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PubMed1997

[Differential types of pulmonary flow in bidirectional cavo-pulmonary anastomosis with an additional flow source].

While Fontan operation is considered a palliative procedure for the treatment of complex congenital heart disease, its morbidity and mortality are certainly not negligible, especially in high-risk patients. In our opinion, a bidirectional cavo-pulmonary anastomosis with an additional source of blood flow to the lungs (Blalock-Taussig shunt, pulmonary artery banding, native pulmonary stenosis) represents a valuable surgical option in this subset of patients. From November 1992 to September 1994, sixteen patients with complex congenital heart disease underwent bidirectional cavo-pulmonary anastomosis, leaving an additional source of blood flow in place (modified Blalock-Taussig shunt in 9 cases, pulmonary artery banding in 6 cases, native pulmonary stenosis in 1 case). Eight of these patients (50%) were reinvestigated after a mean follow-up of 15.7 months (range 1-26 m). It has been possible to differentiate two types of pulmonary blood flow, according to the nature of the additional flow source; in the case of cavo-pulmonary anastomosis and pulmonary artery banding or pulmonary stenosis, pulmonary blood flow was pulsatile and evenly distributed to both lungs, while in the case of bidirectional cavo-pulmonary anastomosis and Blalock-Taussig shunt, pulmonary flow was non pulsatile and asymmetric (angiographic criteria). There were no hospital deaths. Late mortality was 12.5% (2 pts) due to worsening of atrioventricular valve regurgitation. In one of these two patients, prolonged pleural and pericardial effusion occurred. In conclusion, bidirectional cavo-pulmonary anastomosis with an additional flow source is a good alternative to classic or fenestrated Fontan operation in the treatment of complex congenital heart disease. The best results are obtained with an additional flow source represented by pulmonary artery banding or pulmonary stenosis, due to pulsatility and uniform distribution of blood flow in the pulmonary district. Morbility and mortality compare favorably with the rates observed in classic or fenestrated Fontan operation.

Anastomosis, Surgical↗
PubMed1998

Thrombopoietin requires additional megakaryocyte-active cytokines for optimal ex vivo expansion of megakaryocyte precursor cells.

Little is known concerning the interaction of thrombopoietin (TPO) with other megakaryocyte-active cytokines in directing the early events of megakaryocyte development. Culture of CD34(+) cells in interleukins (IL) -1, -6, -11, plus stem cell factor (SCF; S) results in a 10- to 12-fold expansion in total cell numbers, whereas total CD41(+) megakaryocytes are expanded approximately 120-fold over input levels. Addition of TPO to IL-1, -6, -11, S generates a biphasic proliferation of CD41(+) cells, accelerates their rate of production, and results in an ex vivo expansion of more than 200-fold. The addition of Flt-3 ligand (FL) increases CD41+ cell expansion to approximately 380-fold over input levels. In the absence of TPO, approximately 95% of the expanded cells show the phenotype of promegakaryoblasts; TPO and/or FL addition increases CD41 antigen density and ploidy in a subpopulation of promegakaryoblasts. A moderate (approximately sevenfold) expansion of megakaryocyte progenitor cells (colony-forming unit-megakaryocyte) occurs in the presence of IL-1, -6, -11, S, and the addition of TPO to this cocktail yields an approximately 17-fold expansion. We conclude that early proliferative events in megakaryocyte development in vitro are regulated by multiple cytokines, and that TPO markedly affects these early developmental steps. However, by itself, TPO is neither necessary nor sufficient to generate a full proliferative/maturational in vitro response within the megakaryocyte compartment. TPO clearly affects terminal differentiation and the development of (some) high-ploidy human megakaryocytes. However, its limited in vitro actions on human cell polyploidization suggest that additional megakaryocyte-active cytokines or other signals are essential for the maximal development of human megakaryocytes.

Adult↗
PubMed1998

Frequent N addition and clonal relatedness among immunoglobulin lambda light chains expressed in rheumatoid arthritis synovia and PBL, and the influence of V lambda gene segment utilization on CDR3 length.

