Blood Of Healthy People Research Articles

ЭЛЕМЕНТНЫЙ СТАТУС ЗДОРОВЫХ И БОЛЬНЫХ ЖИТЕЛЕЙ ГОРОДА БЛАГОВЕЩЕНСКА

The mineral status of healthy and ill citizens of Blagoveshchensk was studied with the help of atomic absorption spectroscopy. It was found out that in the whole blood of healthy people from Blagoveshchensk in comparison with some average standard rates given in literature, there was a bigger (p<0.001) concentration of Co (3.5 and more times), of Cs (15 times more), of Li (4.5 times more), of Mn (34.3 times more), of Ni (4 times more), and there was significantly less of Cu, Fe, Hg, K, Na, Mg, Rb, Zn. At focal tuberculosis the deficit of Ca and Mg and the excess of Cd, Cr, Cs, Hg, K, Li and Pb were registered. And the other way round, under fibrous-cavernous type in the blood there was a low level of Ca, Mg, Mn and Ni (p<0.001), approximately normal contents of Cu, Fe and Zn, and a high (p<0.001) concentration of Cd, Cr, Cs, Hg, K, Li, Mn, Na, Ni, Pb, Rb. Moreover, in the blood of people with lung tuberculosis the contents of Hg were 3-5 times more than in healthy people. Under the peptic ulcer disease the mineral imbalance was revealed through the decrease in the blood of Ca and Mg level (p<0.001) and the increase of (p<0.001) Cd, Cr, Cs, K, Li, Mn, Na, Ni and Pb concentration.

Comprehensive detection and identification of bacterial DNA in the blood of patients with sepsis and healthy volunteers using next-generation sequencing method - the observation of DNAemia

Blood is considered to be a sterile microenvironment, in which bacteria appear only periodically. Previously used methods allowed only for the detection of either viable bacteria with low sensitivity or selected species of bacteria. The Next-Generation Sequencing method (NGS) enables the identification of all bacteria in the sample with their taxonomic classification. We used NGS for the analysis of blood samples from healthy volunteers (n = 23) and patients with sepsis (n = 62) to check whether any bacterial DNA exists in the blood of healthy people and to identify bacterial taxonomic profile in the blood of septic patients. The presence of bacterial DNA was found both in septic and healthy subjects; however, bacterial diversity was significantly different (P = 0.002) between the studied groups. Among healthy volunteers, a significant predominance of anaerobic bacteria (76.2 %), of which most were bacteria of the order Bifidobacteriales (73.0 %), was observed. In sepsis, the majority of detected taxa belonged to aerobic or microaerophilic microorganisms (75.1 %). The most striking difference was seen in the case of Actinobacteria phyla, the abundance of which was decreased in sepsis (P < 0.001) and Proteobacteria phyla which was decreased in the healthy volunteers (P < 0.001). Our research shows that bacterial DNA can be detected in the blood of healthy people and that its taxonomic composition is different from the one seen in septic patients. Detection of bacterial DNA in the blood of healthy people may suggest that bacteria continuously translocate into the blood, but not always cause sepsis; this observation can be called DNAemia.

Normal level of sepsis-associated phenylcarboxylic acids in human serum.

Previous studies showed that large amounts of phenylcarboxylic acids (PhCAs) are accumulated in a septic patient's blood due to increased endogenous and microbial phenylalanine and tyrosine biotransformation. Frequently, biochemical aromatic amino acid transformation into PhCAs is considered functionally insignificant for people without monogenetic hereditary diseases. The blood of healthy people contains the same PhCAs that are typical for septic patients as shown in this paper. The overall serum PhCAs level was 6µM on average as measured by gas chromatography with flame ionization detection. This level is a stable biochemical parameter indicating the normal metabolism of aromatic amino acids. The concentrations of PhCAs in the metabolic profile of healthy people are distributed as follows: phenylacetic ≈ p-hydroxyphenyllactic > p-hydroxyphenylacetic > phenyllactic ≈ phenylpropionic > benzoic. We conclude that maintaining of stable PhCAs level in the serum is provided as the result of integration of human endogenous metabolic pathways and microbiota.

