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On the distribution of drugs in saliva and blood plasma.

The equilibration of drug concentrations between blood plasma (unbound part) and saliva was studied for selected drugs with different physicochemical properties: Quinidine, sulfamerazine, paracetamol, diazepam and ethanol. From these and other experimental results it is suggested: 1. The concentration ratio between saliva and blood plasma (unbound) can only equal one for basic drugs with a pK a lower than 5.5 and acid drugs with a pK a higher than 8.5 and for pH indifferent drugs. 2. The drug must have a sufficient permeation ability through lipid membranes, valuable by the lipid water partition coefficient.

Blood Proteins↗

[Laser correlation spectroscopy of blood plasma for diagnosis of postradiation sequels].

The method of laser correlation spectroscopy (LCS) of biological fluids, permit to detect fractional composition of biological fluids (in this case--blood plasma). This method have been used to study the late effects of radiation in experimental investigations on animals (irradiation in doses that induce the high frequency of malignant tumors) and on the people living in the zone of Ural Radiation Trace. LCS spectra analysis show the proportion of separate ingredients in the blood plasma in the very bright range of molecular dimensions (d = 1-10000 nm) and for this analysis the special way of classification (semiotic classification) have been proposed. Multicomponent spectra, represented as a histogram (the abscess--diameters of light-scattering particles, ordinate--their per cent in the light-scattering of the whole sample) divide on the separate a priori marked zones with the appropriate means of diameters light-scattering subcomponent. In dependence on the increasing, or decreasing of enclosing in the light-scattering separated subcomponent the program of classification refer this histogram to separate cluster. Each cluster on the basis of preliminary investigations of different pathologic states related to the definite sign reflecting the type of homeostatic alterations (intoxication, allergic, dystrophic, catabolic and their combinations). The detection of the direction of homeostatic alteration and its degree is the main purpose of the semiotic classification of LC-spectra. In this paper it was shown that this way of diagnostic of the nature of homeostatic alterations in the blood plasma is more informative in the evaluation of the weightiness of pathologic state of organism in the comparison with the complexes of laboratory methods, usually used. The method can register immunoglobulin relations, changes in concentrations of lipoproteids and cholesterol and fractional composition of immunocompetent blood cells. The model experiments on animals irradiated in the doses that induce the high frequency of malignant tumors in 12 months thereafter (50 per cent of irradiated rats) have been conducted. With the help of LCS blood plasma it is possible to show the differences in direction of homeostatic changes in animals with and without oncological disease in a long period of time before pathomorphological registration of tumors. At last when 764 individuals living in the Zone of Ural radiation trace have been inspected by the LCS blood plasma it was shown: a. individuals without pathological diagnosis (in the range of 100-150 cz cumulating doses) the radiation action doesn't modify the homeostasis system in practice; b. in individuals with preoncological, oncological, autoimmune and metabolical diseases the modification of homeostasis system in these doses range is noticed. The direction of this modification depend on the nature of pathological process. The methodical simplicity of LCS investigations, rapidity and automatism of analysis together with informative sensitivity of this method testify to perspectives use of LCS blood plasma for the decision of the problem of biodosimetry of irradiation of experimental animals and for monitoring of late effects after low dose irradiation.

Animals↗

In vivo micro particle image velocimetry measurements of blood-plasma in the embryonic avian heart.

The measurement of blood-plasma velocity distributions with spatial and temporal resolution in vivo is inevitable for the determination of shear stress distributions in complex geometries at unsteady flow conditions like in the beating heart. A non-intrusive, whole-field velocity measurement technique is required that is capable of measuring instantaneous flow fields at sub-millimeter scales in highly unsteady flows. Micro particle image velocimetry (muPIV) meets these demands, but requires special consideration and methodologies in order to be utilized for in vivo studies in medical and biological research. We adapt muPIV to measure the blood-plasma velocity in the beating heart of a chicken embryo. In the current work, bio-inert, fluorescent liposomes with a nominal diameter of 400 nm are added to the flow as a tracer. Because of their small dimension and neutral buoyancy the liposomes closely follow the movement of the blood-plasma and allow the determination of the velocity gradient close to the wall. The measurements quantitatively resolve the velocity distribution in the developing ventricle and atrium of the embryo at nine different stages within the cardiac cycle. Up to 400 velocity vectors per measurement give detailed insight into the fluid dynamics of the primitive beating heart. A rapid peristaltic contraction accelerates the flow to peak velocities of 26 mm/s, with the velocity distribution showing a distinct asymmetrical profile in the highly curved section of the outflow tract. In relation to earlier published gene-expression experiments, the results underline the significance of fluid forces for embryonic cardiogenesis. In general, the measurements demonstrate that muPIV has the potential to develop into a general tool for instationary flow conditions in complex flow geometries encountered in cardiovascular research.

