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FORMATION OF H-addition radicals in adenine derivatives: part II.

The formation of H-addition radicals in monocrystals of adenosine, adenosine-HCl, adenine-HCl-1/2H2O, and adenine-2 HCl by X-irradiation has been st-died by using electron spin resonance spectroscopy at 9.5 GHz and at 35 GHz. In all crystals, both H-addition radicals at position C2 and at position C8 were observed. The coupling constants of these two H-addition radicals are different and depend strongly on the protonation state of the adenine base. INDO calculations reproduce well the observed trends of the coupling constants. It is shown that the C2-addition radical is transformed into the C8-addition radical by heat and vice versa the C8-addition into the C2-addition by light of lambda greater than 360 nm.

Adenine↗

X-ray induced inactivation of the sulfhydryl enzyme malate synthase in the presence of various additives. Probing the extent of primary and post-irradiation inactivation and repair by rapid screening on the microlevel.

The sulfhydryl enzyme malate synthase was inactivated by X-irradiation in air-saturated aqueous solution, in the absence or presence of a variety of additives (thiols, antioxienzymes, typical radical scavengers, inorganic salts, buffer components, substrates, products, analogues). Radiation-induced changes of enzymic activity were registered immediately after stop of irradiation and in the post-irradiation period. Repair experiments were initiated by post-irradiation addition of dithiothreitol. Additionally, post-irradiation inactivation was modulated by some further additives. Probing the extent of primary and post-irradiation inactivation and repair was accomplished effectively by screening experiments on the microlevel, and by derivation of normalized efficiency parameters which allowed quick comparisons of the various additives with respect to their protective and repair-promotive efficiencies. Correlations between the efficiency parameters were studied by means of binary and ternary diagrams. Most of the substances added before irradiation were found to protect the enzyme against primary and post-irradiation inactivation and to increase the reparability of the enzyme by dithiothreitol, the extent of the effects depending on the nature (and concentration) of the additives used. Our results indicate that both specific protection (by substrates, products, analogues, and by sulfhydryl agents) and scavenging are responsible for the radioprotective efficiencies of the additives.

Kinetics↗

Radiation-induced hydroxyl addition to purine molecules: EPR and ENDOR study of hypoxanthine hydrochloride monohydrate single crystals.

Three radical species were detected in an EPR/ENDOR study of X-irradiated hypoxanthine.HCl.H2O single crystals at room temperature: RI was identified as the product of net H addition to C8, RII was identified as the product of net H addition to C2, and RIII was identified as the product of OH addition to C8. The observed set of radicals was the same for room-temperature irradiation as for irradiation at 10 K followed by warming the crystals to room temperature; however, the C2 H-addition and C8 OH-addition radicals were not detectable after storage of the crystals for about 2 months at room temperature. Use of selectively deuterated crystals permitted unique assignment of the observed hyperfine couplings, and results of density functional theory calculations on each of the radical structures were consistent with the experimental results. Comparison of these experimental results with others from previous crystal-based systems and model system computations provides insight into the mechanisms by which the biologically important purine C8 hydroxyl addition products are formed. The evidence from solid systems supports the mechanism of net water addition to one-electron oxidized purine bases and demonstrates the importance of a facial approach between the reactants.

Crystallography↗

Performance and nutrient digestibility in weanling pigs as influenced by yeast culture additions to starter diets containing dried whey or one of two fiber sources.

Three experiments were conducted using crossbred weanling pigs (7.2 to 8.6 kg; 25 to 29 d of age) to determine the effect on performance and nutrient digestibility of .75% yeast culture (YC) additions to starter diets containing whey or one of two fiber sources. An 18% CP corn-soybean meal basal diet was used in all experiments. In Exp. 1 (n = 192), the addition of YC did not affect ADG, ADFI, or gain: feed ratios (G:F) of pigs fed diets without or with 15% dried whey in two 5-wk trials. In Exp. 2 (n = 174), ADG and ADFI were not affected by YC addition to diets containing no added fiber, 8% soybean hulls (SH), or 8% peanut hulls (PH) in two 5-wk trials. The addition of SH or PH did not affect ADG or ADFI; however, a YC x SH interaction (P < .05) and a YC x PH interaction (P < .10) for G:F indicated that the addition of SH or PH to the diet in the absence of YC reduced G:F, but in the presence of YC, G:F were maintained. In a 3-wk grower phase of one trial in Exp. 2 (n = 54), SH and PH additions decreased ADG (P < .005), whereas YC additions improved ADG (P < .01), particularly for pigs fed diets that also contained SH (P < .05).(ABSTRACT TRUNCATED AT 250 WORDS)

Animal Nutritional Physiological Phenomena↗

Melanoma and additional primary cancers.

