Lung Tissue Concentrations of Pyrazinamide among Patients with Drug-Resistant Pulmonary Tuberculosis

Science.gov (United States)

Heinrichs, M. Tobias; Nikolaishvili, Ketino; Sabulua, Irina; Bablishvili, Nino; Gogishvili, Shota; Avaliani, Zaza; Tukvadze, Nestani; Little, Brent; Bernheim, Adam; Read, Timothy D.; Guarner, Jeannette; Derendorf, Hartmut; Peloquin, Charles A.; Blumberg, Henry M.; Vashakidze, Sergo

2017-01-01

ABSTRACT Improved knowledge regarding the tissue penetration of antituberculosis drugs may help optimize drug management. Patients with drug-resistant pulmonary tuberculosis undergoing adjunctive surgery were enrolled. Serial serum samples were collected, and microdialysis was performed using ex vivo lung tissue to measure pyrazinamide concentrations. Among 10 patients, the median pyrazinamide dose was 24.7 mg/kg of body weight. Imaging revealed predominant lung lesions as cavitary (n = 6 patients), mass-like (n = 3 patients), or consolidative (n = 1 patient). On histopathology examination, all tissue samples had necrosis; eight had a pH of ≤5.5. Tissue samples from two patients were positive for Mycobacterium tuberculosis by culture (pH 5.5 and 7.2). All 10 patients had maximal serum pyrazinamide concentrations within the recommended range of 20 to 60 μg/ml. The median lung tissue free pyrazinamide concentration was 20.96 μg/ml. The median tissue-to-serum pyrazinamide concentration ratio was 0.77 (range, 0.54 to 0.93). There was a significant inverse correlation between tissue pyrazinamide concentrations and the amounts of necrosis (R = −0.66, P = 0.04) and acid-fast bacilli (R = −0.75, P = 0.01) identified by histopathology. We found good penetration of pyrazinamide into lung tissue among patients with pulmonary tuberculosis with a variety of radiological lesion types. Our tissue pH results revealed that most lesions had a pH conducive to pyrazinamide activity. The tissue penetration of pyrazinamide highlights its importance in both drug-susceptible and drug-resistant antituberculosis treatment regimens. PMID:28373198

Lung Tissue Concentrations of Pyrazinamide among Patients with Drug-Resistant Pulmonary Tuberculosis.

Science.gov (United States)

Kempker, Russell R; Heinrichs, M Tobias; Nikolaishvili, Ketino; Sabulua, Irina; Bablishvili, Nino; Gogishvili, Shota; Avaliani, Zaza; Tukvadze, Nestani; Little, Brent; Bernheim, Adam; Read, Timothy D; Guarner, Jeannette; Derendorf, Hartmut; Peloquin, Charles A; Blumberg, Henry M; Vashakidze, Sergo

2017-06-01

Improved knowledge regarding the tissue penetration of antituberculosis drugs may help optimize drug management. Patients with drug-resistant pulmonary tuberculosis undergoing adjunctive surgery were enrolled. Serial serum samples were collected, and microdialysis was performed using ex vivo lung tissue to measure pyrazinamide concentrations. Among 10 patients, the median pyrazinamide dose was 24.7 mg/kg of body weight. Imaging revealed predominant lung lesions as cavitary ( n = 6 patients), mass-like ( n = 3 patients), or consolidative ( n = 1 patient). On histopathology examination, all tissue samples had necrosis; eight had a pH of ≤5.5. Tissue samples from two patients were positive for Mycobacterium tuberculosis by culture (pH 5.5 and 7.2). All 10 patients had maximal serum pyrazinamide concentrations within the recommended range of 20 to 60 μg/ml. The median lung tissue free pyrazinamide concentration was 20.96 μg/ml. The median tissue-to-serum pyrazinamide concentration ratio was 0.77 (range, 0.54 to 0.93). There was a significant inverse correlation between tissue pyrazinamide concentrations and the amounts of necrosis ( R = -0.66, P = 0.04) and acid-fast bacilli ( R = -0.75, P = 0.01) identified by histopathology. We found good penetration of pyrazinamide into lung tissue among patients with pulmonary tuberculosis with a variety of radiological lesion types. Our tissue pH results revealed that most lesions had a pH conducive to pyrazinamide activity. The tissue penetration of pyrazinamide highlights its importance in both drug-susceptible and drug-resistant antituberculosis treatment regimens. Copyright © 2017 American Society for Microbiology.

Free amino nitrogen concentration correlates to total yeast assimilable nitrogen concentration in apple juice.

Science.gov (United States)

Boudreau, Thomas F; Peck, Gregory M; O'Keefe, Sean F; Stewart, Amanda C

2018-01-01

Yeast assimilable nitrogen (YAN) is essential for yeast growth and metabolism during apple ( Malus x domestica Borkh.) cider fermentation. YAN concentration and composition can impact cider fermentation kinetics and the formation of volatile aroma compounds by yeast. The YAN concentration and composition of apples grown in Virginia, USA over the course of two seasons was determined through analysis of both free amino nitrogen (FAN) and ammonium ion concentration. FAN was the largest fraction of YAN, with a mean value of 51 mg N L -1 FAN compared to 9 mg N L -1 ammonium. Observed YAN values ranged from nine to 249 mg N L -1 , with a mean value of 59 mg N L -1 . Ninety-four percent of all samples analyzed in this study contained yeast to fully utilize all of the fermentable sugars. FAN concentration was correlated with total YAN concentration, but ammonium concentration was not. Likewise, there was no correlation between FAN and ammonium concentration.

Plasma vs heart tissue concentration in humans - literature data analysis of drugs distribution.

Science.gov (United States)

Tylutki, Zofia; Polak, Sebastian

2015-03-12

Little is known about the uptake of drugs into the human heart, although it is of great importance nowadays, when science desires to predict tissue level behavior rather than to measure it. Although the drug concentration in cardiac tissue seems a better predictor for physiological and electrophysiological changes than its level in plasma, knowledge of this value is very limited. Tissue to plasma partition coefficients (Kp) come to rescue since they characterize the distribution of a drug among tissues as being one of the input parameters in physiologically based pharmacokinetic (PBPK) models. The article reviews cardiac surgery and forensic medical studies to provide a reference for drug concentrations in human cardiac tissue. Firstly, the focus is on whether a drug penetrates into heart tissue at a therapeutic level; the provided values refer to antibiotics, antifungals and anticancer drugs. Drugs that directly affect cardiomyocyte electrophysiology are another group of interest. Measured levels of amiodarone, digoxin, perhexiline and verapamil in different sites in human cardiac tissue where the compounds might meet ion channels, gives an insight into how these more lipophilic drugs penetrate the heart. Much data are derived from postmortem studies and they provide insight to the cardiac distribution of more than 200 drugs. The analysis depicts potential problems in defining the active concentration location, what may indirectly suggest multiple mechanisms involved in the drug distribution within the heart. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

Total mercury concentration in common fish species of Lake Victoria ...

African Journals Online (AJOL)

Total mercury (THg) concentration was analysed in muscles of common fish species of Lake Victoria in the eastern and southern parts of the lake using cold vapour Atomic Absorption Spectrophotometric technique. Mercury concentration in all fish species was generally lower than the WHO maximum allowable ...

Exchange of reactive nitrogen compounds: concentrations and fluxes of total ammonium and total nitrate above a spruce canopy

Directory of Open Access Journals (Sweden)

V. Wolff

2010-05-01

Full Text Available Total ammonium (tot-NH₄⁺ and total nitrate (tot-NO₃⁻ provide chemically conservative quantities in the measurement of surface exchange of reactive nitrogen compounds ammonia (NH₃, particulate ammonium (NH₄⁺, nitric acid (HNO₃, and particulate nitrate (NO₃⁻, using the aerodynamic gradient method. Total fluxes were derived from concentration differences of total ammonium (NH₃ and NH₄⁺ and total nitrate (HNO₃ and NO₃⁻ measured at two levels. Gaseous species and related particulate compounds were measured selectively, simultaneously and continuously above a spruce forest canopy in south-eastern Germany in summer 2007. Measurements were performed using a wet-chemical two-point gradient instrument, the GRAEGOR. Median concentrations of NH₃, HNO₃, NH₄⁺, and NO₃⁻ were 0.57, 0.12, 0.76, and 0.48 μg m⁻³, respectively. Total ammonium and total nitrate fluxes showed large variations depending on meteorological conditions, with concentrations close to zero under humid and cool conditions and higher concentrations under dry conditions. Mean fluxes of total ammonium and total nitrate in September 2007 were directed towards the forest canopy and were −65.77 ng m⁻² s⁻¹ and −41.02 ng m⁻² s⁻¹ (in terms of nitrogen, respectively. Their deposition was controlled by aerodynamic resistances only, with very little influence of surface resistances. Including measurements of wet deposition and findings of former studies on occult deposition (fog water interception at the study site, the total N deposition in September 2007 was estimated to 5.86 kg ha⁻¹.

Preliminary evaluation of serum total cholesterol concentrations in dogs with osteosarcoma.

Science.gov (United States)

Leeper, H; Viall, A; Ruaux, C; Bracha, S

2017-10-01

To determine if total serum cholesterol concentrations were altered in dogs with osteosarcoma. To evaluate association of total serum cholesterol concentration with clinical outcomes in dogs with appendicular osteosarcoma. Retrospective, multi-institutional study on 64 dogs with osteosarcoma. Control population consisted of dogs with traumatic bone fractures (n=30) and healthy patients of similar age and weight as those of the osteosarcoma cases (n=31). Survival analysis was done on 35 appendicular osteosarcoma patients that received the current standard of care. Statistical associations were assessed by univariable and multi-variable analysis. Information about age, sex, primary tumour location, total cholesterol concentration, monocytes and lymphocyte counts and alkaline phosphatase were also included. Total cholesterol was elevated above the reference interval (3·89 to 7·12 mmol/L) (150 to 275 mg/dL) in 29 of 64 (45·3%) osteosarcoma-bearing dogs, whereas similar elevations were found in only 3 of 30 (10%) fracture controls (Posteosarcoma. These results suggest that elevated total cholesterol is associated with canine osteosarcoma and may have prognostic significance. © 2017 British Small Animal Veterinary Association.

Can fluconazole concentrations in saliva be used for therapeutic drug monitoring?

NARCIS (Netherlands)

Koks, C. H.; Crommentuyn, K. M.; Hoetelmans, R. M.; Mathôt, R. A.; Beijnen, J. H.

2001-01-01

The saliva/plasma concentration ratio of fluconazole was investigated in 22 HIV-1-infected individuals with an oropharyngeal Candida infection to determine whether saliva fluconazole concentrations could provide useful information for therapeutic drug monitoring in this population. Steady-state

Improved estimates of filtered total mercury loadings and total mercury concentrations of solids from potential sources to Sinclair Inlet, Kitsap County, Washington

Science.gov (United States)

Paulson, Anthony J.; Conn, Kathleen E.; DeWild, John F.

2013-01-01

Previous investigations examined sources and sinks of mercury to Sinclair Inlet based on historic and new data. This included an evaluation of mercury concentrations from various sources and mercury loadings from industrial discharges and groundwater flowing from the Bremerton naval complex to Sinclair Inlet. This report provides new data from four potential sources of mercury to Sinclair Inlet: (1) filtered and particulate total mercury concentrations of creek water during the wet season, (2) filtered and particulate total mercury releases from the Navy steam plant following changes in the water softening process and discharge operations, (3) release of mercury from soils to groundwater in two landfill areas at the Bremerton naval complex, and (4) total mercury concentrations of solids in dry dock sumps that were not affected by bias from sequential sampling. The previous estimate of the loading of filtered total mercury from Sinclair Inlet creeks was based solely on dry season samples. Concentrations of filtered total mercury in creek samples collected during wet weather were significantly higher than dry weather concentrations, which increased the estimated loading of filtered total mercury from creek basins from 27.1 to 78.1 grams per year. Changes in the concentrations and loading of filtered and particulate total mercury in the effluent of the steam plant were investigated after the water softening process was changed from ion-exchange to reverse osmosis and the discharge of stack blow-down wash began to be diverted to the municipal water-treatment plant. These changes reduced the concentrations of filtered and particulate total mercury from the steam plant of the Bremerton naval complex, which resulted in reduced loadings of filtered total mercury from 5.9 to 0.15 grams per year. Previous investigations identified three fill areas on the Bremerton naval complex, of which the western fill area is thought to be the largest source of mercury on the base

Effect of gamma radiation on total antioxidant capacity, total lipid concentration and shelf life of finger millet flour

International Nuclear Information System (INIS)

Lathika; Manupriya, B.R.; Shenoy, K.B.; Patil, S.L.; Somashekarappa, H.M.

2016-01-01

The present study is an attempt to study the impact of gamma radiation on the shelf life, total antioxidant capacity and total lipid concentration of finger millet (Eleusine coracana L.) flour. Finger millet flour was procured from market. Flour samples of 50 g were taken in triplicates in a polyethylene pouch, air sealed and subjected to gamma irradiation doses ranging from 0.25 to 10 kGy and stored in polyethylene bags and plastic containers for a period of 1 year. Within 24 hours of irradiation, the samples were tested for moisture (2 ± 0.2%), total antioxidant capacity (0.12 ± 0.010 mg) and lipid concentration (15 ± 0.4 mg)

Suspended particle and drug ingredient concentrations in hospital dispensaries and implications for pharmacists' working environments.

Science.gov (United States)

Inaba, Ryoichi; Hioki, Atsushi; Kondo, Yoshihiro; Nakamura, Hiroki; Nakamura, Mitsuhiro

2016-03-01

The aim of this study was to assess the present status of working environments for pharmacists, including the concentrations of suspended particles and suspended drug ingredients in dispensaries. We conducted a survey on the work processes and working environment in 15 hospital dispensaries, and measured the concentrations of suspended particles and suspended drug ingredients using digital dust counter and high-performance liquid chromatography tandem mass spectrometry (LC-MS/MS), respectively. Of 25 types of powdered drugs that were frequently handled in the 15 dispensaries surveyed, 11 could be quantitatively determined. The amounts of suspended particles were relatively high, but below the reference value, in three dispensaries without dust collectors. The sedative-hypnotic drug zopiclone was detected in the suspended particles at one dispensary that was not equipped with dust collectors, and the antipyretic and analgesic drug acetaminophen was detected in two dispensaries equipped with dust collectors. There was no correlation between the daily number of prescriptions containing powdered drugs and the concentration of suspended particles in dispensaries. On the basis of the suspended particle concentrations measured, we concluded that dust collectors were effective in these dispensaries. However, suspended drug ingredients were detected also in dispensaries with dust collectors. These results suggest that the drug dust control systems of individual dispensaries should be properly installed and managed.

Clinical significance of 2 h plasma concentrations of first-line anti-tuberculosis drugs

DEFF Research Database (Denmark)

Prahl, Julie B; Johansen, Isik S; Cohen, Arieh S

2014-01-01

OBJECTIVES: To study 2 h plasma concentrations of the first-line tuberculosis drugs isoniazid, rifampicin, ethambutol and pyrazinamide in a cohort of patients with tuberculosis in Denmark and to determine the relationship between the concentrations and the clinical outcome. METHODS: After 6......-207 days of treatment (median 34 days) 2 h blood samples were collected from 32 patients with active tuberculosis and from three patients receiving prophylactic treatment. Plasma concentrations were determined using LC-MS/MS. Normal ranges were obtained from the literature. Clinical charts were reviewed...... failure occurred more frequently when the concentrations of isoniazid and rifampicin were both below the normal ranges (P = 0.013) and even more frequently when they were below the median 2 h drug concentrations obtained in the study (P = 0.005). CONCLUSIONS: At 2 h, plasma concentrations of isoniazid...

Influence of drug concentration on the diffusion parameters of caffeine

Science.gov (United States)

Mustapha, R.Ben; Lafforgue, C.; Fenina, N.; Marty, J.P.

2011-01-01

Background and Objectives: In the fields of the pharmaceutical and cosmetic industries and in toxicology, the study of the skin penetration of molecules is very interesting. Various studies have considered the impact of different physicochemical drug characteristics, skin thickness, and formulations, on the transition from the surface of the skin to the underlying tissues or to the systemic circulation; however, the influence of drug concentration on the permeation flux of molecules has rarely been raised. Our study aims to discover the influence of caffeine concentration in a formulation on the percutaneous penetration from gels, as a result of different dose applications to polysulfate membrane and human skin. Materials and Methods: For this purpose, three identical base gels were used at 1, 3, and 5% of caffeine, to evaluate the effect of the concentration of caffeine on in vitro release through the synthetic membrane and ex vivo permeation through the human skin, using diffusion FranzTM cells. Results: The diffusion through the epidermal tissue was significantly slower than through the synthetic membrane, which recorded an increase of flux with an increase in the concentration of caffeine. The skin permeation study showed that diffusion depended not only on the concentration, but also on the deposited amount of gel. Nevertheless, for the same amount of caffeine applied, the flux was more significant from the less concentrated gel. Conclusion: Among all the different concentrations of caffeine examined, 1% gel of caffeine applied at 5 mg / cm2 showed the highest absorption characteristics across human skin. PMID:21572649

Concentration and flux of total and dissolved phosphorus, total nitrogen, chloride, and total suspended solids for monitored tributaries of Lake Champlain, 1990-2012

Science.gov (United States)

Medalie, Laura

2014-01-01

Annual and daily concentrations and fluxes of total and dissolved phosphorus, total nitrogen, chloride, and total suspended solids were estimated for 18 monitored tributaries to Lake Champlain by using the Weighted Regressions on Time, Discharge, and Seasons regression model. Estimates were made for 21 or 23 years, depending on data availability, for the purpose of providing timely and accessible summary reports as stipulated in the 2010 update to the Lake Champlain “Opportunities for Action” management plan. Estimates of concentration and flux were provided for each tributary based on (1) observed daily discharges and (2) a flow-normalizing procedure, which removed the random fluctuations of climate-related variability. The flux bias statistic, an indicator of the ability of the Weighted Regressions on Time, Discharge, and Season regression models to provide accurate representations of flux, showed acceptable bias (less than ±10 percent) for 68 out of 72 models for total and dissolved phosphorus, total nitrogen, and chloride. Six out of 18 models for total suspended solids had moderate bias (between 10 and 30 percent), an expected result given the frequently nonlinear relation between total suspended solids and discharge. One model for total suspended solids with a very high bias was influenced by a single extreme value; however, removal of that value, although reducing the bias substantially, had little effect on annual fluxes.

Relationship between red wine grades and phenolics. 1. Tannin and total phenolics concentrations.

Science.gov (United States)

Mercurio, Meagan D; Dambergs, Robert G; Cozzolino, Daniel; Herderich, Markus J; Smith, Paul A

2010-12-08

Measuring chemical composition is a common approach to support decisions about allocating foods and beverages to grades related to market value. Red wine is a particularly complex beverage, and multiple compositional attributes are needed to account for its sensory properties, including measurement of key phenolic components such as anthocyanins, total phenolics, and tannin, which are related to color and astringency. Color has been shown to relate positively to red wine grade; however, little research has been presented that explores the relationship between astringency-related components such as total phenolic or tannin concentration and wine grade. The aim of this research has been to investigate the relationship between the wine grade allocations of commercial wineries and total phenolic and tannin concentrations, respectively, in Australian Shiraz and Cabernet Sauvignon wines. Total phenolic and tannin concentrations were determined using the methyl cellulose precipitable (MCP) tannin assay and then compared to wine grade allocations made by winemaker panels during the companies' postvintage allocation process. Data were collected from wines produced by one Australian wine company over the 2005, 2006, and 2007 vintages and by a further two companies in 2007 (total wines = 1643). Statistical analysis revealed a positive trend toward higher wine grade allocation and wines that had higher concentrations of both total phenolics and tannin, respectively. This research demonstrates that for these companies, in general, Cabernet Sauvignon and Shiraz wines allocated to higher market value grades have higher total phenolics and higher tannin concentrations and suggests that these compositional parameters should be considered in the development of future multiparameter decision support systems for relevant commercial red wine grading processes. In addition, both tannin and total phenolics would ideally be included because although, in general, a positive relationship

Dielectric compound parabolic concentrating solar collector with frustrated total internal reflection absorber

Science.gov (United States)

Hull, J. R.

Since its introduction, the concept of nonimaging solar concentrators, as exemplified by the compound parabolic concentrator (CPC) design, has greatly enhanced the ability to collect solar energy efficiently in thermal and photovoltaic devices. When used as a primary concentrator, a CPC can provide significant concentration without the complication of a tracking mechanism and its associated maintenance problems. When used as a secondary, a CPC provides higher total concentration, or for a fixed concentration, tolerates greater tracking error in the primary.

Vertical distribution of total carbon, nitrogen and phosphorus in sediments of Drug Spring Lake, Wudalianchi

Science.gov (United States)

Zeng, Ying; Yang, Chen

2018-02-01

The content of total organic carbon, total nitrogen and total phosphorus in sediments of Drug Spring Lake was detected and their vertical distribution characteristic was analysed. Results showed that there were significant changes to the content of total organic carbon, total nitrogen and total phosphorus in different depth of the columnar sediments. Their highest content both appeared in the interval of 10cm to 25cm corresponding to the period of 1980s to 1990s, when the tourism of Wudalianchi scenic area began to develop. It reflected the impact of human activities on the Drug Spring Lake. That means the regulation was still not enough, although a series of pollution control measures adopted by the government in recent years had initial success.

Effect of gamma irradiation on total carbohydrate concentration of finger millet flour

International Nuclear Information System (INIS)

Lathika; Patil, Shrikant L.; Bhasker Shenoy, K.; Somashekarappa, H.M.

2015-01-01

Ragi or finger millet (Eleusine coracana L.) is one of the common millets in several regions of India. The effect of gamma irradiation, on ragi flour was investigated in the study. Ragi flour is procured from market. Flour samples of 50 gms were taken in triplicates in a polyethylene pouch, air sealed and subjected to gamma irradiation doses ranging from 0.25 to 10 kGy and stored in polyethylene bags and plastic containers for a period of 30 and 90 days. Within 24 hours of irradiation, the samples were tested for total carbohydrate concentration by phenol-sulphuric acid method. The same was repeated after 30 and 90 days of storage. The comparative study showed that, at 0 day, total carbohydrate concentration has decreased slightly when compared to the non-irradiated sample (0.024 mg/ml). The lowest concentration of carbohydrate is seen at 0.025 kGy (0.019mg/ml). The samples stored in polyethylene bag, after 30 days showed both increase (0.056 mg/ml at 0.025 kGy) and decrease (0.04 mg/ml at 10 kGy) in total carbohydrate concentration when compared to control (0.046 mg/ml). 90 days stored samples showed increase in carbohydrate concentration when compared to control (0.029 mg/ml). The highest carbohydrate concentration is seen in 1 kGy dose (0.037 mg/ml). The samples stored at container after 30 days showed both increase (0.045 mg/ml at 5 kGy) and decrease (0.034 mg/ml at 0.025 mg/ml) of carbohydrate concentration when compared to control (0.043 mg/ml). 90 days stored samples showed decrease in carbohydrate concentration when compared to control (0.034 mg/ml). The lowest concentration is seen at 5 kGy (0.022 mg/ml). (author)

Determination of plutonium isotopic ratios and total concentration by gamma ray spectrometry

International Nuclear Information System (INIS)

Despres, Michele.

1980-11-01

A non-destructive method of analysis is being investigated for the control in situ of plutonium isotopic composition and total concentration in different matrix without preliminary calibration. The plutonium isotopic composition is determined by gamma-ray spectrometry using germanium detector systems. The same apparatus is used for direct measuring of the total plutonium concentration in solutions or solids by a differential attenuation technique based on two transmitted gamma rays with energies on both sides of the k shell absorption edge of plutonium [fr

Removal of two polycyclic musks in sewage treatment plants: Freely dissolved and total concentrations

NARCIS (Netherlands)

Artola-Garicano, E.; Borkent, I.; Hermens, J.L.M.; Vaes, W.H.J.

2003-01-01

In the current study, the removal of slowly degradable hydrophobic chemicals in sewage treatment plants (STPs) has been evaluated with emphasis on the combination of free and total concentration data. Free and total concentrations of two polycyclic musks were determined in each compartment of four

25-hydroxyvitamin D, autoantigenic and total antibody concentrations

DEFF Research Database (Denmark)

Thorsen, Steffen Ullitz; Pipper, Christian B; Johannesen, Jesper

2018-01-01

conducted within this field. OBJECTIVE: Our objective was to investigate if higher 25-hydroxyvitamin D (25(OH)D) concentrations were inversely associated with β-cell autoantigens glutamic acid decarboxylase (isoform 65) (GADA) and insulinoma associated antigen-2A (IA-2A). Further, we also wanted to examine......BACKGROUND: B cells have recently entered the stage as an important accessory player in type 1 diabetes (T1D) etiopathogenesis. Experimental studies suggest regulatory functions of vitamin D on B cells. However, only a few human studies, with considerable methodological limitations, have been...... the relationship between 25(OH)D and total antibody concentrations. METHODS: We randomly selected 500 patients with newly diagnosed T1D and 500 siblings for 25(OH)D, antibody and genetic analysis from the population-based Danish Registry of Childhood and Adolescent Diabetes. The relative change (RC) in the mean...

Effect of concentrate feeding strategy on the performance of dairy cows fed total mixed rations

Directory of Open Access Journals (Sweden)

H. KHALILI

2008-12-01

Full Text Available Little information is available concerning the effects of offering additional concentrates with total mixed ration (TMR on milk production. The aim of the present study was to compare TMR representing simplified feeding (TMR1 with TMR combined with a decreasing amount of additional concentrate (TMR2C. Finnish Ayrshire cows (39 were housed in a loose housing barn. TMR1 consisted of a mixed ration of grass silage (0.49 and concentrates (0.51. In TMR2C, the same grass silage and concentrate were mixed in a ratio of 55:45. In TMR2C, cows were offered additional concentrates from automatic feeders differing in composition from the concentrate in TMR1 [6.5 kg d-1 (first 100 days, Phase 1, 3.0 kg d-1 (subsequent 50 days, Phase 2 and no concentrate thereafter (Phase 3]. During the whole experiment (224 days, total consumption of concentrates per cow averaged 2426 kg dry matter (TMR1 and 2414 kg dry matter (TMR2C. There were no significant differences in mean total dry matter, metabolizable energy, crude protein or absorbed amino acid intakes. During Phase 2, total intake of all cows fed TMR2C was one kg lower (P = 0.10 than for cows fed TMR1. This was due to differences in total feed intake of multiparous cows. Average yields (kg d-1 of milk, energy corrected milk, protein, fat and lactose were not significantly different between diets. During Phase 2, primiparous cows tended to produce more energy corrected milk on TMR2C than on TMR1. The results showed that both TMR1 and TMR2C were equal feeding strategies for early lactating cows and cows did not benefit from greater concentrate consumption in early stage of lactation when total consumption of concentrates was similar.;

Determination of diffusible and total hydrogen concentration in coated and uncoated steel

Energy Technology Data Exchange (ETDEWEB)

Mabho, Nonhlangabezo

2010-09-23

The new trend in the steel industry demands thin, flexible, high strength steels with low internal embrittlement. It is a well known fact that the atomic hydrogen which is picked up during production, fabrication and service embrittles the steel. This has led to an extensive research towards the improvement of the quality of metallic materials by focusing on total and diffusible hydrogen concentrations which are responsible for hydrogen embrittlement. Since the internal embrittlement cannot be foreseen, the concentrations of diffusible hydrogen work as indicators while the total hydrogen characterizes the absorbed quantities and quality of that particular product. To meet these requirements, the analytical chemistry methods which include the already existing carrier gas melt (fusion) extraction methods that use infrared and thermal conductivity for total hydrogen detection were applied. The newly constructed carrier gas thermal desorption mass spectroscopy was applied to monitor the diffusible concentration at specific temperatures and desorption rates of hydrogen which will contribute towards the quality of materials during service. The TDMS method also involved the characterization of the energy quantity (activation energy) required by hydrogen to be removed from traps of which irreversible traps are preferred because they enhance the stability of the product by inhibiting the mobility of hydrogen which is detrimental to the metallic structures. The instrumentation for TDMS is quite simple, compact, costs less and applicable to routine analysis. To determine total and diffusible hydrogen, the influence of the following processes: chemical and mechanical zinc coating removal, sample cleaning with organic solvents, conditions for hydrogen absorption by electrolytic hydrogen charging, conditions of hydrogen desorption by storing the sample at room temperature, solid CO{sub 2} and at temperatures of the drier was analysed. The contribution of steel alloys towards

An introduction to predictive modelling of drug concentration in anaesthesia monitors.

Science.gov (United States)

DeCou, J; Johnson, K

2017-01-01

A significant amount of anaesthetists' work involves the prediction of drug effects and interactions to produce a smooth general anaesthetic that minimises drug side effects and promotes rapid emergence. Successfully managing this process requires a basic understanding of drug effects, experience and inevitably some guesswork, since it is difficult (and in some cases impossible) to anticipate all relevant patient and surgical factors. Although data are generally available to allow calculation of plasma drug and effect site concentrations, this is often difficult to apply in complex clinical contexts, particularly when multiple drug types are used. In recent years, manufacturers have developed and incorporated into anaesthetic workstations technologies that use drug pharmacodynamic and pharmacokinetic data to predict drug effects and interactions. Such systems can predict the duration and effects of drugs during anaesthesia and assist the anaesthetist to understand complex drug interactions. With this information available, different drug types, doses and combinations may be tailored in a scientific way to maximise useful effects whilst minimising overdose and side-effects, particularly in high-risk patients. Examples are used to illustrate how such systems can be used in practice, and how drug effects and interactions can be simulated to "rehearse" an anaesthetic before any drugs are actually administered. At present only a small number of anaesthetic workstations use this technology, and as yet they are not able to manage all drugs used in anaesthetic practice. However, such systems have the potential to help anaesthetists manage the complexity of their work, and to provide information on predicted drug effects in a way that is useful and relevant to both experienced anaesthetists and trainees. © 2017 The Association of Anaesthetists of Great Britain and Ireland.

Determination of serum free thyroxine concentration (FT4) by means of fT4-fraction and total thyroxine concentration

International Nuclear Information System (INIS)

Passath, A.; Leb, G.

1985-01-01

A new equilibrium assay for the determination of serum free thyroxine was evaluated in 514 patients. The assay comprises a two-vial-procedure to measure total thyroxine and free thyroxine fraction by use of monoclonal antibodies. Free thyroxine concentrations are calculated from fT 4 -fraction and total thyroxine concentration readings. In euthyroidism the average free thyroxine fraction (%fT 4 ) was 0.011%, in hyperthyroidism this fraction was elevated, in hypothyroidism it was below normal. In patients with TBG anomalies, TBG values were inversely correlated with fT 4 fraction readings. The 'euthyroid reference range' of FT 4 (SPAC ET) was between 0.70 to 1.78ng/dl. This euthyroid range of FT 4 was determined from TT 4 concentrations measured by T 4 -RIA (SPAC T 4 MONO) which were 30% above TT 4 values measured by conventional T 4 -RIA (SPAC T 4 POLY; polyclonal antibodies). However, a different euthyroid range of FT 4 between 0.55 to 1.30 ng/dl was observed as well as by other investigators when conventional T 4 -RIA measurements were used for calculation of FT 4 values. Our results indicate that calculated FT 4 concentration values are highly dependent on the methods used for determination of total thyroxine concentrations. Precision and reproducability of this two vial equilibrium assay did not meet the requirements mandatory for the application as a clinical routine diagnostic procedure, and its general use for this purpose can as yet not be recommended. (Author)

Total mercury concentrations in lionfish (Pterois volitans/miles) from the Florida Keys National Marine Sanctuary, USA.

Science.gov (United States)

Huge, Dane H; Schofield, Pamela J; Jacoby, Charles A; Frazer, Thomas K

2014-01-15

Strategies to control invasive lionfish in the western Atlantic and Caribbean are likely to include harvest and consumption. Until this report, total mercury concentrations had been documented only for lionfish from Jamaica, and changes in concentrations with increasing fish size had not been evaluated. In the Florida Keys, total mercury concentrations in dorsal muscle tissue from 107 lionfish ranged from 0.03 to 0.48 ppm, with all concentrations being less than the regulatory threshold for limited consumption. Mercury concentrations did not vary consistently with standard lengths or wet weights of lionfish. In 2010, lionfish from the upper Keys had mean concentrations that were 0.03-0.04 ppm higher than lionfish from the middle Keys, but mean concentrations did not differ consistently among years and locations. Overall, total mercury concentrations in lionfish were lower than those in several predatory fishes that support commercial and recreational fisheries in Florida. Published by Elsevier Ltd.

Mean total arsenic concentrations in chicken 1989-2000 and estimated exposures for consumers of chicken.

OpenAIRE

Lasky, Tamar; Sun, Wenyu; Kadry, Abdel; Hoffman, Michael K

2004-01-01

The purpose of this study was to estimate mean concentrations of total arsenic in chicken liver tissue and then estimate total and inorganic arsenic ingested by humans through chicken consumption. We used national monitoring data from the Food Safety and Inspection Service National Residue Program to estimate mean arsenic concentrations for 1994-2000. Incorporating assumptions about the concentrations of arsenic in liver and muscle tissues as well as the proportions of inorganic and organic a...

Measurement of thyroid volume, iodine concentration and total iodine content by CT and its clinical significance

International Nuclear Information System (INIS)

Nakaji, Shunsuke; Imanishi, Yoshimasa; Okamoto, Kyouko; Shinagawa, Toshihito

2007-01-01

Recently, Imanishi et al have developed new CT software for quantitative in vivo measurement of thyroid iodine. Using a CT system with the software, we measured volume, iodine concentration and total iodine content of thyroids in 63 controls and 435 patients with various diffuse thyroid diseases and thyroid nodules. In controls, all of them showed no difference between the sexes. Although the iodine concentration of the thyroid showed no difference among children, adults and seniles, the volume and total iodine content of the thyroid appeared smaller in children and seniles than in adults. In addition, although the volume and iodine concentration of the thyroid had two peaks in distribution, the total iodine content had almost normal distribution. Normal range of volume, iodine concentration and total iodine content in adults were 5.2-15.5 cm 3 , 0.28831-0.85919 mg/cm 3 and 2.35-11.69 mg, respectively. In thyroid nodule, there is no significant difference in volume, iodine concentration and total iodine content between benign and malignant nodules. All nodules with iodine concentration of less than 0.00007 mg/cm 3 were benign. No thyroid was higher in iodine concentration than the normal range although the thyroid was lower in 78.7% of patients with diffuse thyroid diseases. In all thyroids with increasing iodine concentration and total iodine content in medication course, thyroidal symptoms and signs were uncontrollable by the medication. In 43.8% of patients with long-period systemic diseases, the thyroid showed abnormality in any of the three. We concluded that quantitative in vivo measurement of thyroid iodine by CT could assist the diagnosis of thyroid diseases and decision of therapeutic methods. (author)

Monitoring total endotoxin and (1 --> 3)-beta-D-glucan at the air exhaust of concentrated animal feeding operations.

Science.gov (United States)

Yang, Xufei; Wang, Xinlei; Zhang, Yuanhui; Lee, Jongmin; Su, Jingwei; Gates, Richard S

2013-10-01

Mitigation of bioaerosol emissions from concentrated animal feeding operations (CAFOs) demands knowledge of bioaerosol concentrations feeding into an end-of-pipe air treatment process. The aim of this preliminary study was to measure total endotoxin and (1 --> 3)-beta-glucan concentrations at the air exhaust of 18 commercial CAFOs and to examine their variability with animal operation type (swine farrowing, swine gestation, swine weaning, swine finishing, manure belt laying hen, and tom turkey) and season (cold, mild, and hot). The measured airborne concentrations of total endotoxin ranged from 98 to 23,157 endotoxin units (EU)/m3, and the airborne concentrations of total (1 --> 3)-beta-D-glucan ranged from 2.4 to 537.9 ng/m3. Animal operation type in this study had a significant effect on airborne concentrations of total endotoxin and (1 --> 3)-beta-D-glucan but no significant effect on their concentrations in total suspended particulate (TSP). Both endotoxin and (1 --> 3)-beta-D-glucan attained their highest airborne concentrations in visited tom turkey buildings. Comparatively, season had no significant effect on airborne concentrations of total endotoxin or (1 --> 3)-beta-D-glucan. Endotoxin and (1 --> 3)-beta-glucan concentrations in TSP dust appeared to increase as the weather became warmer, and this seasonal effect was significant in swine buildings. Elevated indoor temperatures in the hot season were considered to facilitate the growth and propagation of bacteria and fungi, thus leading to higher biocomponent concentrations in TSP.

Population pharmacokinetics and limited sampling strategy for first-line tuberculosis drugs and moxifloxacin

NARCIS (Netherlands)

Magis-Escurra, C.; Later-Nijland, H. M. J.; Alffenaar, J. W. C.; Broeders, J.; Burger, D. M.; van Crevel, R.; Boeree, M. J.; Donders, A. R. T.; van Altena, R.; van der Werf, T. S.; Aarnoutse, R. E.

Therapeutic drug monitoring (TDM) of tuberculosis (TB) drugs currently focuses on peak plasma concentrations, yet total exposure [area under the 24-h concentration-time curve (AUC(0-24))] is probably most relevant to the efficacy of these drugs. We therefore assessed population AUC(0-24) data for

The frequency of drugs among Danish drivers before and after the introduction of fixed concentration limits

DEFF Research Database (Denmark)

Steentoft, Anni; Simonsen, Kirsten Wiese; Linnet, Kristian

2010-01-01

Until July 2007, the driving under the influence of drugs (DUID) legislation in Denmark was based on impairment, evaluated on the basis of a clinical investigation and toxicological analyses, but in 2007 fixed concentration limits were introduced into the Danish traffic legislation. The objective...... for this study was to investigate the prevalence of medication and illicit drugs among Danish drivers before and after 2007.......Until July 2007, the driving under the influence of drugs (DUID) legislation in Denmark was based on impairment, evaluated on the basis of a clinical investigation and toxicological analyses, but in 2007 fixed concentration limits were introduced into the Danish traffic legislation. The objective...

Measurement of total and free docetaxel concentration in human plasma by ultra-performance liquid chromatography-tandem mass spectrometry.

Science.gov (United States)

Rigo-Bonnin, Raül; Cobo-Sacristán, Sara; Gonzalo-Diego, Núria; Colom, Helena; Muñoz-Sánchez, Carmen; Urruticoechea, Ander; Falo, Catalina; Alía, Pedro

2016-01-05

Docetaxel is a semi-synthetic taxane with cytotoxic anti-neoplastic activity and, currently used as anticancer agent in several types of cancer. Docetaxel is highly bound to plasma proteins, and this significantly determines its clearance and activity. Therefore, measurement of free docetaxel in plasma is pharmacologically important when pharmacokinetics is investigated. We developed and validated chromatographic methods by ultra-performance liquid chromatography-tandem mass spectrometry to measure total and free docetaxel concentration in human plasma. The final validated methods involved liquid-liquid extraction followed by dryness under nitrogen evaporation. To measure free docetaxel concentration, sample preparation was preceded by ultrafiltration. Chromatographic separation was achieved using an Acquity(®) UPLC(®) BEH™ (2.1×100 mm id, 1.7 μm) reverse-phase C18 column at a flow rate of 0.4 mL/min, using isocratic elution mode containing ammonium acetate/formic acid in water/methanol (30:70 v/v) as mobile phase. Docetaxel and its internal standard (paclitaxel) were detected by electrospray ionization mass spectrometry in positive ion multiple reaction monitoring mode using mass-to-charge (m/z) transitions of 808.3→527.0 (quantifier) and 808.3→509.0 (qualifier); and 854.3→569.0 (quantifier) and 854,3→509,0 (qualifier), respectively. The run time per sample was 3.5 min. The limits of quantification were 1,95 and 0.42 μg/L and linearity was observed between 1.95 and 1000 and 0.42-100 μg/L for total and free docetaxel, respectively. Coefficients of variation and absolute relative biases were less than 13.8% and 10.0%. Recovery values were greater than 79.4%. Evaluation of the matrix effect showed ion suppression and no carry-over was observed. The validated methods could be useful for both therapeutic drug monitoring and pharmacokinetic studies. They could be applied to daily clinical laboratory practice to measure the concentration of total and free

Effects of total gastrectomy on plasma silicon and amino acid concentrations in men.

Science.gov (United States)

Tatara, Marcin R; Krupski, Witold; Szpetnar, Maria; Dąbrowski, Andrzej; Bury, Paweł; Szabelska, Anna; Charuta, Anna; Boguszewska-Czubara, Anna; Maciejewski, Ryszard; Wallner, Grzegorz

2015-12-01

The aim of the study was to determine one-year effects of total gastrectomy on plasma silicon and free amino acid concentrations in patients and evaluate changes of volumetric bone mineral density (vBMD) in lumbar spine. Eight patients were enrolled to the control (CTR) group. Six patients subjected to total gastrectomy (GX group) were included to the experimental group. vBMD in trabecular and cortical bone was measured in lumbar vertebrae at baseline (before surgery) and one year later using quantitative computed tomography. Plasma concentrations of silicon and free amino acids were determined at baseline and one year later using photometric method and ion-exchange chromatography. Body weights within CTR and GX groups were not different after one-year follow-up when compared to the baseline values (P > 0.05). An average annual decrease of vBMD in the trabecular bone in the gastrectomized patients reached 15.0% in lumbar spine and was significantly different in comparison to the percentage changes observed in CTR group (P = 0.02). One-year percentage change of vBMD in the cortical bone in L1 and L2 has shown significantly decreased values by 10.5 and 9.1% in the GX group when compared to the percentage change observed in the controls (P silicon was significantly lowered by 26.7% one year after the total gastrectomy when compared to the baseline value (P = 0.009). Total gastrectomy in patients has induced severe osteoporotic changes in lumbar spine within one-year period. The observed osteoporotic changes were associated with decreased plasma concentration of silicon indicating importance of exocrine and endocrine functions of stomach for silicon homeostasis maintenance. Gastrectomy-induced bone loss was not related to decreased amino acid concentration in plasma obtained from overnight fasted patients. © 2015 by the Society for Experimental Biology and Medicine.

Relationship between self-reported adherence, antiretroviral drug concentration measurement and self-reported symptoms in patients treated for HIV-1 infection.

Science.gov (United States)

Fabbiani, Massimiliano; Di Giambenedetto, Simona; Cingolani, Antonella; Fanti, Iuri; Colafigli, Manuela; Tamburrini, Enrica; Cauda, Roberto; Navarra, Pierluigi; De Luca, Andrea; Murri, Rita

2016-01-01

The aim of the study was to explore relationships between self-reported adherence, antiretroviral drug concentration measurement (TDM) and self-reported symptoms. We systematically administered to human immunodeficiency (HIV)-infected outpatients a questionnaire evaluating measures of self-reported adherence (missing doses during last week, deviations from the prescribed timing of therapy, self-initiated discontinuations for > 24 or 48 h, exhausting drugs and present sense of how patients are taking therapy) and a panel of referred symptoms (a symptom score was built summing self-reported scores for each listed symptom). We selected patients who completed the questionnaire and also had a TDM (mainly reflecting adherence in the past few days or weeks), thus comparing these two tools as measures of adherence. A total of 130 patients (64.6% males, median age 44 years, 76.2% with HIV RNA HIV RNA symptom score was associated with a lower self-reported adherence and with a higher proportion of undetectable drug levels. Self-reported adherence and TDM showed a correlation and seemed to be comparable tools for adherence estimation. Self-reported symptoms were associated with lower adherence and undetectable drug levels.

The Impact of Serum Drug Concentration on the Efficacy of Imipramine, Pregabalin and their Combination in Painful Polyneuropathy

DEFF Research Database (Denmark)

Sindrup, Søren Hein; Holbech, Jakob Vormstrup; Bach, Flemming W

2017-01-01

OBJECTIVE: The serum concentration-effect relation was explored for first line drugs in neuropathic pain and aimed to determine if efficacy could be increased. METHODS: Data from a randomized, placebo-controlled, cross-over trial on imipramine, pregabalin and their combination in painful...... polyneuropathy were used. Treatment periods were of 4 weeks' duration, outcome was the weekly median of daily pain rated by a 0-10 numeric scale, and drug concentrations were determined by high-performance liquid chromatography. RESULTS: In 47 patients pain was reduced -1.0 (95% CI -1.5:-0.6) by imipramine, -0.......178). There was no correlation between drug concentration and pain reduction for imipramine (r= 0.17, P=0.247), whereas there was a marginally, positive correlation for pregabalin (r=0.28, P=0.057). There was no interaction between treatment and concentration classes (imipramine

Flexing the PECs: Predicting environmental concentrations of veterinary drugs in Canadian agricultural soils.

Science.gov (United States)

Kullik, Sigrun A; Belknap, Andrew M

2017-03-01

Veterinary drugs administered to food animals primarily enter ecosystems through the application of livestock waste to agricultural land. Although veterinary drugs are essential for protecting animal health, their entry into the environment may pose a risk for nontarget organisms. A means to predict environmental concentrations of new veterinary drug ingredients in soil is required to assess their environmental fate, distribution, and potential effects. The Canadian predicted environmental concentrations in soil (PECsoil) for new veterinary drug ingredients for use in intensively reared animals is based on the approach currently used by the European Medicines Agency for VICH Phase I environmental assessments. The calculation for the European Medicines Agency PECsoil can be adapted to account for regional animal husbandry and land use practices. Canadian agricultural practices for intensively reared cattle, pigs, and poultry differ substantially from those in the European Union. The development of PECsoil default values and livestock categories representative of typical Canadian animal production methods and nutrient management practices culminates several years of research and an extensive survey and analysis of the scientific literature, Canadian agricultural statistics, national and provincial management recommendations, veterinary product databases, and producers. A PECsoil can be used to rapidly identify new veterinary drugs intended for intensive livestock production that should undergo targeted ecotoxicity and fate testing. The Canadian PECsoil model is readily available, transparent, and requires minimal inputs to generate a screening level environmental assessment for veterinary drugs that can be refined if additional data are available. PECsoil values for a hypothetical veterinary drug dosage regimen are presented and discussed in an international context. Integr Environ Assess Manag 2017;13:331-341. © 2016 Her Majesty the Queen in Right of Canada

Distribution of Total Suspended Solids Concentration in a River

Directory of Open Access Journals (Sweden)

Ahmad Hanif Asyhar

2012-08-01

Full Text Available Disposal of either industrial or nonindustrial wastewater into a river has a potential to cause riverpollution. Because each load of wastewater discharged into a river contains physical, chemical, and biological parametersthat determine water quality, so that it can affect the dissolved oxygen concentration in a river. Therefore the conductedresearch was aimed to determine the pattern of pollutant dispersion in Surabaya River within the section that is closed tothe Karang Pilang Monitoring Station - Surabaya. Parameter used in this research was Total Suspended Solids (TSS. Themethod used was the finite volume method with Quadratic Upwind Interpolation Convective Kinematics (QUICK schemeby means of developing models of dispersion water pollutants in a river. The governing equation was controlled by the lawsof mass conservation, momentum conservation, and pollution transport equation. Further, these equations were solvedusing numerical calculation and followed by numerical simulation. From the numerical simulation results, it can beconcluded that the magnitude of pollutant dispersion is determined by the initial discharged TSS concentrations into theriver, however the longitudinal direction is more dominantly influenced than in lateral directions.

Bulk metal concentrations versus total suspended solids in rivers: Time-invariant & catchment-specific relationships.

Science.gov (United States)

Nasrabadi, Touraj; Ruegner, Hermann; Schwientek, Marc; Bennett, Jeremy; Fazel Valipour, Shahin; Grathwohl, Peter

2018-01-01

Suspended particles in rivers can act as carriers of potentially bioavailable metal species and are thus an emerging area of interest in river system monitoring. The delineation of bulk metals concentrations in river water into dissolved and particulate components is also important for risk assessment. Linear relationships between bulk metal concentrations in water (CW,tot) and total suspended solids (TSS) in water can be used to easily evaluate dissolved (CW, intercept) and particle-bound metal fluxes (CSUS, slope) in streams (CW,tot = CW + CSUS TSS). In this study, we apply this principle to catchments in Iran (Haraz) and Germany (Ammer, Goldersbach, and Steinlach) that show differences in geology, geochemistry, land use and hydrological characteristics. For each catchment, particle-bound and dissolved concentrations for a suite of metals in water were calculated based on linear regressions of total suspended solids and total metal concentrations. Results were replicable across sampling campaigns in different years and seasons (between 2013 and 2016) and could be reproduced in a laboratory sedimentation experiment. CSUS values generally showed little variability in different catchments and agree well with soil background values for some metals (e.g. lead and nickel) while other metals (e.g. copper) indicate anthropogenic influences. CW was elevated in the Haraz (Iran) catchment, indicating higher bioavailability and potential human and ecological health concerns (where higher values of CSUS/CW are considered as a risk indicator).

Summary of total mercury concentrations in fillets of selected sport fishes collected during 2000-2003 from Lake Natoma, Sacramento County, California

Science.gov (United States)

Saiki, Michael K.; Slotton, Darrell G.; May, Thomas W.; Ayers, Shaun M.; Alpers, Charles N.

2004-01-01

This report summarizes results of total mercury measurements in skinless fillets of sport fishes collected during August 2000, September?October 2002, and July 2003 from Lake Natoma, a small (8,760 acre-feet) afterbay for Folsom Dam on the lower American River. The primary objective of the study was to determine if mercury concentrations in fillets approached or exceeded guidelines for human consumption. The Food and Drug Administration (FDA) human-health action level for methylmercury in commercially caught fish is 1.0 ?g/g (microgram per gram); the U.S. Environmental Protection Agency (USEPA) human-health criterion for methylmercury residue in fish tissue is 0.30 ?g/g. Wet weight concentrations of total mercury in skinless fillets were as high as 0.19 ?g/g in bluegill (Lepomis macrochirus), 0.39 ?g/g in redear sunfish (L. microlophus), 1.02 ?g/g in largemouth bass (Micropterus salmoides), and 1.89 ?g/g in channel catfish (Ictalurus punctatus). Maximum concentrations of mercury in other fish species varied from 0.10 ?g/g in rainbow trout (Oncorhynchus mykiss) to 0.56 ?g/g in white catfish (A-meiurus catus). Altogether, 1 of 86 largemouth bass and 11 of 11 channel catfish exceeded the FDA human-health action level. In addition, 1 of 20 redear sunfish, 26 of 86 largemouth bass, 2 of 3 spotted bass (M. punctulatus), 1 of 1 brown bullhead (A. nebulosus), and 1 of 1 white catfish exceeded the USEPA human-health criterion. These results indicate that some fish species inhabiting Lake Natoma contain undesirably high concentrations of mercury in their skinless fillets.

Citalopram and escitalopram plasma drug and metabolite concentrations: genome-wide associations.

Science.gov (United States)

Ji, Yuan; Schaid, Daniel J; Desta, Zeruesenay; Kubo, Michiaki; Batzler, Anthony J; Snyder, Karen; Mushiroda, Taisei; Kamatani, Naoyuki; Ogburn, Evan; Hall-Flavin, Daniel; Flockhart, David; Nakamura, Yusuke; Mrazek, David A; Weinshilboum, Richard M

2014-08-01

Citalopram (CT) and escitalopram (S-CT) are among the most widely prescribed selective serotonin reuptake inhibitors used to treat major depressive disorder (MDD). We applied a genome-wide association study to identify genetic factors that contribute to variation in plasma concentrations of CT or S-CT and their metabolites in MDD patients treated with CT or S-CT. Our genome-wide association study was performed using samples from 435 MDD patients. Linear mixed models were used to account for within-subject correlations of longitudinal measures of plasma drug/metabolite concentrations (4 and 8 weeks after the initiation of drug therapy), and single-nucleotide polymorphisms (SNPs) were modelled as additive allelic effects. Genome-wide significant associations were observed for S-CT concentration with SNPs in or near the CYP2C19 gene on chromosome 10 (rs1074145, P = 4.1 × 10(-9) ) and with S-didesmethylcitalopram concentration for SNPs near the CYP2D6 locus on chromosome 22 (rs1065852, P = 2.0 × 10(-16) ), supporting the important role of these cytochrome P450 (CYP) enzymes in biotransformation of citalopram. After adjustment for the effect of CYP2C19 functional alleles, the analyses also identified novel loci that will require future replication and functional validation. In vitro and in vivo studies have suggested that the biotransformation of CT to monodesmethylcitalopram and didesmethylcitalopram is mediated by CYP isozymes. The results of our genome-wide association study performed in MDD patients treated with CT or S-CT have confirmed those observations but also identified novel genomic loci that might play a role in variation in plasma levels of CT or its metabolites during the treatment of MDD patients with these selective serotonin reuptake inhibitors. © 2014 The British Pharmacological Society.

Influence of starter culture on total free aminoacids concentration during ripening of Krk cheese

Directory of Open Access Journals (Sweden)

Biljana Radeljević

2013-03-01

Full Text Available The aim of this study was to determine the influence of microbial (commercial starter culture on concentration of total free amino groups (amino acids in cheeses in different ripening stages. Free amino groups were determined by reaction with ninhydrin with cadmium (Cd in the water soluble cheese extract, and were expressed as the concentration of leucine in cheese dry matter. Changes in concentration of total free amino acids during cheese ripening (0th, 30th, 60th, 90th and 120th day were monitored. In water soluble extracts of cheese, the presence of free NH2 groups in all ripening stages was detected, which means smaller peptides and amino acids, whose concentration significantly (P<0.01 increased during ripening. Cheeses produced with and without microbial culture resulted in statistically significant differences (P<0.01 in content amino acids free on the 90th and 120th day of ripening. Cd - ninhydrin method was found to be suitable for cheese ripening monitoring, as well as for determination of the differences in mature characteristics of cheeses, depending on the production process.

Free and total urinary phthalate metabolite concentrations among pregnant women from the Healthy Baby Cohort (HBC), China.

Science.gov (United States)

Zhu, Yingshuang; Wan, Yanjian; Li, Yuanyuan; Zhang, Bin; Zhou, Aifen; Cai, Zongwei; Qian, Zhengmin; Zhang, Chuncao; Huo, Wenqian; Huang, Kai; Hu, Jie; Cheng, Lu; Chang, Huailong; Huang, Zheng; Xu, Bing; Xia, Wei; Xu, Shunqing

2016-03-01

Total urinary phthalate metabolites (the free plus glucuronidated forms) have been frequently measured in the general population. However, data are limited on the free forms which may be more bioactive, especially for sensitive population such as pregnant women. Here the data gap was addressed by measuring concentrations of free and total forms of six phthalate metabolites in 293 urine samples from pregnant women at delivery, who were randomly selected from the prospective Healthy Baby Cohort (HBC), China. We observed detectable concentrations of the total amount of phthalate metabolites in all urine samples. The geometric mean (GM) urinary concentrations of free and total mono-butyl phthalate (MBP) (5.20, 54.49ng/mL) were the highest, followed by mono-(2-ethyl-5-carboxypentyl) phthalate (MECPP) (4.52, 7.27ng/mL). For most of phthalate metabolites, urinary concentrations were significantly higher in women who were nulliparous. Significantly higher concentrations of mono-ethyl phthalate (MEP) and mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP) were found in women who had higher educational level. To our knowledge, this is the first study to report the free and total forms of phthalate metabolites among pregnant women in China. The results suggest that exposure characteristics may be related to parity and education. Copyright © 2015 Elsevier Ltd. All rights reserved.

Dynamics of Total Microcystin LR Concentration in Three Subtropical Hydroelectric Generation Reservoirs in Uruguay, South America.

Science.gov (United States)

González-Piana, Mauricio; Fabián, Daniel; Piccardo, Andrea; Chalar, Guillermo

2017-10-01

This study analyzed the temporal dynamics of total microcystin LR concentrations between the years of 2012 and 2015 in the Bonete, Baygorria and Palmar hydroelectric generation reservoirs in the central region of the Negro River, Uruguay. The three reservoirs showed differents total microcystin LR concentration, with no significant differences among them. Over 20 sampling dates, the three reservoirs exhibited total microcystin LR concentrations on eight occasions that corresponded to a slight to moderate human health risk according to WHO guideline values for recreational waters. By determining the concentration of microcystin LR in cyanobacterial biomass, we identified cyanobacterial populations that occurred over time with varying degrees of toxin production (maximal 85.4 µg/mm 3 ). The microcystin LR concentration in Bonete was positively correlated with temperature (r = 0.587) and cyanobacterial biomass (r = 0.736), in Baygorria with cyanobacterial biomass (r = 0.521), and in Palmar with temperature (r = 0.500) and negatively correlated with ammonia (r = -0.492). Action is needed to reduce the presence of toxic cyanobacteria in these systems. A decrease in the use of agrochemicals and management changes in the reservoir basins could be successful long-term measures.

Total vs. internal element concentrations in Scots pine needles along a sulphur and metal pollution gradient

International Nuclear Information System (INIS)

Rautio, Pasi; Huttunen, Satu

2003-01-01

Different methods should be used for foliar analyses of trees used as bioindicators of pollution, than those analyses used in nutritional studies of trees. - Analysis of foliar elements is a commonly used method for studying tree nutrition and for monitoring the impacts of air pollutants on forest ecosystems. Interpretations based on the results of foliar element analysis may, however, be different in nutrition vs. monitoring studies. We studied the impacts of severe sulphur and metal (mainly Cu and Ni) pollution on the element concentrations (Al, Ca, Cu, Fe, K, Mg, Mn, Ni, P, Pb, S and Zn) in Scots pine (Pinus sylvestris L.) foliage along an airborne sulphur and metal pollution gradient. Emphasis was put on determining the contribution of air-borne particles that have accumulated on needle surfaces to the total foliage concentrations. A comparison of two soil extraction methods was carried out in order to obtain a reliable estimate of plant-available element concentrations in the soil. Element concentrations in the soil showed only a weak relationship with internal foliar concentrations. There were no clear differences between the total and internal needle S concentrations along the gradient, whereas at the plot closest to the metal smelter complex the total Cu concentrations in the youngest needles were 1.3-fold and Ni concentrations over 1.6-fold higher than the internal needle concentrations. Chloroform-extracted surface wax was found to have Ni and Cu concentrations of as high as 3000 and 600 μg/g of wax, respectively. Our results suggest that bioindicator studies (e.g. monitoring studies) may require different foliar analysis techniques from those used in studies on the nutritional status of trees

Drugs in breast milk.

Science.gov (United States)

Hervada, A R; Feit, E; Sagraves, R

1978-09-01

The amount of drug excreted into breast milk is dependent upon the lipid solubility of the medication, the mechanism of transport, the degree of ionization, and change in plasma pH. The higher the lipid solubility, the greater the concentration in human milk. The majority of drugs are transported into mammary blood capillaries by passive diffusion. The rest are transported by reverse pinocytosis. Once the drug has entered the epithelial cells of breast tissue, the drug molecules are excreted into the human milk by active transport, passive diffusion, or apocrine secretion. The amount of free (active) drug available for transport depends on the degree of protein binding the plasma pH. Another factor affecting excretion of drugs is the time when breast feeding occurs. In the 1st few days of life, when colostrum is present, water-soluble drugs pass through the breast more easily than afterwards when milk is produced. Then lipid-soluble drugs cross in higher concentrations. The effect on nursing infants is dependent on the amount excreted into the milk, the total amount absorbed by the infant, and the toxicity of the drug. The use of the following drugs in breast feeding mothers is reviewed: anticoagulants, antihypertensives and diuretics, antimicrobials, drugs affecting the central nervous system (alcohol, chloral hydrate, meprobamate, lithium, and aspirin), marijuana, other drugs (antihistamines, atropine, ergot alkaloids, laxatives, nicotine, iodides, propylthiouracil, theophylline), hormones (insulin, thyroxine, and oral contraceptives), and radiopharmaceuticals.

Correlations of Maternal Buprenorphine Dose, Buprenorphine, and Metabolite Concentrations in Meconium with Neonatal Outcomes

Science.gov (United States)

Kacinko, SL; Jones, HE; Johnson, RE; Choo, RE; Huestis, MA

2009-01-01

For the first time, relationships among maternal buprenorphine dose, meconium buprenorphine and metabolite concentrations, and neonatal outcomes are reported. Free and total buprenorphine and norbuprenorphine, nicotine, opiates, cocaine, benzodiazepines, and metabolites were quantified in meconium from 10 infants born to women who had received buprenorphine during pregnancy. Neither cumulative nor total third-trimester maternal buprenorphine dose predicted meconium concentrations or neonatal outcomes. Total buprenorphine meconium concentrations and buprenorphine/norbuprenorphine ratios were significantly related to neonatal abstinence syndrome (NAS ) scores >4. As free buprenorphine concentration and percentage free buprenorphine increased, head circumference decreased. Thrice-weekly urine tests for opiates, cocaine, and benzodiazepines and self-reported smoking data from the mother were compared with data from analysis of the meconium to estimate in utero exposure. Time of last drug use and frequency of use during the third trimester were important factors associated with drug-positive meconium specimens. The results suggest that buprenorphine and metabolite concentrations in the meconium may predict the onset and frequency of NAS. PMID:18701886

Tree age, fruit size and storage conditions affect levels of ascorbic acid, total phenolic concentrations and total antioxidant activity of 'Kinnow' mandarin juice.