Animals↗

Comparative analysis of blood plasma epidermal growth factor concentrations, hormonal profiles and semen parameters of fertile and infertile males.

The relationship between male reproductive function and the blood plasma level of epidermal growth factor (EGF) is of interest in the light of the role that circulating EGF appears to play in regulating mouse spermatogenesis. We measured the concentrations of EGF in the blood plasma of 39 fertile men (sperm count > 20 x 10(6)/ml) and compared them with those of 31 infertile men (sperm < 20 x 10(6)/ml). Blood plasma levels of follicle stimulating hormone (FSH), luiteinising hormone (LH), prolactin and testosterone were also determined. The infertile patients had mean blood plasma EGF concentrations of 0.75 +/- 0.10 ug/L. The value was significantly lower than that of the fertile group (1.28 +/- 0.14 ug/L; P < 0.005). There were statistically significant differences between the fertile and infertile groups in sperm count, sperm viability, mean forward progression, testosterone, LH and FSH (P values between 0.0001 and 0.023). There was no significant difference in the prolactin concentrations between the two groups. Although overall average blood plasma EGF concentrations are significantly lower in the infertile males, regression analysis failed to reveal any direct relationships among the various parameters studied.

Adult↗

Surface plasmon resonance sensor for heparin measurements in blood plasma.

Surface plasmon resonance (SPR) was used as an affinity biosensor to determine absolute heparin concentrations in human blood plasma samples. Protamine and polyethylene imine (PEI) were evaluated as heparin affinity surfaces. Heparin adsorption onto protamine in blood plasma was specific with a lowest detection limit of 0.2 U/ml and a linear window of 0.2-2 U/ml. Although heparin adsorption onto PEI in buffer solution had indicated superior sensitivity to that on protamine, in blood plasma it was not specific for heparin and adsorbed plasma species to a steady-state equilibrium. By reducing the incubation time and diluting the plasma samples with buffer to 50%, the non-specific adsorption of plasma could be controlled and a PEI pre-treated with blood plasma could be used successfully for heparin determination. Heparin adsorption in 50% plasma was linear between 0.05 and 1 U/ml so that heparin plasma levels of 0.1-2 U/ml could be determined within a relative error of 11% and an accuracy of 0.05 U/ml.

Biosensing Techniques↗

Ozone effects on alpha-1-proteinase inhibitor in vivo: blood plasma inhibitory activity is unchanged.

The possible oxidative inactivation of human blood plasma alpha-1-proteinase inhibitor (alpha-1-PI) by inhaled ozone was assessed. Eleven male volunteers (non-smokers) were exposed to 0.5 ppm ozone for four hours on two consecutive days and ten control subjects were exposed to air under the same conditions. Blood plasma samples, drawn before and after treatment, were assayed for total alpha-1-PI, total protein and elastase inhibitory activity. The amount of active alpha-1-PI in plasma samples was quantitated by titrating porcine pancreatic elastase with increasing amounts of plasma. The importance of constructing titration curves for determinations of this type was demonstrated. No differences were noted in the ratios of total alpha-1-PI/total protein or elastase inhibitory activity/total alpha-1-PI in the plasma from ozone exposed individuals relative to controls. Although inhaled ozone did not result in any significant decrease in the activity of blood plasma alpha-1-PI, these findings do not preclude the possibility of oxidative inactivation of a alpha-1-PI in the lung.

