Institute of Laboratory Medicine

Aarau, Switzerland

Institute of Laboratory Medicine

Aarau, Switzerland
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Janssen S.T.,Institute of Laboratory Medicine | Janssen O.E.,Endokrinologikum Hamburg
Molecular and Cellular Endocrinology | Year: 2017

Thyroid hormones are bound to three major serum transport proteins, thyroxin-binding globulin (TBG), transthyretin (TTR) and human serum albumin (HSA). TBG has the strongest affinity for thyroid hormones, TTR is also found in the cerebrospinal fluid and HSA is the most abundant protein in plasma. Combination defects of either a high affinity TTR or HSA variant do not compensate TBG deficiency, underscoring the dominant role of TBG among the thyroid hormone transport proteins. On the other hand, coexistence of raised affinity TTR and HSA variants causes an augmented hyperthyroxinemia. Variations in thyroid hormone transport proteins may alter thyroid function tests to mimic hypo- or hyperthyroidism. As affected individuals are clinically euthyroid and do not require treatment, identification of thyroid hormone transport protein defects is important to avoid unnecessary diagnostic and therapeutic interventions. Mammals share the multilayered system of thyroid hormone binding proteins with humans. Some of them, especially carnivores, do not express TBG. In dogs, this defect has been shown to be caused by a defective hepatocyte nuclear factor-1 binding site in the TBG promoter, preventing TBG synthesis in the liver. The major endogenous thyroid hormone metabolite 3-iodothyronamine (3-T1AM) exerts marked cryogenic, metabolic, cardiac and central nervous system actions. It is bound to apolipoproteinB-100 (ApoB100), possibly facilitating its cellular uptake via interaction with the low density lipoprotein-receptor. This review summarizes the handling of hydrophobic charged thyroid hormone signaling molecules and their metabolite 3-T1AM in aqueous body fluids and the advantages and limits of their serum distributor proteins. © 2017 Elsevier B.V.

Salkovic-Petrisic M.,University of Zagreb | Osmanovic-Barilar J.,University of Zagreb | Knezovic A.,University of Zagreb | Hoyer S.,University of Heidelberg | And 2 more authors.
Neuropharmacology | Year: 2014

Basic and clinical research has demonstrated that dementia of sporadic Alzheimer's disease (sAD) type is associated with dysfunction of the insulin-receptor (IR) system followed by decreased glucose transport via glucose transporter GLUT4 and decreased glucose metabolism in brain cells. An alternative source of energy is d-galactose (the C-4-epimer of d-glucose) which is transported into the brain by insulin-independent GLUT3 transporter where it might be metabolized to glucose via the Leloir pathway. Exclusively parenteral daily injections of galactose induce memory deterioration in rodents and are used to generate animal aging model, but the effects of oral galactose treatment on cognitive functions have never been tested. We have investigated the effects of continuous daily oral galactose (200 mg/kg/day) treatment on cognitive deficits in streptozotocin-induced (STZ-icv) rat model of sAD, tested by Morris Water Maze and Passive Avoidance test, respectively. One month of oral galactose treatment initiated immediately after the STZ-icv administration, successfully prevented development of the STZ-icv-induced cognitive deficits. Beneficial effect of oral galactose was independent of the rat age and of the galactose dose ranging from 100 to 300 mg/kg/day. Additionally, oral galactose administration led to the appearance of galactose in the blood. The increase of galactose concentration in the cerebrospinal fluid was several times lower after oral than after parenteral administration of the same galactose dose. Oral galactose exposure might have beneficial effects on learning and memory ability and could be worth investigating for improvement of cognitive deficits associated with glucose hypometabolism in AD. © 2013 Elsevier Ltd. All rights reserved.

