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PubMed2003

Validation analysis of probabilistic models of dietary exposure to food additives.

The validity of a range of simple conceptual models designed specifically for the estimation of food additive intakes using probabilistic analysis was assessed. Modelled intake estimates that fell below traditional conservative point estimates of intake and above 'true' additive intakes (calculated from a reference database at brand level) were considered to be in a valid region. Models were developed for 10 food additives by combining food intake data, the probability of an additive being present in a food group and additive concentration data. Food intake and additive concentration data were entered as raw data or as a lognormal distribution, and the probability of an additive being present was entered based on the per cent brands or the per cent eating occasions within a food group that contained an additive. Since the three model components assumed two possible modes of input, the validity of eight (2(3)) model combinations was assessed. All model inputs were derived from the reference database. An iterative approach was employed in which the validity of individual model components was assessed first, followed by validation of full conceptual models. While the distribution of intake estimates from models fell below conservative intakes, which assume that the additive is present at maximum permitted levels (MPLs) in all foods in which it is permitted, intake estimates were not consistently above 'true' intakes. These analyses indicate the need for more complex models for the estimation of food additive intakes using probabilistic analysis. Such models should incorporate information on market share and/or brand loyalty.

Databases, Factual↗
PubMed1999

[Food additives and genetically modified food--a risk for allergic patients?].

Adverse reactions to food and food additives must be classified according to pathogenic criteria. It is necessary to strictly differentiate between an allergy, triggered by a substance-specific immunological mechanism, and an intolerance, in which no specific immune reaction can be established. In contrast to views expressed in the media, by laymen and patients, adverse reactions to additives are less frequent than is believed. Due to frequently "alternative" methods of examination, an allergy to food additives is often wrongly blamed as the cause of a wide variety of symptoms and illness. Diagnosing an allergy or intolerance to additives normally involves carrying out double-blind, placebo-controlled oral provocation tests with food additives. Allergic reactions to food additives occur particularly against additives which are organic in origin. In principle, it is possible that during the manufacture of genetically modified plants and food, proteins are transferred which potentially create allergies. However, legislation exists both in the USA (Federal Drug Administration, FDA) and in Switzerland (Ordinance on the approval process for GM food, GM food additives and GM accessory agents for processing) which require a careful analysis before a genetically modified product is launched, particularly where foreign genes are introduced. Products containing genetically modified organisms (GMO) as additives must be declared. In addition, the source of the foreign protein must be identified. The "Round-up ready" (RR) soya flour introduced in Switzerland is no different from natural soya flour in terms of its allergenic potential. Genetically modified food can be a blessing for allergic individuals if gene technology were to succeed in removing the allergen (e.g. such possibilities exist for rice). The same caution shown towards genetically modified food might also be advisable for foreign food in our diet. Luckily, the immune system of the digestive tract in healthy people tolerates foreign antigens. Food allergies in adults occur mainly among those allergic to pollen.

Adult↗
PubMed1997

Log-additive versus log-linear analysis of lead-contaminated house dust and children's blood-lead levels. Implications for residential dust-lead standards.

The Environmental Protection Agency has been mandated to develop a health-based standard for lead in residential dwellings in the United States. Prior estimates of the relationship between residential dust-lead levels and children's blood-lead concentrations have usually been obtained by using a log-linear regression of blood-lead concentration on levels of lead-contaminated house dust. It remains unknown, however, whether the log-linear model or a frequently cited alternative, the log-additive model, is the preferable regression method for analyzing these data. Secondary analysis of the Lead-in-Dust Study data was undertaken to compare log-additive with log-linear regression analysis for the purpose of developing a health-based dust lead standard. Specifically, we were interested in comparing the log-additive and log-linear analyses in their ability to characterize adequately the relationship of dust-lead loading on various surfaces with blood-lead concentrations among urban children and to develop a predictive model to estimate the risk that a child will develop an elevated blood-lead level on the basis of a known level of dust lead. We used two dust sampling methods, the Baltimore Repair and Maintenance (BRM) vacuum method and the wipe method, to compare the log-linear and log-additive models. The log-linear model was consistently superior to the log-additive model in its ability to explain the variability in the observed blood-lead concentrations of the studied children, for both the wipe sampler and the BRM sampler. In addition, the log-additive model often predicted only a limited increase in the probability of blood-lead concentrations exceeding 10 micrograms/dl as a result of doubling the dust-lead loading exposure, whereas the log-linear model consistently demonstrated a significant increase in the probability of blood-lead concentrations exceeding 10 micrograms/dl. BRM lead loading explained additional variability in blood lead above and beyond that explained by wipe loading for both carpeted and uncarpeted floors. In contrast, wipe-lead loading explained significant additional variability after adjustment for BRM loading for both uncarpeted floors and interior window sills. Although BRM loading better predicted children's blood-lead concentrations than did wipe loading, these differences were not statistically significant. We conclude that the log-linear model explained a greater percentage of the variability in blood-lead concentrations than did the log-additive model, indicating that the log-linear model should be the default model of choice for developing a dust-lead standard.

