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At least 415 records · Page 23Linked to original sources
PubMed1989

Compressed poly(vinyl alcohol)-polycaprolactone admixture as a model to evaluate erodible implants for sustained drug delivery.

An implant may release a drug either by diffusion concurrent with dissolution of the polymeric implant material without depolymerization (Type A) or by bioerosion involving depolymerization (Type B). The Type A material may induce immune response, while the erosion of Type B polymer releases fragments which could cause toxicity problems. It is proposed that a combination of the two types of polymers may attenuate the intensity of immune response and toxicity, because the presence of one in an implant of the same weight reduces the amount of the other. However, it is important to determine first, if sustained delivery may be achieved by such an implant. In this study, partially hydrolyzed poly(vinyl acetate) (PVA) and polycaprolactone (PCL) were chosen as the model Type A, and B polymers, respectively, to evaluate this objective in vitro. Pellet discs were prepared to assess the effects of compression, proportion of PVA to PCL, acetyl content of PVA, PCL hydrolysis catalyst and drug loading, using methylene blue (MB) as a model drug. Results showed that sustained delivery could be effected, but PCL erosion did not occur as planned. Therefore, PCL served only as a passive component of the implant, while PVA was eroded with the release of MB. Consequently, it was inferred that a polymer may not be required as a passive component, which suggested the use of other compounds of known biocompatibility. Tests with insulin in a compressed solid admixture with cholesterol showed that reduction of hyperglycemia in diabetic Wistar rat could be effected reproducibly for at least 2 weeks. Thus, the present study, originally planned to test a proposed concept, indicates that many nonpolymeric materials of known biocompatibility may be suitable for drug delivery implants as well.

Animals↗
PubMed1984

Effects of fat admixture on the strengths of conventional and low-viscosity bone cements.

The diametral tensile and compressive strengths of both conventional doughy and low-viscosity (LVC) bone cements were tested with sequential admixtures of up to 50% (by weight) liquified fat. The addition of as little as 5% (by weight) fat caused a significant reduction (p = 0.05) in the strengths of both cements. The LVC appeared to be affected to a greater degree by fat contaminations than did the conventional cement, although the strengths of the LVC were generally equal to or higher than those of the conventional cement. The enhanced effect of fat contamination on the LVC was thought to be due to the more fluid, tacky nature of this material during administration.

Animals↗
PubMed2002

Amphotericin B/emulsion admixture interactions: an approach concerning the reduction of amphotericin B toxicity.

Mixing Fungizone with a fat emulsion used for nutritional purpose (Intralipid or Lipofundin ) was reported to decrease Amphotericin B (AmB) toxicity in clinical use. In an effort to understand the reason for this phenomenon, spectral and morphological analyses were done for the Fungizone and Fungizone /Lipofundin admixture (FLmix). The absorption spectra analyses showed that not only Fungizone but also FLmix presented spectra that were concentration dependent. Moreover, the spectra of FLmix remained stable until the concentration of 5 x 10(-7) M, and only at 5 x 10(-8) M did they become similar in shape to the Fungizone spectra. Morphological studies revealed that even though emulsion droplets with or without Fungizone presented the same particle size, the former was less electron dense compared with Lipofundin alone. These results suggest a kind of association between Fungizoneand Lipofundin that remains over the whole range of concentrations. This hypothesis was confirmed by in vitro studies in which FLmix presented an important selectivity against human and fungal cells compared with Fungizone. These findings suggest that parenteral emulsions should be able to reduce the AmB toxicity probably by changing the AmB self-association state by binding it with emulsion droplets.

Amphotericin B↗
PubMed2006

Finding the genes underlying adaptation to hypoxia using genomic scans for genetic adaptation and admixture mapping.

