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Stability of nizatidine in total nutrient admixtures.

The stability of nizatidine in total nutrient admixtures (TNAs) and the effect of the drug on the stability of lipid emulsions in the TNAs were studied. Duplicate 1476-mL amino acid-dextrose base solutions were prepared; nizatidine 300 mg was added to one. TNAs were prepared by adding to 75-mL samples of the base solutions Intralipid (KabiVitrum) or Liposyn II (Abbott) and sterile water as needed to achieve final lipid concentrations of 3% and 5%. Triplicate 100-mL samples for each lipid product and concentration were prepared; fat-free samples containing nizatidine were also studied. The theoretical final nizatidine concentration was 150 micrograms/mL. Samples were stored at 22 degrees C for 48 hours. Initially and at 12, 24, and 48 hours, the samples were visually inspected, tested for pH and particle-size distribution, and assayed by high-performance liquid chromatography for nizatidine concentration. No color change, precipitation, creaming, or oiling out was noted. For the 12 TNAs containing nizatidine, mean solution pH during the study was 5.88; stability of the lipid products requires pH values greater than or equal to 5.5. Particle-size distribution did not differ appreciably between the nizatidine-containing and drug-free TNAs. Nizatidine concentrations remained greater than 90% of the initial concentration. Nizatidine at a theoretical concentration of 150 micrograms/mL was stable for 48 hours at 22 degrees C in TNA solutions containing 3% and 5% Intralipid or Liposyn II and did not appear to affect lipid emulsion stability.

Chromatography, High Pressure Liquid↗

[Spectral control of metal admixtures in tetracycline].

Analysis of circular dichroism spectra made it possible to offer a method for estimation of tetracycline solutions contamination with metal ions. By its sensitivity the method is much superior to the spectrophotometric one used at present for determination of the antibiotic purity. In the latter method formation of complexes with metals is traced by batochromic displacement of the absorption spectra. The new method is rapid, relatively selective and requires comparatively small quantities of the substance for the analysis, which provides its use under both laboratory and manufacture conditions. The method is based on identification of the circular dichroism spectra of tetracycline complexes with metals in the long wavelength region. The presence of the circular dichroism concervative bands with strictly defined extremums in the spectra of tetracycline low acid solutions contaminated by multiply charged metal ions allowed vs. the circular dichroism spectra of pure tetracycline sample to conclude that the solution contained admixtures and to suggest their nature. It was shown that the charge, ion radius and tetracycline:metal relation were the factors defining the mark and location of the dichroism band extremums. At lambda(extr)-410-415 nm the tetracycline complexes with light metal ions such as Mg2+, Al3+ and Ca2+ were detected by the circular dichroism negative band in the spectra, while the complexes with heavy metal ions such as Sc3+, Sr3+, Cu3+, Cd3+, Ba2+, Y3+ and the cerium subgroup lanthanides were detected by the circular dichroism positive band. The tetracycline complexes with the lanthanides of the second half of the yttrium subgroup (Ho(3+)-Lu3+) were characterized by the presence of the circular dichroism minimum at lambda(min)-425 nm. When the tetracycline concentration was above 1.5 x 10(-3) M, multiligand complexes with circular dichroism negative extremum at lambda(min)-400 nm formed.

Circular Dichroism↗

Multilocus analyses of admixture and introgression among hybridizing Heliconius butterflies.

Introgressive hybridization is an important evolutionary process and new analytical methods provide substantial power to detect and quantify it. In this study we use variation in the frequency of 657 AFLP fragments and DNA sequence variation from 15 genes to measure the extent of admixture and the direction of interspecific gene flow among three Heliconius butterfly species that diverged recently as a result of natural selection for Miillerian mimicry, and which continue to hybridize. Bayesian clustering based on AFLP genotypes correctly delineated the three species and identified four H. cydno, three H. pachinus, and three H. melpomene individuals that were of mixed ancestry. Gene genealogies revealed substantial shared DNA sequence variation among all three species and coalescent simulations based on the Isolation with Migration (IM) model pointed to interspecific gene flow as its cause. The IM simulations further indicated that interspecific gene flow was significantly asymmetrical, with greater gene flow from H. pachinus into H. cydno (2Nm = 4.326) than the reverse (2Nm = 0.502), and unidirectional gene flow from H. cydno and H. pachinus into H. melpomene (2Nm = 0.294 and 0.252, respectively). These asymmetries are in the directions expected based on the genetics of wing patterning and the probability that hybrids of various phenotypes will survive and reproduce in different mimetic environments. This empirical demonstration of extensive interspecific gene flow is in contrast to a previous study which found little evidence of gene flow between another pair of hybridizing Heliconius species, H. himera and H. erato, and it highlights the critical role of natural selection in maintaining species diversity. Furthermore, these results lend support to the hypotheses that phenotypic diversification in the genus Heliconius has been fueled by introgressive hybridization and that reinforcement has driven the evolution of assortative mate preferences.

