Influence of the glass packing on the contamination of pharmaceutical products by aluminium. Part III: Interaction container-chemicals during the heating for sterilisation

The interaction of chemicals with the container materials during heating for sterilisation was investigated, storing the components of parenteral nutrition solutions individually in sealed glass ampoules and in contact with a rubber stopper, and heating the system at 121 degrees C for 30 min. Subsequently, the aluminium content of the solutions was measured by atomic absorption spectrometry (AAS). The assay was also carried out with acids, alkalis and some complexing agents for Al. The containers were decomposed and also assayed for aluminium. 30 different commercial solutions for parenteral nutrition, stored either in glass or in plastic containers, were assayed measuring the aluminium present in the solutions and in the container materials. The results of all investigated container materials revealed an aluminium content of 1.57% Al in glass, 0.05% in plastic and 4.54% in rubber. The sterilisation procedure showed that even pure water was able to extract Al from glass and rubber, 22.5 +/- 13.3 microg/L and 79.4 +/- 22.7 microg/L respectively, while from plastic the aluminium leached was insignificant. The Al released from glass ampoules laid between 20 microg/L for leucine, ornithine and lysine solutions and 1500 microg/L for solutions of basic phosphates and bicarbonate; from rubber stoppers it reached levels over 500 microg/L for cysteine, aspartic acid, glutamic acid and cystine solutions. Ion-exchange properties and influence of pH can explain the interaction of glass with some chemicals (salts, acids and alkalis), but only an affinity for aluminium could explain the action of some amino acids and other chemicals, as albumin and heparin, on glass and rubber, considering the aluminium release. Experiments with complexing agents for Al allowed to conclude that the higher the stability constant of the complex, the higher the Al release from the container material.     

Influence of the glass packing on the contamination of pharmaceutical products by aluminum. Part I: Salts, glucose, heparin and albumin

The presence of aluminium (Al) in pharmaceutical products used parenterally as sodium and potassium chlorides, glucose, heparin and albumin were investigated with respect to their storage in glass containers. As glasses can have aluminium in their composition, the aluminium may be released from the glass into the solution. The action of the substances above mentioned were investigated storing their solutions in glass and plastic containers, and measuring the aluminium in solution at determined time intervals. The aluminium present in the commercial pharmaceutical products, stored in both plastic and glass containers were also measured. All glass containers were analysed to determine their aluminium content. The aluminium determinations were done by atomic absorption spectrometry. The results showed that aluminium is present in all analysed glasses in a percentage of 0.6 to 3%. Although all substances already have a residual aluminium contamination, the major contribution comes from the glass containers in which their solutions were stored. The contamination arising from glass depends too much on the nature of the substance. While the salts extracted about 400 μg Al/l in 60 days, glucose extracted 150 μg Al/l, and albumin and heparin about 500 μg Al/l in the same time interval. Commercial solutions of glucose contain about 10 μg Al/l when stored in polyethylene and from 350 to 1000 μg Al/l when in glass ampules. Considering all commercial products, solutions stored in plastic containers contained no more than 20 μg Al/l whereas in glass the aluminium contamination reached 1000 μg/l, and in all of them the aluminium increases with the age of the product.     

Influence of the glass packing on the contamination of pharmaceutical products by aluminium. Part I: salts, glucose, heparin and albumin.

The presence of aluminium (Al) in pharmaceutical products used parenterally as sodium and potassium chlorides, glucose, heparin and albumin were investigated with respect to their storage in glass containers. As glasses can have aluminium in their composition, the aluminium may be released from the glass into the solution. The action of the substances above mentioned were investigated storing their solutions in glass and plastic containers, and measuring the aluminium in solution at determined time intervals. The aluminium present in the commercial pharmaceutical products, stored in both plastic and glass containers were also measured. All glass containers were analysed to determine their aluminium content. The aluminium determinations were done by atomic absorption spectrometry. The resuLts showed that aluminium is present in all analysed glasses in a percentage of 0.6 to 3%. Although all substances already have a residual aluminium contamination, the major contribution comes from the glass containers in which their solutions were stored. The contamination arising from glass depends too much on the nature of the substance. While the salts extracted about 400 microg Al/l in 60 days, glucose extracted 150 microg Al/l, and albumin and heparin about 500 microg Al/l in the same time interval. Commercial solutions of glucose contain about 10 microg Al/l when stored in polyethylene and from 350 to 1,000 microg Al/l when in glass ampules. Considering all commercial products, solutions stored in plastic containers contained no more than 20 microg Al/l whereas in glass the aluminium contamination reached 1,000 microg/l, and in all of them the aluminium increases with the age of the product.     