The aim of this study was to examine the occurrence of additional, unrelated primary cancers in patients with melanoma. Data from the hospital-based, melanoma registry of a specialist unit (the Melanoma Unit at Charing Cross Hospital, London, UK) were compared with the incidence rates in a population-based cancer registry (the Thames Cancer Registry). In total, 2076 patients with the histological diagnosis of melanoma established between 1960 and 1997 who were registered with the Melanoma Unit at Charing Cross Hospital, were included in the study. Patterns in time and in the tumour type of the additional cancers were analysed in the cohort. The relative risk of subsequent cancers was evaluated, the number of expected cancers being calculated by applying incidence rates in the population of south-east England to the person-years of follow-up in the cohort. Sixty-six (3%) of the 2076 evaluable patients had a history of, or developed, 69 histologically verified additional cancers, the commonest being colorectal, breast and lymphoma. Twenty-six additional cancers preceded the diagnosis of melanoma by 1-42 years, 16 were diagnosed within 12 months and 27 followed the diagnosis of melanoma, 1-28 years later. Seven cancers occurred after chemotherapy for metastatic melanoma: two colorectal, one bladder, one renal, two myelodysplasias and one acute myeloid leukaemia. The relative risk of additional cancers developing after the diagnosis of melanoma during the 8537 evaluable years-at-risk was 0.64 (95% confidence interval 0.41-0.96; P = 0.0006). Thus, the risk of additional cancers following treatment for metastatic melanoma in this cohort is small. The potential influence of other factors on the occurrence of additional cancers observed overall in this study requires further investigation.

Adolescent↗

Additional cytogenetic changes do not influence the outcome of patients with newly diagnosed acute promyelocytic leukemia treated with an ATRA plus anthracyclin based protocol. A report of the Spanish group PETHEMA.

BACKGROUND AND OBJECTIVES: To analyze in patients with de novo acute promyelocytic leukemia (APL) treated with an ATRA plus anthracyclin-based protocol if the presence of additional cytogenetic aberrations to the t(15;17) influences: 1. clinical and biological presenting features; 2. disease outcome. DESIGN AND METHODS: One hundred and thirteen patients with newly diagnosed APL enrolled in the APL-96 protocol of the Spanish PETHEMA group were studied by conventional karyotyping, FISH and RT-PCR for the PML-RARa fusion. Treatment was homogeneous in all cases and consisted of anthracyclines and ATRA. RESULTS: Additional chromosome aberrations were observed in 30% of cases. The most frequent secondary changes were +8 (14 cases), and abnormalities of chromosomes 9 or 3 (4 patients each), and of chromosomes 1 and 8 (3 cases each). No clinical, biological, morphological, immunophenotypic or molecular differences were observed between the group of APLs with t(15;17) alone and the group of patients with additional changes. Patients with additional changes had a higher rates of complete remission (CR) and 4-year disease-free survival (DFS) (97%, and 97%, respectively) than patients with t(15;17) alone (CR, 70% and DFS, 84%) but these differences were not statistically significant. INTERPRETATION AND CONCLUSIONS: Patients with APL and additional cytogenetic abnormalities do not show different clinical, biological, morphological or molecular features as compared to patients with t(15;17) alone. The prognosis of patients with APL and t(15;17) alone and those with additional changes is similar in both groups. This study indicates that there is no rationale for administering more intensive treatment in APL patients with additional cytogenetic abnormalities receiving ATRA plus anthracycline-based chemotherapy.

Adolescent↗

[The effect of additives on the availability of atropine in transdermal therapeutic systems].

The present paper investigates the effect of 13 liquid and semisolid additives on the pharmaceutical availability of atropine from dermal silicone matrices. The hydrophobic additives isopropylmyristate, linseed oil, methylsilicone oil, olive oil, liquid paraffin, the tensides Abil B 8842, Spans 20, 40, 60, Tweens 40 and 80, and the hydrophilic additives polyethylene glycol 200 and 400 were employed for the study. The additives were incorporated into the silicone matrices in the amount of 5%. The paper aimed to replace polyethylene glycol, used in dermal silicone matrices at present, with a different additive. When using liquid or semisolid additives, a 2 to 3.5-fold increase in pharmaceutical availability of atropine in contrast to the control sample was achieved. The highest values of pharmaceutical availability were obtained with the use of isopropylmyristate, polyethylene glycol 400, olive and linseed oils, and Span 20. The paper discusses the effect of the individual additives on the mechanism of release of atropine from silicone matrices.