Blood Proteins↗

[Characteristics of the antioxidant activity of the blood plasma in patients with hypertension].

A study of the peroxidation of lipids of erythrocytic membranes and blood plasma, antioxidant activity of the blood plasma in 59 patients with hypertensive disease revealed that the initial stages of the disease exacerbation increase of the antioxidant activity is caused by an intensification of peroxidation of cell membrane lipids. A less distinct increase of the antioxidant activity during remission may be due to changes of the blood plasma lipid composition.

Adult↗

Real-time blood plasma polymerase chain reaction for management of disseminated adenovirus infection.

We evaluated the usefulness of quantifying blood plasma adenovirus DNA loads for the management of adenovirus infection. Quantification of adenovirus A, B, and C DNA loads was done with real-time polymerase chain reaction (PCR) assays. Blood plasma specimens obtained from 44 immunocompromised patients were screened prospectively with this method. PCR findings for 36 patients were negative, and none of the patients developed disseminated adenoviral disease. PCR findings for 8 patients were positive; all 8 had invasive adenoviral disease and were treated with cidofovir. Sequential measurements of adenovirus DNA loads were performed to monitor the effect of cidofovir therapy. Decrease in the blood plasma DNA load was significantly higher in patients with a good response to cidofovir than in patients with a poor response and was therefore correlated with survival. Detection of adenovirus DNA in blood plasma appears to be useful for identifying patients at risk for invasive disease. Moreover, quantification of adenovirus DNA loads in plasma is helpful for monitoring the efficacy of antiviral therapy.

Adenoviridae↗

N-delta-acetylornithine and S-methylcysteine in blood plasma.

N-delta-Acetylornithine and S-methylcysteine have been identified as minor components of deproteinized blood plasma of human and bovine blood. Human blood plasma contains a variable amount of acetylornithine, averaging 1.1 +/- 0.4 mumol/l (range 0.8--0.2 mumol/l). Urine contains a very small amount of acetylornithine, approximately 1 nmol/mg creatinine (1 mumol/day). Human blood plasma contains 3.9 +/- 1.9 mumol/l (range 1.4--6.5 mumol/l) of S-methylcysteine. Urine contains approximately 5 nmol/mg creatinine; after acid hydrolysis the amount is increased to 20 nmol/mg creatinine.

Animals↗

Proteomic comparison of human and great ape blood plasma reveals conserved glycosylation and differences in thyroid hormone metabolism.

Most blood plasma proteins are glycosylated. These glycoproteins typically carry sialic acid-bearing sugar chains, which can modify the observed molecular weights and isoelectric points of those proteins during electrophoretic analyses. To explore changes in protein expression and glycosylation that occurred during great ape and human evolution, we subjected multiple blood plasma samples from all these species to high-resolution proteomic analysis. We found very few species-specific differences, indicating a remarkable degree of conservation of plasma protein expression and glycosylation during approximately 12 million years of evolution. A few lineage-specific differences in protein migration were noted among the great apes. The only obvious differences between humans and all great apes were an apparent decrease in transthyretin (prealbumin) and a change in haptoglobin isoforms (the latter was predictable from prior genetic studies). Quantitative studies of transthyretin in samples of blood plasma (synthesized primarily by the liver) and of cerebrospinal fluid (synthesized locally by the choroid plexus of the brain) confirmed approximately 2-fold higher levels in chimpanzees compared to humans. Since transthyretin binds thyroid hormones, we next compared plasma thyroid hormone parameters between humans and chimpanzees. The results indicate significant differences in the status of thyroid hormone metabolism, which represent the first known endocrine difference between these species. Notably, thyroid hormones are known to play major roles in the development, differentiation, and metabolism of many organs and tissues, including the brain and the cranium. Also, transthyretin is known to be the major carrier of thyroid hormone in the cerebrospinal fluid, likely regulating delivery of this hormone to the brain. A potential secondary difference in retinoid (vitamin A) metabolism is also noted. The implications of these findings for explaining unique features of human evolution are discussed.

Animals↗

Prostaglandin E2 levels in blood plasma and in crevicular fluid of advanced periodontitis patients before and after surgical therapy.