Animals↗

Sterility testing of a total nutrient admixture with a biphasic blood-culture system.

The ability of a biphasic blood-culture system to detect microbial contamination of a total nutrient admixture (TNA) was studied. A TNA consisting of amino acids, dextrose, lipid emulsion, electrolytes, and trace elements was prepared under aseptic conditions. Septi-Chek blood-culture bottles were then injected with a TNA sample and with one of various dilutions of five bacterial or fungal suspensions, and an agar slide unit was attached to each bottle. One bottle was injected only with a TNA sample. The bottles were incubated and examined once daily. Each bottle was inverted immediately after inoculation and at each observation time to allow the broth to wash over the agar slide unit. Because the lipid contained in the TNA caused the broth in all bottles to become turbid, it was impossible to determine whether microbial growth was present in the broth. Microbial growth, however, became evident in 24-72 hours on all slide units except the one attached to the bottle that had been injected only with TNA. The Septi-Chek biphasic blood-culture system appears to be useful in evaluating the sterility of TNAs.

Bacteria↗

Activity of octreotide acetate in a total nutrient admixture.

The activity of octreotide acetate in a total nutrient admixture (TNA) and the effect of the drug on the stability of lipid emulsion in the TNA were studied. Octreotide acetate injection was added to a standard solution containing 3% lipids, amino acids, dextrose, electrolytes, vitamins, and trace elements to achieve a theoretical concentration of 45 micrograms/dL. Samples were stored at room temperature for 48 hours. Octreotide concentrations were determined in triplicate by radioimmunoassay; physical stability of the solutions was assessed by lipid particle-size determination, pH measurement, and visual observation of emulsion integrity at 0, 12, 24, and 48 hours. The activity of octreotide in two samples of each solution (with and without lipid) was analyzed immediately after preparation and after seven days under refrigeration. There was no evidence of emulsion breakdown or pH change in any solution over the study period. In addition, particle-size distributions at 48 hours and 7 days were comparable to those at time zero, suggesting physical stability. Octreotide acetate activity was not consistently greater than 90% (mean +/- S.D.) after storage for 48 hours. Octreotide acetate at a theoretical concentration of 45 micrograms/dL in a TNA solution containing 3% lipids appeared to be physically compatible for 48 hours at room temperature and for 7 days under refrigeration. However, the chemical activity of octreotide in TNA was not consistent after storage for 48 hours.

Chemical Phenomena↗

Factor VIII:C, ABO blood groups, and black admixture in a Brazilian sample.

The effects of ABO blood groups and black admixture on the level of factor VIII:C are studied in healthy adults from Salvador, Bahia, Brazil. A racially mixed sample of 125 males was selected as follows: 25 whites, 25 light mulattoes, 25 medium mulattoes, 25 dark mulattoes, and 25 blacks. Levels of both factor VIII:C and K-PTT followed normal distributions. O blood group subjects showed lower factor VIII:C levels (110.20 +/- 30.76%) than non-O blood group members (135.24 +/- 31.42%) (t123 = 4.47; p less than 0.0001) and higher K-PTT levels (37.69 +/- 4.57 s) than non-O blood group subjects (35.25 +/- 3.82 s) (t123 = 3.24; p less than 0.01). By holding ABO blood type constant, there is a significant racial effect (white) on lowering the factor VIII:C level within both blood group O (t43 = 2.23; p less than 0.05) and non-O (t36 = 3.44; p less than 0.002). There is no interaction effect of race and blood group (F = 0.19; p greater than 0.6) on the factor VIII:C levels.

ABO Blood-Group System↗

Rapid admixture blood warming.

A new technique of admixture blood warming allows rapid warming of packed red blood cells by the addition of heated saline. Each 4 degrees C unit of packed red blood cells is mixed with 250 ml of 70 degrees C saline. Diluted blood at 37 degrees C is ready for transfusion in less than 30 seconds.

Blood Transfusion↗

Clinical use of total nutritional admixtures.