Air Pollution, Indoor↗
PubMed1987

Novel blunt-end addition reactions catalyzed by DNA polymerase I of Escherichia coli.

DNA polymerase I (Klenow fragment) of Escherichia coli catalyzes the addition of deoxynucleotides to 3' hydroxyl termini of blunt-ended DNA fragments. The product of the reaction, which we call +1 addition, is found only in very low yield under conditions that permit editing by the 3'----5' exonuclease activity of the wild-type polymerase. A mutant form of the Klenow fragment that lacks detectable 3'----5' exonuclease activity shows an elevated accumulation of the +1 addition product. The mutant enzyme can use any one of the four dNTPs to carry out the reaction when each precursor is provided individually. However, in the presence of all four dNTPs the addition of dATP is strongly preferred. Suppression of the editing function of the wild-type polymerase through the use of high concentrations of exogenous deoxynucleoside monophosphates also results in a significant increase in the amount of +1 addition product formed. The presence of a high dNMP concentration also alters the specificity of the nucleotide addition reaction carried out by the wild-type enzyme. Thus, in addition to dATP, the dNTP which is complementary to the exogenous deoxynucleoside monophosphate, is also used in the +1 addition reaction. A similar effect of dNMPs on the specificity of nucleotide addition was obtained with the mutant Klenow fragment. These results define two pathways for the +1 addition reaction: one that does not require coding information from the DNA template and a second in which coding information is provided by the exogenous dNMP.

Base Sequence↗
PubMed2005

Role of ion pairing in anionic additive effects on the separation of cationic drugs in reversed-phase liquid chromatography.

Mobile phase additives can significantly affect the separation of cationic drugs in reversed-phase liquid chromatography (RPLC). Although there are many applications for anionic additives in RPLC separations, the retention mechanism of basic drugs in the presence of inorganic and highly hydrophilic anionic species in the mobile phase is not at all well understood. Two major retention mechanisms by which anionic additives can influence the retention of cations are: (1) ion pair formation in the mobile phase with subsequent retention of the neutral ion pair; (2) pre-sorption of anionic additives on the stationary phase followed by "dynamic ion-exchange" or "electrostatic interaction" with the analytes. Because the use of ion pair chromatography in the separation of proteins, peptides, and basic drugs is rapidly increasing, understanding the retention mechanism involved is becoming more important, especially for the smaller commonly used hydrophilic anionic additives (e.g., formate HCOO, chloride Cl-, trifluoroacetate CF3COO-, perchlorate ClO4-, and hexafluorophosphate PF6-). In this work, we compared various anionic additives in light of their effects on the retention of basic drugs. As did many others we found that the addition of anionic additives (Cl-, CF3COO-, ClO4-, PF6-) profoundly influences the retention of basic drugs. In order to explain the data and differentiate the mechanisms by which the anionic additives perturb the chromatography, we used ion pair formation constants independently measured by capillary electrophoresis (CE) under the mobile phase conditions (pH, solvent composition) identical to those used in chromatography. Agreement between the predicted and experimental chromatographic data under various conditions was evaluated. Under specific circumstances (e.g., pH, stationary phase, and nature of anionic additive), we conclude that the ion pair mechanism is more important than the dynamic ion-exchange and at other conditions it remains a significant contribution.

