Circadian Phase Dependent Pharmacokinetics of Disopyramide in Mice

The focus of the reported work is investigation of disopyramide chronopharmacokinetics in the mouse. Different groups of male NMRI mice maintained under controlled environmental conditions (LD: 0600-1800) received a single intraperitoneal injection of disopyramide (30mg per kg of body weight) at one of four different fixed time points of a 24-h period, i.e. 1000, 1600, 2200 or 0400. Blood samples were taken 0.5,1,2,3,4 and 6 hr after drug administration and total and free plasma levels of disopyramide were measured by an immunoenzymatic method.

Our data showed statistically significant circadian rhythms in the following pharmacokinetic parameters: highest volume of distribution = 3.91 ± 0.211kg^-1 at 2200 (circadian amplitude, half the peak-to-trough difference relative to the 24-hr mean multiplied by 100, is 34%); highest area under concentration curves = 16.06 ± 1.03μgml^-1hr^-1 at 0400 (circadian amplitude = 43%) and highest clearance = 3.04 ± 0.191hr“kg”¹ at 2200 (circadian amplitude = 21%). Protein binding of the drug was shown to ^he circadian time dependent. Alpha and beta phase elimination half-lives were not found to be significantly circadian phase-dependent. Thus circadian changes in disopyramide clearance may represent circadian changes in the drug's volume of distribution.     

Salivary cortisol concentration after high-intensity interval exercise: Time of day and chronotype effect

Due to personal and working necessities, the time for exercise is often short, and scheduled early in the morning or late in the afternoon. Cortisol plays a central role in the physiological and behavioral response to a physical challenge and can be considered as an index of exercise stress. Therefore, the aim of this study was to evaluate the influence of the circadian phenotype classification on salivary cortisol concentration in relation to an acute session of high-intensity interval exercise (HIIE) performed at different times of the day. Based on the morningness–eveningness questionnaire, 12 M-types (N = 12; age 21 ± 2 years; height 179 ± 5 cm; body mass 74 ± 12 kg, weekly training volume 8 ± 1 hours) and 11 E-types (N = 11; age 21 ± 2 years; height 181 ± 11 cm; body mass 76 ± 11 kg, weekly training volume 7 ± 2 hours) were enrolled in a randomized crossover study. All subjects underwent measurements of salivary cortisol secretion before (PRE), immediately after (POST), and 15 min (+15 min), 30 min (+30 min), 45 min (+45 min) and 60 min (+60 min) after the completion of both morning (08.00 am) and evening (08.00 p.m.) high-intensity interval exercise. Two-way analysis of variance with Tuckey’s multiple comparisons test showed significant increments over PRE-cortisol concentrations in POSTcondition both in the morning (4.88 ± 1.19 ng · mL^?1 vs 6.60 ± 1.86 ng · mL^?1, +26.1%, P < 0.0001, d > 0.8) and in the evening (1.56 ± 0.48 ng · mL^?1 vs 2.34 ± 0.37, +33.4%, P = 0.034, d > 0.6) exercise in all the 23 subject that performed the morning and the evening HIIE. In addition, during morning exercise, significant differences in cortisol concentration between M-types and E-types at POST (5.49 ± 0.98 ng · mL^?1 versus 8.44 ± 1.08 ng · mL^?1, +35%, P < 0.0001, d > 0.8), +15 min (4.52 ± 0.42 ng · mL^?1 versus 6.61 ± 0.62 ng · mL^?1, +31.6%, P < 0.0001, d > 0.8), +30 min (4.10 ± 1.44 ng · mL^?1 versus 6.21 ± 1.60 ng · mL^?1, +34.0%, P < 0.0001, d = 0.7), + 45 min (3.78 ± 0.55 ng · mL^?1 versus 5.80 ± 0.72 ng · mL^?1, +34.9%, P < 0.0001, d = 0.7), and + 60 min condition(3.53 ± 0.45 ng · mL^?1 versus 5.78 ± 1.13 ng · mL^?1, 38.9%, P = 0.0008, d = 0.7) were noted. No statistical significant differences between M-types and E-types during evening HIIE on post-exercise cortisol concentration were detected. E-types showed a higher morning peak of salivary cortisol respect to M-types when performing a HIIE early in the morning and produced higher salivary cortisol concentrations after the cessation of the exercise. Practical applications suggest that it is increasingly important for the exercise professionals to identify the compatibility between time of day for exercising and chronotype to find the individual’s favorable circadian time to perform a HIIE.     

