038/tpj.2012.43.
The Pharmacogenomics Journal 10/2012; · 4.54 Impact Factor
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ABSTRACT: The prevalence of obesity and related health problems is increasing worldwide and also in Germany. It is well known that substantial and sustained weight loss is difficult to accomplish. Therefore, a variety of studies has been performed in order to specify causes for weight gain and create hypotheses for better treatment options.Key factors of this problem are an adaptation of energy metabolism, especially resting metabolic rate (RMR), non-exercise thermogenesis and diet induced thermogenesis.The extremely high failure rate (> 80 %) to keep the reduced weight after successful weight loss is due to adaptation processes of the body to maintain body energy stores. This so called "adaptive thermogenesis" is defined as a smaller than predicted change of energy expenditure in response to changes in energy balance. Adaptive thermogenesis appears to be a major reason for weight regain. The foremost objective of weight-loss programs is the reduction in body fat. However, a concomitant decline in lean tissue can frequently be observed. Since lean body mass (LBM) represents a key determinant of RMR it follows that a decrease in lean tissue could counteract the progress of weight loss.Therefore, with respect to long-term effectiveness of weight reduction programs, the loss of fat mass while maintaining LBM and RMR seems desirable.In this paper we will discuss the mechanisms of adaptive thermogenesis and develop therapeutic strategies with respect to avoiding weight regain successful weight reduction.
DMW - Deutsche Medizinische Wochenschrift 10/2012; 137(43):2223-8. · 0.53 Impact Factor
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ABSTRACT: In hochindustrialisierten Ländern ist die Hyperurikämie eine der häufigsten Stoffwechselstörungen. Erhöhte Serumspiegel der
Harnsäure können zur Präzipitation von Uratkristallen im Bindegewebs- und Skelettsystem sowie in der Niere führen und sich
als Gicht klinisch manifestieren. In mehr als 90% der Hyperurikämien ist eine primär verminderte renale Harnsäureausscheidung
nachweisbar. Trotz der Identifizierung verschiedener Harnsäuretransportproteine konnte deren pathogenetische Beteiligung an
der Auslösung einer primären renalen Harnsäureexkretionsstörung bislang nicht belegt werden. Im Rahmen einer Fall-Kontroll-Studie
mit Hypo- und Normourikosurikern gelang erstmals der Nachweis einer Assoziation von Polymorphismen im Gen des humanen Urat1-Transporters
(hURAT1) mit einer verminderten renalen Uratausscheidung. Der hURAT1 ist ein Transporter organischer Anionen (SLC22A12) und
wird präferenziell in der apikalen Membran proximaler Tubuluszellen exprimiert. Als Antiporter vermittelt er den reabsorptiven
Transport von Urat aus dem Lumen in die Tubuluszelle im Austausch gegen organische und anorganische Anionen. Mutationen im
hURAT1 mit Funktionsverlust sind eine Ursache hereditärer renaler Hypourikämien. Als Hyperurikämiekandidatengen ist der fein regulierte
hURAT1 ein wichtiges Ziel für die Entwicklung und Optimierung neuer diagnostischer Verfahren und pharmakologischer Substanzen zur
Therapie primär-renaler Harnsäureausscheidungsstörungen.
In highly industrialized countries hyperuricemia is one of the most common metabolic disorders. High uric acid blood levels
may lead to the manifestation of gout owing to the precipitation of urate crystals in connective tissue, the skeletal system
and kidneys. A primary reduction of renal uric acid excretion can be detected in more than 90% of all cases of hyperuricemia.
Despite the identification of several uric acid transporting proteins their pathogenetic role for the induction of primary
reduced renal uric acid excretion has not yet been verified. As a result of a case-control study on individuals with normal
and reduced renal uric acid excretion, an association of polymorphisms in the human urate transporter 1 gene (hURAT1) with
primary reduced urate excretion has been demonstrated for the first time. The hURAT1 gene is an organic anion transporter
(SLC22A12), which is preferentially expressed in the apical membrane of proximal renal tubule cells. Functioning as an antiporter,
hURAT1 mediates the uptake of urate from the lumen into proximal tubule cells in exchange for organic and inorganic anions.
Loss-of-function mutations in the hURAT1 gene are a cause of hereditary renal hypouricemia. The precisely regulated hURAT1
is a candidate gene for hyperuricemia and an important target for the development and optimization of new diagnostic approaches
and pharmacological interventions of primary reduced renal uric acid excretion.
Zeitschrift für Rheumatologie 04/2012; 66(7):556-561. · 0.46 Impact Factor
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ABSTRACT: Raumforderungen der Nebenniere zählen zu den häufigsten Tumoren beim Menschen. Sie stellen eine heterogene Gruppe an Erkrankungen
dar, bestehend aus benignen und malignen Nebennierenrindenläsionen, Metastasen, Phäochromozytomen und anderen Tumorentitäten.
Raumforderungen, die ihren Ursprung in den Rinden- oder Markzellen haben, können sich klinisch inapparent verhalten bzw. zu
Hormonexzessen führen, die mild sind oder das Vollbild eines Conn-Syndroms, eines Cushing-Syndroms, eines Androgen- oder Östrogenexzesses
bzw. eines symptomatischen Phäochromozytoms verursachen. Andererseits kann eine Nebennierenrindenhyperplasie die Folge einer
erhöhten ACTH-Sekretion bei Steroidbiosynthesestörungen, bei Glukokortikoidresistenz und beim adrenogenitalen Syndrom oder
die Folge einer erhöhten ACTH-Sekretion bei Morbus Cushing bzw. beim ektopen ACTH-Syndrom sein. Es stehen Algorithmen für
endokrine Untersuchungen, bildgebende Verfahren und Kombinationen zur Verfügung, um die Tumorentitäten sowie ihre Hormonexzesssyndrome
klinisch zu charakterisieren. Neuere Entwicklungen in der Molekularbiologie eröffneten Möglichkeiten zur Identifizierung hereditärer
Tumorsyndrome, die auch mit einer adrenalen Tumorgenese assoziiert sind, und helfen dem Kliniker, individuelle Strategien
für die Weiterbetreuung zu entwickeln.
