Serum selenium levels in Slovak population

Blood serum selenium levels were measured in 576 healthy middle aged adults (40–60 yr, 255 men and 321 women) residing in both urban and rural areas in four districts of Slovakia. Serum selenium was determined by electrothermal AAS. The mean (±SD) serum selenium concentration was 0.852±0.335 μmol/L, ranging from 0.219–2.30 μmol/L. A large proportion of the individuals (19.62%) exhibited serum selenium levels under 0.57 μmol/L (45 μmol/L). There was no significant correlation between serum, selenium concentration and age, sex, and smoking status. There were significant differences between districts. The lowest mean (±SD) serum selenium was 0.664±0.269 μmol/L, the highest mean serum selenium (±SD) was 0.975±0.361 μmol/L. This differences could probably be attributed to the selenium, content in the soil of the different areas, which would contribute to the average daily selenium intake. In comparison with serum selenium levels in other European countries, the concentrations of selenium in the Slovak population are relatively low.     

Comparative Analysis of Serum Zinc, Copper, Manganese, Iron, Calcium, and Magnesium Level and Complexity of Interelement Relations in Generalized Anxiety Disorder Patients

The purpose of the study was to determine the concentration of serum trace and other essential elements of generalized anxiety disorder patients and to find out the relationship between element levels and nutritional status or socioeconomic factors. The study was conducted among 50 generalized anxiety disorder patients and 51 healthy volunteers. Patients were selected and recruited in the study with the help of a clinical psychologist by random sampling. The concentrations of serum trace elements (Zn, Cu, Mn, and Fe) and other two essential elements (Ca and Mg) were determined by graphite furnace and flame atomic absorption spectroscopy. Data were analyzed by independent t test, Pearson’s correlation analysis, regression analysis, and analysis of variance. The serum concentrations of Zn, Cu, Mn, Fe, Ca, and Mg in generalized anxiety disorder patients were 1.069?±?0.40, 1.738?±?0.544, 1.374?±?0.750, 3.203?±?2.065, 108.65?±?54.455, and 21?±?4.055 mg/L, while those were 1.292?±?0.621, 0.972?±?0.427, 0.704?±?0.527, 1.605?±?1.1855, 101.849?±?17.713, and 21.521?±?3.659 mg/L in control subjects. Significantly decreased (p?<?0.05) serum Zn concentration was found in the patient group compared to the control group while serum level of Cu, Mn, and Fe was significantly (p?<?0.05) higher, but the differences of the concentration of Ca and Mg between the patient and control groups were not significant (p?>?0.05). Socioeconomic data revealed that most of the patients were in the lower middle class group and middle-aged. Mean BMI of the control group (23.63?±?3.91 kg/m²) and the patient group (23.62?±?3.77 kg/m²) was within the normal range (18.5–25.0 kg/m²). The data obtained from different interelement relations in the generalized anxiety disorder patients and control group strongly suggest that there is a disturbance in the element homeostasis. So changes in the serum trace element level in generalized anxiety disorder patients occur independently and they may provide a prognostic tool for the diagnosis and treatment of this disease.     

Serum extracellular superoxide dismutase activity as an indicator of zinc status in humans

The present study focused on whether serum extracellular superoxide dimutase (EC-SOD) activity can be used as a functional indicator of marginal zinc deficiency in humans. Subjects in this study were 444 healthy adults over 30 yr of age living a normal rural life in Kyunggi province, Korea. The mean dietary zinc intake of subjects obtained from one 24-h recall was 6.41 ± 4.35 mg and the average serum zinc concentration of the subjects was 11.06 ± 2.44 (μmol/L. Subjects were divided into three groups by serum zinc concentrations: adequate (serum zinc >10.7 (μmol/L), low (serum zinc 9.0–10.7 μmol/L), and very low (serum zinc <9.0 μmol/L) groups. A total of 50 subjects were selected from the three groups for analysis of EC-SOD activities. The EC-SOD activity of subjects increased with increasing serum zinc concentrations, and the activities of the three groups were significantly different as indicated by the Kruskal-Wallis test (p = 0.0239). Also, serum EC-SOD activities were significantly correlated with serum zinc concentrations (r = 0.289,p = 0.04). Serum EC-SOD activities, however, were not significantly correlated to the dietary zinc intakes. In conclusion, these results show that EC-SOD activities are decreased in subjects with low serum zinc concentrations and suggest that EC-SOD activity may be a functional indicator of zinc nutritional status in humans.     