Anions↗
PubMed2005

The use of additional imaging increased specificity and decreased sensitivity in screening mammography.

BACKGROUND AND OBJECTIVES: To examine the use of additional imaging after standard mammographic screening views to better understand the value of these additional testing in improving accuracy. MATERIALS AND METHODS: Statewide population data on screening mammography were used to report accuracy measures at screening and after additional imaging tests. Pathology data from biopsies performed within 1 year following the screening mammogram were used to determine cancer outcome (489 in situ and invasive cancers). Pathologic and population characteristics of women receiving different types of imaging were assessed by chi-square or t-tests. Similar tests compared women with the same imaging and differing outcomes. RESULTS: Of 77,799 women with screening mammograms 9.9% had additional imaging. Additional imaging reduced false positives from 7,765 (100/1,000 mammograms) to 1,112 (14/1,000 mammograms). The majority of false negatives (82%) occurred in women receiving only screening views, and additional imaging increased the number of false negatives from 82 (1/1,000 mammograms) to 115 (1.5/1,000 mammograms). CONCLUSION: Additional imaging can reduce unnecessary biopsy but at the cost of some additional false negatives. Additional imaging's potential for improving the sensitivity of screening is limited because most missed cancers occur in women who do not have additional imaging.

Adult↗
PubMed2004

Comparative mixture effects of JP-8(100) additives on the dermal absorption and disposition of jet fuel hydrocarbons in different membrane model systems.

Jet fuel are complex mixtures of hydrocarbon fuel components and performance additives. Three different membrane systems, silastic, porcine skin and the isolated perfused porcine skin flap (IPPSF) were used to gain insight into the possible mechanism for additive interactions on hydrocarbon component absorption. Influence of JP-8(100) additives on the dermal kinetics of 14C-naphthalene and 14C/3H-dodecane as markers of hydrocarbon absorption, were evaluated using analysis of means (ANOM) and analysis of variance (ANOVA). This study indicated that the naphthalene absorption through silastic membrane was significantly different with JP-8 plus individual additives as compared to controls, i.e. JP-8 and JP-8(100). The porcine skin data indicated that neither individual nor combinations of additives affected naphthalene absorption. The third membrane system (IPPSF) showed that only MDA and BHT were important additives altering naphthalene absorption. MDA was a significant suppressor while BHT was a significant enhancer of naphthalene absorption. MDA significantly decreased dodecane absorption in skin flaps. All individual and combinations of two additives with JP-8 affected naphthalene and dodecane surface retention in silastic membrane. The IPPSF indicated that only 8Q405 is a significant modulator of surface retention for both marker hydrocarbons. The 8Q405 significantly reduced naphthalene contents in dosed silastic and skin indicating a direct interaction between additive and marker hydrocarbons. The MDA and BHT, which significantly retained naphthalene in the stratum corneum of porcine skin individually, led to a statistical decrease in its retention in the stratum corneum when in combination (MDA + BHT) suggesting a potential biological interaction. These observations demonstrate that the single membrane system may not be suitable for the final prediction of complex additive interactions in jet fuels. Rather a combination of different membrane systems may provide the insight to elucidate the possible mechanism for additive interactions. Finally, it is important to assess all components of a chemical mixture since the effects of single components administered alone or as pairs may be confounded when all are present in the complete mixture.

Administration, Topical↗
PubMed2000

The early supra-additive apoptotic response of R3327-G prostate tumors to androgen ablation and radiation is not sustained with multiple fractions.