Science.gov (United States)

Khalid, Samina; Malik, Aman U; Khan, Ahmad S; Shahid, Muhammad; Shafique, Muhammad

2016-03-15

Bioactive compounds (ascorbic acid, total phenolics and total antioxidants) are important constituents of citrus fruit juice; however, information with regard to their concentrations and changes in relation to tree age and storage conditions is limited. 'Kinnow' (Citrus nobilis Lour × Citrus deliciosa Tenora) mandarin juice from fruit of three tree ages (6, 18 and 35 years old) and fruit sizes (large, medium and small) were examined for their bioactive compounds during 7 days under ambient storage conditions (20 ± 2 °C and 60-65% relative humidity (RH)) and during 60 days under cold storage (4 ± 1 °C and 75-80% RH) conditions. Under ambient conditions, a reduction in total phenolic concentrations (TPC) and in total antioxidant activity (TAA) was found for the juice from all tree ages and fruit sizes. Overall, fruit from 18-year-old trees had higher mean TPC (95.86 µg mL(-1) ) and TAA (93.68 mg L(-1) ), as compared to 6 and 35-year-old trees. Likewise, in cold storage, TAA decreased in all fruit size groups from 18 and 35-year-old trees. In all tree age and fruit size groups, TPC decreased initially during 15 days of cold storage and then increased gradually with increase in storage duration. Ascorbic acid concentrations showed an increasing trend in all fruit size groups from 35-year-old trees. Overall, during cold storage, fruit from 18-year-old trees maintained higher mean ascorbic acid (33.05 mg 100 mL(-1) ) concentrations, whereas fruit from 6-year-old trees had higher TAA (153.1 mg L(-1) ) and TPC (115.1 µg mL(-1) ). Large-sized fruit had higher ascorbic acid (32.08 mg 100 mL(-1) ) concentrations and TAA (157.5 mg L(-1) ). Fruit from 18-year-old trees maintained higher TPC and TAA under ambient storage conditions, whereas fruit from 6-year-old trees maintained higher TPC and TAA during cold storage. Small-sized fruit had higher TPC after ambient temperature storage, whereas large fruit size showed higher ascorbic acid concentrations and TAA after cold

X-ray Spectroscopy for Quality Control of Chemotherapy Drugs

International Nuclear Information System (INIS)

Greaves, E. D.; Barros, H.; Bermudez, J.; Sajo-Bohus, L.; Angeli-Greaves, M.

2007-01-01

We develop a method, employing Compton peak standardization and the use of matrix-matched spiked samples with Total Reflection X-ray Fluorescence (TXRF), for the determination of platinum plasma concentrations of patients undergoing chemotherapy with Pt-bearing drugs. Direct blood plasma analysis attains Pt detection limits of 70 ng/ml. Measurement results of prescribed drug doses are compared to achieved blood Pt concentrations indicating a lack of expected correlations. Direct analysis of Pt-containing infused drugs from a variety of suppliers indicates cases of abnormal concentrations which raises quality control issues. We demonstrate the potential usefulness of the method for pharmacokinetic studies or for routine optimization and quality control of Pt chemotherapy treatments

Considerations for effect site pharmacokinetics to estimate drug exposure: concentrations of antibiotics in the lung.

Science.gov (United States)

Rodvold, Keith A; Hope, William W; Boyd, Sara E

2017-10-01

Bronchoalveolar lavage (BAL) and microdialysis have become the most reliable and relevant methods for measuring lung concentrations of antibiotics, with the majority of BAL studies involving either healthy adult subjects or patients undergoing diagnostic bronchoscopy. Emphasis on the amount of drug that reaches the site of infection is increasingly recognized as necessary to determine whether a dose selection will translate to good clinical outcomes in the treatment of patients with pneumonia. Observed concentrations and/or parameters of exposure (e.g. area-under-the-curve) need to be incorporated with pharmacokinetic-pharmacodynamic indices so that rational dose selection can be identified for specific pathogens and types of pneumonic infection (community-acquired vs hospital-acquired bacterial pneumonia, including ventilator-associated bacterial pneumonia). Although having measured plasma or lung concentration-time data from critically ill patients to incorporate into pharmacokinetic-pharmacodynamic models is very unlikely during drug development, it is essential that altered distribution, augmented renal clearance, and renal or hepatic dysfunction should be considered. Notably, the number of published studies involving microdialysis and intrapulmonary penetration of antibiotics has been limited and mainly involve beta-lactam agents, levofloxacin, and fosfomycin. Opportunities to measure in high-resolution effect site spatial pharmacokinetics (e.g. with MALDI-MSI or PET imaging) and in vivo continuous drug concentrations (e.g. with aptamer-based probes) now exist. Going forward these studies could be incorporated into antibiotic development programs for pneumonia in order to further increase the probability of candidate success. Copyright © 2017 Elsevier Ltd. All rights reserved.

Competition effects in cation binding to humic acid: Conditional affinity spectra for fixed total metal concentration conditions

Science.gov (United States)

David, Calin; Mongin, Sandrine; Rey-Castro, Carlos; Galceran, Josep; Companys, Encarnació; Garcés, José Luis; Salvador, José; Puy, Jaume; Cecilia, Joan; Lodeiro, Pablo; Mas, Francesc

2010-09-01

Information on the Pb and Cd binding to a purified Aldrich humic acid (HA) is obtained from the influence of different fixed total metal concentrations on the acid-base titrations of this ligand. NICA (Non-Ideal Competitive Adsorption) isotherm has been used for a global quantitative description of the binding, which has then been interpreted by plotting the Conditional Affinity Spectra of the H + binding at fixed total metal concentrations (CAScTM). This new physicochemical tool, here introduced, allows the interpretation of binding results in terms of distributions of proton binding energies. A large increase in the acidity of the phenolic sites as the total metal concentration increases, especially in presence of Pb, is revealed from the shift of the CAScTM towards lower affinities. The variance of the CAScTM distribution, which can be used as a direct measure of the heterogeneity, also shows a significant dependence on the total metal concentration. A discussion of the factors that influence the heterogeneity of the HA under the conditions of each experiment is provided, so that the smoothed pattern exhibited by the titration curves can be justified.

Microdialysis as a tool for drug quantification in the bronchioles of anaesthetized pigs

DEFF Research Database (Denmark)

Rottbøll, Lisa Amanda Holm; Friis, Christian

2014-01-01

through a tracheostomy into the distal bronchioles using an insertion tube. Intravenously administered inulin served as a marker of extracellular fluid contamination of PELF. Concentrations of free drug in MD fractions were compared to total and non-protein-bound drug concentrations in plasma. Rising...... equipment, the danofloxacin concentrations in PELF were consistent within the different administration groups. The described MD method for drug quantification in PELF is easily accessible and provides repeatable results. However, trace amount of inulin was detected in the MD fractions, suggesting a local...

Comparison of total protein concentration in skeletal muscle as measured by the Bradford and Lowry assays.

Science.gov (United States)

Seevaratnam, Rajini; Patel, Barkha P; Hamadeh, Mazen J

2009-06-01

The Lowry and Bradford assays are the most commonly used methods of total protein quantification, yet vary in several aspects. To date, no comparisons have been made in skeletal muscle. We compared total protein concentrations of mouse red and white gastrocnemius, reagent stability, protein stability and range of linearity using both assays. The Lowry averaged protein concentrations 15% higher than the Bradford with a moderate correlation (r = 0.36, P = 0.01). However, Bland-Altman analysis revealed considerable bias (15.8 +/- 29.7%). Both Lowry reagents and its protein-reagent interactions were less stable over time than the Bradford. The linear range of concentration was smaller for the Lowry (0.05-0.50 mg/ml) than the Bradford (0-2.0 mg/ml). We conclude that the Bradford and Lowry measures of total protein concentration in skeletal muscle are not interchangeable. The Bradford and Lowry assays have various strengths and weaknesses in terms of substance interference and protein size. However, the Bradford provides greater reagent stability, protein-reagent stability and range of linearity, and requires less time to analyse compared to the Lowry assay.

Increase in tiagabine serum concentration with coadministration of gemfibrozil.

Science.gov (United States)

Burstein, Aaron H; Boudreau, Eilis A; Theodore, William H

2009-02-01

To report a case of possible acute tiagabine toxicity secondary to administration of gemfibrozil. A 39-year-old male was taking tiagabine 16 mg orally 3 times per day and carbamazepine 500 mg orally twice per day for complex partial seizures secondary to mesial temporal sclerosis. He was found to have type IV hypertriglyceridemia and was prescribed gemfibrozil. Because he reported severe confusion and altered consciousness shortly after a single 600-mg dose of gemfibrozil, he was admitted for controlled challenge with that drug. A single 300-mg dose of gemfibrozil resulted in lightheadedness and led to a 59% and 75% increase in total tiagabine serum concentrations at 2 and 5 hours, respectively, without significant change in baseline carbamazepine concentrations. This is the first report of an interaction between the widely used antihyperlipidemic drug gemfibrozil and tiagabine. Since tiagabine, which was originally developed as an antiepileptic medication, is now being used widely for a variety of other indications such as anxiety and depression, there is an increased risk for clinically significant interactions with gemfibrozil. Increased total and unbound tiagabine concentrations following a single 300-mg dose of gemfibrozil and reproduction of clinical symptoms with gemfibrozil rechallenge suggests the toxicity our patient experienced was due to a pharmacokinetic drug interaction. Use of the Horn Drug Interaction Probability Scale showed a probable interaction between gemfibrozil and tiagabine.

Low Dose Gamma Irradiation Does Not Affect the Quality or Total Ascorbic Acid Concentration of "Sweetheart" Passionfruit (Passiflora edulis).

Science.gov (United States)

Golding, John B; Blades, Barbara L; Satyan, Shashirekha; Spohr, Lorraine J; Harris, Anne; Jessup, Andrew J; Archer, John R; Davies, Justin B; Banos, Connie

2015-08-26

Passionfruit ( Passiflora edulis , Sims, cultivar "Sweetheart") were subject to gamma irradiation at levels suitable for phytosanitary purposes (0, 150, 400 and 1000 Gy) then stored at 8 °C and assessed for fruit quality and total ascorbic acid concentration after one and fourteen days. Irradiation at any dose (≤1000 Gy) did not affect passionfruit quality (overall fruit quality, colour, firmness, fruit shrivel, stem condition, weight loss, total soluble solids level (TSS), titratable acidity (TA) level, TSS/TA ratio, juice pH and rot development), nor the total ascorbic acid concentration. The length of time in storage affected some fruit quality parameters and total ascorbic acid concentration, with longer storage periods resulting in lower quality fruit and lower total ascorbic acid concentration, irrespective of irradiation. There was no interaction between irradiation treatment and storage time, indicating that irradiation did not influence the effect of storage on passionfruit quality. The results showed that the application of 150, 400 and 1000 Gy gamma irradiation to "Sweetheart" purple passionfruit did not produce any deleterious effects on fruit quality or total ascorbic acid concentration during cold storage, thus supporting the use of low dose irradiation as a phytosanitary treatment against quarantine pests in purple passionfruit.

COMPARISON OF DIFFERENT EXTRACTION METHODS REPRESENTING AVAILABLE AND TOTAL CONCENTRATIONS OF Cd, Cu, Fe, Mn and Zn IN SOIL

Directory of Open Access Journals (Sweden)

Vladimir Ivezić

2013-06-01

Full Text Available Various extraction methods are used to predict plant uptake of trace metals. Most commonly it is total concentration that is used for risk assessment and evaluation of trace metal availability. However, recent studies showed that total concentration is a poor indicator of availability while concentrations in soil solution show good correlation with plant uptake. Present study was conducted on magricultural soils with low levels of trace metals where 45 soil samples were collected from different soil types. The main objective was to compare four different extraction methods and examine how total and reactive (EDTA trace metal concentrations correlate ,with soil solution concentration (in this study determined by water extraction. The samples were analyzed by four extraction methods: strong acid extraction (ultra-pure HNO3 extraction and aqua regia, weak acid extraction by EDTA and the most available fraction, fraction in soil solution, were represented by water extraction (weakest extractant. Five elements were investigated (Cd, Cu, Fe, Mn and Zn. Water extraction significantly correlated with EDTA extraction for Cu, Fe and Mn, while total extraction (HNO3 extraction and aqua regia correlated significantly with water extraction only for Cu. No correlation between water extraction and total extraction confirmed poor role of total concentration as an indicator of availability. EDTA extraction can be used to represent reactive pool of trace metals in soil but it should be also taken with caution when using it to describe available fraction.

Elemental concentration analysis in prostate tissues using total reflection X-ray fluorescence

International Nuclear Information System (INIS)

Leitão, R.G.; Palumbo, A.; Souza, P.A.V.R.; Pereira, G.R.; Canellas, C.G.L.; Anjos, M.J.; Nasciutti, L.E.; Lopes, R.T.

2014-01-01

Prostate cancer (PCa) currently represents the second most prevalent malignant neoplasia in men, representing 21% of all cancer cases. Benign Prostate Hyperplasia (BPH) is an illness prevailing in men above the age of 50, close to 90% after the age of 80. The prostate presents a high zinc concentration, about 10-fold higher than any other body tissue. In this work, samples of human prostate tissues with cancer, BPH and normal tissue were analyzed utilizing total reflection X-ray fluorescence spectroscopy using synchrotron radiation technique (SR-TXRF) to investigate the differences in the elemental concentrations in these tissues. SR-TXRF analyses were performed at the X-ray fluorescence beamline at Brazilian National Synchrotron Light Laboratory (LNLS), in Campinas, São Paulo. It was possible to determine the concentrations of the following elements: P, S, K, Ca, Fe, Cu, Zn and Rb. By using Mann–Whitney U test it was observed that almost all elements presented concentrations with significant differences (α=0.05) between the groups studied. - Highlights: ► Prostate cancer is the most frequently diagnosed form of cancer in men. ► Intracellular Zn is correlated with proliferation, differentiation, or apoptosis. ► The prostate gland accumulate high concentration of Zn. ► SR-TXRF is a technique widely used in the analysis of low concentration in samples

Total flavonoid concentrations of bryophytes from Tianmu Mountain, Zhejiang Province (China: Phylogeny and ecological factors.

Directory of Open Access Journals (Sweden)

Xin Wang

Full Text Available The flavonoids in bryophytes may have great significance in phylogeny and metabolism research. However, to date there has been little research on bryophyte metabolites, especially flavonoids. To redress this somewhat, we determined flavonoid concentrations of bryophytes from Tianmu Mountain through a colorimetric assay and considered the factors influencing the results. This is the first time that the flavonoid contents of bryophytes have been examined in detail. The results revealed a range of total flavonoid concentrations in 90 samples collected from Tianmu Mountain from 1.8 to 22.3 mg/g (w/w. The total flavonoid contents of liverworts were generally higher than those of mosses; acrocarpous mosses had generally higher values than that of pleurocarpous mosses. The total flavonoid contents of bryophytes growing at lower light levels were general higher than those growing in full-sun. The total flavonoid contents of epiphytic bryophytes were highest, while those of aquatic bryophytes were the lowest. Total flavonoid contents of species growing at low-latitudes were much higher than those at high-latitude individuals. In conclusion, total flavonoid contents of bryophytes have some connection with plant phylogeny; more flavonoids might be contained in relatively primitive bryophytes. Meanwhile, the effects of ecological factors on total flavonoid contents of bryophytes exist; light and habitat (especially tree habitat and river habitat might be representative factor.

Serum concentrations of psychotropic drugs in neonates as a PROgnOstic Factor for admission to the neonatology ward and withdrawal symptoms: PROOF-1.

Science.gov (United States)

Sparla, Shirley C A; Coppens, Hans; Evers, Inge M; Stramrood, Claire A I; Pasker-de Jong, Pieternel C M; van der Westerlaken, Monique M L; Hogeman, Paul H G; Malingré, Mirte M

2017-05-01

The aim is to determine whether serum drug concentrations obtained from the neonate's umbilical cord can be used as a prognostic factor for admission to the neonatology ward and the occurrence of withdrawal symptoms. A retrospective observational monocenter cohort study was carried out among pregnant women using psychotropic drugs and their baby. Binary logistic regression was used for the multivariate analysis. Of the 186 neonates included, 22.6% (n=42) were admitted to the neonatology ward, 6.5% (n=12) because of withdrawal. Among women with therapeutic concentrations of psychotropic medication, 22.0% (n=5) of the neonates had withdrawal symptoms. When comparing neonates with therapeutic versus undetectable drug concentrations, an odds ratio of 3.1 (95% confidence interval: 1.1-8.6) was found for admission to the neonatology ward and an odds ratio of 20.5 (95% confidence interval: 2.2-186.1) for the occurrence of withdrawal symptoms. Therapeutic concentrations of psychotropic drugs in neonates' umbilical cord blood correspond with higher odds for admission to the neonatology ward and the occurrence of withdrawal symptoms compared with neonates with undetectable drug concentrations. The measurement of drug concentrations in the neonate may contribute toward the general clinical assessment of the physician to predict the necessity of admission to the neonatology ward and the risk of withdrawal symptoms.

Factors influencing concentrations of dissolved gaseous mercury (DGM) and total mercury (TM) in an artificial reservoir

International Nuclear Information System (INIS)

Ahn, Myung-Chan; Kim, Bomchul; Holsen, Thomas M.; Yi, Seung-Muk; Han, Young-Ji

2010-01-01

The effects of various factors including turbidity, pH, DOC, temperature, and solar radiation on the concentrations of total mercury (TM) and dissolved gaseous mercury (DGM) were investigated in an artificial reservoir in Korea. Episodic total mercury accumulation events occurred during the rainy season as turbidity increased, indicating that the TM concentration was not controlled by direct atmospheric deposition. The DGM concentration in surface water ranged from 3.6 to 160 pg/L, having a maximum in summer and minimum in winter. While in most previous studies DGM was controlled primarily by a photo-reduction process, DGM concentrations tracked the amount of solar radiation only in winter when the water temperature was fairly low in this study. During the other seasons microbial transformation seemed to play an important role in reducing Hg(II) to Hg(0). DGM increased as dissolved organic carbon (DOC) concentration increased (p-value < 0.01) while it increased with a decrease of pH (p-value < 0.01). - Long-term in-situ monitoring of TM and DGM concentrations with various factors was executed in a large artificial reservoir in this study.

Method to determine the activity concentration and total activity of radioactive waste

International Nuclear Information System (INIS)

Angeles C, A.

2001-02-01

A characteristic system of radioactive waste is described to determine the concentration of radionuclides activity and the total activity of bundles of radioactive waste. The system this integrated by three subsystems: - Elevator of drums. - Electromechanics. - Gamma spectroscopy. In the system it is analyzed waste of issuing gamma specifically, and this designed for materials of relative low density and it analyzes materials of cylindrical recipients

An inert 3D emulsification device for individual precipitation and concentration of amorphous drug nanoparticles.

Science.gov (United States)

Lorenz, T; Bojko, S; Bunjes, H; Dietzel, A

2018-02-13

Nanosizing increases the specific surface of drug particles, leading to faster dissolution inside the organism and improving the bioavailability of poorly water-soluble drugs. A novel approach for the preparation of drug nanoparticles in water using chemically inert microfluidic emulsification devices is presented in this paper. A lithographic fabrication sequence was established, allowing fabrication of intersecting and coaxial channels of different depths in glass as is required for 3D flow-focusing. Fenofibrate was used as a model for active pharmaceutical ingredients with very low water solubility in the experiments. It was dissolved in ethyl acetate and emulsified in water, as allowed by the 3D flow-focusing geometry. In the thread formation regime, the drug solution turned into monodisperse droplets of sizes down to below 1 μm. Fast supersaturation occurs individually in each droplet, as the disperse phase solvent progressively diffuses into the surrounding water. Liquid antisolvent precipitation results in highly monodisperse and amorphous nanoparticles of sizes down to 128 nm which can be precisely controlled by the continuous and disperse phase pressure. By comparing optically measured droplet sizes with particle sizes by dynamic light scattering, we could confirm that exactly one particle forms in every droplet. Furthermore, a downstream on-chip concentration allowed withdrawal of major volumes of only the continuous phase fluid which enabled an increase of particle concentration by up to 250 times.

Enzyme-linked immunosorbent assay for total sennosides using anti-sennside A and anti-sennoside B monoclonal antibodies.

Science.gov (United States)

Morinaga, Osamu; Uto, Takuhiro; Sakamoto, Seiichi; Tanaka, Hiroyuki; Shoyama, Yukihiro

2009-01-01

Total sennosides concentration is a very important factor when rhubarb and senna will be used as crude drugs. However, one-step analytical technique for total sennosides has not been reported except HPLC. An enzyme-linked immunosorbent assay (ELISA) for total sennosides concentration by using the combination of anti-sennoside A (SA) and anti-sennoside B (SB) monoclonal antibodies (MAbs) in a single assay has been investigated. Total sennosides concentration in rhubarb and senna samples determined by newly developed assay system showed good agreement with those analyzed by ELISA using anti-SA MAb and anti-SB MAb, respectively.

A comparison of the intrasubject variation in drug exposure between generic and brand-name drugs: a retrospective analysis of replicate design trials.

Science.gov (United States)

Yu, Yang; Teerenstra, Steven; Neef, Cees; Burger, David; Maliepaard, Marc

2016-04-01

The aim of the present study was to investigate whether differences in total and peak drug exposure upon generic substitution are due to differences between formulations or to intrasubject pharmacokinetic variability of the active substance. The study was designed as a retrospective reanalysis of existing studies. Nine replicate design bioequivalence studies representing six drug classes - i.e. for alendronate, atorvastatin, cyclosporin, ebastine, exemestane, mycophenolate mofetil, and ropinirole - were retrieved from the Dutch Medicines Regulatory Authority. In most studies, the intrasubject variability in total and peak drug exposure was comparable for the brand-name [in the range 0.01-0.24 for area under the concentration-time curve (AUCt ) and 0.02-0.29 for peak plasma concentration (Cmax ) on a log scale] and generic (0.01-0.23 for AUCt and 0.08-0.33 for Cmax ) drugs, and was comparable with the intrasubject variability upon switching between those drugs (0.01-0.23 for AUCt and 0.06-0.33 for Cmax ). The variance related to subject-by-formulation interaction could be considered negligible (-0.069 to 0.047 for AUCt and -0.091 to 0.02 for Cmax ). In the investigated studies, the variation in total and peak exposure seen when a patient is switched from a brand-name to a generic drug is comparable with that seen following repeated administration of the brand-name drug in the patient. Only the intrasubject variability seems to play a crucial and decisive role in the variation in drug exposure seen; no additional formulation-dependent variation in exposure is observed upon switching. Thus, our data support that, for the medicines that were included in the present investigation, from a clinical pharmacological perspective, the benefit-risk balance of a generic drug is comparable with that of the brand-name drug. © 2015 The British Pharmacological Society.

Correlation of the concentration of the carbon-associated radiation damage levels with the total carbon concentration in silicon

Energy Technology Data Exchange (ETDEWEB)

Ferenczi, G.; Londos, C.A.; Pavelka, T.; Somogyi, M.; Mertens, A.

1988-01-01

The dominant carbon-related radiation damage center in silicon was studied in detail by deep level transient spectroscopy. Samples with different carbon and oxygen content were implanted with gradually increasing proton fluence. Two energetically closely spaced levels were revealed and tentative identities were assigned. One at E/sub T/+E/sub V/ = 0.344 eV (sigma/sub p/ = 1.1 x 10/sup -16/ cm/sup 2/) is assigned as the C+O/sub i/ complex, and that at E/sub T/+E/sub V/ = 0.370 eV (sigma/sub p/ = 8 x 10/sup -18/ cm/sup 2/) is assigned as the C/sub s/-Si/sub i/-C/sub s/ complex. It was shown that the concentration of these defects is correlated to the total concentration of carbon in the crystal.

HPLC for simultaneous quantification of total ceramide, glucosylceramide, and ceramide trihexoside concentrations in plasma

NARCIS (Netherlands)

Groener, Johanna E. M.; Poorthuis, Ben J. H. M.; Kuiper, Sijmen; Helmond, Mariette T. J.; Hollak, Carla E. M.; Aerts, Johannes M. F. G.

2007-01-01

BACKGROUND: Simple, reproducible assays are needed for the quantification of sphingolipids, ceramide (Cer), and sphingoid bases. We developed an HPLC method for simultaneous quantification of total plasma concentrations of Cer, glucosylceramide (GlcCer), and ceramide trihexoside (CTH). METHODS:

Potential drug-drug interactions with direct oral anticoagulants in elderly hospitalized patients.

Science.gov (United States)

Forbes, Heather L; Polasek, Thomas M

2017-10-01

To determine the prevalence and nature of potential drug-drug interactions (DDIs) with direct oral anticoagulants (DOACs) in elderly hospitalized patients. This was a retrospective observational study. Inclusion criteria were: aged over 65 years; taking apixaban, rivaroxaban or dabigatran; and admitted to the Repatriation General Hospital between April 2014 and July 2015. A list of clinically relevant 'perpetrator' drugs was compiled from product information, the Australian Medicines Handbook, the Australian National Prescribing Service resources, and local health network guidelines. The prevalence and nature of potential DDIs with DOACs was determined by comparing inpatient drug charts with the list of perpetrator drugs. There were 122 patients in the study with a mean age of 82 years. Most patients had nonvalvular atrial fibrillation and were taking DOACs to prevent thrombotic stroke (83%). Overall, 45 patients (37%) had a total of 54 potential DDIs. Thirty-five patients had potential pharmacodynamic DDIs with antidepressants, nonsteroidal anti-inflammatory drugs and antiplatelets (35/122, 29%). Nineteen patients had potential pharmacokinetic DDIs (19/122, 16%). Of these, 68% (13/19) were taking drugs that increase DOAC plasma concentrations (amiodarone, erythromycin, diltiazem or verapamil) and 32% (6/19) were taking drugs that decrease DOAC plasma concentrations (carbamazepine, primidone or phenytoin). There were no cases of patients taking contraindicated interacting drugs. Potential DDIs with DOACs in elderly hospital inpatients are relatively common, particularly interactions that may increase the risk of bleeding. The risk-benefit ratio of DOACs in elderly patients on polypharmacy should always be carefully considered.

Laser ablation-laser induced breakdown spectroscopy for the measurement of total elemental concentration in soils.

Science.gov (United States)

Pareja, Jhon; López, Sebastian; Jaramillo, Daniel; Hahn, David W; Molina, Alejandro

2013-04-10

The performances of traditional laser-induced breakdown spectroscopy (LIBS) and laser ablation-LIBS (LA-LIBS) were compared by quantifying the total elemental concentration of potassium in highly heterogeneous solid samples, namely soils. Calibration curves for a set of fifteen samples with a wide range of potassium concentrations were generated. The LA-LIBS approach produced a superior linear response different than the traditional LIBS scheme. The analytical response of LA-LIBS was tested with a large set of different soil samples for the quantification of the total concentration of Fe, Mn, Mg, Ca, Na, and K. Results showed an acceptable linear response for Ca, Fe, Mg, and K while poor signal responses were found for Na and Mn. Signs of remaining matrix effects for the LA-LIBS approach in the case of soil analysis were found and discussed. Finally, some improvements and possibilities for future studies toward quantitative soil analysis with the LA-LIBS technique are suggested.

Drug Concentration Thresholds Predictive of Therapy Failure and Death in Children With Tuberculosis: Bread Crumb Trails in Random Forests.

Science.gov (United States)

Swaminathan, Soumya; Pasipanodya, Jotam G; Ramachandran, Geetha; Hemanth Kumar, A K; Srivastava, Shashikant; Deshpande, Devyani; Nuermberger, Eric; Gumbo, Tawanda

2016-11-01

 The role of drug concentrations in clinical outcomes in children with tuberculosis is unclear. Target concentrations for dose optimization are unknown.  Plasma drug concentrations measured in Indian children with tuberculosis were modeled using compartmental pharmacokinetic analyses. The children were followed until end of therapy to ascertain therapy failure or death. An ensemble of artificial intelligence algorithms, including random forests, was used to identify predictors of clinical outcome from among 30 clinical, laboratory, and pharmacokinetic variables.  Among the 143 children with known outcomes, there was high between-child variability of isoniazid, rifampin, and pyrazinamide concentrations: 110 (77%) completed therapy, 24 (17%) failed therapy, and 9 (6%) died. The main predictors of therapy failure or death were a pyrazinamide peak concentration <38.10 mg/L and rifampin peak concentration <3.01 mg/L. The relative risk of these poor outcomes below these peak concentration thresholds was 3.64 (95% confidence interval [CI], 2.28-5.83). Isoniazid had concentration-dependent antagonism with rifampin and pyrazinamide, with an adjusted odds ratio for therapy failure of 3.00 (95% CI, 2.08-4.33) in antagonism concentration range. In regard to death alone as an outcome, the same drug concentrations, plus z scores (indicators of malnutrition), and age <3 years, were highly ranked predictors. In children <3 years old, isoniazid 0- to 24-hour area under the concentration-time curve <11.95 mg/L × hour and/or rifampin peak <3.10 mg/L were the best predictors of therapy failure, with relative risk of 3.43 (95% CI, .99-11.82).  We have identified new antibiotic target concentrations, which are potential biomarkers associated with treatment failure and death in children with tuberculosis. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America.

EFFECTS OF COMMONLY USED COOKING PRACTICES ON TOTAL MERCURY CONCENTRATION IN FISH AND THEIR IMPACT ON EXPOSURE ASSESSMENTS

Science.gov (United States)

The effects of cooking practices commonly used by Native Americans on total mercury concentrations in fish were investigated. A preparation factor relating mercury concentrations in fish as prepared for consumption to mercury concentration data as measured in typical environmenta...

Total antioxidative capacity and zinc concentration in dogs suffering from perianal tumours

Directory of Open Access Journals (Sweden)

Brodzki Adam

2015-09-01

Full Text Available The aim of the study was to determine total antioxidative capacity (TAC and zinc concentration in serum of dogs suffering from perianal tumours just before the start of the antihormonal treatment (AHT and one and six months later. The study was performed on 45 dogs divided into two groups: control group suffering from non-malignant tumours (N = 24 and a group with malignant neoplastic changes (N = 21. Serum TAC and zinc concentrations were measured using photometric and atomic absorption spectrophotometric methods. Six months after the start of the AHT, TAC was significantly lower by 10.6% in dogs with malignant tumours when compared to controls (P = 0.03. In the non-malignant group, serum zinc concentration was higher before the treatment than in the malignant group, while the opposite results were observed six months later (P < 0.001. In the non-malignant group, gradually decreasing values of serum zinc concentration at each stage of the investigation were observed, while the opposite results were obtained in the malignant group (P < 0.05. The obtained results indicate that malignant neoplastic process is associated with significantly reduced TAC. Determination of serum zinc concentration in dogs with non-malignant and malignant perianal tumours may have practical diagnostic and prognostic values and may serve towards increasing the effectiveness of AHT monitoring.

Concentration of total proteins in blood plasma of chickens hatched from irradiated eggs with low dose gamma radiation

International Nuclear Information System (INIS)

Vilic, M.; Kraljevic, P.; Miljanic, S.; Simpraga, M.

2005-01-01

It is known that low-dose ionising radiation may have stimulating effects on chickens. Low doses may also cause changes in the concentration of blood plasma total proteins, glucose and cholesterol in chickens. This study investigates the effects of low dose gamma-radiation on the concentration of total proteins in the blood plasma of chickens hatched from eggs irradiated with a dose of 0.15 Gy on incubation days 7 and 19. Results were compared with the control group (chickens hatched from non-irradiated eggs). After hatching, all other conditions were the same for both groups. Blood samples were drawn from the heart, and later from the wing vein on days 1, 3, 5, 7,10, 20, 30 and 42. The concentration of total proteins was determined spectrophotometrically using Boehringer Mannheim GmbH optimised kits. The concentration of total proteins in blood plasma in chickens hatched from eggs irradiated with 0.15 Gy on incubation day 7 showed a statistically significant decrease on the sampling day 3 (P less than 0.05) and 7 (P less than 0.01). The concentration of total proteins in blood plasma in chickens hatched from eggs irradiated with 0.15 Gy on incubation day 19 showed a statistically significant increase only on sampling day 1 (P less than 0.05). These results suggest that exposure of eggs to 0.15 Gy of gamma-radiation on the 7th and 19th day of incubation could produce different effects on the protein metabolism in chickens.(author)

High affinity capture and concentration of quinacrine in polymorphonuclear neutrophils via vacuolar ATPase-mediated ion trapping: Comparison with other peripheral blood leukocytes and implications for the distribution of cationic drugs

Energy Technology Data Exchange (ETDEWEB)

Roy, Caroline; Gagné, Valérie; Fernandes, Maria J.G.; Marceau, François, E-mail: francois.marceau@crchul.ulaval.ca

2013-07-15

Many cationic drugs are concentrated in acidic cell compartments due to low retro-diffusion of the protonated molecule (ion trapping), with an ensuing vacuolar and autophagic cytopathology. In solid tissues, there is evidence that phagocytic cells, e.g., histiocytes, preferentially concentrate cationic drugs. We hypothesized that peripheral blood leukocytes could differentially take up a fluorescent model cation, quinacrine, depending on their phagocytic competence. Quinacrine transport parameters were determined in purified or total leukocyte suspensions at 37 °C. Purified polymorphonuclear leukocytes (PMNLs, essentially neutrophils) exhibited a quinacrine uptake velocity inferior to that of lymphocytes, but a consistently higher affinity (apparent K{sub M} 1.1 vs. 6.3 μM, respectively). However, the vacuolar (V)-ATPase inhibitor bafilomycin A1 prevented quinacrine transport or initiated its release in either cell type. PMNLs capture most of the quinacrine added at low concentrations to fresh peripheral blood leukocytes compared with lymphocytes and monocytes (cytofluorometry). Accumulation of the autophagy marker LC3-II occurred rapidly and at low drug concentrations in quinacrine-treated PMNLs (significant at ≥ 2.5 μM, ≥ 2 h). Lymphocytes contained more LAMP1 than PMNLs, suggesting that the mass of lysosomes and late endosomes is a determinant of quinacrine uptake V{sub max}. PMNLs, however, exhibited the highest capacity for pinocytosis (uptake of fluorescent dextran into endosomes). The selectivity of quinacrine distribution in peripheral blood leukocytes may be determined by the collaboration of a non-concentrating plasma membrane transport mechanism, tentatively identified as pinocytosis in PMNLs, with V-ATPase-mediated concentration. Intracellular reservoirs of cationic drugs are a potential source of toxicity (e.g., loss of lysosomal function in phagocytes). - Highlights: • Quinacrine is concentrated in acidic organelles via V-ATPase-mediated ion

High affinity capture and concentration of quinacrine in polymorphonuclear neutrophils via vacuolar ATPase-mediated ion trapping: Comparison with other peripheral blood leukocytes and implications for the distribution of cationic drugs

International Nuclear Information System (INIS)

Roy, Caroline; Gagné, Valérie; Fernandes, Maria J.G.; Marceau, François

2013-01-01

Many cationic drugs are concentrated in acidic cell compartments due to low retro-diffusion of the protonated molecule (ion trapping), with an ensuing vacuolar and autophagic cytopathology. In solid tissues, there is evidence that phagocytic cells, e.g., histiocytes, preferentially concentrate cationic drugs. We hypothesized that peripheral blood leukocytes could differentially take up a fluorescent model cation, quinacrine, depending on their phagocytic competence. Quinacrine transport parameters were determined in purified or total leukocyte suspensions at 37 °C. Purified polymorphonuclear leukocytes (PMNLs, essentially neutrophils) exhibited a quinacrine uptake velocity inferior to that of lymphocytes, but a consistently higher affinity (apparent K M 1.1 vs. 6.3 μM, respectively). However, the vacuolar (V)-ATPase inhibitor bafilomycin A1 prevented quinacrine transport or initiated its release in either cell type. PMNLs capture most of the quinacrine added at low concentrations to fresh peripheral blood leukocytes compared with lymphocytes and monocytes (cytofluorometry). Accumulation of the autophagy marker LC3-II occurred rapidly and at low drug concentrations in quinacrine-treated PMNLs (significant at ≥ 2.5 μM, ≥ 2 h). Lymphocytes contained more LAMP1 than PMNLs, suggesting that the mass of lysosomes and late endosomes is a determinant of quinacrine uptake V max . PMNLs, however, exhibited the highest capacity for pinocytosis (uptake of fluorescent dextran into endosomes). The selectivity of quinacrine distribution in peripheral blood leukocytes may be determined by the collaboration of a non-concentrating plasma membrane transport mechanism, tentatively identified as pinocytosis in PMNLs, with V-ATPase-mediated concentration. Intracellular reservoirs of cationic drugs are a potential source of toxicity (e.g., loss of lysosomal function in phagocytes). - Highlights: • Quinacrine is concentrated in acidic organelles via V-ATPase-mediated ion trapping

Therapeutic drug monitoring of lopinavir/ritonavir in pregnancy.

LENUS (Irish Health Repository)

Lambert, J S

2011-03-01

The aim of the study was to determine total and unbound lopinavir (LPV) plasma concentrations in HIV-infected pregnant women receiving lopinavir\\/ritonavir (LPV\\/r tablet) undergoing therapeutic drug monitoring (TDM) during pregnancy and postpartum.

HPLC identification and determination of myricetin, quercetin, kaempferol and total flavonoids in herbal drugs

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Svetlana Kulevanova

2003-05-01

Full Text Available A new and rapid HPLC method for identification and determination of myricetin, quercetin, kaempferol and total flavonoids in ten herbal drugs of Macedonian origin is presented. Preparation of samples (Uvae ursi folim, Pruni spinosae flos, Sambuci flos, Betulae folim, Primulae flos, Herniariae herba, Centaurii herba, Tiliae flos, Robiniae pseudoacaciae flos, Bursae pastoris herba included hydrolysis of glycosides and extraction of total aglycones with ethyl acetate. HPLC analysis with UV-diode array detection was carried out on RP C18 column, using 5% acetic acid and acetonitrile in agradient elution mode and column temperature of 30 o C. The monitoring of the elution is performed in the whole UV-range and the acquisition of data for quantitative analysis at 367 nm. Screening of the extracts showed presence of quercetin in nine, kaempferol in seven and myricetin in only one sample. The quantitative analysis showed that the content of quercetin ranged from 0.026-0.506 % (m/m, while for kaempferol it was from traces to 1.246 %. Uvaeursi folium and Pruni spinosae flos were rich in content of quercetin (0.482 % and 0.506 %, respectively, while Pruni spinosae flos and Robiniae pseudoaccaciae flos contained the highest amounts of kaempferol (1.246 % and 0.892 %, respectively. Myricetin was identified and determined only in Betulae folium (0.102 %. The content of total flavonoids in the investigated samples expressed in terms of quercetin ranged from 0.040 to 1.680 %. The proposed HPLC method is convenient for use in routine analysis of myricetin, quercetin and kaempferol, as well as for estimation of total flavonoids content in herbal drugs.

Drug residues recovered in feed after various feedlot mixer truck cleanout procedures.

Science.gov (United States)

Van Donkersgoed, Joyce; Sit, Dan; Gibbons, Nicole; Ramogida, Caterina; Hendrick, Steve

2010-01-01

A study was conducted to determine the effectiveness of two methods of equipment cleanout, sequencing or flushing, for reducing drug carryover in feedlot mixer trucks. Feed samples were collected from total mixed rations before and after various feed mixer equipment cleanout procedures. Medicated rations contained either 11 ppm of tylosin or 166 or 331 ppm of chlortetracycline. There were no differences between sequencing and flushing or between flushing with dry barley and flushing with barley silage in the median proportion of drug recovered in the next ration. A larger drug reduction was achieved using flush material at a volume of 10 versus 5% of the mixer capacity and mixing the flush material for 3 versus 4 min. Regardless of the drug or prescription concentrations in the total mixed rations or the equipment cleanout procedure used, concentrations of chlortetracycline and tylosin recovered were very low.

Total concentration and speciation of heavy metals in biosolids from urban origin; Concentracion total y especiacion de metales pesados en biosolidos de origen urbano origin

Energy Technology Data Exchange (ETDEWEB)

Gonzalez Flores, Eduardo [Laboratorio de Ingenieria Ambiental, Instituto Tecnologico de Puebla, Puebla, Puebla (Mexico)]. E-mail: egonz1962@yahoo.com.mx; Tornero Campante, Mario Alberto [Colegio de Postgraduados - Campus Puebla, San Pedro Cholula, Puebla (Mexico); Angeles Cruz, Yolanda [Laboratorio de Ingenieria Ambiental, Instituto Tecnologico de Puebla, Puebla, Puebla (Mexico); Bonilla y Fernandez, Noemi [Departamento de Agroecologia y Ambiente, Instituto de Ciencias - Benemerita Universidad Autonoma de Puebla, Puebla, Puebla (Mexico)

2009-02-15

The analysis of heavy metals is a very important task to asses the potential environmental and health risk associated with biosolids deposition in agricultural soil. However, it is widely accepted that determination of total concentration of heavy metals does not give an accurate estimation of the potential environmental impact. So, it is necessary to apply speciation studies to obtain suitable information about their bioavailability. This study was carried out on sewage sludge samples collected in a municipal waste-water treatment plant, located in Puebla City (Mexico). They are used for amendment agricultural soil. The speciation of heavy metals (Cd, Cr, Cu, Ni, Pb and Zn) was made using a sequential extraction procedure. The aim was to determine their concentration in bioavailability fractions. It was got the total concentration of heavy metals using acid digestion in a closed system and was determined with atomic absorption spectrometry. The total concentrations of heavy metals were lower than that established by Mexican legislation. The heavy metals are mainly associated with the mineral fraction and organic matter and consequently they show low bioavailability. [Spanish] El analisis de metales pesados es una actividad importante cuando se quiere valorar el potencial riesgo ambiental y de salud asociado con la utilizacion de biosolidos en suelos agricolas. Sin embargo, es ampliamente aceptado que la determinacion del contenido total no da una valoracion apropiada del impacto ambiental causado. Por lo tanto, es necesario realizar estudios de especiacion para obtener informacion mas detallada sobre su biodisponibilidad. Este estudio se llevo a cabo con muestras de lodos residuales producidos en una planta de tratamiento de aguas residuales ubicada en la ciudad de Puebla (Mexico). Estos biosolidos son utilizados para enmendar suelos agricolas. La especiacion de metales pesados (Cd, Cr, Cu, Ni, Pb y Zn) se realizo usando un procedimiento de extraccion secuencial

A Generic Multi-Compartmental CNS Distribution Model Structure for 9 Drugs Allows Prediction of Human Brain Target Site Concentrations

NARCIS (Netherlands)

Yamamoto, Yumi; Valitalo, Pyry A.; van den Berg, Dirk-Jan; Hartman, Robin; van den Brink, Willem; Wong, Yin Cheong; Huntjens, Dymphy R.; Proost, Johannes H.; Vermeulen, An; Krauwinkel, Walter; Bakshi, Suruchi; Aranzana-Climent, Vincent; Marchand, Sandrine; Dahyot-Fizelier, Claire; Couet, William; Danhof, Meindert; van Hasselt, Johan G. C.; de lange, Elizabeth C. M.

Purpose Predicting target site drug concentration in the brain is of key importance for the successful development of drugs acting on the central nervous system. We propose a generic mathematical model to describe the pharmacokinetics in brain compartments, and apply this model to predict human

Diurnal salivary cortisol concentrations in Parkinson’s disease: increased total secretion and morning cortisol concentrations

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Skogar Ö

2011-08-01

Full Text Available Ö Skogar1,4, P-A Fall2, G Hallgren3, J Lökk4, B Bringer2, M Carlsson1, U Lennartsson3, H Sandbjork3, C-J Törnhage51Department of Geriatrics, Ryhov Hospital, Jonkoping, 2Department of Geriatrics, University Hospital, Linkoping, 3Department of Neurology, Skaraborg Hospital, Skovde, 4Institute of Neurobiology, Care Sciences, and Society, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, 5Department of Pediatrics, Skaraborg Hospital, Skövde, SwedenBackground: Parkinson’s disease (PD is a chronic neurodegenerative disorder. There is limited knowledge about the function of the hypothalamic-pituitary-adrenal axis in PD. The primary aim of this prospective study was to analyze diurnal salivary cortisol concentrations in patients with PD and correlate these with age, gender, body mass index (BMI, duration of PD, and pain. The secondary aim was to compare the results with a healthy reference group.Methods: Fifty-nine PD patients, 35 women and 24 men, aged 50–79 years, were recruited. The reference group comprised healthy individuals matched for age, gender, BMI, and time point for sampling. Salivary cortisol was collected at 8 am, 1 pm, and 8 pm, and 8 am the next day using cotton-based Salivette® tubes and analyzed using Spectria® Cortisol I125. A visual analog scale was used for estimation of pain.Results: The median cortisol concentration was 16.0 (5.8–30.2 nmol/L at 8 am, 5.8 (3.0–16.4 at 1 pm, 2.8 (1.6–8.0 at 8 pm, and 14.0 (7.5–28.7 at 8 am the next day. Total secretion and rate of cortisol secretion during the day (8 am–8 pm and the concentration of cortisol on the next morning were lower (12.5 nmol/L in the reference group. No significant correlations with age, gender, BMI, duration of PD, Hoehn and Yahr score, Unified Parkinson’s Disease Rating Scale III score, gait, pain, or cortisol concentrations were found.Conclusion: The neurodegenerative changes in PD does not seem to interfere with the

Intralesional Versus Oral Chloroquine in Cutaneous Leishmaniasis: Comparison of Outcome, Duration of Treatment and Total Dose of Drug

International Nuclear Information System (INIS)

Hanif, M. M.; Akram, K.; Mustafa, G.

2016-01-01

Objective: To compare intralesional versus oral chloroquine in cutaneous leishmaniasis and determine the cure rate, duration of treatment, and total dose of drug. Study Design: Randomized controlled study. Place and Duration of Study: Department of Dermatology, Sheikh Zayed Medical College/Hospital, Rahim Yar Khan, from November 2013 to June 2014. Methodology: Consecutive 86 patients of cutaneous leishmaniasis, with single to multiple lesions of various sizes were enrolled and divided randomly into group A and B for the purpose of intralesional and oral chloroquine administration, respectively to compare the effect of the two routes on duration of treatment and total dose of the drug. SPSS version 16 was used for data analysis after data entry into it. Quantitative variables like, duration, cost and total dose of treatment were calculated as mean and standard deviation and compared by using T-test. P-value of less than 0.05 was taken as significant. Results: Cure rate was 100% in both groups towards the end of treatment. Mean duration of treatment was 9.17 ± 3 weeks in intralesional (A) group as against 11.37 ± 3 weeks in oral (B) group (p = 0.0028). Mean total dose of the drug given to each patient in group A was 5.8 ± 0.5 gm and in group B, it was 19.2 ± 1.5 gm, which is significantly higher (p=0.001). The total cost of treatment in group A was Rs. 90 ± 8 and in group B it was Rs. 91 ± 1 (p=0.446). Conclusion: Duration of treatment is significantly shorter and total dose is lesser with intralesional compared to oral chloroquine in treatment of cutaneous leishmaniasis. (author)

Evaluation of the trace elements and the total mercury concentration in fishes commercialized at the Cubatao city, Sao Paulo, Brazil

International Nuclear Information System (INIS)

Fonseca, Barbara C.; Farias, Luciana A.; Curcho, Michel R.M.; Favaro, Debora I.T.; Braga, Elisabete S.

2009-01-01

This paper evaluates the total Hg and the trace elements As, Br, Co, Cr and Rb concentrations in muscle of commercially important fishes at the Cubatao, Sao Paulo, Brazil, region. The following carnivore species were analysed: jew fish (Micropogonias furnieri), girl leg (Menticirrhus americanus), hake (Macrodon ancylodon), and plant eaters, sardine (Sardella braziliensis) and grey mullet (Mugil liza), representing a total of 58 samples. The analysed trace elements were determined through the neutron analysis activation (NAA) and total Hg, through the atomic absorption spectrometry with cold vapor generation (CV AAS). The analysed elements present a great concentration variation, not only among individuals of the same specie, but also among all the analysed species. The total Hg concentration were highly significant, with the predator species jew fish, girl leg and hake presenting concentrations larger than the non predator species sardine and grey mullet. Nevertheless, the content of total Hg remained bellow the limits established by the Brazilian legislation which is the 500 μg kg -1 for the non predator species, and the 1000 μg -1 for the predator species (humid weight)

Effect of initial total solids concentration on volatile fatty acid production from food waste during anaerobic acidification.

Science.gov (United States)

Wang, Quan; Jiang, Jianguo; Zhang, Yujing; Li, Kaimin

2015-01-01

The effect of initial total solids (TS) concentration on volatile fatty acid (VFAs) production from food waste under mesophilic conditions (35 °C) was determined. VFAs concentration and composition, biogas production, soluble chemical oxygen demand concentration, TS and volatile solids (VS) reduction, and ammonia nitrogen [Formula: see text] release were investigated. The VFAs concentrations were 26.10, 39.68, 59.58, and 62.64 g COD/L at TS contents of 40, 70, 100, and 130 g/L, respectively. While the VFAs' yields ranged from 0.467 to 0.799 g COD/g VSfed, decreased as initial TS increased. The percentage of propionate was not affected by TS concentration, accounting for 30.19-34.86% of the total VFAs, while a higher percentage of butyrate and lower percentage of acetate was achieved at a higher TS concentration. Biogas included mainly hydrogen and carbon dioxide and the maximum hydrogen yield of 148.9 ml/g VSfed was obtained at 130 g TS/L. [Formula: see text] concentration, TS and VS reductions increased as initial TS increased. Considering the above variables, we conclude that initial TS of 100 g/L shall be the most appropriate to VFAs production.

Effects of drugs in subtoxic concentrations on the metabolic fluxes in human hepatoma cell line Hep G2

International Nuclear Information System (INIS)

Niklas, Jens; Noor, Fozia; Heinzle, Elmar

2009-01-01

Commonly used cytotoxicity assays assess the toxicity of a compound by measuring certain parameters which directly or indirectly correlate to the viability of the cells. However, the effects of a given compound at concentrations considerably below EC 50 values are usually not evaluated. These subtoxic effects are difficult to identify but may eventually cause severe and costly long term problems such as idiosyncratic hepatotoxicity. We determined the toxicity of three hepatotoxic compounds, namely amiodarone, diclofenac and tacrine on the human hepatoma cell line Hep G2 using an online kinetic respiration assay and analysed the effects of subtoxic concentrations of these drugs on the cellular metabolism by using metabolic flux analysis. Several changes in the metabolism could be detected upon exposure to subtoxic concentrations of the test compounds. Upon exposure to diclofenac and tacrine an increase in the TCA-cycle activity was observed which could be a signature of an uncoupling of the oxidative phosphorylation. The results indicate that metabolic flux analysis could serve as an invaluable novel tool for the investigation of the effects of drugs. The described methodology enables tracking the toxicity of compounds dynamically using the respiration assay in a range of concentrations and the metabolic flux analysis permits interesting insights into the changes in the central metabolism of the cell upon exposure to drugs.

Comparison of Active Drug Concentrations in the Pulmonary Epithelial Lining Fluid and Interstitial Fluid of Calves Injected with Enrofloxacin, Florfenicol, Ceftiofur, or Tulathromycin

Science.gov (United States)

Foster, Derek M.; Martin, Luke G.; Papich, Mark G.

2016-01-01

Bacterial pneumonia is the most common reason for parenteral antimicrobial administration to beef cattle in the United States. Yet there is little information describing the antimicrobial concentrations at the site of action. The objective of this study was to compare the active drug concentrations in the pulmonary epithelial lining fluid and interstitial fluid of four antimicrobials commonly used in cattle. After injection, plasma, interstitial fluid, and pulmonary epithelial lining fluid concentrations and protein binding were measured to determine the plasma pharmacokinetics of each drug. A cross-over design with six calves per drug was used. Following sample collection and drug analysis, pharmacokinetic calculations were performed. For enrofloxacin and metabolite ciprofloxacin, the interstitial fluid concentration was 52% and 78% of the plasma concentration, while pulmonary fluid concentrations was 24% and 40% of the plasma concentration, respectively. The pulmonary concentrations (enrofloxacin + ciprofloxacin combined) exceeded the MIC90 of 0.06 μg/mL at 48 hours after administration. For florfenicol, the interstitial fluid concentration was almost 98% of the plasma concentration, and the pulmonary concentrations were over 200% of the plasma concentrations, exceeding the breakpoint (≤ 2 μg/mL), and the MIC90 for Mannheimia haemolytica (1.0 μg/mL) for the duration of the study. For ceftiofur, penetration to the interstitial fluid was only 5% of the plasma concentration. Pulmonary epithelial lining fluid concentration represented 40% of the plasma concentration. Airway concentrations exceeded the MIC breakpoint for susceptible respiratory pathogens (≤ 2 μg/mL) for a short time at 48 hours after administration. The plasma and interstitial fluid concentrations of tulathromcyin were lower than the concentrations in pulmonary fluid throughout the study. The bronchial concentrations were higher than the plasma or interstitial concentrations, with over 900

Comparison of Active Drug Concentrations in the Pulmonary Epithelial Lining Fluid and Interstitial Fluid of Calves Injected with Enrofloxacin, Florfenicol, Ceftiofur, or Tulathromycin.

Directory of Open Access Journals (Sweden)

Derek M Foster

Full Text Available Bacterial pneumonia is the most common reason for parenteral antimicrobial administration to beef cattle in the United States. Yet there is little information describing the antimicrobial concentrations at the site of action. The objective of this study was to compare the active drug concentrations in the pulmonary epithelial lining fluid and interstitial fluid of four antimicrobials commonly used in cattle. After injection, plasma, interstitial fluid, and pulmonary epithelial lining fluid concentrations and protein binding were measured to determine the plasma pharmacokinetics of each drug. A cross-over design with six calves per drug was used. Following sample collection and drug analysis, pharmacokinetic calculations were performed. For enrofloxacin and metabolite ciprofloxacin, the interstitial fluid concentration was 52% and 78% of the plasma concentration, while pulmonary fluid concentrations was 24% and 40% of the plasma concentration, respectively. The pulmonary concentrations (enrofloxacin + ciprofloxacin combined exceeded the MIC90 of 0.06 μg/mL at 48 hours after administration. For florfenicol, the interstitial fluid concentration was almost 98% of the plasma concentration, and the pulmonary concentrations were over 200% of the plasma concentrations, exceeding the breakpoint (≤ 2 μg/mL, and the MIC90 for Mannheimia haemolytica (1.0 μg/mL for the duration of the study. For ceftiofur, penetration to the interstitial fluid was only 5% of the plasma concentration. Pulmonary epithelial lining fluid concentration represented 40% of the plasma concentration. Airway concentrations exceeded the MIC breakpoint for susceptible respiratory pathogens (≤ 2 μg/mL for a short time at 48 hours after administration. The plasma and interstitial fluid concentrations of tulathromcyin were lower than the concentrations in pulmonary fluid throughout the study. The bronchial concentrations were higher than the plasma or interstitial concentrations

Concentration of total protein and degree of acidity (pH of saliva when fasting and after breakfasting

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Gemella Nur Illahi

2016-04-01

Full Text Available Background: While fasting, the mouth does not work to eat and drink so that the salivary glands become less active so saliva production decreased and there was a change in eating timewhich is relation to the mastication process that impact on changes in the degree of acidity (pH Objectives: To determine the concentration of total protein and the degree of acidity (pH of saliva when fasting and after breakfasting. Materials and Methods: The study was observational analytic design with longitudinal (follow up study conducted in the Hj. Halima Dg. Sikati Dental Hospital inKandea in July 2015, the sampling method was purposive sampling. Population was 35 clinical students at the Department of Dental Public Health, Faculty of Dentistry Hasanuddin University with a total sample of 16 students who fit the criteria of the study subjects. To calculate the total protein of saliva concentration using Kyltecautoanalyzerand pH meter to measure the acidity of saliva. Data was analyzed was using SPSS version 17.0 (paired t-test, p <0.05. Results: The mean of total protein (% while fasting by 0135% ± 0.026 and the mean total protein (% after breakfasting at 0.179% ± 0.035, while the average degree of acidity (pH during fasting at 7.26 ± 0:24 and the average degree of acidity (pH after breakfasting at 7.66 ± 0.23 with p-value (0.000. Conclusions: An increase in the total protein concentration and acidity (pH after breakfasting.

Serum protein concentration in low-dose total body irradiation of normal and malnourished rats

International Nuclear Information System (INIS)

Viana, W.C.M.; Lambertz, D.; Borges, E.S.; Neto, A.M.O.; Lambertz, K.M.F.T.; Amaral, A.

2016-01-01

Among the radiotherapeutics' modalities, total body irradiation (TBI) is used as treatment for certain hematological, oncological and immunological diseases. The aim of this study was to evaluate the long-term effects of low-dose TBI on plasma concentration of total protein and albumin using prematurely and undernourished rats as animal model. For this, four groups with 9 animals each were formed: Normal nourished (N); Malnourished (M); Irradiated Normal nourished (IN); Irradiated Malnourished (IM). At the age of 28 days, rats of the IN and IM groups underwent total body gamma irradiation with a source of cobalt-60. Total protein and Albumin in the blood serum was quantified by colorimetry. This research indicates that procedures involving low-dose total body irradiation in children have repercussions in the reduction in body-mass as well as in the plasma levels of total protein and albumin. Our findings reinforce the periodic monitoring of total serum protein and albumin levels as an important tool in long-term follow-up of pediatric patients in treatments associated to total body irradiation. - Highlights: • Low-dose total body irradiation (TBI) in children have repercussions in their body-mass. • Long-term total protein and albumin levels are affected by TBI. • The monitoring of total protein and albumin levels are useful in the follow-up of TBI pediatric patients.

Total and methyl mercury concentrations in sediment and water of a constructed wetland in the Athabasca Oil Sands Region

International Nuclear Information System (INIS)

Oswald, Claire J.; Carey, Sean K.

2016-01-01

In the Athabasca Oil Sands Region in northeastern Alberta, Canada, oil sands operators are testing the feasibility of peatland construction on the post-mining landscape. In 2009, Syncrude Canada Ltd. began construction of the 52 ha Sandhill Fen pilot watershed, including a 15 ha, hydrologically managed fen peatland built on sand-capped soft oil sands tailings. An integral component of fen reclamation is post-construction monitoring of water quality, including salinity, fluvial carbon, and priority pollutant elements. In this study, the effects of fen reclamation and elevated sulfate levels on mercury (Hg) fate and transport in the constructed system were assessed. Total mercury (THg) and methylmercury (MeHg) concentrations in the fen sediment were lower than in two nearby natural fens, which may be due to the higher mineral content of the Sandhill Fen peat mix and/or a loss of Hg through evasion during the peat harvesting, stockpiling and placement processes. Porewater MeHg concentrations in the Sandhill Fen typically did not exceed 1.0 ng L −1 . The low MeHg concentrations may be a result of elevated porewater sulfate concentrations (mean 346 mg L −1 ) and an increase in sulphide concentrations with depth in the peat, which are known to suppress MeHg production. Total Hg and MeHg concentrations increased during a controlled mid-summer flooding event where the water table rose above the ground surface in most of the fen. The Hg dynamics during this event showed that hydrologic fluctuations in this system exacerbate the release of THg and MeHg downstream. In addition, the elevated SO 4 2− concentrations in the peat porewaters may become a problem with respect to downstream MeHg production once the fen is hydrologically connected to a larger wetland network that is currently being constructed. - Highlights: • A constructed fen peatland in the Athabasca Oil Sands Region was studied. • Total and methyl mercury concentrations in fen sediment and waters

Parallel monitoring of plasma and intraluminal drug concentrations in man after oral administration of fosamprenavir in the fasted and fed state.

Science.gov (United States)

Brouwers, Joachim; Tack, Jan; Augustijns, Patrick

2007-10-01

The purpose of this study was to explore the feasibility of linking the pharmacokinetic profile of a drug with its gastrointestinal behavior by simultaneously monitoring plasma and intraluminal drug concentrations. Fosamprenavir, a phosphate ester prodrug of the poorly water-soluble HIV-inhibitor amprenavir, was selected as model compound. A single tablet of fosamprenavir (Telzir) was administered to 5 volunteers in the fasted and fed state (simulated by intake of a nutritional drink). Gastric and duodenal fluids were aspirated in function of time and characterized with respect to the concentration of (fos)amprenavir, inorganic phosphate and pH. In parallel, blood samples were collected and analyzed for amprenavir. The observed plasma concentration-time profiles suggested a food-induced delay in the absorption of amprenavir: in the fed state, mean tmax increased by more than 150 min compared to the fasted state. A similar delay was seen in the duodenal appearance of fosamprenavir (concentrations in mM-range) and, after dephosphorylation, amprenavir (concentrations below 160 microM). This observation could be related to the behavior of fosamprenavir in the stomach. In the fasted state, gastric dissolution of fosamprenavir started immediately, resulting in a Cmax of 4 +/- 2 mM after 43 +/- 15 min; however, in the fed state, the fosamprenavir concentration remained below 20 microM for the first 90 min after drug intake. The postponed gastric dissolution may be attributed to a food-induced delay in tablet disintegration. For the first time, the pharmacokinetic profile of a drug was monitored in parallel with its gastrointestinal concentrations. The observed food effect in the plasma concentration-time profile of amprenavir after intake of its phosphate ester prodrug could be related to a food-induced delay in gastric dissolution of fosamprenavir.

Detection of drugs in 275 alcohol-positive blood samples of Korean drivers.

Science.gov (United States)

Kim, Eunmi; Choe, Sanggil; Lee, Juseon; Jang, Moonhee; Choi, Hyeyoung; Chung, Heesun

2016-08-01

Since driving under the influence of drugs (DUID) is as dangerous as drink-driving, many countries regulate DUID by law. However, laws against the use of drugs while driving are not yet established in Korea. In order to investigate the type and frequency of drugs used by drivers in Korea, we analyzed controlled and non-controlled drugs in alcohol-positive blood samples. Total 275 blood samples were taken from Korean drivers, which were positive in roadside alcohol testing. The following analyses were performed: blood alcohol concentrations by GC; screening for controlled drugs by immunoassay and confirmation for positive samples by GC-MS. For the detection of DUID related drugs in blood samples, a total of 49 drugs were selected and were examined by GC-MS. For a rapid detection of these drugs, an automated identification software called "DrugMan" was used. Concentrations of alcohol in 275 blood samples ranged from 0.011 to 0.249% (average 0.119%). Six specimens showed positive results by immunoassay: one methamphetamine and five benzodiazepines I. By GC-MS confirmation, only benzodiazepines in four cases were identified, while methamphetamine and benzodiazepine in two cases were not detected from the presumptive positive blood samples. Using DrugMan, four drugs were detected; chlorpheniramine (5)*, diazepam (4), dextromethorphan (1) and doxylamine (1). In addition, ibuprofen (1), lidocaine (1) and topiramate (1) were also detected as general drugs in blood samples ('*' indicates frequency). The frequency of drug abuse by Korean drivers was relatively low and a total 14 cases were positive in 275 blood samples with a ratio of 5%. However it is necessary to analyze more samples including alcohol negative blood, and to expand the range of drug lists to get the detailed information. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Effects of total replacement of soybean meal and corn on ruminal fermentation, volatile fatty acids, protozoa concentration, and gas production

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A. Bahri

2018-03-01

Full Text Available The main purpose of this study is to evaluate the effect of total replacement of soybean meal and corn with triticale and faba bean or field pea on rumen fermentation, protozoa counts, and gas production of lactating ewes. A total of 30 Sicilo-Sarde ewes were randomly allocated into three groups and were fed 1.8 kg drymatter of oat hay plus 500 g of one of three concentrates: the first concentrate (CS was mainly composed of soybean meal, corn, and barley; the second (TFB was formed by triticale and faba bean; and the third (TFP was composed of triticale and field pea. The type of concentrate did not affect ruminal pH or ammonia nitrogen concentration (P  >  0.05. The individual concentrations of volatile fatty acids showed a significant interaction between the type of concentrate and sampling time (P  <  0.05, except for Butyric and Isobutyric acids. Within a post-feeding time, the pattern of evolution of total volatile fatty, acetic, and propionic acids differed significantly at 2 h post feeding (P  <  0.05, while butyric and valeric acid changed at 0 and 4 h post feeding. The type of concentrate affected the total number of ciliate protozoa and the Isotricha species (P  <  0.05, whereas Entodinium, Ophryoscolex, and Polyplastron were similar among concentrates (P  >  0.05. The cumulative gas production from the in vitro fermentation, the time of incubation, and their interaction was affected by concentrate (P  <  0.001. The substitution of soybean meal and corn in the concentrate with faba bean or field peas and triticale might maintain rumen parameters of dairy ewes.