The complete sequencing the human genome and recent analytical advances have provided the opportunity to perform genome-wide studies of human variation. There is substantial potential for such population-genomic approaches to assist efforts to uncover the historical and demographic histories of human populations. Additionally, these genome-wide datasets allow for investigations of variability among genomic regions. Although all genomic regions in a population have experienced the same demographic events, they have not been affected by these events in precisely the same way. Much of the variability among genomic regions is simply the result of genetic drift (i.e., gene frequency changes resulting from the effects of small breeding-population size), but some is also the result of genetic adaptation, which will only affect the gene under selection and nearby regions. We have used a new DNA typing assay that allows for the genotyping of thousands of SNPs on hundreds of samples to identify regions most likely to have been affected by genetic adaptation. Populations that have inhabited different niches (e.g., high-altitude regions) can be used to identify genes underlying the physiological differences. We have used two methods (admixture mapping and genome scans for genetic adaptation) founded on the population-genomic paradigms to search for genes underlying population differences in response to chronic hypoxia. There is great promise that together these methods will facilitate the discovery of genes influencing hypoxic response.

Alleles↗
PubMed1983

Genetics of diabetes in Nauru: effects of foreign admixture, HLA antigens and the insulin-gene-linked polymorphism.

Genetic factors play a major role in predisposition to diabetes in the Micronesian population of Nauru. In people aged 60 years and older, 83% of full-blooded Nauruans were diabetic compared with 17% of those with ancestral foreign admixture, as detected by HLA typing. HLA distributions also showed a small increased risk for early onset of diabetes (less than 46 years) associated with HLA-Bw22 (Bw56). Variation in the restriction fragment length of DNA near the insulin gene was found, but was not associated with diabetes. The distribution in fragment lengths, previously reported in Caucasoids, was observed in healthy Polynesians, Melanesians and Micronesians.

Adult↗
PubMed1979

Gm allotypes and racial admixture in two Brazilian populations.

The Gm types of 515 inhabitants of Belém and 395 inhabitants of Porto Alegre, Brazil were studied in an attempt to quantitatively estimate ethnic parental contributions. The people from Belém can be characterized as 24% black, 22% Indian, and 54% Caucasian. The Porto Alegre blacks seem to have inherited as much as 53% of their genes from Caucasian ancestors, while the whites living there have inherited 8% of their genes from African ancestors. The admixture values obtained for Belém are very similar if just the Gm system is considered or it plus seven other loci are considered, emphasizing the high efficiency of the Gm markers in such analyses.

Adult↗
PubMed1983

Venous admixture (Qva/Q) and true shunt (Qs/Qt) in ARF patients: effects of PEEP at constant FIO2.

Venous admixture (Qva/Q) in ARF patients is due to both true right to left shunt (Qs/Qt: perfusion of truly unventilated areas) and to maldistribution [Qva-Qs)/Qt: effects of unevenness of ventilation/perfusion ratio). Using the retention rate of sulphur hexafluoride we determined the effects of PEEP on Qs/Qt and (Qva-Qs)/Qt at a constant FIO2 for each patient (0.57 +/- 0.19 SD, range 0.4-0.95). Eleven patients with ARF (treated either by CPPV or CPAP) were studied on 16 occasions. Each measurement was repeated at two levels of PEEP, 5 cm H2O below and 5 cm H2O above the patient's clinically determined PEEP level. The increase in PEEP resulted in: - a decrease in Qva/Q (from 0.37 +/- 0.13 to 0.27 +/- 0.12, p less than 0.01); - a parallel decrease in Qs/Qt (from 0.29 +/- 0.16 to 0.22 +/- 0.14, p less than 0.01); there was a positive correlation between Qva/Q and Qs/Qt changes (r = 0.53, p less than 0.05). No significant variation was demonstrated in (Qva-Qs)/Qt (from 0.074 +/- 0.045 to 0.054 +/- 0.048). On the other hand there was a negative correlation between the fraction of Qva/Q due to the maldistribution and FIO2: (Qva-Qs)/Qva = 0.75-0.86 FIO2 (r = 0.74, p less than 0.01). We conclude that: PEEP decreased Qva/Q mainly through changes in Qs/Qt but did not have a definite effect on (Qva-Qs)/Qt. Maldistribution was responsible for a significant portion of Qva/Q in those ARF patients tolerating a relatively low FIO2 (0.4-0.6).