PURPOSE: The treatment of R3327-G tumor-bearing rats with androgen ablation (AA) via castration results in a supra-additive increase in apoptosis when 2-8 Gy gamma-irradiation (RT) is given as a single dose 3-14 days afterwards. We report here the dose response and effect of multiple fractions on this supra-additive apoptotic response. MATERIALS AND METHODS: Dunning R3327-G tumors were grown in the flanks of Copenhagen rats and the experiments were initiated at a tumor volume of 1.0-1.5 cc. Androgen ablation was achieved by castration 3 days prior to gamma-irradiation. Apoptosis was measured with a terminal deoxynucleotidyl transferase dUTP-biotin nick end-labeling assay 6-h after RT, unless otherwise specified. RESULTS: The dose response of the supra-additive apoptotic response was assessed by irradiating castrated animals with single doses of 2, 4, 8, or 16 Gy (n = 5 per group); tumor cell apoptosis at 6-h following irradiation was 2.4%+/-0.7% (+/- SEM), 4.2%+/-0.8%, 6.5%+/-1.4%, and 1.6%+/-0.3%, respectively. The RT only and AA only controls had < 1% apoptosis. The effect of fractionated RT on apoptosis was investigated to determine if the supra-additive apoptotic response was sustained with repeated 2-8 Gy fractions. When tumor-bearing animals were treated with repeated daily 2-Gy fractions, there was a reduction in the level of the supra-additive apoptotic response. After five 2-Gy fractions at 24-h intervals, apoptosis in the combined treated tumors was at levels seen in the AA controls. This raised the possibility that more than 24 h are required for recovery of the high supra-additive apoptotic levels seen after one fraction. When the interfraction interval was extended to 96 h, there was no significant increase in apoptosis over the additive effect of AA and RT. Although there was a decline in supra-additive apoptosis with repeated fractions, a dose response for tumor growth delay was evident for RT alone using 2.5-Gy fractions. Moreover, the combination of AA + fractionated RT resulted in a supra-additive enhancement in tumor growth delay to 5 cc. CONCLUSION: The early supra-additive apoptotic response from AA and single fraction radiation is not seen at high single fraction doses and is not sustained with repeated fractions. Therefore, the classical apoptotic response that occurs within 24 h of irradiation is not likely to be the main mechanism responsible for any clinical benefit seen with this combination.

Animals↗
PubMed2001

Oxidative addition of the imidazolium cation to zerovalent Ni, Pd, and Pt: a combined density functional and experimental study.

Oxidative addition of different imidazolium cations to zerovalent group 10 metals, to afford heterocyclic carbene complexes, has been investigated by both density functional theory (DFT) and experimental studies. The theoretical analysis shows that addition of imidazoliums to Pt(0) and Ni(0) is more exothermic than to Pd(0), and Ni(0) is predicted to react with a much lower barrier than either Pt(0) or Pd(0). Strongly basic supporting ligands on the metal, as well as cis-chelating ligands, increase the exothermicity of the reaction and also lower the activation barrier. The addition of 2-H imidazoliums is easier and more exothermic than addition of 2-alkylimidazoliums, and a halo-imidazolium is expected to further lower the barrier to oxidative addition and increase the exothermicity. The DFT results show that all three of the metals should be able to oxidatively add imidazolium cations under appropriate conditions. Experimental studies confirmed that oxidative addition is possible, and a number of Pt- and Pd-carbene complexes were prepared via oxidative addition of imidazolium salts to M(0) precursors. Most significantly, oxidative addition of 2-H azolium salts was found to readily occur, and the reaction of 1,3-dimethylimidazolium tetrafluoroborate with Pt(PPh(3))(2) and Pt(PCy(3))(2) affords [PtH(dmiy)(PPh(3))(2)]BF(4) (10) and [PtH(dmiy)(PCy(3))(2)]BF(4) (11), while reaction between 3,4-dimethylthiazolium tetrafluoroborate and Pt(PCy(3))(2) yields [PtH(dmty)(PCy(3))(2)]BF(4) (12) (dmiy = 1,3-dimethylimidazolin-2-ylidene, dmty = 3,4-dimethylthiazolin-2-ylidene). Addition of 2-iodo-1,3,4,5-tetramethylimidazolium tetrafluoroborate to Pt(PPh(3))(4) or Pd(dcype)(dba) yields [PtI(tmiy)(PPh(3))(2)]BF(4) (9) and [PdI(tmiy)(dcype)]BF(4) (14), respectively (tmiy = 1,3,4,5-tetramethylimidazolin-2-ylidene, dcype = 1,3-bis(dicyclohexylphosphino)ethane)). X-ray crystal structures are reported for complexes 9 and 11 (cis and trans). These studies clearly show for the first time that oxidative addition of imidazolium and thiazolium cations is possible, and the results are discussed in terms of the ramifications for catalysis in imidazolium-based ionic liquids with both carbene-based and non-carbene-based complexes.