Effect of aluminium on the mineral nutrition of rice

A study of the effect of increasing aluminium concentration in a dilute nutrient solution on various aspects of the mineral nutrient uptake by the rice plant has shown that aluminium exerts a stimulation on dry matter production and nutrient uptake until a concentration threshold was reached. The value of this threshold was influenced by nutrient solution composition and cultivar. Its location could be calculated by adjusting to the experimental points a rate law from enzyme kinetics on substrate inhibition curve. On the other hand, total uptake of aluminium and its concentration in the tops was a monotonic function of aluminium concentration in the nutrient solution, the effect of which was greatly enhanced by increased phosphate concentration. A sensitive cultivar accumulated more aluminium than a resistant one.The effect of phosphate on the alleviation of aluminium toxicity was slight in the range of concentration studied.Nitrogen uptake either as ammonium or nitrate nitrogen was clearly influenced by aluminium concentration when its instantaneous value was measured by the technique of the continuously flowing culture solution. The ammonium uptake rate of two cultivars different in sensitivity to aluminium was such that the sensitive variety took up less ammonium and acidified less the culture solution flowing through the root sysstem with a residence time of a few hours.Minor elements concentration in the tops of the rice plants did not seem to be greatly influenced by aluminium with the notable exception of manganese, the uptake of which was clearly depressed by increasing aluminium concentration.Attempts were made at using the speciation of the nutrient solutions with or without aluminium complexation by fluoride in order to rank the various ionic forms of aluminium according to their toxicity. It seems that the well-known result of primary toxicity due to the free Al-ion is also true for rice but that some toxicity is associated with the AlSO₄-ion.     

Changes with aging in the levels of amino acids in rat CNS structural elements II. Taurine and small neutral amino acids

Taurine (Tau) and the small neutral amino acids glycine (Gly), serine (Ser), threonine (Thr), and alanine (Ala) were measured in 53 brain areas of 3- and 29-month-old male Fisher 344 rats. The ratio of highest to lowest level was 34 for Tau, 9.1 for Thr, 7.6 for Gly and Ser, and 6.5 for Ala. The heterogeneity was found in numerous areas; for example, Tau levels were more than 90 nmol/mg protein in 6 areas, and less than 20 nmol/mg protein in 10 areas. Similar heterogeneity was found with the other amino acids. The relative distribution of the small neutral amino acids showed several similarities; Tau distribution was different. With age, four amino acids decreased in 10–18 areas, and increased in only 1–3, while Thr increased in more areas than it decreased. The five amino acids of this paper, and the four of the previous paper, are among the amino acids at highest level in the brain; the sequence in their levels shows considerable regional heterogeneity.     

The effect of total parenteral nutrition in the rat on a sub-group of enteroendocrine cells

The effect of total parenteral nutrition (TPN) in rats on a number of enteroendocrine cells was investigated. The rats were given a continuous intravenous infusion of basal TPN solution for 7 days. Samples from duodenum, jejunum and ileum were collected, immunostained and the immunoreactive cells quantified using a computerised morphometrics system. The endocrine cells containing somatostatin, cholecystokinin (CCK), gastric inhibitory polypeptide (GIP), neurotensin and enteroglucagon were investigated. The results demonstrated a significant reduction in the number of CCK cells in the duodenum and jejunum. In the ileum the neurotensin-immunoreactive cells were significantly increased in number (P less than 0.02). No change was seen in the number of cells immunostained for somatostatin, GIP or enteroglucagon. These data indicate that short term TPN has a definite effect on the enteroendocrine cell population which may be linked to the side effects of TPN seen in man.     