Short-term parenteral application of α-tocopherol leads to increased concentration in plasma and tissues of the rat

Numerous studies suggest that supplemental vitamin E prior to or during vast surgeries might diminish or even prevent ischemia/reperfusion-induced injuries. In the present placebo-controlled study male Sprague-Dawley rats were supplemented parenterally or orally with α-tocopherol for three consecutive days. The applied amount of α-tocopherol was 2.3 μmol per day for oral and 1.2 μmol per day for parenteral supplementation. The enrichment of vitamin E concentrations in plasma and tissue samples (aortic endothelium, liver, and lung) was determined by HPLC. The vitamin E level was elevated following intravenous supplementation in plasma (21.4±1.9 μmol/L vs. 10.2±1.7 μmol/L in parenteral control group), in aortic endothelium (1.1±0.2 pmol/mm² vs. 0.5±0.1 pmol/mm²) and in liver and lung (41.3±7.5 pmol/mg vs. 22.9±6.5 pmol/mg and 75.6±13.6 pmol/mg vs. 51.7±5.9 pmol/mg, respectively). Oral supplementation for three days also led to an increased level in liver (38.2±7.7 pmol/mg vs. 22.9±6.6 pmol/mg in oral control group) and in lung (67.8±5.7 pmol/mg vs. 51.7±9.3 pmol/mg) but not in aortic endothelium or plasma (0.8±0.3 pmol/mm² vs. 0.6±0.3 pmol/mm² and 12.0±2.2 μmol/L vs. 10.7±2.6 μol/L.)     

Valorization of Hemicelluloses: Production of Bioxylitol from Poplar Wood Prehydrolyzates by <Emphasis Type="Italic">Candida guilliermondii</Emphasis> FTI 20037

In this study on the valorization of hemicelluloses (a co-product generated during cellulosic bioethanol production), prehydrolyzates obtained from poplar woodchips pretreated in an industrial experimental steam-explosion pilot-plant facility were evaluated for the production of bioxylitol using the yeast, Candida guilliermondii FTI 20037, employing both batch and fed-batch fermentation modes in shake flasks on defined nutrient medium. The prehydrolyzates consisted of monosaccharides (pentose and hexose sugars) as well as xylo-oligosaccharides and undegraded hemicellulose. Xylose (31.6?±?0.57 g/L) was the major sugar in the prehydrolyzates that also contained acetic acid and degradation products of lignin and sugars (phenolic and furanic compounds). Xylose in the prehydrolyzates could be further increased (106.4?±?0.02 g/L) through an acid hydrolysis step (0.6 % (w/v) H₂SO₄). Compounds of a toxic nature in both the acid hydrolyzates and prehydrolyzates were removed by treatment with Amberlite IRA-400 resin (chloride form). Batch fermentation of pure xylose and poplar prehydrolyzate resulted in bioxylitol production of 9.9?±?0.01 and 4.9?±?0.17 g/L, respectively, indicating that the poplar prehydrolyzates exhibited an inhibitory effect on fermentation. After detoxification of the poplar prehydrolyzates, bioxylitol production increased to 8.9?±?0.01 g/L. Fed-batch fermentation of the prehydrolyzate increased the bioxylitol production to 12.39?±?0.33 g/L, while acid hydrolysis followed by detoxification resulted in a maximum bioxylitol production of 22.0?±?0.01 g/L, a 348 % increase. The results demonstrated that acid hydrolysis and detoxification followed by fed-batch fermentation was an efficient way to produce bioxylitol from poplar prehydrolyzates.     

