A Multicenter Study of Stellate Ganglion Block as a Temporizing Treatment for Refractory Ventricular Arrhythmias.

BACKGROUND: Ventricular tachycardia (VT) and ventricular fibrillation (VF) are life-threatening conditions and can be refractory to conventional drug and device interventions. Stellate ganglion blockade (SGB) has been described as an adjunct, temporizing intervention in patients with refractory ventricular arrhythmia. We examined the association of SGB with VT/VF in a multicenter registry. OBJECTIVES: This study examined the efficacy of SGB for treatment/temporization of refractory VT/VF. METHODS: The authors present the first analysis from a multicenter registry of patients treated for refractory ventricular arrhythmia at a clinical site in the Czech Republic and the United States. Data were collected between 2016 and 2022. SGB was performed at the bedside by anesthesiologists and/or cardiologists. Outcomes of interest were VT/VF burden and defibrillations at 24 hours before and after SGB. RESULTS: In total, there were 117 patients with refractory ventricular arrhythmias treated with SGB at Duke (n = 49) and the Institute for Clinical and Experimental Medicine (n = 68). The majority of patients were male (94.0%), were White (87.2%), and had an implantable cardioverter-defibrillator (70.1%). The most common etiology of heart disease was ischemic cardiomyopathy (52.1%), and monomorphic VT was the most common morphology (70.1%). Within 24 hours before SGB (0-24 hours), the median episodes of VT/VF were 7.5 (Q1-Q3: 3.0-27.0), and 24 hours after SGB, the median decreased to 1.0 (Q1-Q3: 0.0-4.5; P < 0.001). At 24 hours before SGB, the median defibrillation events were 2.0 (Q1-Q3: 0.0-8.0), and 24 hours after SGB, the median decreased to 0.0 (Q1-Q3: 0.0-1.0; P < 0.001). CONCLUSIONS: In the largest cohort of patients with treatment-refractory ventricular arrhythmia, we demonstrate that SGB use was associated with a reduction in the ventricular arrhythmia burden and need for defibrillation therapy.

Hazard characterisation for significant mycotoxins in food.

This review updates the current status of activities related to hazard characterisation for mycotoxins, with special reference to regulatory work accomplished within the European Union. Because the relevant information on these topics is widely scattered in the scientific literature, this review intends to provide a condensed overview on the most pertinent aspects. Human health risk assessment is a procedure to estimate the nature and potential for harmful effects of mycotoxins on human health due to exposure to them via contaminated food. This assessment involves hazard identification, hazard characterisation, exposure assessment, and risk characterisation. Mycotoxins covered in this review are aflatoxins, ochratoxin A, cyclopiazonic acid, citrinin, trichothecenes (deoxynivalenol, nivalenol, T-2, and HT-2 toxins), fumonisins, zearalenone, patulin, and ergot alkaloids. For mycotoxins with clear genotoxic/carcinogenic properties, the focus is on the margin of exposure approach. One of its goals is to document predictive characterisation of the human hazard, based on studies in animals using conditions of low exposure. For the other, non-genotoxic toxins, individual 'no adverse effect levels' have been established, but structural analogues or modified forms may still complicate assessment. During the process of hazard characterisation, each identified effect is assessed for human relevance. The estimation of a 'safe dose' is the hazard characterisation endpoint. The final aim of all of these activities is to establish a system, which is able to minimise and control the risk for the consumer from mycotoxins in food. Ongoing research on mycotoxins constantly comes up with new findings, which may have to be implemented into this system.

Investigation of ochratoxin a in blood sausages in the Czech Republic: Comparison with data over Europe.