Acute Disease↗
PubMed1996

Relationship between pulmonary oxygen consumption, lung inflammation, and calculated venous admixture in patients with acute lung injury.

OBJECTIVE: To determine in patients with acute lung injury whether increased pulmonary oxygen consumption (VO2pulm), computed as the difference between oxygen consumption measured by indirect calorimetry (VO2meas) and calculated by the reverse Fick method (VO2Fick), would: (1) correlate with the degree of lung inflammation assessed by bronchoalveolar lavage (BAL); (2) lead to an overestimation of calculated venous admixture (Qva/Qt). DESIGN: Prospective study. SETTING: University hospital, medical intensive care unit. INTERVENTION: None. MEASUREMENTS AND RESULTS: In nine mechanically ventilated patients with acute lung injury (Apache II 12 +/- 5, lung injury score 2 +/- 0.6, mean +/- SD), whole-body VO2 (VO2wb) was determined simultaneously by indirect calorimetry and the reverse Fick technique, after which BAL was immediately performed. VO2meas was significantly higher than VO2Fick (128 +/- 24 and 102 +/- 18 ml/min per m2, respectively, p < 0.001). Median VO2pulm was 25.3 ml/min per m2 (range 1.98-51.5), thus representing 19 +/- 11% of VO2wb. Total BAL cellularity was increased in all patients (median 47, range 24-200 x 10(4)/ml), as was the total polymorphonuclear (PMN) count (median 78 range 5-93 x 10(4)/ml). Macrophage counts were in the normal range. There were raised BAL levels of interleukin-6 (IL-6) (median 945, range 23-1800 ng/ml) and elastase (median 391, range 5-949 ng/ml). Median protein levels were 270 micrograms/ml (range 50-505). There was no correlation between VO2pulm and BAL cellularity, PMNs, elastase, IL-6, or protein. Qva/Qt was 31.7 +/- 8%. Qva/Qt, corrected for the presence of VO2pulm, (Qva/Qtcorr), was 30.3 +/- 8% (P < 0.01 vs Qva/Qt), a 4.2% overestimation due to VO2plum. There was no correlation between Qva/Qt or Qva/Qtcorr and VO2pulm. CONCLUSIONS: In mechanically ventilated patients with acute lung injury, VO2pulm was increased and led to a 19% underestimation of VO2wb determined by the reverse Fick method, as well as to a 4.2% overestimation of calculated Qva/Qt. Lung inflammatory activity was increased, as assessed by BAL cellularity, IL-6 and elastase levels. However, there was no correlation between VO2pulm and the intensity of pulmonary inflammation.

Adult↗
PubMed1997

An extension of the admixture test for the study of genetic heterogeneity in hereditary multiple exostoses.

Hereditary multiple exostoses (EXT) is an autosomal dominant disorder characterized by the presence of multiple cartilage-capped exostoses in the juxta-epiphyseal regions of the long bones. EXT is heterogeneous with at least three different locations currently having been identified on chromosomes 8, 11 and 19. We have tested a series of 29 EXT families for possible linkage to the three disease loci and estimated the probability of linkage of the disease to each locus in our series, by using an extension of the admixture test, which makes modelling of heterogeneous monogenic disease feasible. The maximum likelihood was obtained for proportions of 44%, 28% and 28% of families being linked to chromosome 8, 11 and 19, respectively. The a posteriori probability of linkage of the disease to EXT1, EXT2 and EXT3 was greater than 80% for 8/29, 5/29 and 3/29 families, respectively, and did not give evidence of a fourth locus for the disease. The present approach can be generalized to the investigation of genetic heterogeneity in other monogenic diseases, as it simultaneously estimates the location of each disease gene and the proportion of families linked to each locus.

Chromosomes, Human, Pair 11↗
PubMed2005

Admixture mapping as a gene discovery approach for complex human traits and diseases.