Microcalorimetric method to determine competitive binding action of a psychotropic drug (dipotassium chlorazepate) on L-tryptophan · human serum albumin complex

A mathematical treatment and an original microcalorimetric method are developed to verify an eventual competitive binding between any two substances for the same macromolecule. To apply this method, a competitive binding of L-tryptophan and one benzodiazepin (dipotassium chlorazepate) for human serum albumin is perfectly demonstrated.The association constants and the enthalpy variations are equal to 14 000 ± 2000 M^?1 and ?6.6 ± 0.2 kcal/mol for human serum albumin · tryptophan complex and 13 000 ± 1000 M^?1 and ?10.0 ± 0.2 kcal/mol for human serum albumin · chlorazepate complex. In all cases the stoichiometry is equal to one.The binding of tryptophan to human serum albumin is partially stereospecific; the association constant and the enthalpy variation for D-tryptophan complex are equal, respectively, to 1000 ± 200 M^?1 and ?2.6 ± 0.3 kcal/mol.     

Optimization of nutritional supplements for enhanced lactic acid production utilizing sugar refinery by-products

The present study investigated the synergistic effect of nutritional supplements (amino acid and Tween 80) on lactic acid production by Lactobacillus delbruckii utilizing a sugar refinery by product (cane molasses) in a submerged fermentation process. Initially, the effect of individual factors on lactic acid yield was studied by supplementing amino acids and their combinations, Tween 80 and cane molasses at varying concentrations in production medium. A combination of l-phenylalanine and l-lysine gave a maximum lactic acid yield of 47.89?±?0.1 g/L on a dry cell weight basis at individual factor level. Similarly, maximum lactic acid yield was obtained by supplementing the production medium with 40.0 g/L and 2.0 g/L Tween 80 and cane molasses, respectively, at individual factor level. In order to further improve the lactic acid yield, nutritional supplements were optimized by central composite rotatable design (CCRD) using Minitab 15 software. Shake flask cultivation under optimized conditions, i.e., cane molasses (32.40 g/L), Tween 80 (2.0 g/L) and l-phenylalanine and l-lysine (34.0 mg/L) gave a lactic acid yield of 64.86?±?0.2 g/L, corresponding to 95.0 % of the predicted yield of 67.78?±?0.3 g/L. Batch cultivation performed in 7.5 L bioreactor (working volume: 3.0 L) under optimized conditions gave maximum lactic acid yield and productivity of 79.12?±?0.2 g/L and 3.40 g/L·h, which is higher than previous studies with reduced fermentation time. Screening of lactic acid producing bacteria and characterization of lactic acid was also done.     

In vitro propagation and assessment of genetic integrity of Talinum triangulare (Jacq.) Willd: a valuable medicinal herb

Talinum triangulare is a medicinally important herb and various parts of the plant are used pharmaceutically for the treatment of different diseases. In our study, a rapid and efficient protocol for micropropagation has been developed from shoot tip and nodal explants of T. triangulare. High shooting frequency (93.33?%) was achieved with shoot tip explants when cultured on Murashige and Skoog??s (MS) medium supplemented with 1.0?mg/L 6-benzyl amino purine (BAP) producing an average of 12.50?±?0.23 shoots and 5.07?±?0.02?cm shoot length per explant. A combination of 0.5?mg/L BAP and 0.5?mg/L kinetin was found to be more effective by producing 15.67?±?0.25 shoots and 6.22?±?0.02?cm shoot length per explant. The microshoots were excised and cultured on half-strength MS and full-strength MS medium containing different concentrations of indole-3-acetic acid and indole-3-butyric acid (IBA) for root induction. More number of roots (45.10?±?0.96) with an average length of 5.46?±?0.08?cm was obtained on half-strength MS medium supplemented with 0.5?mg/L IBA. The rooted shoots were successfully transplanted from different planting substrates to the field with a 100?% survival rate. Random amplified polymorphic DNA analysis was carried out using four random decamer primers. The amplification products were monomorphic in the micropropagated plants and were similar to the mother plant. Absence of polymorphism revealed that no variation was induced, thus maintaining the genetic integrity of the micropropagated plants of T. triangulare.     

