Group Of Healthy Adult Volunteers Research Articles

ВОЗРАСТНЫЕ ОСОБЕННОСТИ ФОРМИРОВАНИЯ ВНЕКЛЕТОЧНЫХ ЛОВУШЕК НЕЙТРОФИЛОВ У ЗДОРОВЫХ ЛИЦ И БОЛЬНЫХ ТУБЕРКУЛЁЗОМ

Abstracts. Introduction. Forming a neutrophil extracellular trap (NET) from DNA (NETosis) is considered as a potentially significant marker in the diagnosis of tuberculosis. However, there is practically a lack of data regarding the age-related differences in forming extracellular traps in research publications. Aim. To determine the age-related differences of NETosis in healthy individuals and in tuberculosis (TB) patients. Materials and Methods. The ability of neutrophils to form extracellular traps was investigated in 4 groups: 1) 4-7-year-old children diagnosed with the primary tuberculosis complex, who fell ill within Omsk region; 2) healthy and uninfected children at the same age; 3) adults with tuberculosis, and 4) adults without tuberculosis. For this purpose, isolated fractions of neutrophils from peripheral blood of the groups under research were stimulated with a mixture of bacteria (probiotic) for 30 minutes. In the hanging-drop preparation, we analyzed the proportion of neutrophil extracellular traps and cells in the state of various motility degrees. Results and Discussion. Age-related differences in the ability of neutrophils to form extracellular traps were characterized by a more pronounced response of neutrophils to the NETosis stimulant in children in the control group in comparison with neutrophils isolated from blood in the group of healthy adult volunteers: Neutrophils of children (Me=16.1; Q1=12.8; Q3=18.3) were statistically significantly more intense (p=0.0002) than those of adults (Me=8.6; Q1=7.1; Q3=10.5) and formed filamentous NETs. In the groups of pediatric and adult pulmonary TB patients, the response of neutrophils to the NETosis stimulant was diametrically opposite. Neutrophils of children with primary tuberculosis complex, as of those in the control group, predominantly formed filamentous NETs, but in greater amounts, while neutrophils of adults with infiltrative or focal form and with at most 2 segments involved mainly formed cloudy NETs, whereas filamentous NETs prevailed for the adults in the control group after stimulation. At the same time, proportion of cloudy NETs did not exceed 5% in healthy children and healthy adults. Comparing the findings of our study with literature data, we hypothesized that, most likely, there is a greater increase in PAD4 expression and more pronounced histone H3 citrullination in children’s neutrophils than in those of adults. Conclusions. Our findings indicate more pronounced ex vivo processes induced by NETosis stimulator in both groups of children (healthy individuals and TB patients) as compared to adults in the respective groups, which should be considered by the researchers interpreting the findings of the ability of neutrophils to form extracellular traps in tuberculosis.

Minimising ambient illumination via ambient subtraction: smartphone assessment of jaundice in liver patients via sclera images

Using smartphone images to quantify color presents a noninvasive way to assess jaundice and other color-related biomarkers of the human body. Here we focus on assessing jaundice through accurate bilirubin measurement in adult liver patients, the first time optical imaging has been applied to this cohort. These patients can suffer from very high levels of bilirubin, indicating their severity of liver disease. A smartphone assessment technique for jaundice based around the color of the sclera (white of the eye) extracted from images is being developed, as smartphone imaging enables cheap, non-invasive and quantitative readings. Variations in ambient light cause large changes to recorded pixel values so must be accounted for to ensure that any changes detected are due to changes in jaundice level. Here we suggest the use of an ambient subtraction approach to minimise the effects of ambient light. Pairs of flash/ no-flash images are captured and the extracted values subtracted to yield data as though under a pure flash illumination. We present data demonstrating the technique with a group of healthy adult volunteers. We also present data from a patient study involving adults with liver disease. Images were captured and the bilirubin (jaundice) level predicted from these images before and after subtraction was compared to the ground truth value obtained via blood test. The linear correlation coefficient increased from 0.47 to 0.85 (p < 0.001 in both cases) upon application of subtraction, demonstrating the effectiveness of the technique.