Melanin targeting for intracellular drug delivery: Quantification of bound and free drug in retinal pigment epithelial cells.

Science.gov (United States)

Rimpelä, Anna-Kaisa; Hagström, Marja; Kidron, Heidi; Urtti, Arto

2018-05-31

Melanin binding affects drug distribution and retention in pigmented ocular tissues, thereby affecting drug response, duration of activity and toxicity. Therefore, it is a promising possibility for drug targeting and controlled release in the pigmented cells and tissues. Intracellular unbound drug concentrations determine pharmacological and toxicological actions, but analyses of unbound vs. total drug concentrations in pigmented cells are lacking. We studied intracellular binding and cellular drug uptake in pigmented retinal pigment epithelial cells and in non-pigmented ARPE-19 cells with five model drugs (chloroquine, propranolol, timolol, diclofenac, methotrexate). The unbound drug fractions in pigmented cells were 0.00016-0.73 and in non-pigmented cells 0.017-1.0. Cellular uptake (i.e. distribution ratio Kp), ranged from 1.3 to 6300 in pigmented cells and from 1.0 to 25 in non-pigmented cells. Values for intracellular bioavailability, F ic , were similar in both cells types (although larger variation in pigmented cells). In vitro melanin binding parameters were used to predict intracellular unbound drug fraction and cell uptake. Comparison of predictions with experimental data indicates that other factors (e.g. ion-trapping, lipophilicity-related binding to other cell components) also play a role. Melanin binding is a major factor that leads to cellular uptake and unbound drug fractions of a range of 3-4 orders of magnitude indicating that large reservoirs of melanin bound drug can be generated in the cells. Understanding melanin binding has important implications on retinal drug targeting, efficacy and toxicity. Copyright © 2017. Published by Elsevier B.V.

The relationship between total phenol concentration and the perceived style of extra virgin olive oil

Energy Technology Data Exchange (ETDEWEB)

Gawel, R.; Rogers, D. A. G.

2009-07-01

The degree of bitterness and pungency of a virgin olive oil largely defines its style, and therefore how it is most appropriately used by consumers. In order to assess how Australian olive oil producers interpret the style of their oils, 920 Australian virgin olive oils were classified by their producers as either being mild, medium or robust in style. Although in general, the classifications by producers were associated with the oils total phenol concentration, significant variability in phenol concentration within each style category was observed. The perceived styles of a subset of these oils were further assessed by panels of expert tasters. The expert panels were more discriminating when assigning oils to style categories based on total phenol levels. The producers and the expert panels were in moderate agreement with respect to oil style, with the interpretation of what constitutes a mild oil being the most contentious. (Author) 16 refs.

Sensing methanol concentration in direct methanol fuel cell with total harmonic distortion: Theory and application

International Nuclear Information System (INIS)

Mao Qing; Krewer, Ulrike

2012-01-01

The nonlinear frequency response of a direct methanol fuel cell (DMFC) is studied by analyzing the total harmonic distortion (THD) spectra. The dependence of the THD spectra on methanol concentration and methanol oxidation kinetics is investigated by means of both simulation and experiment. Simulation using a continuous stirred tank reactor network model suggests that the methanol concentration profile in the anode has a strong impact on the THD spectra. The experimentally observed nonlinear behavior of the DMFC anode can be qualitatively reproduced with a model containing a three-step methanol oxidation mechanism with Kauranen–Frumkin/Temkin kinetics. Both experiment and simulation results show that THD value has a monotonic correlation with methanol concentration at certain frequencies and its sensitivity to concentration is improved with increased current amplitude. The monotonic relationship enables the THD to sense the methanol concentration level by the DMFC itself, which is of mayor interest for the portable application as an external sensor for the system can be omitted.

Impact of concentration and rate of intraluminal drug delivery on absorption and gut wall metabolism of verapamil in humans.

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Glaeser, Hartmut; Drescher, Siegfried; Hofmann, Ute; Heinkele, Georg; Somogyi, Andrew A; Eichelbaum, Michel; Fromm, Martin F

2004-09-01

In humans gut wall metabolism can be quantitatively as important as hepatic drug metabolism in limiting the systemic exposure to drugs after oral administration. However, it has been proposed that the role of gut wall metabolism might be overemphasized, because high luminal drug concentrations would lead to a saturation of gut wall metabolism. Therefore we investigated the impact of concentration and rate of intraluminal drug delivery on absorption (F(abs)) and gastrointestinal extraction (E(GI)) of a luminally administered cytochrome P450 (CYP) 3A4 substrate (verapamil) using a multilumen perfusion catheter in combination with a stable isotope technique. Two 20-cm-long, adjacent jejunal segments were isolated with the multilumen perfusion catheter in 7 subjects. In this study 80 mg of unlabeled verapamil (d0-verapamil 15 min) was infused into one segment over a 15-minute period, 80 mg of 3-fold deuterated verapamil (d3-verapamil 240 min) was administered over a 240-minute period into the other segment, and simultaneously, 5 mg of 7-fold deuterated verapamil (d7-verapamil) was injected intravenously over a 15-minute period. The rate of intraluminal drug delivery had only a modest effect on bioavailability of the verapamil isotopes (after correction for F abs ) (F/F abs d3-verapamil 240 min versus d0-verapamil 15 min, 0.24 +/- 0.10 versus 0.20 +/- 0.09; P d3-verapamil 240 min was 0.50 +/- 0.18 compared with 0.59 +/- 0.14 for d0 -verapamil 15 min ( P d0-verapamil 15 min ) correlated strongly with E GI (d3-verapamil 240 min ) (r = 0.94, P d0-verapamil 15 min /d3-verapamil 240 min (r = 0.62, P =.03). Substantial gut wall metabolism of verapamil occurs in humans and can be predicted from ex vivo data by use of shed enterocytes. The different intraluminal concentrations and rates of intraluminal drug delivery did not lead to a pronounced saturation of intestinal drug metabolism.

Determination of the concentration of total suspends solids (TSS) and heavy metals in basin rio Morote, Nicoya, Guanacaste

International Nuclear Information System (INIS)

Sanchez Murillo, Ricardo; Leon, Sandra; Saravia, Ana Yuri; Mena Sanchez, Carlos de

2009-01-01

The total concentration of suspends solids and heavy metals were determined of the Basin of rio Morote. The study spanned six sampling campaigns between April 2003 and May 2005. Sampling points were selected to correspond to places from the high basin to the mouth of the rio Morote in the Golfo de Nicoya. Suspends total solids concentration (TSS) on average exceeds 200 mg/L during the rainy season at the mouth. Enrichment of metals as: Cu, Ni, Cd and Fe was found in riverbed sediments; but not in Pb. The concentration of Zn has been near the limit value (200 mg/kg) in the dry season, value which has been established for the Environmental Protection Agency of United States (EPA). (author) [es

Konsentrasi Protein Total, Albumin, dan Globulin Anak Kambing Peranakan Etawah Setelah Pemberian Berbagai Sediaan Kolostrum* (TOTAL PROTEIN, ALBUMIN, AND GLOBULIN CONCENTRATIONS ON ETTAWAH CROSSBREED NEONATES FOLLOWING THE ADMINISTRATION OF VARIOUS FORM O

Directory of Open Access Journals (Sweden)

Anita Esfandiari

2014-10-01

Full Text Available This experiment was conducted to study the profile of total protein, albumin, and globulin concentrationson Ettawah crossbreed neonates after consuming various colostrums. Twenty four healthy neonatal kidswere used in this study. The neonates were divided into four groups. Each group received fresh maternal(goat colostrum, frozen-thawed bovine colostrum, bovine spray dried colostrum, and bovine powdercommercial colostrum, respectively. Colostrums were given at 10% of body weight directly after birth andfollowed by the same amount every 12 hours, for three days. The blood was taken from jugular vein at 0, 12,24, 48, 72, and 168 hours after birth to determine total protein, albumin, and globulin concentrations.Results of this study indicated that the serum total protein and globulin concentration increased andreached the peak at 24 hours after birth. Compared to the concentration at birth, the increase of totalprotein concentration were 62.77%, 59.26%, 48.05%, and 66.67% in fresh maternal (goat, frozen-thawedbovine, bovine spray dried, and commercial bovine colostrum, respectively. Serum globulin concentrationincreased 4.9, 4.4, 4.8, and 14.6 times in fresh matermnal goat, frozen-thawed bovine, spray dried, andcommercial bovine colostrums respectively, compared to the concentration at birth. In conclusion, theconsumption of various colostrums i.e. fresh maternal goat colostrums, bovine colostrums (frozen-thawed,spray dried and commercial colostrums would increase the concentration of blood total protein and globulin,which both reached the highest concentration at 24 h after birth.

Total protein concentration and diagnostic test results for gray wolf (Canis lupus) serum using Nobuto filter paper strips

Science.gov (United States)

Jara, Rocio F.; Sepúlveda, Carolina; Ip, Hon S.; Samuel, Michael D.

2015-01-01

Nobuto filter paper strips are widely used for storing blood-serum samples, but the recovery of proteins from these strips following rehydration is unknown. Poor recovery of proteins could reduce the concentration of antibodies and antigens and reduce the sensitivity of diagnostic assays. We compared the protein concentration, and its association with test sensitivity, of eluted Nobuto strip samples with paired sera. We collected and froze serum from five gray wolves (Canis lupus) for 8 mo. When thawed, we used a spectrophotometer (absorbance 280 nm) to determine the serum protein concentration for paired sera and Nobuto eluates for each animal in 2-fold serial dilutions. Total protein concentration was similar for both sample storage methods (Nobuto eluates and control sera), except for the undiluted samples in which Nobuto eluates had higher total protein concentrations. Both sample storage methods appear to produce similar results using the SNAP® 4Dx® Test to detect antibodies against pathogens causing Lyme disease, anaplasmosis, and ehrlichiosis as well as antigen for canine heartworm disease.

Concentration, flux, and the analysis of trends of total and dissolved phosphorus, total nitrogen, and chloride in 18 tributaries to Lake Champlain, Vermont and New York, 1990–2011

Science.gov (United States)

Medalie, Laura

2013-01-01

Annual concentration, flux, and yield for total phosphorus, dissolved phosphorus, total nitrogen, and chloride for 18 tributaries to Lake Champlain were estimated for 1990 through 2011 using a weighted regression method based on time, tributary streamflows (discharges), and seasonal factors. The weighted regression method generated two series of daily estimates of flux and concentration during the period of record: one based on observed discharges and a second based on a flow-normalization procedure that removes random variation due to year-to-year climate-driven effects. The flownormalized estimate for a given date is similar to an average estimate of concentration or flux that would be made if all of the observed discharges for that date were equally likely to have occurred. The flux bias statistic showed that 68 of the 72 flux regression models were minimally biased. Temporal trends in the concentrations and fluxes were determined by calculating percent changes in flow-normalized annual fluxes for the full period of analysis (1990 through 2010) and for the decades 1990–2000 and 2000–2010. Basinwide, flow-normalized total phosphorus flux decreased by 42 metric tons per year (t/yr) between 1990 and 2010. This net result reflects a basinwide decrease in flux of 21 metric tons (t) between 1990 and 2000, followed by a decrease of 20 t between 2000 and 2010; both results were largely influenced by flux patterns in the large tributaries on the eastern side of the basin. A comparison of results for total phosphorus for the two separate decades of analysis found that more tributaries had decreasing concentrations and flux rates in the second decade than the first. An overall reduction in dissolved phosphorus flux of 0.7 t/yr was seen in the Lake Champlain Basin during the full period of analysis. That very small net change in flux reflects substantial reductions between 1990 and 2000 from eastern tributaries, especially in Otter Creek and the LaPlatte and Winooski

Accuracy of different sensors for the estimation of pollutant concentrations (total suspended solids, total and dissolved chemical oxygen demand) in wastewater and stormwater.

Science.gov (United States)

Lepot, Mathieu; Aubin, Jean-Baptiste; Bertrand-Krajewski, Jean-Luc

2013-01-01

Many field investigations have used continuous sensors (turbidimeters and/or ultraviolet (UV)-visible spectrophotometers) to estimate with a short time step pollutant concentrations in sewer systems. Few, if any, publications compare the performance of various sensors for the same set of samples. Different surrogate sensors (turbidity sensors, UV-visible spectrophotometer, pH meter, conductivity meter and microwave sensor) were tested to link concentrations of total suspended solids (TSS), total and dissolved chemical oxygen demand (COD), and sensors' outputs. In the combined sewer at the inlet of a wastewater treatment plant, 94 samples were collected during dry weather, 44 samples were collected during wet weather, and 165 samples were collected under both dry and wet weather conditions. From these samples, triplicate standard laboratory analyses were performed and corresponding sensors outputs were recorded. Two outlier detection methods were developed, based, respectively, on the Mahalanobis and Euclidean distances. Several hundred regression models were tested, and the best ones (according to the root mean square error criterion) are presented in order of decreasing performance. No sensor appears as the best one for all three investigated pollutants.

Usefulness of saliva for measurement of 3,4-methylenedioxymethamphetamine and its metabolites: correlation with plasma drug concentrations and effect of salivary pH.

Science.gov (United States)

Navarro, M; Pichini, S; Farré, M; Ortuño, J; Roset, P N; Segura, J; de la Torre, R

2001-10-01

Saliva is an alternative biologic matrix for drugs-of-abuse testing that offers the advantages of noninvasive, rapid, and easy sampling. We studied the excretion profile of 3,4-methylenedioxymethamphetamine (MDMA) and its metabolites in both saliva and plasma, as well the effect of the drug on salivary pH. Saliva and plasma samples were obtained from eight healthy MDMA consumers after ingestion of a single 100-mg dose of the drug. Concentrations of MDMA and its main metabolites, 3,4-methylenedioxyamphetamine (MDA) and 4-hydroxy-3-methoxymethamphetamine (HMMA), in saliva and plasma were measured by gas chromatography-mass spectrometry. Apparent pharmacokinetic parameters for MDMA in saliva were estimated, and the saliva-to-plasma ratio at each time interval was calculated and correlated with salivary pH. MDMA, MDA, and HMMA were detected in saliva. Salivary concentrations of MDMA were 1728.9-6510.6 microg/L and peaked at 1.5 h after drug intake. This was followed by a progressive decrease, with a mean concentration of 126.2 microg/L at 24 h. The saliva-to-plasma ratio was 32.3-1.2, with a peak of 18.1 at 1.5 h after drug administration. Salivary pH seemed to be affected by MDMA administration; pH values decreased by 0.6 units (mean pH values of 6.9 and 6.8 at 1.5 and 4 h after drug administration vs predose pH of 7.4). Measurement of MDMA in saliva is a valuable alternative to determination of plasma drug concentrations in both clinical and toxicologic studies. On-site testing is also facilitated by noninvasive and rapid collection of salivary specimens.

Determination of the total concentration of highly protein-bound drugs in plasma by on-line dialysis and column liquid chromatography: application to non-steroidal anti-inflammatory drugs.

NARCIS (Netherlands)

Herraez-Hernandez, R.; van de Merbel, N.C.; Brinkman, U.A.T.

1995-01-01

The potential of on-line dialysis as a sample preparation procedure for compounds highly bound to plasma proteins is evaluated, using non-steroidal anti-inflammatory drugs as model compounds and column liquid chromatography as the separation technique. Different strategies to reduce the degree of

Determination of the total concentration of highly protein-bound drugs in plasma by on-line dialysis and column liquid chromatography : application to non-steroidal anti-inflammatory drugs

NARCIS (Netherlands)

Herráez-Hernández, R; van de Merbel, N C; Brinkman, U A

1995-01-01

The potential of on-line dialysis as a sample preparation procedure for compounds highly bound to plasma proteins is evaluated, using non-steroidal anti-inflammatory drugs as model compounds and column liquid chromatography as the separation technique. Different strategies to reduce the degree of

Fasting plasma total ghrelin concentrations in monozygotic twins discordant for obesity.

Science.gov (United States)

Leskelä, Piia; Ukkola, Olavi; Vartiainen, Johanna; Rönnemaa, Tapani; Kaprio, Jaakko; Bouchard, Claude; Kesäniemi, Y Antero

2009-02-01

Ghrelin is a hormone that is involved in the regulation of food intake. Neuronal, endocrine, and genetic factors have been shown to regulate plasma ghrelin levels; but the determinants of fasting ghrelin concentrations are not yet fully understood. The main aim was to explore the roles of adiposity and genetic differences in determining fasting plasma total ghrelin levels. We measured total ghrelin levels in a population of 23 monozygotic twin pairs discordant for obesity. In addition, 2 variants of ghrelin gene, namely, Arg51Gln and Leu72Met, were genotyped in 3 populations of monozygotic twin pairs: 23 obesity-discordant, 43 lean-concordant, and 46 obesity-concordant twin pairs. In discordant twins, lean co-twins had higher fasting plasma total ghrelin levels (950 pg/mL, SD = 328 pg/mL) than obese twins (720 pg/mL, SD = 143 pg/mL; P = .003). Arg51Gln-polymorphism of the ghrelin gene was equally distributed between the twin groups. However, there were significant differences in genotype frequencies at the Leu72Met polymorphism between the discordant and obese-concordant groups (P = .003) and between the discordant and lean-concordant groups (P = .011), but not between the 2 concordant groups. In the discordant group, there were fewer Met carriers (4%) than among the obese (17%) or the lean-concordant groups (15%). Plasma total ghrelin levels are affected by acquired obesity independent of genetic background. The Leu72 allele is particularly common among monozygotic twins discordant for obesity, suggesting that this ghrelin allele is more permissive in the regulation of energy balance. The ghrelin gene may thus play a role in the regulation of variability of body weight, such that Leu72 allele carriers are more prone to weight variability in response to environmental factors.

Concentration, flux, and trend estimates with uncertainty for nutrients, chloride, and total suspended solids in tributaries of Lake Champlain, 1990–2014

Science.gov (United States)

Medalie, Laura

2016-12-20

The U.S. Geological Survey, in cooperation with the New England Interstate Water Pollution Control Commission and the Vermont Department of Environmental Conservation, estimated daily and 9-month concentrations and fluxes of total and dissolved phosphorus, total nitrogen, chloride, and total suspended solids from 1990 (or first available date) through 2014 for 18 tributaries of Lake Champlain. Estimates of concentration and flux, provided separately in Medalie (2016), were made by using the Weighted Regressions on Time, Discharge, and Season (WRTDS) regression model and update previously published WRTDS model results with recent data. Assessment of progress towards meeting phosphorus-reduction goals outlined in the Lake Champlain management plan relies on annual estimates of phosphorus flux. The percent change in annual concentration and flux is provided for two time periods. The R package EGRETci was used to estimate the uncertainty of the trend estimate. Differences in model specification and function between this study and previous studies that used WRTDS to estimate concentration and flux using data from Lake Champlain tributaries are described. Winter data were too sparse and nonrepresentative to use for estimates of concentration and flux but were sufficient for estimating the percentage of total annual flux over the period of record. Median winter-to-annual fractions ranged between 21 percent for total suspended solids and 27 percent for dissolved phosphorus. The winter contribution was largest for all constituents from the Mettawee River and smallest from the Ausable River. For the full record (1991 through 2014 for total and dissolved phosphorus and chloride and 1993 through 2014 for nitrogen and total suspended solids), 6 tributaries had decreasing trends in concentrations of total phosphorus, and 12 had increasing trends; concentrations of dissolved phosphorus decreased in 6 and increased in 8 tributaries; fluxes of total phosphorus decreased in 5 and

Calibration of a turbidity meter for making estimates of total suspended solids concentrations and beam attenuation coefficients in field experiments

Science.gov (United States)

Usry, J. W.; Whitlock, C. H.

1981-01-01

Management of water resources such as a reservoir requires using analytical models which describe such parameters as the suspended sediment field. To select or develop an appropriate model requires making many measurements to describe the distribution of this parameter in the water column. One potential method for making those measurements expeditiously is to measure light transmission or turbidity and relate that parameter to total suspended solids concentrations. An instrument which may be used for this purpose was calibrated by generating curves of transmission measurements plotted against measured values of total suspended solids concentrations and beam attenuation coefficients. Results of these experiments indicate that field measurements made with this instrument using curves generated in this study should correlate with total suspended solids concentrations and beam attenuation coefficients in the water column within 20 percent.

Drivers under the influence of drugs of abuse: quantification of cocaine and impaired driving.

Science.gov (United States)

Arroyo, Amparo; Sánchez, Marta; Barberia, Eneko; Barbal, Maria; Marrón, M Teresa; Mora, Agustí

2013-01-01

In recent years, the interest in oral fluid as a biological matrix has significantly increased, particularly for detecting driving under the influence of drugs. In this study, the concentration of cocaine and its relationship with clinical symptoms in drivers suspected of driving under the influence of drugs was evaluated. A total of 154 samples of oral fluid, which tested positive for cocaine in previous immunoassay screening, Cozart Drug Detector System, were confirmed using gas chromatography/mass spectrometry method. In Catalonia, during 2007-2010, there were 1791 samples positive for cocaine among a total of 3468 samples taken from drivers who tested positive for any drug of abuse. The evaluation of clinical symptoms was through a questionnaire that was filled in by the police officers who collected the samples. The mean concentration of cocaine was 4.11 mg/l and median concentration was 0.38 mg/l (range 0.01-345.64 mg/l). Clinical impairment symptoms such as motor coordination, walking, speech, mood and state of pupils were not significant. The testing of oral fluids presents fewer ethical problems than blood or urine.

A meta-analysis of feed digestion in dairy cows. 1. The effects of forage and concentrate factors on total diet digestibility.

Science.gov (United States)

Nousiainen, J; Rinne, M; Huhtanen, P

2009-10-01

A meta-analysis based on published experiments with lactating dairy cows was conducted to study the effects of dietary forage and concentrate factors on apparent total diet digestibility. A data set was collected that included a total of 497 dietary treatment means from 92 studies. The diets were based on grass silage or on legume or whole-crop cereal silages partly or completely substituted for grass silage. The silages were supplemented with concentrates given at a flat rate within a dietary comparison. For the statistical evaluation, the data were divided into 5 subsets to quantify silage (digestibility, 42 diets in 17 studies; fermentation characteristics, 108 diets in 39 studies) and concentrate (amount of supplementation, 142 diets in 59 studies; concentration of crude protein, 215 diets in 82 studies; carbohydrate composition, 66 diets in 23 studies) factors on total diet digestibility. The diet digestibility of dairy cows was determined by total fecal collection or by using acid-insoluble ash as an internal marker. Diet organic matter digestibility (OMD) at a maintenance level of feeding (OMD(m)) was estimated using sheep in vivo or corresponding in vitro digestibility values for the forage and reported ingredient and chemical composition values, with tabulated digestibility coefficients for the concentrate components of the diet. A mixed model regression analysis was used to detect the responses of different dietary factors on apparent total diet digestibility. Improved silage OMD(m) resulting from earlier harvest was translated into improved production-level OMD in cows (OMD(p)). The effects of silage fermentation characteristics on OMD(p) were quantitatively small, although sometimes significant. Concentrate supplementation improved total diet OMD(m), but this was not realized in lactating dairy cows because of linearly decreased neutral detergent fiber (NDF) digestibility as concentrate intake increased. Increasing the concentrate crude protein amount

Prevalence of alcohol and other drugs and the concentrations in blood of drivers killed in road traffic crashes in Sweden.

Science.gov (United States)

Ahlner, Johan; Holmgren, Anita; Jones, Alan Wayne

2014-03-01

Drunk or drug-impaired drivers represent a major public health and societal problem worldwide. Because over 95% of drivers killed on the roads in Sweden are autopsied, reliable information is available about the use of alcohol and/or other drug before the crash. This retrospective 4-year study (2008-2011) used a forensic toxicology database (TOXBASE) to evaluate the concentrations of alcohol and other drugs in blood samples from drivers killed in road-traffic crashes. The mean age of all victims (N = 895) was 48 ± 20 years, and the majority were male (86%). In 504 drivers (56%), the results of toxicological analysis were negative and these victims were older; mean age (± SD) 47 ± 20 years, than alcohol positive cases (35 ± 14 years) and illicit drug users (34 ± 15 years). In 21% of fatalities, blood-alcohol concentration (BAC) was above the statutory limit for driving (0.2 g/L), although the median BAC was appreciably higher (1.72 g/L). Illicit drugs (mainly amphetamine and cannabis) were identified in ~7% of victims, either alone (2.5%), together with alcohol (1.8%) or a prescription drug (2%). The psychoactive prescription drugs identified were mainly benzodiazepines, z-hypnotics and tramadol, which were found in the blood of 7.6% of crash victims. The high median BAC in fatally-injured drivers speaks strongly towards alcohol-induced impairment as being responsible for the crash. Compared with alcohol, the prevalence of illicit and psychoactive prescription drugs was fairly low despite a dramatic increase in the number of drug-impaired drivers arrested by the police after a zero-tolerance law was introduced in 1999.

Total and methyl mercury concentrations and fluxes from small boreal forest catchments in Finland

International Nuclear Information System (INIS)

Porvari, Petri; Verta, Matti

2003-01-01

Peatlands have higher methyl mercury output than uplands. - Total mercury (TotHg) and methyl mercury (MeHg) concentrations were studied in runoff from eight small (0.02-1.3 km 2 ) boreal forest catchments (mineral soil and peatland) during 1990-1995. Runoff waters were extremely humic (TOC 7-70 mg l -1 ). TotHg concentrations varied between 0.84 and 24 ng l -1 and MeHg between 0.03 and 3.8 ng l -1 . TotHg fluxes from catchments ranged from 0.92 to 1.8 g km -2 a -1 , and MeHg fluxes from 0.03 to 0.33 g km -2 a -1 . TotHg concentrations and output fluxes measured in runoff water from small forest catchments in Finland were comparable with those measured in other boreal regions. By contrast, MeHg concentrations were generally higher. Estimates for MeHg output fluxes in this study were comparable at sites with forests and wetlands in Sweden and North America, but clearly higher than those measured at upland or agricultural sites in other studies. Peatland catchments released more MeHg than pure mineral soil or mineral soil catchments with minor area of peatland

Airborne concentrations of metals and total dust during solid catalyst loading and unloading operations at a petroleum refinery.

Science.gov (United States)

Lewis, Ryan C; Gaffney, Shannon H; Le, Matthew H; Unice, Ken M; Paustenbach, Dennis J

2012-09-01

Workers handle catalysts extensively at petroleum refineries throughout the world each year; however, little information is available regarding the airborne concentrations and plausible exposures during this type of work. In this paper, we evaluated the airborne concentrations of 15 metals and total dust generated during solid catalyst loading and unloading operations at one of the largest petroleum refineries in the world using historical industrial hygiene samples collected between 1989 and 2006. The total dust and metals, which included aluminum, cadmium, chromium, cobalt, copper, iron, lead, manganese, molybdenum, nickel, platinum, silicon, silver, vanadium, and zinc, were evaluated in relation to the handling of four different types of solid catalysts associated with three major types of catalytic processes. Consideration was given to the known components of the solid catalysts and any metals that were likely deposited onto them during use. A total of 180 analytical results were included in this analysis, representing 13 personal and 54 area samples. Of the long-term personal samples, airborne concentrations of metals ranged from refinery and perhaps other modern refineries during the timeframe examined. Copyright © 2011 Elsevier GmbH. All rights reserved.

Quantification of total aluminium concentrations in food samples at trace levels by INAA and PIGE methods

International Nuclear Information System (INIS)

Nanda, Braja B.; Acharya, R.

2017-01-01

Total aluminium contents in various food samples were determined by Instrumental Neutron Activation Analysis (INAA) and Particle Induced Gamma-ray Emission (PIGE) methods. A total of 16 rice samples, collected from the field, were analyzed by INAA using reactor neutrons from Dhruva reactor. Whereas a total 17 spices collected from market, were analyzed by both INAA and PIGE methods in conjunction with high resolution gamma-ray spectrometry. Aluminium concentration values were found to be in the range of 19-845 mg kg -1 for spices and 15-104 mg kg -1 for rice samples. The methods were validated by analyzing standard reference materials (SRMs) form NIST. (author)

The current status of community drug testing via the analysis of drugs and drug metabolites in sewage

Directory of Open Access Journals (Sweden)

Malcolm J. Reid

2011-12-01

Full Text Available Over the past few years the analysis of drug residues in sewage has been promoted as a means of estimating the level of drug use in communities. Measured drug residue concentrations in the sewage are used to determine the load (total mass of the drug being used by the entire community. Knowledge of the size or population of the community then allows for the calculation of drug-use relative to population (typically drug-mass/day/1000 inhabitants which facilitates comparisons between differing communities or populations. Studies have been performed in many European countries, including Norway, as well as in the US and Australia. The approach has successfully estimated the use of cocaine, amphetamine, methamphetamine, MDMA, cannabis, nicotine and alcohol. The analysis of biomarkers of drug use in sewage has great potential to support and complement existing techniques for estimating levels of drug use, and as such has been identified as a promising development by the European Monitoring Centre for Drugs and Drug Addiction (EMCDDA; www.emcdda.europa.eu/wastewater-analysis. The approach is not without its challenges, and ongoing collaboration across Europe aims at agreeing upon best-practice and harmonising the methods being used. In Norway development is being performed through the NFR RUSMIDDEL funded DrugMon (www.niva.no/drugmon project that has led to the development of many new techniques, significantly improved our understanding of the uncertainties associated with the approach and allowed the coordination of Europe wide collaboration which has included all important intercalibration exercises. Application of the technique can provide evidence-based and real-time estimates of collective drug use with the resulting data used to improve the much needed estimates of drug use and dependency.

Adequate plasma drug concentrations suggest that amoxicillin can be administered by continuous infusion using elastomeric pumps.

Science.gov (United States)

Arensdorff, Lyne; Boillat-Blanco, Noémie; Decosterd, Laurent; Buclin, Thierry; de Vallière, Serge

2017-09-01

Elastomeric pumps can be useful for the administration of antibiotics in the outpatient setting. To determine amoxicillin degradation in elastomeric pumps, as well as the effectiveness of amoxicillin treatment administered by elastomeric pumps. Antibiotic degradation was measured in elastomeric pumps filled with 6 g of amoxicillin in 240 mL of NaCl 0.9% by drawing samples at 12 h intervals when stored in the fridge for 48 h and when worn around the waist for 24 h. Subsequently nine patients were treated with continuous infusions of 8 or 12 g of amoxicillin per day. Plasma amoxicillin concentrations were measured on each visit to the outpatient parenteral antibiotic therapy unit. Clinical outcome was verified 3 months after the end of treatment. Amoxicillin degradation in elastomeric pumps reached 10% after 48 h in the fridge and an additional 30% when worn around the waist for 24 h. Mean plasma drug concentrations achieved with 12 g of amoxicillin per day were 18.5 mg/L (95% CI 13.5-23.5), which is largely above the MIC of amoxicillin-susceptible bacteria. Nine patients treated for various complicated infections were cured and had no unexpected adverse effects. Adequate plasma drug concentrations and favourable clinical outcomes suggest that amoxicillin can be administered by continuous infusion using elastomeric pumps. This treatment modality does not fulfil formal requirements regarding pharmaceutical stability, but the resulting safety impact in patients is probably limited. Therapeutic drug monitoring and a close clinical follow-up are recommended if this route of administration is chosen. © The Author 2017. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Reduced antituberculosis drug concentrations in HIV-infected patients who are men or have low weight: implications for international dosing guidelines.

Science.gov (United States)

McIlleron, Helen; Rustomjee, Roxana; Vahedi, Mahnaz; Mthiyane, Thuli; Denti, Paolo; Connolly, Catherine; Rida, Wasima; Pym, Alexander; Smith, Peter J; Onyebujoh, Philip C

2012-06-01

Reduced antituberculosis drug concentrations may contribute to unfavorable treatment outcomes among HIV-infected patients with more advanced immune suppression, and few studies have evaluated pharmacokinetics of the first-line antituberculosis drugs in such patients given fixed-dose combination tablets according to international guidelines using weight bands. In this study, pharmacokinetics were evaluated in 60 patients on 4 occasions during the first month of antituberculosis therapy. Multilevel linear mixed-effects regression analysis was used to examine the effects of age, sex, weight, drug dose/kilogram, CD4(+) lymphocyte count, treatment schedule (5 versus 7 days/week), and concurrent antiretrovirals (efavirenz plus lamivudine plus zidovudine) on the area under the concentration-time curve from 0 to 12 h (AUC(0-12)) of the respective antituberculosis drugs and to compare AUC(0-12)s at day 8, day 15, and day 29 with the day 1 AUC(0-12). Median (range) age, weight, and CD4(+) lymphocyte count were 32 (18 to 47) years, 55.2 (34.4 to 98.7) kg, and 252 (12 to 500)/μl. For every 10-kg increase in body weight, the predicted day 29 AUC(0-12) increased by 14.1% (95% confidence interval [CI], 7.5, 20.8), 14.1% (95% CI, -0.7, 31.1), 6.1% (95% CI, 2.7, 9.6) and 6.0% (95% CI, 0.8, 11.3) for rifampin, isoniazid, pyrazinamide, and ethambutol, respectively. Males had day 29 AUC(0-12)s 19.3% (95% CI, 3.6, 35.1) and 14.0% (95% CI, 5.6, 22.4) lower than females for rifampin and pyrazinamide, respectively. Level of immune suppression and concomitant antiretrovirals had little effect on the concentrations of the antituberculosis agents. As they had reduced drug concentrations, it is important to review treatment responses in patients in the lower weight bands and males to inform future treatment guidelines, and revision of doses in these patients should be considered.

Cost-effectiveness of routine measuring of serum drug concentrations and anti-drug antibodies in treatment of rheumatoid arthritis patients with TNF-α blockers

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Laine J

2016-04-01

Full Text Available Juha Laine,1 T Sakari Jokiranta,2,3 Kari K Eklund,4,5 Merja Väkeväinen,1 Kari Puolakka6 1Pfizer Oy, Helsinki, 2United Medix Laboratories Ltd, Espoo, 3Research Programs Unit, Immunobiology, 4Department of Rheumatology, University of Helsinki, 5Helsinki University Central Hospital, Helsinki, 6Department of Medicine, South Karelia, Finland Abstract: Monitoring of anti-drug antibodies (ADAbs or serum concentrations of biologicals in treatment of rheumatoid arthritis could provide an explanation for a loss of efficacy and help in the choice of subsequent medication. Current clinical practices do not generally include such monitoring of tumor necrosis factor (TNF-α blockers on a routine basis. The main aims of this study were to estimate the probabilities of optimal and nonoptimal treatment decisions if infliximab or adalimumab drug trough level (DL and ADAbs are tested or not in rheumatoid arthritis, and to model cost-effectiveness of performing such monitoring on a routine basis. Data on DLs and ADAbs concentrations were obtained in Finland from clinically requested monitoring analyses of 486 and 1,137 samples from patients on adalimumab and infliximab, respectively. DL was within the target range in 42% of samples from adalimumab- and 50.4% of infliximab-treated patients. ADAbs were detected in approximately 20% and 13.5% of samples from adalimumab- and infliximab-treated patients, respectively. ADAbs were found in 52.3% and 41.3% of those with low adalimumab or infliximab DLs, respectively. The monitoring data were incorporated into probabilities for making the optimal treatment decision. Economic impact of clinical decision-making was modeled in a short-term (3–6 months scenario with 100 hypothetical patients. In the model, the combined measurement of DLs and ADAbs was cost-saving compared to the nontesting scenario when the monitoring results affected the treatment decision in at least 2–5 of 100 patients, a proportion which is easily

Doxorubicin-loaded QuadraSphere microspheres: plasma pharmacokinetics and intratumoral drug concentration in an animal model of liver cancer.

Science.gov (United States)

Lee, Kwang-Hun; Liapi, Eleni A; Cornell, Curt; Reb, Philippe; Buijs, Manon; Vossen, Josephina A; Ventura, Veronica Prieto; Geschwind, Jean-Francois H

2010-06-01

The purpose of this study was to evaluate, in vitro and in vivo, doxorubicin-loaded poly (vinyl alcohol-sodium acrylate) copolymer microspheres [QuadraSphere microspheres (QSMs)] for transcatheter arterial delivery in an animal model of liver cancer. Doxorubicin loading efficiency and release profile were first tested in vitro. In vivo, 15 rabbits, implanted with a Vx-2 tumor in the liver, were divided into three groups of five rabbits each, based on the time of euthanasia. Twenty-five milligrams of QSMs was diluted in 10 ml of a 10 mg/ml doxorubicin solution and 10 ml of nonionic contrast medium for a total volume of 20 ml. One milliliter of a drug-loaded QSM solution containing 5 mg of doxorubicin was injected into the tumor feeding artery. Plasma doxorubicin and doxorubicinol concentrations, and intratumoral and peritumoral doxorubicin tissue concentrations, were measured. Tumor specimens were pathologically evaluated to record tumor necrosis. As a control, one animal was blandly embolized with plain QSMs in each group. In vitro testing of QSM doxorubicin loadability and release over time showed 82-94% doxorubicin loadability within 2 h and 6% release within the first 6 h after loading, followed by a slow release pattern. In vivo, the doxorubicin plasma concentration declined at 40 min. The peak doxorubicin intratumoral concentration was observed at 3 days and remained detectable till the study's end point (7 days). Mean percentage tumor cell death in the doxorubicin QSM group was 90% at 7 days and 60% in the bland QSM embolization group. In conclusion, QSMs can be efficiently loaded with doxorubicin. Initial experiments with doxorubicin-loaded QSMs show a safe pharmacokinetic profile and effective tumor killing in an animal model of liver cancer.

Doxorubicin-Loaded QuadraSphere Microspheres: Plasma Pharmacokinetics and Intratumoral Drug Concentration in an Animal Model of Liver Cancer

International Nuclear Information System (INIS)

Lee, Kwang-Hun; Liapi, Eleni A.; Cornell, Curt; Reb, Philippe; Buijs, Manon; Vossen, Josephina A.; Ventura, Veronica Prieto; Geschwind, Jean-Francois H.

2010-01-01

The purpose of this study was to evaluate, in vitro and in vivo, doxorubicin-loaded poly (vinyl alcohol-sodium acrylate) copolymer microspheres [QuadraSphere microspheres (QSMs)] for transcatheter arterial delivery in an animal model of liver cancer. Doxorubicin loading efficiency and release profile were first tested in vitro. In vivo, 15 rabbits, implanted with a Vx-2 tumor in the liver, were divided into three groups of five rabbits each, based on the time of euthanasia. Twenty-five milligrams of QSMs was diluted in 10 ml of a 10 mg/ml doxorubicin solution and 10 ml of nonionic contrast medium for a total volume of 20 ml. One milliliter of a drug-loaded QSM solution containing 5 mg of doxorubicin was injected into the tumor feeding artery. Plasma doxorubicin and doxorubicinol concentrations, and intratumoral and peritumoral doxorubicin tissue concentrations, were measured. Tumor specimens were pathologically evaluated to record tumor necrosis. As a control, one animal was blandly embolized with plain QSMs in each group. In vitro testing of QSM doxorubicin loadability and release over time showed 82-94% doxorubicin loadability within 2 h and 6% release within the first 6 h after loading, followed by a slow release pattern. In vivo, the doxorubicin plasma concentration declined at 40 min. The peak doxorubicin intratumoral concentration was observed at 3 days and remained detectable till the study's end point (7 days). Mean percentage tumor cell death in the doxorubicin QSM group was 90% at 7 days and 60% in the bland QSM embolization group. In conclusion, QSMs can be efficiently loaded with doxorubicin. Initial experiments with doxorubicin-loaded QSMs show a safe pharmacokinetic profile and effective tumor killing in an animal model of liver cancer.

Serum concentrations of cholesterol, apolipoprotein A-I and apolipoprotein B in a total of 1694 meat-eaters, fish-eaters, vegetarians and vegans.

Science.gov (United States)

Bradbury, K E; Crowe, F L; Appleby, P N; Schmidt, J A; Travis, R C; Key, T J

2014-02-01

The objective of this study was to describe serum lipid concentrations, including apolipoproteins A-I and B, in different diet groups. A cross-sectional analysis of a sample of 424 meat-eaters, 425 fish-eaters, 423 vegetarians and 422 vegans, matched on sex and age, from the European Prospective Investigation into Cancer and Nutrition-Oxford cohort. Serum concentrations of total, and high-density lipoprotein (HDL) cholesterol, as well as apolipoproteins A-I and B were measured, and serum non-HDL cholesterol was calculated. Vegans had the lowest body mass index (BMI) and the highest and lowest intakes of polyunsaturated and saturated fat, respectively. After adjustment for age, alcohol and physical activity, compared with meat-eaters, fish-eaters and vegetarians, serum concentrations of total and non-HDL cholesterol and apolipoprotein B were significantly lower in vegans. Serum apolipoprotein A-I concentrations did not differ between the diet groups. In males, the mean serum total cholesterol concentration was 0.87 mmol/l lower in vegans than in meat-eaters; after further adjustment for BMI this difference was 0.76 mmol/l. In females, the difference in total cholesterol between these two groups was 0.6 mmol/l, and after further adjustment for BMI was 0.55 mmol/l. [corrected]. In this study, which included a large number of vegans, serum total cholesterol and apolipoprotein B concentrations were lower in vegans compared with meat-eaters, fish-eaters and vegetarians. A small proportion of the observed differences in serum lipid concentrations was explained by differences in BMI, but a large proportion is most likely due to diet.

Empirical Estimation of Total Nitrogen and Total Phosphorus Concentration of Urban Water Bodies in China Using High Resolution IKONOS Multispectral Imagery

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Jiaming Liu

2015-11-01

Full Text Available Measuring total nitrogen (TN and total phosphorus (TP is important in managing heavy polluted urban waters in China. This study uses high spatial resolution IKONOS imagery with four multispectral bands, which roughly correspond to Landsat/TM bands 1–4, to determine TN and TP in small urban rivers and lakes in China. By using Lake Cihu and the lower reaches of Wen-Rui Tang (WRT River as examples, this paper develops both multiple linear regressions (MLR and artificial neural network (ANN models to estimate TN and TP concentrations from high spatial resolution remote sensing imagery and in situ water samples collected concurrently with overpassing satellite. The measured and estimated values of both MLR and ANN models are in good agreement (R2 > 0.85 and RMSE < 2.50. The empirical equations selected by MLR are more straightforward, whereas the estimated accuracy using ANN model is better (R2 > 0.86 and RMSE < 0.89. Results validate the potential of using high resolution IKONOS multispectral imagery to study the chemical states of small-sized urban water bodies. The spatial distribution maps of TN and TP concentrations generated by the ANN model can inform the decision makers of variations in water quality in Lake Cihu and lower reaches of WRT River. The approaches and equations developed in this study could be applied to other urban water bodies for water quality monitoring.

Factors Effecting the Total Volatile Organic Compound (TVOC Concentrations in Slovak Households

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Ľudmila Mečiarová

2017-11-01

Full Text Available Thirty five Slovak households were selected for an investigation of indoor environmental quality. Measuring of indoor air physical and chemical factors and a questionnaire survey was performed during May 2017. The range of permissible operative temperature was not met in 11% of objects. Relative humidity met the legislative requirements in all monitored homes. Concentrations of total volatile organic compounds (TVOCs were significantly higher in the apartments than in the family houses. The average TVOC levels in the apartments and family houses were 519.7 µg/m3 and 330.2 µg/m3, respectively. Statistical analysis confirmed the effect of indoor air temperature, relative humidity and particulate matter (PM0.5 and PM1 on the levels of TVOCs. Higher TVOC levels were observed also in homes where it is not a common practice to open windows during cleaning activities. Other factors that had a statistically significant effect on concentrations of volatile organic compounds were heating type, attached garage, location of the apartment within residential building (the floor, as well as number of occupants. Higher TVOC concentrations were observed in indoor than outdoor environment, while further analysis showed the significant impact of indoor emission sources on the level of these compounds in buildings. The questionnaire study showed a discrepancy between objective measurement and subjective assessment in the household environment, and pointed to insufficient public awareness about volatile organic compounds (VOCs.

Eimeria Oocyst Concentrations and Species Composition in Litter from Commercial Broiler Farms During Anticoccidial Drug or Live Eimeria Oocyst Vaccine Control Programs.

Science.gov (United States)

Jenkins, Mark C; Parker, Carolyn; Ritter, Donald

2017-06-01

The purpose of this study was to determine if Eimeria oocyst concentrations and species composition in commercial broiler house litter changed during different cycles of anticoccidial drug (ACD) or live Eimeria oocyst vaccine (VAC) control programs and if there was a correlation between Eimeria oocyst levels and broiler performance. Litter samples were collected from a total of 15 different broiler farms encompassing a total of 45 individual houses during at least one complete grow-out cycle over a 21-mo period. Of these 15 broiler farms, three were followed for the entire 21-mo period spanning three ACD and four VAC cycles. Samples were collected at 2, 4, and 7-8 wk of grow-out corresponding to starter, grower, and withdraw periods of the ACD cycle. On a number of occasions, litter samples were obtained just prior to chick placement. Eimeria oocysts were isolated from all samples, counted by microscopy, and extracted for DNA to identify Eimeria species by ITS1 PCR. In general, Eimeria oocyst concentration in litter reached peak levels at 2-4 wk of grow-out regardless of coccidiosis control measure being used. However, peak oocyst numbers were sometimes delayed until 7-8 wk, indicating some level of Eimeria spp. drug resistance or incomplete vaccine coverage. Eimeria maxima , Eimeria acervulina , Eimeria praecox, and Eimeria tenella were generally present in all samples, and no difference in the species composition was noted between houses on a particular farm. While Eimeria species composition was similar among houses, Eimeria spp. oocyst levels exhibited sporadic peaks in one house of a given location's houses. Of particular interest was the observed correlation between E. maxima oocyst abundance and chick mortality. However, no correlation was observed in E. maxima oocyst levels, and the performance parameters adjusted feed conversion ratio and average daily weight gain. This study showed that understanding the dynamics of Eimeria spp. oocyst levels and species

Determination of safety margins for whole blood concentrations of alcohol and nineteen drugs in driving under the influence cases.

Science.gov (United States)

Kristoffersen, Lena; Strand, Dag Helge; Liane, Veronica Horpestad; Vindenes, Vigdis; Tvete, Ingunn Fride; Aldrin, Magne

2016-02-01

Legislative limits for driving under the influence of 20 non-alcohol drugs were introduced in Norway in February 2012. Per se limits corresponding to blood alcohol concentrations (BAC) of 0.2g/kg were established for 20 psychoactive drugs, and limits for graded sanctions corresponding to BACs of 0.5 and 1.2g/kg were determined for 13 of these drugs. This new legislation made it possible for the courts to make sentences based on the analytical results, similar to the situation for alcohol. To ensure that the reported concentration is as least as high as the true concentration, with a 99% safety level, safety margins had to be calculated for each of the substances. Diazepam, tetrahydrocannabinol (THC) and alcohol were used as model substances to establish a new model for estimating the safety margins. The model was compared with a previous used model established several years ago, by a similar yet much simpler model, and they were found to be in agreement. The measurement uncertainties depend on the standard batch used, the work list and the measurements' replicate. A Bayesian modelling approach was used to determine the parameters in the model, using a dataset of 4700 diazepam positive specimens and 5400 THC positive specimens. Different safety margins were considered for low and high concentration levels of diazepam (≤2μM (0.6mg/L) and >2μM) and THC (≤0.01μM (0.003mg/L) and >0.01μM). The safety margins were for diazepam 19.5% (≤2μM) and 34% (>2μM), for THC 19.5% (≤0.01μM) and 24.9% (>0.01μM). Concentration dependent safety margins for BAC were based on a dataset of 29500 alcohol positive specimens, and were in the range 10.4% (0.1g/kg) to 4.0% (4.0g/kg) at a 99% safety level. A simplified approach was used to establish safety margins for the compounds amphetamine, MDMA, methamphetamine, alprazolam, phenazepam, flunitrazepam, clonazepam, nitrazepam, oxazepam, buprenorphine, GHB, methadone, ketamine, cocaine, morphine, zolpidem and zopiclone. The

Anticancer drugs in Portuguese surface waters - Estimation of concentrations and identification of potentially priority drugs.

Science.gov (United States)

Santos, Mónica S F; Franquet-Griell, Helena; Lacorte, Silvia; Madeira, Luis M; Alves, Arminda

2017-10-01

Anticancer drugs, used in chemotherapy, have emerged as new water contaminants due to their increasing consumption trends and poor elimination efficiency in conventional water treatment processes. As a result, anticancer drugs have been reported in surface and even drinking waters, posing the environment and human health at risk. However, the occurrence and distribution of anticancer drugs depend on the area studied and the hydrological dynamics, which determine the risk towards the environment. The main objective of the present study was to evaluate the risk of anticancer drugs in Portugal. This work includes an extensive analysis of the consumption trends of 171 anticancer drugs, sold or dispensed in Portugal between 2007 and 2015. The consumption data was processed aiming at the estimation of predicted environmental loads of anticancer drugs and 11 compounds were identified as potentially priority drugs based on an exposure-based approach (PEC b > 10 ng L -1 and/or PEC c > 1 ng L -1 ). In a national perspective, mycophenolic acid and mycophenolate mofetil are suspected to pose high risk to aquatic biota. Moderate and low risk was also associated to cyclophosphamide and bicalutamide exposition, respectively. Although no evidences of risk exist yet for the other anticancer drugs, concerns may be associated with long term effects. Copyright © 2017 Elsevier Ltd. All rights reserved.

Application of Terahertz Attenuated Total Reflection Spectroscopy to Detect Changes in the Physical Properties of Lactose during the Lubrication Process Required for Drug Formulation.

Science.gov (United States)

Dohi, Masafumi; Momose, Wataru; Yamashita, Kazunari; Hakomori, Tadashi; Sato, Shusaku; Noguchi, Shuji; Terada, Katsuhide

2017-02-01

Manufacturing the solid dosage form of an orally administered drug requires lubrication to enhance manufacturability, ensuring that critical quality attributes such as disintegration and dissolution of the drug product are maintained during manufacture. Here, to evaluate lubrication performance during manufacture, we used terahertz attenuated total reflection (THz-ATR) spectroscopy to detect differences in the physical characteristics of the lubricated powder. We applied a simple formulation prepared by blending granulated lactose as filler with magnesium stearate as lubricant. A flat tablet was prepared using the lubricated powder to acquire sharp THz-ATR absorption peaks of the samples. First, we investigated the effects of lubricant concentration and compression pressure on preparation of the tablet and then determined the effect of the pressure applied to samples in contact with the ATR prism on sample absorption amplitude. We focused on the differences in the magnitudes of spectra at the lactose-specific frequency. Second, we conducted the dynamic lubrication process using a 120-L mixer to investigate differences in the magnitudes of absorption corresponding to the lactose-specific frequency during lubrication. In both studies, enriching the lubricated powder with a higher concentration of magnesium stearate or prolonging blending time correlated with higher magnitudes of spectra at the lactose-specific frequency. Further, in the dynamic lubrication study, the wettability and disintegration time of the tablets were compared with the absorption spectra amplitudes at the lactose-specific frequency. We conclude that THz-ATR spectroscopy is useful for detecting differences in densities caused by a change in the physical properties of lactose during lubrication.

Design and Characterization of a Silk-Fibroin-Based Drug Delivery Platform Using Naproxen as a Model Drug

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Tatyana Dyakonov

2012-01-01

Full Text Available The objective of this proof-of-concept study was to develop a platform for controlled drug delivery based on silk fibroin (SF and to explore the feasibility of using SF in oral drug delivery. The SF-containing matrixes were prepared via spray-drying and film casting, and the release profile of the model drug naproxen sodium was evaluated. Attenuated total reflectance Fourier transform infrared spectroscopy (FTIR has been used to observe conformational changes in SF- and drug-containing compositions. SF-based films, spray-dried microparticles, and matrixes loaded with naproxen were prepared. Both FTIR spectra and in vitro dissolution data demonstrated that SF β-sheet conformation regulates the release profile of naproxen. The controlled release characteristics of the SF-containing compositions were evaluated as a function of SF concentration, temperature, and exposure to dehydrating solvents. The results suggest that SF may be an attractive polymer for use in controlled drug delivery systems.

Reducing surface water total and methyl mercury concentrations and bioavailability using a coagulation-wetland system

Science.gov (United States)

Kraus, T. E.; Fleck, J.; Henneberry, Y. K.; Stumpner, E. B.; Krabbenhoft, D. P.; Bachand, P.; Randall, P.

2013-12-01

With the recent passage of laws regulating concentrations and loads of mercury (Hg) in surface waters, there is a need to develop management practices that will reduce the export of Hg from both point and non-point sources. Coagulation with metal based salts to remove particles and dissolved organic matter (DOM) from solution is a practice commonly employed by drinking water utilities. Because dissolved Hg is associated with particles and DOM, it follows that Hg should also be removed during the coagulation process and end up associated with the organo-metal precipitate, termed flocculate (floc). The effectiveness of iron- and aluminum-based coagulants for removing both inorganic and methyl mercury (IHg and MeHg, respectively) from solution was demonstrated in laboratory studies conducted on agricultural drainage waters of the Sacramento-San Joaquin Delta: dissolved concentrations of MeHg decreased by 80% while IHg decreased by 97% following coagulation. To test the field application of this technology, samples were collected from the inflows and outflows of wetland treatment cells constructed in the central Delta of California. This replicated field experiment includes three replicates each of three inflow waters treatments: (1) iron sulfate addition, (2) polyaluminum chloride addition, and (3) untreated controls. Water entering and exiting the nine treatment cells was sampled approximately monthly over a 1-year period for total Hg and MeHg in both the dissolved and particulate aqueous phases. Initial results confirm that coagulant addition is removing Hg (total and methyl, particulate and dissolved) from solution and sequestering it in the floc. Seasonal effects on DOM concentration and other factors appear to effect whether passage through the wetland cells alters surface water dissolved organic carbon (DOC) and Hg concentrations. Related studies will examine whether the presence of the floc affects the production and fate of MeHg within the wetland cells. If

Estimating spatio-temporal dynamics of stream total phosphate concentration by soft computing techniques.

Science.gov (United States)

Chang, Fi-John; Chen, Pin-An; Chang, Li-Chiu; Tsai, Yu-Hsuan

2016-08-15

This study attempts to model the spatio-temporal dynamics of total phosphate (TP) concentrations along a river for effective hydro-environmental management. We propose a systematical modeling scheme (SMS), which is an ingenious modeling process equipped with a dynamic neural network and three refined statistical methods, for reliably predicting the TP concentrations along a river simultaneously. Two different types of artificial neural network (BPNN-static neural network; NARX network-dynamic neural network) are constructed in modeling the dynamic system. The Dahan River in Taiwan is used as a study case, where ten-year seasonal water quality data collected at seven monitoring stations along the river are used for model training and validation. Results demonstrate that the NARX network can suitably capture the important dynamic features and remarkably outperforms the BPNN model, and the SMS can effectively identify key input factors, suitably overcome data scarcity, significantly increase model reliability, satisfactorily estimate site-specific TP concentration at seven monitoring stations simultaneously, and adequately reconstruct seasonal TP data into a monthly scale. The proposed SMS can reliably model the dynamic spatio-temporal water pollution variation in a river system for missing, hazardous or costly data of interest. Copyright © 2016 Elsevier B.V. All rights reserved.

Planar solar concentrator featuring alignment-free total-internal-reflection collectors and an innovative compound tracker.

Science.gov (United States)

Teng, Tun-Chien; Lai, Wei-Che

2014-12-15

This study proposed a planar solar concentrator featuring alignment-free total-internal-reflection (TIR) collectors and an innovative compound tracker. The compound tracker, combining a mechanical single-axis tracker and scrollable prism sheets, can achieve a performance on a par with dual-axis tracking while reducing the cost of the tracking system and increasing its robustness. The alignment-free TIR collectors are assembled on the waveguide without requiring alignment, so the planar concentrator is relatively easily manufactured and markedly increases the feasibility for use in large concentrators. Further, the identical TIR collector is applicable to various-sized waveguide slab without requiring modification, which facilitates flexibility regarding the size of the waveguide slab. In the simulation model, the thickness of the slab was 2 mm, and its maximal length reached 6 m. With an average angular tolerance of ±0.6°, and after considering both the Fresnel loss and the angular spread of the sun, the simulation indicates that the waveguide concentrator of a 1000-mm length provides the optical efficiencies of 62-77% at the irradiance concentrations of 387-688, and the one of a 2000-mm length provides the optical efficiencies of 52-64.5% at the irradiance concentrations of 645-1148. Alternatively, if a 100-mm horizontally staggered waveguide slab is collocated with the alignment-free TIR collectors, the optical efficiency would be greatly improved up to 91.5% at an irradiance concentration of 1098 (C(geo) = 1200X).

Selective serotonin reuptake inhibitors and venlafaxine in pregnancy: Changes in drug disposition.

Directory of Open Access Journals (Sweden)

Andreas Austgulen Westin

Full Text Available Pregnancy may cause changes in drug disposition. The clinical consequences may be profound and even counterintuitive; in some cases pregnant women may need more than twice their usual drug dose in order to maintain therapeutic drug levels. For antidepressants, evidence on drug disposition in pregnancy is scarce. The aim of this study was to determine the effects of pregnancy on serum levels of selective serotonin reuptake inhibitors (SSRIs and venlafaxine in a large and naturalistic patient material, in order to provide tentative dose recommendations for pregnant women.Using patient data from two routine therapeutic drug monitoring (TDM services in Norway with linkage to the national birth registry, dose-adjusted serum drug concentrations of SSRIs and venlafaxine during pregnancy were compared to the women's own baseline (non-pregnant values, using a linear mixed model.Overall, the TDM databases contained 196,726 serum concentration measurements from 54,393 women. After data linkage and drug selection (SSRIs or venlafaxine only, we identified 367 analyses obtained from a total of 290 pregnancies in 281 women, and 420 baseline observations from the same women. Serum concentrations in the third trimester were significantly lower than baseline for paroxetine (-51%; 95% confidence interval [CI], -66%, -30%; p<0.001, fluvoxamine (-56%; CI, -75%, -23%; p = 0.004 and citalopram (-24%; CI, -38%, -7%; p = 0,007, and higher than baseline for sertraline (+68%; CI, +37%, +106%; p<0.001. For escitalopram, fluoxetine and venlafaxine concentrations did not change significantly.For paroxetine and fluvoxamine the pronounced decline in maternal drug serum concentrations in pregnancy may necessitate a dose increase of about 100% during the third trimester in order to maintain stable concentrations. For fluoxetine, venlafaxine, citalopram, escitalopram and sertraline, the present study indicates that dose adjustments are generally not necessary during pregnancy.

Characteristics of total gaseous mercury concentrations at a coastal area of the Yangtze Delta, China.

Science.gov (United States)

Diao, Chunyan; Li, Jianfeng; Zhang, Bin; Tang, Shichuang

2017-03-01

In this study, we report on total gaseous mercury (TGM) field observations made in the rural area of Shanghai, Chongming Island, China, from September 2009 to April 2012. The average TGM was 2.65 ± 1.73 ng m -3 in Chongming Island, which is higher than the TGM background value of the Northern Hemisphere (1.5-1.7 ng m -3 ); this indicates that to some extent, the Chongming area has been affected by anthropogenic mercury emissions. The observed TGM follows a seasonal pattern; concentrations are highest in winter, followed by autumn, summer, and spring. There is also a clear diurnal variation in TGM. All peak values appear between 7:00 and 9:00 in all four seasons; this appears to be the result of the height change in the atmospheric boundary layer that occurs between day and night. TGM concentrations in Chongming remain high in the westerly wind direction, especially in the southwest direction because of its low frequency, so the greatest source contribution to TGM in Chongming lies to the northwest. Wind speed is also a significant factor affecting TGM, and was negatively correlated with TGM concentrations. TGM is also closely related to carbon monoxide (CO) concentrations, indicating that TGM is impacted by human activities. The slope of the linear fitting of TGM and CO demonstrates that the contribution of noncoal source emissions to TGM in summer is greater than in autumn, mainly because the high temperature and intensive sunlight in summer increase mercury emissions from natural sources. Except for some studies in the coastal areas (e.g., Kang Hwa Island by Kim et al., 2006, An-Myun Island by Kim et al., 2002, and Okinawa by Chan et al., 2008), data specifically for coastal areas are lacking. Monitoring of total gaseous mercury (TGM) in the rural area of Shanghai, Chongming Island, can help us understand mercury distribution.

Free amino nitrogen concentration correlates to total yeast assimilable nitrogen concentration in apple juice

OpenAIRE

Boudreau, Thomas F.; Peck, Gregory M.; O'Keefe, Sean F.; Stewart, Amanda C.

2017-01-01

Abstract Yeast assimilable nitrogen (YAN) is essential for yeast growth and metabolism during apple (Malus x domestica Borkh.) cider fermentation. YAN concentration and composition can impact cider fermentation kinetics and the formation of volatile aroma compounds by yeast. The YAN concentration and composition of apples grown in Virginia, USA over the course of two seasons was determined through analysis of both free amino nitrogen (FAN) and ammonium ion concentration. FAN was the largest f...