Koves B.,South Pest Teaching Hospital | Wullt B.,Institute of Laboratory Medicine
European Urology, Supplements | Year: 2016

The severity of urinary tract infections (UTIs) varies depending on the balance between the virulence of the infecting bacterial strain and the antibacterial host defense. Bacterial virulence is determined by a complex of factors in which bacterial adherence to the uroepithelium is the most important virulence factor, in addition to the production of toxins and the formation of biofilm. In immunocompromised patients and in patients with severely dysfunctional urinary tracts, however, the importance of bacterial virulence factors to cause symptomatic infection is decreased or nullified. The antibacterial host defense in the urinary tract depends mainly on native immunity and inflammation. Specific immunity, with antigen presentation and antibody production, does not play an important role in acute UTI. Recent research has provided a deeper understanding of the inflammation process in UTI and demonstrated that the individual variation of UTI susceptibility and renal damage not only depends on urinary tract dysfunctions but is also influenced by genetic polymorphisms in innate immune receptors and signaling proteins, crucial for the innate antibacterial defenses. The identification of these molecular mechanisms in UTI pathogenesis is an important focus for future research aimed at the development of novel nonantibiotic therapies. Patient summary: The severity of urinary tract infections (UTIs) varies depending on the balance between the infecting bacterial strain and the antibacterial host defense. Bacterial virulence is determined by different virulence factors that enhance bacterial persistence and tissue damage. The susceptibility to an UTI is influenced by dysfunctions of the urinary tract and by genetic mechanisms that control the innate immune response to infections. The severity of urinary tract infections (UTIs) varies depending on the balance between the infecting bacterial strain and the antibacterial host defense. Urologists will need a more microbiology- and immunology-centered perspective to successfully manage the increasing threat of UTIs. © 2016 European Association of Urology.

Soufi M.,University of Marburg | Rust S.,Leibniz Institute For Arterioskleroseforschung | Walter M.,Institute of Laboratory Medicine | Schaefer J.R.,University of Marburg
Gene | Year: 2013

Familial hypercholesterolemia (FH) results from impaired catabolism of plasma low density lipoproteins (LDL), thus leading to high cholesterol, atherosclerosis, and a high risk of premature myocardial infarction. FH is commonly caused by defects of the LDL receptor or its main ligand apoB, together mediating cellular uptake and clearance of plasma LDL. In some cases FH is inherited by mutations in the genes of PCSK9 and LDLRAP1 (ARH) in a dominant or recessive trait. The encoded proteins are required for LDL receptor stability and internalization within the LDLR pathway. To detect the underlying genetic defect in a family of Turkish descent showing unregular inheritance of severe FH, we screened the four candidate genes by denaturing gradient gel electrophoresis (DGGE) mutation analysis. We identified different combinatory mixtures of LDLR- and LDLRAP1-gene defects as the cause for severe familial hypercholesterolemia in this family. We also show for the first time that a heterozygous LDLR mutation combined with a homozygous LDLRAP1 mutation produces a more severe hypercholesterolemia phenotype in the same family than a homozygous LDLR mutation alone. © 2013 Elsevier B.V.

Hildebrandt A.,Friedrich - Schiller University of Jena | Gray J.S.,University College Dublin | Hunfeld K.-P.,Institute of Laboratory Medicine
Infection | Year: 2013

Although best known as an animal disease, human babesiosis is attracting increasing attention as a worldwide emerging zoonosis. Humans are commonly infected by the bite of ixodid ticks. Rare ways of transmission are transplacental, perinatal and transfusion-associated. Infection of the human host can cause a very severe host-mediated pathology including fever, and hemolysis leading to anemia, hyperbilirubinuria, hemoglobinuria and possible organ failure. In recent years, apparently owing to increased medical awareness and better diagnostic methods, the number of reported cases in humans is rising steadily worldwide. Hitherto unknown zoonotic Babesia spp. are now being reported from geographic areas where babesiosis was not previously known to occur and the growing numbers of travelers and immunocompromised individuals suggest that the frequency of cases in Europe will also continue to rise. Our review is intended to provide clinicians with practical information on the clinical management of this rare, but potentially life-threatening zoonotic disease. It covers epidemiology, phylogeny, diagnostics and treatment of human babesiosis and the potential risk of transfusion-transmitted disease with a special focus on the European situation. © 2013 Springer-Verlag Berlin Heidelberg.