The administration of a single mixture of the components of total parenteral nutrition (TPN) constitutes total nutritional admixture (TNA), the safety and efficacy of which in a variety of clinical settings have been confirmed by controlled trials. According to the nitrogen balance and stable isotope methods, TNA is as efficacious as the old system of three bottles with piggyback intravenous fat emulsion in maintaining body nitrogen mass, visceral protein, and liver function. Also, serum concentrations of electrolytes, trace elements, and vitamins can be maintained adequately using the TNA system. The other advantages are the timesaving to the nursing staff, with its hidden savings in cost; the avoidance of a peripheral catheter solely for the infusion of lipid emulsion in addition to the central catheter for TPN in hospitalized patients; and the facility of use in home nutrition programs. The ease of home use has resulted in a greater degree of patient compliance; thus patients receive a mixed-fuel system while avoiding the hazards of a piggyback infusion, with all its potential complications. Among the perceived disadvantages of TNA are a supposed higher frequency of catheter-related sepsis, a view based on in vitro studies that is not borne out by in vivo studies; catheter occlusion by precipitation of calcium salts; and enhanced ability to clear fat and thus fat tolerance with continuous infusion of lipids. Numerous studies have shown that these concerns are unwarranted.

Bacteria↗

[Pest control and yield increase of areca by root-zone application of carbofuran in admixture with fertilizers].

The result of our experiment has shown that by root-zone application of carbofuran in admixture with fertilizers to Areca in spring the serious pest Tirathaba rufivena can be controlled for 4 months during flowering and young fruiting stage and the yield can increase by 50%. The final residual amount of carbofuran in fruits is below 0.1-0.01 ppm or too low to be examined, and there is no decrease in total alkaloid content in fruits.

Alkaloids↗

Gene frequencies and admixture estimates in four Mexican urban centers.

We studied 202 individuals from the city of Leon in Guanajuato state, 228 from Merida, Yucatan, 220 from Oaxaca, Oaxaca, and 257 from Saltillo, Coahuila, to learn the distribution of the ABO, MN, Rh, and Duffy blood groups, serum haptoglobin, albumin, and factor Bf types, and red cell hemoglobin and glucose-6-phosphate dehydrogenase types. With the gene frequencies obtained, we performed admixture measurements with a maximum likelihood method, obtaining a trihybrid model for black, Indian, and white ancestry with the following proportions: 0.084, 0.513, and 0.403 in Leon: 0.059, 0.512, and 0.429 in Merida; 0.018, 0.676, and 0.306 in Oaxaca; and 0.073, 0.547, and 0.380 in Saltillo. The general pattern has high Indian ancestry followed by white and black ancestry. This pattern is congruent with most other studies performed in Mexico, including the east coast, where Indian ancestry predominates despite a clear increase in the black contribution.

Blood Group Antigens↗

[Intrapulmonary venous admixture during open heart surgery].

Monitor-computer study of changes in the ventilatory parameters, hemodynamics, gas exchange has shown that assisted circulation in patients operated on for acquired heart valve defects causes in the postperfusion period a 2-fold increase in intrapulmonary venous admixture (Qs/Qt), which accompanied an increase in alveolar-arterial difference (pO2) and a fall in arterial blood pO2. An increase in Qs/Qt upon assisted circulation is associated with a decrease in ventilation/perfusion pulmonary ratio and possible deterioration of diffuse processes due to hemodilution-induced water balance disturbances. Controlled lung ventilation with positive end respiratory pressure (5-8 cm H2O) partially decreases intrapulmonary shunting and improves arterial blood oxygenation. Positive effect, i. e. improved oxygenating lung capacity and decreased intrapulmonary shunting is achieved with water balance normalization due to early administration of diuretics upon assisted circulation.

Cardiac Surgical Procedures↗

Physical stability of a total nutrient admixture for total parenteral nutrition.

The stability of a total nutrient admixture (TNA) has been postulated to be less than 7 days in refrigerated storage. When a TNA destabilizes, lipid particles coalesce and enlarge. Liposomes larger than 6 microns can obstruct pulmonary capillaries. A TNA containing 1500 ml of 7% Vamin, 1000 ml of 50% dextrose and 500 ml of 10% Intralipid, including the usual electrolytes, minerals and vitamins, was studied. Liposome size was measured in the original Intralipid and the TNA at intervals up to 14 days at 4 degrees C followed by 2 days at 22 degrees C. There was a small increase in liposome size up to 16 days. However, the number of particles larger than 6 microns was insignificant (by light microscopy, 3.9 +/- 2.4 [+/- SD] per 20 high-power fields; by Coulter counter, 99.8% smaller than 1.9 microns, with 0% larger than 6 microns; and by electron microscopy, 100% smaller than 2.0 microns). The osmolality and pH of the TNA were 1472 +/- 31 mOsm/kg and 5.5 +/- 0.1 respectively (mean +/- SD), with no significant change during the study times. The authors concluded that this TNA remains physically stable when refrigerated for 14 days and at room temperature for a further 2 days.