Estimation of some molecular effects of gaseous nitrogen oxide on human blood in vitro

The aim of this work is complex estimation of the nitric oxide action on whole blood of healthy people. We tested the reaction of whole human blood (n=14) to the processing of it with cold NO-containing plasma. We performed direct sparging of blood samples by gaseous flow with NO in a special plant. Cold NO-containing plasma was generated by apparatus "Plazon" (Russia). We tested lactate dehydrogenase activity in direct and reverse reactions, aldehyde dehydrogenase and superoxide dismutase activity, total protein and lactate level, acid-base balance and the partial pressure of gases in blood. For integral assessment of energy metabolism changes a number of derivative parameters (coefficients of energy reaction balance and substrate provision) were used. Our experiments showed, that the processing of whole human blood with NO-containing gas flow (NO concentration--800 ppm) results in significant changes of its physical and chemical parameters. This exposure leads to inhibition of erythrocytes energy metabolism, decreasing plasma antioxidant reserves, developing moderate ionic disorders and acid-base disbalance in blood samples in vitro.

Detection of EBV genomes in plasmablasts/plasma cells and non-B cells in the blood of most patients with EBV lymphoproliferative disorders by using Immuno-FISH

Epstein-Barr virus (EBV) is present in B cells in the blood of healthy people; few studies have looked for EBV in other cell types in blood from patients with lymphoproliferative disorders. We use a new technique combining immunofluorescent cell-surface staining and fluorescent in situ hybridization to quantify both EBV copy number per cell and cell types in blood from patients with high EBV DNA loads. In addition to CD20(+) B cells, EBV was present in plasmablast/plasma cells in the blood of 50% of patients, in monocytes or T cells in a small proportion of patients, and in "non-B, non-T, non-monocytes" in 69% of patients. The mean EBV copy number in B cells was significantly higher than in plasmablast/plasma cells. There was no correlation between EBV load and virus copy number per cell. Although we detected CD21, the EBV B-cell receptor, on EBV-infected B cells, we could not detect it on virus-infected T cells. These findings expand the range of cell types infected in the blood. Determining the number of EBV genomes per cell and the type of cells infected in patients with high EBV loads may provide additional prognostic information for the development of EBV lymphoproliferative diseases.

Secretory Mechanisms and Intercellular Transfer of MicroRNAs in Living Cells

The existence of circulating microRNAs (miRNAs) in the blood of cancer patients has raised the possibility that miRNAs may serve as a novel diagnostic marker. However, the secretory mechanism and biological function of extracellular miRNAs remain unclear. Here, we show that miRNAs are released through a ceramide-dependent secretory machinery and that the secretory miRNAs are transferable and functional in the recipient cells. Ceramide, whose biosynthesis is regulated by neutral sphingomyelinase 2 (nSMase2), triggers secretion of small membrane vesicles called exosomes. The decreased activity of nSMase2 with a chemical inhibitor, GW4869, and a specific small interfering RNA resulted in the reduced secretion of miRNAs. Complementarily, overexpression of nSMase2 increased extracellular amounts of miRNAs. We also revealed that the endosomal sorting complex required for transport system is unnecessary for the release of miRNAs. Furthermore, a tumor-suppressive miRNA secreted via this pathway was transported between cells and exerted gene silencing in the recipient cells, thereby leading to cell growth inhibition. Our findings shed a ray of light on the physiological relevance of secretory miRNAs.

Concentration of selenium in the whole blood and the thyroid tissue of patients with various thyroid diseases.

We investigated the possible differences between the concentrations of selenium in the whole blood and thyroid tissue of patients with thyroid disease. The study comprises 41 women with nodular goiter, 19 women and 2 men with thyroid cancer, 18 women with Graves' disease, and 7 women with thyroiditis. The concentration of selenium was determined by the TRXRF method. The lowest mean selenium level was achieved in the whole blood of women with Graves' disease and the highest in the whole blood of healthy people. In the thyroid cancer tissue, we found the lowest concentration of selenium and the highest in the thyroid gland of women with nodular goiter and Graves' disease. The low selenium levels in the thyroid tissue may increase thyroid cancer risk.