The influence of the length of time after hormonal treatment with [(d‐Ala6, Pro9 NEt)‐mGnRH+metoclopramide] i.e. Ovopel on barbel Barbus barbus (L.) milt quality and quantity indicators

The study purpose was the analysis of barbel Barbus barbus (L.) milt quality and quantity with regard to the time following stimulation with [(D‐Ala⁶, Pro⁹NEt)‐mGnRH+metoclopramide] i.e. Ovopel. Selected parameters such as total volume of milt (TVM, ml), volume of milt per kg of body weight (VOM, ml kg^?1 b.w.), sperm concentration (×10⁹ ml^?1), total sperm production (TSP, ×10⁹), osmolality (mOsm kg^?1) and pH of seminal plasma were determined. Sperm motility was analyzed by the CASA system, i.e. the percentage of sperm motility (MOT, %) and their progressive motility (PRG, %), curvilinear velocity (VCL, μm s^?1) and straight line velocity (VSL, μm s^?1), amplitude of lateral head displacement (ALH, μm), and beat cross frequency (BCF, Hz). Milt was collected from 12 specimens (N = 12), with the first portion obtained 12 h following treatment with Ovopel (1 granule kg^?1 b. w.). Subsequent portions of milt were taken at 24 h intervals, i.e. after 36, 60, 84, 108, and 132 h. The control group (Control, N = 12) was injected with 0.9% NaCl at 0.5 ml kg^?1b.w. from which milt was taken 12 h post injection. The highest TVM, VOM and TSP values were recorded 12 h after Ovopel treatment (3.2 ± 0.7 ml, 36.7 ± 10.5 ml kg^?1 b.w. and 39.1 ± 9.4 × 10⁹, respectively); lowest values were recorded after 132 h (0.8 ± 0.4 ml, 11.1 ± 6.5 ml kg^?1b.w. and 13.7 ± 7.5 × 10⁹, respectively). The highest seminal plasma osmolality values (300.0 ± 42.6 mOsm kg^?1) as well as the lowest sperm concentration (12.5 ± 1.5 × 10⁹ ml^?1) were observed 12 h after Ovopel treatment. No significant differences in the percentage of sperm motility (MOT) were noted during any of the periods after hormonal stimulation, however, a change in the character of their movement (PRG) was observed. The lack of significant differences (P > 0.05) in VCL and VSL values between 12 h and 60–132 h indicates that the lengthening of time does not lead to a decrease in sperm velocity and, therefore, is not likely to have a negative impact on their quality. The highest ALH (1.9 ± 0.2 μm) and BCF (11.5 ± 1.1 Hz) values were observed when the effect of stimulation was most noticeable, i.e. 12 h after Ovopel treatment. Based on the total milt volume and sperm production, the best time for milt collection from barbel is 12 h post‐hormonal treatment; 84 h post‐hormonal treatment, TVM, VOM, TSP and some CASA parameters decreased, which suggest the same aging process in sperm.     

Continuous fermentation to produce xanthan biopolymer: Effect of dilution rate

Single-stage continuous fermentations to produce xanthan gum have been run at dilution rates (D) from 0.023 to 0.196 hr^?1. Xanthan production rate (XPR) was a function of D. XPR increased from 0.34 g/hr/kg at D = 0.023 hr^?1 to the maximum 0.84 g/hr/kg at D = ca. 0.15 hr^?1. At D > 0.15 hr^?1 XPR decreased and at the highest D studied (0.196 hr^?1) was 0.69 g/hr/kg. Yield of xanthan from glucose consumed was 81–89%. Steady states ended between 6.5 and 8.7 turnovers when a variant strain occurred.     

Elimination kinetics and protein binding of theophylline in the rabbit

The detailed elimination kinetics of theophylline were studied in 27 rabbits. Each received a 10 mg/kg intravenous bolus of aminophylline. The theophylline half-life ($\text{T}\text{1}\text{2}$) was 3.8 ± 0.63 hr. The apparent volume of distribution (V_D) and total body clearance (TBC) for theophylline were 439 ± 60 ml/kg and 81.0 ± 17.3 ml/kg·hr respectively. Theophylline protein binding was determined in 10 animals. The mean bound fraction was 74.3 ± 3.9% (range, 68.3–78.0%); the fraction bound was concentration indifferent over a serum concentration range of 5–20 μgm/ml.     

Preparturient changes in plasma concentrations of estrone,estradiol-17β and estradiol-17α in the fetal calf: Effects of dexamethasone infusion

The concentrations of total estrogens in fetal calf plasma were determined during a 6–10 day period immediately before delivery. Comparison was made between levels found in untreated calves and calves infused with dexamethasone at the rate of 0.1, 1.0 and 10 mg/24 hours. In untreated calves the plasma estrone, estradiol-17β and estradiol-17α levels remained relatively constant at 38 ± 7 ng ml^?1 (mean ± SEM n = 3), 46 ± 6 ng ml^?1 and 29 ± 5 ng ml^?1 respectively. Infusion with dexamethasone at 0.1 mg/24 hr (3 calves) and 1.0 mg/24 hr (3 calves) was without dramatic effect on plasma estrogen levels. However, in one fetus infused with 10.0 mg/24 hr the dexamethasone treatment may have caused a transitory rise in the levels of all estrogens examined.     