Blood sausages consisting of groats, pork, porcine offal, fat, blood, and spices are very popular in the Czech Republic. All these ingredients are potential sources of dietary exposure to ochratoxin A (OTA). OTA has a strong affinity to serum proteins in porcine blood. Thus, the contamination of blood sausages with OTA can be expected. This study aims to evaluate OTA in 200 samples of porcine blood sausages purchased at the Czech market during 2020-2021. The analytical method high-performance liquid chromatography coupled with fluorescence detection with pre-treatment using immunoaffinity columns was employed to determine OTA. The limit of detection was 0.03 ng/g and the limit of quantification 0.10 ng/g. Recovery was 71.6 %. All samples were positive at contents ranging from 0.15 to 5.68 ng/g with a mean of 1.47 ng/g, and a median of 1.26 ng/g. A total of 66% of these samples contained OTA content exceeding the maximum limit of 1 ng/g set in Italy. This study demonstrates that the Czech population is exposed to OTA from blood sausages. The proposed preliminary action limit for OTA in blood sausages should be set at 1 ng/g. No regulatory limits for OTA in blood sausages have been established yet in the European Union legislation. To protect human health, further monitoring of OTA in these products is necessary.

Natural Occurrence of Ochratoxin A in Spices Marketed in the Czech Republic during 2019-2020.

Spices are a popular ingredient in cuisine worldwide but can pose a health risk as they are prone to fungal infestation and mycotoxin contamination. The purpose of this study was to evaluate ochratoxin A (OTA) in 54 single-kind traditional and less traditional spices, each of which was purchased in six samples of different batches (324 samples in total) at the Czech market during 2019-2020. The HPLC-FLD method with pre-treatment by immunoaffinity columns was employed to determine OTA. The limits of detection and quantification were 0.03 ng g-1 and 0.10 ng g-1, respectively. A total of 101 (31%) samples of 19 spice kinds were positive at concentrations ranging from 0.11-38.46 ng g-1. Only turmeric was contaminated with an OTA level exceeding the European Union limits. However, most spices have no regulation, thus further extensive monitoring of various mycotoxins in various kinds of spices is necessary. Chilli and black pepper are the most studied spices for OTA contamination, however, many other kinds of spice can also be highly contaminated, but studies on them are less common, rare, or have not yet been performed. The uniqueness of this study lies in the wide range of spice types studied for the presence of OTA on the Czech market.

Investigation of ochratoxin A biomarkers in biological materials obtained from patients suffering from renal cell carcinoma.

Ochratoxin A (OTA) exposure can result in chronic renal diseases and cancer. The incidence of kidney, renal pelvis, and ureter malignant neoplasms in the Czech Republic is approximately 29.5 renal tumours per 100,000 inhabitants. The question arises whether mycotoxins are also involved in kidney disease and cancer. A sensitive validated analytical methodology, based on an immunoaffinity clean-up followed by HPLC with fluorescence detection, was developed to explore whether OTA accumulates in clear renal cell carcinoma-adenocarcinoma in Czech patients. Simultaneously, DNA-adducts and OTA metabolites were qualitatively analysed in tissues and urine. OTA was analysed in 33 kidney and tumour samples from 26 men and 7 women collected during nephrectomy from patients of the East Bohemian region from 2015 to 2017. OTA was found in 76% of the analysed samples. Its concentrations ranged from not detectable to 390 ng/kg with a median of 167 ng/kg in kidney samples and from not detectable to 430 ng/kg with a median of 122 ng/kg in tumour samples. Urinary OTA metabolites and DNA adducts were qualitatively analysed for the corresponding 20 patients. The presence of some OTA metabolites such as ochratoxin A hydroquinone and/or decarboxylated ochratoxin A hydroquinone correlate with the presence of OTA-DNA adducts.

Complex Analysis of Antioxidant Activity, Abscisic Acid Level, and Accumulation of Osmotica in Apple and Cherry In Vitro Cultures under Osmotic Stress.

Plant response to osmotic stress is a complex issue and includes a wide range of physiological and biochemical processes. Extensive studies of known cultivars and their reaction to drought or salinity stress are very important for future breeding of new and tolerant cultivars. Our study focused on the antioxidant activity, accumulations of osmotica, and the content of abscisic acid in apple (cv. "Malinové holovouské", "Fragrance", "Rubinstep", "Idared", "Car Alexander") and cherry (cv. "Regina", "Napoleonova", "Kastánka", "Sunburst", "P-HL-C") cultivated in vitro on media containing different levels of polyethylene glycol PEG-6000. Our results indicated that the studied genotypes responded differently to osmotic stress manifested as reduction in the leaf relative water content (RWC) and increment in the activities of antioxidant enzymes, proline, sugars, and abscisic acid content. Overall, cherry cultivars showed a smaller decrease in percentage RWC and enzymatic activities, but enhanced proline content compared to the apple plants cultivars. Cultivars "Rubinstep", "Napoleonova", and "Kastánka" exhibited higher antioxidant capacity and accumulation of osmoprotectants like proline and sorbitol that can be associated with the drought-tolerance system.