Administration, Cutaneous↗

[Effects of CaCOC addition under Zn supply on wheat seedlings growth and Zn uptake].

High concentration calcium carbonate in calcareous soils usually limits plant Zn uptake. In this paper, a solution culture experiment was conducted to study the effects of CaCO3 addition with or no Zn supply on the growth and Zn uptake of three genotypes winter wheat seedlings. The results showed that Zn supply or CaCO3 addition had no significant effects on seedlings biomass and root/canopy ratio, and there was no significant difference among the three genotypes. CaCO3 addition led to leaf chlorosis. No matter with or no Zn supply, CaCO3 addition had no significant effects on the Zn concentration and accumulation in wheat root, stem, and leaf. Zn supply increased the Zn concentration in Yuanfeng 998, Zhongyu 6, and Xiaoyan 22 by 80.0%, 104.8% and 139.6%, respectively. For Yuanfeng 998, a sensitive genotype to Zn-deficiency, the increment of Zn concentration and accumulation was much lower than that of Zhongyu 6 and Xiaoyan 22, non-sensitive genotypes to Zn-deficiency. Zn supply or CaCO3 addition had no significant effects on the P content in root, stem, and leaf, but the corresponding P content of Yuanfeng 998 was obviously lower than that of the other two genotypes. Zn supply greatly decreased the P/Zn ratio in root, stem and leaf, and CaCO3 addition also showed the same tendency. Under Zn-deficiency, CaCO3 addition caused leaf chlorosis, but did not decrease wheat plant Zn uptake. In conclusion, at least under solution culture condition, high concentration calcium carbonate had no obvious inhibitory effect on plant zinc uptake, and whether this situation was true in calcareous soils is worthy to be further investigated.

Biomass↗

Acetylcholine and histamine interact supra-additively on bronchomotor tone in guinea-pigs in vivo: a possible consequence of the relationship between airways resistance and calibre.

Histamine and acetylcholine administered simultaneously to anaesthetized guinea-pigs result in a bronchoconstriction greater than that of the sum of the individual bronchoconstrictor effects of histamine and acetylcholine administered separately, i.e., a supra-additive interaction. In contrast, a supra-additive effect of acetylcholine and histamine on the isolated tracheal strip did not occur. At a pretreatment concentration of acetylcholine of 5 microM, histamine concentration-response curves were shifted rightwards, i.e., a less than additive interaction, suggesting that, at higher concentrations, histamine and acetylcholine do not act as independent agonists on guinea-pig tracheal smooth muscle. There was no supra-additive interaction between histamine and acetylcholine on tracheal segment tension when measured in situ. These observations suggest that there is no direct interaction between histamine and acetylcholine on the airways smooth muscle cell capable of explaining the supra-additive interaction in vivo. Hexamethonium pretreatment did not alter the magnitude of this supra-additive interaction indicating that an indirect interaction involving autonomic control of airways calibre does not contribute to this phenomenon. The selectivity of the supra-additive interaction for changes in airways resistance rather than compliance, together with the negative evidence for either a direct or an indirect pharmacological interaction between histamine and acetylcholine, suggest that the interaction may result from the physical relationship between airways resistance and airways calibre.

Acetylcholine↗

[Effect of additions of the carbon and nitrogen sources on the NADP+ and NAD+ level in the mycelium of a producing strain of P. nigricans Thom].

The levels of NADP+ and NAD+ in the mycelium of a cultured strain of P. nigricans Thom grown on the mineral medium with 2 per cent of glucose were studied as dependent on the time and method of addition of glucose. NaNO3 or their mixture to the medium, i. e. a single addition simultaneously with the spore inoculation or on the 7th day of the culture development, divided additions on the 5th--7th days. It was shown that addition of the above sources simultaneously with inoculation affected the levels of both dinucleotides by the 5th and 8th days. Analogous additions on the 7th day in 24 hours decreased the level of NAD+, while the NADP+ concentration increased after addition of a mixture of glucose and NANO3 and remained unchanged on their separate addition. When the above sources were added in divided doses the level of NADP+ increased till the 7th day and that of NAD+ till the end of the experiment (the 8th day).