Postmortem Blood Concentrations of R- and S-Enantiomers of Methadone and EDDP in Drug Users: Influence of Co-Medication and P-glycoprotein Genotype

DEFF Research Database (Denmark)

Buchard, Anders; Linnet, Kristian; Johansen, Sys Stybe

2010-01-01

We investigated toxicological and pharmacogenetic factors that could influence methadone toxicity using postmortem samples. R- and S-methadone were measured in femoral blood from 90 postmortem cases, mainly drug users. The R-enantiomer concentrations significantly exceeded that of the S-enantiome......We investigated toxicological and pharmacogenetic factors that could influence methadone toxicity using postmortem samples. R- and S-methadone were measured in femoral blood from 90 postmortem cases, mainly drug users. The R-enantiomer concentrations significantly exceeded that of the S...

Total lead concentration in new decorative enamel paints in Lebanon, Paraguay and Russia.

Science.gov (United States)

Clark, C Scott; Speranskaya, Olga; Brosche, Sara; Gonzalez, Hebe; Solis, Daniela; Kodeih, Naji; Roda, Sandy; Lind, Caroline

2015-04-01

Lead concentrations in new enamel decorative paints were determined in three countries in different areas of the world where data were not previously available. The average total lead concentration of the enamel decorative paints purchased in Lebanon, Paraguay and Russia was 24,500ppm (ppm, dry weight), more than 270 times the current limit of 90ppm in Canada and in the United States. Sixty-three percent of these paints contained concentrations greater than 90ppm. Fifty-nine percent contained concentrations greater than 600ppm, the current limit in some countries. The maximum concentrations found were 236,000ppm in Lebanon, 169,000ppm in Paraguay and 52,900ppm in Russia. An average of 29% of the samples contained exceedingly high lead concentrations, >=10,000ppm. Five brands of paint were sampled in each of Lebanon and Paraguay and seven in Russia. Three colors from each brand were analyzed. For five of the six samples of the two brands in Lebanon with affiliations outside the country, the lead concentrations ranged from 1360ppm to 135,000ppm. In Lebanon the maximum concentration in the Egypt-affiliated brand (Sipes) was 135,000ppm and the maximum for the USA-affiliated brand (Dutch Boy) was 32,400ppm. Lead was not detected in any paints from the three of the four brands of paint purchased in Paraguay that had headquarters/affiliations in other countries (Brazil-Coralit), Germany (Suvinil) and USA (Novacor)). Two of the three paints from each of the other Paraguay brands contained high levels of lead with the maximum concentrations of 108,000 and 168,000ppm; one of these brands was manufactured under a license from ICI in the Netherlands. All of the paints purchased in Russia were from Russian brands and were manufactured in Russia. All three paints from one brand contained below detection levels of lead. The maximum levels of lead in the other six brands in Russia ranged from 3230 to 52,900ppm. The two brands with the highest lead concentration, TEKS and LAKRA

Importance of Dissolved Neutral Hg-Sulfides, Energy Rich Organic Matter and total Hg Concentrations for Methyl Mercury Production in Sediments

Science.gov (United States)

Drott, A.; Skyllberg, U.

2007-12-01

Methyl mercury (MeHg) is the mercury form that biomagnifies to the greatest extent in aquatic food webs. Therefore information about factors determining MeHg concentrations is critical for accurate risk assessment of contaminated environments. The concentration of MeHg in wetlands and sediments is the net result of: 1) methylation rates, 2) demethylation rates, and 3) input/output processes. In this study, the main controls on Hg methylation rates and total concentrations of MeHg, were investigated at eight sites in Sweden with sediments that had been subjected to local Hg contamination either as Hg(0), or as phenyl-Hg. Sediments were selected to represent a gradient in total Hg concentration, temperature climate, salinity, primary productivity, and organic C content and quality. Most sediments were high in organic matter content due to wood fibre efflux from pulp and paper industry. The pore water was analysed for total Hg, MeHg, DOC, H2S(aq), pH, DOC, Cl and Br. The chemical speciation of Hg(II) and MeHg in pore water was calculated using equilibrium models. Potential methylation and demethylation rates in sediments were determined in incubation experiments at 23° C under N2(g) for 48 h, after addition of isotopically enriched 201Hg(II) and Me204Hg. In all surface (0-20 cm) sediments there was a significant (pdetermined specific potential methylation rate constant (Km, day-1) and % MeHg (concentrations of MeHg normalized to total Hg) in the sediment. This indicates that MeHg production overruled degradation and input/output processes of MeHg in surface sediments, and that % MeHg in surface sediments may be used as a proxy for net production of MeHg. To our knowledge, these are the first data showing significant positive relationships between short term (48 h) MeHg production and longer term accumulation of MeHg, across a range of sites with different properties (1). If MeHg was not normalized to total Hg, the relationship was not significant. For sub-sets of

A new application of micellar liquid chromatography in the determination of free ampicillin concentration in the drug-human serum albumin standard solution in comparison with the adsorption method.

Science.gov (United States)

Stępnik, Katarzyna E; Malinowska, Irena; Maciejewska, Małgorzata

2016-06-01

The determination of free drug concentration is a very important issue in the field of pharmacology because only the unbound drug fraction can achieve a pharmacological effect. Due to the ability to solubilize many different compounds in micellar aggregates, micellar liquid chromatography (MLC) can be used for direct determination of free drug concentration. Proteins are not retained on the stationary phase probably due to the formation of protein - surfactant complexes which are excluded from the pores of stationary phase. The micellar method is simple and fast. It does not require any pre-preparation of the tested samples for analysis. The main aim of this paper is to demonstrate a completely new applicability of the analytical use of MLC concerning the determination of free drug concentration in the standard solution of human serum albumin. The well-known adsorption method using RP-HPLC and the spectrophotometric technique was applied as the reference method. The results show that the free drug concentration value obtained in the MLC system (based on the RP-8 stationary phase and CTAB) is similar to that obtained by the adsorption method: both RP-HPLC (95.83μgmL(-1), 79.86% of free form) and spectrophotometry (95.71μgmL(-1), 79.76%). In the MLC the free drug concentration was 93.98μgmL(-1) (78.3%). This indicates that the obtained results are within the analytical range of % of free ampicillin fraction and the MLC with direct sample injection can be treated like a promising method for the determination of free drug concentration. Copyright © 2016 Elsevier B.V. All rights reserved.

Drug-Target Kinetics in Drug Discovery.

Science.gov (United States)

Tonge, Peter J

2018-01-17

The development of therapies for the treatment of neurological cancer faces a number of major challenges including the synthesis of small molecule agents that can penetrate the blood-brain barrier (BBB). Given the likelihood that in many cases drug exposure will be lower in the CNS than in systemic circulation, it follows that strategies should be employed that can sustain target engagement at low drug concentration. Time dependent target occupancy is a function of both the drug and target concentration as well as the thermodynamic and kinetic parameters that describe the binding reaction coordinate, and sustained target occupancy can be achieved through structural modifications that increase target (re)binding and/or that decrease the rate of drug dissociation. The discovery and deployment of compounds with optimized kinetic effects requires information on the structure-kinetic relationships that modulate the kinetics of binding, and the molecular factors that control the translation of drug-target kinetics to time-dependent drug activity in the disease state. This Review first introduces the potential benefits of drug-target kinetics, such as the ability to delineate both thermodynamic and kinetic selectivity, and then describes factors, such as target vulnerability, that impact the utility of kinetic selectivity. The Review concludes with a description of a mechanistic PK/PD model that integrates drug-target kinetics into predictions of drug activity.

Extensively and Pre-Extensively Drug Resistant Tuberculosis in Clinical Isolates of Multi-Drug Resistant Tuberculosis Using Classical Second Line Drugs (Levofloxacin and Amikacin)

International Nuclear Information System (INIS)

Mirza, I. A.; Khan, F. A.; Khan, K. A.; Satti, L.; Ghafoor, T.; Fayyaz, M.

2015-01-01

Objective:To find out the frequency of Extensively Drug Resistant (XDR) and pre-XDR tuberculosis in clinical isolates of Multi-Drug Resistant (MDR) Tuberculosis (TB) by determining the susceptibilities against Levofloxacin and Amikacin (classical second line antituberculosis drugs). Study Design: A descriptive cross-sectional study. Place and Duration of Study: Microbiology Department, Armed Forces Institute of Pathology (AFIP), Rawalpindi, from September 2011 to August 2013. Methodology: Amikacin (AK) and Levofloxacin (LEVO) were obtained in chemically pure form from Sigma (Taufkirchen, Germany). The breakpoint concentration used for AK was 1.0 micro g/ml and for LEVO 2.0 micro g/ml. Mycobacterial Growth Indicator Tube (MGIT) 960 system was used to carry out drug susceptibility testing as per recommended protocol. Results: A total of 3 MDR-TB isolates (3 percentage) turned out to be XDR-TB based upon simultaneous resistance to injectable second line antituberculosis drug AK and one of the fluoro-quinolones (LEVO). A total of 24 MDR-TB isolates (24 percentage) were found to be pre-XDR based upon resistance to LEVO alone. Treatment status record of patients with XDR and pre-XDRTB isolates revealed that majority of patients had received fluoroquinolones (FQs) during the course of treatment. Conclusion: XDR-TB has started to emerge in MDR-TB isolates in our set up. The worrying sign is the high frequency of pre-XDR tuberculosis. Urgent steps need to be taken to stem the tide of pre-XDR-TB in our population. It is thus recommended to develop facilities to carry out drug susceptibility testing to monitor the status of pre-XDR and XDR-TB in our population. (author)

Drug diffusion across skin with diffusivity spatially modulated

Science.gov (United States)

Montoya Arroyave, Isabel

2014-05-01

A diffusion and delivery model of a drug across the skin with diffusivity spatially modulated is formulated and solved analytically using computer algebra. The model is developed using one-dimensional diffusion equation with a diffusivity which is a function of position in the skin; with an initial condition which is describing that the drug is initially contained inside a therapeutic patch; with a boundary condition according to which the change in concentration in the patch is minimal, such that assumption of zero flux at the patch-skin interface is valid; and with other boundary condition according to which the microcirculation in the capillaries just below the dermis carries the drug molecules away from the site at a very fast rate, maintaining the inner concentration at 0. The model is solved analytically by the method of the Laplace transform, with Bromwich integral and residue theorem. The concentration profile of the drug in the skin is expressed as an infinite series of Bessel functions. The corresponding total amount of delivered drug is expressed as an infinite series of decreasing exponentials. Also, the corresponding effective time for the therapeutic patch is determined. All computations were performed using computer algebra software, specifically Maple. The analytical results obtained are important for understanding and improving currentapplications of therapeutic patches. For future research it is interesting to consider more general models of spatial modulation of the diffusivity and the possible application of other computer algebra software such as Mathematica and Maxima.

Determination of protein concentration in raw milk by mid-infrared fourier transform infrared/attenuated total reflectance spectroscopy.

Science.gov (United States)

Etzion, Y; Linker, R; Cogan, U; Shmulevich, I

2004-09-01

This study investigates the potential use of attenuated total reflectance spectroscopy in the mid-infrared range for determining protein concentration in raw cow milk. The determination of protein concentration is based on the characteristic absorbance of milk proteins, which includes 2 absorbance bands in the 1500 to 1700 cm(-1) range, known as the amide I and amide II bands, and absorbance in the 1060 to 1100 cm(-1) range, which is associated with phosphate groups covalently bound to casein proteins. To minimize the influence of the strong water band (centered around 1640 cm(-1)) that overlaps with the amide I and amide II bands, an optimized automatic procedure for accurate water subtraction was applied. Following water subtraction, the spectra were analyzed by 3 methods, namely simple band integration, partial least squares (PLS) and neural networks. For the neural network models, the spectra were first decomposed by principal component analysis (PCA), and the neural network inputs were the spectra principal components scores. In addition, the concentrations of 2 constituents expected to interact with the protein (i.e., fat and lactose) were also used as inputs. These approaches were tested with 235 spectra of standardized raw milk samples, corresponding to 26 protein concentrations in the 2.47 to 3.90% (weight per volume) range. The simple integration method led to very poor results, whereas PLS resulted in prediction errors of about 0.22% protein. The neural network approach led to prediction errors of 0.20% protein when based on PCA scores only, and 0.08% protein when lactose and fat concentrations were also included in the model. These results indicate the potential usefulness of Fourier transform infrared/attenuated total reflectance spectroscopy for rapid, possibly online, determination of protein concentration in raw milk.

IFCC reference measurement procedure for substance concentration determination of total carbon dioxide in blood, plasma or serum

NARCIS (Netherlands)

Burnett, RW; Covington, AK; Fogh-Andersen, N; Kulpmann, WR; Lewenstam, A; Mas, AHJ; VanKessel, AL; Zijlstra, WG

A reference measurement procedure for substance concentration determination of total CO, in blood, plasma (the anticoagulant is usually heparin) or serum is described. The document covers the principle of the method, the materials and equipment needed and essential aspects of the procedure. The

Linezolid Trough Concentrations Correlate with Mitochondrial Toxicity-Related Adverse Events in the Treatment of Chronic Extensively Drug-Resistant Tuberculosis.

Science.gov (United States)

Song, Taeksun; Lee, Myungsun; Jeon, Han-Seung; Park, Yumi; Dodd, Lori E; Dartois, Véronique; Follman, Dean; Wang, Jing; Cai, Ying; Goldfeder, Lisa C; Olivier, Kenneth N; Xie, Yingda; Via, Laura E; Cho, Sang Nae; Barry, Clifton E; Chen, Ray Y

2015-11-01

Long-term linezolid use is limited by mitochondrial toxicity-associated adverse events (AEs). Within a prospective, randomized controlled trial of linezolid to treat chronic extensively drug-resistant tuberculosis, we serially monitored the translational competence of mitochondria isolated from peripheral blood of participants by determining the cytochrome c oxidase/citrate synthase activity ratio. We compared this ratio with AEs associated with mitochondrial dysfunction. Linezolid trough concentrations were determined for 38 participants at both 600 mg and 300 mg doses. Those on 600 mg had a significantly higher risk of AE than those on 300 mg (HR 3·10, 95% CI 1·23-7 · 86). Mean mitochondrial function levels were significantly higher in patients before starting linezolid compared to their concentrations on 300 mg (P = 0·004) or 600 mg (P linezolid trough concentrations were associated with lower mitochondrial function levels (Spearman's ρ = - 0.48; P = 0.005). Mitochondrial toxicity risk increased with increasing linezolid trough concentrations, with all patients with mean linezolid trough > 2 μg/ml developing an AE related to mitochondrial toxicity, whether on 300 mg or 600 mg. Therapeutic drug monitoring may be useful to prevent the development of mitochondrial toxicity associated with long-term linezolid use.

Total and bioavailable arsenic concentration in arid soils and its uptake by native plants from the pre-Andean zones in Chile.

Science.gov (United States)

Díaz, O; Tapia, Y; Pastene, R; Montes, S; Núñez, N; Vélez, D; Montoro, R

2011-06-01

Arsenic is the most important contaminant of the environment in northern Chile. Soil samples and plant organs from three native plant species, Pluchea absinthioides, Atriplex atacamensis and Lupinus microcarpus, were collected from arid zones in order to determine the total and bioavailable arsenic concentrations in soils and to assess the bioconcentration factor (BCF) and transport index (Ti) of arsenic in the plants. Total arsenic concentrations in soils (pH 8.3-8.5) where A. atacamensis and P. absinthioides were collected, reached levels considered to be contaminated (54.3 ± 15.4 and 52.9 ± 9.9 mg kg⁻¹, respectively), and these values were approximately ten times higher than in soils (pH 7.6) where L. microcarpus was collected. Bioavailable arsenic ranged from 0.18 to 0.42% of total arsenic concentration. In the three plant species, arsenic concentration in leaves were significantly (p ≤ 0.05) higher than in roots. L. microcarpus showed the highest arsenic concentration in its leaves (9.7 ± 1.6 mg kg⁻¹) and higher values of BCF (1.8) and Ti (6.1), indicating that this species has a greater capacity to accumulate and translocate the metalloid to the leaf than do the other species.

Green Pharmaceutical Analysis of Drugs Coformulated with Highly Different Concentrations Using Spiking and Manipulation of Their Ratio Spectra.

Science.gov (United States)

Ayoub, Bassam M

2017-07-01

Introducing green analysis to pharmaceutical products is considered a significant approach to preserving the environment. This method can be an environmentally friendly alternative to the existing methods, accompanied by a validated automated procedure for the analysis of a drug with the lowest possible number of samples. Different simple spectrophotometric methods were developed for the simultaneous determination of empagliflozin (EG) and metformin (MT) by manipulating their ratio spectra in their application on a recently approved pharmaceutical combination, Synjardy tablets. A spiking technique was used to increase the concentration of EG in samples prepared from the tablets to allow for the simultaneous determination of EG with MT without prior separation. Validation parameters according to International Conference on Harmonization guidelines were acceptable over a concentration range of 2-12 μg/mL for both drugs using derivative ratio and ratio subtraction coupled with extended ratio subtraction. The optimized methods were compared using one-way analysis of variance and proved to be suitable as ecofriendly approaches for industrial QC laboratories.

Association between worldwide dietary and lifestyle patterns with total cholesterol concentrations and DALYs for infectious and cardiovascular diseases: an ecological analysis.

Science.gov (United States)

Oggioni, C; Cena, H; Wells, J C K; Lara, J; Celis-Morales, C; Siervo, M

2015-12-01

Global dietary and lifestyle trends are primary risk factors for communicable and non-communicable diseases. An ecological analysis was conducted to examine the association of global dietary and lifestyle patterns with total cholesterol concentrations. This study also investigated whether total cholesterol modified the association between dietary and lifestyle habits with disability-adjusted-life-years-lost (DALYs) for infectious and cardiovascular diseases (CVDs). Country-specific mean total cholesterol concentrations and DALYs for infectious and CVDs were obtained. Data were then matched to country-specific food and energy availability for consumption and information on obesity, physical inactivity, urbanization, gross domestic product (GDP), life expectancy and smoking. Stepwise multiple regression models were developed to identify significant predictors of total cholesterol concentrations and DALYs for infectious and CVDs. Life expectancy and egg and meat consumption were significantly associated with cholesterol concentrations. DALYs for infectious diseases were associated with smoking, life expectancy and per capita GDP. Smoking was the only predictor of DALYs for CVDs. The improvement of socio-demographic conditions and economic growth is likely to reduce the burden of communicable diseases in developing countries. A concurring increase in non-communicable diseases is expected, and these results have, yet again, identified smoking as a primary risk factor for CVDs. Copyright © 2015 Ministry of Health, Saudi Arabia. Published by Elsevier Ltd. All rights reserved.

Hepatic drug clearance following traumatic injury.

Science.gov (United States)

Slaughter, R L; Hassett, J M

1985-11-01

Trauma is a complex disease state associated with physiologic changes that have the potential to alter hepatic drug clearance mechanisms. These responses include alterations in hepatic blood flow, reduction in hepatic microsomal activity, reduction in hepatic excretion processes, and changes in protein binding. Hepatic blood flow is influenced by sympathomimetic activity. Both animal and human studies demonstrate an initial reduction and subsequent increase in hepatic blood flow, which coincides with an observed increase and subsequent return to normal in serum catecholamine concentrations. Unfortunately, there are no human studies that address the importance these findings may have to the clearance processes of high intrinsic clearance compounds. Animal studies of trauma indicate that hepatic microsomal activity is depressed during the post-traumatic period. Reduction in the hepatic clearance of antipyrine, a model low intrinsic compound, has also been demonstrated in animal models of trauma. In addition to these effects, hepatic excretion of substances such as indocyanine green and bilirubin have been demonstrated to be impaired in both traumatized animals and humans. Finally, substantial increases in the serum concentration of the binding protein alpha 1-acid glycoprotein occur in trauma patients. This has been reported to be associated with subsequent decreases in the free fraction of lidocaine and quinidine. In addition to changing serum drug concentration/response relationships, the pharmacokinetic behavior of drugs bound to alpha 1-acid glycoprotein should also change. Preliminary observations in our laboratory in a dog model of surgically-induced trauma have shown a reduction in the total clearance of lidocaine and reduction in free lidocaine concentration.(ABSTRACT TRUNCATED AT 250 WORDS)

Role of drug transporters and drug accumulation in the temporal acquisition of drug resistance

International Nuclear Information System (INIS)

Hembruff, Stacey L; Laberge, Monique L; Villeneuve, David J; Guo, Baoqing; Veitch, Zachary; Cecchetto, Melanie; Parissenti, Amadeo M

2008-01-01

Anthracyclines and taxanes are commonly used in the treatment of breast cancer. However, tumor resistance to these drugs often develops, possibly due to overexpression of drug transporters. It remains unclear whether drug resistance in vitro occurs at clinically relevant doses of chemotherapy drugs and whether both the onset and magnitude of drug resistance can be temporally and causally correlated with the enhanced expression and activity of specific drug transporters. To address these issues, MCF-7 cells were selected for survival in increasing concentrations of doxorubicin (MCF-7 DOX-2 ), epirubicin (MCF-7 EPI ), paclitaxel (MCF-7 TAX-2 ), or docetaxel (MCF-7 TXT ). During selection cells were assessed for drug sensitivity, drug uptake, and the expression of various drug transporters. In all cases, resistance was only achieved when selection reached a specific threshold dose, which was well within the clinical range. A reduction in drug uptake was temporally correlated with the acquisition of drug resistance for all cell lines, but further increases in drug resistance at doses above threshold were unrelated to changes in cellular drug uptake. Elevated expression of one or more drug transporters was seen at or above the threshold dose, but the identity, number, and temporal pattern of drug transporter induction varied with the drug used as selection agent. The pan drug transporter inhibitor cyclosporin A was able to partially or completely restore drug accumulation in the drug-resistant cell lines, but had only partial to no effect on drug sensitivity. The inability of cyclosporin A to restore drug sensitivity suggests the presence of additional mechanisms of drug resistance. This study indicates that drug resistance is achieved in breast tumour cells only upon exposure to concentrations of drug at or above a specific selection dose. While changes in drug accumulation and the expression of drug transporters does occur at the threshold dose, the magnitude of

A SUMMARY OF TOTAL MERCURY CONCENTRATIONS IN FLORA AND FAUNA NEAR CONTAMINANT SOURCES IN THE GULF OF MEXICO

Science.gov (United States)

This report summarizes total mercury concentrations for environmental media collected from near-coastal areas including those impacted by contaminant sources common to the Gulf of Mexico. Water, sediment, fish, blue crabs, oysters, clams, mussels, periphyton and seagrasses were ...

Method to determine the activity concentration and total activity of radioactive waste; Metodo para determinar la concentracion de actividad y actividad total de desechos radiactivos

Energy Technology Data Exchange (ETDEWEB)

Angeles C, A

2001-02-15

A characteristic system of radioactive waste is described to determine the concentration of radionuclides activity and the total activity of bundles of radioactive waste. The system this integrated by three subsystems: - Elevator of drums. - Electromechanics. - Gamma spectroscopy. In the system it is analyzed waste of issuing gamma specifically, and this designed for materials of relative low density and it analyzes materials of cylindrical recipients.

Plasma Drug Concentrations of Orally Administered Rosuvastatin in Hispaniolan Amazon Parrots (Amazona ventralis).

Science.gov (United States)

Beaufrère, Hugues; Papich, Mark G; Brandão, João; Nevarez, Javier; Tully, Thomas N

2015-03-01

Atherosclerotic diseases are common in pet psittacine birds, in particular Amazon parrots. While hypercholesterolemia and dyslipidemia have not definitely been associated with increased susceptibility to atherosclerosis in parrots, these are important and well-known risk factors in humans. Therefore statin drugs such as rosuvastatin constitute the mainstay of human treatment of dyslipidemia and the prevention of atherosclerosis. No pharmacologic studies have been performed in psittacine birds despite the high prevalence of atherosclerosis in captivity. Thirteen Hispaniolan Amazon parrots were used to test a single oral dose of 10 mg/kg of rosuvastatin with blood sampling performed according to a balanced incomplete block design over 36 hours. Because low plasma concentrations were produced in the first study, a subsequent pilot study using a dose of 25 mg/kg in 2 Amazon parrots was performed. Most plasma samples for the 10 mg/kg dose and all samples for the 25 mg/kg dose had rosuvastatin concentration below the limits of quantitation. For the 10 mg/kg study, the median peak plasma concentration and time to peak plasma concentration were 0.032 μg/mL and 2 hours, respectively. Our results indicate that rosuvastatin does not appear suitable in Amazon parrots as compounded and used at the dose in this study. Pharmacodynamic studies investigating lipid-lowering effects of statins rather than pharmacokinetic studies may be more practical and cost effective in future studies to screen for a statin with more ideal properties for potential use in psittacine dyslipidemia and atherosclerotic diseases.

The relationship between total phenol concentration and the perceived style of extra virgin olive oil

Directory of Open Access Journals (Sweden)

2009-06-01

Full Text Available The degree of bitterness and pungency of a virgin olive oil largely defines its style, and therefore how it is most appropriately used by consumers. In order to assess how Australian olive oil producers interpret the style of their oils, 920 Australian virgin olive oils were classified by their producers as either being mild, medium or robust in style. Although in general, the classifications by producers were associated with the oils’ total phenol concentration, significant variability in phenol concentration within each style category was observed. The perceived styles of a subset of these oils were further assessed by panels of expert tasters. The expert panels were more discriminating when assigning oils to style categories based on total phenol levels. The producers and the expert panels were in moderate agreement with respect to oil style, with the interpretation of what constitutes a mild oil being the most contentious.

El grado de amargor y picante de un aceite de oliva define en gran manera su tipo, y, por tanto, también su uso más apropiado por el consumidor. Para evaluar cómo los productores australianos de aceite de oliva interpretan el tipo de sus aceites, 920 aceites de oliva virgen australianos fueron clasificados por sus productores en tipo suave, medio o fuerte. Aunque, en general, la clasificación de los productores estuvo asociada a la concentración de fenoles totales de los aceites, se observó una variabilidad significativa en la concentración de fenoles en cada tipo de aceite. Los tipos percibidos en un subgrupo de estos aceites fueron además evaluados por paneles de catadores expertos. Los paneles de expertos fueron más discriminantes cuando asignaron los aceites a los diversos tipos basándose en el nivel de fenoles totales. Los productores y los paneles de expertos estuvieron en relativamente de acuerdo con respecto al tipo de aceite, si bien la interpretación de qué es un aceite suave fue la m

A targeted liposome delivery system for combretastatin A4: formulation optimization through drug loading and in vitro release studies.

Science.gov (United States)

Nallamothu, Ramakrishna; Wood, George C; Kiani, Mohammad F; Moore, Bob M; Horton, Frank P; Thoma, Laura A

2006-01-01

Efficient liposomal therapeutics require high drug loading and low leakage. The objective of this study is to develop a targeted liposome delivery system for combretastatin A4 (CA4), a novel antivascular agent, with high loading and stable drug encapsulation. Liposomes composed of hydrogenated soybean phosphatidylcholine (HSPC), cholesterol, and distearoyl phosphoethanolamine-PEG-2000 conjugate (DSPE-PEG) were prepared by the lipid film hydration and extrusion process. Cyclic arginine-glycine-aspartic acid (RGD) peptides with affinity for alphav beta3-integrins overexpressed on tumor vascular endothelial cells were coupled to the distal end of polyethylene glycol (PEG) on the liposomes sterically stabilized with PEG (non-targeted liposomes; LCLs). Effect of lipid concentration, drug-to-lipid ratio, cholesterol, and DSPE-PEG content in the formulation on CA4 loading and its release from the liposomes was studied. Total liposomal CA4 levels obtained increased with increasing lipid concentration in the formulation. As the drug-to-lipid ratio increased from 10:100 to 20:100, total drug in the liposome formulation increased from 1.05+/-0.11 mg/mL to 1.55+/-0.13 mg/mL, respectively. When the drug-to-lipid ratio was further raised to 40:100, the total drug in liposome formulation did not increase, but the amount of free drug increased significantly, thereby decreasing the percent of entrapped drug. Increasing cholesterol content in the formulation decreased drug loading. In vitro drug leakage from the liposomes increased with increase in drug-to-lipid ratio or DSPE-PEG content in the formulation; whereas increasing cholesterol content of the formulation up to 30 mol-percent, decreased CA4 leakage from the liposomes. Ligand coupling to the liposome surface increased drug leakage as a function of ligand density. Optimized liposome formulation with 100 mM lipid concentration, 20:100 drug-to-lipid ratio, 30 mol-percent cholesterol, 4 mol-percent DSPE-PEG, and 1 mol

Total and available heavy metal concentrations in soils of the Thriassio plain (Greece) and assessment of soil pollution indexes.

Science.gov (United States)

Massas, Ioannis; Kalivas, Dionisios; Ehaliotis, Constantions; Gasparatos, Dionisios

2013-08-01

The Thriassio plain is located 25 km west of Athens city, the capital of Greece. Two major towns (Elefsina and Aspropyrgos), heavy industry plants, medium to large-scale manufacturing, logistics plants, and agriculture comprise the main land uses of the studied area. The aim of the present study was to measure the total and available concentrations of Cr, Zn, Ni, Pb, Co, Mn, Ba, Cu, and Fe in the top soils of the plain, and to asses soil contamination by these metals by using the geoaccumulation index (I geo), the enrichment factor (EF), and the availability ratio (AR) as soil pollution indexes. Soil samples were collected from 90 sampling sites, and aqua regia and DTPA extractions were carried out to determine total and available metal forms, respectively. Median total Cr, Zn, Ni, Pb, Co, Mn, Ba, Cu, and Fe concentrations were 78, 155, 81, 112, 24, 321, 834, 38, and 16 × 10(3) mg kg(-1), respectively. The available fractions showed much lower values with medians of 0.4, 5.6, 1.7, 6.9, 0.8, 5.7, 19.8, 2.1, and 2.9 mg kg(-1). Though median total metal concentrations are not considered as particularly high, the I geo and the EF values indicate moderate to heavy soil enrichment. For certain metals such as Cr, Ni, Cu, and Ba, the different distribution patterns between the EFs and the ARs suggest different origin of the total and the available metal forms. The evaluation of the EF and AR data sets for the soils of the two towns further supports the argument that the EFs can well demonstrate the long-term history of soil pollution and that the ARs can adequately portray the recent history of soil pollution.

A high-protein diet increases postprandial but not fasting plasma total homocysteine concentrations: A dietary controlled, crossover trial in healthy volunteers

NARCIS (Netherlands)

Verhoef, P.; Vliet, T. van; Olthof, M.R.; Katan, M.B.

2005-01-01

Background: A high plasma concentration of total homocysteine (tHcy) is associated with increased risk of cardiovascular disease. A high protein intake and hence a high intake of methionine-the sole dietary precursor of homocysteine-may raise plasma tHcy concentrations. Objectives: We studied

A high-protein diet increases postprandial but not fasting plasma total homocysteine concentrations : A dietary controlled, crossover trial in healthy volunteers

NARCIS (Netherlands)

Verhoef, Petra; Van Vliet, Trinette; Olthof, Margreet R.; Katan, Martijn B.

2005-01-01

Background: A high plasma concentration of total homocysteine (tHcy) is associated with increased risk of cardiovascular disease. A high protein intake and hence a high intake of methionine-the sole dietary precursor of homocysteine-may raise plasma tHcy concentrations. Objectives: We studied

Using pharmacokinetics to predict the effects of pregnancy and maternal-infant transfer of drugs during lactation.

Science.gov (United States)

Anderson, Gail D

2006-12-01

Knowledge of pharmacokinetics and the use of a mechanistic-based approach can improve our ability to predict the effects of pregnancy for medications when data are limited. Despite the many physiological changes that occur during pregnancy that could theoretically affect absorption, bioavailability does not appear to be altered. Decreased albumin and alpha(1)-acid glycoprotein concentrations during pregnancy will result in decreased protein binding for highly bound drugs. For drugs metabolised by the liver, this can result in misinterpretation of total plasma concentrations of low extraction ratio drugs and overdosing of high extraction ratio drugs administered by non-oral routes. Renal clearance and the activity of the CYP isozymes, CYP3A4, 2D6 and 2C9, and uridine 5'-diphosphate glucuronosyltransferase are increased during pregnancy. In contrast, CYP1A2 and 2C19 activity is decreased. The dose of a drug an infant receives during breastfeeding is dependent on the amount excreted into the breast milk, the daily volume of milk ingested and the average plasma concentration of the mother. The lipophilicity, protein binding and ionisation properties of a drug will determine how much is excreted into the breast milk. The milk to plasma concentration ratio has large inter- and intrasubject variability and is often not known. In contrast, protein binding is usually known. An extensive literature review was done to identify case reports including infant concentrations from breast-fed infants exposed to maternal drugs. For drugs that were at least 85% protein bound, measurable concentrations of drug in the infant did not occur if there was no placental exposure immediately prior to or during delivery. Knowledge of the protein binding properties of a drug can provide a quick and easy tool to estimate exposure of an infant to medication from breastfeeding.

A high-protein diet increases postprandial but not fasting plasma total homocysteine concentrations: a dietary controlled, crossover trial in healthy volunteers

NARCIS (Netherlands)

Verhoef, P.; Vliet, van T.; Olthof, M.R.; Katan, M.B.

2005-01-01

Background: A high plasma concentration of total homocysteine (tHcy) is associated with increased risk of cardiovascular disease. A high protein intake and hence a high intake of methionine¿the sole dietary precursor of homocysteine¿may raise plasma tHcy concentrations. Objectives: We studied

Methods and results of reconstruction of 131I concentration in milk from total beta-activity measurements in Belarus after Chernobyl

International Nuclear Information System (INIS)

Savkin, Mikhail; Shinkarev, Sergey; Titov, Alexey

2008-01-01

Full text: During the first few weeks following the Chernobyl accident a large scale monitoring of radioactive contamination of foodstuffs locally produced was carried out in the most contaminated areas of Belarus. Due to a lack of spectrometric instruments, radiometric devices (DP-100) were used for beta activity measurements mostly of milk and milk products. Because the intake of 131 I with milk was the main contributor of the thyroid dose for the Belarus population, it is very important to reconstruct levels of 131 I in milk for Belarus settlements. The purpose of the paper is to present the methods and results of assessing the 13I concentration in milk based on historical records of total-beta activity measurements carried out in April-June 1986 in Belarus. The results of reconstruction of the 131 I concentration in milk will be used in on-going epidemiologic studies of a cohort of Belarus children. About 20,000 total-beta activity measurements were used in the analysis; for about 50% of those, the measurement result exceeded the minimum detectable activity. Estimates of 131 I concentration in milk at the date of sampling and of time-integrated milk concentrations were reconstructed for 482 settlements in Gomel Oblast and for 100 settlements in Mogilev Oblast, the most contaminated areas in Belarus, where at least one milk measurement was available. The assessment of the 131 I concentrations in milk involved: 1) An analysis of the calibration coefficients of the detectors for radionuclides available in milk (the main radionuclides were 131 I, 132 4Cs, 137 Cs, 89 Sr, 90 Sr); and 2) An assessment of the relative activity distribution of those radionuclides in milk. Only measurements made before 21 May 1986 were considered to be reliable, as the measurements conducted late May and in June were found to be unreliable because of the decrease in 131 I concentrations and the growing influence of other radionuclides with longer half-lives. Analysis of multiple

Plasma concentrations of fentanyl with subcutaneous infusion in palliative care patients.

OpenAIRE

Miller, R S; Peterson, G M; Abbott, F; Maddocks, I; Parker, D; McLean, S

1995-01-01

1. Plasma concentrations of fentanyl were measured by g.c. in 20 patients (median age: 75 years and range: 54-86 years; eight females) in palliative care receiving the drug by continuous s.c. infusion (median rate: 1200 micrograms day-1 and range: 100-5000 micrograms day-1). 2. The infusion rate was significantly related to the duration of therapy (Spearman rho = 0.56, P < 0.05). The total steady-state plasma concentrations of fentanyl ranged between 0.1 and 9 ng ml-1, with a median of 1 ng m...

Concentration of airborne Staphylococcus aureus (MRSA and MSSA), total bacteria, and endotoxins in pig farms.

Science.gov (United States)

Masclaux, Frederic G; Sakwinska, Olga; Charrière, Nicole; Semaani, Eulalia; Oppliger, Anne

2013-06-01

Pigs are very often colonized by Staphylococcus aureus and transmission of such pig-associated S. aureus to humans can cause serious medical, hygiene, and economic problems. The transmission route of zoonotic pathogens colonizing farm animals to humans is not well established and bioaerosols could play an important role. The aim of this study was to assess the potential occupational risk of working with S. aureus-colonized pigs in Switzerland. We estimated the airborne contamination by S. aureus in 37 pig farms (20 nursery and 17 fattening units; 25 in summer, 12 in winter). Quantification of total airborne bacterial DNA, airborne Staphylococcus sp. DNA, fungi, and airborne endotoxins was also performed. In this experiment, the presence of cultivable airborne methicillin-resistant S. aureus (MRSA) CC398 in a pig farm in Switzerland was reported for the first time. Airborne methicillin-sensitive S. aureus (MSSA) was found in ~30% of farms. The average airborne concentration of DNA copy number of total bacteria and Staphylococcus sp. measured by quantitative polymerase chain reaction was very high, respectively reaching values of 75 (± 28) × 10(7) and 35 (± 9.8) × 10(5) copy numbers m(-3) in summer and 96 (± 19) × 10(8) and 40 (± 12) × 10(6) copy numbers m(-3) in winter. Total mean airborne concentrations of endotoxins (1298 units of endotoxin m(-3)) and fungi (5707 colony-forming units m(-3)) exceeded the Swiss recommended values and were higher in winter than in summer. In conclusion, Swiss pig farmers will have to tackle a new emerging occupational risk, which could also have a strong impact on public health. The need to inform pig farmers about biological occupational risks is therefore crucial.

SU-F-19A-08: Optimal Time Release Schedule of In-Situ Drug Release During Permanent Prostate Brachytherapy

International Nuclear Information System (INIS)

Cormack, R; Ngwa, W; Makrigiorgos, G; Tangutoori, S; Rajiv, K; Sridhar, S

2014-01-01

Purpose: Permanent prostate brachytherapy spacers can be used to deliver sustained doses of radiosentitizing drug directly to the target, in order to enhance the radiation effect. Implantable nanoplatforms for chemo-radiation therapy (INCeRTs) have a maximum drug capacity and can be engineered to control the drug release schedule. The optimal schedule for sensitization during continuous low dose rate irradiation is unknown. This work studies the optimal release schedule of drug for both traditional sensitizers, and those that work by suppressing DNA repair processes. Methods: Six brachytherapy treatment plans were used to model the anatomy, implant geometry and calculate the spatial distribution of radiation dose and drug concentrations for a range of drug diffusion parameters. Three state partial differential equations (cells healthy, damaged or dead) modeled the effect of continuous radiation (radiosensitivities α,β) and cellular repair (time tr) on a cell population. Radiosensitization was modeled as concentration dependent change in α,β or tr which with variable duration under the constraint of fixed total drug release. Average cell kill was used to measure effectiveness. Sensitization by means of both enhanced damage and reduced repair were studied. Results: Optimal release duration is dependent on the concentration of radiosensitizer compared to the saturation concentration (csat) above which additional sensitization does not occur. Long duration drug release when enhancing α or β maximizes cell death when drug concentrations are generally over csat. Short term release is optimal for concentrations below saturation. Sensitization by suppressing repair has a similar though less distinct trend that is more affected by the radiation dose distribution. Conclusion: Models of sustained local radiosensitization show potential to increase the effectiveness of radiation in permanent prostate brachytherapy. INCeRTs with high drug capacity produce the greatest

Spectrophotometric Method for the Determination of Two Coformulated Drugs with Highly Different Concentrations. Application on Vildagliptin and Metformin Hydrochloride

Science.gov (United States)

Zaazaa, H. E.; Elzanfaly, E. S.; Soudi, A. T.; Salem, M. Y.

2016-03-01

A new smart simple validated spectrophotometric method was developed for the determination of two drugs one of which is in a very low concentration compared to the other. The method is based on spiking and dilution then simple mathematical manipulation of the absorbance spectra. This method was applied for the determination of a binary mixture of vildagliptin and metformin hydrochloride in the ratio 50:850 in laboratory prepared mixtures containing both drugs in this ratio and in pharmaceutical dosage form with good recoveries. The developed method was validated according to ICH guidelines and can be used for routine quality control testing.

Changes in serum concentrations of total and free testosterone in young and middle-aged men

International Nuclear Information System (INIS)

Wang Guohong; Xu Ruiji; Zhang Zhongshu

2011-01-01

To determine changes in serum concentrations of total and free testosterone in young and middle-aged men.the healthy men (n=126) were divided 20-29 yr, 30-39 yr and 40-49 yr three groups,their serum levels of total testosterone (T), free testosterone (FT), luteinizing hormone (LH), follicle-stimulating hormone (FSH), sex hormone binding globulin (SHBG) and estradiol (E2) were detected. The results were statically analyzed. The results showed that the levels of serum T and FT was found significantly decreased in 30-39 yr group than in 20-29 yr group (15.06±13 nmol/L vs 20.41±86 nmol/L, P<0.01; 9.36±95 pg/L vs 11.48±88 pg/L, P<0.05; respectively). There were young trends that age-related decline in androgen levels. (authors)

Control of drug releasing from biodegradable polymer drug delivery system by gamma-ray irradiation

International Nuclear Information System (INIS)

Yoshioka, Sumie; Aso, Yukio; Kojima, Shigeo

1999-01-01

In order to introduce the drug to the target organ, we developed a gel to control the drug releasing velocity by response to change of temperature by means of γ-ray irradiation to gelatin-GMA modified dextran mixture aqueous solution. A certain level of molecular weight of drug is necessary. The response to the temperature (change of drug releasing velocity) was affected by the concentration of gelatin and the modification rate of GMA. The Higuchi equation was applied to the releasing of β-galactosidase from gelatin-dextran gel and the releasing velocity was calculated. The releasing velocity decreased with increasing GMA modification rate at 37degC and 15degC. The releasing velocity of β-galactosidase decreased with increasing the concentration of gelatin at 15degC, but the velocity increased with increasing the concentration at 37degC. These results indicated that the good drug releasing conditions are obtained by controlling the GMA modification rate and the concentration of gelatin. (S.Y.)

Pill content, dose and resulting plasma concentrations of 3,4-methylendioxymethamphetamine (MDMA) in recreational 'ecstasy' users.

Science.gov (United States)

Morefield, Kate M; Keane, Michael; Felgate, Peter; White, Jason M; Irvine, Rodney J

2011-07-01

To improve our understanding of the pharmacology of 'ecstasy' in recreational environments; in particular, to describe the composition of ecstasy pills, patterns of ecstasy use and the relationship between dose of 3,4-methylendioxymethamphetamine (MDMA) and resulting plasma concentrations. A naturalistic observational study of 56 experienced 'ecstasy' users in recreational settings in Australia. Drug use patterns (number of pills consumed, other drugs consumed). drug content of pills and resultant plasma concentrations of MDMA and related drugs were assessed by gas chromatography/mass spectrometry (GC/MS). Ecstasy pills generally contained MDMA, but this was often combined with other drugs such as 3,4-ethylendioxyethylamphetamine (MDEA) and methamphetamine. The dose of MDMA per pill ranged from 0 to 245 mg and users consumed from one-half to five pills, with the total dose consumed ranging up to 280 mg. Plasma concentrations of MDMA increased with number of pills consumed and cumulative MDMA dose. Use of larger numbers of pills was associated with extended exposure to the drug. MDMA is the major active drug in ecstasy pills, but there is a high degree of variation in doses. Use of multiple pills over the course of one session is common and results in a sustained increase in MDMA plasma concentrations over a number of hours. This is likely to lead to a much greater exposure of the brain to MDMA than would be predicted from controlled single-dose pharmacokinetic studies. © 2011 The Authors, Addiction © 2011 Society for the Study of Addiction.

Total and methyl mercury concentrations in sediment and water of a constructed wetland in the Athabasca Oil Sands Region.

Science.gov (United States)

Oswald, Claire J; Carey, Sean K

2016-06-01

In the Athabasca Oil Sands Region in northeastern Alberta, Canada, oil sands operators are testing the feasibility of peatland construction on the post-mining landscape. In 2009, Syncrude Canada Ltd. began construction of the 52 ha Sandhill Fen pilot watershed, including a 15 ha, hydrologically managed fen peatland built on sand-capped soft oil sands tailings. An integral component of fen reclamation is post-construction monitoring of water quality, including salinity, fluvial carbon, and priority pollutant elements. In this study, the effects of fen reclamation and elevated sulfate levels on mercury (Hg) fate and transport in the constructed system were assessed. Total mercury (THg) and methylmercury (MeHg) concentrations in the fen sediment were lower than in two nearby natural fens, which may be due to the higher mineral content of the Sandhill Fen peat mix and/or a loss of Hg through evasion during the peat harvesting, stockpiling and placement processes. Porewater MeHg concentrations in the Sandhill Fen typically did not exceed 1.0 ng L(-1). The low MeHg concentrations may be a result of elevated porewater sulfate concentrations (mean 346 mg L(-1)) and an increase in sulphide concentrations with depth in the peat, which are known to suppress MeHg production. Total Hg and MeHg concentrations increased during a controlled mid-summer flooding event where the water table rose above the ground surface in most of the fen. The Hg dynamics during this event showed that hydrologic fluctuations in this system exacerbate the release of THg and MeHg downstream. In addition, the elevated SO4(2-) concentrations in the peat porewaters may become a problem with respect to downstream MeHg production once the fen is hydrologically connected to a larger wetland network that is currently being constructed. Copyright © 2016 Elsevier Ltd. All rights reserved.

A Comparison of Concentrations of Sodium and Related Nutrients (Potassium, Total Dietary Fiber, Total and Saturated Fat, and Total Sugar) in Private-Label and National Brands of Popular, Sodium-Contributing, Commercially Packaged Foods in the United States.

Science.gov (United States)

Ahuja, Jaspreet K C; Pehrsson, Pamela R; Cogswell, Mary

2017-05-01

Private-label brands account for about one in four foods sold in US supermarkets. They provide value to consumers due to their low cost. We know of no US studies comparing the nutrition content of private-label products with corresponding national brand products. The objective was to compare concentrations of sodium and related nutrients (potassium, total dietary fiber, total and saturated fat, and total sugar) in popular sodium-contributing, commercially packaged foods by brand type (national or private-label brand). During 2010 to 2014, the Nutrient Data Laboratory of the US Department of Agriculture obtained 1,706 samples of private-label and national brand products from up to 12 locations nationwide and chemically analyzed 937 composites for sodium and related nutrients. The samples came from 61 sodium-contributing, commercially packaged food products for which both private-label and national brands were among the top 75% to 80% of brands for US unit sales. In this post hoc comparative analysis, the authors assigned a variable brand type (national or private label) to each composite and determined mean nutrient contents by brand type overall and by food product and type. The authors tested for significant differences (Pfoods sampled, differences between brand types were not statistically significant for any of the nutrients studied. However, differences in both directions exist for a few individual food products and food categories. Concentrations of sodium and related nutrients (potassium, total dietary fiber, total and saturated fat, and total sugar) do not differ systematically between private-label and national brands, suggesting that brand type is not a consideration for nutritional quality of foods in the United States. The study data provide public health officials with baseline nutrient content by brand type to help focus US sodium-reduction efforts. Published by Elsevier Inc.

Pharmacokinetic-pharmacodynamic modeling of antipsychotic drugs in patients with schizophrenia Part I : The use of PANSS total score and clinical utility

NARCIS (Netherlands)

Reddy, Venkatesh Pilla; Kozielska, Magdalena; Suleiman, Ahmed Abbas; Johnson, Martin; Vermeulen, An; Liu, Jing; de Greef, Rik; Groothuis, Geny M. M.; Danhof, Meindert; Proost, Johannes H.

Background: To develop a pharmacokinetic-pharmacodynamic (PK-PD) model using individual-level data of Positive and Negative Syndrome Scale (PANSS) total score to characterize the antipsychotic drug effect taking into account the placebo effect and dropout rate. In addition, a clinical utility (CU)

The J-shape association of ethanol intake with total homocysteine concentrations: the ATTICA study

Directory of Open Access Journals (Sweden)

Pitsavos Christos

2004-10-01

Full Text Available Abstract Background Epidemiological studies suggest a non-monotonic effect of alcohol consumption on cardiovascular risk, while there is strong evidence concerning the involvement of homocysteine levels on thrombosis. The aim of this work was to evaluate the association between usual ethanol consumption and homocysteine levels, in cardiovascular disease free adults. Methods From May 2001 to December 2002 we randomly enrolled 1514 adult men and 1528 women, without any evidence of cardiovascular disease, stratified by age – gender (census 2001, from the greater area of Athens, Greece. Among the variables ascertained we measured the daily ethanol consumption and plasma homocysteine concentrations. Results Data analysis revealed a J-shape association between ethanol intake (none, 48 gr per day and total homocysteine levels (mean ± standard deviation among males (13 ± 3 vs. 11 ± 3 vs. 14 ± 4 vs. 18 ± 5 vs. 19 ± 3 μmol/L, respectively, p Conclusion We observed a J-shape relationship between homocysteine concentrations and the amount of ethanol usually consumed.

Total and size-resolved particle number and black carbon concentrations in urban areas near Schiphol airport (the Netherlands)

NARCIS (Netherlands)

Keuken, M.P.; Moerman, M.; Zandveld, P.; Henzing, J.S.; Hoek, G.

2015-01-01

The presence of black carbon, and size-resolved and total particle number concentrations (PNC) were investigated in the vicinity of Schiphol airport in the Netherlands, the fourth busiest airport in Europe. Continuous measurements were conducted between March and May 2014at Adamse Bos, located 7km

Human drug metabolism: an introduction

National Research Council Canada - National Science Library

Coleman, Michael D

2010-01-01

... metabolism and its impact on patient welfare. After underlining the relationship between efficacy, toxicity and drug concentration, the book then considers how metabolizing systems operate and how they impact upon drug concentration...

Changes of Serum Total and Free Testosterone Concentrations in Male Chronic Hemodialysis Patients with Secondary Hyperparathyroidism in Response to Cinacalcet Treatment

Directory of Open Access Journals (Sweden)

Piotr Kuczera

2016-01-01

Full Text Available Background/Aims: Calcium sensing receptor (CaSR is expressed, among others also in testis. Cinacalcet binds to the CaSR, increases sensitivity of CaSR to serum calcium and is used in the treatment of secondary hyperparathyroidism (sHPT in chronic hemodialysis patients (HDP. In most of male HDP, serum testosterone concentration is lower than in healthy males. The aim of this study was to assess the influence of six-month treatment with cinacalcet on the serum total and free testosterone concentration in male HDP with sHPT. Methods: 38 male, hemodialysed CKD patients with sHPT (PTH>300 pg/ml were enrolled into the study. In each patient serum PTH, total testosterone (TT and free testosterone (FT concentrations were assessed before the first dose of cinacalcet and then after 3 and 6 months of treatment. The results are presented as means with 95% confidence interval. Results: In 33 patients who completed the study cinacalcet treatment caused significant decrease of serum PTH from 1143 pg/ml (828 - 1458 pg/ml at the baseline, to 809 pg/ml (487 - 1132pg/ml after 3 month of treatment (p = 0.002, and to 607 pg/ml (281 - 934pg/ml; p Conclusion: Treatment with cinacalcet decreases serum total and free testosterone concentration in male hemodialysed patients with chronic kidney disease and secondary hyperparathyroidism.

Biological and life-history factors affecting total mercury concentrations in Arctic charr from Heintzelman Lake, Ellesmere Island, Nunavut

International Nuclear Information System (INIS)

Velden, Shannon van der; Reist, James D.; Babaluk, John A.; Power, Michael

2012-01-01

A snapshot sample of Arctic charr (Salvelinus alpinus) from Heintzelman Lake (81°42′N, 66°56′W), Ellesmere Island, Canada was used to elucidate the biological and life-history factors potentially influencing individual total mercury (THg) concentrations. Migratory history was significant, with anadromous fish having a lower mean THg concentration (64 μg/kg ww) than the non-anadromous Arctic charr (117 μg/kg ww). The increase in individual THg concentration with age was shown to be independent of length-at-age when large and small individuals within the same age groups were compared. Similarly, the diets of individual Arctic charr were comparable regardless of size, and there was no apparent ontogenetic shift in diet that could explain differences in length-at-age or THg concentration among fast- and slow-growing groups of fish (i.e., fish of the same age but differing sizes). Maturity state was also not related to THg concentration, but appears to be related to differences in length-at-age, with slow-growing fish allocating more energy to reproduction than fast-growing conspecifics. The differences in THg concentration among individual Arctic charr were best explained by fish age. We suggest that the increase in mercury concentration with age can be altered by a shift in diet (e.g., to piscivory) or habitat (e.g., anadromy), but is otherwise unaffected by changes in size or length-at-age. -- Highlights: ► Total mercury concentrations ([THg]) were measured in Arctic charr from a single lake in the Canadian high Arctic. ► Anadromous Arctic charr had a significantly lower mean [THg] (64 μg/kg ww) than the non-anadromous fish (117 μg/kg ww). ► Length-at-age (i.e., average somatic growth rate) was not related to mean [THg] when same-age groups were compared. ► Prey resource use, determined by δ 13 C and δ 15 N isotopes and gut contents, was similar among fast- and slow-growing fish. ► Maturity state was not related to [THg], but the slow

Concentration, size, and density of total suspended particulates at the air exhaust of concentrated animal feeding operations.

Science.gov (United States)

Yang, Xufei; Lee, Jongmin; Zhang, Yuanhui; Wang, Xinlei; Yang, Liangcheng

2015-08-01

Total suspended particulate (TSP) samples were seasonally collected at the air exhaust of 15 commercial concentrated animal feeding operations (CAFOs; including swine finishing, swine farrowing, swine gestation, laying hen, and tom turkey) in the U.S. Midwest. The measured TSP concentrations ranged from 0.38 ± 0.04 mg m⁻³ (swine gestation in summer) to 10.9 ± 3.9 mg m⁻³ (tom turkey in winter) and were significantly affected by animal species, housing facility type, feeder type (dry or wet), and season. The average particle size of collected TSP samples in terms of mass median equivalent spherical diameter ranged from 14.8 ± 0.5 µm (swine finishing in winter) to 30.5 ± 2.0 µm (tom turkey in summer) and showed a significant seasonal effect. This finding affirmed that particulate matter (PM) released from CAFOs contains a significant portion of large particles. The measured particle size distribution (PSD) and the density of deposited particles (on average 1.65 ± 0.13 g cm⁻³) were used to estimate the mass fractions of PM10 and PM2.5 (PM ≤ 10 and ≤ 2.5 μm, respectively) in the collected TSP. The results showed that the PM10 fractions ranged from 12.7 ± 5.1% (tom turkey) to 21.1 ± 3.2% (swine finishing), whereas the PM2.5 fractions ranged from 3.4 ± 1.9% (tom turkey) to 5.7 ± 3.2% (swine finishing) and were smaller than 9.0% at all visited CAFOs. This study applied a filter-based method for PSD measurement and deposited particles as a surrogate to estimate the TSP's particle density. The limitations, along with the assumptions adopted during the calculation of PM mass fractions, must be recognized when comparing the findings to other studies.

Repurposing salicylanilide anthelmintic drugs to combat drug resistant Staphylococcus aureus.

Science.gov (United States)

Rajamuthiah, Rajmohan; Fuchs, Beth Burgwyn; Conery, Annie L; Kim, Wooseong; Jayamani, Elamparithi; Kwon, Bumsup; Ausubel, Frederick M; Mylonakis, Eleftherios

2015-01-01

Staphylococcus aureus is a Gram-positive bacterium that has become the leading cause of hospital acquired infections in the US. Repurposing Food and Drug Administration (FDA) approved drugs for antimicrobial therapy involves lower risks and costs compared to de novo development of novel antimicrobial agents. In this study, we examined the antimicrobial properties of two commercially available anthelmintic drugs. The FDA approved drug niclosamide and the veterinary drug oxyclozanide displayed strong in vivo and in vitro activity against methicillin resistant S. aureus (minimum inhibitory concentration (MIC): 0.125 and 0.5 μg/ml respectively; minimum effective concentration: ≤ 0.78 μg/ml for both drugs). The two drugs were also effective against another Gram-positive bacteria Enterococcus faecium (MIC 0.25 and 2 μg/ml respectively), but not against the Gram-negative species Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacter aerogenes. The in vitro antimicrobial activity of niclosamide and oxyclozanide were determined against methicillin, vancomycin, linezolid or daptomycin resistant S. aureus clinical isolates, with MICs at 0.0625-0.5 and 0.125-2 μg/ml for niclosamide and oxyclozanide respectively. A time-kill study demonstrated that niclosamide is bacteriostatic, whereas oxyclozanide is bactericidal. Interestingly, oxyclozanide permeabilized the bacterial membrane but neither of the anthelmintic drugs exhibited demonstrable toxicity to sheep erythrocytes. Oxyclozanide was non-toxic to HepG2 human liver carcinoma cells within the range of its in vitro MICs but niclosamide displayed toxicity even at low concentrations. These data show that the salicylanilide anthelmintic drugs niclosamide and oxyclozanide are suitable candidates for mechanism of action studies and further clinical evaluation for treatment of staphylococcal infections.

Impact of orphan drugs on Latvian budget.

Science.gov (United States)

Logviss, Konstantins; Krievins, Dainis; Purvina, Santa

2016-05-11

Number of orphan medicinal products on the market and number of rare disease patients, taking these usually expensive products, are increasing. As a result, budget impact of orphan drugs is growing. This factor, along with the cost-effectiveness of orphan drugs, is often considered in the reimbursement decisions, directly affecting accessibility of rare disease therapies. The current study aims to assess the budget impact of orphan drugs in Latvia. Our study covered a 5-year period, from 2010 to 2014. Impact of orphan drugs on Latvian budget was estimated from the National Health Service's perspective. It was calculated in absolute values and relative to total pharmaceutical market and total drug reimbursement budget. A literature review was performed for comparison with other European countries. Orphan drug annual expenditure ranged between EUR 2.065 and 3.065 million, with total 5-year expenditure EUR 12.467 million. It constituted, on average, 0.84 % of total pharmaceutical market and 2.14 % of total drug reimbursement budget, respectively. Average annual per patient expenditures varied widely, from EUR 1 534 to EUR 580 952. The most costly treatment was enzyme replacement therapy (Elaprase) for MPS II. Glivec had the highest share (34 %) of the total orphan drug expenditure. Oncological drugs represented more than a half of the total orphan drug expenditure, followed by drugs for metabolic and endocrine conditions and medicines for cardiopulmonary diseases. Three indications: Ph+ CML, MPS II, and PAH accounted for nearly 90 % of the total orphan drug expenditure. Budget impact of orphan drugs in Latvia is very small. It increased slightly over a period of five years, due to the slight increase in the number of patients and the number of orphan drugs reimbursed. Current Latvian drug reimbursement system is not sufficient for most orphan drugs.

Target-mediated drug disposition model for drugs with two binding sites that bind to a target with one binding site.

Science.gov (United States)

Gibiansky, Leonid; Gibiansky, Ekaterina

2017-10-01

The paper extended the TMDD model to drugs with two identical binding sites (2-1 TMDD). The quasi-steady-state (2-1 QSS), quasi-equilibrium (2-1 QE), irreversible binding (2-1 IB), and Michaelis-Menten (2-1 MM) approximations of the model were derived. Using simulations, the 2-1 QSS approximation was compared with the full 2-1 TMDD model. As expected and similarly to the standard TMDD for monoclonal antibodies (mAb), 2-1 QSS predictions were nearly identical to 2-1 TMDD predictions, except for times of fast changes following initiation of dosing, when equilibrium has not yet been reached. To illustrate properties of new equations and approximations, several variations of population PK data for mAbs with soluble (slow elimination of the complex) or membrane-bound (fast elimination of the complex) targets were simulated from a full 2-1 TMDD model and fitted to 2-1 TMDD models, to its approximations, and to the standard (1-1) QSS model. For a mAb with a soluble target, it was demonstrated that the 2-1 QSS model provided nearly identical description of the observed (simulated) free drug and total target concentrations, although there was some minor bias in predictions of unobserved free target concentrations. The standard QSS approximation also provided a good description of the observed data, but was not able to distinguish between free drug concentrations (with no target attached and both binding site free) and partially bound drug concentrations (with one of the binding sites occupied by the target). For a mAb with a membrane-bound target, the 2-1 MM approximation adequately described the data. The 2-1 QSS approximation converged 10 times faster than the full 2-1 TMDD, and its run time was comparable with the standard QSS model.

Senegalese artisanal gold mining leads to elevated total mercury and methylmercury concentrations in soils, sediments, and rivers

Directory of Open Access Journals (Sweden)

Jacqueline R. Gerson

2018-01-01

Full Text Available The largest source of global mercury (Hg anthropogenic inputs to the environment is derived from artisanal and small-scale gold mining (ASGM activities in developing countries. While our understanding of global Hg emissions from ASGM is growing, there is limited empirical documentation about the levels of total mercury (THg and methylmercury (MeHg contamination near ASGM sites. We measured THg and MeHg concentrations in soil (n = 119, sediment (n = 22, and water (n = 25 from four active ASGM villages and one non-ASGM reference village in Senegal, West Africa. Nearly all samples had THg and MeHg concentrations that exceeded the reference village concentrations and USEPA regulatory standards. The highest median THg concentrations were found in huts where mercury-gold amalgams were burned (7.5 μg/g, while the highest median MeHg concentrations and percent Hg as MeHg were found in river sediments (4.2 ng/g, 0.41%. Median river water concentrations of THg and MeHg were also elevated compared to values at the reference site (22 ng THg/L, 0.037 ng MeHg/L in ASGM sites. This study provides direct evidence that Hg from ASGM is entering both the terrestrial and aquatic ecosystems where it is converted in soils, sediment, and water to the neurotoxic and bioavailable form of MeHg.