Journal Article↗
PubMed2003

Evidence for a lack of reactivity of carotenoid addition radicals towards oxygen: a laser flash photolysis study of the reactions of carotenoids with acylperoxyl radicals in polar and non-polar solvents.

In this paper, we report the results of a laser flash photolysis study of the reactions of a range of carotenoids with acylperoxyl radicals in polar and nonpolar solvents. The results show, for the first time, that carotenoid addition radicals do not react with oxygen to form carotenoid peroxyl radicals; an observation which is of significance in relation to antioxidant/pro-oxidant properties of carotenoids. Acylperoxyl radicals, generated by photolysis of ketone precursors in oxygenated solvents, display high reactivity toward carotenoids in both polar and nonpolar solvents, but the nature of the carotenoid radicals formed is dependent on solvent polarity. In hexane, acylperoxyl radicals react with carotenoids with rate constants in the region of 10(9) M(-1) s(-1) and give rise to transient absorption changes in the visible region that are attributed to the formation of addition radicals. All of the carotenoids show bleaching in the region of ground-state absorption and, with the exception of 7,7'-dihydro-beta-carotene (77DH), no distinct absorption features due to addition radicals are observed beyond the ground state absorption region. For 77DH, the addition radical displays an absorption band that is spectrally resolved from the parent carotenoid absorption. The rate of decay of the 77DH addition radical is unaffected by oxygen in the concentration range 10(-4)-10(-2) M, suggesting that these resonance-stabilized carbon-centered radicals are not scavenged by oxygen. At low incident laser intensities, the 77DH addition radical decay kinetics are 1st order with k(1) approximately 4 x 10(3) s(-1) at room temperature. The 1st order decay is attributed to an intramolecular cyclization process, which is supported by the substantial negative entropies of activation obtained from measurements of the decay rate constants for different 77DH addition radicals as a function of temperature. No transient absorption features are observed in the red or near-infrared regions in hexane for any of the carotenoids studied. In polar solvents such as methanol, acylperoxyl radicals also react with carotenoids with rate constants in the region of 10(9) M(-1) s(-1), but give rise to transient absorption changes in both the visible and the red/near-infrared regions, where it is evident that there are two distinct species. For 77DH, the addition radical absorption around 450 nm is still evident, although its kinetic behavior differs from its behavior in hexane. For 77DH and zeta-carotene (zeta-CAR) the spectral and kinetic resolution of the various absorption bands simplifies kinetic analysis. The kinetic evidence suggests that addition radical formation precedes formation of the two near-infrared absorbing species, and that the kinetics of the addition radical decay match the kinetics of formation of the first of these species (NIR1, absorbing at shorter wavelengths). The decay of NIR1 leads to NIR2, which is attributed to the carotenoid radical cation. The solvent dielectric constant dependence of the relative amounts of NIR1 and NIR2 formed leads us to speculate that NIR1 is an ion-pair. However, an alternative assignment for NIR1 is an isomer of the radical cation. The results, in terms of the pattern of reactivity the carotenoids display and of the properties of the carotenoid radicals formed, are discussed in relation to the antioxidant/pro-oxidant properties of carotenoids.

Antioxidants↗
PubMed2000

Requirements for the dGTP-dependent repeat addition processivity of recombinant Tetrahymena telomerase.

Telomerase is a reverse transcriptase responsible for adding simple sequence repeats to chromosome 3'-ends. The template for telomeric repeat synthesis is carried within the RNA component of the telomerase ribonucleoprotein complex. Telomerases can copy their internal templates with repeat addition processivity, reusing the same template multiple times in the extension of a single primer. For some telomerases, optimal repeat addition processivity requires high micromolar dGTP concentrations, a much higher dGTP concentration than required for processive nucleotide addition within a repeat. We have investigated the requirements for dGTP-dependent repeat addition processivity using recombinant Tetrahymena telomerase. By altering the template sequence, we show that repeat addition processivity retains the same dGTP-dependence even if dGTP is not the first nucleotide incorporated in the second repeat. Furthermore, no dNTP other than dGTP can stimulate repeat addition processivity, even if it is the first nucleotide incorporated in the second repeat. Using structural variants of dGTP, we demonstrate that the stimulation of repeat addition processivity is specific for dGTP base and sugar constituents but requires only a single phosphate group. However, all nucleotides that stimulate repeat addition processivity also inhibit or compete with dGTP incorporation into product DNA. By assaying telomerase complexes reconstituted with a variety of altered templates, we find that repeat addition processivity has an unanticipated template or product sequence specificity. Finally, we show that a novel, nascent product DNA binding site establishes dGTP-dependent repeat addition processivity.