Effects of sow nutrition during gestation on within-litter birth weight variation: a review

The increasing demand for efficiency in pork production requires great specialization of all sectors involved in this activity. In this context, the development of strategies that could reduce undesirable traits related with negative effects on piglet survival and postnatal growth and development are essential for the pig industry. Currently, special attention is given to variation in birth weight, as some evidences suggest an increased within-litter birth weight variation in modern sows. This variation has been shown to be associated with preweaning mortality, variable weights at weaning and deteriorated growth performance, which results in economic losses and lower efficiency. Therefore, understanding the factors that can influence the events that occur during gestation and that have an impact on the fetal growth and development are important to achieve better efficiency and also to develop strategies that can be used to achieve increased within-litter uniformity of piglet birth weight. This study concludes that even at a given placental size, fetal growth may vary because of differences in placental vascularization and efficiency. Feeding extra feed or energy during late gestation only marginally improves birth weight, and positive effects are not consistent between different studies. The detrimental effects of protein restriction on fetal growth during early gestation may be due to altered placental and endometrial angiogenesis and growth, which leads to a reduction in placental-fetal blood flow, nutrient supply from mother to the fetuses and ultimately to fetal growth retardation. The number of studies that attempted to influence within-litter birth weight variation by means of sow nutrition during gestation is limited. Therefore, more research concerning sow nutrition during gestation associated with the provision of balanced diets to meet requirements of the sows and fetuses are still required. This knowledge may subsequently provide starting points for the design of nutritional strategies that can influence within-litter birth variation.     

Nutritive effects of d-amino acids on the silkworm, Bombyx mori

Nutritive effects of d-amino acids on the silkworm, Bombyx mori, were investigated by growth experiments using defined diets and also by analysis of free amino acids in the larval haemolymph. None of the d-forms of the usual ten essential amino acids could be utilized effectively, although d-methionine was utilized in lieu of the l-form only to a limited extent and d-histidine gave a positive but smaller effect than d-methionine. d-Proline, its l-form being semi-essential for the silkworm, was not utilized. d-Leucine, and to a lesser extent d-alanine and d-serine, were found to be somewhat toxic. Comparison of free amino acid patterns in the haemolymph of the fifth-instar larvae, which fed on diets either lacking l-forms of histidine, methionine and leucine singly or including the d-forms singly in place of these l-forms, supported the results of the growth experiments.     

Elevated serum chromium in patients on total parenteral nutrition and the ionic species of contaminant chromium

Chromium (Cr), an essential micronutrient required for glucose metabolism, was found in high concentrations in up to 94% of the patients on short-term total parenteral nutrition. Approximately 50% had serum levels >10-fold of normal (upper reference value of 3.8 nmol/L), about 18% were >20-fold, and about 2% were 40-fold higher. The major Cr contaminant was detected in the amino acid constituents, and was found to have the trivalent ionic form. Although trivalent Cr is reported to be less genotoxic, further study is required to determine the effects on cells exposed to high concentrations of this element during parenteral nutrition over an extended period of time.     

不同营养治疗途径对重症急性胰腺炎大鼠血浆氨基酸谱和电解质的影响

目的比较不同配方肠内营养(EN)和肠外营养(PN)制剂对重症急性胰腺炎(SAP)大鼠血浆氨基酸谱和电解质水平的影响。方法建立大鼠SAP模型,根据SAP营养代谢配制专用EN配方(EN-S)和含益生元(PRE)的EN配方(RPE-EN)。40只大鼠随机分为正常对照组(A组)、SAP+EN-S组(B组)、SAP+PRE-EN组(C组)、SAP+商品EN组(D组)和SAP+PN组(E组),营养治疗持续7 d,检测血浆氨基酸谱和电解质水平。结果B~E组主要氨基酸和总氨基酸水平显著低于A组(P<0.05),D组天门冬氨酸、蛋氨酸和赖氨酸水平显著低于B组(P<0.05)和C组,而谷氨酸、精氨酸、丙氨酸和苯丙氨酸显著低于C组(P<0.05),低于B组但无显著性差异;B~E组血清铁显著低于A组(P<0.05),D组的血清铁显著低于C组(P<0.05),除C组外,其余各组的血浆钠显著低于A组。结论EN-S配方在提高某些氨基酸水平上作用优于商品EN;含PRE微生态营养制剂具有改善蛋白质代谢和电解质平衡的作用;短期应用EN和PN对SAP动物蛋白质代谢和电解质平衡作用无显著性差异。     

A simplified management of the in situ evaluation of feedstuffs in ruminants: Application to the study of the digestive availability of protein and amino acids corrected for the ruminal microbial contamination