Circadian rhythm in QT interval is preserved in mice deficient of potassium channel interacting protein 2

Potassium Channel Interacting Protein 2 (KChIP2) is suggested to be responsible for the circadian rhythm in repolarization duration, ventricular arrhythmias, and sudden cardiac death. We investigated the hypothesis that there is no circadian rhythm in QT interval in the absence of KChIP2. Implanted telemetric devices recorded electrocardiogram continuously for 5 days in conscious wild-type mice (WT, n = 9) and KChIP2^?/? mice (n = 9) in light:dark periods and in complete darkness. QT intervals were determined from all RR intervals and corrected for heart rate (QT₁₀₀ = QT/(RR/100)^1/2). Moreover, QT intervals were determined from complexes within the RR range of mean-RR ± 1% in the individual mouse (QT_mean-RR). We find that RR intervals are 125 ± 5 ms in WT and 123 ± 4 ms in KChIP2^?/? (p = 0.81), and QT intervals are 52 ± 1 and 52 ± 1 ms, respectively(p = 0.89). No ventricular arrhythmias or sudden cardiac deaths were observed. We find similar diurnal (light:dark) and circadian (darkness) rhythms of RR intervals in WT and KChIP2^?/? mice. Circadian rhythms in QT₁₀₀ intervals are present in both groups, but at physiological small amplitudes: 1.6 ± 0.2 and 1.0 ± 0.3 ms in WT and KChIP2^?/?, respectively (p = 0.15). A diurnal rhythm in QT₁₀₀ intervals was only found in WT mice. QT_mean-RR intervals display clear diurnal and circadian rhythms in both WT and KChIP2^?/?. The amplitude of the circadian rhythm in QT_mean-RR is 4.0 ± 0.3 and 3.1 ± 0.5 ms in WT and KChIP2^?/?, respectively (p = 0.16). In conclusion, KChIP2 expression does not appear to underlie the circadian rhythm in repolarization duration.     

A Counter-Current Acid Leaching Process for the Remediation of Contaminated Soils from a Small-Arms Shooting Range

The objective of this research was to use a counter-current leaching process (CCLP) with leachate treatment to develop a remediation process for contaminated soils at a small-arms shooting range (SASR). The soil contaminant concentrations were 245 mg Cu kg^?1, 3,368 mg Pb kg^?1, 73 mg Sb kg^?1, and 177 mg Zn kg^?1. The CCLP includes three acid leaching steps (1M H₂SO₄ + 4M NaCl, t = 1 h, T = 20°C, soil suspension = 100 g L^?1), followed by one water rinsing step (1 h). Seven counter-current remediation cycles were completed, and the average resulting metal removals were 93.2 ± 3.5% of Cu, 91.5 ± 5.7% of Pb, 82.2 ± 10.9% of Sb, and 30.0 ± 11.4% of Zn. The metal leaching performances decreased with the number of completed cycles. Soil treated with the CCLP with leachate treatment process met the USEPA threshold criteria of 5 mg Pb L^?1 in the TCLP leachate. The CCLP allows a decrease of the water use by 32.9 m³ t^?1 and the chemicals’ consumption by approximately 2,650 kg H₂SO₄, 6,014 kg NaCl, and 1,150 kg NaOH per ton of treated soil, in comparison to standard leaching processes. This corresponds to 78%, 69%, 83%, and 67% of reduction, respectively.     

Effect of different doses of organic fertilizer (cow dung) on pond productivity and fish biomass in stillwater ponds