Analysis of the Activated Partial Thromboplastin Time Test Using Mathematical Modeling

Activated partial thromboplastin time (APTT) is a laboratory test for the diagnosis of blood coagulation disorders. The test consists of two stages: The first one is the preincubation of a plasma sample with negatively charged materials (kaolin, ellagic acid etc.) to activate factors XII and XI; the second stage begins after the addition of calcium ions that triggers a chain of calcium-dependent enzymatic reactions resulting in fibrinogen clotting. Mathematical modeling was used for the analysis of the APTT test. The process of coagulation was described by a set of coupled differential equations that were solved by the numerical method. It was found that as little as 2.3×10 −9 μM of factor XIIa (1/10 000 of its plasma concentration) is enough to cause the complete activation of factor XII and prekallikrein (PK) during the first 20 s of the preincubation phase. By the end of this phase, kallikrein (K) is completely inhibited, residual activity of factor XIIa is 54%, and factor XI is activated by 26%. Once a clot is formed, factor II is activated by 4%, factor X by 5%, factor IX by 90%, and factor XI by 39%. Calculated clotting time using protein concentrations found in the blood of healthy people was 40.5 s. The most pronounced prolongation of APTT is caused by a decrease in factor X concentration.

Small molecules originating from microbes (SMOM) and their role in microbes–host relationship

A hypothesis proposed, according to which non-specific purulent-inflammatory processes are mainly caused by disturbances at low-molecular level—i.e. by small molecules originating from microbes (SMOM), while SMOM homeostasis decompensation takes the leading role in complex polyfactorial pathogenesis of sepsis. The hypothesis is logically justified by understanding the reasonableness for creation within the ontogenesis the system of signal molecules, which would serve as mediators for informational exchange between microorganisms and host’s cells. To check this hypothesis we’ve studied blood of 25 healthy donors and 161 patients with various conditions (peritonitis, endocarditis, infections of urinary tract etc.) using Gas chromatography-Mass spectrometry. In all cases we detected SMOMs-fatty acids (hydroxy-acids, branched, unsaturated and cyclopropanoic acids), aldehydes, alcohol’s and phenyl-carbonic substances, that are never normally synthesized by mammals, but are structural components or metabolites of microorganisms. The quantitative and qualitative characteristics of SMOMs varied significantly in patients from those of healthy people. Substances of low molecular weight—that are the structural components of normal endogenous microflora and dominate in blood of healthy people—have disappeared or were present in very low quantities. Meanwhile concentration of bacterial molecules that are rarely found in healthy persons, has increased by 10–100 times. Other SMOMs, never present in healthy people, were also found. The data obtained stand pro the hypothesis on constant presence of SMOMs in blood of healthy and ill individuals and allow to formulate the Concept on Homeostasis of small molecules originating from microbes; serious break up of this homeostasis (decompensation of SMOM homeostasis) serves as inductor of general inflammatory response, septic shock and multisystem organ failure. Keywords: microbial markers, phenylcarbonic compounds, gas chromatography–mass spectrometry, fatty acids, homeostasis, human blood, non-antibiotics, sepsis.

Small molecules originating from microbes (SMOM) and their role in microbes-host relationship

A hypothesis proposed, according to which non-specific purulent-inflammatory processes are mainly caused by disturbances at low-molecular level - i.e. by small molecules originating from microbes (SMOM), while SMOM homeostasis decompensation takes the leading role in complex polyfactorial pathogenesis of sepsis. The hypothesis is logically justified by understanding the reasonableness for creation within the ontogenesis the system of signal molecules, which would serve as mediators for informational exchange between microorganisms and host's cells. To check this hypothesis we've studied blood of 25 healthy donors and 161 patients with various conditions (peritonitis, endocarditis, infections of urinary tract etc.) using Gas chromatography-Mass spectrometry. In all cases we detected SMOMs - fatty acids (hydroxy-acids, branched, unsaturated and cyclopropanoic acids), aldehydes, alcohol's and phenyl-carbonic substances, that are never normally synthesized by mammals, but are structural components or metabolites of microorganisms. The quantitative and qualitative characteristics of SMOMs varied significantly in patients from those of healthy people. Substances of low molecular weight - that are the structural components of normal endogenous microflora and dominate in blood of healthy people - have disappeared or were present in very low quantities. Meanwhile concentration of bacterial molecules that are rarely found in healthy persons, has increased by 10-100 times. Other SMOMs, never present in healthy people, were also found. The data obtained stand pro the hypothesis on constant presence of SMOMs in blood of healthy and ill individuals and allow to formulate the Concept on Homeostasis of small molecules originating from microbes; serious break up of this homeostasis (decompensation of SMOM homeostasis) serves as inductor of general inflammatory response, septic shock and multisystem organ failure.

