Estimation of CYP2C19 activity by the omeprazole hydroxylation index at a single point in time after intravenous and oral administration

Objective The purpose of this study was to identify the common time point to achieve hydroxylation index (HI: omeprazole plasma concentration/5-hydroxyomeprazole plasma concentration) reflecting AUC_OPZ/AUC_5OH-OPZ after intravenous (IV) and oral (PO) administration. Methods Twenty young and 28 elderly healthy subjects, including different CYP2C19 genotypes, were enrolled in the study. The young subjects received either 40 mg PO or 20 mg IV omeprazole, whereas the elderly subjects received 10 mg IV. The relation between AUC_OPZ/AUC_5OH-OPZ and HI was determined by Spearman’s rank correlation. Multiple stepwise linear regression analysis was performed to identify the common time point to calculate HI that reflects AUC_OPZ/AUC_5OH-OPZ after IV. Results In the correlation between HI and AUC_OPZ/AUC_5OH-OPZ IV at observed time points, HI_3h showed the highest correlation coefficients (r = 0.894, p < 0.001) in all 48 subjects. The correlation of HI between IV and PO at observed time points showed that HI_3h was highest (r = 0.916, p < 0.001) in 20 young subjects. Additionally, there was no significant difference between HI_3h of IV and that of PO (12.9 ± 15.9 and 12.9 ± 15.1, p = 0.997). The regression equation of HI_3h was the best to estimate AUC_OPZ/AUC_5OH-OPZ (AUC_OPZ/AUC_5OH-OPZ = 1.37 • HI_3h + 0.18 • Age – 7.83, r ² = 0.883, p < 0.001). Conclusions This study demonstrated that HI_3h after omeprazole IV was able to estimate AUC_OPZ/AUC_5OH-OPZ, as well as HI_3h after PO. Additionally, CYP2C19 activity can be estimated more definitely by using HI after omeprazole IV without intestinal absorption.     

Concentrations of toxic heavy metals in ambient particulate matter in an industrial area of northeastern China

This paper investigates concentrations of various heavy metals in ambient particulate matter (PM) and provide evidence for prevention from air pollution. The concentrations of heavy metal components in the PM were determined by inductively coupled plasma/Mass spectrometry (ICP/MS) from September 2000 to August 2002 in a northeast industrial city in China. Concentrations of Cd, Mn, Pb, Ni, Cr and As in the PM were 9.3, 461.9, 588.7, 69.5, 205.7 and 57.4 ng/m³ in the industrial area, and 5.7, 245.5, 305.0, 31.4, 58.8 and 32.5 ng/m³ in the main road, respectively. Concentrations of these heavy metals except Cd were significantly higher in the industrial area and main road than those in the suburban area (P < 0.05 or P < 0.01). The change curves of the six heavy metal concentrations show their concentrations increased in the winter and spring, but decreased in the summer and autumn. The results indicate that concentrations of the metals in the PM are relatively high in the industrial area and main road. __________ Translated from Journal of Dalian Medical University, 2007, 29(4): 332–335 [译自: 大连医科大学学报]     

Non-carcinogenic risk assessment induced by heavy metals content of the bottled water in Iran

Recently, the exposure to heavy metals from bottled waters raised huge concerns. In this context, for the first time the risk of non-carcinogenic exposure by the heavy metals in Iranian drinking water was assessed. Therefore, by using the obtained data in our previous published study, the target hazard quotient (THQ) and total target hazard quotient (TTHQ) by considering to the sexuality of consumers were calculated. THQ in females were determined as significantly higher (p??Pb?>?Hg?>?Cd?>?Cu, respectively. The minimum and maximum of THQ for the males were observed in age groups of?+65 and 1–3?years, respectively. The minimum and maximum of THQ for females were noted in age groups of 11–14 and 1–3?years, respectively. Since TTHQ for all ages were less than 1 (p?相似文献   

Growth response of the duckweed <Emphasis Type="Italic">Lemna gibba</Emphasis> L. to copper and nickel phytoaccumulation

To assess the tolerance and phytoaccumulation ability of the duckweed Lemna gibba L. to copper (Cu) and nickel (Ni), the plants were exposed to different concentrations of Cu and Ni (0.1–2.0 mg/l) under laboratory conditions. The results showed that Cu and Ni were tolerated by L. gibba at concentrations ≤0.3 and ≤0.5 mg/l, respectively. However, plant growth decreased by 50% (I₅₀) when the medium contained 0.45 mg Cu/l or 0.75 mg Ni/l. The observed LCI (lowest concentration causing complete inhibition) were 0.5 and 1.0 mg/l respectively in the presence of Cu and Ni. Results from metal analysis in plant biomass revealed a high accumulation of Cu (1.5 mg g⁻¹ DW), a low accumulation of Ni (0.5 mg g⁻¹ DW) within the plants and a corresponding decrease of metals in the water. The removal percentage of Cu was about 60–80%. We conclude that the duckweed L. gibba L. showed a higher accumulation potential for Cu from polluted water than Ni after 4 days of exposure.     