Admixture mapping (AM) is a special form of conventional meiotic or recombination mapping for disease gene discovery in humans that exploits naturally occurring genetic and phenotypic differences existing in populations between which recent gene flow has occurred. Essentially, mates from two different "parental" populations with different allelic and disease-predisposing mutation profiles will produce "admixed" offspring whose genomes will be mixtures of the genomes associated with the parental populations. Strong linkage disequilibrium (LD) will exist for several generations between neighboring loci of admixed individuals and can be exploited for identifying the genomic location of trait-influencing loci. Although it may be a very clever strategy for identifying genes that influence human traits and diseases, AM can be problematic. We review the foundations, basic strategies, resources, and settings necessary for AM. We conclude that AM has potential in the identification of disease-predisposing loci, but this potential may only exist in a limited number of realistic settings.

Chromosome Mapping↗
PubMed1990

Discerning the latent structure of hypothetical psychosis proneness through admixture analysis.

The application of psychometric procedures to a normal population sample to detect individuals with increased liability for schizophrenia is a useful methodological adjunct to the traditional genetic high-risk strategy. A necessary and reasonable step in the process of establishing the utility of a viable psychometric index of schizotypy is the formal investigation of the latent structure of psychometric values. The present study used admixture analysis to examine the distribution of scores on the Perceptual Aberration Scale (PAS), an objective measure of hypothetical psychosis-proneness, in a randomly ascertained sample of 18-year-old university students (n = 707). We applied parametric methods that assumed normally distributed component distributions; viewed in this context, our results are hypothesis-generating and not definitive confirmation of specific hypotheses. Within our methodological framework, the results provide strong evidence for the commingling of normal distributions, even after allowing for unequal variances across components and after removing skewness. The overall distribution of power-transformed data is consistent with the existence of three qualitatively distinct classes of PAS responders. We discuss our results in light of Meehl's model of schizotaxia, a "mixed model" of inheritance of liability to schizophrenia, and we review the methodological implications of our findings for future research.

Adolescent↗
PubMed1992

Immunogenicity of a Streptococcus pneumoniae type 4 polysaccharide--protein conjugate vaccine is decreased by admixture of high doses of free saccharide.

In this study we report that the priming capacity of a Streptococcus pneumoniae type 4 polysaccharide-protein conjugate to booster immunizations with the native capsular polysaccharide is dose dependent. Furthermore, it is shown by admixture experiments that simultaneous administration of high doses of free saccharide (0.5-25 micrograms) of different chain lengths (varying from M(r) 1.6-120 kDa) decreases the anti-polysaccharide antibody response. Presence of low doses of saccharide (up to 10%), which are usually present in conjugates prepared by the carbodiimide coupling procedure, did not influence the anti-polysaccharide antibody response in adult and neonatal mice.

Animals↗
PubMed1990

The ventricle-brain ratio (VBR) in functional psychoses: an admixture analysis.

An admixture analysis of the ventricle-brain ratio (VBR) on the computed tomographic (CT) scans of 72 patients with functional psychosis and 50 healthy controls was made, to determine whether two distinct distributions could be demonstrated. The patients showed a more positively skewed distribution, and a significantly higher mean VBR, but there was no evidence of more than one underlying normal distribution of values. The use of VBR alone to define a biologically separate subgroup of patients is not supported.

Adolescent↗
PubMed1992

Long-term stability of 5-fluorouracil and folinic acid admixtures.

5-Fluorouracil (5-FU) and d,1-folinic acid (FA) are used in association to treat a wide variety of malignancies. The stability and the compatibility of 5-FU and FA in combination in intravenous admixtures were studied under various storage conditions and with drug concentrations matching their clinical use (0.9% sodium chloride, 5% dextrose, protected from light or not). 5-FU and FA concentrations (mg/ml) were 6.5 or 50 and 4.0 or 30.8, respectively. Successive aliquots of the drugs mixtures were withdrawn during 60 h from 500 ml glass bottles and 500 ml polyvinyl chloride (PVC) bags (at room temperature) and during 120 h from cassettes (at 32 degrees C). Drug concentrations were measured by high performance liquid chromatography. For all conditions tested, the changes in 5-FU and FA relative to the initial concentrations remained within the assay reproducibility (10%). In complement, infrared Fourier transformation spectrophotometry has not shown a significant fixation of FA or 5-FU on the PVC bags, in all tested conditions. Under the conditions examined above 5-FU and FA can be mixed in the same container for their use in cancer chemotherapy. This can have practical consequences by simplifying the widely used treatment protocols associating 5-FU and FA.