Efflux of Glutathione and Glutathione Complexes from Human Erythrocytes in Response to Inorganic Arsenic Exposure

The objective of the present study was to investigate if arsenic exposure results in glutathione efflux from human erythrocytes. Arsenite significantly depleted intracellular nonprotein thiol level in a time- and concentration-dependent manner. The intracellular nonprotein thiol level was decreased to 0.767?±?0.0017???mol/ml erythrocyte following exposure to 10?mM of arsenite for 4?h. Extracellular nonprotein thiol level was increased concomitantly with the intracellular decrease and reached to 0.481?±?0.0005???mol/ml erythrocyte in 4?h. In parallel with the change in extracellular nonprotein thiol levels, significant increases in extracellular glutathione levels were detected. Extracellular glutathione levels reached to 0.122?±?0.0013, 0.226?±?0.003, and 0.274?±?0.004???mol/ml erythrocyte with 1, 5, and 10?mM of arsenite, respectively. Dimercaptosuccinic acid treatment of supernatants significantly increased the glutathione levels measured in the extracellular media. Utilization of MK571 and verapamil, multidrug resistance-associated protein 1 and Pgp inhibitors, decreased the rate of glutathione efflux from erythrocytes suggesting a role for these membrane transporters in the process. The results of the present study indicate that human erythrocytes efflux glutathione in reduced free form and in conjugated form or forms that can be recovered with dimercaptosuccinic acid when exposed to arsenite.     

The Influences of Chromium Supplementation on Glycemic Control,Markers of Cardio-Metabolic Risk,and Oxidative Stress in Infertile Polycystic ovary Syndrome Women Candidate for In vitro Fertilization: a Randomized,Double-Blind,Placebo-Controlled Trial

This study was carried out to investigate the effects of chromium intake on glycemic control, markers of cardio-metabolic risk, and oxidative stress in infertile polycystic ovary syndrome (PCOS) women candidate for in vitro fertilization (IVF). This randomized double-blind, placebo-controlled trial was done among 40 subjects with infertile PCOS candidate for IVF, aged 18–40 years old. Individuals were randomly allocated into two groups to take either 200 μg/day of chromium (n?=?20) or placebo (n?=?20) for 8 weeks. Biochemical parameters were assessed at baseline and at end-of-trial. Compared with the placebo, taking chromium supplements led to significant reductions in fasting plasma glucose (??2.3?±?5.7 vs. +?0.9?±?3.1 mg/dL, P?=?0.03), insulin levels (??1.4?±?2.1 vs. +?0.4?±?1.7 μIU/mL, P?=?0.004), homeostatic model of assessment for insulin resistance (??0.3?±?0.5 vs. +?0.1?±?0.4, P?=?0.005), and a significant increase in quantitative insulin sensitivity check index (+?0.004?±?0.008 vs. ??0.001?±?0.008, P?=?0.03). In addition, chromium supplementation significantly decreased serum triglycerides (??19.2?±?33.8 vs. +?8.3?±?21.7 mg/dL, P?=?0.004), VLDL- (??3.8?±?6.8 vs. +?1.7?±?4.3 mg/dL, P?=?0.004) and total cholesterol concentrations (??15.3?±?26.2 vs. ??0.6?±?15.9 mg/dL, P?=?0.03) compared with the placebo. Additionally, taking chromium supplements was associated with a significant increase in plasma total antioxidant capacity (+?153.9?±?46.1 vs. ??7.8?±?43.9 mmol/L, P?<?0.001) and a significant reduction in malondialdehyde values (?0.3?±?0.3 vs. +?0.1?±?0.2 μmol/L, P?=?0.001) compared with the placebo. Overall, our study supported that chromium administration for 8 weeks to infertile PCOS women candidate for IVF had beneficial impacts on glycemic control, few variables of cardio-metabolic risk, and oxidative stress.     