The importance of AIF ROI selection in DCE-MRI renography: Reproducibility and variability of renal perfusion and filtration

Purpose The aim of this study was to investigate (a) the effect the choice of the region of interest (ROI) defining the aortic input function (AIF) has on the estimation of renal perfusion and filtration in dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) renography, and (b) the reproducibility of these parameters. Using renal DCE-MRI and a three-compartment model analysis, this work evaluated the effect two different AIFs, derived from variable sized ROIs in the aorta, has on calculating DCE-MRI renal perfusion and filtration values in a group of healthy adult volunteers who underwent two consecutive renal DCE-MRI studies. Methods Fifteen healthy volunteers underwent two DCE-MRI studies under similar physiological conditions. Oblique-coronal DCE-MRI data volumes were acquired on a 1.5 T Siemens Avanto scanner with a 3D-FLASH pulse-sequence (TE/TR = 0.53/1.63 ms, flip angle = 17°, acquisition matrix = 128 × 104 voxels, strong fat saturation, PAT factor = 2 (GRAPPA) and 400 mm × 325 mm FOV). Each dynamic dataset consisted of 18 slices of 7.5 mm thickness (no gap) and an in-plane resolution of 3.1 mm × 3.1 mm, acquired every 2.5 s for not less than 5 minutes. During the MR scan a dose of 0.05 mmol (0.1 mL) kg −1 body weight of dimeglumine gadopentetate (Magnevist) was injected intravenously (2 mL s −1 injection rate), followed by a 15 mL saline flush at the same rate, using a MR-compatible automated injector (Spectris). Two AIFs were defined for each volunteer by drawing two ROIs in the aorta for each study. Renal perfusion and glomerular filtration rate (GFR) values were then calculated for each of the AIFs using a modified Tofts Renal Model (TRM). Both renal perfusion and GFR were expressed in mL min −1 100 mL −1 of tissue. Results and conclusion Inter-individual reproducibility tests for renal perfusion and glomerular filtration rate showed that the size of AIF ROIs significantly affects calculated values of perfusion and GFR ( p-values <0.02). No significant differences were observed when comparing perfusion and GFR values in the same volunteer between scans performed on different days ( p-values >0.22). From our study we conclude that while DCE-MRI derived indices of renal function are reproducible in the same individual when imaged on different days, the size of the aortic ROI and hence the AIF has a significant influence on calculated renal perfusion and GFR values. Currently there is no accepted standard for drawing the aortic ROI and no standardized approach for the AIF definition in renal DCE-MRI studies.

Interindividual Variability in Response to Sodium Dichromate–Induced Oxidative DNA Damage: Role of the Ser326Cys Polymorphism in the DNA-Repair Protein of 8-Oxo-7,8-Dihydro-2′-Deoxyguanosine DNA Glycosylase 1