Aflatoxins: History, Significant Milestones, Recent Data on Their Toxicity and Ways to Mitigation.

In the early 1960s the discovery of aflatoxins began when a total of 100,000 turkey poults died by hitherto unknown turkey "X" disease in England. The disease was associated with Brazilian groundnut meal affected by Aspergillus flavus. The toxin was named Aspergillus flavus toxin-aflatoxin. From the point of view of agriculture, aflatoxins show the utmost importance. Until now, a total of 20 aflatoxins have been described, with B1, B2, G1, and G2 aflatoxins being the most significant. Contamination by aflatoxins is a global health problem. Aflatoxins pose acutely toxic, teratogenic, immunosuppressive, carcinogenic, and teratogenic effects. Besides food insecurity and human health, aflatoxins affect humanity at different levels, such as social, economical, and political. Great emphasis is placed on aflatoxin mitigation using biocontrol methods. Thus, this review is focused on aflatoxins in terms of historical development, the principal milestones of aflatoxin research, and recent data on their toxicity and different ways of mitigation.

A Review on Mycotoxins and Microfungi in Spices in the Light of the Last Five Years.

Spices are imported worldwide mainly from developing countries with tropical and/or subtropical climate. Local conditions, such as high temperature, heavy rainfall, and humidity, promote fungal growth leading to increased occurrence of mycotoxins in spices. Moreover, the lack of good agricultural practice (GAP), good manufacturing practice (GMP), and good hygienic practice (GHP) in developing countries are of great concern. This review summarizes recent data from a total of 56 original papers dealing with mycotoxins and microfungi in various spices in the last five years. A total of 38 kinds of spices, 17 mycotoxins, and 14 microfungi are discussed in the review. Worldwide, spices are rather overlooked in terms of mycotoxin regulations, which usually only cover aflatoxins (AFs) and ochratoxin A (OTA). In this paper, an extensive attention is devoted to the limits on mycotoxins in spices in the context of the European Union (EU) as well as other countries. As proven in this review, the incidence of AFs and OTA, as well as other mycotoxins, is relatively high in many spices; thus, the preparation of new regulation limits is advisable.

Presence of Mycotoxins in Milk Thistle (Silybum marianum) Food Supplements: A Review.

The consumption of herbal-based supplements, which are believed to have beneficial effects on human health with no side effects, has become popular around the world and this trend is still increasing. Silybum marianum (L.) Gaertn, commonly known as milk thistle (MT), is the most commonly studied herb associated with the treatment of liver diseases. The hepatoprotective effects of active substances in silymarin, with silybin being the main compound, have been demonstrated in many studies. However, MT can be affected by toxigenic micro-fungi and contaminated by mycotoxins with adverse effects. The beneficial effect of silymarin can thus be reduced or totally antagonized by mycotoxins. MT has proven to be affected by micro-fungi of the Fusarium and Alternaria genera, in particular, and their mycotoxins. Alternariol-methyl-ether (AME), alternariol (AOH), beauvericin (BEA), deoxynivalenol (DON), enniatin A (ENNA), enniatin A1 (ENNA1), enniatin B (ENNB), enniatin B1 (ENNB1), HT-2 toxin (HT-2), T-2 toxin (T-2), tentoxin (TEN), and zearalenone (ZEA) seem to be most significant in MT-based dietary supplements. This review focuses on summarizing cases of mycotoxins in MT to emphasize the need for strict monitoring and regulation, as mycotoxins in relation with MT-based dietary supplements are not covered by European Union legislation.

Analyses of biomarkers of exposure to nephrotoxic mycotoxins in a cohort of patients with renal tumours.