Effect of All-Trans Retinoic Acid on the Differentiation of U87 Glioma Stem/Progenitor Cells

GSPCs (glioma stem/progenitor cells) were isolated from U87 glioma cell lines by serum-free neural stem cell medium. Four concentrations (1, 2, 4, and 8 μmol/L) of ATRA (all-trans retinoic acid) were used to induce the differentiation of GSPCs in the medium with or without growth factors. The effect of ATRA on the differentiation of GSPCs was analyzed by flow cytometry, real-time-PCR, and immunofluorescence. The differentiation of GSPCs could be induced by 1 or 2 μmol/L ATRA when GSPCs were cultured in growth factor-free medium. The detection of real-time-PCR showed that the level of GFAP (glial fibrillary acidic protein) mRNA of differentiated GSPCs in the growth factor-free medium containing 1 μmol/L ATRA group was significantly higher than that in the control group, and there was no significant difference in the level of TUBB-3 mRNA between the two groups. The GSPCs suffered apoptosis in the growth factor-free medium containing 4 or 8 μmol/L ATRA. The differentiation of GSPCs could not be induced by ATRA when GSPCs were cultured in the medium containing growth factors. The percentage of cells in G0/G1 phase was 84.26 ± 2.24 %, and the percentage of apoptosis was 18.95 ± 2.53 % in experimental groups which was similar to those in the control group. In conclusion, ATRA has certain capacity to induce differentiation of GSPCs, while its effective concentration should be controlled strictly. The differentiation of GSPCs induced by ATRA cannot antagonize the formidable differential inhibition of epidermal growth factor and basic fibroblast growth factor.     

Increased plasma concentration of 4-pyridone-3-carboxamide-1-ß-D-ribonucleoside (4PYR) in lung cancer. Preliminary studies

Abstract

4-pyridone-3-carboxamide-1-β-D-ribonucleoside (4PYR) is a new nicotinamide derivative, which is potentially toxic to the endothelium. Dysfunction of the endothelium promotes cancer cell proliferation, invasiveness, and inflammatory signaling. The aim of this study was to analyze 4PYR concentration in the plasma of lung cancer patients and its relationship to other known biochemical parameters associated with the endothelium function.

The concentration of 4PYR, nicotinamide, 1-methylnicotinamide (MNA), amino acids, and their derivatives were measured in samples obtained from patients with primary squamous cell carcinoma (n?=?48) and control group (n?=?100).

The concentration of 4PYR and 4PYR/MNA ratio were significantly higher in lung cancer patients as compared to controls (0.099?±?0.009 vs. 0.066?±?0.006?µmol/L and 1.10?±?0.08 vs. 1.97?±?0.15, respectively). The plasma arginine/asymmetric dimethylarginine (Arg/ADMA) ratio was considerably lower in lung cancer patients (253?±?17 vs. 369?±?19) as well as plasma MNA (0.057?±?0.004 vs. 0.069?±?0.003?µmol/L). There was no difference in the plasma concentrations of nicotinamide and nicotinamide riboside in both groups (0.116?±?0.019 vs. 0.131?±?0.014 and 0.102?±?0.006 vs. 0.113?±?0.011, respectively).

In this study, a higher 4PYR concentration was observed for the first time in patients with squamous cell carcinoma. This change may be related to the endothelial dysfunction that promote cancer progression since 4PYR and its derivatives are known to disrupt glycolytic pathway.     

Oxalic acid enhances Cr tolerance in the accumulating plant Leersia hexandra Swartz

This study examined the relationship between oxalic acid and Cr tolerance in an accumulating plant Leersia hexandra Swartz. The plants grown in hydroponics were exposed to Cr at 0, 5, 30, and 60 mg/L (without oxalate), and 0, 40, and 80 mg/L concentrations of Cr (with 70 mg/L oxalate or without oxalate). The results showed that more than 50% of Cr in shoots was found in HCl-extracted fraction (chromium oxalate) when the plants were exposed to Cr. Cr supply significantly increased oxalate concentration in shoots of L. hexandra (p < 0.05), but did not increase oxalate concentration in roots. Under 80 mg/L Cr stress, electrolyte leakages from roots and shoots with oxalate treatment were both significantly lower than those without oxalate treatment (p < 0.05), indicating exogenous oxalate supply alleviated Cr-induced membrane damage. Oxalate added to growth solution ameliorated reduction of biomass and inhibition of root growth induced by Cr, which demonstrated that application of oxalate helped L. hexandra tolerate Cr stress. However, oxalate supply did not affect the Cr concentrations both in roots and shoots of L. hexandra. These results suggest that oxalic acid may act as an important chelator and takes part in detoxifying chromium in internal process of L. hexandra.     