Kovac M.,Blood Transfusion Institute of Serbia | Mitic G.,Institute of Laboratory Medicine | Kovac Z.,Serbian Institute for Oncology and Radiology of Serbia
Journal of Clinical Pharmacy and Therapeutics | Year: 2012

What is known and Objective: Medline search disclosed 10 case reports of interactions between oral anticoagulants and miconazole oral gel, but none so far between nystatin solution and anticoagulants. We report on change in anticoagulant activity with use of different topical antifungal drugs, miconazole oral gel and vaginal suppositories, and nystatin solution. Methods: We conducted a retrospective study that included 43 patients on stable anticoagulation before the introduction of topical antifungal drugs. Miconazole oral gel was prescribed for 32 patients, nystatin solution for eight patients and miconazole vaginal suppositories for three patients. Results and Discussion: Nineteen (44·2%) of the patients reported bleeding complications and some of these were severe. Fifteen of 32 who used miconazole oral gel and four of 8 of those who used nystatin solution were affected. Before use of the antifungal drugs, the mean weekly warfarin dose in the nystatin group was 14·5 mg, and after antifungal drugs, 9 mg, P = 0·038, while the mean international normalized ratio (INR) before antifungal drugs was 2·5 (range 1·9-3·5) and afterwards it was 10·6 (range 4·5-19·3), P = 0·0001. In the miconazole oral gel group the mean weekly warfarin dose was 15·7 mg, and after 10·8 mg, P = 0·008, while the mean INR before antifungal drugs was 2·44 (range 1·92-3·18) and afterwards it was 8·8 (range 4·9-16·9), P < 0·0001. What is new and Conclusion: Miconazole oral gel and topically applied nystatin solution have equally strong effects on warfarin activity and can provoke major bleeding. Prospective evaluation of this effect is called for. However, based on our results the warfarin dose adjustment appears necessary when the anticoagulant is used concomitantly with those topical antifungals. © 2011 Blackwell Publishing Ltd.

Nuding S.,Robert Bosch GmbH | Nuding S.,University of Tübingen | Frasch T.,Institute of Laboratory Medicine | Schaller M.,University of Tübingen | And 2 more authors.
Antimicrobial Agents and Chemotherapy | Year: 2014

Accelerating rates of health care-associated infections caused by Clostridium difficile, with increasing recurrence and rising antibiotic resistance rates, have become a serious problem in recent years. This study was conducted to explore whether a combination of antibiotics with human antimicrobial peptides may lead to an increase in antibacterial activity. The in vitro activities of the antimicrobial peptides HBD1 to HBD3, HNP1, HD5, and LL-37 and the antibiotics tigecycline, moxifloxacin, piperacillintazobactam, and meropenem alone or in combination against 10 toxinogenic and 10 nontoxinogenic C. difficile strains were investigated. Bacterial viability was determined by flow cytometry and toxin production by enzyme-linked immunosorbent assay (ELISA). When combined at subinhibitory concentrations, antimicrobial peptides and antibiotics generally led to an additive killing effect against toxinogenic and nontoxinogenic C. difficile strains. However, LL-37 and HBD3 acted in synergism with all the antibiotics that were tested. Electron microscopy revealed membrane perturbation in bacterial cell walls by HBD3. In 3 out of 10 toxinogenic strains, HBD3, LL-37, piperacillin-tazobactam, and meropenem administration led to an increased toxin release which was not neutralized by the addition of HNP1. Antimicrobial peptides increase the bacterial killing of antibiotics against C. difficile regardless of the antibiotics' mode of action. Membrane perturbation in or pore formation on the bacterial cell wall may enhance the uptake of antibiotics and increase their antibacterial effect. Therefore, a combination of antibiotics with antimicrobial peptides may represent a promising novel approach to the treatment of C. difficile infections. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