The Czech Republic occupies the first place in the world in the frequency of renal and other urinary tract tumours, but their aetiology is unknown. To explore whether carcinogenic and nephrotoxic mycotoxins may contribute to kidney diseases in the Czech population, biomarkers of ochratoxin A (OTA) and citrinin (CIT) exposure were determined in biological specimens from a cohort of 50 patients with malignant renal tumours. Biomarker analyses in blood and urine samples used validated targeted methods for measuring OTA and CIT plus dihydrocitrinone (DH-CIT) after enrichment of analytes by specific immunoaffinity clean-up. OTA and CIT plus its metabolite DH-CIT were frequently detected in patient urine samples (OTA 62%; CIT 91%; DH-CIT 100%). The concentration ranges in urine were 1-27.8 ng/L for OTA, 2-87 ng/L for CIT and 2-160 ng/L for DH-CIT. The analyses of blood samples revealed also a frequent co-occurrence of OTA and CIT, in the ranges of 40-870 ng/L serum for OTA and 21-182 ng/L plasma for CIT. This first analysis of biomarkers in blood and urine samples of Czech patients revealed no major differences in comparison with published data for the general healthy Czech and European populations. Nonetheless, a frequent co-occurrence of CIT and OTA biomarkers in patient samples may be of interest with regard to potential interactions with other risk factors for renal disease.

Investigation of patulin and citrinin in grape must and wine from grapes naturally contaminated by strains of Penicillium expansum.

Twenty three strains of Penicillium expansum, as a predominant species, were isolated from 23 (92%) out of 25 grape samples of 17 different grape varieties. The results of the identification of P. expansum strains were confirmed by a PCR method. Most of the isolates of P. expansum (21/23, 91%), when tested for toxigenicity, were bi-toxigenic: they produced citrinin (CIT) and particularly high amounts of patulin (PAT). A validated UPLC-MS/MS method for the determination of PAT and CIT was applied. The limits of quantification (LOQ) for PAT and CIT in grape must and toxigenicity testing samples were 100 and 2 ng/g, respectively. The results of PAT and CIT quantification in 23 grape must samples demonstrated the occurrence of PAT in 10 (43%) grape must samples (mean: 171 ng/g; median: 50 ng/g; and range: 143-644 ng/g) and the occurrence of CIT in two (9%) grape must samples (mean: 1 ng/g; median: 1 ng/g; and range: 2.5-3.5 ng/g). This is the first report on the natural occurrence of CIT in grape must. A validated HPLC-UV-VIS method for the determination of PAT in wine samples was applied, and concentrations in all 23 wine samples were below the LOQ (<10 ng/g).

Occurrence of ochratoxin A in Astragalus propinquus root and its transfer to decoction.

The aim of this study was to conduct a survey assessing (a) the ochratoxin A (OTA) content in different samples of Astragalus propinquus root (AR), one of the fundamental herbs in traditional Chinese medicine, and (b) the rate of OTA transfer to AR decoctions that are traditionally used to reduce general weakness and increase overall vitality. A validated method of high-performance liquid chromatography with fluorescence detection (HPLC-FLD) was used to determine OTA concentrations in AR samples and AR decoctions. The limit of quantification was 0.35 ng/g; the recovery of the HPLC method for AR samples was 82%; and the relative standard deviation (SD) of repeatability was 2.6%. All 40 tested AR samples were positive, with a mean value of 451.0 ng/g (range, 28.8-1700.0 ng/g). The transfer rate of OTA to decoctions, from a naturally contaminated and homogenized AR sample (internal reference material) with a concentration of OTA of 288.9 ng/g ± 12.3 (SD), was 83.4% ± 8.5 (SD). We believe it is necessary to continue OTA monitoring in AR and other herbal products, estimate the actual human usual intake, and perform health risk assessment.

Transfer of ochratoxin A from raw black tea to tea infusions prepared according to the Turkish tradition.