BACKGROUND: In rheumatoid arthritis (RA), B-lineage cells in the synovial membrane secrete large amounts of immunoglobulin that contribute to tissue destruction. The CDR3 of an immunoglobulin light chain is formed by rearrangements of VL and JL gene segments. Addition of non-germline-encoded (N) nucleotides at V(D)J joins by the enzyme terminal deoxynucleotidyl transferase (TdT) enhances antibody diversity. TdT was previously thought to be active in B cells only during heavy chain rearrangement, but we and others reported unexpectedly high levels of N addition in kappa light chains. We also found clonally related kappa chains bearing unusually long CDR3 intervals in RA synovium, suggesting oligoclonal expansion of a set of atypical B lymphocytes. In this study, we analyzed lambda light chain expression to determine if N addition occurs throughout immunoglobulin gene rearrangement and to compare CDR3 lengths of lambda and kappa light chains in RA patients and normal individuals. MATERIALS AND METHODS: Reverse transcription-polymerase chain reaction (RT-PCR) amplification of V lambda III transcripts was performed on RA synovia and peripheral blood lymphocytes (PBL) and normal PBL for which kappa repertoires were previously analyzed. Representative lambda + PCR products were cloned and sequenced. RESULTS: Analysis of 161 cDNA clones revealed that N addition occurs in lambda light chains of RA patients and normal controls. The lambda light chain repertoires in RA were enriched for long CDR3 intervals. In both RA and controls, CDR3 lengths were strongly influenced by which V lambda gene segment was present in the rearrangement. Five sets of clonally related sequences were found in RA synovia and PBL; one set was found in normal PBL. CONCLUSIONS: In humans, unlike mice, N addition enhances antibody diversity at all stages of immunoglobulin assembly, and the structural diversity of lambda CDR3 intervals is greater than that of kappa light chains. Clonally related V lambda gene segments in RA support an antigen-driven B-cell response.

Amino Acid Sequence↗
PubMed1978

The use of food additives in Sweden.

Recently it was demonstrated that the levels of some added colours in food sold in Sweden were such that the recommended daily intake (ADI) could easily be exceeded by the consumer (Ahlborg et al. Vår Föda, 26, 1974, 194-217). New regulations concerning the use of food colours in Sweden came into force on July 1st, 1975. The collection of information on the use of food additives in products sold on the Swedish market has not been extended to cover other food additives such as preservatives and antioxidants. This study is based upon details of about 10,000 food products containing food additives. The material is being computerised and work on the evaluation is in progress. The new investigation demonstrates that the use of food colours has decreased and that very few products now contain high levels of food colours. Data will be presented concerning the levels and total amounts of preservatives, antioxidants and other food additives used in different groups of food products.

Food Additives↗
PubMed2026

Dynamic and non-additive gene regulation shapes maize responses to simultaneous salt and cold stress.

Salt and cold stresses often occur together in nature and severely impact crop productivity, yet their transcriptional regulation remains poorly understood. Here, we conducted a time-series transcriptomic analysis of maize under salt, cold, and their combination at 0, 6, 12, and 24 h. Differential expression analysis revealed dynamic, condition-specific gene responses grouped into eight distinct temporal patterns. Promoter motif analysis of genes within each pattern identified 5-39 significantly enriched motifs, with over 40% lacking known counterparts, suggesting the involvement of previously uncharacterized cis-regulatory elements in stress-responsive transcriptional regulation. By comparing combined stress responses to the sum of single-stress effects, we found that about 74% of DEGs showed non-additive patterns, suggesting that combined stress triggers a distinct transcriptional program. Evolutionary analysis showed that additive DEGs tend to be more recently evolved, subject to weaker purifying selection, and enriched in transposed duplications, contrasting with the stronger constraint observed in non-additive DEGs. WGCNA identified 24 co-expression modules, among which 65 hub DEGs were detected in modules significantly correlated with specific stress conditions. Furthermore, we reconstructed 228, 20, and 200 sequential transcription factor cascades spanning 6 h, 12 h, and 24 h under cold, salt, and combined stress, respectively, with no cascade shared across all three conditions. Together, these results reveal that maize responses to combined salt and cold stress are largely non-additive and temporally dynamic, with distinct evolutionary patterns underlying different response types, offering insights and candidate regulators for enhancing crop stress resilience.