Amino Acids↗

Stability of famotidine 20 and 50 mg/L in total nutrient admixtures.

The stability of famotidine in total nutrient admixtures (TNAs) containing dextrose, an intravenous fat emulsion (IVF), and high or low concentrations of amino acids was studied. Famotidine was added to TNA solutions to final concentrations of 20 and 50 mg/L. TNA 1 contained 20% dextrose, IVF 40 g/L, and amino acids 42.5 g/L, and TNA 2 contained 25% dextrose, IVF 25 g/L, and amino acids 21.25 g/L. Control solutions of TNAs 1 and 2 without famotidine were also studied. All solutions were stored at 4 degrees C for 24 hours and then at 20-22 degrees C for 24 hours. The solutions were observed for signs of creaming or coalescence and measured for pH, famotidine concentration, and particle size at 0, 24, and 48 hours. No signs of creaming or coalescence were observed in control or test solutions throughout the study period. Famotidine in TNAs 1 and 2 showed a less than 5% change in concentration over the 48-hour period. Neither time nor amino acid concentration had any significant effect on famotidine concentration. Similarly, there were no significant differences in emulsion particle size between control solutions and TNAs containing famotidine and no significant changes in particle size over time. Famotidine 20 and 50 mg/L is stable in the TNAs tested when stored at 4 degrees C for 24 hours and then at 20-22 degrees C for 24 hours. Famotidine did not appear to disrupt the integrity of the emulsion system.

Chromatography, High Pressure Liquid↗

Stability of famotidine 20 and 40 mg/L in total nutrient admixtures.

The stability of famotidine in two types of total nutrient admixtures (TNAs), one containing 5% intravenous fat emulsion of long-chain triglycerides and the other, of medium- and long-chain triglycerides, was studied. The TNAs, which contained lipids, glucose, amino acids, electrolytes, vitamins, and trace elements, were prepared aseptically in ethylene-vinyl acetate containers. Famotidine 40 mg was added to both types of TNAs and famotidine 80 mg was added to both types to yield concentrations of 20 and 40 mg/L (expressed hereafter as micrograms per milliliter), respectively. A control solution was prepared for each type of TNA. Samples were removed at 0, 12, 24, 48, and 72 hours for measurement of pH and of famotidine concentration by high-performance liquid chromatography; the solutions were visually inspected for color changes, creaming, and formation of precipitates. Particle size distributions were measured at 72 hours and compared with those for the control solutions at time zero. No appreciable changes in pH occurred over 72 hours, and no physicochemical changes were observed. Famotidine 20 and 40 micrograms/mL was stable for at least 72 hours in both types of TNAs. There was no variation in particle size distribution. Famotidine appears to be stable for up to 72 hours at room temperature in the TNAs studied, and it appears not to alter the integrity of the two lipid emulsions.

Chemical Phenomena↗

[Balance of substances during catalytic oxidation of water admixtures by hydrogen peroxide].

Kinetics of CO2 and O2 production was investigated in the following systems: H2O - H2O2 - C6H5OH - siderite, H2O - H2O2 - HCl - siderite, H2O - H2O2 - siderite, H2O - HCl - siderite. A general equation describing the kinetics of phenol oxidation to yield carbon dioxide was derived: Vco2 = k2[C6H5OH]0.55 [H2O2]2 [Fe2+]2, where [Fe2+] denotes iron in the catalyst. The rate of oxygen production in the presence of phenol and siderite was described as Vo2 = k1 [H2O2]1.46. The CO2/O2 ratio in the concentration range 0.5-2.0 M H2O2 increased from 12.8 to 87.2 vol. %. The conversion degree of 0.05 M C6H5OH to carbon dioxide after 35 min oxidation in the presence of 0.5 g of the catalyst and at t = 21 degrees C reached 99.8%. As a result of chemical reactions between hydrogen of the admixtures and oxygen of the oxidizing agent as well as catalytic decomposition of hydrogen peroxide, the amount of pure water in the system increases. Due to reclamation of water containing wastes produced by one person, the total amount of additional water in space mission is estimated to make 204 kg per year.

Carbon Dioxide↗

Cellular site and mode of Fv-2 gene action. II. Conditional protection of Fv-2ss cells by admixture with Fv-2rr cells.

