Rudolf Gesztelyi

The complex role of vitamin D in autoimmune diseases.

Vitamin D, besides having well‐known control functions of calcium and phosphorus metabolism, bone formation and mineralization, also has a role in the maintenance of immune‐homeostasis. The immune‐regulatory role of vitamin D affects both the innate and adaptive immune system contributing to the immune‐tolerance of self‐structures. Impaired vitamin D supply/regulation, amongst other factors, leads to the development of autoimmune processes in animal models of various autoimmune diseases. The administration of vitamin D in these animals leads to improvement of immune‐mediated symptoms. Moreover, in human autoimmune diseases, such as multiple sclerosis, or rheumatoid arthritis the pathogenic role of vitamin D has been described. The review aims at describing the complex immune‐regulatory role of vitamin D from the cellular level through autoimmune animal models and depicting the known contribution of vitamin D in the pathogenesis of human autoimmune diseases.

Resveratrol: A Multifunctional Cytoprotective Molecule

Several recent studies have shown the protective effects of resveratrol in various experimental conditions and pathological animal models. Clinical studies also indicate the beneficial effects of resveratrol in different human diseases. Resveratrol produces a cascade against of events from the initial death-provoking signal, DNA fragmentation, and cell death. Researchers recognized the beneficial effect of resveratrol, as an important component, of the overall injury that occurs in various disorders such as oxidative stress, myocardial injury, anticancer activity, antidiabetic activity, and antihypercholesterolemic effects. Many mechanisms have been proposed for the initiation of protective effects of resveratrol in various pathological events, and considerable evidence exists to indicate that many mediators are involved in the resveratrol-induced protection. The present review focuses on the history, and the beneficial effects and mechanisms of resveratrol in oxidative stress, myocardial injury, anticancer-, antidiabetic- and antihypercholesterolemic activities, and discusses those therapeutic tools, which warrant becoming clinically important.

Screening for depressive symptoms in the acute phase of stroke

Depressive symptoms can often be observed after stroke. We prospectively evaluated patients at a stroke unit in order to determine the occurrence and severity of depressive symptoms in the acute phase of stroke in 82 patients 7 +/- 2 days after admission to the stroke unit. Severity of stroke was evaluated by the Scandinavian and Orgogozo scales and the Barthel index. Severity of depressive symptoms was measured by the 13-item Beck scale. Mean age of the patients was 65.8 years. No gender difference was observed in the severity of stroke or depressive symptoms. DSM-IV criteria of adjustment disorder with depressed mood were fulfilled by 27% of the patients. In this group, stroke was significantly more severe by the Barthel, Orgogozo, and Scandinavian scales (p < 0.001). Whereas Beck score was at least 10 in 19.5%, severe depressive symptoms (Beck score > or = 15) occurred in less than 5% of patients with acute stroke. Those who could not walk by themselves or who were aphasic had significantly higher mean Beck scores (6.3 +/- 5.1 vs 2.4 +/- 3.1, p < 0.001, and 7.0 +/- 5.8 vs 3.4 +/- 3.9, p = 0.002). Significant correlation was found between the severity of stroke and that of the depressive symptoms (r = -0.56, -0.58, and -0.54 for the Scandinavian, Orgogozo, and Barthel scales, p < 0.001).

Summative interaction between astaxanthin, Ginkgo biloba extract (EGb761) and vitamin C in suppression of respiratory inflammation: a comparison with ibuprofen.

In this study, combinations of Ginkgo biloba leaf extract (EGb761) plus the carotenoid antioxidant astaxanthin (ASX) and vitamin C were evaluated for a summative dose effect in the inhibition of asthma‐associated inflammation in asthmatic guinea‐pigs. Ovalbumin‐sensitized Hartley guinea‐pigs challenged with ovalbumin aerosol to induce asthma, were administered EGb761, ASX, vitamin C or ibuprofen. Following killing, bronchoalveolar lavage (BAL) fluid was evaluated for inflammatory cell infiltrates and lung tissue cyclic nucleotide content. Each parameter measured was significantly altered to a greater degree by drug combinations, than by each component acting independently. An optimal combination was identified that included astaxanthin (10 mg/kg), vitamin C (200 mg/kg) and EGb761 (10 mg/kg), resulting in counts of eosinophils and neutrophils each 1.6‐fold lower; macrophages 1.8‐fold lower, cAMP 1.4‐fold higher; and cGMP 2.04‐fold higher than levels in untreated, asthmatic animals (p < 0.05). In conclusion, EGb761, ASX and vitamin C are shown here to interact summatively to suppress inflammation with efficacy equal to or better than ibuprofen, a widely used non‐steroidal antiinflammatory drug (NSAID). Such combinations of non‐toxic phytochemicals constitute powerful tools for the prevention of onset of acute and chronic inflammatory disease if consumed regularly by healthy individuals; and may also augment the effectiveness of therapy for those with established illness. Copyright