AIM: The aim of the study was to determine PGE2 levels in venous blood plasma (VBP), gingival blood plasma (GBP) and gingival crevicular fluid (GCF) in advanced periodontal patients before and after 6 months surgical treatment. PATIENTS AND METHODS: There were 12 patients aged 28-45 years and seven healthy subjects as controls included into the study. Clinical parameters such as PLI, GI, BI, PD, AL and bone height % from radiographs were recorded before and after treatment. PGE2 levels were determined by radioimmunoassay (125 I RIA Kit, NEN(R)). RESULTS: Before treatment the mean VBP, GBP and GCF PGE2 levels in periodontal patients were higher than healthy controls (P < 0.001, Student's t-test). Six months after treatment the mean levels of PGE2 in VBP, GBP and GCF were significantly reduced in patients with improvement of clinical and roentgenological parameters (P < 0.001, Student's t-test). CONCLUSIONS: It can be concluded that PGE2 is involved in the pathogenesis of periodontal disease. The inflamed periodontal tissues may produce significant amount of PGE2 and the degree of inflammation might be determined by the ratios of PGE2. The lower levels of PGE2 in blood plasma and in gingival crevicular fluid after treatment are signs of improvement of periodontal disease.

Adult↗

Analysis of blood plasma proteins in patients with Alzheimer's disease by two-dimensional electrophoresis, sequence homology and immunodetection.

Blood plasma proteins of patients with Alzheimer's disease (AD; senile dementia) and non-AD-type dementia were resolved by two-dimensional electrophoresis and identified by migration position in the electrophoresis pattern, sequence homology, and immunodetection by using antibodies. For the control experiments, blood plasma proteins of a healthy young individual and non-dementia patients were examined in a manner similar to that of the plasma samples of AD patients. In the plasma sample of the healthy young individual, more than 350 spots of silver-stained proteins were observed and among these spots, 73 spots were identified. Blood plasma proteins of the AD and non-AD-type dementia patients were compared with those of the control and non-dementia patients. In the blood plasma samples of five AD patients, three patients had apolipoprotein E4, and another patient showed apolipoprotein L and complement factor H. For the AD-related proteins apolipoprotein E, tau-1, and presenilin 2, proteins were examined by immunostaining with antibodies, in both AD and non-AD patients. Among the three samples of non-AD-type dementia patients, one was distinguishable by amyloid A proteins, and the other by haptoglobin isoforms.

Adult↗

Residual HIV-1 RNA in blood plasma of patients taking suppressive highly active antiretroviral therapy.

CONTEXT: Despite suppressive treatment with highly active antiretroviral therapy (HAART), replication-competent virus can still be isolated from peripheral blood mononuclear cells and genital cells of many individuals receiving suppressive HAART. OBJECTIVE: To determine whether free virion RNA can be detected in the blood plasma and/or genital tract fluids from patients receiving suppressive HAART. DESIGN: Prospective cohort study conducted from November 1998 to May 1999. SETTING: Academic medical center. PATIENTS: Human immunodeficiency virus 1-infected individuals (20 men and 2 women) shown in our laboratories to have fewer than 50 copies/mL of HIV-1 RNA in peripheral blood plasma while taking suppressive HAART. MAIN OUTCOME MEASURES: Free virion RNA levels in peripheral blood plasma and genital fluids, quantified using an ultrasensitive reverse transcriptase polymerase chain reaction able to quantify cell-free virion RNA to a lower limit of 5 copies/mL and qualitatively detect viral RNA below this level. RESULTS: In all 22 patients, residual viral RNA could be detected in the peripheral blood plasma (mean level, 17 copies/mL). The presence of viral RNA suggests that ongoing viral replication is occurring, albeit at low levels, in each patient evaluated. Viral RNA levels were lower in most patients' genital fluids compared with blood plasma and in 12 patients were undetectable. CONCLUSIONS: These data suggest that low-level replication of HIV-1 in patients taking suppressive HAART may be demonstrated not only in peripheral blood mononuclear cells but also in peripheral plasma as cell-free virion RNA. Complete ablation of viral replication may require intensification of antiretroviral therapies beyond standard suppressive HAART.