Zea mays↗
PubMed2003

Adverse reactions to food additives.

There are thousands of additives used by the food industry for a variety of purposes in the foods we eat. However, only a small number have been implicated in causing adverse reactions in humans. Although there are reported cases of individuals who have reactions to single additives, most of the medical literature involves patients with asthma or chronic idiopathic urticaria/angioedema whose conditions are exacerbated after ingestion of food additives. Many of these reports are characterized by poorly controlled challenge procedures. Recent studies performed under properly controlled conditions imply that sensitivity to food additives in patients with chronic urticaria/angioedema is very uncommon.

Food Additives↗
PubMed1984

Adverse reactions to drug additives.

There is a long list of additives used by the pharmaceutical industry. Most of the agents used have not been implicated in hypersensitivity reactions. Among those that have, only reactions to parabens and sulfites have been well established. Parabens have been shown to be responsible for rare immunoglobulin E-mediated reactions that occur after the use of local anesthetics. Sulfites, which are present in many drugs, including agents commonly used to treat asthma, have been shown to provoke severe asthmatic attacks in sensitive individuals. Recent studies indicate that additives do not play a significant role in "hyperactivity." The role of additives in urticaria is not well established and therefore the incidence of adverse reactions in this patient population is simply not known. In double-blind, placebo-controlled studies, reactions to tartrazine or additives other than sulfites, if they occur at all, are indeed quite rare for the asthmatic population, even for the aspirin-sensitive subpopulation.

Anesthetics, Local↗
PubMed1984

FDA's priority-based assessment of food additives. I. Preliminary results.

The principles outlined in the Bureau of Foods' recently published Toxicological Principles for the Safety Assessment of Direct Food Additives and Color Additives Used in Food (the Redbook) have been systematically applied to a Bureau of Foods food additive data base comprising nearly 1600 food and color additives and synthetic flavoring substances. The present publication is the first of several papers reviewing and analyzing the results of this work. This paper describes the content and organization of the scientific data base that the Bureau has compiled, and presents some preliminary general conclusions regarding the processing of these data according to Redbook principles.

Animals↗
PubMed1999

Simultaneous determination of antioxidants, preservatives and sweeteners permitted as additives in food by mixed micellar electrokinetic chromatography.

A micellar electrokinetic chromatography method was developed to simultaneously analyse commonly used food additives. The additive mixture, comprising propyl gallate, octyl gallate, dodecyl gallate, butylated hydroxyanisole, butylated hydroxytoluene, tertiary butylhydroquinone, p-hydroxybenzoic acid methyl ester, p-hydroxybenzoic acid ethyl ester, benzoic acid, sorbic acid, saccharin, aspartame and acesulfame-K, was not resolved using single surfactant micellar systems consisting of sodium dodecyl sulfate (SDS), sodium cholate (SC) or sodium deoxycholate (SDC). The separation of these additives using mixed micellar systems, involving SDS/SC, SDS/SDC and SC/SDC, was investigated. Organic solvents were added to the mixed micellar phases to optimise the separation. The mixture was successfully separated using a 20 mM borate buffer with 35 mM SC, 15 mM SDS and 10% methanol added at pH 9.3. Additives in cola beverages and low-joule jam were investigated and quantified using this method.

Antioxidants↗
PubMed2003

EU assessment of enterococci as feed additives.