Increased production of asymmetric dimethylarginine (ADMA) in ankylosing spondylitis: Association with other clinical and laboratory parameters

OBJECTIVE Asymmetric dimethylarginine (ADMA) has been associated with atherosclerosis, vascular diseases and, recently, also with arthritis including rheumatoid arthritis (RA) and ankylosing spondylitis (AS). METHODS Serum ADMA, arginine and symmetric dimethylarginine (SDMA) levels were assessed by liquid chromatography in 61 AS and 26 osteoarthritis (OA) patients with no known cardiovascular disease. RESULTS Serum ADMA levels were significantly increased in AS compared to OA patients (0.95 ± 0.17 μM versus 0.70 ± 0.25 μM; p < 0.001). There were no differences in serum arginine and SDMA levels. Serum ADMA levels also positively correlated with age (R = 0.258; p = 0.043), body mass index (R = 0.368; p = 0.003), erythrocyte sedimentation rate (R = 0.329; p = 0.009) and ADMA levels negative correlated with chest expansion (R = -0.251; p = 0.04). No correlations were found between ADMA levels and disease duration, pain intensity, BASDAI, BASFI, BASMI, quality of life, CRP, HLA-B27 positivity, endothelial dysfunction or carotid atherosclerosis. CONCLUSION ADMA may serve as a marker of systemic inflammation and may reflect functional immobility in AS. Further studies are needed to assess the possible role of ADMA in AS and AS-related vascular disease.

Isolation and Analysis of Bioactive Constituents of Sour Cherry (Prunus cerasus) Seed Kernel: An Emerging Functional Food

A plant-based diet reduces the risk for the development of several chronic diseases, such as ischemic heart disease or cancer due to natural compounds found in plants. Numerous cereals, berries, fruits, and vegetables, including sour cherry (Prunus cerasus), which is a favored fruit worldwide, contain biological active components. The antioxidant components of the sour cherry seed kernel have not been investigated until now. The aim of our study was to isolate and analyze the bioactive constituents of sour cherry seed kernel. We separated the oil fraction of the kernel; then the remaining solid fraction was dried, and the oil-free kernel extract was further analyzed. Our results show that sour cherry seed kernel oil contains vegetable oils including unsaturated fatty acids, oleic acids, alpha-tocopherol, tocotrienols, and tocopherol-like components. The components of the solid fraction include various bioactive structures such as polyphenols, flavonoids, vegetable acids, and pro- and anthocyanidins, which could have useful therapeutic effects in the prevention of various vascular diseases.

Postischemic cardiac recovery in heme oxygenase-1 transgenic ischemic/reperfused mouse myocardium

Heme oxygenase‐1 (HO‐1) transgenic mice (Tg) were created using a rat HO‐1 genomic transgene. Transgene expression was detected by RT‐PCR and Western blots in the left ventricle (LV), right ventricle (RV) and septum (S) in mouse hearts, and its function was demonstrated by the elevated HO enzyme activity. Tg and non‐transgenic (NTg) mouse hearts were isolated and subjected to ischemia/reperfusion. Significant post‐ischemic recovery in coronary flow (CF), aortic flow (AF), aortic pressure (AOP) and first derivative of AOP (AOPdp/dt) were detected in the HO‐1 Tg group compared to the NTg values. In HO‐1 Tg hearts treated with 50 μmol/kg of tin protoporphyrin IX (SnPPIX), an HO enzyme inhibitor, abolished the post‐ischemic cardiac recovery. HO‐1 related carbon monoxide (CO) production was detected in NTg, HO‐1 Tg and HO‐1 Tg + SnPPIX treated groups, and a substantial increase in CO production was observed in the HO‐1 Tg hearts subjected to ischemia/reperfusion. Moreover, in ischemia/reperfusion‐induced tissue Na+ and Ca2+ gains were reduced in HO‐1 Tg group in comparison with the NTg and HO‐1 Tg + SnPPIX treated groups; furthermore K+ loss was reduced in the HO‐1 Tg group. The infarct size was markedly reduced from its NTg control value of 37 ± 4% to 20 ± 6% (P < 0.05) in the HO‐1 Tg group, and was increased to 47 ± 5% (P < 0.05) in the HO‐1 knockout (KO) hearts. Parallel to the infarct size reduction, the incidence of total and sustained ventricular fibrillation were also reduced from their NTg control values of 92% and 83% to 25% (P < 0.05) and 8% (P < 0.05) in the HO‐1 Tg group, and were increased to 100% and 100% in HO‐1 KO−/− hearts. Immunohistochemical staining of HO‐1 was intensified in HO‐1 Tg compared to the NTg myocardium. Thus, the HO‐1 Tg mouse model suggests a valuable therapeutic approach in the treatment of ischemic myocardium.