The effects of five (5 000, 10 000, 15 000, 20 000, 24 000 kg ha^?1 year^?1) different doses of organic fertilizer (cow dung) were studied on pond productivity in terms of plankton production and fish biomass in freshwater fish ponds. The grow out period was 60 days. Physico-chemical factors of pond waters were also monitored. With an increase in the fertilizer dose, biochemical oxygen demand (BOD) (1.7 ± 0.1 – 10.35 ± 0.05 mg L^?1), O-PO₄ (0.04 ± 0.0 – 0.77 ± 0.02 mg L^?1) and NH₄-N (0.03 ± 0.02 – 0.32 ± 0.02 mg L^?1) increased significantly (P < 0.05). Alkalinity (79.0 ± 1.6 – 164.0 ± 3.8 mg L^?1) also increased with the increase in fertilizer dose, declining after 60 and 75 days (48.8 ± 1.13 – 67.9 ± 2.1 mg L^?1). NO₃-N was maximum (1.66 ± 0.2 mg L^?1) in the ponds which received cow dung at 15 000 kg ha^?1 year^?1, and declined (0.94 ± 0.5 mg L^?1) at higher doses. Dissolved oxygen (DO) remained significantly high (4.7 mg L^?1) up to the third (15 000 kg ha^?1 year^?1) treatment. Highest plankton population (phytoplankton 17 350.0 ± 1 250.0 no L^?1), zooplankton (373.0 ± 22.0 no L^?1), species diversity (phytoplankton 3.0, zooplankton 2.3), fish biomass (4.45 kg) and specific growth rate (SGR) (2.36 % body weight (BW) d^?1) were also observed in ponds which were treated with fertilizer at 15 000 kg ha^?1 year^?1. However, at higher doses, a decline in these parameters (phytoplankton, 0.0 – 8 810.0 ± 690.0 no L^?1; zooplankton, 0.0 – 205.0 ± 25.0 no L^?1; fish biomass, 2.3 kg; SGR, 1.25 % body weight (BW) d^?1) was observed. Furthermore, with a decrease in the water temperature from 24 °C (on day 60) to 21 °C (on day 75), a decline in nutrient release, plankton population L^?1 and species diversity was observed. Sediment analysis indicated that with an increase in the fertilizer dosage, a significant and progressive increase in the accumulation of organic carbon (0.787 ± 0.006 – 0.935 ± 0.01), total nitrogen (0.877 ± 0.071 – 1.231 ± 0.03), NH₄-N (54.4 ± 0.57 – 68.95 ± 0.81), NO₃-N (78.5 ± 1.21 – 98.5 ± 0.35), total P (140.0 ± 0.50 – 151.0 ± 1.27) and soluble P (7.15 ± 0.18 – 10.1 ± 0.56) took place; similarly, electrical conductivity (EC) values of sediment also increased progressively (from 200.0 ± 7.1–300.0 ± 10.63 μ mhos cm^?1).     

Effects of photophase entrainment on mating of the codling moth

Only 25.6% and 15.4% of adult male laboratory-reared diet-fed codling moths, Laspeyresia pomonella (L.), of a Polish strain mated in a field cage when they were reared from egg to adult with regimens of 1800–2400 or 2200–0400 hr darkness, respectively. However, 38.5%, 29.5%, and 29.4% of similar males mated (apple-reared from egg through larva in a 2200–0400 hr dark regime) after shifting the dark regimen in the late 5th instar to 1800–0400, 2200–0400 hr, or continuous dark, respectively.

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Résumé Une souche polonaise de Laspeyresia pomonella est élevée en laboratoire sur aliment artificiel, et soumise, de l'uf à l'adulte, à deux types de régime 1800–2400 h ou 2200–0400 h d'obscurité. Les adultes mâles issus de ces élevages et testés pour l'aptitude à l'accouplement dans des cages en nature, ne s'accouplèrent respectivement que dans la proportion de 25,6% et 15,4%. Toutefois on observe 38,5%, 29,5% et 29,4% d'accouplement avec des mâles comparables provenant d'élevages nourris sur pommes, et selon un régime de 2200–0400 h d'obscurité remplacé au cours du 5ème et dernier stade larvaire par 1800–0400, 2200–0400 h ou par l'obscurité continue.

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Financial support for this investigation was provided by the USDA under PL-480 Project PL-ARS-15 and the International Atomic Energy Agency Contract 13072. Mention of a proprietary product in this paper does not constitute an endorsement of this product by the USDA.     

Ultramicroassay for plasma renin concentration in the rat using the antibody-trapping technique

Using the antibody-trapping technique, picogram quantities of angiotensin-I generated during 24 hr of incubation at 37°C were stable and fully protected against peptidases. The method employs purification of angiotensin-I antisera on DEAE-cellulose and purification of renin substrate by affinity chromatography using specific antirenin antibodies in order to remove endogenous renin. The assay was performed in a single tube without a transfer step in a total volume of 30 μl at pH 6,5 with incubation for 24 hr at 37°C. With a normal rat plasma renin concentration of 5 × 10^?4 GU ml^?1, the detection limit was 10 nl or a total of 5 × 10^?9 GU. In the range 20–125 nl, precision was ±10%.     