Animals↗
PubMed2006

Different ratios of lactide and glycolide in PLGA affect the surface property and protein delivery characteristics of the PLGA microspheres with hydrophobic additives.

This study investigated whether the surface quantities of the additives and protein delivery characteristics for protein-loaded PLGA 85 (85:15), PLGA75 (75:25) and PLGA 50 (50:50) microspheres with hydrophobic additives, phosphatidylcholine (PC) as a model, are affected by the different ratios of lactide and glycolide in PLGA polymers. By applying phospholipids analysis, surface PC quantities of the microspheres are 2.1 +/- 1.2, 1.2 +/- 0.3 and 1.0 +/- 0.7 Pg (n = 3) per mg of PLGA 85, PLGA 75 and PLGA 50 microspheres with PC addition, respectively, that are affected by the ratio of lactide and glycolide in PLGA. The addition of PC causes the decreased encapsulation efficiency (E.E.) of albumin of the microspheres and the decreased percentages of E.E. are negative correspondent to ratio of lactide and glycolide in PLGA (e.g. -13.5, -20.2 and -24.5% for PLGA 85, PLGA 75 and PLGA 50, respectively) compared with those without addition. The cumulative releases of albumin were influenced by the ratio of lactide and glycolide in PLGA for both PC addition and non-addition microspheres. Moreover, the additions of PC reduce the initial burst and cumulative releases of albumin of the microspheres compared with those of non-added ones. Further investigation suggests that resistant water uptake of PC added microspheres may play a role on affecting those reduced protein release behaviours. In conclusion, the different ratios of lactide and glycolide in PLGA affect the surface quantities of PC, E.E. and cumulative release profiles of albumin for the PLGA microspheres with PC addition. The results of the study may help the better practical applications for protein delivery of the microspheres with hydrophobic additives.

Albumins↗
PubMedDate not supplied

Additives to reduce ammonia and odor emissions from livestock wastes: a review.

This paper reviews the use of additives to reduce odor and ammonia (NH3) emissions from livestock wastes. Reduction of NH3 volatilization has been shown to be possible, particularly with acidifying and adsorbent additives, and potential exists to develop further practical and cost-effective additives in this area. Masking, disinfecting, and oxidizing agents can provide short-term control of malodor, but as the capacity of these additives is finite, they require frequent reapplication. Microbial-based digestive additives may offer a solution to this problem as they are regenerative, but they appear to have been developed without a thorough understanding of microbiological processes occurring in livestock wastes. Currently, their use to reduce odor or NH3 emissions cannot be recommend. If the potential of these types of additives is to be realized, research needs to shift from simply evaluating these unknown products to investigating known strains of bacteria or enzymes with known modes of action. To protect the farmers' interest, standard independent test procedures are required to evaluate efficacy. Such tests should be simple and quantify the capacity of the additive to perform as claimed. The principle use of additives needs to be identified and addressed during their development. Producers may not use effective additives in one area if they further compound other problems that they perceived to be more important. There is the potential to use additives to treat other problems associated with livestock wastes, particularly to improve handling properties, reduce pollution potential to watercourses, and reduce pathogenic bacteria. Further work is required in these areas.

Absorption↗
PubMed1989

Estimation of additive maternal and cytoplasmic genetic variances in animal models.