Carbon↗

[Additional doses of oral morphine on demand].

It is very important to relief the pain of terminally ill patients. Populalization of WHO "Cancer Pain Relief" saved many cancer pain suffered patients. The patients in hospital may get enough pain relief as soon as they suffer the pain by their medical stuffs. But It spend much more time to relieve the pain, I write prescription of regular use morphine and additional morphine. Additional dose is 1/4 of regular dose. When they suffer any pain, they may take additional morphine on their demand. Six terminally ill patients were given additional morphine. Four of 6 used the additional morphine for once to 4 times. They were satisfied the effect of additional, they did not use. Their pain did not increase. I suppose, they knew the means of pain relief then they were free from the anxiety of increasing pain. Decreasing the anxiety reduce their pain. Additional doses of morphine on demand are very useful to relieve the pain of the patients at home.

Administration, Oral↗

Differences in health status of older adults with pain in the hip or knee only and with additional mobility restricting conditions.

OBJECTIVE: To determine differences in health status of people aged 55 to 74 years with pain in the hip or knee only and with additional mobility restricting conditions. METHODS: A subsample from a community based study on pain, disability, comorbidity, and radiological osteoarthritis (OA) was used to identify a group with current pain in the hip or knee only (n = 62), a group with additional mobility restricting conditions (n = 124), and a reference group without pain and radiological OA (n = 72). Health status was measured with the IRGL instrument (Impact of Rheumatic diseases on General health and Lifestyle). Additional mobility restricting conditions were self-reported. RESULTS: The most reported additional conditions were more widespread joint pain and stiffness, and cardiovascular and respiratory problems. The group with pain in the hip or knee only had less mobility than the reference group (p < 0.05), but had higher mobility (p < 0.05), less pain (p < 0.001), less psychological distress (p < 0.01), and less effect of symptoms on daily life (p < 0.001) than the group with additional conditions. No differences were found in background variables or comorbidity. Multivariate logistic regression analysis showed that the group with additional conditions differed from the group with knee or hip pain only with respect to joint pain (OR 1.18), cheerfulness (OR 0.9), and effect on daily life (OR 1.1). CONCLUSION: The health status of people with pain in the hip or knee only is comparable to that of a reference group without pain. Health status is lower when pain in the hip or knee is present in combination with additional mobility restricting conditions. This last group is at greater risk of psychological distress and physical dysfunctioning.

Activities of Daily Living↗

Evaluation of certain food additives.

This report represents the conclusions of a Joint FAO/WHO Expert Committee convened to evaluate the safety of various food additives, with a view to recommending acceptable daily intakes (ADIs) and to prepare specifications for the identity and purity of food additives. The first part of the report contains a general discussion of the principles governing the toxicological evaluation of food additives (including flavouring agents), assessments of intake, and the establishment and revision of specifications for food additives. A summary follows of the Committee's evaluations of toxicological and intake data on various specific food additives (Beeswax, Candelilla wax, Calcium L-5-Methyltetrahydrofolic acid (L-5-MTHF), Phospholipase A1 from Fusarium venenatum expressed in Aspergillus oryzae, Pullulan, Quillaia extract Type 1, Quillaia extract Type 2) and seven groups of flavouring agents. Annexed to the report are tables summarizing the Committee's recommendations for ADIs of the food additives, recommendations on the flavouring agents considered, changes in the status of specifications, and further information requested or desired.

Animals↗

An analysis of the possibility for health implications of joint actions and interactions between food additives.

The possibility that structurally unrelated food additives could show either joint actions or interactions has been assessed based on their potential to share common sites and mechanisms of action or common pathways of elimination. All food additives approved in the European Union and allocated numerical acceptable daily intake values were studied, initially based on the reports by the FAO-WHO Joint Expert Committee for Food Additives. Target organs were identified based on the effects reported at doses above the no-observed-adverse-effect level (NOAEL) in animal and human studies. The descriptions of the pathological and other changes reported were used to assess whether different additives, sharing the same target organ, would produce a common toxic effect. In all but a very few cases, the possibility of joint actions or interactions could be excluded on scientific grounds. The exceptions were on the liver (curcumin, thiabendazole, propyl gallate, and BHT), the kidney (diphenyl, o-phenylphenol, and ferrocyanide salts), the blood (azorubine and propyl gallate), and the thyroid (erythosine, thiabendazole, and nitrate). Toxicokinetic interactions were considered unlikely because of the low dosages involved, the diverse nature of the routes of metabolism and elimination, and the fact that enzyme induction or inhibition would have influenced selection of the NOAEL. Many of those additives which could not be excluded from showing joint actions or interactions would have low intakes; in some cases they were alternatives for the same application, thereby further lowering the combined intake. In consequence, joint actions or interactions between additives do not represent a significant health concern.