Temporal dynamics and growth of Actinophrys sol (Sarcodina: Heliozoa), the top predator in an extremely acidic lake

1. The in situ abundance, biomass and mean cell volume of Actinophrys sol (Sarcodina: Heliozoa), the top predator in an extremely acidic German mining lake (Lake 111; pH 2.65), were determined over three consecutive years (spring to autumn, 2001–03). 2. Actinophrys sol exhibited pronounced temporal and vertical patterns in abundance, biomass and mean cell volume. Increasing from very low spring densities, maxima in abundance and biomass were observed in late June/early July and September. The highest mean abundance recorded during the study was 7 × 10³ Heliozoa L^?1. Heliozoan abundance and biomass were higher in the epilimnion than in the hypolimnion. Actinophrys sol cells from this acidic lake were smaller than individuals of the same species found in other aquatic systems. 3. We determined the growth rate of A. sol using all potential prey items available in, and isolated and cultured from, Lake 111. Prey items included: single‐celled and filamentous bacteria of unknown taxonomic affinity, the mixotrophic flagellates Chlamydomonas acidophila and Ochromonas sp., the ciliate Oxytricha sp. and the rotifers Elosa worallii and Cephalodella hoodi. Actinophrys sol fed over a wide‐size spectrum from bacteria to metazoans. Positive growth was not supported by all naturally available prey. Actinophrys sol neither increased in cell number (k) nor biomass (k_b) when starved, with low concentrations of single‐celled bacteria or with the alga Ochromonas sp. Positive growth was achieved with single‐celled bacteria (k = 0.22 ± 0.02 d^?1; k_b = ?0.06 ± 0.02 d^?1) and filamentous bacteria (k = 0.52 ± <0.01 d^?1; k_b = 0.66 d^?1) at concentrations greater than observed in situ, and the alga C. acidophila (up to k = 0.43 ± 0.03 d^?1; k_b = 0.44 ± 0.04 d^?1), the ciliate Oxytricha sp. (k = 0.34 ± 0.01 d^?1) and in mixed cultures containing rotifers and C. acidophila (k = 0.23 ± 0.02–0.32 ± 0.02 d^?1; maximum k_b = 0.42 ± 0.05 d^?1). The individual‐ and biomass‐based growth of A. sol was highest when filamentous bacteria were provided. 4. Existing quantitative carbon flux models for the Lake 111 food web can be updated in light of our results. Actinophrys sol are omnivorous predators supported by a mixed diet of filamentous bacteria and C. acidophila in the epilimnion. Heliozoa are important components in the planktonic food webs of ‘extreme’ environments.     

Pharmacokinetics of propetamphos following intravenous administration in the F344 rat

Propetamphos [(E)-l-methylethyl 3[[(ethylamino)methoxyphosphinothioyl]oxy]-2-bu-tenoate], the active ingredient in Safrotin,® is an organophosphate developed by Sandoz, Ltd.® (Switzerland) as an insecticide (1). Although metabolism of propetamphos has been previously investigated (2,3), there is no pharmacokinetic data available in the literature. The current studies were undertaken to investigate the pharmacokinetics of propetamphos following intravenous administration in male and female Fischer 344 (F344) rats. Rats were dosed via an indwelling jugular cannula at a dose of 12 mg/kg (one-tenth the oral LD-50). Blood samples were withdrawn via the cannula at predetermined timepoints to quantitate plasma concentrations of propetamphos over time. Propetamphos is highly bound to plasma proteins (free fraction = 0.06). Free propetamphos concentration in plasma vs. time data were analyzed by noncompartmental methods. The terminal elimination rate constant, λ, was significantly different for males versus females (0.015 min^?1 for males and 0.037 min^?1 for females, p = 0.001). Plasma was cleared of unbound propetamphos at rates of 0.559 ± 0.069 and 0.828 ± 0.181 L/min/kg for males and females (mean ± standard error). Mean residence times (MRTs) for propetamphos in the body for males and females were 28.3 ± 5.7 and 14.4 ± 3.5 min, and the volume of distribution at steady state (Vss) was 14.7 ± 2.6 and 12.3 ± 4.5 L/kg. The differences in these parameters, clearance (CI), MRT, and Vss, were not statistically significant at the p < 0.05 level for males versus females, but MRT was nearly significantly different (p = 0.08). Because of the rapid elimination of propetamphos from plasma following intravenous administration, it is unlikely that propetamphos would bioaccumulate in environmentally exposed animals. Although the pharmacokinetic parameters were not statistically different for males and females in these studies, there was a clear clinical difference in their susceptibility to propetamphos toxicity. Female rats presented with overt signs of organophosphate intoxication, whereas males were only slightly effected. The observed gender-related clinical difference in susceptibility to toxicity suggests that there may be a difference in the extent of elimination due to activation versus detoxication of propetamphos in males and females. Another possible explanation for the clinical difference in propetamphos toxicity is that inhibition of acetyl-cholinesterase by the activated, oxygenated form of propetamphos (propetamphos oxon) may be greater in females than in males.     