Although the genotoxic mechanism(s) of hexavalent chromium (CrVI) carcinogenicity remain to be fully elucidated, intracellular reduction of CrVI and concomitant generation of reactive intermediates including reactive oxygen species and subsequent oxidative damage to DNA is believed to contribute to the process of carcinogenesis. In the current study, substantial interindividual variation (7.19-25.84% and 8.79-34.72% tail DNA as assessed by conventional and FPG-modified comet assay, respectively) in levels of DNA strand breaks after in vitro treatment of WBC with sodium dichromate (100 micromol/L, 1 hour) was shown within a group of healthy adult volunteers (n = 72) as assessed by both comet and formamidopyrimidine glycosylase-modified comet assays. No statistically significant correlation between glutathione S-transferases M1 or T1, NADPH quinone oxidoreductase 1 (codon 187) and X-ray repair cross complementation factor 1 (codon 194) genotypes and individual levels of DNA damage were observed. However, individuals homozygous for the Cys(326) 8-oxo 7,8-dihydro-2'-deoxyguanosine glycosylase 1 (OGG1) polymorphism had a statistically significant elevation of formamidopyrimidine glycosylase-dependent oxidative DNA damage after treatment with sodium dichromate when compared with either Ser(326)/Ser(326) or Ser(326)/Cys(326) individuals (P = 0.008 and P = 0.003, respectively). In contrast, no effect of OGG1 genotype on background levels of oxidative DNA damage was observed. When individuals were divided on the basis of OGG1 genotype, Cys(326)/Cys(326) individuals had a statistically significant (P < 0.05, one-way ANOVA followed by Tukey test) higher ratio of oxidative DNA damage to plasma antioxidant capacity than either Ser(326)/Ser(326) or Ser(326)/Cys(326) individuals. The results of this study suggest that the Cys(326)/Cys(326) OGG1 genotype may represent a phenotype that is deficient in the repair of 8-oxo-7,8-dihydro-2'-deoxyguanosine, but only under conditions of cellular oxidative stress. We hypothesize that this may be due to oxidation of the Cys(326) residue. In conclusion, the homozygous Cys(326) genotype may represent a biomarker of individual susceptibility of lung cancer risk in individuals that are occupationally exposed to CrVI.

Padronização normativa de eletro-oculografia em adultos

PURPOSE: To determine normative values for EOG in a group of healthy adult volunteers, according to the standard protocol recommended by the International Society for Clinical Eletrophisiology of Vision - ISCEV. METHODS: 33 volunteers aging from 18 to 55 years (mean=26.75±10.50) were included in the study. EOG was recorded by skin electrodes positioned in the external canthi of the eyes, with LED stimulus presented in a Ganzfeld dome. Subject's task was to fix the LED stimulus either straight ahead or with saccadic horizontal movements. The potential difference between the cornea and posterior pole of the eye was recorded each minute. The examination was done in 3 phases: 1- pre-adaptation; 2- dark (scotopic) and 3- light (photopic). The Arden ratio was calculated as the proportion between the maximum peak amplitude in the light phase divided by the minimum peak amplitude in the dark. RESULTS: At the scotopic phase, the minimum peak amplitude occurred between 14 and 21 minutes after the beginning of the stimulation (mean=17.82±2.11 min) and the amplitude ranged from 206 to 635 µV (mean 365.73±122.52 µV). At the photopic phase the maximun peak amplitude occurred between 27 and 34 minutes (mean=30.06±1.80 min); the amplitude ranged from 646 to 1250 µV (mean= 950.70±179.16 µV). Arden ratio ranged from 1.85 to 4.02 with a lower normal limit of 1.92 and the upper limit of 4.00. CONCLUSION: The results obtained in this study are comparable to those previously reported in the literature, with a lower normal limit of 1.92 for Arden ratio. These values will be helpful to evaluate patients with several retinal disorders. Inclusion of other age groups will provide extended normative data.

An evaluation of the acidogenic potential of asthma inhalers

Aim: The aims of the present study were firstly to investigate the inherent pH and titratable acidity of commercially available paediatric asthma inhalers in the United Kingdom and secondly to assess their in vivo acidogenic potential (saliva pH and plaque pH (PpH) tests) in a group of healthy adult volunteers. Materials and methods: Manually actuated metered dose inhaler (MDI) and dry powder inhaler (DPI) formulations of all available preventor (glucocorticoids, disodium chromoglycate), reliever (β 2 agonists) and combination asthma medication were investigated. The inherent pH and titratable acidity of 18 inhalers were determined and analysed using t-tests, ANOVA and post hoc Tukey’s tests. Following this the oral pH responses after inhaler use were assessed in 14 healthy adult volunteers (complying with the FNDH criteria, 1985) who participated in a random blind study to determine both the salivary pH (SpH) and plaque pH following inhaler use. Non-parametric tests of significance (Mann-Whitney and Wilcoxon Signed-Ranked Tests) were used to analyse pH responses according to vehicle of delivery (MDI/DPI), lactose content and generic drug. Results: The inherent pH of the DPIs ( n=8, mean pH=5.06) was significantly lower ( P<0.005) than that of the MDIs ( n=10, mean pH=6.45) and the titratable acidity of the lactose-based DPIs was twice that of the non-lactose-based DPIs ( P<0.000). Lactose-based DPIs produced significantly lower salivary pH and plaque pH readings, greater maximum pH drops from baseline pH and larger areas below baseline pH in comparison with that of all other inhalers tested ( P<0.05). All inhalers, however, failed to depress plaque pH below pH 6. Conclusions: Although none of the inhalers were able to demonstrate an acidogenic response below the “critical” pH, the substantial pH drops observed with the lactose-based DPIs may be an important consideration for enamel demineralisation.