Two pathways for maternal genetic effects to act on production traits are additive maternal and cytoplasmic. Estimation of these variances have generally assumed that the correct maternal pathway is known. A method is described that allows simultaneous estimation of additive maternal and cytoplasmic genetic variances as well as additive direct genetic variances and error variances using an animal model. Data were simulated assuming an additive maternal model, cytoplasmic model, or both. The method was tested by analyzing the data under the true or incorrect maternal model using REML with an animal model that accounted for additive genetic relationships. Additive direct, additive maternal, cytoplasmic, and error variances were correctly partitioned when estimated under the true model. However, when additive maternal or cytoplasmic genetic effects were ignored in the model used for analysis, estimates of additive direct variance were significantly inflated. Also, under an additive maternal genetic model, a small cytoplasmic variance was estimated although none was present in the data.

Analysis of Variance↗
PubMed1994

Additive and nonadditive genetic variances for milk yield, fertility, and lifetime performance traits of dairy cattle.

Additive and nonadditive genetic variances were estimated for yield traits and fertility for three subsequent lactations and for lifetime performance traits of purebred and crossbred dairy cattle populations. Traits were milk yield, energy-corrected milk yield, fat percentage, protein percentage, calving interval, length of productive life, and lifetime FCM of purebred Simmental, Simmental including crossbreds, and Braunvieh crossed with Brown Swiss. Data files ranged from 66,740 to 375,093 records. An approach based on pedigree information for sire and maternal grandsire was used and included additive, dominance, and additive by additive genetic effects. Variances were estimated using the tildehat approximation to REML. Heritability estimated without nonadditive effects in the model was overestimated, particularly in presence of additive by additive variance. Dominance variance was important for most traits; for the lifetime performance traits, dominance was clearly higher than additive variance. Additive by additive variance was very high for milk yield and energy-corrected milk yield, especially for data including crossbreds. Effect of inbreeding was low in most cases. Inclusion of nonadditive effects in genetic evaluation models might improve estimation of additive effects and may require consideration for dairy cattle breeding programs.

Animals↗
PubMed2000

The preoptic area in the hypothalamus is the source of the additional respiratory drive at raised body temperature in anaesthetised rats.

In mammals that use the ventilatory system as the principal means of increasing heat loss, raising body temperature causes the adoption of a specialised breathing pattern known as panting and this is mediated by the thermoregulatory system in the preoptic area of the hypothalamus. In these species an additional respiratory drive is also present at raised body temperature, since breathing can reappear at low Pa,CO2 levels, when stimulation of chemoreceptors is minimal. It is not known whether the preoptic area is also the source of this additional drive. Rats do not pant but do possess this additional respiratory drive at raised body temperatures. We have therefore tested whether the preoptic area of the hypothalamus is the source of this additional respiratory drive in rats. Urethane anaesthesia and hyperoxia were used in eleven rats to minimise behavioural and chemical drives to breathe. The presence of the additional respiratory drive was indicated if rhythmic diaphragmatic EMG activity reappeared during hypocapnia (a mean Pa,CO2 level of 21+/-2 mm Hg, n = 11), induced by mechanical ventilation. The additional respiratory drive was absent at normal body temperature (37¿C). When the temperature of the whole body was raised using an external source of radiant heat, the additional respiratory drive appeared at 40.6+/-0.5 degrees C (n = 3). In two further rats this drive was induced at normal body temperature by localised warming in the preoptic area of the intact hypothalamus. The additional respiratory drive appeared at similar temperatures to those in control rats in three rats following isolation of the hypothalamus from more rostral areas of the brain. In contrast, the additional respiratory drive failed to appear at these temperatures in three rats after isolating the hypothalamus from the caudal brainstem, by sectioning pathways medial to the medial forebrain bundle. Since the preoptic area is known to contain thermoreceptors and to receive afferents from peripheral thermoreceptors, the results show that this area is also the source of the additional respiratory drive at raised body temperature in anaesthetised rats.

Anesthesia, Intravenous↗
PubMed1995

Addition of urapidil or metoprolol to the treatment of hypertensive non-responders to nifedipine monotherapy: efficacy and metabolic effects. Italian Urapidil Study Group.