BACKGROUND: Ochratoxin A (OTA) is a natural contaminant of food including tea with multiple toxic effects, which poses a threat to human health. In terms of lifestyle, the Turkish population is a frequent visitor of tearooms, and the traditional Turkish tea preparation is one of the most popular ways of preparing tea infusion. RESULTS: The aim of this study was to investigate OTA transfer from raw black tea to the tea infusion prepared according to the Turkish tradition. A high-performance liquid chromatography method with a limit of quantification of 0.35 ng g-1 was used for OTA determination. The OTA amount in raw black teas from Turkey ranged from ≤0.35 ng g-1 up to 56.7 ng g-1 . An homogenised sample of black tea naturally contaminated with 55.0 ng g-1 was used to prepare infusions. The OTA transfer from the black tea to the infusion was found to be 41.5% ± 7%. CONCLUSION: These data are important for the realisation of a 'Total Diet study' (TDS). The TDS can be a complementary tool to estimate the population dietary exposure to OTA across the entire diet by analysing main foods prepared 'as consumed' (tea infusions) and not 'as purchased' (raw tea). © 2017 Society of Chemical Industry.

Mycotoxins as human carcinogens-the IARC Monographs classification.

Humans are constantly exposed to mycotoxins (e.g. aflatoxins, ochratoxins), mainly via food intake of plant and animal origin. The health risks stemming from mycotoxins may result from their toxicity, in particular their carcinogenicity. In order to prevent these risks, the International Agency for Research on Cancer (IARC) in Lyon (France)-through its IARC Monographs programme-has performed the carcinogenic hazard assessment of some mycotoxins in humans, on the basis of epidemiological data, studies of cancer in experimental animals and mechanistic studies. The present article summarizes the carcinogenic hazard assessments of those mycotoxins, especially aflatoxins (aflatoxin B1, B2, G1, G2 and M1), fumonisins (fumonisin B1 and B2) and ochratoxin A (OTA). New information regarding the genotoxicity of OTA (formation of OTA-DNA adducts), the role of OTA in oxidative stress and the identification of epigenetic factors involved in OTA carcinogenesis-should they indeed provide strong evidence that OTA carcinogenicity is mediated by a mechanism that also operates in humans-could lead to the reclassification of OTA.

Ochratoxin A: 50 Years of Research.

Since ochratoxin A (OTA) was discovered, it has been ubiquitous as a natural contaminant of moldy food and feed. The multiple toxic effects of OTA are a real threat for human beings and animal health. For example, OTA can cause porcine nephropathy but can also damage poultries. Humans exposed to OTA can develop (notably by inhalation in the development of acute renal failure within 24 h) a range of chronic disorders such as upper urothelial carcinoma. OTA plays the main role in the pathogenesis of some renal diseases including Balkan endemic nephropathy, kidney tumors occurring in certain endemic regions of the Balkan Peninsula, and chronic interstitial nephropathy occurring in Northern African countries and likely in other parts of the world. OTA leads to DNA adduct formation, which is known for its genotoxicity and carcinogenicity. The present article discusses how renal carcinogenicity and nephrotoxicity cause both oxidative stress and direct genotoxicity. Careful analyses of the data show that OTA carcinogenic effects are due to combined direct and indirect mechanisms (e.g., genotoxicity, oxidative stress, epigenetic factors). Altogether this provides strong evidence that OTA carcinogenicity can also occur in humans.

Transfer of ochratoxin A into tea and coffee beverages.

Ochratoxin A (OTA) is nephrotoxic, hepatotoxic, immunotoxic, neurotoxic, reprotoxic, teratogenic, and carcinogenic (group 2B), being characterized by species and sex differences in sensitivity. Despite the fact that OTA is in some aspects a controversial topic, OTA is the most powerful renal carcinogen. The aim of this study was to make a small survey concerning OTA content in black tea, fruit tea, and ground roasted coffee, and to assess OTA transfer into beverages. OTA content was measured using a validated and accredited HPLC-FLD method with a limit of quantification (LOQ) of 0.35 ng/g. The OTA amount ranged from LOQ up to 250 ng/g in black tea and up to 104 ng/g in fruit tea. Black tea and fruit tea, naturally contaminated, were used to prepare tea infusions. The transfer from black tea to the infusion was 34.8% ± 1.3% and from fruit tea 4.1% ± 0.2%. Ground roasted coffee naturally contaminated at 0.92 ng/g was used to prepare seven kinds of coffee beverages. Depending on the type of process used, OTA transfer into coffee ranged from 22.3% to 66.1%. OTA intakes from fruit and black tea or coffee represent a non-negligible human source.