The ruminal effective degradability (RED) and intestinal effective digestibility (IED) for dry matter, crude protein (CP) and amino acids (AA) were estimated by a simplified in situ method using pooled samples from rumen-incubated residues, which represented the ruminal outflow of undegraded feed. The effect of microbial contamination in the rumen was corrected using ¹⁵N infusion techniques. Studies were carried out for soybean meal (SBM), barley grain (BG) and lucerne hay (LH) in three wethers cannulated in the rumen and the duodenum. Uncorrected values of RED for CP obtained either by mathematical integration or our simplified method were similar in all feeds. Microbial N in the pooled samples of SBM, BG and LH were 2%, 11% and 24% of total N, respectively. However, intestinal incubation eliminated this microbial charge by 100%, 99% and 88%, respectively. With microbial corrections, RED showed an increase, and IED showed a decrease, except for SBM. With this correction, intestinal digested CP was reduced by 2% in SBM, 13% in BG and 34% in LH. Corrected IED of AA was relatively similar in SBM (97–99%). However, large variations were observed in BG (74–93%) and in LH (10–88%). Digestion in the rumen and intestine changed the essential AA pattern. Overall, our results support that AA digestion is affected by the characteristics of their radicals and their contents in plant cell wall proteins. The accurate estimation of feed metabolisable AA or protein requires effective measures that are corrected by ruminal microbial contamination. The proposed in situ method largely simplifies these tasks and allows a more complete and less expensive feed evaluation.     

Influx and efflux of amino acids from Zea mays L. roots and their implications for N nutrition and the rhizosphere

The aim of the study was to investigate the ability of Zea mays L. roots to regulate the amount of free amino acids present in the rhizosphere. The active uptake of amino acids was shown to conform to Michaelis-Menten kinetics. Comparison of amino acid-N and NO₃-N kinetic parameters and soil solution concentrations showed that root uptake of free amino acids from soil may contribute significantly to a plant's N budget. The influx of amino acids also helps to minimize net C/N losses to the soil, and is therefore important in regulating the size of the rhizosphere microbial population. Experimental data and a computer simulation model of amino acid influx/efflux in a sterile solution culture, showed that roots were capable of re-sorping over 90% of the amino acids previously lost into solution as a result of passive diffusion.     

Influence of the nitrogen source and concentration on N fractions and free amino acid levels of grape vine explants

The influence of the source of inorganic nitrogen (KNO₃, (NH₄)₂SO₄ and NH₄NO₃) and its concentration (5, 10, 20 and 30 mM N) on total N incorporation, as well as on N distribution into different fractions (amminiacal, amino, amide and protein) and on free amino acid levels has been determined in grape vine explants cultured in vitro.Increasing concentrations of the nitrogen source resulted in increased total N content in tissues. This effect was small for KNO₃, higher for (NH₄)₂SO₄ and maximal for NH₄NO₃. In addition, nitrate promoted an increase in amino-N only, whereas ammonium increased both the ammoniacal-N and the amino-N fractions. Incorporation of N into amide-N and protein-N were not affected significantly by the N sources tested.The application of increasing quantities of N enhanced the accumulation of most free amino acids, especially arginine, alanine and proline, but to different extents, depending on both the N source and its concentration. The combination of ammonium and nitrate resulted in a higher accumulation of amino acids than that observed with either one of the two forms alone.     

HPLC法分析乳清蛋白对糖尿病模型小鼠血浆氨基酸组分的影响

为寻求有效的氨基酸分离方法并探讨乳清蛋白对2型糖尿病防治的作用机制,采用HPLC法分析乳清蛋白中氨基酸组分及含量;分别以0％、10％、20％和40％的乳清蛋白(WP)灌胃1型、2型糖尿病模型组、正常组小鼠,4周后观察各组血浆氨基酸的变化.乳清蛋白中亮氨酸、异亮氨酸、缬氨酸分别占氨基酸总量的14.40％、5.93％和5....     