Relationship of high energy expenditure and variation in dietary intake with reporting accuracy on 7 day food records and diet histories in a group of healthy adult volunteers.

To assess the accuracy of reporting from both a diet history and food record and identify some of the characteristics of more accurate reporters in a group of healthy adult volunteers for an energy balance study. Prospective measurements in free-living people. Wollongong, Australia. Fifteen healthy volunteers (seven male, eight female; aged 22-59 y; body mass index (BMI) 19-33 kg/m(2)) from the local community in the city of Wollongong, Australia. Measurement of energy intake via diet history interview and 7 day food records, total energy expenditure by the doubly labelled water technique over 14 days, physical activity by questionnaire, and body fat by dual-energy X-ray absorptiometry. Increased misreporting of energy intake was associated with increased energy expenditure (r=0.90, P<0.0001, diet history; r(S)=0.79, P=0.0005, food records) but was not associated with age, sex, BMI or body fat. Range in number of recorded dinner foods correlated positively with energy expenditure (r(S)=0.63, P=0.01) and degree of misreporting (r(S)=0.71, P=0.003, diet history; r(S)=0.63, P=0.01, food records). Variation in energy intake at dinner and over the whole day identified by the food records correlated positively with energy expenditure (r=0.58, P=0.02) and misreporting on the diet history (r=0.62, P=0.01). Subjects who are highly active or who have variable dietary and exercise behaviour may be less accurate in reporting dietary intake. Our findings indicate that it may be necessary to screen for these characteristics in studies where accuracy of reporting at an individual level is critical.

CHANGES OF OXIDATIVE AND LIPOPEROXIDATIVE METABOLISM IN PATIENTS WITH ACUTE VIRAL MYOCARDITIS

Objective: To study the changes of oxidative metabolism and lipoperoxidative metabolism in patients with acute viral myocarditis (AVM), and to research pathological chain reactions of a series of free radicals, and oxidative damage and lipoperoxidative damage in AVM patients' bodies. Methods: A random paired control design was used to investigate 70 cases of AVM patients and 70 cases of healthy adult volunteers (HAV) on the basis of contents of nitric oxide (NO), lipoperoxide (LPO) in plasma, and LPO in red blood cell (RBC) as well as activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) in RBC as revealed by spectrophotometric assays. Results: Compared with the average values (AV) of the above biochemical parameters (BP) in the HAV group, the AV of NO in plasma, and LPO in plasma and in RBC in the AVM group were significantly increased (P=0.0001), while the AV of SOD, CAT and GSH-Px in the AVM group were significantly decreased (P=0.0001). Conclusion: The findings in this study suggested that in the AVM patients bodies the metabolism of NO was disturbed, and the pathological chain reactions of a series of free radicals were so severely aggravated, as to cause the oxidative damage and lipoperoxidative damage in the AVM patients' bodies.