Soil quality around a solid waste dumpsite in Port Harcourt, Nigeria

The levels of soil parameters and selected heavy metals around a solid waste dumpsite receiving untreated wastes from all sources and a control site within Port Harcourt, Nigeria have been examined. Top soil (0–15 cm) and sediment samples were collected and analysed for pH value, particle size, total nitrogen, potassium, available phosphorus, organic matter, effective cation exchange capacity, cadmium, nickel and lead using standard methods. The results showed that the waste dump contributed to the high levels of nutrients and heavy metals. The dry season mean concentrations were: organic matter (5.28 ± 1.34% or 132,422.4 kg ha^?1), K (1.60 ± 0.52 meq per 100 g), N (0.09 ± 0.06% or 2257.2 kg ha^?1), Av.P (15.11 ± 7.57 μg g^?1), Cd (1.34 ± 0.72 μg g^?1), Ni (4.10 ± 1.63 μg g^?1) and Pb (38.85 ± 22.18 μg g^?1) while the wet season mean concentrations were organic matter (5.46 ± 1.39% or 136,936.8 kg ha^?1), K (2.79 ± 0.81 meq per 100 g), N (0.10 ± 0.05% or 2508 kg ha^?1), Av.P (9.22 ± 2.69 μg g^?1), Cd (1.72 ± 1.22 μg g^?1), Ni (14.95 ± 14.94 μg g^?1) and Pb (53.50 ± 40.09 μg g^?1). There was efficient mineralization process in the area. The texture of soil on the main dumpsite was loamy sand, which suggests that the ground water in the area is susceptible to contamination by surface pollutants. The texture of soil at the control site is sandy loam while sediment has the textural class of sand. Decomposed organic materials and agricultural activities influenced the texture of soils. The soils from the main dump and sediment were slightly alkaline while the control soil was moderately acidic. In both seasons, a significant variation exists (P < 0.05) between the metal concentrations in soil at the main dump and those in the sediments with a positive correlation (r = 0.572149) in the wet season and (r = 0.956647) in the dry season. The presence of liming materials and activities of microorganisms on the waste dump increased the pH of the soils. The accumulation of nutrients results in the luxuriant growth of plants/crops on the waste dump.     

Circadian Variation in the Uptake of Tryptophan by Cortical Synaptosomes of the Rat Brain

The kinetics of the high affinity uptake system for L-tryptophan (L-Try)have been measured over 24 hr in cortical synaptosome preparations of rat brain. Both the K_m and V_max, of the uptake process showed a statistically significant 24 hr variation. The highest K_m value, 6.71 ± 10^-5 M, was measured at the beginning of the light phase and the lowest value, 4.23 ± 10^-5 M, 6 hr into the dark phase. V_max was highest at the end of the dark phase (10.43 nmol/mg/5 min) and lowest (4.80 nmol/mg/5 min) 3 hr into the dark phase. In contrast, there was no variation over 24 hr in the V_max/K_m ratio. These results suggest that the high affinity uptake process serves to ensure a constant rate of L-tryptophan entry into the neuron in the face of circadian or ultradian variations in extracellular concentration of tryptophan.     

Welfare status of cultured seabass (Dicentrarchus labrax L.) and seabream (Sparus aurata L.) assessed by blood parameters and tissue characteristics