Drug Interactions↗

Primary mutagenicity screening of food additives currently used in Japan.

Salmonella/microsome tests (Ames tests) and chromosomal aberration tests in vitro using a Chinese hamster fibroblast cell line were carried out on 190 synthetic food additives and 52 food additives derived from natural sources, all of which are currently used in Japan. Fourteen out of 200 tested in the Ames assay showed positive effects and 54 out of 242 were positive in the chromosome test. Three additives (erythorbic acid, chlorine dioxide and beet red) were positive only in the Ames test, although their mutagenic potentials were relatively weak, while 43 additives were positive only in the chromosome test. Eleven additives (calcium hypochlorite, cinnamic aldehyde, L-cysteine monohydrochloride, Food Green No. 3 (Fast Green FCF), hydrogen peroxide, potassium bromate, sodium chlorite, sodium hypochlorite, sodium nitrite, cacao pigment and caramel) were positive in both the Ames test and the chromosome test. The usefulness of such primary screening tests combining two different genetic end-points, gene mutation and chromosomal aberration, and some correlation between mutagenicity and carcinogenicity of food additives are discussed.

Animals↗

Artificial food additive intolerance in patients with angio-oedema and urticaria.

43 children who presented with angio-oedema and/or urticaria and who responded to an additive-free diet were challenged with artificial food additives in a double-blind study. 24 children reacted to 1 or more of the additives. 18 children did not react to any additives and remained well when a normal diet was re-introduced. Aspirin sensitivity was found in only 1 of the 24 children who could not tolerate additives. Atopy was less common in these patients than in the general population. The mechanism of additive intolerance is unknown and double-blind challenge is the only reliable means of diagnosis.

Adolescent↗

Analytical methods for food-contact materials additives in olive oil simulant at sub-mg kg-1 level.

Methods of analysis for four additives (two antioxidants, IRGANOX 245 and 1035; an ultraviolet absorber, CHIMMASORB 81; and an optical brightening agent, UVITEX OB) in olive oil are reported. These additives have the potential to migrate from food-contact materials into the European Union fatty food simulant olive oil, which is the most difficult matrix for analysis. The additives were chosen because they differed in their chemically active groups, had different functions within the polymer, have low proposed specific migration limits and are commonly used in food-contact materials such as polystyrenes and polyolefins. The proposed analytical methods for the additives are simple, rapid, inexpensive and also broadly applicable to the aqueous food simulants. All methods were evaluated by constructing calibration curves, measurement of recovery and precision, and determining the limits of detection. Most of the methods involve direct injection of an olive oil solution for high-performance liquid chromatography analysis with ultraviolet-visible or fluorescence detection. The methods allowed establishment of additive stability and measurement of migration of the selected additives into olive oil at different time-temperature conditions used in migration studies into food simulants.

Antioxidants↗

Identification of two additives, locust bean gum (E-410) and guar gum (E-412), in food products by DNA-based methods.

Locust bean gum (E-410) and guar gum (E-412) are high molecular weight galactomannans used by the food industry as versatile food additives. The compounds, although chemically closely related, do not have the same functional properties when used in foods, and the substitution or unadvertised addition of either could change the desired qualities of the product. Analytical discrimination between E-410 and E-412 is technically difficult since they only differ in their galactose: mannose ratios, being 1 : 4 and 1 : 2 for locust bean gum and guar gum, respectively. A qualitative DNA-based method is reported for the authentication of additives E-410 and E-412 in finished food products (ice cream, dehydrated desserts, milk derivatives, dehydrated soups, salad dressing, marmalade and meat) from small quantities of food. DNA sequences from the nuclear ribosomal spacers of Ceratonia siliqua and Cyamopsis tetragonoloba, the plant sources of E-410 and E-412, respectively, were used to design polymerase chain reaction primers specific for each additive (PA23/PA21 and PG22/PG21). Twenty-two foods were analysed for the presence of E-410 and E-412 additives by this single-step polymerase chain reaction-based method. Positive DNA amplifications with the E-410 and/or E-412 primers were obtained in all 19 samples reported to contain either additive.

Animals↗