In vivo studies with a Candida tropicalis isolate exhibiting paradoxical growth in vitro in the presence of high concentration of caspofungin

We investigated the activity of caspofungin against a Candida tropicalis clinical isolate showing paradoxical growth in vitro. BALB/c mice immunosuppressed by cyclophosphamide were infected intraperitoneally using 107 CFU/mouse. Caspofungin was administered intraperitoneally once daily for 5 days or as a single dose using the following doses: 0.12, 0.25, 1, 2, 3, 5, and 15 mg/kg. The single dose of caspofungin was effective only at 5 and 15 mg/kg concentrations (100% survival). Five-day caspofungin treatment led to 100% survival at doses of 1 mg/kg or higher. Caspofungin treatment significantly decreased the number of viable yeasts in the peritoneal lavage samples as well as in the infected abscesses at doses 1, 3, 5, and 15 mg/kg caspofungin as compared to the untreated control (P<0.001 in all cases), and even to the group treated with 0.12 mg/kg caspofungin (P<0.05 in all cases). At 2 mg/kg caspofungin dose, sterilization of the internal organs was reproducibly incomplete, suggesting that the role of paradoxical growth in the late clinical failure cannot be excluded.

Serum asymmetric dimethylarginine negatively correlates with intima-media thickness in early-onset atherosclerosis.

Background: Asymmetric dimethylarginine (ADMA) assumes a significant role in atherosclerosis by inhibiting the endothelial nitric oxide synthase (eNOS). Moreover, ADMA inhibits the inducible NOS (iNOS), the isoform that triggers atherosclerosis via peroxynitrite formation. Therefore, we investigated whether ADMA is a risk or protective factor in the atherosclerotic process. Intima-media thickness (IMT) of the common carotid artery, a surrogate for vascular diseases, was chosen as the outcome variable of interest. Methods: Sixty patients younger than 55 years having at least 30% stenosis of the internal carotid artery and 30 age- and gender-matched controls were recruited at a community-based neurosonological laboratory. We investigated relatively young patients to circumvent the confounding effect age has in the development of atherosclerosis. Results: The IMT showed a negative correlation with ADMA upon analysis of the pooled data (Spearman correlation coefficient –0.300, p = 0.0041) and the atherosclerotic stratum (Spearman correlation coefficient –0.323, p = 0.012). A multiple linear regression model containing all determinant factors of IMT previously identified by simple regression was used to further quantify the relationship between IMT and ADMA. The negative association between IMT and ADMA remained statistically significant (β: –0.510, CI: –0.894, –0.127; p = 0.010), furthermore it was even stronger in the atherosclerotic stratum (β: –0.67, CI: –1.16, –0.18; p = 0.008). Conclusions: A minimal increase in ADMA concentration may be protective by inhibiting iNOS but not eNOS in states where iNOS is induced, e.g. inflammation accompanying atherosclerosis.

In Vitro Study of Candida tropicalis Isolates Exhibiting Paradoxical Growth in the Presence of High Concentrations of Caspofungin

ABSTRACT Paradoxical growth was noted in RPMI 1640 and antibiotic medium 3 in the case of 14 and 1 of 15 Candida tropicalis strains, respectively, at a caspofungin concentration of 12.5 μg/ml using minimum fungicidal concentration tests. Time-kill assays showed that against isolates killed at lower concentrations, caspofungin at a concentration of 12.5 μg/ml was only fungistatic.