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Maximilian Ledochowski

Publications and source records attributed to Maximilian Ledochowski.

10 recordsLinked to original sources
PubMed2005

Antioxidants may increase the probability of developing allergic diseases and asthma.

In addition to genetic predisposition, a lack of triggers for Th1 immune response like exposure to infections, endotoxins and dirt in childhood are supposed to be responsible for the higher incidence of allergic rhinitis and asthma (hygiene hypothesis). In vitro, beverages rich in antioxidants like green tea and wine were found to suppress formation of Th1-type cytokine interferon-gamma. Due to the existing cross-regulatory interplay between Th1- and Th2-type immune response, these beverages may thus slow-down Th1-type immune response and thereby favour an over-production of Th2-type cytokines. Also food rich in antioxidants may increase the risk of atopic disease. Thus, not only a lack of triggers for Th1 type immune response, but also a nutrition rich in antioxidants suppressing interferon-gamma would result in a persistence of Th2-type immune response and increase the susceptibility for allergic reactions and asthma. In addition to improved hygienic standards in the past decades, also social changes including the availability of functional food and food enriched in antioxidants may have increased the prevalence of atopic diseases in Western countries.

Antioxidants↗
PubMed2003

Interaction of sertraline with Candida species selectively attenuates fungal virulence in vitro.

This study investigated whether the interaction between isolates of Candida albicans (n=7), Candida parapsilosis (n=3), Candida krusei (n=2), Candida dubliniensis (n=1) and sertraline, a typical selective serotonin reuptake inhibitor, alters candidal virulence. Sertraline treatment of Candida spp. significantly (P<0.05) affected hyphal elongation, phospholipase activity, production of secreted aspartyl proteinases and fungal viability. In addition, monocyte-derived macrophages (MDMs) treated with sertraline reduced inhibition of blastoconidia germination in comparison to MDMs alone. In conclusion, our findings suggest that the interaction between sertraline and Candida spp. may also diminish the virulence properties of this fungal pathogen in vivo.

Aspartic Acid Endopeptidases↗
PubMed2003

Moderate hyperhomocysteinaemia and immune activation in patients with rheumatoid arthritis.

BACKGROUND: Moderate hyperhomocysteinaemia related to folate deficiency has been described in patients with cardiovascular risk and also in patients with autoimmune diseases including rheumatoid arthritis (RA). METHODS: In 33 patients with RA, serum concentrations of homocysteine and cysteine, of B-vitamins folate and vitamin B(12), and of immune activation markers neopterin and soluble 75-kDa TNF-receptor (sTNF-R75) were measured. RESULTS: A significant proportion of patients presented with elevated homocysteine and cysteine concentrations in comparison to reference ranges of healthy control persons. Moderate hyperhomocysteinaemia coincided with decreased serum folate and with higher concentrations of sTNF-R75 and neopterin, but it was rather independent from methotrexate (MTX) therapy. CONCLUSIONS: The coincidence of higher homocysteine and lower folate concentrations with increased concentrations of immune activation markers in patients with RA suggests that immune activation could be involved in the development of hyperhomocysteinaemia.

Adult↗
PubMed2003

Antifungal properties of 5-hydroxytryptamine (serotonin) against Candida species in vitro.

In this study the minimal inhibitory concentration (MIC) and minimal fungicidal concentration (MFC) of 5-hydroxytryptamine (5 HT, serotonin) against clinical isolates of Candida albicans (n = 11), Candida glabrata (n = 9), Candida tropicalis (n = 10) and Candida parapsilosis (ATCC 22019) using a broth microdilution test were investigated. In addition, it was examined whether delayed regrowth as a post-antifungal effect results following short exposure to 5 HT. 5 HT showed antifungal activity towards all isolates of Candida spp. The isolates yielded comparable MIC and MFC values of 5 HT in the range 0.91-7.34 mM and 1.83-14.68 mM, respectively. A lag in regrowth was dependent on the concentration tested. Treatment for 3 h at concentrations of 5 HT below and equipotent to the MFC resulted in a delayed regrowth of 8-12 h for isolates of Candida spp. In conclusion, these in vitro studies clearly demonstrate antifungal effects of 5 HT. Identifying the mode of action could be of great help in developing and researching new antifungal drugs.

Antifungal Agents↗
PubMed2003

Association between increased serum cholesterol and signs of depressive mood.