Corticosterone in relation to tissue cadmium, mercury and selenium concentrations and social status of male lesser scaup (Aythya affinis)

Combined lesser scaup (Aythya affinis) and greater scaup (A. marila) populations have declined steadily from the 1970s. Accompanying the population decline have been two shifts in lesser scaup demographics: a decrease in the proportion of young birds and an increase in male to female ratio. In addition, there are concerns about potential effects of contaminants and trace elements. These metals may influence the stress response and corticosterone secretion. We examined impacts of cadmium, selenium and mercury on the stress response in relation to social status in male lesser scaup near Yellowknife, NWT May to June 2004 and 2005. Kidney cadmium and liver selenium and mercury ranged 0.78–93.6, 2.12–9.64, and 0.56–3.71 μg/g, dry weight, respectively. Results suggest that corticosterone release may be influenced by complex contaminant interactions in relation to body condition and body size. When cadmium was high and birds were in good body condition, there was a negative relationship between liver selenium and corticosterone (R ² = 0.60, n = 10, P = 0.008) but not in birds with poor body condition (R ² = 0.07, n = 9, P = 0.50). Unfortunately we were unable to draw any conclusions about metals and social status in relation to corticosterone or glucose and T₄. This study emphasizes the complex nature of biological systems and the importance of considering interactions to characterize effects of metals.     

Acetylcholinesterase activities in marine snail (Cronia contracta) as a biomarker of neurotoxic contaminants along the Goa coast, West coast of India

The measurement of acetylcholinesterase (AChE) activity is used worldwide as a biomarker of environmental contamination due to neurotoxic substances. In the present study the AChE activities was measured in marine snails (Cronia contracta) collected seasonally from six sampling sites (viz. Arambol, Anjuna, Dona Paula, Vasco, Velsao and Palolem) along the Goa coast during the pre-monsoon (April, 2004), monsoon (September, 2004) and post-monsoon (November, 2004) periods. The AChE activities in C. contracta showed wide variation along the Goa coast. It was found to be quite high at the reference site, Palolem (23.97, 21.72 and 24.85) throughout the sampling period (April–November, 2004). The AChE activities in C. contracta decreased significantly at Vasco (44.6–52.4% reduction) followed by Dona Paula (24.9–36.2% reduction), Velasao (10.8–35.9% reduction), Arambol (12.6–37.3% reduction) and Anjuna (0–12.7% reduction). Such a significant variation of AChE activities in the marine snail along the Goa coast can be attributed to neurotoxic substances prevalent in those regions. The high concentration of different neurotoxic metals (lead, cadmium, copper, manganese and iron) and petroleum hydrocarbons in the tissues of the marine snails at Dona Paula, Vasco and Velsao clearly substantiate reduction of AChE activities in C. contracta. The in vitro studies on the inhibition of AChE by different metals and PHC indicated that lead, cadmium and copper are the most predominant inhibitor. Based on the AChE activities in C. contracta the sampling sites along the Goa coast can be classified into three major clusters such as highly contaminated sites (Dona Paula, Vasco and Velsao), moderately contaminated sites (Arambol, Anjuna) and least contaminated site (Palolem).Special Issue on Biomarkers of Marine Pollution and Bioremediation     

Pharmacological evaluation of a modified conflict procedure: punished drinking in non-water-deprived rats

Rationale: Conflict procedures used to detect anxiolytic-like activity of drugs often rely on maintaining strict schedules of water or food availability. It is ethically and practically desirable to reduce such states of deprivation in animal testing. Objective: The purpose of the present experiment was to develop and pharmacologically characterize a conflict drinking procedure that did not require the use of water-deprived animals. Methods: Rats were tested during daily sessions with alternating unpunished drinking (no tone: lick=sucrose solution) and signaled punished drinking (tone: lick=sucrose+shock) components, and developed individual steady baselines over a brief training period (approximately 3–4 weeks). The drugs tested i.p. were the positive allosteric modulators of γ-amino butyric acid_A (GABA)_A receptors, diazepam (0.03–30 mg/kg), chlordiazepoxide (0.03–30 mg/kg), lorazepam (0.03–10 mg/kg), zolpidem (0.3–10 mg/kg), pentobarbital (1–30 mg/kg), pregnanolone (1–30 mg/kg), and bretazenil (0.03– 10 mg/kg); the 5-hydroxy tryptamine_1A (HT)_1A-mediated anxiolytics, buspirone (1–10 mg/kg) and ipsapirone (1–17 mg/kg); and the negative controls d-amphetamine (0.3–3 mg/kg), haloperidol (0.01–0.3 mg/kg), morphine (0.3–17 mg/kg), and imipramine (0.3–30 mg/kg). Results: The experimental procedure was sensitive to increases in punished drinking by the GABA_A-positive modulators, consistent with their known or putative anxiolytic activity. Further, the 5-HT_1A-mediated anxiolytics increased punished drinking, although to a lesser extent and over a more narrow dose range than did the GABAergic drugs. In contrast, d-amphetamine, haloperidol, morphine, and imipramine failed to increase punished drinking up to doses that decreased unpunished drinking. Conclusions: The present results indicate that water deprivation is not a necessary condition to engender drinking conflict behavior or to obtain pharmacological effects similar to those obtained with other classical conflict procedures. Received: 23 November 1998 / Final version: 15 March 1999     