Perne A.,Medical University of Vienna | Hainfellner J.A.,Medical University of Vienna | Womastek I.,Medical University of Vienna | Haushofer A.,Institute of Laboratory Medicine | And 2 more authors.
Archives of Pathology and Laboratory Medicine | Year: 2012

Context.-The newest generation hematology analyzer, Sysmex XE-5000 (Sysmex Corporation, Kobe, Japan) is equipped with an improved body fluid analysis mode. Objective.-To evaluate the applicability of the XE-5000 analyzer to white blood cell (WBC) analysis in cerebrospinal fluid (CSF). Design.-A total of 425 routinely collected, consecutive CSF samples were included in the study. For a comparison of total WBC counts, the results of routine chamber counts were grouped into categories of 0 to 5 (n = 330)> .5 to 10 (n = 36)>.10 to 50 (n = 39)> .50 to 200 (n = 15), and>200 (n = 5) WBC/μL. Microscopic differential counts were performed using cytospins from 276 samples. Results were grouped according to the percent content of polymorphonuclear (PMN) cells, 0% to 25% (n = 263)> .25% to 50% (n = 7)> .50% to 75% (n = 3), and >75% to 100% (n = 3) of WBC. Corresponding results of XE-5000 analysis were matched to these particular count categories. Results.-For total WBC counts, the proportions of samples correctly classified by the XE-5000 from the percentage groups described above were 88%, 47%, 72%, 93%, and 100%, respectively. After the two lowest count categories were combined into one range of 0 to 10 WBC/μL, matches increased to 95%. For PMN counts in the 0% to 25% group, 37% of samples were misclassified by the XE-5000. Conversely, for samples with microscopic PMN counts of more than 25%, there was a trend toward underestimation by the XE-5000. Mismatches were most pronounced in samples with fewer than 10 WBC/μL. Conclusions.-The Sysmex XE-5000 hematology analyzer yields valid total CSF cell counts and may be considered an acceptable alternative to the traditional chamber method, even for samples with low WBC counts. However, it cannot be recommended as a suitable alternative for manual differential cytologic workup.

Minder E.I.,Institute of Laboratory Medicine | Schneider-Yin X.,Institute of Laboratory Medicine
Expert Review of Clinical Pharmacology | Year: 2014

The application of afamelanotide, an α-melanocyte stimulating hormone agonistic analogue to protoporphyria, a disease with absolute sunlight-intolerance is discussed. The clinics, genetics and existing therapies of protoporphyria are described. The physiological receptor-mediated intracellular signaling of α-melanocyte stimulating hormone and effects of receptor variants are outlined. The pharmacological action of afamelanotide and the rationale behind its application in protoporphyria are given. The results of several Phase II and III and safety issues are discussed. The trial results were significant, although the effects were not very large in absolute terms, and the risk-safety profile is favorable today. Based on the high compliance rate and the excellent consistency in clinical effectiveness during six years of compassionate use program in Switzerland, we expect afamelanotide and analogues to become a prospective therapeutic tool. Moreover, we hope that dosage forms suitable for children will be developed in future, as children and adolescents suffer most in protoporphyria. © 2015 Informa UK, Ltd.

Paasch U.,University of Leipzig | Grunewald S.,University of Leipzig | Kratzsch J.,Institute of Laboratory Medicine | Glander H.-J.,University of Leipzig
Fertility and Sterility | Year: 2010

A case-cohort study of 2,157 patients, aged 17-67 years was performed to assess the impact of body mass index and age on male fertility. Using a multiple regression analysis across the total cohort, only age correlated significantly with all spermiogram parameters and serum hormones, but in patients aged 20-30 years (n = 617) the total sperm count was significantly negatively correlated with body mass index. Copyright © 2010 American Society for Reproductive Medicine, Published by Elsevier Inc.

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