Distribution of Proteins in Erythrocyte Membranes from Patients with Hypertension

The distribution of characteristic proteins in erythrocyte membranes was studied in patients with essential hypertension (EH) (n = 44), secondary hypertension of renal genesis (n = 42), and healthy persons (n = 44). Densitograms of gels analyzed after electrophoresis of erythrocyte ghosts showed a twofold increase in the amount of band 4.5 (Mw = 52-59 kD) and band 6 (Mw = 35 kD) polypeptides in EH patients as compared to that in healthy persons. Radioimmunoassay with monoclonal antibodies obtained to the sarcoplasmic reticulum (SR) of heart muscle has demonstrated that the amount of the antibodies bound to fragmented erythrocyte membranes from EH persons is greater by at least 28% than that in healthy people. Patients with secondary arterial hypertension of renal genesis did not reveal a significant difference in binding of monoclonal antibodies as compared to the control group. Thus, erythrocyte membranes from EH subjects are different from those taken from the blood of healthy people by the increased amount of bands 4.5 and 6 proteins.

Leukemia and the reducing property of viruses.

Investigations of native blood of healthy people and of patients with acute leukemia have shown that the disease might be caused by a strongly reducing substance, which is presumably a virus. Evidence for this conclusion was obtained mainly by electron spin resonance (ESR) studies and by the determination of the catalase activity. ESR spectra of leukemic blood revealed an additional signal not present in spectra of healthy blood. Investigation of different blood fractions has shown that this signal is caused by a species present in the leukocytes only. Addition of reduced glutathione to healthy blood immediately after blood drawing resulted in the same signal. On the contrary, oxidizing substances, such as oxidized glutathione and KMnO4, added to the blood of leukemic patients immediately after its drawing, caused a disappearance of this signal depending on the concentration. Since the strongly reducing substances causes a reduction in the concentration of the oxidizing substances in biological systems, the H2O2 levels should be also affected and, thus, the catalase activity, too. As expected, the activity of this enzyme in the leukemic blood seems to be considerably lower than in healthy blood.

The blood chemistry of the lower monkeys

A comparative biochemical examination of the blood of healthy people and of lower monkeys was conducted. The content of various proteins and mineral substances in the blood of lower monkeys (Macacusrhesus) was compared with that in healthy people. Certain differences in the content of proteins and in the distribution of the nonprotein nitrogen substances in the blood of human beings as compared to the blood of lower monkeys may be considered to be species specific. On the other hand the indices of the mineral metabolism in lower animals show a considerable similarity to these indices in man. Therefore, a further profound study of the nitrogen metabolism indices has future prospects from the comparative-biochemical point of view.

On the question of spontaneous gangrene in young subjects. Oberthus (Revue de chir., 1927, No. 9)

Oberthus, referring to the etiology of gangrene, notes a particular predisposition of the Jewish race to it. Anatomical substrate of gangrene is degenerative changes of arterial walls expressed in destruction of the inner elastic layer and intimal loosening by granulation tissue with subsequent obliteration of the artery, in the absence of any traces of thrombosis. He considers Oppel's theory untenable, because: a) the fact of hyperadrenalineemia in gangrene is not proved (blood of healthy people may have the same vasoconstrictive properties, and gangrene was sometimes observed in people with one adrenal gland); b) blood changes (hyperglycemia, increased number of erythrocytes, etc.) in this disease fluctuate from time to time. ) in this disease fluctuate in the range close to normal and uncharacteristic; c) in the removed adrenal glands are found hypertrophy of the cortical layer, but not of the brain layer, which produces adrenaline.

On the Experimental use of Antiserums in Acute Insanity

During the past year we have frequently used antiserums experimentally in cases of acute insanity because we have been led to believe from our observations that many of these cases, either primarily or secondarily, are suffering from bacterial infection. The grounds upon which we base this belief are that we frequently find hyperleucocytosis, and in forty-eight out of seventy-six cases examined we have found bacterial agglutinines in the blood which do not exist in the blood of healthy people.