Particular micro-organisms such as enterococcal strains are used as probiotics in feed. Observations indicate a positive effect of such strains on the gut flora, especially for young animals or during feed transition phases. This favourable effect is perceived by the farmers as a means of maintenance of the health status of the animals (e.g. less diarrhoea) and results in significant improvement of animal performance. Micro-organisms have been used since the end of the 1980s in animal feeds and were strictly regulated in 1993, when they were introduced under the scope of Council Directive 70/524/EEC of 23 November 1970 on additives in animal nutrition on feed additives. After a transition period, which ended in the year 2000, every microbial strain must now be assessed by the EU bodies and authorised by a Commission Regulation, before it can be placed on the market for use in feedingstuffs. Council Directive 70/524/EEC on feed additives is based on three main principles: (1) pre-market authorisation, (2) positive list principle, and (3) thorough risk assessment of the effect of a particular strain on human and animal health as well as on the environment. Therefore, before introducing a new enterococcal strain preparation or promote a new use of an approved product, a dossier has to be submitted to the authorities, following the guidelines, as published in Commission Directive 94/40/EEC [Commission Directive 94/40/EC of 22 July 1994 amending Council Directive 87/153/EEC fixing guidelines for the assessment of additives in animal nutrition]. These guidelines contain detailed evaluation methods. The safety requirements refer to (1) the target animal categories, (2) the consumer and the environment (presence of toxins and virulence factors as well as antibiotic resistance and transferability are assessed), and (3) the workers, based on requirements of Council Directive 89/391/EEC.

Animal Feed↗
PubMed2002

The comet assay with 8 mouse organs: results with 39 currently used food additives.

We determined the genotoxicity of 39 chemicals currently in use as food additives. They fell into six categories-dyes, color fixatives and preservatives, preservatives, antioxidants, fungicides, and sweeteners. We tested groups of four male ddY mice once orally with each additive at up to 0.5xLD(50) or the limit dose (2000mg/kg) and performed the comet assay on the glandular stomach, colon, liver, kidney, urinary bladder, lung, brain, and bone marrow 3 and 24h after treatment. Of all the additives, dyes were the most genotoxic. Amaranth, Allura Red, New Coccine, Tartrazine, Erythrosine, Phloxine, and Rose Bengal induced dose-related DNA damage in the glandular stomach, colon, and/or urinary bladder. All seven dyes induced DNA damage in the gastrointestinal organs at a low dose (10 or 100mg/kg). Among them, Amaranth, Allura Red, New Coccine, and Tartrazine induced DNA damage in the colon at close to the acceptable daily intakes (ADIs). Two antioxidants (butylated hydroxyanisole (BHA) and butylated hydroxytoluene (BHT)), three fungicides (biphenyl, sodium o-phenylphenol, and thiabendazole), and four sweeteners (sodium cyclamate, saccharin, sodium saccharin, and sucralose) also induced DNA damage in gastrointestinal organs. Based on these results, we believe that more extensive assessment of food additives in current use is warranted.

Animals↗
PubMed2001

Efficacy of leukotriene receptor antagonist in chronic urticaria. A double-blind, placebo-controlled comparison of treatment with montelukast and cetirizine in patients with chronic urticaria with intolerance to food additive and/or acetylsalicylic acid.

BACKGROUND: The cause and pathogenesis of chronic urticaria are still poorly understood. IgE-independent reactions, are common in adult patients with chronic urticaria, who have daily spontaneous occurrence of weals. H(1)-receptor antagonists (antihistamines) are the major class of therapeutic agents used in the management of urticaria and angioedema. Nevertheless, chronic urticaria is often difficult to treat and may not be controlled by antihistamines alone. It has been postulated that mediators other than histamine, such as kinins, prostaglandin and leukotrienes, may be responsible for some of the symptoms in urticaria which are not controlled by antihistamines. In this study, which was randomized double-blind, placebo-controlled, we compare the clinical efficacy and safety of montelukast (MT) 10 mg given once a day and cetirizine (CET) 10 mg given once a day with placebo (PLA), in the treatment of patients with chronic urticaria who have positive challenge to acetylsalicylic acid (ASA) and/or food additives. PATIENTS AND METHODS: A group of 51 patients, ranging in age from 15 to 71 years, with chronic urticaria and positive challenge to food additives and/or ASA, participated in this study for a period of 4 weeks, starting from a 3-day run-in. The assessment of the efficacy was based on scores of daily urticaria symptoms. RESULTS: MT significantly increased the percentage of symptom-free days for hive and itch. Analysis of frequency distribution of urticaria scores for each symptom gave similar results (MT vs. CET and MT vs. PLA, P < 0.001). The interference with sleep due to their skin condition was also lower in the group treated with MT (P < 0.001). In addition, the median number of days without the rescue medication was significantly higher in the MT group (24 days) than both the CET and the PLA groups (18 days, P < 0.001, and 20 days, P < 0.001, respectively). Finally, a low incidence of adverse events was observed in this study. CONCLUSION: The results of this comparative study demonstrate that montelukast orally administered once a day is very effective for the treatment of cutaneous symptoms in patients with chronic urticaria due to food additives and/or ASA.