Influences of chia flour and the concentration of total solids on the characteristics of ‘dulce de leche’ from goat milk

Directory of Open Access Journals (Sweden)

Marcia Alves CHAVES

2018-03-01

Full Text Available Abstract A factorial categorical design totalling six treatments was applied to investigate the influence of the substitution of corn starch with whole and partially defatted chia flour under the technical characteristics (centesimal composition, instrumental analyses, and sensory evaluation and nutritional disorders (composition of fatty acids and index of the nutritional quality of the lipid fraction of ‘dulce de leche’ concentrated to 72 and 78 °B. The treatments with chia flour concentrated to 72 °B showed higher moisture content and lower compression force, and when the concentration range increased to 78 °B, the levels of total lipids amounted up to 1.40 times when compared to treatment with corn starch. The polyunsaturated fatty acids, particularly omega-3 and omega-6 levels, were higher in treatments with chia flour on both tracks of concentration, allowing a reduction in the atherogenic index and thrombogenic index effects and the n-6/n-3 ratio. The treatments of ‘dulce de leche’ with a lower concentration of soluble solids obtained greater acceptance and consumer purchase intention. The application of whole chia flour in small proportions and in the concentration of 72 °B was the most appropriate under the studied conditions, showing improvement in the nutritional quality and with good technical aspects of candy made with goat milk.

Understanding drugs in breast cancer through drug sensitivity screening.

Science.gov (United States)

Uhr, Katharina; Prager-van der Smissen, Wendy J C; Heine, Anouk A J; Ozturk, Bahar; Smid, Marcel; Göhlmann, Hinrich W H; Jager, Agnes; Foekens, John A; Martens, John W M

2015-01-01

With substantial numbers of breast tumors showing or acquiring treatment resistance, it is of utmost importance to develop new agents for the treatment of the disease, to know their effectiveness against breast cancer and to understand their relationships with other drugs to best assign the right drug to the right patient. To achieve this goal drug screenings on breast cancer cell lines are a promising approach. In this study a large-scale drug screening of 37 compounds was performed on a panel of 42 breast cancer cell lines representing the main breast cancer subtypes. Clustering, correlation and pathway analyses were used for data analysis. We found that compounds with a related mechanism of action had correlated IC50 values and thus grouped together when the cell lines were hierarchically clustered based on IC50 values. In total we found six clusters of drugs of which five consisted of drugs with related mode of action and one cluster with two drugs not previously connected. In total, 25 correlated and four anti-correlated drug sensitivities were revealed of which only one drug, Sirolimus, showed significantly lower IC50 values in the luminal/ERBB2 breast cancer subtype. We found expected interactions but also discovered new relationships between drugs which might have implications for cancer treatment regimens.

Total allowable concentrations of monomeric inorganic aluminum and hydrated aluminum silicates in drinking water.

Science.gov (United States)

Willhite, Calvin C; Ball, Gwendolyn L; McLellan, Clifton J

2012-05-01

Maximum contaminant levels are used to control potential health hazards posed by chemicals in drinking water, but no primary national or international limits for aluminum (Al) have been adopted. Given the differences in toxicological profiles, the present evaluation derives total allowable concentrations for certain water-soluble inorganic Al compounds (including chloride, hydroxide, oxide, phosphate and sulfate) and for the hydrated Al silicates (including attapulgite, bentonite/montmorillonite, illite, kaolinite) in drinking water. The chemistry, toxicology and clinical experience with Al materials are extensive and depend upon the particular physical and chemical form. In general, the water solubility of the monomeric Al materials depends on pH and their water solubility and gastrointestinal bioavailability are much greater than that of the hydrated Al silicates. Other than Al-containing antacids and buffered aspirin, food is the primary source of Al exposure for most healthy people. Systemic uptake of Al after ingestion of the monomeric salts is somewhat greater from drinking water (0.28%) than from food (0.1%). Once absorbed, Al accumulates in bone, brain, liver and kidney, with bone as the major site for Al deposition in humans. Oral Al hydroxide is used routinely to bind phosphate salts in the gut to control hyperphosphatemia in people with compromised renal function. Signs of chronic Al toxicity in the musculoskeletal system include a vitamin D-resistant osteomalacia (deranged membranous bone formation characterized by accumulation of the osteoid matrix and reduced mineralization, reduced numbers of osteoblasts and osteoclasts, decreased lamellar and osteoid bands with elevated Al concentrations) presenting as bone pain and proximal myopathy. Aluminum-induced bone disease can progress to stress fractures of the ribs, femur, vertebrae, humerus and metatarsals. Serum Al ≥100 µg/L has a 75-88% positive predictive value for Al bone disease. Chronic Al

A mechanistic compartmental model for total antibody uptake in tumors.

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Thurber, Greg M; Dane Wittrup, K

2012-12-07

Antibodies are under development to treat a variety of cancers, such as lymphomas, colon, and breast cancer. A major limitation to greater efficacy for this class of drugs is poor distribution in vivo. Localization of antibodies occurs slowly, often in insufficient therapeutic amounts, and distributes heterogeneously throughout the tumor. While the microdistribution around individual vessels is important for many therapies, the total amount of antibody localized in the tumor is paramount for many applications such as imaging, determining the therapeutic index with antibody drug conjugates, and dosing in radioimmunotherapy. With imaging and pretargeted therapeutic strategies, the time course of uptake is critical in determining when to take an image or deliver a secondary reagent. We present here a simple mechanistic model of antibody uptake and retention that captures the major rates that determine the time course of antibody concentration within a tumor including dose, affinity, plasma clearance, target expression, internalization, permeability, and vascularization. Since many of the parameters are known or can be estimated in vitro, this model can approximate the time course of antibody concentration in tumors to aid in experimental design, data interpretation, and strategies to improve localization. Copyright © 2012 Elsevier Ltd. All rights reserved.

Prediction of purine derivatives, creatinine and total nitrogen concentrations in urine by FT-Near-lnfrared Reflectance spectroscopy (FT-NIR)

International Nuclear Information System (INIS)

Susmel, P.; Piani, B.; Toso, B.; Stefanon, B.

2004-01-01

The objective of this study was to provide an alternative method for the determination of purine derivatives (PD, which include allantoin, uric acid, hypoxanthine and xanthine), creatinine and total nitrogen (N) concentrations in urine. About 180 urine samples from cattle, buffaloes and rabbit were collected and analyzed for PD by HPLC, creatinine by spectrophotometry and N by Kjeldahl method. The urine samples were then analyzed by Fourier Transformed Near Infrared Reflectance Spectroscopy (FT-NIR) to find conformity between this technique and the HPLC and colorimetric methods. FT-NIR can predict allantoin, uric acid, hypoxanthine, xanthine, creatinine, total N and sum of N in both allantoin and uric acid with a satisfactory level of accuracy: the determination coefficient (r 2 ) of validation ranged from 0.888% for uric acid to 0.982% for total N. The coefficients of determination for allantoin, creatinine and sum of N in both allantoin and uric acid were 0.92, 0.894 and 0.90%, respectively. Hypoxanthine and xanthine in urine samples were not detectable by NIRS, probably because of their low concentrations, and therefore they were not considered for instrumental calibration. (author)

Use of the Vettest 8008 and refractometry for determination of total protein, albumin, and globulin concentrations in feline effusions.

Science.gov (United States)

Papasouliotis, Kostas; Murphy, Kate; Dodkin, Steve; Torrance, Andy G

2002-01-01

Pleural and peritoneal effusion is a common clinical finding in feline practice. Determination of fluid albumin (ALB) and globulin (GLOB) concentrations in addition to total protein (TP) concentration can be helpful in diagnosing or ruling out certain diseases in cats, especially feline infectious peritonitis (FIP). The objective of this study was to compare effusion TP, ALB, and GLOB results obtained by a refractometer and a bench-top dry chemistry analyzer with those results obtained by a reference method. Twenty-six pleural and 14 peritoneal effusion samples were analyzed from 40 cats with various diseases. TP and ALB concentrations were determined by a reference automated wet chemistry analyzer (Kone Specific, Kone Instruments, Espoo, Finland), a bench-top dry chemistry analyzer (Vettest 8008, IDEXX Laboratories Ltd, Chalfont St Peter, UK), and a refractometer (Atago SPR-T2, Atago Co, Tokyo, Japan). GLOB, albumin to globulin (A/G) ratio, and globulins as a percentage of total proteins (GLOB%) were calculated. Results were analyzed by paired t tests, difference plots, and Deming s regression analysis. Correlation coefficients (r) for TP with Vettest versus Kone and refractometer versus Kone methods were.97 and.94, respectively. GLOB and GLOB% values were significantly higher and A/G ratios were significantly lower with Vettest versus Kone methods. Correlation coefficients for ALB, GLOB, GLOB% and A/G ratio with Vettest versus Kone methods were.86,.93,.82, and.73, respectively. Although correlation with other methods was good, the refractometer underestimated TP concentrations in 3 samples. The refractometer is an acceptable method for determination of TP concentration in feline effusions. The Vettest 8008 also is an acceptable method for the determination of TP and ALB concentrations, however, calculated A/G ratios obtained with the Vettest are unacceptable.

Comparison of concentrations of drugs between blood samples with and without fluoride additive-important findings for Δ9-tetrahydrocannabinol and amphetamine.

Science.gov (United States)

Wiedfeld, Christopher; Krueger, Julia; Skopp, Gisela; Musshoff, Frank

2018-02-17

Fluoride is a common stabilizing agent in forensic toxicology to avoid the frequent problem of degradation of drugs in blood samples especially described for cocaine. In cases only samples with addition of fluoride are available, it is a crucial question if also concentrations of common drugs other than cocaine (amphetamines, opiates and cannabinoids) are affected by fluoride. So far, there are only rare literature data available on discrepant results especially for Δ 9 -tetrahydrocannabinol (THC). In this study, comparative analysis of positive tested paired routine plasma/serum samples (n = 375), collected at the same time point (one device with and one without fluoride), was carried out with special focus on cannabinoids. Samples were measured with validated routine liquid chromatography-tandem mass spectrometry methods for THC, 11-hydroxy-THC (THC-OH), 11-nor-9-carboxy-THC (THC-COOH), cocaine, benzoylecgonine, ecgonine methyl ester, morphine, codeine, amphetamine, methamphetamine, 3,4-methylenedioxymethamphetamine, 3,4-methylenedioxyamphetamine, and 3,4-methylenedioxyethylamphetamine, and results were statistically evaluated. Beside the expected stabilization effect on cocaine and the consequently reduced concentration of ecgonine methyl ester in fluoride samples, benzoylecgonine was elevated compared to respective samples without fluoride. Most importantly, new findings were significantly reduced mean concentrations of THC (- 17%), THC-OH (- 17%), and THC-COOH (- 22%) in fluoride samples. Mean amphetamine concentration was significantly higher in samples with the additive (+ 6%). For the other amphetamine type of drugs as well as for morphine and codeine, no significant differences could be seen. Whenever specified thresholds have been set, such as in most European countries, the use of different blood sample systems may result in a motorist being differently charged or prosecuted. The findings will support forensic toxicologists at the

Evaluation of the trace elements and the total mercury concentration in fishes commercialized at the Cubatao city, Sao Paulo, Brazil; Avaliavao da concentracao de elementos traco e de mercurio total em pescados comercializados na cidade de Cubatao, Estado de Sao Paulo

Energy Technology Data Exchange (ETDEWEB)

Fonseca, Barbara C.; Farias, Luciana A.; Curcho, Michel R.M.; Favaro, Debora I.T., E-mail: ba_cortopassi@hotmail.co [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil); Braga, Elisabete S., E-mail: edsbraga@usp.b [Universidade de Sao Paulo (LABNUT/USP), SP (Brazil). Inst. Oceanografico. Lab. de Nutrientes, Macronutrientes e Tracos no Oceano

2009-07-01

This paper evaluates the total Hg and the trace elements As, Br, Co, Cr and Rb concentrations in muscle of commercially important fishes at the Cubatao, Sao Paulo, Brazil, region. The following carnivore species were analysed: jew fish (Micropogonias furnieri), girl leg (Menticirrhus americanus), hake (Macrodon ancylodon), and plant eaters, sardine (Sardella braziliensis) and grey mullet (Mugil liza), representing a total of 58 samples. The analysed trace elements were determined through the neutron analysis activation (NAA) and total Hg, through the atomic absorption spectrometry with cold vapor generation (CV AAS). The analysed elements present a great concentration variation, not only among individuals of the same specie, but also among all the analysed species. The total Hg concentration were highly significant, with the predator species jew fish, girl leg and hake presenting concentrations larger than the non predator species sardine and grey mullet. Nevertheless, the content of total Hg remained bellow the limits established by the Brazilian legislation which is the 500 {mu}g kg{sup -1} for the non predator species, and the 1000 {mu}g{sup -1} for the predator species (humid weight)

Plasma concentrations of fentanyl with subcutaneous infusion in palliative care patients.

Science.gov (United States)

Miller, R S; Peterson, G M; Abbott, F; Maddocks, I; Parker, D; McLean, S

1995-12-01

1. Plasma concentrations of fentanyl were measured by g.c. in 20 patients (median age: 75 years and range: 54-86 years; eight females) in palliative care receiving the drug by continuous s.c. infusion (median rate: 1200 micrograms day-1 and range: 100-5000 micrograms day-1). 2. The infusion rate was significantly related to the duration of therapy (Spearman rho = 0.56, P Infusion rates and both total and unbound plasma concentrations of fentanyl were correlated (Spearman rho = 0.92, P infusion in the palliative care setting, which necessitates careful titration of dosage according to individual clinical response.

pH buffers for sea water media based on the total hydrogen ion concentration scale

Science.gov (United States)

Dickson, Andrew G.

1993-01-01

Published e.m.f. values measured using the cell ? where p° = 101.325 kPa, and BH + and B are the conjugate acid-base pairs of 2-aminopyridine, 2-amino-2-hydroxymethyl-1,3-propanediol (tris), tetrahydro-1,4-isoxazine (morpholine), and 2-amino-2-methyl-1, 3-propanediol (bis), have been re-evaluated to assign pH values based on the "total" hydrogen ion concentration scale to equimolal ( m =0.04 mol kg -1) buffer solutions based on these compounds. These pH values are consistent with the best available equilibrium constants for acid-base processes in sea water and such pH buffers can be used as pH calibration standards to measure accurate values for oceanic pH on the "total" hydrogen ion pH scale. In addition, the published e.m.f. results for these various amine bases have been used to calculate their respective acidity constants on this pH scale.

Effect of lipid-lowering and anti-hypertensive drugs on plasma homocysteine levels

Directory of Open Access Journals (Sweden)

Jutta Dierkes

2007-03-01

Full Text Available Jutta Dierkes, Claus Luley, Sabine WestphalInstitute of Clinical Chemistry and Biochemistry, University Hospital Magdeburg, Germany Abstract: Elevated plasma concentrations of homocysteine, a sulfur-containing amino acid, are a risk factor for coronary, cerebral and peripheral artery disease. Next to other factors, drugs used for the prevention or treatment of cardiovascular disease may modulate plasma homocysteine levels. Thus, a drug induced homocysteine increase may counteract the desired cardioprotective effect. The aim is to summarize the current knowledge on the effect of two important classes of drugs, lipid-lowering drugs and anti-hypertensive drugs, on homocysteine metabolism. Among the lipid-lowering drugs, especially the fibric acid derivatives, which are used for treatment of hypertriglyceridemia and low HDL-cholesterol, are associated with an increase of homocysteine by 20%–50%. This increase can be reduced, but not totally avoided by the addition of folic acid, vitamin B12 and B6 to fibrates. HMG-CoA reductase inhibitors (statins do not influence homocysteine concentrations substantially. The effects of nicotinic acid and n3-fatty acids on the homocysteine concentrations are less clear, more studies are necessary to clarify their influence on homocysteine. Antihypertensive drugs have also been studied with respect to homocysteine metabolism. A homocysteine increase has been shown after treatment with hydrochlorothiazide, a lowering was observed after treatment with ß-blockers, but no effect with ACE-inhibitors. The clinical significance of the homocysteine elevation by fibrates and thiazides is not clear. However, individual patients use these drugs for long time, indicating that even moderate increases may be important.Keywords: homocysteine, fibrates, diuretics, cardiovascular disease

Geographic and temporal patterns of variation in total mercury concentrations in blood of harlequin ducks and blue mussels from Alaska.

Science.gov (United States)

Savoy, Lucas; Flint, Paul; Zwiefelhofer, Denny; Brant, Heather; Perkins, Christopher; Taylor, Robert; Lane, Oksana; Hall, Jeff; Evers, David; Schamber, Jason

2017-04-15

We compared total mercury (Hg) concentrations in whole blood of harlequin ducks (Histrionicus histrionicus) sampled within and among two geographically distinct locations and across three years in southwest Alaska. Blue mussels were collected to assess correlation between Hg concentrations in locally available forage and birds. Mercury concentrations in harlequin duck blood were significantly higher at Unalaska Island (0.31±0.19 mean±SD, μg/g blood) than Kodiak Island (0.04±0.02 mean±SD, μg/g blood). We found no evidence for annual variation in blood Hg concentration between years at Unalaska Island. However, blood Hg concentration did vary among specific sampling locations (i.e., bays) at Unalaska Island. Findings from this study demonstrate harlequin ducks are exposed to environmental sources of Hg, and whole blood Hg concentrations are associated with their local food source. Copyright © 2017 Elsevier Ltd. All rights reserved.

Evaluation of antibacterial and anthelmintic activities with total phenolic contents of Piper betel leaves

Science.gov (United States)

Akter, Kazi Nahid; Karmakar, Palash; Das, Abhijit; Anonna, Shamima Nasrin; Shoma, Sharmin Akter; Sattar, Mohammad Mafruhi

2014-01-01

Objective: The study was conducted to investigate the antibacterial and anthelmintic activities and to determine total phenolic contents of methanolic extract of Piper betel leaves. Materials and Methods: The extract was subjected to assay for antibacterial activity using both gram positive and gram negative bacterial strains through disc diffusion method; anthelmintic activity with the determination of paralysis and death time using earthworm (Pheritima posthuma) at five different concentrations and the determination of total phenolic contents using the Folin-ciocalteau method. Results: The extract showed significant (pbetel leaves extract, therefore it may be processed for further drug research. PMID:25386394

Determination of free cyanide and total cyanide concentrations in surface and underground waters in Bogoso and its surrounding areas in Ghana

Directory of Open Access Journals (Sweden)

S. Obiri

2007-08-01

Full Text Available Concentrations of free cyanide and total cyanide in water samples in Bogoso and its surrounding areas in Ghana have been measured in this study. Concentrations of free cyanide and total cyanide were found to be above the maximum permissible discharge limit of effluent from mining companies into natural waters set by Environmental Protection Agency, Ghana (GEPA. A comparison of the results obtained in this study with permissible levels set by US Environmental Protection Agency and the World Health Organization reveals that surface waters in the study areas are highly polluted with cyanide and it's not safe for human consumptions. This means that, the resident in and around Bogoso are at risk.

In vitro fermentation of total mixed diets differing in concentrate proportion: relative effects of inocula and substrates.

Science.gov (United States)

Serment, Amélie; Giger-Reverdin, Sylvie; Schmidely, Philippe; Dhumez, Ophélie; Broudiscou, Laurent P; Sauvant, Daniel

2016-01-15

In vitro techniques are used to predict ruminant feedstuff values or characterise rumen fermentation. As the results are influenced by several factors, such as the relative effects of inocula and substrates, this study aimed to examine in vitro incubation of two total mixed rations (substrates) differing in their proportion of concentrate [low (L): 350 g kg(-1) vs. high (H): 700 g kg(-1)] incubated in inocula provided by goats fed either a L or a H diet. Gas production and composition in carbon dioxide (CO2), methane (CH4 ) and hydrogen (H2), volatile fatty acids (VFAs), soluble carbohydrates (SCs) and ammonia (NH3) concentrations, and pH of the fermentation fluid were measured. In comparison with the L inoculum and L substrate, the H ones produced more CO2 and CH4 gas, which led to higher SCs and VFA concentrations, and lower acetate-to-propionate ratio and NH3 concentration, with a predominant effect of the inoculum. The effects of the inocula and of the substrates were additive using donor animals adapted to the diets. © 2015 Society of Chemical Industry.

Determination of arsenic in water samples by Total Reflection X-Ray Fluorescence using pre-concentration with alumina

Energy Technology Data Exchange (ETDEWEB)

Barros, Haydn [Laboratorio de Fisica Nuclear, Dpto. De Fisica, Universidad Simon Bolivar, Sartenejas, Baruta (Venezuela, Bolivarian Republic of); Marco Parra, Lue-Meru, E-mail: luemerumarco@yahoo.e [Universidad Centroccidental Lisandro Alvarado, Dpto. Quimica y Suelos, Decanato de Agronomia, Tarabana, Cabudare, Edo.Lara (Venezuela, Bolivarian Republic of); Bennun, Leonardo [Universidad de Concepcion, Concepcion (Chile); Greaves, Eduardo D. [Laboratorio de Fisica Nuclear, Dpto. De Fisica, Universidad Simon Bolivar, Sartenejas, Baruta (Venezuela, Bolivarian Republic of)

2010-06-15

The determination of arsenic in water samples requires techniques of high sensitivity. Total Reflection X-Ray Fluorescence (TXRF) allows the determination but a prior separation and pre-concentration procedure is necessary. Alumina is a suitable substrate for the selective separation of the analytes. A method for separation and pre-concentration in alumina, followed by direct analysis of the alumina is evaluated. Quantification was performed using the Al-K{alpha} and Co-K{alpha} lines as internal standard in samples prepared on an alumina matrix, and compared to a calibration with aqueous standards. Artificial water samples of As (III) and As (V) were analyzed after the treatment. Fifty milliliters of the sample at ppb concentration levels were mixed with 10 mg of alumina. The pH, time and temperature were controlled. The alumina was separated from the slurry by centrifugation, washed with de-ionized water and analyzed directly on the sample holder. A pre-concentration factor of 100 was found, with detection limit of 0.7 {mu}gL{sup -1}. The percentage of recovery was 98% for As (III) and 95% for As (V) demonstrating the suitability of the procedure.

Determination of arsenic in water samples by Total Reflection X-Ray Fluorescence using pre-concentration with alumina

International Nuclear Information System (INIS)

Barros, Haydn; Marco Parra, Lue-Meru; Bennun, Leonardo; Greaves, Eduardo D.

2010-01-01

The determination of arsenic in water samples requires techniques of high sensitivity. Total Reflection X-Ray Fluorescence (TXRF) allows the determination but a prior separation and pre-concentration procedure is necessary. Alumina is a suitable substrate for the selective separation of the analytes. A method for separation and pre-concentration in alumina, followed by direct analysis of the alumina is evaluated. Quantification was performed using the Al-Kα and Co-Kα lines as internal standard in samples prepared on an alumina matrix, and compared to a calibration with aqueous standards. Artificial water samples of As (III) and As (V) were analyzed after the treatment. Fifty milliliters of the sample at ppb concentration levels were mixed with 10 mg of alumina. The pH, time and temperature were controlled. The alumina was separated from the slurry by centrifugation, washed with de-ionized water and analyzed directly on the sample holder. A pre-concentration factor of 100 was found, with detection limit of 0.7 μgL -1 . The percentage of recovery was 98% for As (III) and 95% for As (V) demonstrating the suitability of the procedure.

Treatment of Renal Cell Carcinoma with 2-Stage Total en bloc Spondylectomy after Marked Response to Molecular Target Drugs

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Yasuhiro Inoue

2013-01-01

Full Text Available Metastatic renal cell carcinoma of the bone occurs at a high rate, and the prognosis is poor. In general, total en bloc spondylectomy is considered when there is only one vertebral metastasis and the primary disease is treated. However, palliative surgery is selected when the primary disease is not being treated or metastasis occurs to an important organ. We encountered a patient in whom lung and vertebra metastases were already present at the time of the first examination at our department and the prognosis was considered poor. However, molecular targeted therapy was markedly effective and enabled 2-stage total en bloc spondylectomy. As of one year after total en bloc spondylectomy, the condition has improved to cane gait, and surgery for lung metastasis is planned. Molecular target drugs might markedly change the current therapeutic strategy for renal cell carcinoma.

Comparison of direct sampling and brochoalveolar lavage for determining active drug concentrations in the pulmonary epithelial lining fluid of calves injected with enrofloxacin or tilmicosin.

Science.gov (United States)

Foster, D M; Sylvester, H J; Papich, M G

2017-12-01

Antibiotic distribution to interstitial fluid (ISF) and pulmonary epithelial fluid (PELF) was measured and compared to plasma drug concentrations in eight healthy calves. Enrofloxacin (Baytril ® 100) was administered at a dose of 12.5 mg/kg subcutaneously (SC), and tilmicosin (Micotil ® 300) was administered at a dose of 20 mg/kg SC. PELF, sampled by two different methods-bronchoalveolar lavage (BAL) and direct sampling (DS)-plasma, and ISF were collected from each calf and measured for tilmicosin, enrofloxacin and its metabolite ciprofloxacin by HPLC. Pharmacokinetic analysis was performed on the concentrations in each fluid, for each drug. The enrofloxacin/ciprofloxacin concentration as measured by AUC in DS samples was 137 ± 72% higher than in plasma, but in BAL samples, this value was 535 ± 403% (p enrofloxacin/ciprofloxacin concentrations collected by DS were significantly different than those collected by BAL, but the tilmicosin concentrations were not significantly different between the two methods. Concentrations of enrofloxacin/ciprofloxacin exceeded the MIC values for bovine respiratory disease pathogens but tilmicosin did not reach MIC levels for these pathogens in any fluids. © 2017 John Wiley & Sons Ltd.

Comparison of Plasma, Saliva, and Hair Levetiracetam Concentrations.

Science.gov (United States)

Karaś-Ruszczyk, Katarzyna; Kuczyńska, Julita; Sienkiewicz-Jarosz, Halina; Kurkowska-Jastrzębska, Iwona; Bienkowski, Przemyslaw; Restel, Magdalena; Samochowiec, Jerzy; Mierzejewski, Pawel

2017-06-01

Previous findings revealed high correlations between serum/plasma and saliva levetiracetam concentrations, indicating saliva as an alternative matrix for monitoring levetiracetam therapy. Levetiracetam concentration in the hair, which could reflect long-term drug exposure and patients' compliance, has not been systematically tested, as yet. The aim of this study was to determine the correlation between plasma, saliva, and hair levetiracetam concentrations in 47 patients with epilepsy. Plasma, saliva, and hair levetiracetam concentrations were measured by liquid chromatography-tandem mass spectrometry with positive ionization. Levetiracetam saliva and plasma concentrations were highly correlated (r = 0.93). Plasma concentrations were not influenced by sex, age, and other concomitant antiepileptic drugs. Levetiracetam hair concentrations correlated with plasma concentrations (r = 0.36) but not daily dose (mg/kg). Drug hair concentrations were not influenced by hair color or treatment (dyed). The results tend to indicate that saliva may be a reliable alternative to plasma for monitoring levetiracetam concentrations. Levetiracetam can also be detected in human hair.

Differential mechanism of Escherichia coli Inactivation by (+)-limonene as a function of cell physiological state and drug's concentration.

Science.gov (United States)

Chueca, Beatriz; Pagán, Rafael; García-Gonzalo, Diego

2014-01-01

(+)-limonene is a lipophilic antimicrobial compound, extracted from citrus fruits' essential oils, that is used as a flavouring agent and organic solvent by the food industry. A recent study has proposed a common and controversial mechanism of cell death for bactericidal antibiotics, in which hydroxyl radicals ultimately inactivated cells. Our objective was to determine whether the mechanism of Escherichia coli MG1655 inactivation by (+)-limonene follows that of bactericidal antibiotics. A treatment with 2,000 μL/L (+)-limonene inactivated 4 log10 cycles of exponentially growing E. coli cells in 3 hours. On one hand, an increase of cell survival in the ΔacnB mutant (deficient in a TCA cycle enzyme), or in the presence of 2,2'-dipyridyl (inhibitor of Fenton reaction by iron chelation), thiourea, or cysteamine (hydroxyl radical scavengers) was observed. Moreover, the ΔrecA mutant (deficient in an enzyme involved in SOS response to DNA damage) was more sensitive to (+)-limonene. Thus, this indirect evidence indicates that the mechanism of exponentially growing E. coli cells inactivation by 2,000 μL/L (+)-limonene is due to the TCA cycle and Fenton-mediated hydroxyl radical formation that caused oxidative DNA damage, as observed for bactericidal drugs. However, several differences have been observed between the proposed mechanism for bactericidal drugs and for (+)-limonene. In this regard, our results demonstrated that E. coli inactivation was influenced by its physiological state and the drug's concentration: experiments with stationary-phase cells or 4,000 μL/L (+)-limonene uncovered a different mechanism of cell death, likely unrelated to hydroxyl radicals. Our research has also shown that drug's concentration is an important factor influencing the mechanism of bacterial inactivation by antibiotics, such as kanamycin. These results might help in improving and spreading the use of (+)-limonene as an antimicrobial compound, and in clarifying the controversy about

Effect of intravenous drug administration mode on drug distribution in a tumor slab: a finite Fourier transform analysis.

Science.gov (United States)

Subramaniam, B; Claudius, J S

1990-03-08

Cancer therapy using chemotherapeutic drugs frequently involves injection of the drug into the body through some intravenous mode of administration, viz, continuous (drip) infusion or single/multiple bolus injection(s). An understanding of the effect of the various modes of administration upon tumor penetration of drug is essential to rational design of drug therapy. This paper investigates drug penetration into a model tumor of slab geometry (between two capillaries) in which the overall transport rate of drug is limited by intra-tumor transport characterized by an effective diffusion coefficient. Employing the method of Finite Fourier Transforms (FFT), analytical solutions have been obtained for transient drug distribution in both the plasma and the tumor following three modes of administration, viz, continuous infusion, single bolus injection and equally-spaced equal-dose multiple bolus injections, of a given amount of drug. The qualitative trends exhibited by the plasma drug distribution profiles are consistent with reported experimental studies. Two concepts, viz, the dimensionless decay constant and the plasma/tumor drug concentration trajectories, are found to be particularly useful in the rational design of drug therapy. The dimensionless decay constant provides a measure of the rate of drug decay in the plasma relative to the rate of drug diffusion into the tumor and is thus characteristic of the tumor/drug system. The magnitude of this parameter dictates the choice of drug administration mode for minimizing drug decay in the plasma while simultaneously maximizing drug transport into the tumor. The concentration trajectories provide a measure of the plasma drug concentration relative to the tumor drug concentration at various times following injection. When the tumor drug concentration exceeds the plasma drug concentration, the drug will begin to diffuse out of the tumor. Knowledge of the time at which this diffusion reversal occurs is especially useful

A case-control study estimating accident risk for alcohol, medicines and illegal drugs.

Directory of Open Access Journals (Sweden)

Kim Paula Colette Kuypers

Full Text Available The aim of the present study was to assess the risk of having a traffic accident after using alcohol, single drugs, or a combination, and to determine the concentrations at which this risk is significantly increased.A population-based case-control study was carried out, collecting whole blood samples of both cases and controls, in which a number of drugs were detected. The risk of having an accident when under the influence of drugs was estimated using logistic regression adjusting for gender, age and time period of accident (cases/sampling (controls. The main outcome measures were odds ratio (OR for accident risk associated with single and multiple drug use. In total, 337 cases (negative: 176; positive: 161 and 2726 controls (negative: 2425; positive: 301 were included in the study.Main findings were that 1 alcohol in general (all the concentrations together caused an elevated crash risk; 2 cannabis in general also caused an increase in accident risk; at a cut-off of 2 ng/mL THC the risk of having an accident was four times the risk associated with the lowest THC concentrations; 3 when ranking the adjusted OR from lowest to highest risk, alcohol alone or in combination with other drugs was related to a very elevated crash risk, with the highest risk for stimulants combined with sedatives.The study demonstrated a concentration-dependent crash risk for THC positive drivers. Alcohol and alcohol-drug combinations are by far the most prevalent substances in drivers and subsequently pose the largest risk in traffic, both in terms of risk and scope.

21 CFR 862.1270 - Estrogens (total, in pregnancy) test system.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Estrogens (total, in pregnancy) test system. 862.1270 Section 862.1270 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... Test Systems § 862.1270 Estrogens (total, in pregnancy) test system. (a) Identification. As estrogens...

Determination of human and Sprague-Dawley rat trimethylseleonium ion and total selenium urine concentrations from endogenous body selenium pool by neutron activation analysis

International Nuclear Information System (INIS)

Blotcky, A.J.; Claassen, J.P.; Rack, E.P.

1992-01-01

This study determined trimethylselenonium ion [TMSe,(CH 3 ) 3 Se + ] and total organic selenium cationic species urinary excretion values for healthy human subjects and Sprague-Dawley rats fed regular diets. The only source of TMSe was from the endogenous selenium body pool. Total selenium concentration in urine was determined by instrumental neutron activation analysis. TMSe and total selenium cationic species concentrations and percent of total selenium urine excretion were determined by chemical neutron activation analysis and coupled anion-cation exchange chromatography and anion-exchange chromatography, respectively. Within experimental error, mean values for TMSe and cationic species as percent selenium were comparable for both human subjects and Sprague-Dawley rats. This study suggested that TMSe excreated in urine by healthy human subjects and Sprague-Dawley rats fed a normal diet is not a minor but a general metabolite of selenium ingested in a normal diet. (author) 27 refs.; 1 fig.; 2 tabs

The use of autologous concentrated growth factors to promote syndesmosis fusion in the Agility total ankle replacement. A preliminary study.

Science.gov (United States)

Coetzee, J Chris; Pomeroy, Gregory C; Watts, J David; Barrow, Craig

2005-10-01

The Agility (DePuy, Warsaw, Indiana) total ankle replacement has been in use since 1984. One of the most common complications continues to be delayed union or nonunions of the distal tibiofibular syndesmosis. In the reported studies on the Agility ankle the delayed union and nonunion rate can be as high as 38%. Since 1999, 114 Agility total ankle replacements were done at two centers in the United States without the use of autologous concentrated growth factors. Since July of 2001, 66 Agility ankles were implanted with Symphony (DePuy, Warsaw, Indiana) augmented bone grafting. The standard operative technique was followed in all the patients. Prospective data was collected on all patients. The standard ankle radiographs were taken preoperatively and postoperative at 8 weeks, 12 weeks, 16 weeks, 6 months, and yearly. CT scans were obtained at 6 months if fusion at the syndesmosis was questionable. The Graphpad Instat software (Graphpad Software Inc., San Diego, CA) was used for statistical analysis. The two-tailed unpaired t-test was used, and the value ankle replacements without autologous concentrated growth factors 70 fused at 8 weeks (61%), 14 fused at 12 weeks (12%), 13 fused at 6 months (12%). There were 17 nonunions (15%); delayed unions (3 to 6 months) and nonunions, therefore, equaled 27%. The syndesmosis fused in 50 of the 66 ankle replacements (76%) that had autologous concentrated growth fractures at 8 weeks (76%); 12 fused at 3 months (18%), 2 fused at 6 months (3%), 2 had nonunions (3%). Delayed unions (3 to 6 months) and nonunions equaled 6%. There was a statistically significant improvement in the 8- and 12-week fusion rates, and a statistically significant reduction in delayed unions and nonunions. Autologous concentrated growth factors appear to make a significant positive difference in the syndesmosis union rate in total ankle replacements.

Time-series MODIS image-based retrieval and distribution analysis of total suspended matter concentrations in Lake Taihu (China).

Science.gov (United States)

Zhang, Yuchao; Lin, Shan; Liu, Jianping; Qian, Xin; Ge, Yi

2010-09-01

Although there has been considerable effort to use remotely sensed images to provide synoptic maps of total suspended matter (TSM), there are limited studies on universal TSM retrieval models. In this paper, we have developed a TSM retrieval model for Lake Taihu using TSM concentrations measured in situ and a time series of quasi-synchronous MODIS 250 m images from 2005. After simple geometric and atmospheric correction, we found a significant relationship (R = 0.8736, N = 166) between in situ measured TSM concentrations and MODIS band normalization difference of band 3 and band 1. From this, we retrieved TSM concentrations in eight regions of Lake Taihu in 2007 and analyzed the characteristic distribution and variation of TSM. Synoptic maps of model-estimated TSM of 2007 showed clear geographical and seasonal variations. TSM in Central Lake and Southern Lakeshore were consistently higher than in other regions, while TSM in East Taihu was generally the lowest among the regions throughout the year. Furthermore, a wide range of TSM concentrations appeared from winter to summer. TSM in winter could be several times that in summer.

Relation between CYP2D6 Genotype, Phenotype and Therapeutic Drug Concentrations among Nortriptyline and Venlafaxine Users in Old Age Psychiatry

NARCIS (Netherlands)

Berm, E; Kok, R.; Hak, E; Wilffert, B

2016-01-01

Objectives: To determine relations between drug concentrations and the cytochrome P450-CYP2D6 genotype or phenotype among elderly patients treated with nortriptyline or venlafaxine. Methods: A post-hoc analysis of a clinical trial was performed. Patients were grouped into phenotypes according to the

Optimization of Drug Delivery by Drug-Eluting Stents.

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Franz Bozsak

Full Text Available Drug-eluting stents (DES, which release anti-proliferative drugs into the arterial wall in a controlled manner, have drastically reduced the rate of in-stent restenosis and revolutionized the treatment of atherosclerosis. However, late stent thrombosis remains a safety concern in DES, mainly due to delayed healing of the endothelial wound inflicted during DES implantation. We present a framework to optimize DES design such that restenosis is inhibited without affecting the endothelial healing process. To this end, we have developed a computational model of fluid flow and drug transport in stented arteries and have used this model to establish a metric for quantifying DES performance. The model takes into account the multi-layered structure of the arterial wall and incorporates a reversible binding model to describe drug interaction with the cells of the arterial wall. The model is coupled to a novel optimization algorithm that allows identification of optimal DES designs. We show that optimizing the period of drug release from DES and the initial drug concentration within the coating has a drastic effect on DES performance. Paclitaxel-eluting stents perform optimally by releasing their drug either very rapidly (within a few hours or very slowly (over periods of several months up to one year at concentrations considerably lower than current DES. In contrast, sirolimus-eluting stents perform optimally only when drug release is slow. The results offer explanations for recent trends in the development of DES and demonstrate the potential for large improvements in DES design relative to the current state of commercial devices.

Pharmacokinetic-Pharmacodynamic (PKPD) Analysis with Drug Discrimination.

Science.gov (United States)

Negus, S Stevens; Banks, Matthew L

2016-08-30

Discriminative stimulus and other drug effects are determined by the concentration of drug at its target receptor and by the pharmacodynamic consequences of drug-receptor interaction. For in vivo procedures such as drug discrimination, drug concentration at receptors in a given anatomical location (e.g., the brain) is determined both by the dose of drug administered and by pharmacokinetic processes of absorption, distribution, metabolism, and excretion that deliver drug to and from that anatomical location. Drug discrimination data are often analyzed by strategies of dose-effect analysis to determine parameters such as potency and efficacy. Pharmacokinetic-Pharmacodynamic (PKPD) analysis is an alternative to conventional dose-effect analysis, and it relates drug effects to a measure of drug concentration in a body compartment (e.g., venous blood) rather than to drug dose. PKPD analysis can yield insights on pharmacokinetic and pharmacodynamic determinants of drug action. PKPD analysis can also facilitate translational research by identifying species differences in pharmacokinetics and providing a basis for integrating these differences into interpretation of drug effects. Examples are discussed here to illustrate the application of PKPD analysis to the evaluation of drug effects in rhesus monkeys trained to discriminate cocaine from saline.

Postabsorption concentration peaks with brand-name and generic verapamil: a double-blind, crossover study in elderly hypertensive patients.

Science.gov (United States)

Saseen, J J; Porter, J A; Barnette, D J; Bauman, J L; Zajac, E J; Carter, B L

1997-06-01

The pharmacokinetic actions, bioequivalence, and cardiovascular effects of two verapamil products were studied in a randomized, double-blind, crossover study in eight elderly hypertensive patients (median age, 69.5 years; range, 60-79 years) given brand-name or generic immediate-release verapamil in 120-mg twice-daily doses for 14 days. Blood pressures, heart rates, P-R intervals; and serum concentrations of R-/S-verapamil and norverapamil were measured multiple times in patients during the last day of each therapy. Median blood pressure decreased more with generic verapamil than with the brand-name drug, with the largest difference occurring at 0.5 hours (137/74 mmHg versus 144.5/80.5 mmHg; P = 0.05 and 0.091, respectively). Pharmacokinetic parameters were not different for the two products (P generic product, compared with the brand-name drug, had mean area under the concentration-time curve (time 0 to 12 hours) ratios (90% CI) of 1.09 (0.78-1.52), 1.16 (0.87-1.55) and 1.11 (0.81-1.52) for R-, S-, and total verapamil. Seventy concentration peaks (31 with the brand-name drug, 39 with the generic drug) appeared between 8 and 24 hours. Median percentages of increase of these peaks, compared with those of previous concentrations, were 48.3% and 36.3% for brand-name and generic drugs, respectively. Fifty of the 70 peaks (71%) were associated with a stereospecific concentration peak of norverapamil and, temporally, with meals. Our findings suggest that whereas the two verapamil products may not be bioequivalent by Food and Drug Administration criteria, the observed differences in effects were not clinically significant in this elderly population. Multiple concentration peaks after absorption were observed in all patients with both verapamil products and were perhaps related to enterohepatic recirculation.

Toward the establishment of standardized in vitro tests for lipid-based formulations. 2. The effect of bile salt concentration and drug loading on the performance of type I, II, IIIA, IIIB, and IV formulations during in vitro digestion.

Science.gov (United States)

Williams, Hywel D; Anby, Mette U; Sassene, Philip; Kleberg, Karen; Bakala-N'Goma, Jean-Claude; Calderone, Marilyn; Jannin, Vincent; Igonin, Annabel; Partheil, Anette; Marchaud, Delphine; Jule, Eduardo; Vertommen, Jan; Maio, Mario; Blundell, Ross; Benameur, Hassan; Carrière, Frédéric; Müllertz, Anette; Pouton, Colin W; Porter, Christopher J H

2012-11-05

The LFCS Consortium was established to develop standardized in vitro tests for lipid-based formulations (LBFs) and to examine the utility of these tests to probe the fundamental mechanisms that underlie LBF performance. In this publication, the impact of bile salt (sodium taurodeoxycholate, NaTDC) concentration and drug loading on the ability of a range of representative LBFs to generate and sustain drug solubilization and supersaturation during in vitro digestion testing has been explored and a common driver of the potential for drug precipitation identified. Danazol was used as a model poorly water-soluble drug throughout. In general, increasing NaTDC concentrations increased the digestion of the most lipophilic LBFs and promoted lipid (and drug) trafficking from poorly dispersed oil phases to the aqueous colloidal phase (AP(DIGEST)). High NaTDC concentrations showed some capacity to reduce drug precipitation, although, at NaTDC concentrations ≥3 mM, NaTDC effects on either digestion or drug solubilization were modest. In contrast, increasing drug load had a marked impact on drug solubilization. For LBFs containing long-chain lipids, drug precipitation was limited even at drug loads approaching saturation in the formulation and concentrations of solubilized drug in AP(DIGEST) increased with increased drug load. For LBFs containing medium-chain lipids, however, significant precipitation was evident, especially at higher drug loads. Across all formulations a remarkably consistent trend emerged such that the likelihood of precipitation was almost entirely dependent on the maximum supersaturation ratio (SR(M)) attained on initiation of digestion. SR(M) defines the supersaturation "pressure" in the system and is calculated from the maximum attainable concentration in the AP(DIGEST) (assuming zero precipitation), divided by the solubility of the drug in the colloidal phases formed post digestion. For LBFs where phase separation of oil phases did not occur, a

Randomized Clinical Trial of Periarticular Drug Injection used in combination Patient-Controlled Analgesia versus Patient-Controlled Analgesia Alone in Total Knee Arthroplasty

Directory of Open Access Journals (Sweden)

MN Sabran

2008-11-01

Full Text Available This is a prospective randomized clinical trial to compare use of a combination of periarticular drug injection with patient- controlled analgesia (PCA to PCA alone in post-total knee arthroplasty (TKA. Thirty patients who were admitted for unilateral total knee arthroplasty were selected randomly into an Injection group or a Standard group. The periarticular injection contained Ropivacaine, Ketorolac and Adrenaline, given intra-operatively. The mean amount of opioid used was 22.87 mmol/L in the Injection group as compared to 39.78 mmol/L in the Standard group (p = 0.026. The Injection group had lower pain score at rest and during exercise (p=0.021, p=0.041, respectively, as well as better return to function (p=0.026 and shorter hospital stay (6.1 days, Injection; 7.5 days, Standard, p=0.027. Overall, the group receiving periarticular drugs injection had less pain, less narcotic usage, earlier return to function, similar experience of adverse effects and shorter hospital stays.

Vaginal drug distribution modeling.

Science.gov (United States)

Katz, David F; Yuan, Andrew; Gao, Yajing

2015-09-15

This review presents and applies fundamental mass transport theory describing the diffusion and convection driven mass transport of drugs to the vaginal environment. It considers sources of variability in the predictions of the models. It illustrates use of model predictions of microbicide drug concentration distribution (pharmacokinetics) to gain insights about drug effectiveness in preventing HIV infection (pharmacodynamics). The modeling compares vaginal drug distributions after different gel dosage regimens, and it evaluates consequences of changes in gel viscosity due to aging. It compares vaginal mucosal concentration distributions of drugs delivered by gels vs. intravaginal rings. Finally, the modeling approach is used to compare vaginal drug distributions across species with differing vaginal dimensions. Deterministic models of drug mass transport into and throughout the vaginal environment can provide critical insights about the mechanisms and determinants of such transport. This knowledge, and the methodology that obtains it, can be applied and translated to multiple applications, involving the scientific underpinnings of vaginal drug distribution and the performance evaluation and design of products, and their dosage regimens, that achieve it. Copyright © 2015 Elsevier B.V. All rights reserved.

Assessment of conservation easements, total phosphorus, and total suspended solids in West Fork Beaver Creek, Minnesota, 1999-2012

Science.gov (United States)

Christensen, Victoria G.; Kieta, Kristen A.

2014-01-01

This study examined conservation easements and their effectiveness at reducing phosphorus and solids transport to streams. The U.S. Geological Survey cooperated with the Minnesota Board of Water and Soil Resources and worked collaboratively with the Hawk Creek Watershed Project to examine the West Fork Beaver Creek Basin in Renville County, which has the largest number of Reinvest In Minnesota land retirement contracts in the State (as of 2013). Among all conservation easement programs, a total of 24,218 acres of agricultural land were retired throughout Renville County, and 2,718 acres were retired in the West Fork Beaver Creek Basin from 1987 through 2012. Total land retirement increased steadily from 1987 until 2000. In 2000, land retirement increased sharply because of the Minnesota River Conservation Reserve Enhancement Program, then leveled off when the program ended in 2002. Streamflow data were collected during 1999 through 2011, and total phosphorus and total suspended solids data were collected during 1999 through 2012. During this period, the highest peak streamflow of 1,320 cubic feet per second was in March 2010. Total phosphorus and total suspended solids are constituents that tend to increase with increases in streamflow. Annual flow-weighted mean total-phosphorus concentrations ranged from 0.140 to 0.759 milligrams per liter, and annual flow-weighted mean total suspended solids concentrations ranged from 21.3 to 217 milligrams per liter. Annual flow-weighted mean total phosphorus and total suspended solids concentrations decreased steadily during the first 4 years of water-quality sample collection. A downward trend in flow-weighted mean total-phosphorus concentrations was significant from 1999 through 2008; however, flow-weighted total-phosphorus concentrations increased substantially in 2009, and the total phosphorus trend was no longer significant. The high annual flow-weighted mean concentrations for total phosphorus and total suspended solids

Remote sensing estimation of the total phosphorus concentration in a large lake using band combinations and regional multivariate statistical modeling techniques.

Science.gov (United States)

Gao, Yongnian; Gao, Junfeng; Yin, Hongbin; Liu, Chuansheng; Xia, Ting; Wang, Jing; Huang, Qi

2015-03-15

Remote sensing has been widely used for ater quality monitoring, but most of these monitoring studies have only focused on a few water quality variables, such as chlorophyll-a, turbidity, and total suspended solids, which have typically been considered optically active variables. Remote sensing presents a challenge in estimating the phosphorus concentration in water. The total phosphorus (TP) in lakes has been estimated from remotely sensed observations, primarily using the simple individual band ratio or their natural logarithm and the statistical regression method based on the field TP data and the spectral reflectance. In this study, we investigated the possibility of establishing a spatial modeling scheme to estimate the TP concentration of a large lake from multi-spectral satellite imagery using band combinations and regional multivariate statistical modeling techniques, and we tested the applicability of the spatial modeling scheme. The results showed that HJ-1A CCD multi-spectral satellite imagery can be used to estimate the TP concentration in a lake. The correlation and regression analysis showed a highly significant positive relationship between the TP concentration and certain remotely sensed combination variables. The proposed modeling scheme had a higher accuracy for the TP concentration estimation in the large lake compared with the traditional individual band ratio method and the whole-lake scale regression-modeling scheme. The TP concentration values showed a clear spatial variability and were high in western Lake Chaohu and relatively low in eastern Lake Chaohu. The northernmost portion, the northeastern coastal zone and the southeastern portion of western Lake Chaohu had the highest TP concentrations, and the other regions had the lowest TP concentration values, except for the coastal zone of eastern Lake Chaohu. These results strongly suggested that the proposed modeling scheme, i.e., the band combinations and the regional multivariate

Sonophoresis Using Ultrasound Contrast Agents: Dependence on Concentration.

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Donghee Park

Full Text Available Sonophoresis can increase skin permeability to various drugs in transdermal drug delivery. Cavitation is recognized as the predominant mechanism of sonophoresis. Recently, a new logical approach to enhance the efficiency of transdermal drug delivery was tried. It is to utilize the engineered microbubble and its resonant frequency for increase of cavitation activity. Actively-induced cavitation with low-intensity ultrasound (less than ~1 MPa causes disordering of the lipid bilayers and the formation of aqueous channels by stable cavitation which indicates a continuous oscillation of bubbles. Furthermore, the mutual interactions of microbubble determined by concentration of added bubble are also thought to be an important factor for activity of stable cavitation, even in different characteristics of drug. In the present study, we addressed the dependence of ultrasound contrast agent concentration using two types of drug on the efficiency of transdermal drug delivery. Two types of experiment were designed to quantitatively evaluate the efficiency of transdermal drug delivery according to ultrasound contrast agent concentration. First, an experiment of optical clearing using a tissue optical clearing agent was designed to assess the efficiency of sonophoresis with ultrasound contrast agents. Second, a Franz diffusion cell with ferulic acid was used to quantitatively determine the amount of drug delivered to the skin sample by sonophoresis with ultrasound contrast agents. The maximum enhancement ratio of sonophoresis with a concentration of 1:1,000 was approximately 3.1 times greater than that in the ultrasound group without ultrasound contrast agent and approximately 7.5 times greater than that in the control group. These results support our hypothesis that sonophoresis becomes more effective in transdermal drug delivery due to the presence of engineered bubbles, and that the efficiency of transdermal drug delivery using sonophoresis with

Sonophoresis Using Ultrasound Contrast Agents: Dependence on Concentration.

Science.gov (United States)

Park, Donghee; Song, Gillsoo; Jo, Yongjun; Won, Jongho; Son, Taeyoon; Cha, Ohrum; Kim, Jinho; Jung, Byungjo; Park, Hyunjin; Kim, Chul-Woo; Seo, Jongbum

2016-01-01

Sonophoresis can increase skin permeability to various drugs in transdermal drug delivery. Cavitation is recognized as the predominant mechanism of sonophoresis. Recently, a new logical approach to enhance the efficiency of transdermal drug delivery was tried. It is to utilize the engineered microbubble and its resonant frequency for increase of cavitation activity. Actively-induced cavitation with low-intensity ultrasound (less than ~1 MPa) causes disordering of the lipid bilayers and the formation of aqueous channels by stable cavitation which indicates a continuous oscillation of bubbles. Furthermore, the mutual interactions of microbubble determined by concentration of added bubble are also thought to be an important factor for activity of stable cavitation, even in different characteristics of drug. In the present study, we addressed the dependence of ultrasound contrast agent concentration using two types of drug on the efficiency of transdermal drug delivery. Two types of experiment were designed to quantitatively evaluate the efficiency of transdermal drug delivery according to ultrasound contrast agent concentration. First, an experiment of optical clearing using a tissue optical clearing agent was designed to assess the efficiency of sonophoresis with ultrasound contrast agents. Second, a Franz diffusion cell with ferulic acid was used to quantitatively determine the amount of drug delivered to the skin sample by sonophoresis with ultrasound contrast agents. The maximum enhancement ratio of sonophoresis with a concentration of 1:1,000 was approximately 3.1 times greater than that in the ultrasound group without ultrasound contrast agent and approximately 7.5 times greater than that in the control group. These results support our hypothesis that sonophoresis becomes more effective in transdermal drug delivery due to the presence of engineered bubbles, and that the efficiency of transdermal drug delivery using sonophoresis with microbubbles depends on the

Comparative analysis of total mercury concentrations in anadromous and non-anadromous Arctic charr (Salvelinus alpinus) from eastern Canada

International Nuclear Information System (INIS)

Velden, S. van der; Evans, M.S.; Dempson, J.B.; Muir, D.C.G.; Power, M.

2013-01-01

Previous research has documented that total mercury concentrations ([THg]) are lower in anadromous Arctic charr than in non-anadromous conspecifics, but the two life-history forms have rarely been studied together. Here, data from nine pairs of closely-located anadromous and non-anadromous Arctic charr populations were used to explore the impact of biological and life-history factors on individual [THg] across a range of latitudes (49–81° N) in eastern Canada. Unadjusted mean [THg] ranged from 20 to 114 ng/g wet weight (ww) in anadromous populations, and was significantly higher in non-anadromous populations, ranging from 111 to 227 ng/g ww. Within-population variations in [THg] were best explained by fish age, and were often positively related to fork-length and δ 15 N-inferred trophic level. Differences in [THg] were not related to differences in length-at-age (i.e., average somatic growth rate) among populations of either life-history type. Mercury concentrations were not related to site latitude in either the anadromous or non-anadromous fish. We conclude that the difference in Arctic charr [THg] with life-history type could not be explained by differences in fish age, fork-length, trophic position, or length-at-age, and discuss possible factors contributing to low mercury concentrations in anadromous, relative to freshwater, fish. - Highlights: ► Total mercury concentrations ([THg]) were measured in 9 co-located anadromous and non-anadromous Arctic charr populations. ► Mean [THg] in non-anadromous populations exceeded mean [THg] in spatially paired anadromous populations. ► Among-individual variation in [THg] was best explained by fish age. ► The lower [THg] in anadromous fish could not be explained by differences in age, fork-length, trophic level, or growth rate. ► Variations in Arctic charr [THg] were independent of latitude (49–81° N) in eastern Canada

Potential Drug-Drug Interactions among Patients prescriptions collected from Medicine Out-patient Setting.

Science.gov (United States)

Farooqui, Riffat; Hoor, Talea; Karim, Nasim; Muneer, Mehtab

2018-01-01

To identify and evaluate the frequency, severity, mechanism and common pairs of drug-drug interactions (DDIs) in prescriptions by consultants in medicine outpatient department. This cross sectional descriptive study was done by Pharmacology department of Bahria University Medical & Dental College (BUMDC) in medicine outpatient department (OPD) of a private hospital in Karachi from December 2015 to January 2016. A total of 220 prescriptions written by consultants were collected. Medications given with patient's diagnosis were recorded. Drugs were analyzed for interactions by utilizing Medscape drug interaction checker, drugs.com checker and stockley`s drug interactions index. Two hundred eleven prescriptions were selected while remaining were excluded from the study because of unavailability of the prescribed drugs in the drug interaction checkers. In 211 prescriptions, two common diagnoses were diabetes mellitus (28.43%) and hypertension (27.96%). A total of 978 medications were given. Mean number of medications per prescription was 4.6. A total of 369 drug-drug interactions were identified in 211 prescriptions (175%). They were serious 4.33%, significant 66.12% and minor 29.53%. Pharmacokinetic and pharmacodynamic interactions were 37.94% and 51.21% respectively while 10.84% had unknown mechanism. Number wise common pairs of DDIs were Omeprazole-Losartan (S), Gabapentine- Acetaminophen (M), Losartan-Diclofenac (S). The frequency of DDIs is found to be too high in prescriptions of consultants from medicine OPD of a private hospital in Karachi. Significant drug-drug interactions were more and mostly caused by Pharmacodynamic mechanism. Number wise evaluation showed three common pairs of drugs involved in interactions.

Plasma drug concentrations and clinical effects of a peripheral alpha-2-adrenoceptor antagonist, MK-467, in horses sedated with detomidine.

Science.gov (United States)

Vainionpää, Mari H; Raekallio, Marja R; Pakkanen, Soile A E; Ranta-Panula, Ville; Rinne, Valtteri M; Scheinin, Mika; Vainio, Outi M

2013-05-01

To investigate plasma drug concentrations and the effect of MK-467 (L-659'066) on sedation, heart rate and gut motility in horses sedated with intravenous (IV) detomidine. Experimental randomized blinded crossover study. Six healthy horses. Detomidine (10 μg kg(-1) IV) was administered alone (DET) and in combination with MK-467 (250 μg kg(-1) IV; DET + MK). The level of sedation and intestinal sounds were scored. Heart rate (HR) and central venous pressure (CVP) were measured. Blood was collected to determine plasma drug concentrations. Repeated measures anova was used for HR, CVP and intestinal sounds, and the Student's t-test for pairwise comparisons between treatments for the area under the time-sedation curve (AUCsed ) and pharmacokinetic parameters. Significance was set at p Detomidine-induced intestinal hypomotility was prevented by MK-467. AUCsed was significantly higher with DET than DET + MK, but maximal sedations scores did not differ significantly between treatments. MK-467 lowered the AUC of the plasma concentration of detomidine, and increased its volume of distribution and clearance. MK-467 prevented detomidine induced bradycardia and intestinal hypomotility. MK-467 did not affect the clinical quality of detomidine-induced sedation, but the duration of the effect was reduced, which may have been caused by the effects of MK-467 on the plasma concentration of detomidine. MK-467 may be useful clinically in the prevention of certain peripheral side effects of detomidine in horses. © 2013 The Authors. Veterinary Anaesthesia and Analgesia © 2013 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesia and Analgesia.

Seafood sold in Sweden contains BMAA: A study of free and total concentrations with UHPLC–MS/MS and dansyl chloride derivatization

Directory of Open Access Journals (Sweden)

Matilda L. Salomonsson

2015-01-01

Full Text Available β-N-Methylamino-l-alanine (BMAA is a potential neurotoxin associated with the aquatic environment. Validated analytical methods for the quantification of both free and total concentrations of BMAA were used in an investigation of seafood purchased from different grocery stores in Uppsala, Sweden. The analysis was performed using ultra high performance liquid chromatography-electrospray ionization-tandem mass spectrometry (UHPLC-ESI–MS/MS and detection of BMAA as a dansyl derivate. The determined concentrations of free BMAA (after a simple trichloroacetic acid extraction in mussels and scallops were up to 0.46 μg g−1 wet homogenate. The total BMAA (after hydrochloric acid hydrolysis levels were between 0.29 and 7.08 μg g−1 wet mussel homogenate. The highest concentration of total BMAA was found in imported cooked and canned mussels which contained about ten times the quantity of BMAA measured in domestic cooked and frozen mussels. In this study it was also concluded that BMAA could be detected in seafood origin from four different continents. The risks associated with human exposure to BMAA through food are unknown today. However, the results of this study show that imported seafood in Sweden contain BMAA, indicating that this area needs more investigation, including a risk assessment regarding the consumption of e.g., mussels, scallops and crab.

Seafood sold in Sweden contains BMAA: A study of free and total concentrations with UHPLC-MS/MS and dansyl chloride derivatization.

Science.gov (United States)

Salomonsson, Matilda L; Fredriksson, Elisabeth; Alfjorden, Anders; Hedeland, Mikael; Bondesson, Ulf

2015-01-01

β- N -Methylamino-l-alanine (BMAA) is a potential neurotoxin associated with the aquatic environment. Validated analytical methods for the quantification of both free and total concentrations of BMAA were used in an investigation of seafood purchased from different grocery stores in Uppsala, Sweden. The analysis was performed using ultra high performance liquid chromatography-electrospray ionization-tandem mass spectrometry (UHPLC-ESI-MS/MS) and detection of BMAA as a dansyl derivate. The determined concentrations of free BMAA (after a simple trichloroacetic acid extraction) in mussels and scallops were up to 0.46 μg g -1 wet homogenate. The total BMAA (after hydrochloric acid hydrolysis) levels were between 0.29 and 7.08 μg g -1 wet mussel homogenate. The highest concentration of total BMAA was found in imported cooked and canned mussels which contained about ten times the quantity of BMAA measured in domestic cooked and frozen mussels. In this study it was also concluded that BMAA could be detected in seafood origin from four different continents. The risks associated with human exposure to BMAA through food are unknown today. However, the results of this study show that imported seafood in Sweden contain BMAA, indicating that this area needs more investigation, including a risk assessment regarding the consumption of e.g., mussels, scallops and crab.

Concentrations of oligomers and polymers of proanthocyanidins in red and purple rice bran and their relationships to total phenolics, flavonoids, antioxidant capacity and whole grain color.

Science.gov (United States)

Chen, Ming-Hsuan; McClung, Anna M; Bergman, Christine J

2016-10-01

Proanthocyanidins, a flavonoids subgroup, are proposed to have chronic disease modulation properties. With the eventual goal of enhancing rice phytonutrient concentrations, we investigated the genotypic variation of the concentrations of individual oligomers and polymers of proanthocyanidins in red and purple rice brans. A 4.3-fold variation in total proanthocyanidins (sum of oligomers and polymers) in the extractable fraction was found and the concentration was highly correlated with total phenolics, total flavonoids and antiradical capacity. Variation in the proportion of oligomers and polymers existed, with monomers to trimers, 4-6mers, 7-10mers and polymers accounting for 7, 18, 26.5 and 48.7%, respectively, of the total. The redness value a(∗) of whole grain rice measured in CIE L(∗)a(∗)b(∗) color space was negatively and positively correlated with extractable and non-extractable proanthocyanidins, respectively. The variation found indicates it is possible to select rice with bran containing high levels of total proanthocyanidins and specific degree of polymerization profiles. Published by Elsevier Ltd.