Significance of magnetic resonance image and blood manganese measurement for the assessment of brain manganese during total parenteral nutrition in rats

In this study, we report on the influence of trace elements (TE) on signal intensities of nuclear magnetic resonance images (MRI), both in vivo and in vitro. Optimal parameters for the assessment of Mn concentration in the brain of rats on total parenteral nutrition were established. For the in vitro study, Mn and trace element solutions, one containing Zn, Cu, Fe, and I (TE-4) and another containing the above elements plus Mn (TE-5), were diluted with physiological saline or with rat brain homogenate and used to measure signal intensities in MRI. Concentration-dependent signal hyperintensity was observed in both cases in the Mn and the TE-5 solutions, but no effect was observed with the TE-4 solution. The signal increase was greater for brain tissue homogenates. In the in vivo study, the experimental animals were maintained under total parenteral nutrition (TPN) with a standard clinical dose of TE-5 and/or with 10-fold the clinical dose of TE-4 and TE-5 for 1 wk. Only rats that were receiving the increased TE-5 dose showed signal hyperintensity on MRI. Positive correlations were observed among the signal hyperintensity, the blood Mn concentrations, and that of the rat brain. Our results suggest that Mn in TE preparations may be the cause of signal hyperintensity on MRI in a concentration-dependent fashion, and that MRI and measurement of blood Mn may be used to estimate Mn accumulation in brain tissue.     

早产儿住院期间输注高剂量氨基酸对其营养状况的改善效果

为了探讨早期输注高剂量氨基酸对早产儿营养状况的影响,本研究选取我院2013年2月～2014年2月收治的120例早产儿,分为三组按不同剂量进行静脉氨基酸营养治疗,观察相关的身体指标、营养指标和生理指标。结果显示,高剂量组早产儿的日平均体质量增长量、周平均身长增长量、周平均头围增长量、周平均上臂围增长量明显高于中、低剂量组,（p＜0．05）;高剂量组早产儿平均体重下百分比、平均恢复出生体质量天数、平均静脉营养天数、平均住院天数均明显低于中、低剂量组,（p ＜0．05）;治疗第7日时高剂量组的尿素（BUN）水平明显高于中、低剂量组（p ＜0．05）,而三组间血肌酐（SCr）、直接胆红素（DBIL）、pH 值的差异无统计学意义（p ＞0．05）;高剂量组的免疫水平各项指标均显著优于其他两组（p ＜0．05）。本研究表明,高剂量氨基酸输注可以更好地改善早产儿的营养状况。     

Surface transformation of bioactive glass in bioreactors simulating microgravity conditions. Part II: numerical simulations

The effects of simulated microgravity on the surface modification of bioactive glass (BG) in solution were studied using a numerical method. Models were developed for estimating the mass transfers of different chemical species from the surface of bioactive glass particles (microcarriers) suspended in the rotating liquid medium of a NASA-designed high aspect ratio vessel (HARV) bioreactor and on the bottom surface of a static vial. The concentration profiles resulting from chemical reactions and ionic transports were ascertained. Numerical results for the transport under simulated microgravity in the HARV and at normal gravity in the static vial were compared. These results were also compared with those of experiments to verify the enhancement of the reaction kinetics under simulated microgravity conditions. The experimental and numerical studies confirm that simulated microgravity conditions lead to the quick achievement of bioactive glass surface modification.     

Studies on the mechanism of induction of hypercholesterolemia in rabbits by high dietary levels of amino acids

Increasing the proportion of an amino acid mixture corresponding to casein in a low-fat, cholesterol-free, semipurified diet fed to rabbits causes a progressive increase in serum total and low density lipoprotein cholesterol, and the effect appears to be due primarily to the essential amino acids in the mixture. Our recent studies have also shown that the variations in serum cholesterol in response to different levels of the amino acid mixture are not associated with any changes in fecal excretion of cholesterol or bile acids. Further attempts to understand the mechanism of action of dietary amino acids on serum cholesterol levels have shown the following: (1) no correlation with levels of plasma amino acids, either in the fasting or postprandial state: (2) no correlation with serum levels of thyroid hormones: (3) no relationship to activity of hepatic or intestinal microsomal hydroxymethylglutaryl coenzyme A reductase: (4) no corresponding effects on the activities of cholesterol esterifying enzymes of intestinal mucosa: and (5) no correlation with the degree of esterification of cholesterol in very low or low density lipoproteins. Further studies are required to identify the specific amino acids responsible for the hypercholesterolemic effects and to determine the mechanisms involved.