Acetates↗
PubMed2000

Effect of sausage ingredients and additives on the production of enterocin A and B by Enterococcus faecium CTC492. Optimization of in vitro production and anti-listerial effect in dry fermented sausages.

Enterocin A and B in Enterococcus faecium CTC492 were co-induced by the different factors assayed in this study (r = 0.93) and followed primary metabolic kinetics. Enterocin production was significantly inhibited by sausage ingredients and additives, with the exception of nitrate. The addition of sodium chloride and pepper decreased production 16-fold. The temperature and pH influenced enterocin production, with optima between 25 and 35 degrees C, and from 6.0 to 7.5 of initial pH. The maximum activity was achieved, under favourable growth conditions, with MRS supplemented with sucrose (2%) plus glucose (0.25%) and Tween-80 (1%). MRS concentration, NaCl plus pepper addition, absence of Tween-80 in the growth medium, incubation at 45 degrees C and an initial pH under 5.5 were detrimental to bacteriocin production. Stress conditions did not favour enterocin production. Desadsorption was Tween-dependent. Enterocin A activity in the crude extracts stored at -80 degrees C was better preserved than enterocin B (when tested against their specific indicator strain), but anti-listerial activity remained intact. Applied as anti-listerial additives in dry fermented sausages, enterocins significantly diminished Listeria counts by 1. 13 log (P < 0.001), while Enterococcus faecium CTC492 added as starter culture did not significantly reduce Listeria counts (P > 0. 1) compared with the standard starter culture (Bac-). Enterocins A and B could be considered as extra biopreservative hurdles for listeria prevention in dry fermented sausages.

Bacteriocins↗
PubMed2002

Accelerated solvent extraction of animal feedingstuffs for microbial growth inhibition screening for the presence of antimicrobial feed additives.

Three plate systems (combinations of indicator organism and growth medium) were evaluated for the detection of analytical standards of the banned feed additives avoparcin, bacitracin zinc, spiramycin, tylosin and virginiamycin. When authorized in the EU, the previously recommended minimum inclusion rate (MIR) for each compound was 5 mg kg(-1). One of the plate systems (Micrococcus luteus ATCC 10240, nutrient agar) detected all five additives. This plate was used in a further study that evaluated the suitability of accelerated solvent extraction (ASE) as a first step in the development of a rapid single-plate screening assay. A drug-free (negative control) feedingstuff was fortified with the compounds (0-50 mg kg(-1)), extracted by ASE and the extracts applied to the plate at each of three pH ranges - unadjusted extract (pH 5.7-5.9), pH 6.5 and 8.0. At pH 6.5, sub-MIR concentrations of virginiamycin and tylosin were detectable. Avoparcin was detectable at 6.3 mg kg(-1). The detection of zinc bacitracin was#10; pH-independent (10 mg kg(-1)). At pH 8.0, spiramycin was detectable at 5.4 mg kg(-1). Mean +/- SD analytical recoveries from fortified feedingstuffs (n = 10) ranged from 57 +/- 1.5% for avoparcin to 96 +/- 4% for virginiamycin. The five additives were also detectable following ASE extraction from a range of different feedingstuffs fortified with each of the drugs. A further 24 compounds permitted for use in animal feeds were tested. Of these, nine were detectable at their recommended MIR. It is concluded that ASE is a versatile technique suitable for the automated extraction of a range of antimicrobials from animal feedingstuffs. Employing ASE with this single-plate detection system permits the rapid antimicrobial screening of animal feedingstuffs and allows the detection of the banned additives. Whilst the method is applicable as a screening test, more specific postscreening methods would be necessary for subsequent identification (and quantification) of antimicrobials in screening-positive samples.

Animal Feed↗
PubMedDate not supplied

An evaluation of the decision tree approach for assessing priorities for safety testing of food additives.