Physical Properties of Stimulated and Unstimulated Tears

It has long been assumed that unstimulated tears are more thoroughly equilibrated with epithelial secretions than stimulated tears, since they are in contact with tarsal, bulbar and corneal surfaces for longer. It was also believed from results with model solutions that soluble mucin is responsible for the observed surface tension and viscosity of tears. If longer contact means more mucin is dissolved in the aqueous tears, then the surface activity (surface tension lowered by mucin) and viscosity (raised by mucin) of tears should therefore be enhanced in unstimulated over stimulated tears.Pools of stimulated and minimally-stimulated tears were collected from a group of healthy adult volunteers by glass capillary. Viscosities were measured in the Contraves Low Shear 30 rheometer over the range of shear rates 0–130 sec−1. Surface tension was measured in the collection capillaries by a micro-technique, before and after refrigerated storage. Both surface tension and viscosity were determined for a variety of tear proteins and mucins.No significant difference was found between the viscosity/shear rate plots of stimulated and unstimulated tear samples. The viscosities of solutions of individual tear proteins were low, except for the combination of lysozyme and secretory IgA. Surface tensions were also similar in both cases, and unchanged by storage at room temperature or refrigeration, indicating no significant loss of surface-active material by adsorption on the capillary walls. Results with model mucin solutions gave a variety of results indicating either little surface activity or losses due to wall adsorption. Tear proteins, individually or in combination, did not lower surface tension to the level of tears.Tear viscosity seems not to depend on the level of dissolved mucins. This suggests either that a constant level of these is picked up even by short-term contact with ocular surfaces, or that viscosity arises from currently unknown materials which vary little with tear flow rate. This type of shear-dependent viscosity is most easily simulated in model solutions with polyionic linear macromolecules, including mucins. The contribution of individual proteins to overall viscosity is small, but combinations including lysozyme show tear-like characteristics, and may indicate that proteins whose concentration is relatively independent of tear flow rate combine with other tear components (possibly including mucins or lipids) to produce their full effect on tear viscosity. The surface tension results suggest that mucins are not of primary importance. Theories of tear film structure and performance need revision.

Lorazepam pharmacodynamics and pharmacokinetics in children

We evaluated the effects of low doses of lorazepam on episodic versus long-term memory, attention, and somatic and affective symptoms, as well as its pharmacokinetics, in a group of 16 children aged 2.8 to 14.2 years. Psychologic assessments of each child were performed twice before intravenous administration of lorazepam (0.03 mg/kg), and 1 1/2 hours and 24 hours after lorazepam; there were no significant changes in long-term memory, attention, or somatic symptoms. There was a significant decrease in affective symptoms at 1 1/2 hours (p = 0.011), with a trend toward decreased anxiety at 1 1/2 and 24 hours after lorazepam (p = 0.026 and 0.028, respectively). There was also a selective anterograde amnestic effect in 5 of 16 children after lorazepam (p = 0.06). Mean (+/- SD) lorazepam systemic clearance was 1.3 +/- 0.4 ml/min/kg, with a terminal half-life of 10.5 +/- 2.9 hours and an unbound clearance of 15.9 +/- 5.2 ml/min/kg. A group of healthy adult volunteers who were given lorazepam had a mean systemic clearance of 1.0 +/- 0.4 ml/min/kg, somewhat less than that of the children (p = 0.069). There were no significant differences in any lorazepam pharmacokinetic parameter between those children who did versus those who did not have changes in affective symptoms or amnesia. These data should be helpful in establishing the dose of lorazepam in children, as the drug becomes more widely used as an antiemetic, premedicant, and anticonvulsant agent.

Intestinal Permeability in Dermatitis Herpetiformis

Differential absorption of D-xylose and 3-0-methyl-D-glucose, and unmediated intestinal permeation (simple diffusion) of lactulose and L-rhamnose, have been investigated in 20 patients with dermatitis herpetiformis. Both iso-osmolar and hyperosmolar test solutions were employed and the results were compared with those obtained from a group of healthy adult volunteers. The findings in each patient have been correlated with small intestinal histology. The majority of patients with villous atrophy had abnormally raised intestinal lactulose permeation and lactulose/rhamnose permeability ratios, whereas patients with normal small intestinal morphological grading did not differ significantly from the healthy control group in this respect. There was a high incidence of delayed plasma D-xylose absorption peaks in dermatitis herpetiformis irrespective of small intestinal histological findings. These results imply that abnormal intestinal permeability in dermatitis herpetiformis is the result of gluten-induced damage to the mucosa rather than an inherent primary defect. It is therefore improbable that the rash in this condition is purely a manifestation of increased intestinal permeation of antigen.