A REVIEW ON OSMOTIC DRUG DELIVERY SYSTEM

OpenAIRE

Harnish Patel; Upendra Patel; Hiren Kadikar; Bhavin Bhimani; Dhiren Daslaniya; Ghanshyam Patel

2012-01-01

Conventional oral drug delivery systems supply an instantaneous release of drug, which cannot control the release of the drug and effective concentration at the target site. This kind of dosing pattern may result in constantly changing, unpredictable plasma concentrations. Drugs can be delivered in a controlled pattern over a long period of time by the process of osmosis. Osmotic devices are the most promising strategy based systems for controlled drug delivery. They are the most reliable con...

Illicit drugs and their metabolites in 36 rivers that drain into the Bohai Sea and north Yellow Sea, north China.

Science.gov (United States)

Wang, De-Gao; Zheng, Qiu-Da; Wang, Xiao-Ping; Du, Juan; Tian, Chong-Guo; Wang, Zhuang; Ge, Lin-Ke

2016-08-01

Illicit drugs and their metabolites have recently been recognized as an emerging group of contaminants due to their potential ecotoxicological impact in aquatic ecosystems. To date, information on the occurrence of these compounds in the aquatic environment of China remains limited. In this study, we collected surface water samples from 36 rivers in north China that discharge into the Bohai Sea and north Yellow Sea and measured the concentrations of amphetamine-like compounds, ketamines, cocainics, and opioids. The occurrence and spatial patterns of these substances show significant differences between the rivers and regions. Two designer drugs, methamphetamine (METH) and ketamine (KET), were the most abundant compounds detected in the entire set of samples (detection frequency of 92 and 69 %). The concentrations of METH and KET ranged from illicit drugs consumed in China. The high concentrations of these illicit drugs and their metabolites were found in areas that have a high population density. The riverine input of total illicit drugs into the Bohai Sea and north Yellow Sea was estimated to be in the range of 684 to 1160 kg per year.

Raltegravir cerebrospinal fluid concentrations in HIV-1 infection.

Directory of Open Access Journals (Sweden)

Aylin Yilmaz

2009-09-01

Full Text Available Raltegravir is an HIV-1 integrase inhibitor currently used in treatment-experienced HIV-1-infected patients resistant to other drug classes. In order to assess its central nervous system penetration, we measured raltegravir concentrations in cerebrospinal fluid (CSF and plasma in subjects receiving antiretroviral treatment regimens containing this drug.Raltegravir concentrations were determined by liquid chromatography tandem mass spectrometry in 25 paired CSF and plasma samples from 16 HIV-1-infected individuals. The lower limit of quantitation was 2.0 ng/ml for CSF and 10 ng/ml for plasma.Twenty-four of the 25 CSF samples had detectable raltegravir concentrations with a median raltegravir concentration of 18.4 ng/ml (range, <2.0-126.0. The median plasma raltegravir concentration was 448 ng/ml (range, 37-5180. CSF raltegravir concentrations correlated with CSF:plasma albumin ratios and CSF albumin concentrations.Approximately 50% of the CSF specimens exceeded the IC(95 levels reported to inhibit HIV-1 strains without resistance to integrase inhibitors. In addition to contributing to control of systemic HIV-1 infection, raltegravir achieves local inhibitory concentrations in CSF in most, but not all, patients. Blood-brain and blood-CSF barriers likely restrict drug entry, while enhanced permeability of these barriers enhances drug entry.

Raltegravir cerebrospinal fluid concentrations in HIV-1 infection.

Science.gov (United States)

Yilmaz, Aylin; Gisslén, Magnus; Spudich, Serena; Lee, Evelyn; Jayewardene, Anura; Aweeka, Francesca; Price, Richard W

2009-09-01

Raltegravir is an HIV-1 integrase inhibitor currently used in treatment-experienced HIV-1-infected patients resistant to other drug classes. In order to assess its central nervous system penetration, we measured raltegravir concentrations in cerebrospinal fluid (CSF) and plasma in subjects receiving antiretroviral treatment regimens containing this drug. Raltegravir concentrations were determined by liquid chromatography tandem mass spectrometry in 25 paired CSF and plasma samples from 16 HIV-1-infected individuals. The lower limit of quantitation was 2.0 ng/ml for CSF and 10 ng/ml for plasma. Twenty-four of the 25 CSF samples had detectable raltegravir concentrations with a median raltegravir concentration of 18.4 ng/ml (range, <2.0-126.0). The median plasma raltegravir concentration was 448 ng/ml (range, 37-5180). CSF raltegravir concentrations correlated with CSF:plasma albumin ratios and CSF albumin concentrations. Approximately 50% of the CSF specimens exceeded the IC(95) levels reported to inhibit HIV-1 strains without resistance to integrase inhibitors. In addition to contributing to control of systemic HIV-1 infection, raltegravir achieves local inhibitory concentrations in CSF in most, but not all, patients. Blood-brain and blood-CSF barriers likely restrict drug entry, while enhanced permeability of these barriers enhances drug entry.

Effect of dietary poly unsaturated fatty acids on total brain lipid concentration and anxiety levels of electron beam irradiated mice

International Nuclear Information System (INIS)

Suchetha Kumari; Bekal, Mahesh

2013-01-01

The whole brain irradiation causes injury to the nervous system at various levels. Omega-3 poly unsaturated fatty acids are very much essential for the growth and development of nervous system. Dietary supplementation of these nutrients will promote the development of injured neuronal cells. Therefore this study was undertaken to establish the role of Omega-3 poly unsaturated fatty acids on total brain lipid concentration, lipid peroxidation and anxiety levels in the irradiated mice. The effect of Electron Beam Radiation (EBR) on total brain lipid concentration, lipid peroxidation and anxiety level were investigated in male Swiss albino mice. The study groups were subjected to a sub-lethal dose of EBR and also the flax seed extract and fish oil were given orally to the irradiated mice. Irradiated groups show significant elevation in anxiety levels when compared to control group, indicating the acute radiation effects on the central nervous system. But the oral supplementation of dietary PUFA source decrees the anxiety level in the irradiated group. The analysis of lipid peroxidation showed a significant level of changes when compared between control and radiation groups. Dietary PUFA supplementation showed a significant level of decrease in the lipid peroxidation in the irradiated groups. The observation of total lipids in brain shows decrease in concentration in the irradiated groups, the differences in the variables follow the similar patterns as of that the MDA levels. This study suggests that the dietary intake of PUFAs may help in prevention and recovery of the oxidative stress caused by radiation. (author)

Compatibility of 5-fluorouracil and total parenteral nutrition solutions.

Science.gov (United States)

Hardin, T C; Clibon, U; Page, C P; Cruz, A B

1982-01-01

The physicochemical stability and availability of 0.1% 5-fluorouracil solutions in D5W and a typical total parenteral nutrition solution (hypertonic dextrose and crystalline amino acids) were studied in both glass and Viaflex delivery systems. Serial samples collected over a 48-hour period were assayed for 5-fluorouracil concentration using a high performance liquid chromatographic technique. Changes in the pH as well as precipitate formation were also investigated. There was no reduction in the amount of 5-fluorouracil at 48 hours in either the glass or plastic system, regardless of whether the drug was added to D5W or to the total parenteral nutrition solution. No pH changes or precipitates were observed. These findings indicate that 5-fluorouracil is compatible with and available from total parenteral solutions of hypertonic dextrose and amino acid in both plastic and glass containers. Use of such a system would allow for (1) a reduction in vascular access in patients receiving both treatments and (2) continued administration of nutritional support without the requirement for additional fluid volume.

Effect of sucralfate on total carbon dioxide concentration in horses subjected to a simulated race test.

Science.gov (United States)

Caltabilota, T J; Milizio, J G; Malone, S; Kenney, J D; McKeever, K H

2010-02-01

The purpose of this study was to test the hypothesis that sucralfate, a gastric ulcer medication, would alter plasma concentrations of total carbon dioxide (tCO2), lactate (LA), sodium (Na+), potassium (K+), chloride (Cl-) and total protein (TP), as well as calculated plasma strong ion difference (SID) and packed cell volume (PCV) in horses subjected to a simulated race test (SRT). Six unfit Standardbred mares (approximately 520 kg, 9-18 years) were used in a randomized crossover design with the investigators blinded to the treatment given. The horses were assigned to either a control (40-50 mL apple sauce administered orally (PO)) or a sucralfate (20 mg/kg bodyweight dissolved in 40-50 mL apple sauce administered PO) group. Each horse completed a series of SRTs during which blood samples were taken via jugular venipuncture at five sampling intervals (prior to receiving treatment, prior to SRT, immediately following exercise, and at 60 and 90 min post-SRT). During the SRTs, each horse ran on a treadmill fixed on a 6% grade for 2 min at a warm-up speed (4 m/s) and then for 2 min at a velocity predetermined to produce VO2max. Each horse then walked at 4 m/s for 2 min to complete the SRT. Plasma tCO2, electrolytes, LA, and blood PCV and TP were analysed at all intervals. No differences (P>0.05) were detected between control and sucralfate for any of the measured variables. There were differences (P<0.05) in tCO2, SID, PCV, TP, LA and electrolyte concentrations relative to sampling time. However, these differences were attributable to the physiological pressures associated with acute exercise and were not an effect of the medication. It was concluded that sucralfate did not alter plasma tCO2 concentration in this study. Copyright (c) 2008 Elsevier Ltd. All rights reserved.

Biodegradable drug-eluting nanofiber-enveloped implants for sustained release of high bactericidal concentrations of vancomycin and ceftazidime: in vitro and in vivo studies

Directory of Open Access Journals (Sweden)

Hsu YH

2014-09-01

Full Text Available Yung-Heng Hsu,1,2 Dave Wei-Chih Chen,1 Chun-Der Tai,3 Ying-Chao Chou,1,2 Shih-Jung Liu,2 Steve Wen-Neng Ueng,1 Err-Cheng Chan4 1Department of Orthopedic Surgery, Chang Gung Memorial Hospital, Guishan Township, 2Department of Mechanical Engineering, Chang Gung University, Guishan Township, 3Graduate Institute of Medical Mechatronics, Chang Gung University, Guishan Township, 4School of Medical Technology, Chang Gung University, Guishan Township, Taiwan Abstract: We developed biodegradable drug-eluting nanofiber-enveloped implants that provided sustained release of vancomycin and ceftazidime. To prepare the biodegradable nanofibrous membranes, poly(D,L-lactide-co-glycolide and the antibiotics were first dissolved in 1,1,1,3,3,3-hexafluoro-2-propanol. They were electrospun into biodegradable drug-eluting membranes, which were then enveloped on the surface of stainless plates. An elution method and a high-performance liquid chromatography assay were employed to characterize the in vivo and in vitro release rates of the antibiotics from the nanofiber-enveloped plates. The results showed that the biodegradable nanofiber-enveloped plates released high concentrations of vancomycin and ceftazidime (well above the minimum inhibitory concentration for more than 3 and 8 weeks in vitro and in vivo, respectively. A bacterial inhibition test was carried out to determine the relative activity of the released antibiotics. The bioactivity ranged from 25% to 100%. In addition, the serum creatinine level remained within the normal range, suggesting that the high vancomycin concentration did not affect renal function. By adopting the electrospinning technique, we will be able to manufacture biodegradable drug-eluting implants for the long-term drug delivery of different antibiotics. Keywords: biodegradable nanofiber-enveloped plates, electrospinning, antibiotics, release characteristics

Effects of Spray-Drying and Choice of Solid Carriers on Concentrations of Labrasol® and Transcutol® in Solid Self-Microemulsifying Drug Delivery Systems (SMEDDS

Directory of Open Access Journals (Sweden)

Christopher Wai-Kei Lam

2013-01-01

Full Text Available Solid self-microemulsifying drug delivery systems (SMEDDS have been used increasingly for improving the bioavailability of hydrophobic drugs. Labrasol® and Transcutol® are used widely as surfactant and solubilizer in the formulation of solid SMEDDS. We investigated the effects of spray-drying and the use of different solid carriers on concentrations of Labrasol® and Transcutol® in solid SMEDDS with scutellarin as the formulated drug. Liquid and gas chromatography tandem mass spectrometry (LC-MS and GC-MS methods were developed for measuring low concentrations of Labrasol® and Transcutol®. In the preparation of solid SMEDDS, lactose, hydroxypropylmethyl cellulose (HPMC and microcrystalline cellulose (MCC were used as solid carriers. Judging from the retention ratios of Labrasol® and Transcutol®, the droplet size of solid SMEDDS increased after spray-drying of liquid SMEDDS, and concentrations of these excipients decreased after the solidifying procedure. In such reduction, Lactose and HPMC were found to preserve Labrasol® and Transcutol® better than MCC during spray-drying, and the resultant droplet sizes were smaller than that of MCC. Labrasol® and Transcutol® showed good thermal stability at 60 °C degree for 10 days. It can be concluded that spray-drying could increase the droplet size of solid SMEDDS and decreased the concentration of Labrasol® and Transcutol® therein, while water-soluble solid carriers could preserve Labrasol® and Transcutol® better than insoluble carriers in the solid SMEDDS.

Determination of total concentration of chemically labeled metabolites as a means of metabolome sample normalization and sample loading optimization in mass spectrometry-based metabolomics.

Science.gov (United States)

Wu, Yiman; Li, Liang

2012-12-18

For mass spectrometry (MS)-based metabolomics, it is important to use the same amount of starting materials from each sample to compare the metabolome changes in two or more comparative samples. Unfortunately, for biological samples, the total amount or concentration of metabolites is difficult to determine. In this work, we report a general approach of determining the total concentration of metabolites based on the use of chemical labeling to attach a UV absorbent to the metabolites to be analyzed, followed by rapid step-gradient liquid chromatography (LC) UV detection of the labeled metabolites. It is shown that quantification of the total labeled analytes in a biological sample facilitates the preparation of an appropriate amount of starting materials for MS analysis as well as the optimization of the sample loading amount to a mass spectrometer for achieving optimal detectability. As an example, dansylation chemistry was used to label the amine- and phenol-containing metabolites in human urine samples. LC-UV quantification of the labeled metabolites could be optimally performed at the detection wavelength of 338 nm. A calibration curve established from the analysis of a mixture of 17 labeled amino acid standards was found to have the same slope as that from the analysis of the labeled urinary metabolites, suggesting that the labeled amino acid standard calibration curve could be used to determine the total concentration of the labeled urinary metabolites. A workflow incorporating this LC-UV metabolite quantification strategy was then developed in which all individual urine samples were first labeled with (12)C-dansylation and the concentration of each sample was determined by LC-UV. The volumes of urine samples taken for producing the pooled urine standard were adjusted to ensure an equal amount of labeled urine metabolites from each sample was used for the pooling. The pooled urine standard was then labeled with (13)C-dansylation. Equal amounts of the (12)C

The role of dust storms in total atmospheric particle concentrations at two sites in the western U.S.

Science.gov (United States)

Neff, Jason C.; Reynolds, Richard L.; Munson, Seth M.; Fernandez, Daniel; Belnap, Jayne

2013-01-01

Mineral aerosols are produced during the erosion of soils by wind and are a common source of particles (dust) in arid and semiarid regions. The size of these particles varies widely from less than 2 µm to larger particles that can exceed 50 µm in diameter. In this study, we present two continuous records of total suspended particle (TSP) concentrations at sites in Mesa Verde and Canyonlands National Parks in Colorado and Utah, USA, respectively, and compare those values to measurements of fine and coarse particle concentrations made from nearby samplers. Average annual concentrations of TSP at Mesa Verde were 90 µg m−3 in 2011 and at Canyonlands were 171 µg m−3 in 2009, 113 µg m−3 in 2010, and 134 µg m−3 in 2011. In comparison, annual concentrations of fine (diameter of 2.5 µm and below) and coarse (2.5–10 µm diameter) particles at these sites were below 10 µg m−3 in all years. The high concentrations of TSP appear to be the result of regional dust storms with elevated concentrations of particles greater than 10 µm in diameter. These conditions regularly occur from spring through fall with 2 week mean TSP periodically in excess of 200 µg m−3. Measurement of particles on filters indicates that the median particle size varies between approximately 10 µm in winter and 40 µm during the spring. These persistently elevated concentrations of large particles indicate that regional dust emission as dust storms and events are important determinants of air quality in this region.

Herb-drug interactions.

Science.gov (United States)

Fugh-Berman, A

2000-01-08

Concurrent use of herbs may mimic, magnify, or oppose the effect of drugs. Plausible cases of herb-drug interactions include: bleeding when warfarin is combined with ginkgo (Ginkgo biloba), garlic (Allium sativum), dong quai (Angelica sinensis), or danshen (Salvia miltiorrhiza); mild serotonin syndrome in patients who mix St John's wort (Hypericum perforatum) with serotonin-reuptake inhibitors; decreased bioavailability of digoxin, theophylline, cyclosporin, and phenprocoumon when these drugs are combined with St John's wort; induction of mania in depressed patients who mix antidepressants and Panax ginseng; exacerbation of extrapyramidal effects with neuroleptic drugs and betel nut (Areca catechu); increased risk of hypertension when tricyclic antidepressants are combined with yohimbine (Pausinystalia yohimbe); potentiation of oral and topical corticosteroids by liquorice (Glycyrrhiza glabra); decreased blood concentrations of prednisolone when taken with the Chinese herbal product xaio chai hu tang (sho-salko-to); and decreased concentrations of phenytoin when combined with the Ayurvedic syrup shankhapushpi. Anthranoid-containing plants (including senna [Cassia senna] and cascara [Rhamnus purshiana]) and soluble fibres (including guar gum and psyllium) can decrease the absorption of drugs. Many reports of herb-drug interactions are sketchy and lack laboratory analysis of suspect preparations. Health-care practitioners should caution patients against mixing herbs and pharmaceutical drugs.

Refractometry for quality control of anesthetic drug mixtures.

Science.gov (United States)

Stabenow, Jennifer M; Maske, Mindy L; Vogler, George A

2006-07-01

Injectable anesthetic drugs used in rodents are often mixed and further diluted to increase the convenience and accuracy of dosing. We evaluated clinical refractometry as a simple and rapid method of quality control and mixing error detection of rodent anesthetic or analgesic mixtures. Dilutions of ketamine, xylazine, acepromazine, and buprenorphine were prepared with reagent-grade water to produce at least 4 concentration levels. The refraction of each concentration then was measured with a clinical refractometer and plotted against the percentage of stock concentration. The resulting graphs were linear and could be used to determine the concentration of single-drug dilutions or to predict the refraction of drug mixtures. We conclude that refractometry can be used to assess the concentration of dilutions of single drugs and can verify the mixing accuracy of drug combinations when the components of the mixture are known and fall within the detection range of the instrument.

Target concentration intervention: beyond Y2K.

Science.gov (United States)

Holford, N H

2001-01-01

Target concentration intervention (TCI) is proposed as an alternative conceptual strategy to therapeutic drug monitoring (TDM). It is argued that the idea of a therapeutic range has limited the interpretation of measured drug concentrations and diminished the anticipated clinical benefit to patients by use of an oversimplified pharmacodynamic model. TCI on the other hand embraces pharmacokinetic and pharmacodynamic concepts and uses the idea of a target effect and associated target concentration to make rational individual dose decisions.

Is the Total Concentration of a Heavy Metal in Soil a Suitable Tool for Assessing the Environmental Risk? Considering the Case of Copper

Science.gov (United States)

Fernández-Calviño, David; Pérez-Rodríguez, Paula; Nóvoa-Muñoz, Juan Carlos; Estévez, Manuel Arias

2017-01-01

National legislation concerning soil pollution by heavy metals in different countries is mostly based on the total heavy metal concentration levels allowed in different soils. As soil pollution is an issue of worldwide concern, here we develop a laboratory exercise for students in which they must check the suitability of a total metal…

Determination of As concentration in earthworm coelomic fluid extracts by total-reflection X-ray fluorescence spectrometry

Science.gov (United States)

Allegretta, Ignazio; Porfido, Carlo; Panzarino, Onofrio; Fontanella, Maria Chiara; Beone, Gian Maria; Spagnuolo, Matteo; Terzano, Roberto

2017-04-01

Earthworms are often used as sentinel organisms to study As bioavailability in polluted soils. Arsenic in earthworms is mainly sequestrated in the coelomic fluids whose As content can therefore be used to asses As bioavalability. In this work, a method for determining As concentration in coelomic fluid extracts using total-reflection X-ray fluorescence spectrometry (TXRF) is presented. For this purpose coelomic fluid extracts from earthworms living in three polluted soils and one non-polluted (control) soil have been collected and analysed. A very simple sample preparation was implemented, consisting of a dilution of the extracts with polyvinyl alcohol (PVA) using a 1:8 ratio and dropwise deposition of the sample on the reflector. A detection limit of 0.2 μg/l and quantification limit of 0.6 μg/l was obtained in the diluted samples, corresponding to 2 μg/l and 6 μg/l in the coelomic fluid extracts, respectively. This allowed to quantify As concentration in coelomic fluids extracted from earthworms living in soils polluted with As at concentrations higher than 20 mg/kg (considered as a pollution threshold for agricultural soils). The TXRF method has been validated by comparison with As concentrations in standards and by analysing the same samples by ICP-MS, after acid digestion of the sample. The low limit of detection, the proven reliability of the method and the little sample preparation make TXRF a suitable, cost-efficient and "green" technique for the analysis of As in earthworm coelomic fluid extracts for bioavailability studies.

Distribution of primaquine in human blood: Drug-binding to alpha 1-glycoprotein

International Nuclear Information System (INIS)

Kennedy, E.; Frischer, H.

1990-01-01

To clarify the distribution of the antimalarial primaquine in human blood, we measured the drug separately in the liquid, cellular, and ultrafiltrate phases. Washed red cells resuspended at a hematocrit of 0.4 were exposed to a submaximal therapeutic level of 250 ng/ml of carbon 14-labeled primaquine. The tracer was recovered quantitatively in separated plasma and red cells. Over 75% of the total labeled drug was found in red cells suspended in saline solution, but only 10% to 30% in red cells suspended in plasma. The plasma effect was not mediated by albumin. Studies with alpha 1-acid glycoprotein (AGP), tris(2-butoxyethyl)phosphate, an agent that displaces AGP-bound drugs, and cord blood known to have decreased AGP established that primaquine binds to physiologic amounts of the glycoprotein in plasma. Red cell primaquine concentration increased linearly as AGP level fell and as the free drug fraction rose. We suggest that clinical blood levels of primaquine include the red cell fraction or whole blood level because (1) erythrocytic primaquine is a sizable and highly variable component of the total drug in blood; (2) this component reflects directly the free drug in plasma, and inversely the extent of binding to AGP; (3) the amount of free primaquine may influence drug transport into specific tissues in vivo; and (4) fluctuations of AGP, an acute-phase reactant that increases greatly in patients with malaria and other infections, markedly affect the partition of primaquine in blood. Because AGP binds many basic drugs, unrecognized primaquine-drug interactions may exist

21 CFR 131.115 - Concentrated milk.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 2 2010-04-01 2010-04-01 false Concentrated milk. 131.115 Section 131.115 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN CONSUMPTION MILK AND CREAM Requirements for Specific Standardized Milk and Cream § 131.115...

Are dietary choline and betaine intakes determinants of total homocysteine concentration?

Science.gov (United States)

Elevated homocysteine concentrations are associated with an increased risk of cardiovascular disease and a decline in cognitive function. Intakes of choline and betaine, as methyl donors, may affect homocysteine concentrations. The objective was to examine whether choline and betaine intakes, assess...

Total reflection x-ray fluorescence spectroscopy as a tool for evaluation of iron concentration in ferrofluids and yeast samples

Energy Technology Data Exchange (ETDEWEB)

Kulesh, N.A., E-mail: nikita.kulesh@urfu.ru [Ural Federal University, Mira 19, 620002 Ekaterinburg (Russian Federation); Novoselova, I.P. [Ural Federal University, Mira 19, 620002 Ekaterinburg (Russian Federation); Immanuel Kant Baltic Federal University, 236041 Kaliningrad (Russian Federation); Safronov, A.P. [Ural Federal University, Mira 19, 620002 Ekaterinburg (Russian Federation); Institute of Electrophysics UD RAS, Amundsen 106, 620016 Ekaterinburg (Russian Federation); Beketov, I.V.; Samatov, O.M. [Institute of Electrophysics UD RAS, Amundsen 106, 620016 Ekaterinburg (Russian Federation); Kurlyandskaya, G.V. [Ural Federal University, Mira 19, 620002 Ekaterinburg (Russian Federation); University of the Basque Country UPV-EHU, 48940 Leioa (Spain); Morozova, M. [Ural Federal University, Mira 19, 620002 Ekaterinburg (Russian Federation); Denisova, T.P. [Irkutsk State University, Karl Marks 1, 664003 Irkutsk (Russian Federation)

2016-10-01

In this study, total reflection x-ray fluorescent (TXRF) spectrometry was applied for the evaluation of iron concentration in ferrofluids and biological samples containing iron oxide magnetic nanoparticles obtained by the laser target evaporation technique. Suspensions of maghemite nanoparticles of different concentrations were used to estimate the limitation of the method for the evaluation of nanoparticle concentration in the range of 1–5000 ppm in absence of organic matrix. Samples of single-cell yeasts grown in the nutrient media containing maghemite nanoparticles were used to study the nanoparticle absorption mechanism. The obtained results were analyzed in terms of applicability of TXRF for quantitative analysis in a wide range of iron oxide nanoparticle concentrations for biological samples and ferrofluids with a simple established protocol of specimen preparation. - Highlights: • Ferrofluids and yeasts samples were analysed by TXRF spectroscopy. • Simple protocol for iron quantification by means of TXRF was proposed. • Results were combined with magnetic, structural, and morphological characterization. • Preliminary conclusion on nanoparticles uptake mechanism was made.

Total reflection x-ray fluorescence spectroscopy as a tool for evaluation of iron concentration in ferrofluids and yeast samples

International Nuclear Information System (INIS)

Kulesh, N.A.; Novoselova, I.P.; Safronov, A.P.; Beketov, I.V.; Samatov, O.M.; Kurlyandskaya, G.V.; Morozova, M.; Denisova, T.P.

2016-01-01

In this study, total reflection x-ray fluorescent (TXRF) spectrometry was applied for the evaluation of iron concentration in ferrofluids and biological samples containing iron oxide magnetic nanoparticles obtained by the laser target evaporation technique. Suspensions of maghemite nanoparticles of different concentrations were used to estimate the limitation of the method for the evaluation of nanoparticle concentration in the range of 1–5000 ppm in absence of organic matrix. Samples of single-cell yeasts grown in the nutrient media containing maghemite nanoparticles were used to study the nanoparticle absorption mechanism. The obtained results were analyzed in terms of applicability of TXRF for quantitative analysis in a wide range of iron oxide nanoparticle concentrations for biological samples and ferrofluids with a simple established protocol of specimen preparation. - Highlights: • Ferrofluids and yeasts samples were analysed by TXRF spectroscopy. • Simple protocol for iron quantification by means of TXRF was proposed. • Results were combined with magnetic, structural, and morphological characterization. • Preliminary conclusion on nanoparticles uptake mechanism was made.

Pesticides, selected elements, and other chemicals in adult total diet samples October 1979-September 1980

International Nuclear Information System (INIS)

Gartrell, M.J.; Craun, J.C.; Podrebarac, D.S.; Gunderson, E.L.

1985-01-01

The US Food and Drug Administration (FDA) conducts Total Diet Studies to determine the dietary intake of selected pesticides, industrial chemicals, and elements (including radionuclides). These studies involve the retail purchase and analysis of foods representative of the diets of infants, toddlers, and adults. The individual food items are separated into a number of food groups, each of which is analyzed as a composite. This report summarizes the results for adult Total Diet samples collected in 20 cities between October 1979 and September 1980. The average concentration, range of concentrations, and calculated average daily intake of each chemical found are presented by food group. The average daily intakes of the chemicals are similar to those found in the several preceding years and are within acceptable limits. The results for samples collected during the same period that represent the diets of infants and toddlers are reported separately

21 CFR 862.1470 - Lipid (total) test system.

Science.gov (United States)

2010-04-01

... used in the diagnosis and treatment of various diseases involving lipid metabolism and atherosclerosis... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Lipid (total) test system. 862.1470 Section 862.1470 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED...

Interaction of cephalosporin drugs with dodecyltrimethylammonium Bromide

International Nuclear Information System (INIS)

Hoque, Md. Anamul; Hossain, Mohammed Delwar; Khan, Mohammed Abdullah

2013-01-01

Highlights: • We carry out the interaction of cephalosporin drugs with DTAB conductometrically. • We examine the effect of drugs on the critical micelle concentration of DTAB. • Three critical micelle concentrations are obtained for drug- DTAB system. • Electrostatic and hydrophobic interactions between drugs and DTAB are proposed. • Drug supported micelle formation of DTAB is much favoured in aq. solution of K 2 SO 4 . -- Abstract: The interaction of three cephalosporin drugs namely cefadroxyl monohydrate (CFM), cephalexin monohydrate (CLM) and cephradine monohydrate (CDM) with dodecyltrimethylammonium Bromide (DTAB) has been carried out by conductance measurements in aqueous medium and in aqueous solution of K 2 SO 4 salt over temperature range of (303.15 to 318.15) K. For pure DTAB and drug-DTAB systems, three critical micelle concentrations were obtained. The third critical micelle concentration (c ∗ 3 ) indicates that the spherical micelle turns into rod shape that is sphere to rod transition. The c ∗ values of DTAB are changed due to the addition of cephalosporin drugs. In addition, the change of the values of c ∗ 1 , c ∗ 2 and c ∗ 3 with increase of the concentration of drugs indicate the presence of interaction between drug and DTAB. The c ∗ values indicate that micellization for the cephalosporins-surfactant systems in water follow the order: CFM-surfactant ∗ values for the cephalosporins - DTAB systems in aqueous K 2 SO 4 are lower in magnitude than those in pure water and the values decrease with increase of the concentrations of K 2 SO 4 at a particular temperature. A significant decrease of c ∗ values in the presence of K 2 SO 4 for cephalosporins-DTAB systems indicates that drug supported ionic micelle formation is much favoured in aqueous K 2 SO 4 solution compared to that in pure water. For cephalosporin-DTAB systems, ΔG 0 m values are negative which indicate that the drugs mediated ionic micelle formation processes are

Enhanced drug delivery capabilities from stents coated with absorbable polymer and crystalline drug

OpenAIRE

Carlyle, Wenda C.; McClain, James B.; Tzafriri, Abraham R.; Bailey, Lynn; Zani, Brett G.; Markham, Peter M.; Stanley, James R.L.; Edelman, Elazer R.

2012-01-01

Current drug eluting stent (DES) technology is not optimized with regard to the pharmacokinetics of drug delivery. A novel, absorbable-coating sirolimus-eluting stent (AC-SES) was evaluated for its capacity to deliver drug more evenly within the intimal area rather than concentrating drug around the stent struts and for its ability to match coating erosion with drug release. The coating consisted of absorbable poly-lactide-co-glycolic acid (PLGA) and crystalline sirolimus deposited by a dry-p...

Early antiretroviral therapy and potent second-line drugs could decrease HIV incidence of drug resistance.

Science.gov (United States)

Shen, Mingwang; Xiao, Yanni; Rong, Libin; Meyers, Lauren Ancel; Bellan, Steven E

2017-06-28

Early initiation of antiretroviral therapy (ART) reduces the risk of drug-sensitive HIV transmission but may increase the transmission of drug-resistant HIV. We used a mathematical model to estimate the long-term population-level benefits of ART and determine the scenarios under which earlier ART (treatment at 1 year post-infection, on average) could decrease simultaneously both total and drug-resistant HIV incidence (new infections). We constructed an infection-age-structured mathematical model that tracked the transmission rates over the course of infection and modelled the patients' life expectancy as a function of ART initiation timing. We fitted this model to the annual AIDS incidence and death data directly, and to resistance data and demographic data indirectly among men who have sex with men (MSM) in San Francisco. Using counterfactual scenarios, we assessed the impact on total and drug-resistant HIV incidence of ART initiation timing, frequency of acquired drug resistance, and second-line drug effectiveness (defined as the combination of resistance monitoring, biomedical drug efficacy and adherence). Earlier ART initiation could decrease the number of both total and drug-resistant HIV incidence when second-line drug effectiveness is sufficiently high (greater than 80%), but increase the proportion of new infections that are drug resistant. Thus, resistance may paradoxically appear to be increasing while actually decreasing. © 2017 The Author(s).

The potential for portable X-ray fluorescence determination of soil copper at ancient metallurgy sites, and considerations beyond measurements of total concentrations.

Science.gov (United States)

Tighe, M; Rogan, G; Wilson, S C; Grave, P; Kealhofer, L; Yukongdi, P

2018-01-15

Copper (Cu) at ancient metallurgy sites represents the earliest instance of anthropogenically generated metal pollution. Such sites are spread across a wide range of environments from Eurasia to South America, and provide a unique opportunity to investigate the past and present extent and impact of metalworking contamination. Establishing the concentration and extent of soil Cu at archaeometallurgy sites can enhance archaeological interpretations of site use but can also, more fundamentally, provide an initial indication of contamination risk from such sites. Systematic evaluations of total soil Cu concentrations at ancient metalworking sites have not been conducted, due in part to the limitations of conventional laboratory-based protocols. In this paper, we first review what is known about Cu soil concentrations at ancient metallurgy sites. We then assess the benefits and challenges of portable X-ray fluorescence spectrometry (pXRF) as an alternative, rapid technique for the assessment of background and contaminant levels of Cu in soils. We conclude that pXRF is an effective tool for identifying potential contamination. Finally, we provide an overview of some major considerations beyond total Cu concentrations, such as bioavailability assessments, that will need to be considered at such sites to move toward a complete assessment of environmental and human risk. Copyright © 2017 Elsevier Ltd. All rights reserved.

Projecting future drug expenditures--2009.

Science.gov (United States)

Hoffman, James M; Shah, Nilay D; Vermeulen, Lee C; Doloresco, Fred; Martin, Patrick K; Blake, Sharon; Matusiak, Linda; Hunkler, Robert J; Schumock, Glen T

2009-02-01

Drug expenditure trends in 2007 and 2008, projected drug expenditures for 2009, and factors likely to influence drug expenditures are discussed. Various factors are likely to influence drug expenditures in 2009, including drugs in development, the diffusion of new drugs, drug safety concerns, generic drugs, Medicare Part D, and changes in the drug supply chain. The increasing availability of important generic drugs and drug safety concerns continue to moderate growth in drug expenditures. The drug supply chain remains dynamic and may influence drug expenditures, particularly in specialized therapeutic areas. Initial data suggest that the Medicare Part D benefit has influenced drug expenditures, but the ultimate impact of the benefit on drug expenditures remains unclear. From 2006 to 2007, total U.S. drug expenditures increased by 4.0%, with total spending rising from $276 billion to $287 billion. Drug expenditures in clinics continue to grow more rapidly than in other settings, with a 9.9% increase from 2006 to 2007. Hospital drug expenditures increased at a moderate rate of only 1.6% from 2006 to 2007; through the first nine months of 2008, hospital drug expenditures increased by only 2.8% compared with the same period in 2007. In 2009, we project a 0-2% increase in drug expenditures in outpatient settings, a 1-3% increase in expenditures for clinic-administered drugs, and a 1-3% increase in hospital drug expenditures.

Therapeutic drug monitoring of lopinavir/ritonavir in pregnancy.

LENUS (Irish Health Repository)

Lambert, J S

2012-02-01

OBJECTIVES: The aim of the study was to determine total and unbound lopinavir (LPV) plasma concentrations in HIV-infected pregnant women receiving lopinavir\\/ritonavir (LPV\\/r tablet) undergoing therapeutic drug monitoring (TDM) during pregnancy and postpartum. METHODS: Women were enrolled in the study who were receiving the LPV\\/r tablet as part of their routine prenatal care. Demographic and clinical data were collected and LPV plasma (total) and ultrafiltrate (unbound) concentrations were determined in the first, second and third trimesters using high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS\\/MS). Postpartum sampling was performed where applicable. Antepartum and postpartum trough concentrations (C(trough) ) were compared independently [using analysis of variance (anova)] and on a longitudinal basis (using a paired t-test). RESULTS: Forty-six women were enrolled in the study (38 Black African). Forty women initiated LPV\\/r treatment in pregnancy. Median (range) gestation at initiation was 25 (15-36) weeks and median (range) baseline CD4 count and viral load were 346 (14-836) cells\\/muL and 8724 (<50-267408) HIV-1 RNA copies\\/mL, respectively. Forty women (87%) had LPV concentrations above the accepted minimum effective concentration for wild-type virus (MEC; 1000 ng\\/mL). Geometric mean (95% confidence interval [CI]) total LPV concentrations in the first\\/second [3525 (2823-4227) ng\\/mL; n=16] and third [3346 (2813-3880) ng\\/mL; n=43] trimesters were significantly lower relative to postpartum [5136 (3693-6579) ng\\/mL; n=12] (P=0.006). In a paired analysis (n=12), LPV concentrations were reduced in the third trimester [3657 (2851-4463) ng\\/mL] vs. postpartum (P=0.021). No significant differences were observed in the LPV fraction unbound (fu%). Conclusions The above target concentrations achieved in the majority of women and similarities in the fu% suggest standard dosing of the LPV\\/r tablet is appropriate during pregnancy

Drug: D08821 [KEGG MEDICUS

Lifescience Database Archive (English)

Full Text Available D08821 Drug Concentrated human red blood cells; Red cells concentrates -leukocytes... reduced (RCC-LR) (TN); Irradiated red cells concentrates -leukocytes reduced (Ir-RCC-LR) (TN) ... PubChem: 96025504 ...

Total serum vitamin C concentration in pregnant women: implications for a healthy pregnancy Concentração total de vitamina C na gestante: implicações para uma gestação saudável

Directory of Open Access Journals (Sweden)

Garba Ibrahim Hassan

2006-09-01

Full Text Available OBJECTIVES: total serum vitamin C (L-ascorbic acid concentration was measured in 90 pregnant women, 30 in each trimester (age range 18-35 years and a control group of age-matched non-pregnant women. METHODS: total serum vitamin C concentration was measured using the 2.4-dinitrophenylhydrazine method which involves the conversion of vitamin C to dehydroascorbic acid in the presence of copper (II ions and subsequent measurement of the resulting bis-hydrazone at 540nm. RESULTS: the total vitamin C concentration in the first trimester was 2.55 ± 0.82 mg/dl and 2.32 ± 0.40 mg/dl and 0.77 ± 0.10 mg/dl in the second and third trimesters respectively. Relative to serum total vitamin C concentration in the controls (3.15 ± 0.13 mg/dl these values are significantly lower (p OBJETIVOS: a concentração sérica total de vitamina C (ácido 1-ascórbico foi medida em 90 mulheres grávidas sendo 30 em cada trimestre (idade de 18-35 anos e um grupo controle, pareado por idade, de mulheres não grávidas. MÉTODOS: a concentração sérica total de vitamina C foi medida usando o método 2.4-dinitrofenilhidrazina que envolve a conversão de vitama C a ácido dehidroascorbico na presença de íons cobre II e, em seguida, medindo a resultante bi-hidrazona em 540 nm. RESULTADOS: a concentração total de vitamina C no primeiro semestre foi de 2.55 ± 0,13 mg/dL e de 2,32 ± 0,40 mg/dL e 0,77 ± 0,10 mg/dL no segundo e terceiro trimestres, respectivamente. Estes valores são significativamente mais baixos do que nos controles (3,15 ± 0,13 mg/dL(p<0,05. CONCLUSÕES: reduzida concentração de vitamina C sérica na gestação pode indicar a sua utilização para retirar o excesso de espécies oxigênio-reativas e manter a homeostase normal. Assim, recomenda-se a suplementação de vitamina C na gestação para aumentar o seu baixo nível no organismo e previnir a predisposição para o baixo peso ao nascer, parto prematuro e pré-eclâmpsia, condições associadas

Drug adsorption to plastic containers and retention of drugs in cultured cells under in vitro conditions.

Science.gov (United States)

Palmgrén, Joni J; Mönkkönen, Jukka; Korjamo, Timo; Hassinen, Anssi; Auriola, Seppo

2006-11-01

Loss of drug content during cell culture transport experiment can lead to misinterpretations in permeability analysis. This study analyses drug adsorption to various plastic containers and drug retention in cultured cells under in vitro conditions. The loss of various drugs to polystyrene tubes and well plates was compared to polypropylene and glass tubes both in deionised water and buffer solution. In cellular uptake experiments, administered drugs were obtained from cultured cells by liquid extraction. Samples were collected at various time points and drug concentrations were measured by a new HPLC-MS/MS method. Acidic drugs (hydrochlorothiazide, naproxen, probenicid, and indomethacin) showed little if any sorption to all tested materials in either water or buffer. In the case of basic drugs, substantial loss to polystyrene tubes and well plates was observed. After 4.5 h, the relative amount remaining in aqueous test solution stored in polystyrene tubes was 64.7 +/- 6.8%, 38.4 +/- 9.1%, 31.9 +/- 6.7%, and 23.5 +/- 6.1% for metoprolol, medetomidine, propranolol, and midazolam, respectively. Interestingly, there was no significant loss of drugs dissolved in buffer to any of the tested materials indicating that buffer reduced surficial interaction. The effect of drug concentration to sorption was also tested. Results indicated that the higher the concentration in the test solution the lower the proportional drug loss, suggesting that the polystyrene contained a limited amount of binding sites. Cellular uptake studies showed considerable retention of drugs in cultured cells. The amounts of absorbed drugs in cellular structures were 0.45%, 4.88%, 13.15%, 43.80%, 23.57% and 11.22% for atenolol, metoprolol, medetomidine, propranolol, midazolam, and diazepam, respectively. Overall, these findings will benefit development and validation of further in vitro drug permeation experiments.

Bioaccumulation of heavy metals in the earthworms Lumbricus rubellus and Aporrectodea caliginosa in relation to total and available metal concentrations in field soils

International Nuclear Information System (INIS)

Hobbelen, P.H.F.; Koolhaas, J.E.; Gestel, C.A.M. van

2006-01-01

The aim of this study was to determine important metal pools for bioaccumulation by the earthworms Lumbricus rubellus and Aporrectodea caliginosa in soils with high binding capacity. Cd, Cu and Zn concentrations in soil, pore water and CaCl 2 extracts of soil, in leaves of the plant species Urtica dioica and in earthworms were determined at 15 field sites constituting a gradient in metal pollution. Variations in the Cu and Cd concentrations in L. rubellus and Cu concentrations in A. caliginosa were best explained by total soil concentrations, while variation in Cd concentration in A. caliginosa was best explained by pore water concentrations. Zn concentrations in L. rubellus and A. caliginosa were not significantly correlated to any determined variable. It is concluded that despite low availability, earthworms in floodplain soils contain elevated concentrations of Cu and Cd, suggesting that uptake takes place not only from the soluble metal concentrations. - Earthworms in floodplain soils not only accumulate heavy metals from soluble metal pools

Bioaccumulation of heavy metals in the earthworms Lumbricus rubellus and Aporrectodea caliginosa in relation to total and available metal concentrations in field soils

Energy Technology Data Exchange (ETDEWEB)

Hobbelen, P.H.F. [Department of Animal Ecology, Faculty of Earth and Life Sciences, Vrije Universiteit Amsterdam, De Boelelaan 1085, 1081 HV Amsterdam (Netherlands)]. E-mail: phobbelen@usgs.gov; Koolhaas, J.E. [Department of Animal Ecology, Faculty of Earth and Life Sciences, Vrije Universiteit Amsterdam, De Boelelaan 1085, 1081 HV Amsterdam (Netherlands); Gestel, C.A.M. van [Department of Animal Ecology, Faculty of Earth and Life Sciences, Vrije Universiteit Amsterdam, De Boelelaan 1085, 1081 HV Amsterdam (Netherlands)

2006-11-15

The aim of this study was to determine important metal pools for bioaccumulation by the earthworms Lumbricus rubellus and Aporrectodea caliginosa in soils with high binding capacity. Cd, Cu and Zn concentrations in soil, pore water and CaCl{sub 2} extracts of soil, in leaves of the plant species Urtica dioica and in earthworms were determined at 15 field sites constituting a gradient in metal pollution. Variations in the Cu and Cd concentrations in L. rubellus and Cu concentrations in A. caliginosa were best explained by total soil concentrations, while variation in Cd concentration in A. caliginosa was best explained by pore water concentrations. Zn concentrations in L. rubellus and A. caliginosa were not significantly correlated to any determined variable. It is concluded that despite low availability, earthworms in floodplain soils contain elevated concentrations of Cu and Cd, suggesting that uptake takes place not only from the soluble metal concentrations. - Earthworms in floodplain soils not only accumulate heavy metals from soluble metal pools.

Variable Linezolid Exposure in Intensive Care Unit Patients-Possible Role of Drug-Drug Interactions.

Science.gov (United States)

Töpper, Christoph; Steinbach, Cathérine L; Dorn, Christoph; Kratzer, Alexander; Wicha, Sebastian G; Schleibinger, Michael; Liebchen, Uwe; Kees, Frieder; Salzberger, Bernd; Kees, Martin G

2016-10-01

Standard doses of linezolid may not be suitable for all patient groups. Intensive care unit (ICU) patients in particular may be at risk of inadequate concentrations. This study investigated variability of drug exposure and its potential sources in this population. Plasma concentrations of linezolid were determined by high-performance liquid chromatography in a convenience sample of 20 ICU patients treated with intravenous linezolid 600 mg twice daily. Ultrafiltration applying physiological conditions (pH 7.4/37°C) was used to determine the unbound fraction. Individual pharmacokinetic (PK) parameters were estimated by population PK modeling. As measures of exposure to linezolid, area under the concentration-time curve (AUC) and trough concentrations (Cmin) were calculated and compared with published therapeutic ranges (AUC 200-400 mg*h/L, Cmin 2-10 mg/L). Coadministered inhibitors or inducers of cytochrome P450 and/or P-glycoprotein were noted. Data from 18 patients were included into the PK evaluation. Drug exposure was highly variable (median, range: AUC 185, 48-618 mg*h/L, calculated Cmin 2.92, 0.0062-18.9 mg/L), and only a minority of patients had values within the target ranges (6 and 7, respectively). AUC and Cmin were linearly correlated (R = 0.98), and classification of patients (underexposed/within therapeutic range/overexposed) according to AUC or Cmin was concordant in 15 cases. Coadministration of inhibitors was associated with a trend to higher drug exposure, whereas 3 patients treated with levothyroxine showed exceedingly low drug exposure (AUC ∼60 mg*h/L, Cmin linezolid is highly variable and difficult to predict in ICU patients, and therapeutic drug monitoring seems advisable. PK drug-drug interactions might partly be responsible and should be further investigated; protein binding appears to be stable and irrelevant.

Total mercury concentrations in anadromous Northern Dolly Varden from the northwestern Canadian Arctic: A historical baseline study

Energy Technology Data Exchange (ETDEWEB)

Tran, L., E-mail: l5tran@uwaterloo.ca [Department of Biology, University of Waterloo, Waterloo, Ontario N2L 3G1 (Canada); Reist, J.D. [Fisheries and Oceans Canada, Winnipeg, Manitoba R3T 2N6 (Canada); Power, M., E-mail: m3power@uwaterloo.ca [Department of Biology, University of Waterloo, Waterloo, Ontario N2L 3G1 (Canada)

2015-03-15

Previous research has documented the significance of total mercury (THg) as a northern contaminant in general and of fish in particular. While much research has been devoted to documenting both spatial and temporal changes in THg in consumed fish, little effort has been directed at understanding patterns of THg in Dolly Varden (Salvelinus malma), a prized subsistence species throughout the western North American Arctic. Here we report historical THg concentrations for anadromous Dolly Varden from 10 populations in the Yukon and Northwest Territories sampled across a range of latitudes (67–69°N) and longitudes (136–141°W) between the years 1988–91. Unadjusted mean THg concentrations ranged from 15 to 254 ng/g wet weight. Length-adjusted THg concentrations were significantly different among sites, but were not related to latitude or longitude. Within and among populations, THg was significantly related to fork-length, age, δ{sup 15}N, and δ{sup 13}C, with the variation in THg found among populations being best explained by size. The data serve as an important baseline against which future changes in THg levels in this important subsistence fishery may be compared to determine the significance of any observed trends. - Highlights: • THg were measured in Dolly Varden from the Yukon and Northwest Territories. • Length-adjusted THg concentrations were not related to latitude or longitude. • Among-population variation in THg was best explained by fork-length. • Length-adjusted THg concentrations were related to age, δ{sup 15}N, and δ{sup 13}C. • Mean THg were below Health Canada’s consumption guideline for commercial fish.

Total mercury concentrations in anadromous Northern Dolly Varden from the northwestern Canadian Arctic: A historical baseline study

International Nuclear Information System (INIS)

Tran, L.; Reist, J.D.; Power, M.

2015-01-01

Previous research has documented the significance of total mercury (THg) as a northern contaminant in general and of fish in particular. While much research has been devoted to documenting both spatial and temporal changes in THg in consumed fish, little effort has been directed at understanding patterns of THg in Dolly Varden (Salvelinus malma), a prized subsistence species throughout the western North American Arctic. Here we report historical THg concentrations for anadromous Dolly Varden from 10 populations in the Yukon and Northwest Territories sampled across a range of latitudes (67–69°N) and longitudes (136–141°W) between the years 1988–91. Unadjusted mean THg concentrations ranged from 15 to 254 ng/g wet weight. Length-adjusted THg concentrations were significantly different among sites, but were not related to latitude or longitude. Within and among populations, THg was significantly related to fork-length, age, δ 15 N, and δ 13 C, with the variation in THg found among populations being best explained by size. The data serve as an important baseline against which future changes in THg levels in this important subsistence fishery may be compared to determine the significance of any observed trends. - Highlights: • THg were measured in Dolly Varden from the Yukon and Northwest Territories. • Length-adjusted THg concentrations were not related to latitude or longitude. • Among-population variation in THg was best explained by fork-length. • Length-adjusted THg concentrations were related to age, δ 15 N, and δ 13 C. • Mean THg were below Health Canada’s consumption guideline for commercial fish

Serum caffeine concentrations and short-term outcomes in premature infants of ⩽29 weeks of gestation.

Science.gov (United States)

Alur, P; Bollampalli, V; Bell, T; Hussain, N; Liss, J

2015-06-01

Caffeine is effective in the treatment of apnea of prematurity but it is not well known if the therapeutic concentration of the drug has an impact on other neonatal outcomes such as chronic lung disease (CLD). The aim of this study was to determine if there is an association between caffeine concentrations and the incidence of CLD in premature infants of ⩽29 weeks of gestation. A retrospective chart review of all the infants born ⩽29 weeks of gestation from 2007 to 2011, who survived until discharge or 36 weeks postmenstrual age, was conducted. Caffeine concentrations were obtained weekly on infants getting the drug. Average caffeine concentrations (ACCs) were determined for the duration of caffeine therapy and correlated with CLD, length of stay (LOS), oxygen at discharge (OD), duration of ventilation (DV) and total charges for hospitalization for each patient. Of the 222 eligible infants, 198 met the inclusion criteria. ACC for infants without CLD was 17.0±3.8 μg ml(-1) compared with infants with CLD 14.3±6.1 μg ml(-1) (P14.5 μg ml(-1)) had lower incidence of patent ductus arteriosus, lesser number of days on ventilator and oxygen, lesser need for diuretics, lower incidence of CLD, were more likely to go home without supplemental OD and had lower LOS and lower total hospital charges (all differences were significant PCLD. Receiver operating curve analysis confirmed a significant predictive ability of caffeine concentration for CLD with a cutoff concentration of 14.5 μg ml(-1) (sensitivity of 42.6 and specificity of 86.8). The AUC (area under the curve) for the prediction of CLD was 0.632 (95% confidence interval 0.56-0.69, P=0.009). Caffeine concentrations >14.5 μg ml(-1) were strongly correlated with reduced CLD in infants born at ⩽29 weeks of gestation. Higher caffeine concentrations were associated with decreased total hospital charges, DV, OD and LOS. Additional randomized trials are needed to confirm these findings, to

Plant assemblage composition and soil P concentration differentially affect communities of AM and total fungi in a semi-arid grassland.

Science.gov (United States)

Klabi, Rim; Bell, Terrence H; Hamel, Chantal; Iwaasa, Alan; Schellenberg, Mike; Raies, Aly; St-Arnaud, Marc

2015-01-01

Adding inorganic P- and N-fixing legumes to semi-arid grasslands can increase forage yield, but soil nutrient concentrations and plant cover may also interact to modify soil fungal populations, impacting short- and long-term forage production. We tested the effect of plant assemblage (seven native grasses, seven native grasses + the domesticated N-fixing legume Medicago sativa, seven native grasses + the native N-fixing legume Dalea purpurea or the introduced grass Bromus biebersteinii + M. sativa) and soil P concentration (addition of 0 or 200 P2O5 kg ha(-1) at sowing) on the diversity and community structure of arbuscular mycorrhizal (AM) fungi and total fungi over two consecutive years, using 454-pyrosequencing of 18S rDNA and ITS amplicons. Treatment effects were stronger in the wet year (2008) than the dry year (2009). The presence of an N-fixing legume with native grasses generally increased AM fungal diversity, while the interaction between soil P concentration and plant assemblage modified total fungal community structure in 2008. Excluding interannual variations, which are likely driven by moisture and plant productivity, AM fungal communities in semi-arid grasslands appear to be primarily affected by plant assemblage composition, while the composition of other fungi is more closely linked to soil P. © FEMS 2014. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Total antioxidant status in women with breast cancer

International Nuclear Information System (INIS)

Mahmood, I.H.; Abdullah, K.S.; Abdullah, M.S.

2009-01-01

Objective: To measure the concentration of total antioxidant status (TAS) in women with breast cancer. Methodology: This is a case control study conducted in Al-Salam Hospital and Department of Pharmacology in Mosul Medical College. Twenty women having histologically confirmed breast cancer and twenty age-matched healthy volunteer women participated in the study. Serum total antioxidant status (TAS) was measured in both groups. Results: Mean TAS of the patient group (0.91 +- 0.32 mmol/l) was significantly lower (P<0.001) than that of the control group (1.82 +- 0.14 mmol/l). Conclusion: The present study demonstrated that women with breast cancer have a low level of TAS as compared to those of healthy women. It further emphasizes the growing concern that oxidative damage may occur in those patients that exhaust the antioxidant defense of the body leading to a low levels of TAS. Administration of antioxidant supplements such as a combination of vitamins A, C and E are necessary in women at high risk of developing breast cancer or after surgery or with anticancer drugs. (author)

Drugs Cheaper Than Threepenny: The Market of Extremely Low-Priced Drugs within the National Health Insurance in Taiwan

Science.gov (United States)

Chou, Li-Fang

2014-01-01

While most drug policy researches paid attention to the financial impact of expensive drugs, the market situation of low-priced drugs in a country was seldom analyzed. We used the nationally representative claims datasets to explore the status within the National Health Insurance (NHI) in Taiwan. In 2007, a total of 12,443 distinct drug items had been prescribed 853,250,147 times with total expenditure of 105,216,950,198 new Taiwan dollars (NTD). Among them, 7,366 oral drug items accounted for 701,353,383 prescribed items and 68,133,988,960 NTD. Besides, 2,887 items (39.2% of oral drug items) belonged to cheap drugs with the unit price ≤1 NTD (about 0.03 of US dollar). While the top one item among all oral drugs had already a market share of 5.0%, 30 items 30.3% and 107 items 50.0%, the cheap drugs with aggregate 332,893,462 prescribed items (47.5% of all prescribed oral drug items) only accounted for 2,750,725,433 NTD (4.0% of expenditure for oral drugs and 2.6% of total drug expenditure). The drug market of Taiwan's NHI was abundant in cheap drugs. The unreasonably low prices of drugs might not guarantee the quality of pharmaceutical care and the sustainability of a healthy pharmaceutical industry in the long run. PMID:24719568

The validation of an invitro colonic motility assay as a biomarker for gastrointestinal adverse drug reactions

International Nuclear Information System (INIS)

Keating, Christopher; Martinez, Vicente; Ewart, Lorna; Gibbons, Stephen; Grundy, Luke; Valentin, Jean-Pierre; Grundy, David

2010-01-01

Motility-related gastrointestinal adverse drug reactions (GADRs), such as constipation and diarrhea, are some of the most frequently reported adverse events associated with the clinical development of new chemical entities, and for marketed drugs. However, biomarkers capable of detecting such GADRs are lacking. Here, we describe an in vitro assay developed to detect and quantify changes in intestinal motility as a surrogate biomarker for constipation/diarrhea-type GADRs. In vitro recordings of intraluminal pressure were used to monitor the presence of colonic peristaltic motor complexes (CPMCs) in mouse colonic segments. CPMC frequency, contractile and total mechanical activity were assessed. To validate the assay, two experimental protocols were conducted. Initially, five drugs with known gastrointestinal effects were tested to determine optimal parameters describing excitation and inhibition as markers for disturbances in colonic motility. This was followed by a 'blinded' evaluation of nine drugs associated with or without clinically identified constipation/diarrhea-type GADRs. Concentration-response relationships were determined for these drugs and the effects were compared with their maximal free therapeutic plasma concentration in humans. The assay detected stimulatory and inhibitory responses, likely correlating to the occurrence of diarrhea or constipation. Concentration-related effects were identified and potential mechanisms of action were inferred for several drugs. Based on the results from the fourteen drugs assessed, the sensitivity of the assay was calculated at 90%, with a specificity of 75% and predictive capacity of 86%. These results support the potential use of this assay in screening for motility-related GADRs during early discovery phase, safety pharmacology assessment.

Financial Burden of Cancer Drug Treatment in Lebanon.

Science.gov (United States)

Elias, Fadia; Khuri, Fadlo R; Adib, Salim M; Karam, Rita; Harb, Hilda; Awar, May; Zalloua, Pierre; Ammar, Walid

2016-01-01

The Ministry of Public Health (MOPH) in Lebanon provides cancer drugs free of charge for uninsured patients who account for more than half the total caseload. Other categories of cancer care are subsidized under more stringent eligibility criteria. MOPH's large database offers an excellent opportunity to analyze the cost of cancer treatment in Lebanon. Using utilization and spending data accumulated at MOPH during 20082013, the cost to the public budget of cancer drugs was assessed per case and per drug type. The average annual cost of cancer drugs was 6,475$ per patient. Total cancer drug costs were highest for breast cancer, followed by chronic myeloid leukemia (CML), colorectal cancer, lung cancer, and NonHodgkin's lymphoma (NHL), which together represented 74% of total MOPH cancer drug expenditure. The annual average cancer drug cost per case was highest for CML ($31,037), followed by NHL ($11,566). Trastuzumab represented 26% and Imatinib 15% of total MOPH cancer drug expenditure over six years. Sustained increase in cancer drug cost threatens the sustainability of MOPH coverage, so crucial for socially vulnerable citizens. To enhance the bargaining position with pharmaceutical firms for drug cost containment in a small market like Lebanon, drug price comparisons with neighboring countries which have already obtained lower prices may succeed in lowering drug costs.

Nonsmoker Exposure to Secondhand Cannabis Smoke. III. Oral Fluid and Blood Drug Concentrations and Corresponding Subjective Effects.

Science.gov (United States)

Cone, Edward J; Bigelow, George E; Herrmann, Evan S; Mitchell, John M; LoDico, Charles; Flegel, Ronald; Vandrey, Ryan

2015-09-01

The increasing use of highly potent strains of cannabis prompted this new evaluation of human toxicology and subjective effects following passive exposure to cannabis smoke. The study was designed to produce extreme cannabis smoke exposure conditions tolerable to drug-free nonsmokers. Six experienced cannabis users smoked cannabis cigarettes [5.3% Δ(9)-tetrahydrocannabinol (THC) in Session 1 and 11.3% THC in Sessions 2 and 3] in a closed chamber. Six nonsmokers were seated alternately with smokers during exposure sessions of 1 h duration. Sessions 1 and 2 were conducted with no ventilation and ventilation was employed in Session 3. Oral fluid, whole blood and subjective effect measures were obtained before and at multiple time points after each session. Oral fluid was analyzed by ELISA (4 ng/mL cutoff concentration) and by LC-MS-MS (limit of quantitation) for THC (1 ng/mL) and total THCCOOH (0.02 ng/mL). Blood was analyzed by LC-MS-MS (0.5 ng/mL) for THC, 11-OH-THC and free THCCOOH. Positive tests for THC in oral fluid and blood were obtained for nonsmokers up to 3 h following exposure. Ratings of subjective effects correlated with the degree of exposure. Subjective effect measures and amounts of THC absorbed by nonsmokers (relative to smokers) indicated that extreme secondhand cannabis smoke exposure mimicked, though to a lesser extent, active cannabis smoking. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Total and cytosolic concentrations of twenty metals/metalloids in the liver of brown trout Salmo trutta (Linnaeus, 1758) from the karstic Croatian river Krka.

Science.gov (United States)

Dragun, Zrinka; Filipović Marijić, Vlatka; Krasnići, Nesrete; Ivanković, Dušica; Valić, Damir; Žunić, Jakov; Kapetanović, Damir; Smrzlić, Irena Vardić; Redžović, Zuzana; Grgić, Ivana; Erk, Marijana

2018-01-01

Total and cytosolic concentrations of twenty metals/metalloids in the liver of brown trout Salmo trutta (Linnaeus, 1758) were studied in the period from April 2015 to May 2016 at two sampling sites on Croatian river Krka, to establish if river water contamination with metals/metalloids downstream of Knin town has influenced metal bioaccumulation in S. trutta liver. Differences were observed between two sites, with higher concentrations of several elements (Ag, As, Ca, Co, Na, Se, Sr, V) found downstream of Knin town, whereas few others (Cd, Cs, Mo, Tl) were, unexpectedly, increased at the Krka River spring. However, total metal/metalloid concentrations in the liver of S. trutta from both sites of the Krka River were still mainly below previously reported levels for pristine freshwaters worldwide. The analysis of seasonal changes of metal/metalloid concentrations in S. trutta liver and their association with fish sex and size mostly indicated their independence of fish physiology, making them good indicators of water contamination and exposure level. Metal/metalloid concentrations in the metabolically available hepatic cytosolic fractions reported in this study are the first data of that kind for S. trutta liver, and the majority of analyzed elements were present in the cytosol in the quantity higher than 50% of their total concentrations, thus indicating their possible availability for toxic effects. However, the special attention should be directed to As, Cd, Cs, and Tl, which under the conditions of increased exposure tended to accumulate more within the cytosol. Although metal/metalloid concentrations in S. trutta liver were still rather low, monitoring of the Krka River water quality and of the health status of its biota is essential due to a trend of higher metal/metalloid bioaccumulation downstream of Knin town, especially taking into consideration the proximity of National Park Krka and the need for its conservation. Copyright © 2017 Elsevier Inc. All

Drug-drug Interactions of Statins Potentially Leading to Muscle-Related Side Effects in Hospitalized Patients.