In this publication we report an evaluation of the decision tree scheme of Cramer, Ford and Hall (1978) for assigning priorities for toxicity testing of chemicals. The original scheme has been modified to allow more chemical structures to be considered and to take into account recent advances in toxicology. The majority of the food additives permitted in either the UK, USA or Canada have been processed through the modified decision tree questionnaire and their classification compared with currently available chronic toxicity data. A large proportion of the additives (53/73) assigned to the lowest toxicity (I) class have a low order of chronic oral toxicity as do many of the compounds assigned to the moderate toxicity (II) class. Although the majority of the additives assigned to the highest toxicity (III) class are substantially more toxic than those in the lower toxicity classes, some relatively innocuous compounds reached this classification. In addition, a few toxic compounds were assigned to the lowest toxicity class. The reasons for these incorrect assignments are discussed. It was concluded that the decision tree approach, although less discriminating than originally suggested, remains a useful method for classifying compounds in terms of their probable toxicity and that further modifications to the tree could be made.

Accident Prevention↗
PubMed1996

Comparison of official methods for 'readily oxidizable substances' in propionic acid as a food additive.

The official methods for 'readily oxidizable substances (ROS)' in propionic acid as a food additive were compared. The methods examined were those adopted in the Compendium of Food Additive Specifications (CFAS) by the Joint FAO-WHO Expert Committee on Food Additives, FAO, The Japanese Standards for Food Additives (JSFA) by the Ministry of Health and Welfare, Japan, and the Food Chemicals Codex (FCC) by the National Research Council, USA. The methods given in CFAS and JSFA are the same (potassium permanganate consumption). However, by this method, manganese (VII) in potassium permanganate was readily reduced to colourless manganese(II) with some substances contained in the propionic acid before reacting with aldehydes, which are generally considered as 'readily oxidizable substances', to form brown manganese (IV) oxide. The FCC method (bromine consumption) for 'ROS' could be recommended because it was able to obtain quantitative results of 'ROS', including aldehydes.

Aldehydes↗
PubMedDate not supplied

The assessment of food additive usage and consumption: the Commission perspective.

Directive 89/107/EEC on food additives authorized for foodstuffs intended for human consumption includes the requirement that 'all food additives must be kept under continuous observation and must be re-evaluated whenever necessary in the light of changing conditions of use and new scientific information'. During the period June 1994 to March 1995, three specific directives have been adopted, each of them including an obligation for Member States to introduce systems to monitor the usage and consumption of food additives and to report their findings to the Commission within 3 years. They also require the Commission to submit reports to the European Parliament on changes in the additives market, the levels of use and consumption, and to propose amendments to the conditions of use if necessary within 5 years. This paper examines the legal obligations of the Member States and the Commission and proposes practical interpretation of the requirements which would allow realistic and comparable monitoring systems to be set up in the Member States within the limits of their scarce resources. The importance of focusing on public health-related aspects is stressed and consideration is given to the role of the various interested parties and the nature of the Commission's co-ordination responsibility.

Europe↗
PubMedDate not supplied

Estimation of food additive intake: methodology overview.

Any attempt to estimate food additive intake will require some level of screening to reduce the scale of the problem to a manageable level. Even then the process should always begin with crude estimates of food intake and of food additive usage level. The starting point for the latter may be the maximum permitted levels as laid down in the relevant regulations. If at that point the data are deemed acceptable, the process ends. If further requirements are needed they can be for both food intake data and food additive usage levels. Refinement may involve disaggregation of gross categories into more precise categories but research needs to be done to establish the true value of highly refined data. It remains possible that the distribution of the intakes of refined categories is similar to that of the crude categories. Intake data should relate to the population who consume the foods containing the additive in question and even then at some higher level such as the 97.5th percentile. Whether the use of this extreme is acceptable as numbers of subjects diminish in any age and sex breakdown of data remains to be seen. We also need to know something of the dietary habits and sociodemographic characteristics of high consumers and to devise ways of obtaining data for consumers-only from household budget data. Finally we need to know more of how to increase the precision of estimating the percentage of consumers, perhaps combining food frequency questionnaires with 3-day records.

Diet Surveys↗