Anti-HIV Agents↗

Quantitation of doxapram in blood, plasma and urine.

Methods for the quantitation of doxapram in blood, plasma and urine have been developed. Following extraction, gas-liquid chromatography was used to separate doxapram from basic metabolites. Doxapram was detected by mass spectrometry for blood and plasma assays, and by flame ionisation for urine assays. The limit of reliable quantitation in blood and plasma was 10 ng and in urine 500 ng, the coefficients of variation being 6.37%, 1.72% and 2.31% respectively. To illustrate the clinical applicability of the assay methods, plasma, blood and urine levels were monitored in a premature newborn following an intravenous infusion of doxapram.

Apnea↗

"ULtra-clean" isotope diultion/mass spectrometic analyses for lead in human blood plasma indicated that most reported values are artificially high.

We measured lead concentrations in venous blood plasma from two subjects, one having a typical exposure and the other a high exposure to lead. Our preliminary data, obtained by isotope dilution/mass spectrometric techniques in an ultra-clean laboratory, show lead concentrations of 0.02 mug/L and 2 mug/L, respectively, in their blood plasma, and 110 mug/L and 800 mug/L, respectively, in samples of whole blood. These results indicate that plasma lead concentrations previously reported have been overestimated by a large factor, and that further improvements in analytical procedures are needed in most laboratories before data on lead concentratios in blood plasma can be properly interpreted. Our preliminary data indicate a positive correlation between lead intake and lead concentrations in blood plasma.

Adult↗

[Chromatographic transcortin analysis of the blood plasma in tumor-bearing rats].

The binding of 3H corticosterone was studied comparatively in partly purified preparations of blood plasma transcortin in intact and tumor-bearing rats at the 12th day after transplantation. By means of chromatography on DEAE-cellulose and hydroxylapatite transcortin was purified about 200 times. It was demonstrated that the content of bound 3H corticosterone in 1 mg of protein in blood plasma preparations from tumor-bearing animals is 3.5 times less than in the plasma of intact rats. The observed reduction of the transcortin binding capacity in the blood plasma of rats with Walker carcinosarcoma is retained also in purified preparations of the blood plasma tanscortin of tumor-bearing rats.

Adsorption↗

[Studies on endocrine and spermatogenic testicular function. 5. Relationship between dietary protein quality and blood plasma levels of free and bound testosterone in adult rats].

The blood plasma content of testosterone-linking globulins, free testosterone, and total testosterone in 80 adult Wistar rats which received different qualities of feed proteins was determined by means of balancing dialysis and ultracentrifugation, using 3H-testosterone. The first group received casein with four per cent methionine added, the second maize gluten complement with amino acid, and the third casein with methionine and gelatin in a 2:3 ratio, while the fourth group was fed pure maize gluten diet. (Biological valence declined in the given order.) Assays of 100 ml blood plasma of each animal in the first and second groups gave 0.9 mug of testosterone-linking globulins (0.18 mug in third and fourth groups), about 9.0 mug total testosterone (2.5 mug in third and fourth groups), and some 1.4 mug free testosterone (0.55 mug in third and fourth groups). Discussed in this paper is the possible mechanism of regulation by which feed protein quality leads to variation of free testosterone levels in the blood plasma.

Animals↗

[Correlation between changes in lungs and the composition of amino acids in blood plasma caused by industrial dust. II. Studies on workers occupationally exposed to industrial dust].

Results of determination of free aminoacids in blood plasma of workers exposed to ceramic and grinding dusts as well as welding fumes are presented. In the blood plasma of those employed in ceramic factory or welders a significant decrease of free aminoacids in comparison with the control group was found except for hydroxyproline, whose content increased during the 25 year-employment. In experiments on animals a significant increase of total aminoacids content in lungs with simultaneous decrease of free aminoacids amount in blood plasma was observed. Similar changes in workers' blood plasma make us conclude that aminoacids content in human lungs may also increase, which is indicative of fibrinogenic processes.

Amino Acids↗