Science.gov (United States)

Bucsa, Camelia; Farcas, Andreea; Leucuta, D; Mogosan, Cristina; Bojita, M; Dumitrascu, D L

2015-01-01

The associations of drugs that may interact with the statins resulting in elevated serum concentration of the statins are an important risk factor for statin induced muscle disorders. We aimed to determine the prevalence of these associations in all hospitalized patients that had been prescribed statins before/during hospitalization and to find out how often they are associated with muscle-related side effects. This prospective, non-interventional study performed in two internal medicine departments included patients with statin therapy before/during hospitalization. Data on each patient demographic characteristics, co-morbidities and treatment was collected from medical charts and interviews. We evaluated patients' therapy for the targeted associations using Thomson Micromedex Drug Interactions checker and we ranked the identified drug-drug interactions (DDIs) accordingly. Each patient with statin treatment before admission was additionally interviewed in order to identify muscular symptoms. In 109 patients on statin treatment we found 35 potential (p) DDIs of statins in 30 (27.5%) patients, most of which were in the therapy before admission (27 pDDIs). The pDDIs were moderate (20 pDDIs) and major (15 pDDIs). Of the total number of pDDIs, 24 were targeting the muscular system. The drugs most frequently involved in the statins' pDDIs were amiodarone and fenofibrate. Two of the patients with pDDIs reported muscle pain, both having additional risk factors for statin induced muscular effects. The prevalence of statins' pDDIs was high in our study, mostly in the therapy before admission, with only a small number of pDDIs resulting in clinical outcome.

Cardiotoxicity of copper-based antineoplastic drugs casiopeinas is related to inhibition of energy metabolism

International Nuclear Information System (INIS)

Hernandez-Esquivel, Luz; Marin-Hernandez, Alvaro; Pavon, Natalia; Carvajal, Karla; Moreno-Sanchez, Rafael

2006-01-01

Isolated rat hearts were perfused with glucose, octanoate or glucose + octanoate and different concentrations of the copper-based antineoplastic drugs casiopeina II-gly (CSII) or casiopeina III-i-a (CSIII). In isolated perfused hearts with glucose + octanoate, both casiopeinas induced diminution in cardiac work and O 2 consumption with half-maximal inhibitory concentrations (IC 5 ) of 4 (CSII) and 4.6 (CSIII) μM, after 1 h of perfusion. Strong inhibition of the pyruvate and 2-oxoglutarate dehydrogenases as well as total creatine kinase by casiopeinas suggested that ATP generation by oxidative phosphorylation and its transfer towards myofibrils were targets for these drugs. In consequence, the cellular contents of ATP and phosphocreatine were also lowered by casiopeinas. Remarkably, casiopeinas were less toxic than adriamycin (IC 5 = 2.6 μM), a well-known potent cardiotoxic and antineoplastic drug, which has a wide clinical use. In an open-chest animal, which is a more physiological model than the isolated heart, femoral administration of 1 μM drug revealed that CSII was innocuous very likely due to strong binding to serum albumin, whereas adriamycin induced again a potent cardiotoxic effect (diminution in heart rate and severe depression of systolic blood pressure). Thus, it seems that casiopeinas are a group of new antineoplastic drugs with milder secondary toxic effects than proven drugs such as adriamycin

Effect of dental restorative materials on total antioxidant capacity and calcium concentration of unstimulated saliva.

Science.gov (United States)

Ramezani, Gholam H; Moghadam, Mona-Momeni; Saghiri, Mohammad-Ali; Garcia-Godoy, Franklin; Asatourian, Armen; Aminsobhani, Mohsen; Scarbecz, Mark; Sheibani, Nader

2017-01-01

To evaluate the effect of dental amalgam and composite restorations on total antioxidant capacity (TAC) and calcium (Ca) ion concentration of unstimulated saliva. Forty-eight children aged 6-10 years selected and divided into three groups of sixteen (8 males, 8 females). In group A and B, samples consisted of two class II dental composite or amalgam restorations, while in group C samples were caries-free (control group). Unstimulated saliva from all samples was collected and TAC was measured by spectrophotometry using an adaptation of 2, 2'-azino-di-(3-ethylbenzthiazoline-6-sulphonate) (ABTS) assay. The Ca ion level was estimated by an auto- analyzer. Data were analyzed with one- and two-way ANOVA test, at a p difference between groups ( p differences within and between groups ( p Gender is an effective factor in changes induced in oral cavity as females showed more emphatic reaction to dental filling materials than males. Patients who have dental restorations, especially dental composites, should pay more attention to their dental hygiene, because dental restorations can increase oxidative stress and decrease Ca ion level in saliva, which might jeopardize remineralization process of tooth structures after demineralization. Key words: Amalgam, caries, composite, saliva, total antioxidant capacity.

Pharmacokinetics of Botanical Drugs and Plant Extracts.

Science.gov (United States)

Dominguez More, Gina Paola; Cardenas, Paola Andrea; Costa, Geison M; Simoes, Claudia M O; Aragon, Diana Marcela

2017-01-01

Botanical drugs contain plant extracts, which are complex mixtures of compounds. As with conventional drugs, it is necessary to validate their efficacy and safety through preclinical and clinical studies. However, pharmacokinetic studies for active constituents or characteristic markers in botanical drugs are rare. The objective of this review was to investigate the global state of the art in pharmacokinetic studies of active ingredients present in plant extracts and botanical drugs. A review of pharmacokinetics studies of chemical constituents of plant extracts and botanical drugs was performed, with a total of 135 studies published between January 2004 and February 2015 available in recognized scientific databases. Botanical preparations were mainly found in the form of aqueous extracts of roots and rhizomes. The most widely studied species was Salvia miltiorrhiza Bunge, and the compound most frequently used as a pharmacokinetic marker was berberine. Most studies were performed using the Sprague Dawley rat model, and the preparations were mainly administered orally in a single dose. Quantification of plasma concentrations of pharmacokinetic markers was performed mainly by liquid-liquid extraction, followed by high performance liquid chromatography coupled to mass spectrometry detector. In conclusion, in recent years there has been an increasing interest among researchers worldwide in the study of pharmacokinetics of bioactive compounds in botanical drugs and plant extracts, especially those from the Traditional Chinese Medicine. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Drug and alcohol abuse: The pattern and magnitude of the problem

Energy Technology Data Exchange (ETDEWEB)

Ajayi, P.A.

1996-12-31

In the last 12 months, many more cases of alcohol and drug (substance) abuse in the workplace were seen in the Escravos operations of Chevron Nigeria Limited than in previous years. This called the attention to the rising prevalence of drug and alcohol abuse in contradistinction to reports from similar organizations in other parts of the world. Chevron Nigeria has a written Drug and Alcohol Policy which has been dormant for some time because of the apparent rarity of the problem of substance abuse in the workplace. This Policy is being reviewed to broaden its scope and make it more effective. A total of 30 employees were tested for drugs and alcohol .6 exceeded the legal limits of Blood Alcohol Concentration (BAC) and 5 tested positive for drugs. Tests were mainly post-accident, reasonable cause and random. The common substances abused were alcohol, cannabis, cocaine and morphine in that order. The findings are compared with those of similar organizations in UK and USA. Efforts to control substance abuse in the workplace are being put into place.

Modeling the drug transport in the anterior segment of the eye.

Science.gov (United States)

Avtar, Ram; Tandon, Deepti

2008-10-02

The aim of the present work is the development of a simple mathematical model for the time course concentration profile of topically administered drugs in the anterior chamber aqueous humor and investigation of the effects of various model parameters on the aqueous humor concentration of lipophilic and hydrophilic drugs. A simple pharmacokinetic model for the transient drug transport in the anterior segment has been developed by using the conservation of mass in the precorneal tear film, Fick's law of diffusion and Michaelis-Menten kinetics of drug metabolism in cornea, and the conservation of mass in the anterior chamber. An analytical solution describing the drug concentration in the anterior chamber has been obtained. The model predicts that an increase in the drug metabolic (consumption) rate in the corneal epithelium reduces the drug concentration in the anterior chamber for both lipophilic and hydrophilic molecules. A decrease in the clearance rate and distribution volume of the drug in the anterior chamber raises the aqueous humor concentration significantly. It is also observed that decay rate of drug concentration in the anterior chamber is higher for lipophilic molecules than that for hydrophilic molecules. The bioavailability of drugs applied topically to the eye may be improved by a rise in the precorneal tear volume, diffusion coefficient in corneal epithelium and distribution coefficient across the endothelium anterior chamber interface, and by reducing the drug metabolism, drug clearance rate and distribution volume in anterior chamber.

Principal component analysis and neurocomputing-based models for total ozone concentration over different urban regions of India

Science.gov (United States)

Chattopadhyay, Goutami; Chattopadhyay, Surajit; Chakraborthy, Parthasarathi

2012-07-01

The present study deals with daily total ozone concentration time series over four metro cities of India namely Kolkata, Mumbai, Chennai, and New Delhi in the multivariate environment. Using the Kaiser-Meyer-Olkin measure, it is established that the data set under consideration are suitable for principal component analysis. Subsequently, by introducing rotated component matrix for the principal components, the predictors suitable for generating artificial neural network (ANN) for daily total ozone prediction are identified. The multicollinearity is removed in this way. Models of ANN in the form of multilayer perceptron trained through backpropagation learning are generated for all of the study zones, and the model outcomes are assessed statistically. Measuring various statistics like Pearson correlation coefficients, Willmott's indices, percentage errors of prediction, and mean absolute errors, it is observed that for Mumbai and Kolkata the proposed ANN model generates very good predictions. The results are supported by the linearly distributed coordinates in the scatterplots.

Venetoclax (ABT-199) Might Act as a Perpetrator in Pharmacokinetic Drug-Drug Interactions.

Science.gov (United States)

Weiss, Johanna; Gajek, Thomas; Köhler, Bruno Christian; Haefeli, Walter Emil

2016-02-24

Venetoclax (ABT-199) represents a specific B-cell lymphoma 2 (Bcl-2) inhibitor that is currently under development for the treatment of lymphoid malignancies. So far, there is no published information on its interaction potential with important drug metabolizing enzymes and drug transporters, or its efficacy in multidrug resistant (MDR) cells. We therefore scrutinized its drug-drug interaction potential in vitro. Inhibition of cytochrome P450 enzymes (CYPs) was quantified by commercial kits. Inhibition of drug transporters (P-glycoprotein (P-gp, ABCB1), breast cancer resistance protein (BCRP), and organic anion transporting polypeptides (OATPs)) was evaluated by the use of fluorescent probe substrates. Induction of drug transporters and drug metabolizing enzymes was quantified by real-time RT-PCR. The efficacy of venetoclax in MDR cells lines was evaluated with proliferation assays. Venetoclax moderately inhibited P-gp, BCRP, OATP1B1, OATP1B3, CYP3A4, and CYP2C19, whereas CYP2B6 activity was increased. Venetoclax induced the mRNA expression of CYP1A1, CYP1A2, UGT1A3, and UGT1A9. In contrast, expression of ABCB1 was suppressed, which might revert tumor resistance towards antineoplastic P-gp substrates. P-gp over-expression led to reduced antiproliferative effects of venetoclax. Effective concentrations for inhibition and induction lay in the range of maximum plasma concentrations of venetoclax, indicating that it might act as a perpetrator drug in pharmacokinetic drug-drug interactions.

Study on recovering directly the commercial cerium oxide and total of residue rare earths from Dongpao bastnasite concentrate

International Nuclear Information System (INIS)

Nguyen Trong Hung; Nguyen Thanh Chung; Luu Xuan Dinh

2003-01-01

A technology for decomposition roasting and sequential leaching processes of Dong Pao bastnasite concentrate to recover directly commercial cerium oxide and total of residue rare earth elements from the leaching solution of the roasted product have been investigated. The bastnasite concentrate is initially roasted at temperature range of 600 - 650 degC and for time of 4 hrs in order to decompose and convert the hardly soluble carbonate forms of ore into easily soluble oxide. The roasted solid is then leached with sulfuric acid solution of 6N at 60 degC for 4 hrs to convert rare earths in oxide and fluoride form into rare earth sulfate. The recovery yield of rare earths of these stages is more than 95%. The attention has especially been paid on recovering directly the commercial cerium oxide and total of residue rare earth element from the above leaching solution. Complex ions of CeSO 4 2+ , Ce(SO 4 ) 2 , Ce(SO 4 ) 3 2- and Ce(SO 4 ) 4 4- exist in aqueous solution of cerium (IV) sulfate. Based on the property, the method of ion - sieve with DOWEX cation resin column has been applied to estimating separation of the ceric complex anions from Ln(III). The survey showed that most of the ceric complex anions are separated from total of residue rare earths. The latter which are absorbed in the cation column are recovered by elution of HCl of 4N. The recovery yield of cerium can only be reached 20% but the purity of that is very high, can be reached 99.6%. About 5 kg of CeO 2 of high grade and 5 kg of TREO of commercial specification have been produced. (author)

Evaluation of Flexible Tacrolimus Drug Concentration Monitoring Approach in Patients Receiving Extended-Release Once-Daily Tacrolimus Tablets.

Science.gov (United States)

Philosophe, Benjamin; Leca, Nicolae; West-Thielke, Patricia M; Horwedel, Timothy; Culkin-Gemmell, Christine; Kistler, Kristin; Stevens, Daniel R

2018-02-20

The majority of United States kidney transplant patients are treated with tacrolimus, a drug effective in preventing graft rejection, but with a narrow therapeutic range, necessitating close monitoring to avoid increased risks of transplant rejection or toxicity if the tacrolimus concentration is too low or too high, respectively. The trough drug concentration tests are time sensitive; patients treated on a twice-daily basis have blood draws exactly 12 hours after their previous dose. The schedule's rigidity causes problems for both patients and health care providers. Novel once-daily tacrolimus formulations such as LCPT (an extended-release tablet by Veloxis Pharmaceuticals, Inc., Cary, North Carolina) have allowed for blood draws on a once-daily basis; however, even that schedule can be restrictive. Results from tests taken either before or after that 24-hour target time may be discarded, or worse, may lead to inappropriate dose changes. Data from ASTCOFF, a phase 3B pharmacokinetic clinical trial (NCT02339246), demonstrated that the unique pharmacokinetic curve of LCPT may allow for a therapeutic monitoring window that extends for 3 hours before or after the 24-hour monitoring target. Furthermore, important tools to help clinicians interpret these levels, such as formulas to estimate the 24-hour trough level if an alternative monitoring time is used, were constructed from these data. These study results give treating clinicians access to data that allow them to safely use and monitor LCPT in their patients and expand the body of evidence surrounding differentiation and practical application of the novel LCPT tacrolimus formulation. © 2018, The Authors. The Journal of Clinical Pharmacology published by Wiley Periodicals, Inc. on behalf of American College of Clinical Pharmacology.

Studies on the mechanism of the epileptiform activity induced by U18666A. II. concentration, half-life and distribution of radiolabeled U18666A in the brain

Energy Technology Data Exchange (ETDEWEB)

Cenedella, R.J.; Sarkar, C.P.; Towns, L.

1982-06-01

The concentration, half-life, and distribution in brain of U18666A, a drug that can drastically alter cerebral lipids and induce a chronic epileptiform state, was determined following both acute and chronic drug administration. U18666A specifically labeled with tritium was prepared by custom synthesis. Brain levels of 1 x 10(-6)M and higher were reached soon after giving an acute 10-mg/kg dose (i.p. or s.c.) of U18666A containing 7-/sup 3/H-U18666A of known specific activity. A steady state concentration of 1 to 2 x 10(-6)M was reached with chronic injection of 10 mg/kg every 4th day, a treatment schedule that results in altered brain lipids and induction of epilepsy if begun soon after birth. The disappearance of U18666A from both brain and serum was described by two similar biexponential processes, a brief rapid clearance (t1/2 . 10 h) and a sustained and much slower one (t1/2 . 65 h). Brain levels of the drug were about 10 times higher than serum at all times examined. Few differences were seen in the regional distribution of radiolabeled drug in brain as determined by both direct analysis and by autoradiographic examination; but the drug did concentrate in lipid-rich subcellular fractions. For example, the synaptosome and myelin fractions each contained about 25-35% of both the total /sup 3/H-labeled drug and total lipid in whole brain. The lipid composition of these fractions was drastically altered in treated animals. In conclusion, the chronic epileptiform state induced by U18666A does not appear to involve localization of the drug in a specific brain region or particular cell type. Rather, the condition could involve localization of the drug in lipid-rich membranes and marked changes in the composition of these membranes.

Relationship of nocturnal concentrations of melatonin, gamma-aminobutyric acid and total antioxidants in peripheral blood with insomnia after stroke: study protocol for a prospective non-randomized controlled trial

Institute of Scientific and Technical Information of China (English)

Wei Zhang; Fang Li; Tong Zhang

2017-01-01

Melatonin and gamma-aminobutyric acid (GABA) have been shown to regulate sleep. The nocturnal concentrations of melatonin, GABA and total antioxidants may relate to insomnia in stroke patients. In this prospective single-center non-randomized controlled clinical trial performed in the China Rehabilitation Research Center, we analyzed the relationship of nocturnal concentrations of melatonin, GABA and total antioxidants with insomnia after stroke. Patients during rehabilitation of stroke were recruited and assigned to the insomnia group or non-insomnia group. Simultaneously, persons without stroke or insomnia served as normal controls. Each group contained 25 cases. The primary outcome was nocturnal concentrations of melatonin, GABA and total antioxidants in peripheral blood. The secondary outcomes were Pittsburgh Sleep Quality Index, Insomnia Severity Index, Epworth Sleepiness Scale, Fatigue Severity Scale, Morningness-Eveningness Questionnaire (Chinese version), and National Institute of Health Stroke Scale. The relationship of nocturnal concentrations of melatonin, GABA and total antioxidants with insomnia after stroke was analyzed and showed that they were lower in the insomnia group than in the non-insomnia group. The severity of stroke was higher in the insomnia group than in the non-insomnia group. Correlation analysis demonstrated that the nocturnal concentrations of melatonin and GABA were associated with insomnia after stroke. This trial was regis-tered at ClinicalTrials.gov, identifier: NCT03202121.

Interdependence of initial cell density, drug concentration and exposure time revealed by real-time impedance spectroscopic cytotoxicity assay

DEFF Research Database (Denmark)

Caviglia, Claudia; Zor, Kinga; Canepa, Silvia

2015-01-01

We investigated the combined effect of the initial cell density (12 500, 35 000, 75 000, and 100 000 cells cm−2) and concentration of the anti-cancer drug doxorubicin on HeLa cells by performing timedependent cytotoxicity assays using real-time electrochemical impedance spectroscopy. A correlation...... between the rate of cell death and the initial cell seeding density was found at 2.5 μM doxorubicin concentration, whereas this was not observed at 5 or 100 μM. By sensing the changes in the cell–substrate interaction using impedance spectroscopy under static conditions, the onset of cytotoxicity...... was observed 5 h earlier than when using a standard colorimetric end-point assay (MTS) which measures changes in the mitochondrial metabolism. Furthermore, with the MTS assay no cytotoxicity was observed after 15 h of incubation with 2.5 μM doxorubicin, whereas the impedance showed at this time point cell...

Evaluation of five commercially available assays and measurement of serum total protein concentration via refractometry for the diagnosis of failure of passive transfer of immunity in foals.

Science.gov (United States)

Davis, Rachel; Giguère, Steeve

2005-11-15

To determine and compare sensitivity, specificity, accuracy, and predictive values of measurement of serum total protein concentration by refractometry as well as 5 commercially available kits for the diagnosis of failure of passive transfer (FPT) of immunity in foals. Prospective study. 65 foals with various medical problems and 35 clinically normal foals. IgG concentration in serum was assessed by use of zinc sulfate turbidity (assay C), glutaraldehyde coagulation (assay D), 2 semiquantitative immunoassays (assays F and G), and a quantitative immunoassay (assay H). Serum total protein concentration was assessed by refractometry. Radial immunodiffusion (assays A and B) was used as the reference method. For detection of IgG or = 6.0 g/dL indicated adequate IgG concentrations. Most assays were adequate as initial screening tests. However, their use as a definitive test would result in unnecessary treatment of foals with adequate IgG concentrations.

A paradigm shift in pharmacokinetic-pharmacodynamic (PKPD) modeling: rule of thumb for estimating free drug level in tissue compared with plasma to guide drug design.

Science.gov (United States)

Poulin, Patrick

2015-07-01

A basic assumption in pharmacokinetics-pharmacodynamics research is that the free drug concentration is similar in plasma and tissue, and, hence, in vitro plasma data can be used to estimate the in vivo condition in tissue. However, in a companion manuscript, it has been demonstrated that this assumption is violated for the ionized drugs. Nonetheless, these observations focus on in vitro static environments and do not challenge data with an in vivo dynamic system. Therefore, an extension from an in vitro to an in vivo system becomes the necessary next step. The objective of this study was to perform theoretical simulations of the free drug concentration in tissue and plasma by using a physiologically based pharmacokinetics (PBPK) model reproducing the in vivo conditions in human. Therefore, the effects of drug ionization, lipophilicity, and clearance have been taken into account in a dynamic system. This modeling exercise was performed as a proof of concept to demonstrate that free drug concentration in tissue and plasma may also differ in a dynamic system for passively permeable drugs that are ionized at the physiological pH. The PBPK model simulations indicated that free drug concentrations in tissue cells and plasma significantly differ for the ionized drugs because of the pH gradient effect between cells and interstitial space. Hence, a rule of thumb for potentially performing more accurate PBPK/PD modeling is suggested, which states that the free drug concentration in tissue and plasma will differ for the ionizable drugs in contrast to the neutral drugs. In addition to the pH gradient effect for the ionizable drugs, lipophilicity and clearance effects will increase or decrease the free drug concentration in tissue and plasma for each class of drugs; thus, higher will be the drug lipophilicity and clearance, lower would be the free drug concentration in plasma, and, hence, in tissue, in a dynamic in vivo system. Therefore, only considering the value of free

Local drug delivery - the early Berlin experience: single drug administration versus sustained release.

Science.gov (United States)

Speck, Ulrich; Scheller, Bruno; Rutsch, Wolfgang; Laule, Michael; Stangl, Verena

2011-05-01

Our initial investigations into restenosis inhibition by local drug delivery were prompted by reports on an improved outcome of coronary interventions, including a lower rate of target lesion revascularisation, when the intervention was performed with an ionic instead of non-ionic contrast medium. Although this was not confirmed in an animal study, the short exposure of the vessel wall to paclitaxel dissolved in contrast agent or coated on balloons proved to be efficacious. A study comparing three methods of local drug delivery to the coronary artery in pigs indicated the following order of efficacy in inhibiting neointimal proliferation: paclitaxel-coated balloons > sirolimus-eluting stents, sustained drug release > paclitaxel in contrast medium. Cell culture experiments confirmed that cell proliferation can be inhibited by very short exposure to the drug. Shorter exposure times require higher drug concentrations. Effective paclitaxel concentrations in porcine arteries are achieved when the drug is dissolved in contrast medium or coated on balloons. Paclitaxel is an exceptional drug in that it stays in the treated tissue for a long time. This may explain the long-lasting efficacy of paclitaxel-coated balloons, but does not disprove the hypothesis that the agent blocks a process initiating long-lasting excessive neointimal proliferation, which occurs early after vessel injury.

The analysis of a trace amount of elements in crude drugs

International Nuclear Information System (INIS)

Wakayama, I.; Akagawa, J.; Yase, Y.; Yoshida, S.; Sasajima, Kazuhisa

2001-01-01

The concentrations and the pharmacological actions of iron and zinc in nearly 30 kinds of crude drugs of Chinese medicine are studied using the neutron activation analysis, quantitatively. The quantitative analytical results are also compared with the semi-quantitative analytical results of iron and zinc obtained by particle induced X-ray emission spectroscopy. The crude drugs with higher iron concentration were almost drugs for the mentality. The crude drugs with highest zinc concentration were also the drugs for the mentality. (H. Katsuta)

Comparison of refractometry and biuret assay for measurement of total protein concentration in canine abdominal and pleural fluid specimens.

Science.gov (United States)

Rose, Alexandra; Funk, Deborah; Neiger, Reto

2016-04-01

To compare total protein (TP) concentrations in canine pleural and abdominal fluid specimens as measured by refractometry and biuret assay. Diagnostic test evaluation. Data regarding 92 pleural and 148 abdominal fluid specimens from dogs with various diseases. TP concentrations in fluid specimens as measured by refractometry and biuret assay were recorded. Strength of association between sets of measurements was assessed by Spearman rank correlations and Bland-Altman plots. Optimal concentration cutoff for diagnostic discrimination between exudate and nonexudate was identified by construction of receiver operating characteristic curves. Median TP concentration in pleural fluid specimens was 2.7 g/dL (range, 0.3 to 4.8 g/dL) for refractometry and 2.9 g/dL (range, 0.7 to 5.8 g/dL) for biuret assay. Median TP concentration in abdominal fluid specimens was 3.5 g/dL (range, 0.1 to 6.0 g/dL) for refractometry and 3.5 g/dL (range, 0.6 to 5.7 g/dL) for biuret assay. Correlation was significant between refractometric and biuret results for pleural (ρ = 0.921) and abdominal (ρ = 0.908) fluid. Bland-Altman plots revealed bias of -0.18 g/dL for pleural fluid and -0.03 g/dL for abdominal fluid for refractometry versus biuret assay. With a TP concentration of ≥ 3 g/dL used to distinguish exudate from nonexudate, sensitivity of refractometry was 77% for pleural fluid and 80% for abdominal fluid. Specificity was 100% and 94%, respectively. Refractometry yielded acceptable results for measurement of TP concentration in canine pleural and abdominal fluid specimens, providing a more rapid and convenient method than biuret assay.

Drug-loaded electrospun mats of poly(vinyl alcohol) fibres and their release characteristics of four model drugs

Science.gov (United States)

Taepaiboon, Pattama; Rungsardthong, Uracha; Supaphol, Pitt

2006-05-01

Mats of PVA nanofibres were successfully prepared by the electrospinning process and were developed as carriers of drugs for a transdermal drug delivery system. Four types of non-steroidal anti-inflammatory drug with varying water solubility property, i.e. sodium salicylate (freely soluble in water), diclofenac sodium (sparingly soluble in water), naproxen (NAP), and indomethacin (IND) (both insoluble in water), were selected as model drugs. The morphological appearance of the drug-loaded electrospun PVA mats depended on the nature of the model drugs. The 1H-nuclear magnetic resonance results confirmed that the electrospinning process did not affect the chemical integrity of the drugs. Thermal properties of the drug-loaded electrospun PVA mats were analysed by differential scanning calorimetry and thermogravimetric analysis. The molecular weight of the model drugs played a major role on both the rate and the total amount of drugs released from the as-prepared drug-loaded electrospun PVA mats, with the rate and the total amount of the drugs released decreasing with increasing molecular weight of the drugs. Lastly, the drug-loaded electrospun PVA mats exhibited much better release characteristics of the model drugs than drug-loaded as-cast films.

Total flavonoids content in the raw material and aqueous extractives from Bauhinia monandra Kurz (Caesalpiniaceae).

Science.gov (United States)

Fernandes, Ana Josane Dantas; Ferreira, Magda Rhayanny Assunção; Randau, Karina Perrelli; de Souza, Tatiane Pereira; Soares, Luiz Alberto Lira

2012-01-01

The aim of this work was to evaluate the spectrophotometric methodology for determining the total flavonoid content (TFC) in herbal drug and derived products from Bauhinia monandra Kurz. Several analytical parameters from this method grounded on the complex formed between flavonoids and AlCl₃ were evaluated such as herbal amount (0.25 to 1.25 g); solvent composition (ethanol 40 to 80%, v/v); as well as the reaction time and AlCl₃ concentration (2 to 9%, w/v). The method was adjusted to aqueous extractives and its performance studied through precision, linearity and preliminary robustness. The results showed an important dependence of the method response from reaction time, AlCl₃ concentration, sample amount, and solvent mixture. After choosing the optimized condition, the method was applied for the matrixes (herbal material and extractives), showing precision lower than 5% (for both parameters repeatability and intermediate precision), coefficient of determination higher than 0.99, and no important influence could be observed for slight variations from wavelength or AlCl₃ concentration. Thus, it could be concluded that the evaluated analytical procedure was suitable to quantify the total flavonoid content in raw material and aqueous extractives from leaves of B. monandra.

Anti-addiction drug ibogaine inhibits voltage-gated ionic currents: A study to assess the drug's cardiac ion channel profile

International Nuclear Information System (INIS)

Koenig, Xaver; Kovar, Michael; Rubi, Lena; Mike, Agnes K.; Lukacs, Peter; Gawali, Vaibhavkumar S.; Todt, Hannes; Hilber, Karlheinz; Sandtner, Walter

2013-01-01

The plant alkaloid ibogaine has promising anti-addictive properties. Albeit not licenced as a therapeutic drug, and despite hints that ibogaine may perturb the heart rhythm, this alkaloid is used to treat drug addicts. We have recently reported that ibogaine inhibits human ERG (hERG) potassium channels at concentrations similar to the drugs affinity for several of its known brain targets. Thereby the drug may disturb the heart's electrophysiology. Here, to assess the drug's cardiac ion channel profile in more detail, we studied the effects of ibogaine and its congener 18-Methoxycoronaridine (18-MC) on various cardiac voltage-gated ion channels. We confirmed that heterologously expressed hERG currents are reduced by ibogaine in low micromolar concentrations. Moreover, at higher concentrations, the drug also reduced human Na v 1.5 sodium and Ca v 1.2 calcium currents. Ion currents were as well reduced by 18-MC, yet with diminished potency. Unexpectedly, although blocking hERG channels, ibogaine did not prolong the action potential (AP) in guinea pig cardiomyocytes at low micromolar concentrations. Higher concentrations (≥ 10 μM) even shortened the AP. These findings can be explained by the drug's calcium channel inhibition, which counteracts the AP-prolonging effect generated by hERG blockade. Implementation of ibogaine's inhibitory effects on human ion channels in a computer model of a ventricular cardiomyocyte, on the other hand, suggested that ibogaine does prolong the AP in the human heart. We conclude that therapeutic concentrations of ibogaine have the propensity to prolong the QT interval of the electrocardiogram in humans. In some cases this may lead to cardiac arrhythmias. - Highlights: • We study effects of anti-addiction drug ibogaine on ionic currents in cardiomyocytes. • We assess the cardiac ion channel profile of ibogaine. • Ibogaine inhibits hERG potassium, sodium and calcium channels. • Ibogaine’s effects on ion channels are a potential

Association Of Serum Total Bilirubin Level With Diabetic Retinopathy In Type 2 Diabetes Mellitus.

Science.gov (United States)

Ghaffar, Tahir; Marwat, Zahid Irfan; Ullah, Fahim; Khan, Salman; Hassan Aamir, Aziz Ul

2016-01-01

Serum bilirubin has anti-inflammatory, antioxidant and immunological properties. It is considered a protective substance against atherosclerotic and microvascular complications of diabetes mellitus (DM). This study was designed to find the association between total serum bilirubin concentration and diabetic retinopathy (DR). This case control study was conducted in the Department of Endocrinology, Diabetes and Metabolic Diseases, Hayatabad Medical Complex, Peshawar. Type-2 DM patients more than 18 years of age of either gender with duration of T2DM more than 6 months were included and sub categorized in two groups. Cases (DM with DR) and Controls (DM without DR) while patients with acute and chronic liver diseases, haemolytic anaemia, history of chronic alcohol consumption, use of hepatotoxic drugs (anti-tuberculous, anti-epileptic), women on oral contraceptive pills were excluded. All participants underwent ophthalmic examination at diabetic retinopathy screening clinic followed by pre designed set of investigations. A total of 152 patients, 76 cases and 76 controls were included. Serum bilirubin concentration was found inversely and independently (p 0.000) associated and inversely co related (r -0.345and p 0.000) with prevalence of DR. Cases were concentrated in the lower quartiles of serum bilirubin concentration and vice versa. Low haemoglobin (p 0.00) and longer duration of DM (0.003) were independently and directly associated with prevalence of DR. Serum bilirubin concentration is inversely and independently associated and inversely correlated with the prevalence of DR and may predict progression of DR over time.

21 CFR 169.176 - Concentrated vanilla extract.

Science.gov (United States)

2010-04-01

... content of ethyl alcohol is not less than 35 percent by volume. (b) The specified name of the food is... 21 Food and Drugs 2 2010-04-01 2010-04-01 false Concentrated vanilla extract. 169.176 Section 169.176 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED...

21 CFR 862.1710 - Total triiodothyronine test system.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Total triiodothyronine test system. 862.1710... Systems § 862.1710 Total triiodothyronine test system. (a) Identification. A total triiodothyronine test system is a device intended to measure the hormone triiodothyronine in serum and plasma. Measurements...

Influence of tiamulin concentration in feed on its bioavailability in piglets.

Science.gov (United States)

Riond, J L; Schreiber, F; Wanner, M

1993-01-01

Tiamulin pharmacokinetic parameters were determined in 8 2-month-old male improved Swiss Landrace piglets after intake of 2,000 mg/kg feed, 500 mg/kg feed, 12.5 mg/ml aqueous solution administered via a stomach tube and 180 mg/kg feed offered ad libitum. In all cases, the total tiamulin dose received was 10 mg/kg body weight (bw) per day. For the 2,000 mg/kg and 500 mg/kg treatments, animals were restrictively fed a commercial mix in amounts corresponding to 3-fold their maintenance requirement of digestible energy. The piglets first individually received the amount of medicated feed and immediately thereafter the rest of the daily ration. The highest tiamulin serum concentrations (Cmax), the largest area under the curve (AUC0-->infinity), the largest absorption rate constant (Ka), and the shortest time at which the maximum serum concentration occurred (tmax) were obtained after administration via stomach tube followed in the respective order by the 2,000 mg/kg, 500 mg/kg and 180 mg/kg treatments. Ad libitum feeding of the medicated mix at 180 mg/kg failed to provide tiamulin serum concentration above minimum inhibitory concentrations (MIC) of some representative microorganisms. In conclusion, tiamulin concentration in medicated feed strongly influences its rate and extent of absorption and consequently serum concentrations. Larger tiamulin concentration in feed enhances its bioavailability. The common practice adopted by national regulatory agencies for the registration of a new drug is to conduct pharmacokinetic studies after administration agencies for the registration of a new drug is to conduct pharmacokinetic studies after administration via a stomach tube. This practice should be reevaluated because this mode of administration does not correspond to that in routine use.

Drug poisoning deaths in Sweden show a predominance of ethanol in mono-intoxications, adverse drug-alcohol interactions and poly-drug use.

Science.gov (United States)

Jones, A W; Kugelberg, F C; Holmgren, A; Ahlner, J

2011-03-20

Over a 10-year period (1998-2007) all deaths in Sweden classified by forensic pathologists as fatal drug poisonings (N = 6894) were retrieved from a toxicology database (TOXBASE) belonging to the National Board of Forensic Medicine. The deaths were further classified as suicides N = 2288 (33%), undetermined N = 2260 (33%) and accidental N = 2346 (34%). The average age (± SD) of all victims was 49.1 ± 15.9 years and men 47.4 ± 15.6 years were 5-year younger than women 52.2 ± 15.8 years (p intoxications) was found in 22% of all poisoning deaths (p intoxication deaths were mostly ethanol-related (N = 976) and the mean and median blood-alcohol concentration (BAC) was 3.06 g/L and 3.10 g/L, respectively. The BAC decreased as the number of additional drugs in blood increased from 2.15 g/L with one drug to 1.25 g/L with 6 or more drugs. The mean (median) concentrations of non-alcohol drugs in mono-intoxication deaths were morphine (N = 93) 0.5mg/L (0.2mg/L), amphetamine (N = 39) 2.0mg/L (1.2mg/L), dextropropoxyphene (N = 33) 3.9 mg/L (2.9 mg/L), dihydro-propiomazine (N = 32) 1.6 mg/L (1.0mg/L) and 7-amino-flunitrazepam (N = 28), 0.4 mg/L (0.3mg/L). Elevated blood morphine in these poisoning deaths mostly reflected abuse of heroin as verified by finding 6-monoacetyl morphine (6-MAM) in the blood samples. When investigating drug poisoning deaths a comprehensive toxicological analysis is essential although the results do not reveal the extent of prior exposure to drugs or the development of pharmacological tolerance. The concentrations of drugs determined in post-mortem blood are one element in the case. The autopsy report, the police investigation, the findings at the scene and eye-witness statements should all be carefully considered when the cause and manner of death are determined. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

Study on drug resistance of mycobacterium tuberculosis in patients with pulmonary tuberculosis by drug resistance gene detecting

International Nuclear Information System (INIS)

Wang Wei; Li Hongmin; Wu Xueqiong; Wang Ansheng; Ye Yixiu; Wang Zhongyuan; Liu Jinwei; Chen Hongbing; Lin Minggui; Wang Jinhe; Li Sumei; Jiang Ping; Feng Bai; Chen Dongjing

2004-01-01

To investigate drug resistance of mycobacterium tuberculosis in different age group, compare detecting effect of two methods and evaluate their the clinical application value, all of the strains of mycobacterium tuberculosis were tested for resistance to RFP, INH SM PZA and EMB by the absolute concentration method on Lowenstein-Jensen medium and the mutation of the rpoB, katG, rpsL, pncA and embB resistance genes in M. tuberculosis was tested by PCR-SSCP. In youth, middle and old age group, the rate of acquired drug resistance was 89.2%, 85.3% and 67.6% respectively, the gene mutation rate was 76.2%, 81.3% and 63.2% respectively. The rate of acquired drug resistance and multiple drug resistance in youth group was much higher than those in other groups. The gene mutation was correlated with drug resistance level of mycobacterium tuberculosis. The gene mutation rate was higher in strains isolated from high concentration resistance than those in strains isolated from low concentration resistance. The more irregular treatment was longer, the rate of drug resistance was higher. Acquired drug resistance varies in different age group. It suggested that surveillance of drug resistence in different age group should be taken seriously, especially in youth group. PCR - SSCP is a sensitive and specific method for rapid detecting rpoB, katG, rpsL, pncA and embB genes mutations of MTB. (authors)

Total hepatocellular disposition profiling of rosuvastatin and pitavastatin in sandwich-cultured human hepatocytes.

Science.gov (United States)

Kanda, Katsuhiro; Takahashi, Ryosuke; Yoshikado, Takashi; Sugiyama, Yuichi

2018-04-09

This study describes the total disposition profiling of rosuvastatin (RSV) and pitavastatin (PTV) using a single systematic procedure called D-PREX (Disposition Profile Exploration) in sandwich-cultured human hepatocytes (SCHH). The biliary excretion fractions of both statins were clearly observed, which were significantly decreased dependent on the concentration of Ko143, an inhibitor for breast cancer resistance protein (BCRP). Ko143 also decreased the basolateral efflux fraction of RSV, whereas that of PTV was not significantly affected. To understand these phenomena, effects of Ko143 on biliary excretion (BCRP and multidrug resistance-associated protein (MRP) 2) and basolateral efflux (MRP3 and MRP4) transporters were examined using transporter-expressing membrane vesicles. BCRP, MRP3 and MRP4-mediated transport of RSV was observed, and Ko143 inhibited these transporters except MRP3. BCRP and MRP4 also mediated the transport of PTV, but the Ko143-mediated inhibition was only clear for BCRP. These results might explain the Ko143-mediated complete and partial inhibition of the biliary excretion and the basolateral efflux of RSV, respectively, in SCHH. In conclusion, D-PREX with sequential sampling of supernatants prior to cell lysis enables the evaluation of total drug disposition profiles resulting from complex interplays of intracellular pathways, which would provide high-throughput evaluation of drug disposition during drug discovery. Copyright © 2018 The Japanese Society for the Study of Xenobiotics. Published by Elsevier Ltd. All rights reserved.

Correlation between CT and MRI findings of chronic subdural hematomas, and total hemoglobin, oxyhemoglobin and methemoglobin concentrations in hematomas

Energy Technology Data Exchange (ETDEWEB)

Tane, Kazuyuki [Osaka Medical Coll., Takatsuki (Japan)

2000-06-01

The authors investigated the correlation between the neuroradiological findings (computerized tomography (CT) scan and magnetic resonance (MR) image) of chronic subdural hematomas (CSDH) and the fractions in those hematomas (hemoglobin (Hb), oxyhemoglobin (oxy-Hb), and methemoglobin (met-Hb)). Thirty-three patients with a total of forty lesions were chosenas subjects, all with CSDH showing almost homogenous findings in CT scans and MR images. The density in the patients' CT scans was divided into high density, iso-density and low density. The intensity in their MR images was also divided into high intensity, isointensity and low intensity, and the correlation of these to the Hb, oxy-Hb and met-Hb concentrations calculated from the absorption spectrum of the hematoma sampled during the operation was examined. The CT findings were highly correlated to the Hb and oxy-Hb, concentrations and the CT scans of the hematomas with an Hb concentration above 9.4 g/dl all showed high density. The T1-weighted MR image and met-Hb concentration also showed a high correlation, and the images of the hematomas with a met-Hb concentration above 0.4 g/dl all showed high intensity. These results indicated that the fraction in the content of CSDH was predictable from the image findings. To obtain prior knowledge of the content of a hematoma seemed extremely useful for the clucidation of the pathogenesis of CSDH and for deciding its therapeutic policy. (author)

Correlation between CT and MRI findings of chronic subdural hematomas, and total hemoglobin, oxyhemoglobin and methemoglobin concentrations in hematomas

International Nuclear Information System (INIS)

Tane, Kazuyuki

2000-01-01

The authors investigated the correlation between the neuroradiological findings (computerized tomography (CT) scan and magnetic resonance (MR) image) of chronic subdural hematomas (CSDH) and the fractions in those hematomas (hemoglobin (Hb), oxyhemoglobin (oxy-Hb), and methemoglobin (met-Hb)). Thirty-three patients with a total of forty lesions were chosenas subjects, all with CSDH showing almost homogenous findings in CT scans and MR images. The density in the patients' CT scans was divided into high density, iso-density and low density. The intensity in their MR images was also divided into high intensity, isointensity and low intensity, and the correlation of these to the Hb, oxy-Hb and met-Hb concentrations calculated from the absorption spectrum of the hematoma sampled during the operation was examined. The CT findings were highly correlated to the Hb and oxy-Hb, concentrations and the CT scans of the hematomas with an Hb concentration above 9.4 g/dl all showed high density. The T1-weighted MR image and met-Hb concentration also showed a high correlation, and the images of the hematomas with a met-Hb concentration above 0.4 g/dl all showed high intensity. These results indicated that the fraction in the content of CSDH was predictable from the image findings. To obtain prior knowledge of the content of a hematoma seemed extremely useful for the clucidation of the pathogenesis of CSDH and for deciding its therapeutic policy. (author)

"Time for dabs": Analyzing Twitter data on marijuana concentrates across the U.S.

Science.gov (United States)

Daniulaityte, Raminta; Nahhas, Ramzi W; Wijeratne, Sanjaya; Carlson, Robert G; Lamy, Francois R; Martins, Silvia S; Boyer, Edward W; Smith, G Alan; Sheth, Amit

2015-10-01

Media reports suggest increasing popularity of marijuana concentrates ("dabs"; "earwax"; "budder"; "shatter; "butane hash oil") that are typically vaporized and inhaled via a bong, vaporizer or electronic cigarette. However, data on the epidemiology of marijuana concentrate use remain limited. This study aims to explore Twitter data on marijuana concentrate use in the U.S. and identify differences across regions of the country with varying cannabis legalization policies. Tweets were collected between October 20 and December 20, 2014, using Twitter's streaming API. Twitter data filtering framework was available through the eDrugTrends platform. Raw and adjusted percentages of dabs-related tweets per state were calculated. A permutation test was used to examine differences in the adjusted percentages of dabs-related tweets among U.S. states with different cannabis legalization policies. eDrugTrends collected a total of 125,255 tweets. Almost 22% (n=27,018) of these tweets contained identifiable state-level geolocation information. Dabs-related tweet volume for each state was adjusted using a general sample of tweets to account for different levels of overall tweeting activity for each state. Adjusted percentages of dabs-related tweets were highest in states that allowed recreational and/or medicinal cannabis use and lowest in states that have not passed medical cannabis use laws. The differences were statistically significant. Twitter data suggest greater popularity of dabs in the states that legalized recreational and/or medical use of cannabis. The study provides new information on the epidemiology of marijuana concentrate use and contributes to the emerging field of social media analysis for drug abuse research. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Greater Efficacy of Total Thyroidectomy versus Radioiodine Therapy on Hyperthyroidism and Thyroid-Stimulating Immunoglobulin Levels in Patients with Graves' Disease Previously Treated with Antithyroid Drugs

Science.gov (United States)

Kautbally, Shakeel; Alexopoulou, Orsalia; Daumerie, Chantal; Jamar, François; Mourad, Michel; Maiter, Dominique

2012-01-01

Aims We compared the effects of total thyroidectomy (TTx) and radioiodine (RAI) administration on the course of thyroid hormones and thyroid-stimulating immunoglobulins (TSI) in patients with Graves' disease. Methods We retrospectively studied 80 patients initially treated with antithyroid drugs and requiring either RAI (8.3 ± 1.7 mCi of 131I; n = 40) or TTx (n = 40) as second-line therapy. Results The TTx and RAI groups were not different, except for larger goiter, higher FT3 and more frequent Graves' orbitopathy at diagnosis in the surgery group (p antithyroid drugs. PMID:24783007

Dissolution rate enhancement of the poorly water-soluble drug Tibolone using PVP, SiO2, and their nanocomposites as appropriate drug carriers.

Science.gov (United States)

Papadimitriou, Sofia; Bikiaris, Dimitrios

2009-09-01

Creation of immediate release formulations for the poorly water-soluble drug Tibolone through the use of solid dispersions (SDs). SD systems of Tibolone (Tibo) with poly(vinylpyrrolidone) (PVP), fumed SiO(2) nanoparticles, and their corresponding ternary systems (PVP/SiO(2)/Tibo) were prepared and studied in order to produce formulations with enhanced drug dissolution rates. The prepared SDs were characterized by the use of differential scanning calorimetry and wide-angle X-ray diffractometry techniques. Also dissolution experiments were performed. From the results it was concluded that PVP as well as SiO(2) can be used as appropriate carriers for the amorphization of Tibo, even when the drug is used at high concentrations (20-30%, w/w). This is due to the evolved interactions taking place between the drug and the used carriers, as was verified by Fourier transform infrared spectroscopy. At higher concentrations the drug was recrystallized. Similar are the observations on the ternary PVP/SiO(2)/Tibo SDs. The dissolution profiles of the drug in PVP/Tibo and SiO(2)/Tibo SDs are directly dependent on the physical state of the drug. Immediately release rates are observed in SD with low drug concentrations, in which Tibo was in amorphous state. However, these release profiles are drastically changed in the ternary PVP/SiO(2)/Tibo SDs. An immediate release profile is observed for low drug concentrations and an almost sustained release as the concentration of Tibo increases. This is due to the weak interactions that take place between PVP and SiO(2), which result in alterations of the characteristics of the carrier (PVP/SiO(2) nanocomposites). Immediate release formulation was created for Tibolone as well as new nanocomposite matrices of PVP/SiO((2)), which drastically change the release profile of the drug to a sustained delivery.

The Female Genital Tract Microbiome Is Associated With Vaginal Antiretroviral Drug Concentrations in Human Immunodeficiency Virus-Infected Women on Antiretroviral Therapy.

Science.gov (United States)

Donahue Carlson, Renee; Sheth, Anandi N; Read, Timothy D; Frisch, Michael B; Mehta, C Christina; Martin, Amy; Haaland, Richard E; Patel, Anar S; Pau, Chou-Pong; Kraft, Colleen S; Ofotokun, Igho

2017-11-15

The female genital tract (FGT) microbiome may affect vaginal pH and other factors that influence drug movement into the vagina. We examined the relationship between the microbiome and antiretroviral concentrations in the FGT. Over one menstrual cycle, 20 human immunodeficiency virus (HIV)-infected women virologically suppressed on tenofovir (TFV) disoproxil fumarate/emtricitabine and ritonavir-boosted atazanavir (ATV) underwent serial paired cervicovaginal and plasma sampling for antiretroviral concentrations using high-performance liquid chromatography-tandem mass spectrometry. Analysis of 16S ribosomal RNA gene sequencing of cervicovaginal lavage clustered each participant visit into a unique microbiome community type (mCT). Participants were predominantly African American (95%), with a median age of 38 years. Cervicovaginal lavage sequencing (n = 109) resulted in a low-diversity mCT dominated by Lactobacillus (n = 40), and intermediate-diversity (n = 28) and high-diversity (n = 41) mCTs with abundance of anaerobic taxa. In multivariable models, geometric mean FGT:plasma ratios varied significantly by mCT for all 3 drugs. For both ATV and TFV, FGT:plasma was significantly lower in participant visits with high- and low-diversity mCT groups (all P < .02). For emtricitabine, FGT:plasma was significantly lower in participant visits with low- vs intermediate-diversity mCT groups (P = .002). Certain FGT mCTs are associated with decreased FGT antiretroviral concentrations. These findings are relevant for optimizing antiretrovirals used for biomedical HIV prevention in women. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

Therapeutic drug monitoring: how to improve drug dosage and patient safety in tuberculosis treatment

Directory of Open Access Journals (Sweden)

Giovanni Sotgiu

2015-03-01

Full Text Available In this article we describe the key role of tuberculosis (TB treatment, the challenges (mainly the emergence of drug resistance, and the opportunities represented by the correct approach to drug dosage, based on the existing control and elimination strategies. In this context, the role and contribution of therapeutic drug monitoring (TDM is discussed in detail. Treatment success in multidrug-resistant (MDR TB cases is low (62%, with 7% failing or relapsing and 9% dying and in extensively drug-resistant (XDR TB cases is even lower (40%, with 22% failing or relapsing and 15% dying. The treatment of drug-resistant TB is also more expensive (exceeding €50 000 for MDR-TB and €160 000 for XDR-TB and more toxic if compared to that prescribed for drug-susceptible TB. Appropriate dosing of first- and second-line anti-TB drugs can improve the patient's prognosis and lower treatment costs. TDM is based on the measurement of drug concentrations in blood samples collected at appropriate times and subsequent dose adjustment according to the target concentration. The ‘dried blood spot’ technique offers additional advantages, providing the rationale for discussions regarding a possible future network of selected, quality-controlled reference laboratories for the processing of dried blood spots of difficult-to-treat patients from reference TB clinics around the world.

Performance, behaviour and meat quality of beef heifers fed concentrate and straw offered as total mixed ration or free-choice

Energy Technology Data Exchange (ETDEWEB)

Iraira, S.P.; Madruga, A.; Pérez-Juan, M.; Ruíz-de-la-Torre, J.; Rodríguez-Prado, M.; Calsamiglia, S.; Manteca, X.; Ferret, A.

2015-07-01

Eighteen Simmental heifers were fed concentrate and barley straw offered as a total mixed ration (TMR) or separately as a free choice (FCH) to compare performance, behaviour, and meat quality. The heifers were assigned to treatments in a randomized complete block design. Animals were allotted to roofed pens with 3 animals per pen, and 3 pens per treatment. Intake of concentrate, average daily gain, and gain to feed ratio were not different between diets, being on average 7.6 kg/day, 1.38 kg/day and 0.18 kg/kg, respectively. Straw intake was greater in TMR than in FCH treatment (0.7 vs 0.3 kg/day, respectively; p<0.001). Crude protein intake, neutral detergent fibre intake and water consumption did not differ between treatments. Time spent eating was longer in FCH than in TMR (p=0.001), whereas time spent ruminating and total chewing time were longer (p<0.01) in TMR than in FCH. The number of displacements resulting from competition for feed in the main feeder in TMR treatment tended to be greater than in FCH treatment. There were no differences in the carcass characteristics and quality of meat of animals assigned to the different feeding methods, but the percentage of 18:2 n-6 was higher in FCH treatment. In summary, these results suggest that the use of TMR as a feeding method in beef cattle fed high concentrate diets did not affect performance and increased time spent ruminating with a potential decrease of ruminal acidosis incidence. (Author)

STUDY ON THE CONCENTRATION EFFECT OF Nb2O5-ZAA CATALYST TOWARDS TOTAL CONVERSION OF BIODIESEL IN TRANSESTERIFICATION OF WASTED COOKING OIL

Directory of Open Access Journals (Sweden)

Astuti Tri Padmaningsih

2010-06-01

Full Text Available Study on the concentration effect of Nb2O5-ZAA catalyst towards total conversion of biodiesel has been conducted. The natural zeolite (ZA was activated by dipping in NH4Cl solution and was calcined using N2 atmosphere at 500 °C for 5h to produce the ZAA sample. The Nb2O5-ZAA catalyst was made by mixing the activated natural zeolite (ZAA, Nb2O5 3 % (w/w and oxalic acid 10 % (w/w solution, until the paste was formed, followed by drying and calcining the catalyst for 3 h at 500 °C under N2 atmosphere. Catalyst characterizations were conducted by measuring acidity with NH3 gas using gravimetric method and porosimetric analysis using N2 gas adsorption based on the BET equation by surface area analyzer instrument. The Nb2O5-ZAA catalyst was then used as an acid catalyst in free fatty acid esterification reaction of wasted cooking oil in methanol medium with variation of catalyst concentration: 1.25%; 2.5%; 3.75% and 5% towards the weight of oil+methanol. The reaction was continued by transesterification of triglyceride in the used cooking oil using NaOH catalyst in methanol medium. For comparison, the esterification reaction using H2SO4 catalyst 1.25% towards the weight of oil+methanol has been conducted as well. Methyl ester (biodiesel product was analyzed using Gas Chromatography (GC and Gas Chromatography-Mass Spectrometry (GC-MS. The characters of biodiesel were analyzed using American Society for Testing and Materials (ASTM method. The results showed that modification of ZAA by impregning Nb2O5 3% (w/w increased the total catalyst acidity from 5.00 mmol/g to 5.65 mmol/g. The Nb2O5-ZAA catalyst has specific surface area of 60.61 m2/g, total pore volume of 37.62x10-3 cc/g and average pore radius of 12.41 Å. The Nb2O5-ZAA catalyst with concentration of 1.25%-5% produced higher total conversion of biodiesel than that of H2SO4 catalyst 1.25%. The Nb2O5-ZAA catalyst with concentration of 3.75% produced the highest total conversion of biodiesel, i

Identification of intestinal loss of a drug through physiologically based pharmacokinetic simulation of plasma concentration-time profiles.

Science.gov (United States)

Peters, Sheila Annie

2008-01-01

Despite recent advances in understanding of the role of the gut as a metabolizing organ, recognition of gut wall metabolism and/or other factors contributing to intestinal loss of a compound has been a challenging task due to the lack of well characterized methods to distinguish it from first-pass hepatic extraction. The implications of identifying intestinal loss of a compound in drug discovery and development can be enormous. Physiologically based pharmacokinetic (PBPK) simulations of pharmacokinetic profiles provide a simple, reliable and cost-effective way to understand the mechanisms underlying pharmacokinetic processes. The purpose of this article is to demonstrate the application of PBPK simulations in bringing to light intestinal loss of orally administered drugs, using two example compounds: verapamil and an in-house compound that is no longer in development (referred to as compound A in this article). A generic PBPK model, built in-house using MATLAB software and incorporating absorption, metabolism, distribution, biliary and renal elimination models, was employed for simulation of concentration-time profiles. Modulation of intrinsic hepatic clearance and tissue distribution parameters in the generic PBPK model was done to achieve a good fit to the observed intravenous pharmacokinetic profiles of the compounds studied. These optimized clearance and distribution parameters are expected to be invariant across different routes of administration, as long as the kinetics are linear, and were therefore employed to simulate the oral profiles of the compounds. For compounds with reasonably good solubility and permeability, an area under the concentration-time curve for the simulated oral profile that far exceeded the observed would indicate some kind of loss in the intestine. PBPK simulations applied to compound A showed substantial loss of the compound in the gastrointestinal tract in humans but not in rats. This accounted for the lower bioavailability of the

Managing Drug-Drug Interaction Between Ombitasvir, Paritaprevir/Ritonavir, Dasabuvir, and Mycophenolate Mofetil.

Science.gov (United States)

Lemaitre, Florian; Ben Ali, Zeineb; Tron, Camille; Jezequel, Caroline; Boglione-Kerrien, Christelle; Verdier, Marie-Clémence; Guyader, Dominique; Bellissant, Eric

2017-08-01

No drug-drug interaction study has been conducted to date for the combination of ombitasvir, paritaprevir/ritonavir, dasabuvir (3D), and mycophenolic acid (MPA). We here report the case of a hepatitis C virus-infected patient treated with 3D and MPA for vasculitis. In light of the threat of drug-drug interaction, the concentration of MPA was measured before, during, and 15 days after the end of the 3D treatment. Similar values were found at all 3 time points, thus indicating that there is probably no need to adapt MPA dosage to 3D.

Dimethadione embryotoxicity in the rat is neither correlated with maternal systemic drug concentrations nor embryonic tissue levels

Energy Technology Data Exchange (ETDEWEB)

Ozolinš, Terence R.S., E-mail: ozolinst@queensu.ca [Department of Biomedical and Molecular Sciences, Program in Pharmacology and Toxicology, Queen’s University, Botterell Hall, Kingston, ON K7L 3N6 (Canada); Weston, Andrea D. [Currently at Applied Biotechnology/Lead Discovery, Bristol-Myers Squibb, 5 Research Pkwy Wallingford, CT 06492-1996 (United States); Perretta, Anthony [Currently at Pfizer Research and Development, Eastern Point Road, Groton, CT 06340 (United States); Thomson, Jason J. [Currently at Yale Stem Cell Center, Yale School of Medicine, PO Box 208073, New Haven, CT 06520-8073 (United States); Brown, Nigel A. [Division of Basic Medical Sciences, St. George’s University of London, UK SW17 0RE (United Kingdom)

2015-11-15

Pregnant rats treated with dimethadione (DMO), the N-demethylated metabolite of the anticonvulsant trimethadione, produce offspring having a 74% incidence of congenital heart defects (CHD); however, the incidence of CHD has high inter-litter variability (40–100%) that presents a challenge when studying the initiating events prior to the presentation of an abnormal phenotype. We hypothesized that the variability in CHD incidence was the result of differences in maternal systemic concentrations or embryonic tissue concentrations of DMO. To test this hypothesis, dams were administered 300 mg/kg DMO every 12 h from the evening of gestational day (GD) 8 until the morning of GD 11 (six total doses). Maternal serum levels of DMO were assessed on GD 11, 12, 13, 14, 15, 18 and 21. Embryonic tissue concentrations of DMO were assessed on GD 11, 12, 13 and 14. In a separate cohort of GD 12 embryos, DMO concentrations and parameters of growth and development were assessed to determine if tissue levels of DMO were correlated with these endpoints. Embryos were exposed directly to different concentrations of DMO with whole embryo culture (WEC) and their growth and development assessed. Key findings were that neither maternal systemic concentrations nor tissue concentrations of DMO identified embryos that were sensitive or resistant to DMO in vivo. Direct exposure of embryos to DMO via WEC also failed to show correlations between embryonic concentrations of DMO with developmental outcomes in vitro. We conclude that neither maternal serum nor embryonic tissue concentrations of DMO predict embryonic outcome. - Highlights: • Dimethadione (DMO) induces septation defects (VSD) in rat offspring. • Despite high rate of VSD defects inter-litter variability is 40–100%. • Maternal and embryonic concentrations of DMO were assessed. • Neither serum nor tissue levels of DMO were correlated with embryotoxicity.

Dimethadione embryotoxicity in the rat is neither correlated with maternal systemic drug concentrations nor embryonic tissue levels

International Nuclear Information System (INIS)

Ozolinš, Terence R.S.; Weston, Andrea D.; Perretta, Anthony; Thomson, Jason J.; Brown, Nigel A.

2015-01-01

Pregnant rats treated with dimethadione (DMO), the N-demethylated metabolite of the anticonvulsant trimethadione, produce offspring having a 74% incidence of congenital heart defects (CHD); however, the incidence of CHD has high inter-litter variability (40–100%) that presents a challenge when studying the initiating events prior to the presentation of an abnormal phenotype. We hypothesized that the variability in CHD incidence was the result of differences in maternal systemic concentrations or embryonic tissue concentrations of DMO. To test this hypothesis, dams were administered 300 mg/kg DMO every 12 h from the evening of gestational day (GD) 8 until the morning of GD 11 (six total doses). Maternal serum levels of DMO were assessed on GD 11, 12, 13, 14, 15, 18 and 21. Embryonic tissue concentrations of DMO were assessed on GD 11, 12, 13 and 14. In a separate cohort of GD 12 embryos, DMO concentrations and parameters of growth and development were assessed to determine if tissue levels of DMO were correlated with these endpoints. Embryos were exposed directly to different concentrations of DMO with whole embryo culture (WEC) and their growth and development assessed. Key findings were that neither maternal systemic concentrations nor tissue concentrations of DMO identified embryos that were sensitive or resistant to DMO in vivo. Direct exposure of embryos to DMO via WEC also failed to show correlations between embryonic concentrations of DMO with developmental outcomes in vitro. We conclude that neither maternal serum nor embryonic tissue concentrations of DMO predict embryonic outcome. - Highlights: • Dimethadione (DMO) induces septation defects (VSD) in rat offspring. • Despite high rate of VSD defects inter-litter variability is 40–100%. • Maternal and embryonic concentrations of DMO were assessed. • Neither serum nor tissue levels of DMO were correlated with embryotoxicity.