Adrenal masses are one of the most common tumors in humans. They are a very heterogenous group of diseases and include benign
and malignant adrenocortical lesions, metastases, pheochromocytomas and other entities. Adrenal masses originating from steroidogenic
or chromaffin cells may be silent or the source of subclinical or overt hormone excess, such as primary aldosteronism, hypercortisolism
or symptomatic catecholamine excess. On the other hand, adrenal hyperplasia may be the result of excess ACTH secretion in
steroid biosynthesis disorders with deficient glucocorticoid secretion, in glucocorticoid resistance, in Cushing’s disease,
or ectopic ACTH syndrome. Algorithms for endocrine testing, imaging studies and their combination are available for defining
the tumor entity and for the characterization of the hormone excess syndromes. Recent developments in molecular biology have
provided tools for testing for hereditary tumor syndromes associated with adrenal tumorigenesis and to establish strategies
for further treatment and follow-up.
Der Internist 04/2012; 48(9):971-986. · 0.30 Impact Factor
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ABSTRACT: Der beste Weg, Diabetes mellitus zu heilen ist, ihn zu verhindern. Mehrere große internationale Studien belegen, dass die
Prävention des Diabetes mellitus und seiner Begleitkomplikationen erfolgreich durchführbar und kosteneffektiv ist. Danach
haben Lebensstiländerungen oder frühe medikamentöse Interventionen bei 25–60% der Risikopersonen einen diabetespräventiven
Effekt und reduzieren mit großer Wahrscheinlichkeit auch das kardiovaskuläre Risiko. Diese Studien bilden die Evidenzbasis,
entscheidend aber ist die praktische und flächendeckende Umsetzung in Programme zur Diabetesprävention, anerkannt als Leistung
der gesetzlichen Krankenkassen.
Die Realisierung eines solchen Vorhabens erfordert viele Partner, die interdisziplinär und berufsgruppenübergreifend kooperieren.
Daher wurden unter der Schirmherrschaft des Nationalen Aktionsforums Diabetes mellitus (NAFDM) wesentliche Voraussetzungen
für ein nationales Präventionsprogramm erarbeitet. Erforderlich ist die Implementierung einer Leitlinie zur Diabetesprävention,
die Ziele und Standards für konkrete Interventionsmaßnahmen sowie Evaluationskriterien beinhaltet. Eine entscheidende Rolle
kommt in diesem Konzept dem Präventionsmanager und einer prozessbegleitenden Qualitätskontrolle zu.
Die Implementierung strukturierter Präventionsmanagementprogramme ermöglicht eine flächendeckende Realisierung der Diabetesprävention,
ohne das Gesundheitsbudget stark zu belasten. Sich der Herausforderung der Primärprävention zu stellen, erfordert die aktive
Zusammenarbeit aller Partner und ist nur langfristig erfolgreich umzusetzen. Dies stellt allerdings ein lohnendes Investment
für die Betroffenen, die klinische und wissenschaftliche Diabetologie und das Gesundheitswesen in Deutschland dar.
The most efficient way to manage diabetes and its complications is to prevent the disease from developing. Recent studies
have convincingly demonstrated that the prevention of diabetes and its complications are possible and cost-efficient. Lifestyle
intervention and also early pharmacologic preventive strategies have yielded a 25–60% diabetes risk reduction and a promising
reduction of cardiovascular risk. These findings offer the evidence base, however, the delivery of intervention and care is
essential. The challenge, therefore, is the management of prevention and intervention programs considering scientific aspects
and practical requirements during implementation. This can only be addressed in a coordinated interdisciplinary and cross-sector
setting and requires the development of a comprehensive, integrated prevention management program. The implementation of a
National Diabetes Prevention Program derived from evidence-based practical management guidelines is essential. Developing
the role of the prevention manager and continuous evaluation and quality control are key factors in performing high quality
intervention and care. Implementing managed prevention programs will enable nationwide prevention of diabetes mellitus without
consuming a large amount of resources. This process will be challenging and time-consuming, requiring many partners but resulting
in a profitable health investment.
Ernährung - Wissenschaft und Praxis 04/2012; 1(3):108-115.
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Molecular psychiatry 04/2012; 17(4):351. · 15.05 Impact Factor
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ABSTRACT: The development of new drugs for the treatment of type 2 diabetes (T2DM) and metabolic disorders is currently one of the most innovative areas of drug development. However, a considerable number of newly developed drugs have either not reached the market and were stopped late in development or have been withdrawn after initial approval soon after market authorization due to serious safety concerns. How can drug safety problems be anticipated and, even more important, how can adverse events definitely caused by a drug be differentiated from incidences of naturally occurring diseases? This review article will provide an update about the state of the art treatment of type 2 diabetes and reflect on the newest available study evidence on glitazones, incretin mimetics (GLP-1 agonists and DPP-4 inhibitors), SGLT-2 inhibitors (gliflocines) and pan-PPAR agonists (glitazars). Furthermore, new and still experimental approaches for the treatment of T2DM, such as bardoxolone, salsalate and anakinra will be briefly reviewed.
Der Internist 03/2012; 53(4):478, 480-5, 487. · 0.30 Impact Factor