Seabass (SBS) and seabream (SBM) juveniles were reared with the goal of obtaining three different final densities (SINT = 40 kg m^?3; INT = 20 kg m^?3; SEM = 0.2 kg m^?3) to ascertain the effects thereof on the welfare of the fish. Significant blood metabolites and hepatic glycogen were determined every 3 months and at harvest. Trials lasted 18 months in seabass and 17 months in seabream. At the end of experiment the main biometric productive parameters and quality of body composition were also recorded. Regarding intensively reared seabass (SINT‐SBS, INT‐SBS), the plasma triglycerids, total cholesterol and transaminases (AST, ALT) were always significantly higher than in semi‐intensively maintained fish (SEM‐SBS). At the final sampling in the SINT‐SBS batch, the total protein and glucose were also markedly increased. Conversely, at harvest the liver glycogen content decreased in SINT‐SBS (34 ± 8 mg g^?1 liver) with respect to INT‐SBS (57 ± 12 mg g^?1 liver) and SEM‐SBS (63 ± 11 mg g^?1 liver). No differences among groups were observed for creatine kinase (CK) and lactate dehydrogenase (LDH). With regard to seabream, SINT‐SBM and INT‐SBM constantly showed plasma triglycerids and total cholesterol as being significantly higher when compared to SEM‐SBM. In the final two blood samplings, SINT‐SBM exhibited the most elevated values for LDH. At harvest, AST, ALT, total protein and glucose markedly increased in SINT‐SBM, whereas liver glycogen content was reduced (22.5 ± 9 mg g^?1 liver), more than in INT‐SBM (70 ± 16 mg g^?1 liver) and SEM‐SBM (75 ± 20 mg g^?1 liver). In both seabass and seabream, body composition was very similar in the different stocking densities, except for total cholesterol. Total n‐3 polyunsaturated fatty acid (PUFA) in seabream was significantly different from fish of the semi‐intensive groups; however, nutritional values and fatty acid profiles were equally good. The intermediate final density of seabass and seabream at 20 kg m^?3 seemed to give the best results in terms of their well being when compared to fish reared at 40 kg m^?3. The absence of differences in blood metabolites and hepatic glycogen levels between the intensive batch and the semi‐intensive groups until harvest was a reference to the positive status of the fish. A density of 20 kg m^?3 can be considered acceptable for farm strategy planning for raising healthy on‐growing seabass and seabream juveniles.     

Production of salidroside and polysaccharides in Rhodiola sachalinensis using airlift bioreactor systems

Rhodiola sachalinensis is widely used in traditional Chinese medicine, and salidroside and polysaccharides are its important bioactive compounds. This study used airlift bioreactor systems to produce mass bioactive compounds through callus culture. Several factors affecting callus biomass and bioactive compound accumulation were investigated. Callus growth was vigorous in a bioreactor system, and the growth ratio was 2.8-fold higher in bioreactor culture than in agitated-flask culture. Callus biomass and polysaccharide content were favorable at 0.1 air volume per culture volume per min (vvm), whereas favorable salidroside content was observed at a high air volume (0.2 vvm). The maximum yields of salidroside (7.90 mg l^?1) and polysaccharide (2.87 g l^?1) were obtained at 0.1 vvm. Inoculum density greatly affected callus biomass and bioactive compound accumulation, and the highest biomass and contents or yields of salidroside and polysaccharide were determined at a high inoculum density of 12.5 g l^?1. The level of hydrogen ion concentration (pH) at 5.8 improved callus biomass accumulation. Acidic medium (pH 4.8) stimulated salidroside synthesis but higher pH level (7.8) promoted polysaccharide accumulation. The highest yields of both bioactive compounds were obtained at pH 5.8. Methyl jasmonate (MeJA) participated in synthesis promotion of bioactive compounds, and the contents and yields of salidroside [4.75 mg g^?1 dry weight (DW), 58.43 mg l^?1] and polysaccharides (392.41 mg g^?1 DW, 4.79 g l^?1) were at maximum at 125 and 150 μmol of MeJA. Therefore, bioreactor systems can be used to produce R. sachalinensis bioactive compounds, and callus culture in a bioreactor can be as an alternative method for supplying materials for commercial drug production.     

Seasonal variation in steroid hormones and blood parameters in cage-farmed European sea bass (Dicentrarchus labrax L.)

For a period of 1 year, some blood parameters were evaluated on a monthly basis in a population of adult European sea bass (Dicentrarchus labrax L.) intensively reared in floating marine cages (Ionian Sea, Mediterranean). From April (13 months old) to July (16 months old) males (35–50%) and sexually indeterminate individuals were collected. From August to March (24 months old) only males were sampled. During this period the percentage of spermiated males was highest (100%) from November (20 months old) to January (22 months old). Plasma testosterone in males was inversely related to sunlight (h month^?1) and was elevated between October and January, when males first achieved sexual maturity. Testosterone showed the highest value (0.49 ± 0.02 ng ml^?1) in January and the lowest (0.09 ± 0.02 ng ml^?1) in March. Haematocrit, red blood cell counts and haemoglobin concentration were elevated from November to March, being inversely related to sunlight. The two latter parameters were also inversely related to daily food intake. Haematocrit, red blood cell counts and haemoglobin concentration were highest in December [53 ± 1%, (5.36 ± 0.06) × 10⁶ mm^?3, 10.08 ± 0.14 g 100 ml^?1, respectively] and lowest in June [35 ± 1%, (3.33 ± 0.05) × 10⁶ mm^?3, 6.47 ± 0.13 g 100 ml^?1, respectively]. White blood cell counts were not correlated with sea water temperature, sunlight or daily food intake. They were highest in February [(8.45 ± 0.20) × 10⁴ mm^?3] and lowest in April [(6.07 ± 0.14) × 10⁴ mm^?3]. Total plasma protein concentration (4.88 ± 0.11–5.93 ± 0.10 g 100 ml^?1) and mean cell volume (93.3 ± 0.9–105.5 ± 1.8 μm³) showed small fluctuations throughout the year. Sexual maturity appears to be a major factor that significantly affects haemopoiesis of D. labrax. This study contributes to the evaluation of normal levels of some blood parameters in European sea bass, which are helpful for the assessment of physiological status and health of this species.     