Fv-2ss marrow cells are protected in vivo from Friend virus-induced erythroleukemia by admixture with a preponderance of Fv-2rr marrow cells. This was demonstrated both in allophenic (mosaic) mice and in bone marrow chimeras constructed from C57BL/6 strains differing at Fv-2 and an enzyme marker (glucose phosphate isomerase). The bone marrow chimeras were constructed by injection of marrow cells from Fv-2ss mice into unirradiated Fv-2rr mice. Bone marrow chimeras derived from this procedure produced 1%-2% donor (Fv-2ss) erythrocytes; this level of chimerism was maintained indefinitely. All the bone marrow chimeras as well as allophenic mice with less than 20% Fv-2ss red cells failed to develop any of the symptoms of Friend disease after infection with the polycythemic strain of Friend virus. The Fv-2rr-mediated protection of Fv-2ss marrow cells could be reversed by pretreatment of the two types of chimeras with either monoclonal or polyclonal antithymocyte antisera. Chimeras treated with either reagent and infected with Friend virus developed symptoms of Friend disease and experienced a shift in their erythrocyte mosaic composition favoring cells of the susceptible genotype. These results are consistent with the notion that a functioning immune system plays a role in the Fv-2rr-mediated protection of Fv-2ss Friend virus target cells. Furthermore, these studies establish conditions whereby a small population of sensitive strain cells in an overwhelming background of resistant strain cells can be selectively expanded. Such conditions could be useful in efforts to clone the Fv-2 gene.

Animals↗

Growth of bacteria and fungi in total nutrient admixtures.

Total nutrient admixtures (TNAs) containing dextrose, amino acids, and fat emulsion were evaluated for their ability to support bacterial and fungal growth. The following solutions were tested: a standard adult total parenteral nutrient (TPN) solution with dextrose, amino acids, and electrolytes, a standard neonatal TPN solution with dextrose, amino acids, and electrolytes, a 10% fat emulsion, a 20% fat emulsion, a TNA with 40% of the total calories as fat, a TNA with 25% of the total calories as fat, a neonatal TNA with 25% of the total calories as fat, a control (fat emulsion was replaced with an equal amount of sterile water) for solution 5, and a control for solution 6. Serial dilutions of each solution were inoculated with 5 X 10(5) bacteria/mL or 5 X 10(3) fungi/mL, incubated, and visually rated on a scale of 0 (no growth) to 4 (maximal growth). Bacterial growth of Pseudomonas aeruginosa, Staphylococcus aureus, Staph. epidermidis, Streptococcus faecalis, and Group JK Corynebacterium was greater in the TNA solutions than in the control or standard TPN solutions. Escherichia coli, Candida tropicalis, and C. albicans grew in all solutions tested. Torulopsis glabrata grew better in solutions that did not contain fat emulsion. Growth characteristics did not differ significantly between the adult and neonatal (more dilute) solutions. The addition of fat emulsion to TPN solutions enhances the ability of these solutions to support bacterial growth; this possibility must be considered when evaluating patients for this type of total parenteral nutrition therapy.

Bacteria↗

Effect of various nutrient ratios on the emulsion stability of total nutrient admixtures.

The emulsion stability of total nutrient admixtures (TNAs) containing various ratios of amino acids (AA):carbohydrate (CHO):fat (FAT) was studied. Eight different TNA formulations were prepared in duplicate using AA supplied as 8.5% crystalline AA (FreAmine III), CHO supplied as 70% dextrose injection, and FAT supplied as 10 or 20% lipid emulsion (Soyacal). The eight formulations represented AA:CHO:FAT ratios (v:v:v) of 2:1:1, 1:1:1, 1:1:1/2, and 1:1:1/4, respectively, with each lipid concentration. TNAs also contained identical concentrations of electrolytes, trace elements, vitamins, and heparin. TNAs were stored at 4 degrees C for 14 days and then at ambient temperature (22-25 degrees C) for another four days. All TNAs were analyzed for gross visual appearance, pH, osmolality, and particle size and distribution on day 0 and periodically throughout the study period. Particle size was measured by photon-correlation spectrometry and negative-phase light microscopy. Visual examination revealed the presence of creaming in all TNAs, which could be dispersed by gentle agitation. The pH of each TNA decreased slightly during the study period, while the osmolality showed little variation. The mean diameter of particles in the TNAs remained close to that in the original lipid emulsions; 95% of all particles in the TNAs were less than 0.454 micron in diameter, which is within the size range of natural lipid particles or chylomicrons. Based on examination of particle size, each TNA formulation was stable for 18 days under the conditions of this study.

Drug Stability↗