Hypercholesterolemia is associated with an increased risk of atherosclerosis and coronary heart disease. Therefore, therapeutic lowering of cholesterol is an important preventive measure of cardiac morbidity and death. As one side effect, cholesterol-lowering drugs appear to increase the mortality due to suicides or violence, and low lipid concentrations were found to be associated with trait measures of depression. We compared serum cholesterol concentrations and the Beck Depression Rating Scale (Beck's score) in 604 otherwise healthy outpatients who visited the physician's office for a medical health check-up; 65.4% of individuals presented with serum cholesterol concentrations > or = 5.2 mmol/l (> 200 mg/dl) and 5.3% had elevated Beck's score (> 19), indicative for depression. Beck's score was higher in patients with cholesterol concentrations above the 75th percentile (= 6.2 mmol/l; U = 31221, p < 0.02, Mann-Whitney U-test), and Beck's score correlated with cholesterol concentrations and with age. Thus, in contrast to the widely accepted view, in our study, higher cholesterol concentrations were associated with signs of depressive mood. Hypercholesterolemia may not necessarily increase the risk of depressive mood, conversely, increased intake of fat and carbohydrates by individuals with depressive mood may increase cholesterol levels.

Adolescent↗
PubMed2003

Increased degradation of tryptophan in blood of patients with rheumatoid arthritis.

OBJECTIVE: Activation of the enzyme indoleamine-(2,3)-dioxygenase (IDO) by interferon (IFN)-g leads to enhanced tryptophan conversion to kynurenine. In consequence of chronic immune activation, tryptophan availability is reduced, leading to inhibition of cell proliferation as protein synthesis is affected. Tryptophan deprivation due to IDO activation could therefore be effective in abrogating processes with high metabolic turnover, thus modulating cellular immune response. METHODS: Concentrations of tryptophan, kynurenine, and neopterin were measured by HPLC in the sera of 38 patients with rheumatoid arthritis (RA). The kynurenine:tryptophan ratios (kyn/trp) were calculated to estimate IDO activity. RESULTS: Tryptophan concentrations were lower in patients with RA (median, interquartile range: 44.95 microM, 40.31-49.95 microM) compared to healthy blood donors (62.62 microM, 57.27-74.61 microM; p < 0.001). Kynurenine in patients (1.86 microM, 1.54-2.31 microM) did not differ from controls (2.06 microM, 1.58-2.65 microM; NS). The kyn/trp ratio was higher in patients (42.39 mM/M, 37.02-48.60 mM/M) than in controls (31.72 mM/M; 27.95-35.03 mM/M; p < 0.001). Kynurenine concentrations (rs = 0.611; p < 0.001) and kyn/trp ratios (rs = 0.621; p < 0.001) correlated with neopterin concentrations, which indicate stimulated cellular immune response in patients with RA. CONCLUSIONS: The data point to a role of immune activation and Th1-type cytokine INF-g to induce elevated tryptophan degradation in patients with RA.

Arthritis, Rheumatoid↗
PubMed2002

Neopterin production, tryptophan degradation, and mental depression--what is the link?

The cytokine interferon-gamma stimulates human monocytes/macrophages to release large amounts of neopterin. Increased neopterin concentrations in body fluids of patients are observed during diseases with activated cellular (=TH1-type) immune response such as allograft rejection, virus infections, autoimmune disorders, or malignant tumors but also in neurodegenerative diseases or during pregnancy. In various cells interferon-gamma induces indoleamine 2,3-dioxygenase (IDO) which degrades tryptophan via the kynurenine pathway. Therefore like increased neopterin formation, enhanced tryptophan degradation is observed in diseases concomitant with cellular immune activation. Disturbed metabolism of tryptophan affects biosynthesis of neurotransmitter 5-hydroxytryptamine (serotonin), and it appears to be associated with an increased susceptibility for depression. In fact, enhanced neopterin concentrations together with increased degradation of tryptophan and low serum levels of tryptophan correlate with neuropsychiatric abnormalities like cognitive decline and depressive symptoms especially in long-lasting and chronic diseases. Activation of IDO could represent an important link between the immunological network and the pathogenesis of depression.

Depressive Disorder↗
PubMed2002

Antifungal properties of 5-hydroxytryptamine (serotonin) against Aspergillus spp. in vitro.

This study shows that 5-hydroxytrypatmine (5-HT, serotonin) is fungicidal towards conidia and hyphae of clinical isolates of Aspergillus (A.) fumigatus, A. flavus and A. terreus. The minimal fungicidal concentrations for Aspergillus conidia and hyphae ranged between 14.68 to 117.5 mM and 29.37 to 235 mM during 24 and 48 h of incubation. Several serotonin receptor antagonists (5-HT2, 5-HT3) studied in vitro did not influence antifungal activity.

Antifungal Agents↗