This study compared the effects on blood pressure and some metabolic variables of a 3-month period addition therapy of urapidil or metoprolol in 273 hypertensive non-responders to nifedipine sustained release (SR) monotherapy. This was a randomised, open-label, controlled, parallel-group comparative study, followed by another 3-month period during which all patients received the combination nifedipine SR-urapidil independently of the treatment they were previously randomized to. Both treatments caused significant falls in systolic (SBP) and diastolic blood pressure (DBP) when compared with the nifedipine SR monotherapy phase. The addition of urapidil to nifedipine SR caused a significant blood pressure reduction of 16.6/13.6 mmHg (p < 0.001), whereas after metoprolol the decrease was of 15.1/14 mmHg (p < 0.001). While in the overall population there was no statistically significant difference between the reduction caused by the two antihypertensive agents added to nifedipine SR, significant differences (DBP, p < 0.05; SBP, p < 0.01) were observed in the group of 51 patients aged at least 60 years. Total cholesterol and LDL-cholesterol were significantly reduced (p < 0.001) after the addition of urapidil to nifedipine SR, while, on the contrary, the addition of metoprolol to nifedipine SR was followed by a significant rise (p = 0.001). The changes caused by the two agents were statistically different among them (p < 0.01). The non-atherogenic HDL-cholesterol did not change during the addition of urapidil or metoprolol to nifedipine SR, while, the HDL/total cholesterol ratio was significantly increased after the addition of urapidil (p < 0.01) and unmodified after the addition of metoprolol. Between-group analysis showed a significant difference (p = 0.005). Serum triglycerides did not change in the urapidil plus nifedipine SR group but significantly increased in the metoprolol plus nifedipine SR group (p < 0.001); between-group difference was not statistically significant. Plasma glucose was unchanged after the addition of urapidil whereas it was significantly (p < 0.001) increased in the metoprolol-added group with a between-group difference statistically significant (p < 0.05). When metoprolol was substituted by urapidil during the second 3-month period, the negative effects on glucose, total cholesterol, LDL cholesterol and triglycerides were abolished while in the group already treated with urapidil plus nifedipine SR the favourable effects of urapidil plus nifedipine SR on total cholesterol, LDL-cholesterol and HDL/total cholesterol ratio were significantly increased compared with the end of the first 3-month treatment. The results of this study show that when urapidil and metoprolol are added to non-responders to nifedipine SR therapy there is a clinically and statistically relevant blood pressure reduction with both agents, with a therapeutic advantage for the combination urapidil + nifedipine SR in patients more than 60 years old. Moreover, the addition of urapidil was associated with a more favourable effect on serum lipids and glucose than that produced by the addition of metoprolol.

Adult↗
PubMed2001

Increased leukotriene production by food additives in patients with atopic dermatitis and proven food intolerance.

Recently, we identified a subgroup of patients with atopic dermatitis (AD) with a clinical relevant food intolerance proven by double blind placebo controlled challenge. In search of possible pathomechanisms involved in this food intolerance, which leads to aggravation of the disease, the aim of the present study was to determine sulfidoleukotriene production in these patients using isolated leucocytes from the peripheral blood after stimulation with different food additives. Leukotriene production of peripheral leucocytes was detected by incubation of isolated cells with the food additives at different concentrations ranging from 0.2 to 200 microg/mL after pre-stimulation with IL-3. Ten non-atopic donors (A), nine AD patients of the diet responder group with negative oral provocation test against food additives (B) and nine patients of the responder group with positive reactions after the oral provocation test (C) were investigated. In the non-atopic group (A), no increased sulfidoleukotriene (sLT) release was observed for all food additives tested. In group B, increased sLT production was determined using tartrazine in one patient (1/9) and using nitrite in two patients (2/9), whereas sLT production remained below the cut-off range in all patients of group B (9/9) using benzoate, metabisulfite and salicylate. By contrast, in group C increased sLT production was observed with food colour mix in 1/9, with tartrazine in 3/9, with benzoate in 4/9, with nitrite in 5/9, with salicylate in 2/9 and with metabisulfite in 1/9. However, no increased sLT concentration was determined in the presence of the tested food additives in two patients of group C. Increased sLT production by peripheral leucocytes in the presence of single food additives was observed in the majority of patients with a proven food intolerance towards food additives proven by double-blind-placebo-controlled challenges. These food additives were particulary tartrazine, benzoate and nitrite. These findings indicate that single food additives as aggravating factors in AD patients may trigger the disease through increased sLT production as a pathophysiological mechanism.

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