Comparison of serum leptin, glucose, total cholesterol and total protein levels in fertile and repeat breeder cows

Directory of Open Access Journals (Sweden)

Saime Guzel

2014-12-01

Full Text Available In the present study we measured serum glucose, leptin, total cholesterol and total protein concentrations in repeat breeder cows and compared them with fertile cows. For this aim, 20 repeat breeder cows and 20 fertile cows were used as material. Repeat breeder cows were found to have lower levels of leptin and glucose as compared with fertile ones. No significant differences in total cholesterol and total protein levels were observed between the two groups. No significant correlation of leptin with glucose, total cholesterol and total protein was observed in fertile and repeat breeder cows. Low concentrations of glucose and leptin can have some effects on reproductive problems as repeat breeder and help to understand potential mechanisms impairing fertility in repeat breeder cows.

Assessment of the total uranium concentration in surface and underground water samples from the Caetite region, Bahia, Brazil

International Nuclear Information System (INIS)

Silva, Julia Grasiela Batista; Geraldo, Luiz Paulo; Yamazaki, Ione Makiko

2011-01-01

At the region of Caetite, BA, it is located the largest uranium mine in exploration at present days in Brazil. During the uranium extraction process, it may be having an environmental contamination by this heavy metal due to rain water and other natural transport mechanism, with potential exposition risk to the local population. The aim of this work was to investigate the total uranium concentration in surface and underground water samples collected at the Caetite region, using the nuclear track registration technique (SSNTD) in a polycarbonate plastic. A 100 mL volume of water samples were initially treated in 10 mL of HNO 3 (PA) and concentrated by evaporation at a temperature around 80 deg C. The resulting residue was diluted to a total volume of 25 mL without pass it to a filter. About 10 μL of this solution was deposited on the plastic detector surface (around 1.0 cm 2 area) together with 5 μL of a Cyastat detergent solution (5%) and evaporated under an infrared lamp. All the resulting deposits of non volatile constituents were irradiated, together with a uranium standard sample, at the IPEN-IEA-R1 (3.5 MW) nuclear reactor for approximately 3 min. After irradiations, chemical etching of the plastic detectors was carried out at 60 deg C, for 65 min. in a NaOH (6N) solution. The fission tracks were counted scanning all the deposit area of the polycarbonate plastic detector with a system consisting of an optical microscope together with a video camera and TV monitor. The average values of uranium concentrations obtained in this work ranged from (0.95±0.19) μg.L -1 to (25.60±3.3) μg.L -1 . These results were compared to values reported in the literature for water samples from other regions and discussed in terms of safe limits recommended by WHO -World Health Organization and CONAMA - Conselho Nacional do Meio Ambiente. (author)

Assessment of the total uranium concentration in surface and underground water samples from the Caetite region, Bahia, Brazil

Energy Technology Data Exchange (ETDEWEB)

Silva, Julia Grasiela Batista; Geraldo, Luiz Paulo [Centro Universitario da Fundacao Educacional de Barretos (UNIFEB), (SP) (Brazil); Yamazaki, Ione Makiko [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil)

2011-07-01

At the region of Caetite, BA, it is located the largest uranium mine in exploration at present days in Brazil. During the uranium extraction process, it may be having an environmental contamination by this heavy metal due to rain water and other natural transport mechanism, with potential exposition risk to the local population. The aim of this work was to investigate the total uranium concentration in surface and underground water samples collected at the Caetite region, using the nuclear track registration technique (SSNTD) in a polycarbonate plastic. A 100 mL volume of water samples were initially treated in 10 mL of HNO{sub 3} (PA) and concentrated by evaporation at a temperature around 80 deg C. The resulting residue was diluted to a total volume of 25 mL without pass it to a filter. About 10 {mu}L of this solution was deposited on the plastic detector surface (around 1.0 cm{sup 2} area) together with 5 {mu}L of a Cyastat detergent solution (5%) and evaporated under an infrared lamp. All the resulting deposits of non volatile constituents were irradiated, together with a uranium standard sample, at the IPEN-IEA-R1 (3.5 MW) nuclear reactor for approximately 3 min. After irradiations, chemical etching of the plastic detectors was carried out at 60 deg C, for 65 min. in a NaOH (6N) solution. The fission tracks were counted scanning all the deposit area of the polycarbonate plastic detector with a system consisting of an optical microscope together with a video camera and TV monitor. The average values of uranium concentrations obtained in this work ranged from (0.95{+-}0.19) {mu}g.L{sup -1} to (25.60{+-}3.3) {mu}g.L{sup -1}. These results were compared to values reported in the literature for water samples from other regions and discussed in terms of safe limits recommended by WHO -World Health Organization and CONAMA - Conselho Nacional do Meio Ambiente. (author)

Target mediated drug disposition with drug-drug interaction, Part II: competitive and uncompetitive cases.

Science.gov (United States)

Koch, Gilbert; Jusko, William J; Schropp, Johannes

2017-02-01

We present competitive and uncompetitive drug-drug interaction (DDI) with target mediated drug disposition (TMDD) equations and investigate their pharmacokinetic DDI properties. For application of TMDD models, quasi-equilibrium (QE) or quasi-steady state (QSS) approximations are necessary to reduce the number of parameters. To realize those approximations of DDI TMDD models, we derive an ordinary differential equation (ODE) representation formulated in free concentration and free receptor variables. This ODE formulation can be straightforward implemented in typical PKPD software without solving any non-linear equation system arising from the QE or QSS approximation of the rapid binding assumptions. This manuscript is the second in a series to introduce and investigate DDI TMDD models and to apply the QE or QSS approximation.

Drug-drug interactions as a determinant of elevated lithium serum levels in daily clinical practice

NARCIS (Netherlands)

Wilting, [No Value; Movig, KL; Moolenaar, M; Hekster, YA; Brouwers, [No Value; Heerdink, ER; Nolen, WA; Egberts, AC

Objective: Lithium is a drug with a narrow therapeutic window. Concomitantly used medication is a potentially influencing factor of lithium serum concentrations. We conducted a multicentre retrospective case-control study with the aim of investigating lithium-related drug interactions as

The influence of drug distribution and drug-target binding on target occupancy : The rate-limiting step approximation

NARCIS (Netherlands)

Witte, de W.E.A.; Vauquelin, G.; Graaf, van der P.H.; Lange, de E.C.M.

2017-01-01

The influence of drug-target binding kinetics on target occupancy can be influenced by drug distribution and diffusion around the target, often referred to as "rebinding" or "diffusion-limited binding". This gives rise to a decreased decline of the drug-target complex concentration as a result of a

Altered drug metabolism during pregnancy: hormonal regulation of drug-metabolizing enzymes.

Science.gov (United States)

Jeong, Hyunyoung

2010-06-01

Medication use during pregnancy is prevalent, but pharmacokinetic information of most drugs used during pregnancy is lacking in spite of known effects of pregnancy on drug disposition. Accurate pharmacokinetic information is essential for optimal drug therapy in mother and fetus. Thus, understanding how pregnancy influences drug disposition is important for better prediction of pharmacokinetic changes of drugs in pregnant women. Pregnancy is known to affect hepatic drug metabolism, but the underlying mechanisms remain unknown. Physiological changes accompanying pregnancy are probably responsible for the reported alteration in drug metabolism during pregnancy. These include elevated concentrations of various hormones such as estrogen, progesterone, placental growth hormones and prolactin. This review covers how these hormones influence expression of drug-metabolizing enzymes (DMEs), thus potentially responsible for altered drug metabolism during pregnancy. The reader will gain a greater understanding of the altered drug metabolism in pregnant women and the regulatory effects of pregnancy hormones on expression of DMEs. In-depth studies in hormonal regulatory mechanisms as well as confirmatory studies in pregnant women are warranted for systematic understanding and prediction of the changes in hepatic drug metabolism during pregnancy.

Influence of multidrug resistance and drug transport proteins on chemotherapy drug metabolism.

Science.gov (United States)

Joyce, Helena; McCann, Andrew; Clynes, Martin; Larkin, Annemarie

2015-05-01

Chemotherapy involving the use of anticancer drugs remains an important strategy in the overall management of patients with metastatic cancer. Acquisition of multidrug resistance remains a major impediment to successful chemotherapy. Drug transporters in cell membranes and intracellular drug metabolizing enzymes contribute to the resistance phenotype and determine the pharmacokinetics of anticancer drugs in the body. ATP-binding cassette (ABC) transporters mediate the transport of endogenous metabolites and xenobiotics including cytotoxic drugs out of cells. Solute carrier (SLC) transporters mediate the influx of cytotoxic drugs into cells. This review focuses on the substrate interaction of these transporters, on their biology and what role they play together with drug metabolizing enzymes in eliminating therapeutic drugs from cells. The majority of anticancer drugs are substrates for the ABC transporter and SLC transporter families. Together, these proteins have the ability to control the influx and the efflux of structurally unrelated chemotherapeutic drugs, thereby modulating the intracellular drug concentration. These interactions have important clinical implications for chemotherapy because ultimately they determine therapeutic efficacy, disease progression/relapse and the success or failure of patient treatment.

The effects of and interactions between the maturity of grass silage and concentrate starch source when offered as total mixed rations on the performance of dairy cows

DEFF Research Database (Denmark)

Tahir, M.N.; Lund, Peter; Hetta, M.

2013-01-01

identical proportions of forage (51%) and concentrate (49%). Total tract digestibility was estimated by determining indigestible NDF (iNDF) concentrations in feeds and faeces and using iNDF as an internal marker. The feeds’ ruminal degradation parameters were determined using both in situ (nylon bag...

Serum total homocystein, folate and vitamin B12 levels and their correlation with antipsychotic drug doses in adult male patients with chronic schizophrenia.

Science.gov (United States)

Eren, Esin; Yeğin, Ayşenur; Yilmaz, Necat; Herken, Hasan

2010-01-01

Elevated blood levels of homocysteine (hCY) have been associated with schizophrenic male patients. However, controversy remains regarding the association between lowered plasma folate and vitamin B12, hyperhomocysteinemia, and schizophrenia. Sixty-six (66) male patients with chronic schizophrenia were investigated to test the hypotheses that alterations in Hcy, folate, and vitamin B12 levels might be related to the antipsychotic drug doses used in treatment. Serum total homocysteine, folic acid, and vitamin B12 levels were determined by chemiluminescence methods in both patients and control subjects. The patients were grouped according to the antipsychotic drug doses used in their treatment. Patients had higher homocysteine levels but they did not differ from controls in terms of folate and vitamin B12 levels. On the other hand, only folate levels were negatively correlated in the patient group treated with higher therapeutic doses of chlorpromazine equivalents (> 400 mg/day) compared to the patient group with lower doses (< 400 mg/day). Our findings show that higher typical antipsychotic drugs may play a role as modifiying factor for folate metabolism in chronic schizoprenic male patients.

Total renin after gonadotropin stimulation in polycystic ovarian disease.

Science.gov (United States)

Matinlauri, I; Anttila, L; Jaatinen, T A; Koskinen, P; Aalto, M; Irjala, K; Nikkanen, V

1995-02-01

To examine the influence of polycystic ovarian disease (PCOD) on the levels of total renin in plasma and follicular fluid (FF) after stimulation with hMG. Comparative study of the plasma and FF concentrations of total renin in women with and without PCOD after stimulation with hMG. In vitro fertilization-embryo transfer program at the Department of Obstetrics and Gynecology, the University Central Hospital of Turku, Finland. Thirty-six women undergoing IVF-ET for infertility with (n = 10) or without (n = 26) ultrasonographically diagnosed PCOD. Of the latter group, 15 women had tubal infertility, and the rest suffered from an anovulatory infertility and reacted with PCO-like ovarian response to stimulation. The concentrations of total renin in plasma and FF, serum E2, and protein in FF. The concentrations of plasma total renin after the gonadotropin stimulation were significantly higher in the PCOD and PCO-like groups when compared with the tubal group. The concentration of total renin in FF and the ratio of total renin per protein in FF were higher in the PCOD and PCO-like groups than in the tubal group, but the differences did not reach statistical significance. Positive correlations were found between the plasma total renin and serum E2 concentrations in the PCO-like and in the tubal group and between plasma total renin concentrations and the number of mature follicles in all groups. Follicular fluid total renin did not correlate with FF protein in any group. All findings were independent of the total hMG dosage used and the body mass index of the patients. In the present study the concentrations of total renin in plasma were enhanced markedly after gonadotropin stimulation in women with PCOD compared with women having tubal infertility. The pattern of the hormonal secretions revealed a group of infertile patients reacting biochemically like women with PCOD.

Anti-addiction drug ibogaine inhibits voltage-gated ionic currents: A study to assess the drug's cardiac ion channel profile

Energy Technology Data Exchange (ETDEWEB)

Koenig, Xaver; Kovar, Michael; Rubi, Lena; Mike, Agnes K.; Lukacs, Peter; Gawali, Vaibhavkumar S.; Todt, Hannes [Center for Physiology and Pharmacology, Department of Neurophysiology and -pharmacology, Medical University of Vienna, 1090 Vienna (Austria); Hilber, Karlheinz, E-mail: karlheinz.hilber@meduniwien.ac.at [Center for Physiology and Pharmacology, Department of Neurophysiology and -pharmacology, Medical University of Vienna, 1090 Vienna (Austria); Sandtner, Walter [Center for Physiology and Pharmacology, Institute of Pharmacology, Medical University of Vienna, 1090 Vienna (Austria)

2013-12-01

The plant alkaloid ibogaine has promising anti-addictive properties. Albeit not licenced as a therapeutic drug, and despite hints that ibogaine may perturb the heart rhythm, this alkaloid is used to treat drug addicts. We have recently reported that ibogaine inhibits human ERG (hERG) potassium channels at concentrations similar to the drugs affinity for several of its known brain targets. Thereby the drug may disturb the heart's electrophysiology. Here, to assess the drug's cardiac ion channel profile in more detail, we studied the effects of ibogaine and its congener 18-Methoxycoronaridine (18-MC) on various cardiac voltage-gated ion channels. We confirmed that heterologously expressed hERG currents are reduced by ibogaine in low micromolar concentrations. Moreover, at higher concentrations, the drug also reduced human Na{sub v}1.5 sodium and Ca{sub v}1.2 calcium currents. Ion currents were as well reduced by 18-MC, yet with diminished potency. Unexpectedly, although blocking hERG channels, ibogaine did not prolong the action potential (AP) in guinea pig cardiomyocytes at low micromolar concentrations. Higher concentrations (≥ 10 μM) even shortened the AP. These findings can be explained by the drug's calcium channel inhibition, which counteracts the AP-prolonging effect generated by hERG blockade. Implementation of ibogaine's inhibitory effects on human ion channels in a computer model of a ventricular cardiomyocyte, on the other hand, suggested that ibogaine does prolong the AP in the human heart. We conclude that therapeutic concentrations of ibogaine have the propensity to prolong the QT interval of the electrocardiogram in humans. In some cases this may lead to cardiac arrhythmias. - Highlights: • We study effects of anti-addiction drug ibogaine on ionic currents in cardiomyocytes. • We assess the cardiac ion channel profile of ibogaine. • Ibogaine inhibits hERG potassium, sodium and calcium channels. • Ibogaine’s effects on

Drug Interactions between some antiepileptic and certain hypocholesterolaemic drugs in irradiated animals

International Nuclear Information System (INIS)

Shaaban, D.M.L.

2015-01-01

Drug Interactions between antiepileptic drug such as phenytoin and certain hypercholesterolaemia drug namely rosuvastatin were investigated on several biological parameters. Phenytoin (60 mg/kg i.p) and rosuvastatin (1.25 mg/kg i.p) were given either alone and in combination to normal and irradiated animals to investigate drug interactions between the test drugs. Anticonvulsant activity was evaluated using pentylenetetrazole in a dose (80 mg/kg i.p) in normal and irradiated mice. Brain neurotransmitters (glutamate and GABA) were investigated. Lipid profile (total cholesterol (TC), Triacylglycerol (TG), High density lipoprotein-cholesterol (HDL-C) and low density lipoprotein- cholesterol (LDL-C) were determined. Liver functions such as serum Aspartate amino transferase (AST) and serum alanine amino transferase (ALT) were also estimated. Oxidative stress bio markers namely serum malondialdehyde (MDA), serum nitric oxide (NO) and blood superoxide dismutase activity (SOD) were studied. Histopathological examinations of brain and liver tissues were performed. Administration of phenytoin concurrently with rosuvastatin is not recommended in patients receiving radiotherapy as dangerous side effects on liver functions and lipid profile may occur. The interactions between the two drugs in normal rats improve liver functions and lipid peroxidation. Apart from the action of the combination on total cholesterol, it improves lipid profile pattern. Rosuvastatin administration in combination with phenytoin may have additive anticonvulsant activity.

Changes in total carbohydrate and total antioxidant activity induced by gamma irradiation of wheat flour

International Nuclear Information System (INIS)

Manupriya, B.R.; Shenoy, K. Bhasker; Patil, Shrikant L.; Somashekarappa, H.M.

2015-01-01

Wheat is a staple food grain in India after rice and occupies number one position in the world. The wheat crop not only gives food grains but also gives fodder for animals. Among many preservation methods irradiation is a current technique used to overcome infestation, contamination and spoilage of stored grains. The present study is aimed to check the changes in composition of irradiated wheat flour. Wheat flour was exposed to five different irradiation doses (0.25 KGy, 0.5KGy, 1KGy, 5KGy and 10 KGy) by using 60 Co gamma-irradiation chamber. Irradiated flour was stored in air sealed polyethylene pouch and plastic container at room temperature for different time intervals (0 th day, 1 month and 3 months). The stored flour was checked for total antioxidant activity by phosphomolybdate method and total carbohydrates concentration by phenol-sulphuric acid method. On 0 th day total antioxidant activity and total carbohydrate concentration was found to be increased at 0.5KGy (0.113 mg/ml and 0.045 mg/ml respectively) when compared to control (0.79 mg/ml and 39.5 mg/ml). Similarly for 1 month stored samples of air sealed polyethylene pouch total antioxidant activity and total carbohydrate concentration was observed to be increased at 0.5KGy (0.117 mg/ml and 0.045mg/ml respectively) when compared to control (0.096 mg/ml and 0.035 mg/ml). But in case of stored samples of plastic container total antioxidant activity increased at 0.25KGy (0.060 mg/ml) and total carbohydrate increased at 5KGy (0.051 mg/ml). Increased and decreased values were found in both factors for 3 months stored samples of air sealed polyethylene pouch and plastic container. Total antioxidant activity increased at 5KGy (0.072 mg/ml) for polyethylene bag samples and at 0.5KGy (0.137 mg/ml) for plastic container sample. Same way total carbohydrate concentration increased at 0.25KGy (0.046 mg/ml) and at 1KGy (0.045 mg/ml) respectively. This increase is due to affects of γ-irradiation on biomolecules by

Validated assay for the simultaneous quantification of total vincristine and actinomycin-D concentrations in human EDTA plasma and of vincristine concentrations in human plasma ultrafiltrate by high-performance liquid chromatography coupled with tandem mass spectrometry

NARCIS (Netherlands)

Damen, Carola W. N.; Israëls, Trijn; Caron, Huib N.; Schellens, Jan H. M.; Rosing, Hilde; Beijnen, Jos H.

2009-01-01

A sensitive, specific and efficient high-performance liquid chromatography/tandem mass spectrometry (HPLC/MS/MS) assay for the simultaneous determination of total vincristine and actinomycin-D concentrations in human plasma and an assay for the determination of unbound vincristine are presented.

Seasonal variations of total 234Th and dissolved 238U concentration activities in surface water of Bransfield Strait, Antarctica, from March to October 2011

International Nuclear Information System (INIS)

Lapa, Flavia V.; Oliveira, Joselene de; Costa, Alice M.R.; Braga, Elisabete S.

2013-01-01

In this study the naturally occurring radionuclides 234 Th and 238 U were used to investigate the magnitude of upper ocean particulate organic carbon export in Bransfield Strait, Southern Ocean. This region is the largest oceanic high-nitrate low-chlorophyll (HNLC) area in the world and is known to contribute to regulate of the atmospheric CO 2 via the biological pump. Due to its different geochemical behavior in seawater, the resulting U/Th disequilibria can be easily used to constrain the transport rates of particles and reaction processes between solution and particulate phases. Sampling occurred during the summer (March and November) 2011. Total 234 Th activities in surface seawater samples ranged from 1.3 to 3.7 dpm L -1 (station EB 011) during March/11 campaign, while in October/11 total 234 Th activity concentrations varied from 1.4 to 2.9 dpm L -1 . Highest total 234 Th activities were found late in the austral summer season. Activity concentrations of dissolved 238 U in surface seawater varied from 2.1 to 2.4 dpm L -1 . Taking into account all sampling stations established in March and October/11 the relative variability of total 234 Th distribution was 22%. (author)

Effect of ascorbic acid and dehydration on concentrations of total phenolics, antioxidant capacity, anthocyanins, and color in fruits.

Science.gov (United States)

Rababah, Taha M; Ereifej, Khalil I; Howard, L

2005-06-01

The purpose of this investigation was to report on the total phenolics, anthocyanins, and oxygen radical absorbance capacity (ORAC) of strawberry, peach, and apple, the influence of dehydration and ascorbic acid treatments on the levels of these compounds, and the effect of these treatments on fruit color. Results showed that fresh strawberry had the highest levels for total phenolics [5317.9 mg of chlorogenic acid equivalents (CAE)/kg], whereas lower levels were found in fresh apple and peach (3392.1 and 1973.1 mg of CAE/kg, respectively), and for anthocyanins (138.8 mg/kg), whereas lower levels were found in fresh apple and peaches (11.0 and 18.9 mg/kg, respectively; fresh strawberry had an ORAC value of 62.9 mM/kg Trolox equivalents. The fresh apple and peach were found to have ORAC values of 14.7 and 11.4 mM/kg of Trolox equivalents, respectively. The color values indicated that the addition of 0.1% ascorbic acid increased the lightness (L) and decreased the redness (a) and yellowness (b) color values of fresh strawberry, peach, and apple, sliced samples, and the puree made from them. Also, results showed that dehydration is a good method to keep the concentrations of total phenolics and anthocyanins and ORAC values at high levels.

Intracellular Drug Bioavailability: Effect of Neutral Lipids and Phospholipids.

Science.gov (United States)

Treyer, Andrea; Mateus, André; Wiśniewski, Jacek R; Boriss, Hinnerk; Matsson, Pär; Artursson, Per

2018-06-04

Intracellular unbound drug concentrations are the pharmacologically relevant concentrations for targets inside cells. Intracellular drug concentrations are determined by multiple processes, including the extent of drug binding to intracellular structures. The aim of this study was to evaluate the effect of neutral lipid (NL) and phospholipid (PL) levels on intracellular drug disposition. The NL and/or PL content of 3T3-L1 cells were enhanced, resulting in phenotypes (in terms of morphology and proteome) reminiscent of adipocytes (high NL and PL) or mild phospholipidosis (only high PL). Intracellular bioavailability ( F ic ) was then determined for 23 drugs in these cellular models and in untreated wild-type cells. A higher PL content led to higher intracellular drug binding and a lower F ic . The induction of NL did not further increase drug binding but led to altered F ic due to increased lysosomal pH. Further, there was a good correlation between binding to beads coated with pure PL and intracellular drug binding. In conclusion, our results suggest that PL content is a major determinant of drug binding in cells and that PL beads may constitute a simple alternative to estimating this parameter. Further, the presence of massive amounts of intracellular NLs did not influence drug binding significantly.

Total and cause-specific mortality by moderately and markedly increased ferritin concentrations

DEFF Research Database (Denmark)

Ellervik, Christina; Marott, Jacob Louis; Tybjærg-Hansen, Anne

2014-01-01

. Stepwise increasing concentrations of ferritin were associated with a stepwise increased risk of premature death overall (log rank, P = 2 × 10(-22)), with median survival of 55 years at ferritin concentrations ≥600 μg/L, 72 years at 400-599 μg/L, 76 years at 200-399 μg/L, and 79 years at ferritin

Direct binding of radioiodinated monoclonal antibody to tumor cells: significance of antibody purity and affinity for drug targeting or tumor imaging

International Nuclear Information System (INIS)

Kennel, S.J.; Foote, L.J.; Lankford, P.K.; Johnson, M.; Mitchell, T.; Braslawsky, G.R.

1983-01-01

For MoAb to be used efficiently for drug targeting and tumor imaging, the fraction of antibody binding to tumor cells must be maximized. The authors have studied the binding of 125 I MoAb in three different tumor systems. The fraction of antibody that could be bound to the cell surface was directly proportional to the antibody purity. The affinity constant also limits the fraction of antibody that can bind to cells at a given antigen concentration. Rearrangement of the standard expression for univalent equilibrium binding between two reactants shows that in antigen excess, the maximum fraction of antibody that can bind =Ka[Ag total]/1 + Ka[Ag total]. Binding data using four different MoAb with three cell systems confirm this relationship. Estimates for reasonable concentrations of tumor antigens in vivo indicate that antibodies with binding constants less than 10 8 M -1 are not likely to be useful for drug targeting or tumor imaging

Determination of optical properties, drug concentration, and tissue oxygenation in human pleural tissue before and after Photofrin-mediated photodynamic therapy

Science.gov (United States)

Ong, Yi Hong; Padawer-Curry, Jonah; Finlay, Jarod C.; Kim, Michele M.; Dimofte, Andreea; Cengel, Keith; Zhu, Timothy C.

2018-02-01

PDT efficacy depends on the concentration of photosensitizer, oxygen, and light delivery in patient tissues. In this study, we measure the in-vivo distribution of important dosimetric parameters, namely the tissue optical properties (absorption μa (λ) and scattering μs ' (λ) coefficients), photofrin concentration (cphotofrin), blood oxygen saturation (%StO2), and total hemoglobin concentration (THC), before and after PDT. We characterize the inter- and intra-patient heterogeneity of these quantities and explore how these properties change as a result of PDT treatment. The result suggests the need for real-time dosimetry during PDT to optimize the treatment condition depending on the optical and physiological properties.

“Time for dabs”: Analyzing Twitter data on marijuana concentrates across the U.S.

Science.gov (United States)

Daniulaityte, Raminta; Nahhas, Ramzi W.; Wijeratne, Sanjaya; Carlson, Robert G.; Lamy, Francois R.; Martins, Silvia S.; Boyer, Edward W.; Smith, G. Alan; Sheth, Amit

2015-01-01

Aims Media reports suggest increasing popularity of marijuana concentrates (“dabs”; “earwax”; “budder”; “shatter; “butane hash oil”) that are typically vaporized and inhaled via a bong, vaporizer or electronic cigarette. However, data on the epidemiology of marijuana concentrate use remain limited. This study aims to explore Twitter data on marijuana concentrate use in the U.S. and identify differences across regions of the country with varying cannabis legalization policies. Methods Tweets were collected between October 20 and December 20, 2014, using Twitter's streaming API. Twitter data filtering framework was available through the eDrugTrends platform. Raw and adjusted percentages of dabs-related tweets per state were calculated. A permutation test was used to examine differences in the adjusted percentages of dabs-related tweets among U.S. states with different cannabis legalization policies. Results eDrugTrends collected a total of 125,255 tweets. Almost 22% (n=27,018) of these tweets contained identifiable state-level geolocation information. Dabs-related tweet volume for each state was adjusted using a general sample of tweets to account for different levels of overall tweeting activity for each state. Adjusted percentages of dabs-related tweets were highest in states that allowed recreational and/or medicinal cannabis use and lowest in states that have not passed medical cannabis use laws. The differences were statistically significant. Conclusions Twitter data suggest greater popularity of dabs in the states that legalized recreational and/or medical use of cannabis. The study provides new information on the epidemiology of marijuana concentrate use and contributes to the emerging field of social media analysis for drug abuse research. PMID:26338481

Association of serum total bilirubin level with diabetic retinopathy in type 2 diabetes mellitus

International Nuclear Information System (INIS)

Ghaffar, T.; Khan, S.; Aamir, A.U.H.; Marwat, Z.I.

2016-01-01

Serum bilirubin has anti-inflammatory, antioxidant and immunological properties. It is considered a protective substance against atherosclerotic and microvascular complications of diabetes mellitus (DM). This study was designed to find the association between total serum bilirubin concentration and diabetic retinopathy (DR). Methods: This case control study was conducted in the Department of Endocrinology, Diabetes and Metabolic Diseases, Hayatabad Medical Complex, Peshawar. Type-2 DM patients more than 18 years of age of either gender with duration of T2DM more than 6 months were included and sub categorized in two groups. Cases (DM with DR) and Controls (DM without DR) while patients with acute and chronic liver diseases, haemolytic anaemia, history of chronic alcohol consumption, use of hepatotoxic drugs (anti-tuberculous, anti-epileptic), women on oral contraceptive pills were excluded. All participants underwent ophthalmic examination at diabetic retinopathy screening clinic followed by pre designed set of investigations. Results: A total of 152 patients, 76 cases and 76 controls were included. Serum bilirubin concentration was found inversely and independently (p 0.000) associated and inversely co related (r -0.345 and p 0.000) with prevalence of DR. Cases were concentrated in the lower quartiles of serum bilirubin concentration and vice versa. Low haemoglobin (p 0.00) and longer duration of DM (0.003) were independently and directly associated with prevalence of DR. Conclusion: Serum bilirubin concentration is inversely and independently associated and inversely correlated with the prevalence of DR and may predict progression of DR over time. (author)

Postmortem Femoral Blood Concentrations of Risperidone

DEFF Research Database (Denmark)

Linnet, Kristian; Johansen, Sys Stybe

2014-01-01

Postmortem femoral blood concentrations of the antipsychotic drug risperidone and the active metabolite 9-hydroxyrisperidone were determined by an achiral LC-MS/MS method in 38 cases. The cause of death was classified as unrelated to risperidone in 30 cases, in which the sum of the concentration ...

Antimicrobial Drugs in the Home, United Kingdom

OpenAIRE

McNulty, Cliodna A.M.; Boyle, Paul; Nichols, Tom; Clappison, Douglas P.; Davey, Peter

2006-01-01

A total of 6% of 6,983 households in the United Kingdom had leftover antimicrobial drugs, and 4% had standby antimicrobial drugs. Respondents with leftover drugs were more educated, more knowledgeable about antimicrobial drugs, younger, and female. Of respondents with leftover drugs, 44% kept them in case of future need, and 18% had taken these drugs without medical advice.

Flujo y concentración de proteínas en saliva total humana Salivary flow rate and protein concentration in human whole saliva

Directory of Open Access Journals (Sweden)

JOSÉ ANTONIO BANDERAS-TARABAY

1997-09-01

Full Text Available Objetivo. Determinar los promedios de flujo salival y la concentración de proteínas totales en una población joven del Estado de México. Material y métodos. Se seleccionaron 120 sujetos a quienes se les colectó saliva total humana (STH no estimulada y estimulada, la cual se analizó por medio de gravimetría y espectrofotometría (LV/LU; se calcularon medidas de tendencia central y de dispersión; posteriormente, se correlacionaron estos datos con los índices CPOD y CPITN. Resultados. Los sujetos estudiados mostraron un promedio de flujo salival (ml/min ± DE en STH no estimulada de 0.397±.26, y en STH estimulada, de 0.973±.53. El promedio en la concentración de proteínas (mg/ml ± DE fue de 1.374±.45 en STH no estimulada y de 1.526±.44 en STH estimulada. Las mujeres presentaron un menor porcentaje de flujo salival y mayor concentración de proteínas. No se observaron correlaciones entre el flujo y la concentración de proteínas totales y el CPOD y CPITN; sin embargo, sí las hubo con otras variables. Conclusiones. Estos hallazgos podrían estar asociados con el grado de nutrición, las características genéticas y los niveles de salud bucal en nuestra población. El presente estudio representa la fase inicial de la creación de una base de datos en sialoquímica, cuya meta será identificar los parámetros que indiquen el riesgo de enfermedades sistémicas o bucodentales.Objective. To determine the average salivary flow rates and total protein concentrations in a population of the State of Mexico. Material and methods. A gravimetric and spectrophotometric analysis was applied to 120 subjects in total resting and stimulated whole saliva and results were correlated with the DMFT and CPITN indexes. Results. Subjects allowed average salivary flow rate (ml/min ± SD in non-stimulated human whole saliva (HWS of 0.397±.26 and in stimulated HWS of 0.973±.53. Average protein concentration was (mg/ml ± SD 1.374±.45 in non

Relationship of bifenthrin sediment concentrations to grain size and total organic carbon in California waterbodies: implications for ecological risk.

Science.gov (United States)

Hall, Lenwood W; Anderson, Ronald D

2014-12-01

A summary analysis of data sets from six California waterbodies was conducted to determine the relationship of bifenthrin sediment concentrations to: % sand/gravel; % silt; % clay; % silt/clay and % total organic carbon (TOC). The relationship of TOC to % sand/gravel, % silt, % clay, and % silt/clay was also analyzed. Statistically significant and meaningful direct relationships were reported between bifenthrin and % TOC, % silt, % clay and % silt/clay while a significant and meaningful inverse relationship was reported between bifenthrin and % sand/gravel. A significant and meaningful inverse relationship was reported between % TOC and % sand/gravel, while a significant and meaningful direct relationship was reported between % TOC and % silt, % clay and % silt/clay. Significant bifenthrin sediment concentrations would not be expected in non-depositional (sand/gravel) areas which have been reported to be dominant in various streams in California's Central Valley and are also the preferred habitat for many benthic macroinvertebrate taxa.

Does the placebo effect modulate drug bioavailability? Randomized cross-over studies of three drugs.

Science.gov (United States)

Hammami, Muhammad M; Yusuf, Ahmed; Shire, Faduma S; Hussein, Rajaa; Al-Swayeh, Reem

2017-05-23

Medication effect is the sum of its drug, placebo, and drug*placebo interaction effects. It is conceivable that the interaction effect involves modulating drug bioavailability; it was previously observed that being aware of caffeine ingestion may prolong caffeine plasma half-life. This study was set to evaluate such concept using different drugs. Balanced single-dose, two-period, two-group, cross-over design was used to compare the pharmacokinetics of oral cephalexin, ibuprofen, and paracetamol, each described by its name (overt) or as placebo (covert). Volunteers and study coordinators were deceived as to study aim. Drug concentrations were determined blindly by in-house, high performance liquid chromatography assays. Terminal-elimination half-life (t ½ ) (primary outcome), maximum concentration (C max ), C max first time (T max ), terminal-elimination-rate constant (λ), area-under-the-concentration-time-curve, to last measured concentration (AUC T ), extrapolated to infinity (AUC I ), or to T max of overt drug (AUC Overttmax ), and C max /AUC I were calculated blindly using standard non-compartmental method. Covert-vs-overt effect on drug pharmacokinetics was evaluated by analysis-of-variance (ANOVA, primary analysis), 90% confidence interval (CI) using the 80.00-125.00% bioequivalence range, and percentage of individual pharmacokinetic covert/overt ratios that are outside the +25% range. Fifty, 30, and 50 healthy volunteers (18%, 10%, and 6% females, mean (SD) age 30.8 (6.2), 31.4 (6.6), and 31.2 (5.4) years) participated in 3 studies on cephalexin, ibuprofen, and paracetamol, respectively. Withdrawal rate was 4%, 0%, and 4%, respectively. Eighteen blood samples were obtained over 6, 10, and 14 h in each study period of the three drugs, respectively. ANOVA showed no significant difference in any pharmacokinetic parameter for any of the drugs. The 90% CIs for AUC T , AUC I , C max , AUC Overttmax , and C max /AUC I were within the bioequivalence range, except

Total Flavonoids Content in the Raw Material and Aqueous Extractives from Bauhinia monandra Kurz (Caesalpiniaceae

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Ana Josane Dantas Fernandes

2012-01-01

Full Text Available The aim of this work was to evaluate the spectrophotometric methodology for determining the total flavonoid content (TFC in herbal drug and derived products from Bauhinia monandra Kurz. Several analytical parameters from this method grounded on the complex formed between flavonoids and AlCl3 were evaluated such as herbal amount (0.25 to 1.25 g; solvent composition (ethanol 40 to 80%, v/v; as well as the reaction time and AlCl3 concentration (2 to 9%, w/v. The method was adjusted to aqueous extractives and its performance studied through precision, linearity and preliminary robustness. The results showed an important dependence of the method response from reaction time, AlCl3 concentration, sample amount, and solvent mixture. After choosing the optimized condition, the method was applied for the matrixes (herbal material and extractives, showing precision lower than 5% (for both parameters repeatability and intermediate precision, coefficient of determination higher than 0.99, and no important influence could be observed for slight variations from wavelength or AlCl3 concentration. Thus, it could be concluded that the evaluated analytical procedure was suitable to quantify the total flavonoid content in raw material and aqueous extractives from leaves of B. monandra.

Prevalence of alcohol and drugs among car and van drivers killed in road accidents in Norway: an overview from 2001 to 2010.

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Christophersen, Asbjørg S; Gjerde, Hallvard

2014-01-01

To examine the prevalence of alcohol and drugs in blood samples collected from car and van drivers killed in traffic accidents in Norway during the time period from 2001 to 2010. Blood samples (n = 676, 63% of all killed drivers) were analyzed for alcohol, psychoactive medications, and illicit drugs. The cutoff limits for positive results were set according to the new legislative limits under the Norwegian Road Traffic Act. The results were assessed in relation to sex and age, time of day and day of week, and single- versus multiple-vehicle and all investigated vehicle accidents. Alcohol or one or more drugs was detected in samples from 40.2 percent of all investigated drivers, with 28.7 percent showing blood concentrations of at least 5 times the legislative limits. For the investigated female drivers, the total prevalence was 24.0 percent. Among the single-vehicle accidents, alcohol or drugs was found in 63.8 percent of the cases, with 49.1 percent showing blood concentrations of at least 5 times the legislative limits. Alcohol was detected in 25.3 and 49.1 percent of samples from all investigated drivers and among drivers killed in single-vehicle accidents, respectively. Psychoactive medications were found in 14.4 and 17.7 percent and illicit drugs in 14.1 and 19.2 percent, respectively. The most commonly detected group of medications was benzodiazepines, and amphetamines and tetrahydrocannabinol were the most commonly detected illicit drugs. The prevalence of alcohol alone was highest among drivers under the age of 25, and the combination of alcohol with other drugs was highest among drivers under the age of 35. Drivers between the ages of 25 and 54 showed the highest prevalence of medications and/or illicit drugs without the presence of alcohol. The highest prevalence of alcohol or drugs was found among drivers killed in single-vehicle accidents on weeknights (83.8%) and on weekend nights (89.3%). The findings confirm that a large number of fatally injured

Effect of Na2SO3 concentration to drug loading and drug release of ascorbic acid in chitosan edible film as drug delivery system membrane

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Kistriyani Lilis

2018-01-01

Full Text Available Chitosan is a type of carbohydrate compounds produced from waste marine products, in particular the class of shrimp, crabs and clams. Chitosan is often process into edible films and utilized for food packaging also has potential as a membrane for drug delivery system. Drug loading and drug release can be controlled by improve the characteristics of the membrane by adding crosslinker. The purpose of this research is to study the effect of addition of crosslinker to the rate of loading and release of ascorbic acid in the chitosan edible film. Na2SO3 was used as crosslinker. Two grams of chitosan was dissolved into 100 ml of distilled water. Acetic acid and plasticizer were added in the solution then heated at 50°C. Na2SO3 solution with mass various of Na2SO3 dissolved, 01026 0.3; and 0.5 grams were added about 30 mL to make edible film. The analysis include of drug loading, drug release and tensile strength. The result showed that the loading of edible film with crosslinker 0.15 g; 0.3 g; and 0.5 g respectively were 60.98 ppm; 52.53 ppm; and 40.88 ppm, meanwhile for the release with crosslinker 0.15 g; 0.3 g; and 0.5 g respectively were 3.78 ppm; 5.72 ppm; and 5.97 ppm.

Grapefruit and drug interactions.

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2012-12-01

Since the late 1980s, grapefruit juice has been known to affect the metabolism of certain drugs. Several serious adverse effects involving drug interactions with grapefruit juice have been published in detail. The components of grapefruit juice vary considerably depending on the variety, maturity and origin of the fruit, local climatic conditions, and the manufacturing process. No single component accounts for all observed interactions. Other grapefruit products are also occasionally implicated, including preserves, lyophylised grapefruit juice, powdered whole grapefruit, grapefruit seed extract, and zest. Clinical reports of drug interactions with grapefruit juice are supported by pharmacokinetic studies, each usually involving about 10 healthy volunteers, in which the probable clinical consequences were extrapolated from the observed plasma concentrations. Grapefruit juice inhibits CYP3A4, the cytochrome P450 isoenzyme most often involved in drug metabolism. This increases plasma concentrations of the drugs concerned, creating a risk of overdose and dose-dependent adverse effects. Grapefruit juice also inhibits several other cytochrome P450 isoenzymes, but they are less frequently implicated in interactions with clinical consequences. Drugs interacting with grapefruit and inducing serious clinical consequences (confirmed or very probable) include: immunosuppressants, some statins, benzodiazepines, most calcium channel blockers, indinavir and carbamazepine. There are large inter-individual differences in enzyme efficiency. Along with the variable composition of grapefruit juice, this makes it difficult to predict the magnitude and clinical consequences of drug interactions with grapefruit juice in a given patient. There is increasing evidence that transporter proteins such as organic anion transporters and P-glycoprotein are involved in interactions between drugs and grapefruit juice. In practice, numerous drugs interact with grapefruit juice. Although only a few

Application of Hill's equation for estimating area under the concentration-time curve (AUC) and use of time to AUC 90% for expressing kinetics of drug disposition.

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Cheng, Hsien C

2009-01-01

Half life and its derived pharmacokinetic parameters are calculated on an assumption that the terminal phase of drug disposition follows a constant rate of disposition. In reality, this assumption may not necessarily be the case. A new method is needed for analyzing PK parameters if the disposition does not follow a first order PK kinetic. Cumulative area under the concentration-time curve (AUC) is plotted against time to yield a hyperbolic (or sigmoidal) AUC-time relationship curve which is then analyzed by Hill's equation to yield AUC(inf), time to achieving AUC50% (T(AUC50%)) or AUC90% (T(AUC90%)), and the Hill's slope. From these parameters, an AUC-time relationship curve can be reconstructed. Projected plasma concentration can be calculated for any time point. Time at which cumulative AUC reaches 90% (T(AUC90%)) can be used as an indicator for expressing how fast a drug is cleared. Clearance is calculated in a traditional manner (i.v. dose/AUC(inf)), and the volume of distribution is proposed to be calculated at T(AUC50%) (0.5 i.v. dose/plasma concentration at T(AUC50%)). This method of estimating AUC is applicable for both i.v. and oral data. It is concluded that the Hill's equation can be used as an alternative method for estimating AUC and analysis of PK parameters if the disposition does not follow a first order kinetic. T(AUC90%) is proposed to be used as an indicator for expressing how fast a drug is cleared from the system.

21 CFR 146.150 - Canned concentrated orange juice.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 2 2010-04-01 2010-04-01 false Canned concentrated orange juice. 146.150 Section... Fruit Juices and Beverages § 146.150 Canned concentrated orange juice. (a) Canned concentrated orange... labeling of ingredients prescribed for frozen concentrated orange juice by § 146.146, except that it is not...

Metal ions diffusion through polymeric matrices: A total reflection X-ray fluorescence study

International Nuclear Information System (INIS)

Boeykens, S.; Caracciolo, N.; D'Angelo, M.V.; Vazquez, C.

2006-01-01

This work proposes the use of X-ray fluorescence with total reflection geometry to explore the metal ions transport in aqueous hydrophilic polymer solutions. It is centered in the study of polymer concentration influence on ion diffusion. This subject is relevant to various and diverse applications, such as drug controlled release, microbiologic corrosion protection and enhanced oil recovery. It is anticipated that diffusion is influenced by various factors in these systems, including those specific to the diffusing species, such as charge, shape, molecular size, and those related to the structural complexity of the matrix as well as any specific interaction between the diffusing species and the matrix. The diffusion of nitrate salts of Ba and Mn (same charge, different hydrodynamic radii) through water-swollen polymeric solutions and gels in the 0.01% to 1% concentration ranges was investigated. The measurements of the metal concentration were performed by TXRF analysis using the scattered radiation by the sample as internal standard. Results are discussed according to different physical models for solute diffusion in polymeric solutions

Improved Tumor-Specific Drug Accumulation by Polymer Therapeutics with pH-Sensitive Drug Release Overcomes Chemotherapy Resistance.

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Heinrich, Anne-Kathrin; Lucas, Henrike; Schindler, Lucie; Chytil, Petr; Etrych, Tomáš; Mäder, Karsten; Mueller, Thomas

2016-05-01

The success of chemotherapy is limited by poor selectivity of active drugs combined with occurrence of tumor resistance. New star-like structured N-(2-hydroxypropyl) methacrylamide (HPMA) copolymer-based drug delivery systems containing doxorubicin attached via a pH-sensitive hydrazone bond were designed and investigated for their ability to overcome chemotherapy resistance. These conjugates combine two strategies to achieve a high drug concentration selectively at the tumor site: (I) high accumulation by passive tumor targeting based on enhanced permeability and retention effect and (II) pH-sensitive site-specific drug release due to an acidic tumor microenvironment. Mice bearing doxorubicin-resistant xenograft tumors were treated with doxorubicin, PBS, poly HPMA (pHPMA) precursor or pHPMA-doxorubicin conjugate at different equivalent doses of 5 mg/kg bodyweight doxorubicin up to a 7-fold total dose using different treatment schedules. Intratumoral drug accumulation was analyzed by fluorescence imaging utilizing intrinsic fluorescence of doxorubicin. Free doxorubicin induced significant toxicity but hardly any tumor-inhibiting effects. Administering at least a 3-fold dose of pHPMA-doxorubicin conjugate was necessary to induce a transient response, whereas doses of about 5- to 6-fold induced strong regressions. Tumors completely disappeared in some cases. The onset of response was differential delayed depending on the tumor model, which could be ascribed to distinct characteristics of the microenvironment. Further fluorescence imaging-based analyses regarding underlying mechanisms of the delayed response revealed a related switch to a more supporting intratumoral microenvironment for effective drug release. In conclusion, the current study demonstrates that the concept of tumor site-restricted high-dose chemotherapy is able to overcome therapy resistance. Mol Cancer Ther; 15(5); 998-1007. ©2016 AACR. ©2016 American Association for Cancer Research.

Pricing behaviour of pharmacies after market deregulation for OTC drugs: the case of Germany.

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Stargardt, Tom; Schreyögg, Jonas; Busse, Reinhard

2007-11-01

To examine the price reactions of German pharmacies to changes made to OTC drug regulations in 2004. Prior to these changes, regulations guaranteed identical prices in all German pharmacies. Two years after market deregulation, 256 pharmacies were surveyed to determine the retail prices of five selected OTC drugs. A probit regression model was used to identify factors that increased the likelihood of price changes. In addition, 409 pharmacy consumers were interviewed to gather information on their knowledge of the regulatory changes and to better explain consumer behaviour. Data was collected on a total of 1215 prices. Two years after deregulation, 23.1% of the participating pharmacies had modified the price of at least one of the five OTCs included in our study. However, in total, only 7.5% of the prices differed from their pre-deregulation level. The probit model showed that population density and the geographic concentration of pharmacies were significantly associated with price changes. Interestingly, the association with the geographic concentration of pharmacies was negative. The consumer survey revealed that 47.1% of those interviewed were aware of the deregulation. Our findings indicate that, two years after deregulation, very few pharmacies had made use of individual pricing strategies; price competition between pharmacies in Germany is thus taking place only a very small scale.

Population pharmacokinetic study of benznidazole in pediatric Chagas disease suggests efficacy despite lower plasma concentrations than in adults.

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Jaime Altcheh

2014-05-01

Full Text Available Chagas disease, caused by the parasite Trypanosoma cruzi, can lead to long term cardiac morbidity. Treatment of children with benznidazole is effective, but no pediatric pharmacokinetics data are available and clinical pharmacology information on the drug is scarce.Prospective population pharmacokinetic (PK cohort study in children 2-12 years old with Chagas disease treated with oral benznidazole 5-8 mg/kg/day BID for 60 days. (clinicaltrials.gov #NCT00699387.Forty children were enrolled in the study. Mean age was 7.3 years. A total of 117 samples were obtained from 38 patients for PK analysis. A one compartment model best fit the data. Weight-corrected clearance rate (CL/F showed a good correlation with age, with younger patients having a significantly higher CL/F than older children and adults. Simulated median steady-state benznidazole concentrations, based on model parameters, were lower for children in our study than for adults and lowest for children under 7 years of age. Treatment was efficacious in the 37 patients who completed the treatment course, and well tolerated, with few, and mild, adverse drug reactions (ADRs.Observed benznidazole plasma concentrations in children were markedly lower than those previously reported in adults (treated with comparable mg/kg doses, possibly due to a higher CL/F in smaller children. These lower blood concentrations were nevertheless associated to a high therapeutic response in our cohort. Unlike adults, children have few adverse reactions to the drug, suggesting that there may be a direct correlation between drug concentrations and incidence of ADRs. Our results suggest that studies with lower doses in adults may be warranted.ClinicalTrials.gov NCT00699387.

Characterization and quantitation of aprepitant drug substance polymorphs by attenuated total reflectance fourier transform infrared spectroscopy.

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Helmy, Roy; Zhou, George X; Chen, Yadan W; Crocker, Louis; Wang, Tao; Wenslow, Robert M; Vailaya, Anant

2003-02-01

In this study, we report the use of attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FT-IR) for the identification and quantitation of two polymorphs of Aprepitant, a substance P antagonist for chemotherapy-induced emesis. Mixtures of the polymorph pair were prepared by weight and ATR-FT-IR spectra of the powdered samples were obtained over the wavelength range of 700-1500 cm(-1). Significant spectral differences between the two polymorphs at 1140 cm(-1) show that ATR-FT-IR can provide definitive identification of the polymorphs. To investigate the feasibility of ATR-FT-IR for quantitation of polymorphic forms of Aprepitant, a calibration plot was constructed with known mixtures of the two polymorphs by plotting the peak ratio of the second derivative of absorbance spectra against the weight percent of form II in the polymorphic mixture. Using this novel approach, 3 wt % of one crystal form could be detected in mixtures of the two polymorphs. The accuracy of ATR-FT-IR in determining polymorph purity of the drug substance was tested by comparing the results with those obtained by X-ray powder diffractometry (XRPD). Indeed, polymorphic purity results obtained by ATR-FT-IR were found to be in good agreement with the predictions made by XRPD and compared favorably with actual values in the known mixtures. The present study clearly demonstrates the potential of ATR-FT-IR as a quick, easy, and inexpensive alternative to XRPD for the determination of polymorphic identity and purity of solid drug substances. The technique is ideally suited for polymorph analysis, because it is precise, accurate, and requires minimal sample preparation.

Prevalence of alcohol and drugs among motorcycle riders killed in road crashes in Norway during 2001-2010.

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Christophersen, Asbjørg S; Gjerde, Hallvard

2015-07-01

The aim of the study was to examine the prevalence of alcohol and drugs in blood samples from motorcycle riders who died in road crashes in Norway from 2001 to 2010. An additional aim was to compare the prevalence of alcohol and drugs in blood samples from fatally injured motorcycle riders and car drivers who died during the same time period. Blood samples from motorcycle riders who died within 24h after the accident (n=207, 63% of all killed riders), were analysed for alcohol, psychoactive drugs (medicinal and illicit drugs). The cut-off concentrations for alcohol and drugs findings in blood samples (i.e., the drug concentrations above which a finding was regarded as positive) were set according to the legislative limits under the Norwegian Road Traffic Act. Results were assessed in relation to age, sex, time of the day and week, and single versus multiple-vehicle accidents. Alcohol or drugs were found in 27.1 percent of all investigated riders. For riders killed in single or multiple-vehicle accidents, alcohol or drugs were found in 44.6 and 15.3 percent, respectively. Alcohol was the most frequently found substance for all age groups and most prevalent in samples from riders below 25 years who died in single-vehicle accidents (45.8 percent). Drugs were most often found among riders between 25 and 34 years (19.6 percent in total and 25.9% for those killed in single-vehicle crashes). The prevalence of alcohol or drugs was highest among riders killed in single-vehicle accidents during weekend days and nights (60.9 and 65.2 percent). Alcohol and drugs were less often found in samples from killed motorcycles riders than in samples from car and van drivers (40.2 percent). For single-vehicle accidents, the total prevalence of alcohol or drugs among killed motorcycles riders and car drivers was 44.6 percent and 63.8 percent, respectively. The same pattern of alcohol and drugs was found among the two groups, except that the prevalence among motorcycle riders was lower

Exploring drug-target interaction networks of illicit drugs.

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Atreya, Ravi V; Sun, Jingchun; Zhao, Zhongming

2013-01-01

Drug addiction is a complex and chronic mental disease, which places a large burden on the American healthcare system due to its negative effects on patients and their families. Recently, network pharmacology is emerging as a promising approach to drug discovery by integrating network biology and polypharmacology, allowing for a deeper understanding of molecular mechanisms of drug actions at the systems level. This study seeks to apply this approach for investigation of illicit drugs and their targets in order to elucidate their interaction patterns and potential secondary drugs that can aid future research and clinical care. In this study, we extracted 188 illicit substances and their related information from the DrugBank database. The data process revealed 86 illicit drugs targeting a total of 73 unique human genes, which forms an illicit drug-target network. Compared to the full drug-target network from DrugBank, illicit drugs and their target genes tend to cluster together and form four subnetworks, corresponding to four major medication categories: depressants, stimulants, analgesics, and steroids. External analysis of Anatomical Therapeutic Chemical (ATC) second sublevel classifications confirmed that the illicit drugs have neurological functions or act via mechanisms of stimulants, opioids, and steroids. To further explore other drugs potentially having associations with illicit drugs, we constructed an illicit-extended drug-target network by adding the drugs that have the same target(s) as illicit drugs to the illicit drug-target network. After analyzing the degree and betweenness of the network, we identified hubs and bridge nodes, which might play important roles in the development and treatment of drug addiction. Among them, 49 non-illicit drugs might have potential to be used to treat addiction or have addictive effects, including some results that are supported by previous studies. This study presents the first systematic review of the network

The relationship of endogenous plasma concentrations of β-Hydroxy β-Methyl Butyrate (HMB) to age and total appendicular lean mass in humans.

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Kuriyan, Rebecca; Lokesh, Deepa P; Selvam, Sumithra; Jayakumar, J; Philip, Mamatha G; Shreeram, Sathyavageeswaran; Kurpad, Anura V

2016-08-01

The maintenance of muscle mass and muscle strength is important for reducing the risk of chronic diseases. The age- related loss of muscle mass and strength is associated with adverse outcomes of physical disability, frailty and death. β-Hydroxy β-Methyl Butyrate (HMB), a metabolite of leucine, has beneficial effects on muscle mass and strength under various catabolic conditions. The objectives of the present study were to determine if age- related differences existed in endogenous plasma HMB levels, and to assess if HMB levels correlated to total appendicular lean mass and forearm grip strength. Anthropometry, dietary and physical activity assessment, and the estimation of fasting plasma HMB concentrations and handgrip strength were performed on the 305 subjects (children, young adults and older adults). Lean mass, which serves as a surrogate for muscle mass was measured using dual energy X-ray absorptiometry (DEXA). Mean plasma HMB concentrations were significantly lower with increasing age groups, with children having highest mean HMB concentration (pHMB concentrations. A significant positive correlation between HMB concentrations and appendicular lean mass normalized for body weight (%), appendicular lean mass (r=0.37; pHMB concentrations in young adults (r=0.58; pHMB concentrations in humans and the HMB concentrations were positively correlated with appendicular lean mass and hand grip strength in young adults and older adults group. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

21 CFR 146.145 - Orange juice from concentrate.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 2 2010-04-01 2010-04-01 false Orange juice from concentrate. 146.145 Section 146... Juices and Beverages § 146.145 Orange juice from concentrate. (a) Orange juice from concentrate is the food prepared by mixing water with frozen concentrated orange juice as defined in § 146.146 or with...

Therapeutic drug monitoring of isoniazid and rifampicin during anti-tuberculosis treatment in Auckland, New Zealand.

Science.gov (United States)

Maze, M J; Paynter, J; Chiu, W; Hu, R; Nisbet, M; Lewis, C

2016-07-01

There is uncertainty as to the optimal therapeutic concentrations of anti-tuberculosis drugs to achieve cure. To characterise the use of therapeutic drug monitoring (TDM), and identify risk factors and outcomes for those with concentrations below the drug interval. Patients treated for tuberculosis (TB) who had rifampicin (RMP) or isoniazid (INH) concentrations measured between 1 January 2005 and 31 December 2012 were studied retrospectively. Matched concentrations and drug dosing time were assessed according to contemporary regional drug intervals (RMP > 6 μmol/l, INH > 7.5 μmol/l) and current international recommendations (RMP > 10 μmol/l, INH > 22 μmol/l). Outcomes were assessed using World Health Organization criteria. Of 865 patients, 121 had concentrations of either or both medications. RMP concentrations were within the regional drug intervals in 106/114 (93%) and INH in 91/100 (91%). Concentrations were within international drug intervals for RMP in 76/114 (67%) and INH in 53/100 (53%). Low weight-based dose was the only statistically significant risk factor for concentrations below the drug interval. Of the 35 patients with low concentrations, 21 were cured, 9 completed treatment and 5 transferred out. There were no relapses during follow-up (mean 66.5 months). There were no clinically useful characteristics to guide use of TDM. Many patients had concentrations below international therapeutic intervals, but were successfully treated.

Trace elements in natural drugs determined by INAA

International Nuclear Information System (INIS)

Chen Kehshaw; Tseng Chialiang; Lin Tehsien

1993-01-01

Natural drugs are widely used for diuretic, phlegm elimination and stomach invigoration purposes. Seventy-five of the most common remedies used by Chinese people have been subjected to trace element survey analysis by instrumental neutron activation. Within this large number of different natural products, fourteen trace elements (K, Sc, Cr, Fe, Co, Zn, Br, Rb, Cs, La, Sm, Eu, Au and Th) are commonly detected. Among these elements, Fe had the highest concentration followed by Zn, and Rb, Sm, Eu and Au were found to have the lowest concentrations. Although the three groups of natural drugs exhibit a widely different therapeutic action, the concentration ranges of the fourteen elements were very similar. While this suggests no apparent specific role for the trace elements in the drug function, parallels are drawn between the known drug related functions of Rb, Zn, Br, Fe, Co and K and the levels of elements found in the natural drugs. It is concluded that the various natural drugs also provide human benefits through supplements of essential elements such as Fe, Zn, Cr, Sc, Rb and Co. (author) 13 refs.; 5 tabs

The impact of total suspended particulate concentration on workers’ health at ceramic industry

Science.gov (United States)

Sintorini, M. M.

2018-01-01

Ceramic production process pollutes the air with particulate matter at high concentration and has negative impact on the workers. The objective of this research was to determine the particulate concentration in the air and to analyse its impact on the workers. This research used cross sectional method to correlate the particulate concentration, temperature, humidity, smoke level and level of workers’ compliance with safety regulations. Sampling was conducted from April to May 2012 in three locations, i.e. exposure area (Mass Preparation I, II) and non-exposure area (Forming area). In the exposure area (Mass Preparation I and II) where the particulate concentrations were 22.3673 mg/m3 and 14.8277 mg/m3, and 58.33%, the workers had bad health status. In the non-exposure area, where the particulate concentration was 3.2185 mg/m3 and 25% the workers had bad health status. The Odds Ratio among the workers in exposure area was 4.2 times higher than the workers in the non-exposure area.

Clinically relevant potential drug-drug interactions among outpatients: A nationwide database study.

Science.gov (United States)

Jazbar, Janja; Locatelli, Igor; Horvat, Nejc; Kos, Mitja

2018-06-01

Adverse drug events due to drug-drug interactions (DDIs) represent a considerable public health burden, also in Slovenia. A better understanding of the most frequently occurring potential DDIs may enable safer pharmacotherapy and minimize drug-related problems. The aim of this study was to evaluate the prevalence and predictors of potential DDIs among outpatients in Slovenia. An analysis of potential DDIs was performed using health claims data on prescription drugs from a nationwide database. The Lexi-Interact Module was used as the reference source of interactions. The influence of patient-specific predictors on the risk of potential clinically relevant DDIs was evaluated using logistic regression model. The study population included 1,179,803 outpatients who received 15,811,979 prescriptions. The total number of potential DDI cases identified was 3,974,994, of which 15.6% were potentially clinically relevant. Altogether, 9.3% (N = 191,213) of the total population in Slovenia is exposed to clinically relevant potential DDIs, and the proportion is higher among women and the elderly. After adjustment for cofactors, higher number of medications and older age are associated with higher odds of clinically relevant potential DDIs. The burden of DDIs is highest with drug combinations that increase risk of bleeding, enhance CNS depression or anticholinergic effects or cause cardiovascular complications. The current study revealed that 1 in 10 individuals in the total Slovenian population is exposed to clinically relevant potential DDIs yearly. Taking into account the literature based conservative estimate that approximately 1% of potential DDIs result in negative health outcomes, roughly 1800 individuals in Slovenia experience an adverse health outcome each year as a result of clinically relevant potential interactions alone. Copyright © 2017 Elsevier Inc. All rights reserved.

Elemental concentration in normal skin and fibroepithelial polip lesions by synchrotron radiation total reflection X-ray fluorescence technique

International Nuclear Information System (INIS)

Soares, Julio C.A.C.R.; Canellas, Catarine G.L.; Lopes, Ricardo T.; Anjos, Marcelino J.

2011-01-01

In this work, the concentrations of trace elements were measured in acrochordon, a skin lesion also known as skin tag or fibroepithelial polyp, as well as in normal skin from the same patient. The samples were analysed by Synchrotron Radiation Total Reflection X- ray Fluorescence (SRTXRF) in the Synchrotron Light National Laboratory (LNLS) in Campinas/Sao Paulo-Brazil. The collection of lesion and healthy skin samples, including papillary dermis and epidermis, has involved 17 patients. It was evaluated the presence of P, S, Cl, K, Ca, Cr, Mn, Fe, Cu, Zn, Br and Rb in the paired samples, which were compared, and significant differences were found in some of them. (author)

The interpretation of hair analysis for drugs and drug metabolites.

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