Drug Combinations↗
PubMed2005

Evaluation of blends tincal waste, volcanic tuff, bentonite and fly ash for use as a cement admixture.

The evaluation of blends tincal waste (TW), fly ash (FA), bentonite (BE), volcanic tuff (VT) for use as a cement admixture was investigated. The properties examined include setting time, expansion, water requirement, specific surface and compressive strength of cement mixtures. The results revealed that the early compressive strength decrease with increasing tincal waste, due to tincal waste increasing initial setting time of the cement. The tincal waste and volcanic tuff of cement mixtures increased and there was reduction in compressive strength. The more the tincal waste increased the greater retardation there was initial setting time this may be attributed to containing high amount B2O3 and MgO content. The tincal waste and fly ash increased with expansion increased. Water requirement increased as the Blaine fineness of the cement mixtures increased. The results obtained were compared with standards and five batches were advised as suitable for the standard.

Bentonite↗
PubMed2005

Direct determination of ciprofloxacin in admixtures with metronidazol and ampicillin by NMR.

Methods to analyse mixtures of pharmaceutical compounds are often based on chromatographic separations coupled to UV detectors. These procedures typically have to verify with other methods that the specificity is sufficient because structural information is sometimes too limited. NMR methods can be particularly useful in the analysis of admixtures of antibiotics such as ciprofloxacin because of the inherent high selectivity. This can even be extended by the measurement of diffusion coefficients that help to identify the relevant signal for quantification. Taking advantage of the resolving power of NMR an analytical procedure to directly measure ciprofloxacin without separation steps is presented. The diffusion coefficients of the three components were measured. Tests of precision (repeatability) and recovery of ciprofloxacin without any separation steps in the presence of metronidazol and ampicillin were conducted.

Ampicillin↗
PubMed2006

Solid-liquid distribution of selected concrete admixtures in hardened cement pastes.

The distribution between hardened cement paste and cement pore water of selected concrete admixtures (BZMs), i.e., sulfonated naphthalene-formaldehyde condensate (NS), lignosulfonate (LS) and a gluconate-containing plasticiser used at the Paul Scherrer Institute for waste conditioning, was measured. Sorption data were fitted to a single-site Langmuir isotherm with affinity constants K=(19+/-4)dm(3)g(-1) for NS, K=(2.1+/-0.6) dm(3)g(-1) for LS and sorption capacities q=(81+/-16)g kg(-1) for NS, q=(43+/-8)g kg(-1) for LS. In the case of gluconate, a two-site Langmuir sorption model was necessary to fit the data satisfactorily. Sorption parameters for gluconate were K(1)=(2+/-1)x10(6)dm(3)mol(-1) and q(1)=(0.04+/-0.02)mol kg(-1) for the stronger binding site and K(2)=(2.6+/-1.1)x10(3)dm(3)mol(-1) and q(2)=(0.7+/-0.3)mol kg(-1) for the weaker binding site. Desorption of these BZMs from cement pastes and pore water in cement specimens prepared in the presence of the BZMs were then used to test the model. It was found that only minor parts of NS and LS could be mobilised as long as the cement composition was intact, whereas the sorption of gluconate was found to be reversible. The Langmuir model makes valuable predictions in the qualitative sense in that the pore water concentration of the BZMs is reduced by several orders of magnitude as compared to the initial concentrations. In view of the necessity for conservative predictions used in the safety analysis for disposal of radioactive waste, however, the predictions are unsatisfactory in that the measured pore water concentrations of NS and LS were considerably larger than the predicted values. This conclusion does not apply for gluconate, because its concentration in cement pore water was below the detection limit of approximately 50 nM.

Anion Exchange Resins↗