Pharmacokinetics of theophylline: a dose-range study.

1 Pharmacokinetics of theophylline were investigated in a group of healthy adult volunteers (non smokers and on xanthine-free diet) following single oral administration of 125, 250, 375 and 500 mg doses as tablets (Theodel). 2 Absorption of theophylline was rapid and followed first-order kinetics. Plasma curves were fitted according to a one compartment open model. 3 There was a linear relationship (P less than 0.001) between plasma Cmax or AUCx values and the administered dose. The analysis of variance showed that the pharmacokinetic parameters of theophylline (t1/2 abs, tmax, t1/2 beta, CL, CLR, Vd and F) were not modified at any dose. 4 Absorption of the drug was complete since the recovery in urine of theophylline (13.7 to 16.8% of the dose) and its major metabolites, 1,3-dimethyluric acid (35 to 42%), 1-methyluric acid (21.3 to 26.7%) and 3-methylxanthine (11.5 to 13.7%), accounted for the administered dose. Some impairment of demethylation to 3-methylxanthine was observed in two subjects, however the percentage of theophylline and its major metabolites excreted in urine was constant for all the four doses. 5 On the basis of these results, after single oral administration, elimination of theophylline followed first-order kinetics in the range of doses investigated (1.62 to 10.42 mg/kg).

The metabolism of subcutaneous adipose tissue in the immediate postnatal period of human newborns. 2. Developmental changes in the metabolism of 14 C-(U)-D-glucose and in enzyme activities of phosphofructokinase (PFK; EC. 2.7.1.11) and -hydroxyacyl-CoA dehydrogenase (HAD; EC. 1.1.1.35).

Extract: Changes in the in vitro metabolism of subcutaneous adipose tissue have been compared in normal human newborns from 2 hr to 2 weeks of age. A group of healthy adult volunteers was also included. Samples were obtained by using a needle biopsy technique. More of the isotope from 14C-(U)-D-glucose was incorporated into triglycerides (P < 0.05) and also oxidized by suspensions of adipose cells from infants 2–3 hr of age than in older infants (P < 0.01). The ratio of radioactivity in carbon dioxide to radioactivity in triglyceride was also significantly greater in 2− to 3-hr-old infants than in older neonates (P < 0.05). Thin layer chromatography of the total lipid extract showed the greatest amount of radioactivity in the triglycerides, a small amount in 1,3-diglycerides and 1,2-diglycerides, and a trace in fatty acids and monogiycerides. These findings were compared with the developmental changes in two key enzymes: phosphofructokinase (PFK), which represents the glycolytic pathway, and β-hydroxyacyl-coenzyme A (CoA) dehydrogenase (HAD), which is involved in the β oxidation of fatty acids. The activity ratio of these enzymes decreased with age. In a preparation of isolated mitochondria, HAD activity increased with age (P < 0.001). These changes in substrate utilization and enzyme activity are consistent with an active metabolism of glucose in the subcutaneous adipose tissue in the first hours of life and relatively greater catabolism of fatty acids in older newborns. Speculation: Subcutaneous adipose tissue of human newborns is in many respects more active metabolically than the same tissue in adults. For example, lipolysis and reesterification seem to be more active, at least shortly after birth, and oxygen consumption is increased. This tissue is easily and safely accessible for examination, It responds sensitively to the metabolic situation of the newborn and could be effectively used as a source of information regarding peculiarities of newborns in whom fetal development was abnormal, such as premature delivery, intrauterine growth retardation, and maternal diabetes. Such studies might provide important information for the management of high risk infants.