Seasonal changes in the concentration of estrogens and testosterone in the plasma of the stallion

A blood sample was taken from each of 15 stallions at monthly intervals for 14 consecutive months. Plasma concentrations of estrogens and testosterone were measured by radioimmunoassay methods. Estrogens in peripheral blood were present in much higher amounts than testosterone and were principally in a water-soluble, solvolyzable form (> 98%). The major component in the solvolyzed extracts behaved chromatographically as estrone. The mean plasma level (± S.E.) of estrogens averaged across months was 52.9 ± 4.5 ng ml^?1. Individual stallions showed considerable month-to-month variation; for example, single monthly samples ranged from 29.5 to 160.6 ng ml^?1 for the stallion with the highest single value.The highest mean monthly concentration was 69 ± ng ml^?1 in May, and plasma levels were < 40 ng ml^?1 during November and December. For the 11 Thoroughbred stallions in the study, the mean concentrations of estrogens were 73 ± 5.8 ng ml^?1 for May to July and 45 ± 4.1 ng ml^?1 for November to January (P > 0.001).The mean monthly concentrations (± S.E.) of testosterone ranged from 0.22 ± 0.05 to 0.90 ± 0.14 ng ml^?1, and individual samples ranged from < 0.02 to 2.8 ng ml^?1 of plasma. While the highest mean level of testosterone was seen in September, there was a significant difference (P < 0.01) between the values in the breeding season (May–July, 0.73 ± 0.07 ng ml^?1) and the non-breeding season (November–January, 0.38 ± 0.08 ng ml^?1). No marked seasonal changes were observed, however, in testosterone levels in several stallions. It was concluded that plasma estrogen levels may provide a more sensitive index of endocrine function of the testes in the stallion.     

Blood clearance and occupational exposure for <Superscript>177</Superscript>Lu-DOTATATE compared to <Superscript>177</Superscript>Lu-PSMA radionuclide therapy

The main target of this work is to examine blood clearance and external exposure for ¹⁷⁷Lu-DOTATATE compared with new emerging ¹⁷⁷Lu-PSMA therapy. Blood clearance and radiation exposure of 31 patients treated with 5.5?±?1.1 GBq ¹⁷⁷Lu-DOTATATE were compared to those of 23 patients treated with 7.4 GBq ¹⁷⁷Lu-PSMA. Dose rates were measured at several distances and time points up to 120 h after treatment. Blood samples were collected conjunctively after infusion. Caregiver’s cumulative dose was measured by means of an OSL (optically stimulated luminescence) dosimeter for 4–5 days and medical staff’s dose was also estimated using electronic personal dosimeters. Finger dose was determined via ring TLD (Thermoluminescence Dosimeter) for radiopharmacists and nurses. Dose rates due to ¹⁷⁷Lu-DOTATATE at a distance of 1 m, 4 h and 6 h after infusion, were 3.0?±?2.8 and 2?±?1.9 µSv/(h GBq), respectively, while those due to ¹⁷⁷Lu-PSMA were 3.1?±?0.8 and 2.2?±?0.9 µSv/(h GBq). Total effective dose of 17 caregivers was 100–200 µSv for ¹⁷⁷Lu-DOTATATE therapy. Mean effective doses to nurses and radiopharmacists were 5 and 4 µSv per patient, respectively, while those for physicists and physicians were 2 µSv per patient. For ¹⁷⁷Lu-DOTATATE, effective half-life in blood and early elimination phase were 0.31?±?0.13 and 4.5?±?1 h, while they were found as 0.4?±?0.1 and 5?±?1 h, respectively, for ¹⁷⁷Lu-PSMA. The first micturition time following ¹⁷⁷Lu-DOTATATE infusion was noted after 36?±?14 min, while the second and third voiding times were after 74?±?9 and 128?±?41 min, respectively. It is concluded that blood clearance and radiation exposure for ¹⁷⁷Lu-DOTATATE are very similar to those for ¹⁷⁷Lu-PSMA, and both treatment modalities are reasonably reliable for outpatient treatment, since the mean dose rate [2.1 µSv/(h GBq)] decreased below the dose rate that allows release of the patient from the hospital (20 µSv/h) after 6 h at 1 m distance.