Optimization of propionic acid production in apple pomace extract with Propionibacterium freudenreichii

Abstract

Sequential optimization of propionate production using apple pomace was studied. All experiments were performed in a static flask in anaerobic conditions. Effect of apple pomace as nitrogen source against conventional N sources (yeast extract, peptone) was studied. The double increase was observed in propionic acid production while using yeast extract and peptone (0.29?±?0.01?g/g), as against the use of only apple pomace extract (APE) (0.14?±?0.01?g/g). Intensification of propionic acid fermentation was also achieved by increasing the pH control frequency of the culture medium from 24-(0.29?±?0.01?g/g) to 12-hour intervals (30?°C) (0.30?±?0.02?g/g) and by increasing the temperature of the culture from 30 to 37?°C (12-hour intervals of pH control) (0.32?±?0.01?g/g). An important factor in improving the parameters of fermentation was the addition of biotin to the medium. The 0.2?mg/L dose of biotin allowed to attain 7.66?g/L propionate with a yield of 0.38?±?0.03?g/g (12-hour intervals of pH control, 37?°C).     

Role of diagnostic factors associated with antioxidative status and expression of matrix metalloproteinases (MMPs) in patients with cancer therapy induced ocular disorders

Background

Cancer patients when treated with different chemotherapeutic drugs often develop mild to severe sight threatening diseases during or after chemotherapy. The mechanism involved in the pathogenesis of ocular toxicities is poorly understood. Oxidative stress, inflammation and MMPs (angiogenic factor) are involved in the progression of chemotherapy related ocular disorders.

Content of amino acids in axons from the CNS of the lobster

The contents of alanine, proline, glycine, GABA, glutamate, and aspartate were measured in four bundles of axons (designated areas A through D) from the circumesophageal connective of the lobster (Homarus americanus). The contents of these amino acids were also determined in individual axons within specific bundles and in the external sheath covering the circumesophageal connective. Within the nerve bundles the levels of aspartate were highest of the amino acids measured, ranging from 1.95 ± 0.12 m̈mol/mg protein in area C to 7.55 ± 0.54 m̈mol/mg protein in area B. On the other hand, GABA had the lowest value in the four bundles; its highest level was found in area C (0.083 ± 0.006 m̈mol/mg protein) and the lowest in area B (none detected). The content of glycine ranged from 1.63 ± 0.14 (area C) to 2.52 ± 0.32 m̈mol/mg protein in area A; that for glutamate ranged from 0.390 ± 0.019 (area C) to 1.01 ± 0.103 (area B). The contents of alanine and proline changed relatively little from bundle-to-bundle. The content of aspartate was the highest of any of the amino acids assayed in individual axons (with diameters in the range of 40 to 65 m̈) dissected from areas B and C. Glycine had the next highest content followed in order by glutamate, proline, and alanine. GABA was not detected in these axons. With the exception of GABA (which could not be detected), aspartate had the lowest level (0.066 ± 0.017) and glycine had the highest level (2.00 ± 0.498 m̈mol/mg protein) in the external sheath covering the the circumesophageal connective.     

Chemiluminescent measurement of oxalate in serum by detection of hydrogen peroxide generated through oxalate oxidase

Today, chemiluminescence detection reactions have become popular in analytical biochemistry essentially due to their high sensitivity. A chemiluminescent synthetic system (luminol/porphyrin) was successfully used to measure serum oxalate by determination of hydrogen peroxide generated through oxalate oxidase (EC 1.2.3.4.). This new method is efficient and simple, highly sensitive and the results obtained in normal adult subjects are in good agreement with those of approved methods. This original application of such a chemiluminescent system allowed us to achieve a sensitive serum oxalate assay (detection limit of 0.2 μmol/L) characterized by a low serum volume (200 μL) required for analysis. © 1997 John Wiley & Sons, Ltd.     

Serum Levels of Antioxidants (Zn, Cu, Se) in Healthy Volunteers Living in Tehran

Zinc (Zn), copper (Cu), and selenium (Se) are well-known as essential trace elements. These elements attract a great interest, not only in the scientific world, but also in the public option. The aim of this study was to evaluate the serum Zn, Cu, and Se levels in healthy volunteers (60 females and 55 males) living in Tehran. The age (6–62 years) and sex of the subjects, as well as drug and tobacco consumption, were registered. The concentrations of these elements were determined by atomic absorption spectrometry. The serum levels of Zn, Cu, and Se in the normal population of Tehran was 0.89?±?0.16 mg/L, 0.95?±?0.20 mg/L, and 99.10?±?21.78 μg/L, respectively. There was no significant gender-related difference in serum Zn concentration (p?<?0.15). However, a significant difference (p?<?0.05) in both Cu and Se levels was observed between males and females.     

Effect of Basal Gastric Acid Secretion on the Pharmacodynamics of Ranitidine

Twelve patients with inactive ulcer disease were administered placebo and ranitidine via bolus and continuous intravenous infusions, at doses ranging from 50 every 8 h, to 12.5 mg/h for 24 h. Gastric acid was collected for 20 min each h for 24 h, and ranitidine serum concentrations were measured ± every 2 h, during each of the six study periods. Cosinor analysis of gastric acid secretion during placebo treatment revealed a significant circadian rhythm in all subjects. Mesor acid output ranged from 1.7 to 11.6 mmol/h (mean 5.6 ± 2.8 mmol/h) and the amplitude ranged from 0.7 to 6.5 mmol/h (mean 2.8 ±1.6 mmol/h). Peak acid output (acrophase) occurred at 10 p.m. ± 3 h. A pharmacodynamic model, relating ranitidine serum concentration to hourly acid secretion, was derived, which incorporated the circadian change in basal acid output. Data for this fractional response model included basal acid secretion–as determined by time of day, measured acid secretion, and associated serum ranitidine concentration. The 50% inhibitory concentration (IC₅₀) for ranitidine ranged from 10-75 ng/ml, with a mean of 44 ng/ml. The variation in IC₅₀ and in basal acid secretion combined to produce a wide variation in the pharmacodynamic response to ranitidine. The model-predicted serum concentrations, required to maintain acid secretion at 0.1 mmol/h, ranged from 250 to 1550 ng/ml, at the time of peak evening acid secretion. Despite a constant degree of acid inhibition by ranitidine during the day, higher serum concentrations are required during times of peak acid output to maintain adequate suppression of hydrogen ion secretion.     

Nutritional factors of inflammation induction or lipid mechanism of endotoxin transport

Integral parameters of bacterial lipopolysaccharide concentration and antiendotoxin immunity activity were determined in the blood serum of subjects with two extreme variants of eating disorders: obesity and anorexia nervosa (in its clinical model, long-term starvation). The results of the study showed that obese patients had initially higher endotoxin concentrations (2.41 ± 0.11 vs 1.13 ± 0.05 EU/mL in the control), which significantly decreased as a result taking a course of orlistat or after starvation (for no longer than 20 days) (to 1.34 ± 0.04 and 1.01 ± 0.09 EU/mL, respectively). The decrease in the endotoxin serum level was associated with an increase in the concentration of high-density lipoproteins (HDLs) and a decrease in the concentration of low-density lipoproteins (LDLs). This allowed us to assume that the complex of the latter with the endotoxin is the LDL fraction that may function as a depot of the hydrophobic form of the lipopolysaccharide molecule in the bloodstream. Long-term starvation (starting from day 20) led to the appearance of symptoms characteristic of septic states, which was preceded by a twofold increase in the concentration of the endotoxin and antibodies against the enterobacterial common antigen and subsequent increase in the level of anti-glycolipid antibodies (from 133.2 ± 2.6 to 355.6 ± 15.0 optical density arbitrary units) starting from day 25?C27 of starvation, which is characteristic for the initial phase of the systemic inflammatory response syndrome.