Effect of heavy metal exposure on blood haemoglobin concentration and methemoglobin percentage in Lumbricus terrestris

The earthworm haemoglobin (Hb) is a large extracellular hemoprotein flowing in a closed circulatory system. In spite of the fundamental role of this respiratory pigment in earthworm physiology, little is known about its sensitivity to environmental pollutants. The aim of the present work was to investigate the possible effect of heavy metal (cadmium, copper, mercury) exposure on Hb concentration and oxidation state (methemoglobin formation) in the earthworm Lumbricus terrestris. In addition, the tissue concentration of metallothioneins, a well-known biomarker of heavy metal exposure, was determined as an indicator of metal uptake. The animals were exposed to increasing concentrations of Cd, Cu and Hg utilizing the standard acute toxicity test, “Filter paper test” for 48 h. Exposure to heavy metals (10⁻⁵–10⁻³ M for Cd, 10⁻⁴–10⁻³ M for Hg, and 10⁻⁴–10⁻² M for Cu) was found to increase haemoglobin concentration in L. terrestris, although the magnitude of such an increase was dependent on the metal. In addition, metal exposure led to the formation of methemoglobin. Compared to other known biological responses to heavy metals, such as metallothionein induction, methemoglobin increase showed a higher sensitivity and a higher percentage variation in exposed organisms, showing to be a possible suitable biomarker of exposure/effect to be included in a multi biomarker strategy in earthworm in soil monitoring assessment.     

Grapefruit juice can increase the plasma concentrations of oral methylprednisolone

Objective: To investigate whether the pharmacokinetics of orally administered methylprednisolone and plasma cortisol concentrations are affected by administration of grapefruit juice. Methods: In a randomised, two-phase, cross-over study, ten healthy subjects received either 200 ml double-strength grapefruit juice or water three times a day for 2 days. On day 3, 16 mg methylprednisolone was given orally with 200 ml grapefruit juice or water. Additionally, 200 ml grapefruit juice or water was ingested 0.5 h and 1.5 h after methylprednisolone administration. Plasma concentrations of methylprednisolone and cortisol were determined using liquid chromatography/mass spectrometry (LC/MS/MS) over a 47-h period. Results: Grapefruit juice increased the total area under the plasma methylprednisolone concentration–time curve (AUC_0–∞) by 75% (P < 0.001) and the elimination half-life (t _1/2) of methylprednisolone by 35% (P < 0.001). The peak plasma concentration of methylprednisolone (C_max) was increased by 27% (P < 0.01). Grapefruit juice delayed the time to the C_max from 2.0 h to 3.0 h (P < 0.05). There was no significant difference in the plasma cortisol concentrations, measured after methylprednisolone administration, between the water and grapefruit juice phases. However, grapefruit juice slightly decreased the morning plasma cortisol concentrations before methylprednisolone administration (P < 0.05). Conclusions: Grapefruit juice given in high amounts moderately increases the AUC_0–∞ and t _1/2 of oral methylprednisolone. The increase in t _1/2 suggests that grapefruit juice can affect the systemic methylprednisolone metabolism. The clinical significance of the grapefruit juice–methylprednisolone interaction is small, but in some sensitive subjects high doses of grapefruit juice might enhance the effects of oral methylprednisolone. Received: 17 February 2000 / Accepted in revised form: 9 May 2000     

Heavy metal (Pb,Cu, Zn,and Cd) concentrations in the water and muscle of common carp (Cyprinus carpio) fish and associated non-carcinogenic risk assessment: Alagol wetland in the Golestan,Iran

Short- and long-term exposure to heavy metals can be dangerous for human health. One of the main routes of exposure to heavy metals is intake of seafood such as fish. In this study, lead (Pb), copper (Cu), zinc (Zn), and cadmium (Cd) concentration in the water and muscle of C. Carpio fish was measured and non-carcinogenic risk of these heavy metals was estimated. The mean (range) concentrations of Cu, Zn, Pb, and Cd were 7.92?±?7.99 (1.22–39.43?mg/kg), 120.90?±?106.25 (1.15–477?mg/kg), 5.84?±?5.22 (ND-21.86?mg/kg), and 0.027?±?0.043 (ND-0.14). Except Cd, the concentrations of Cu, Zn, and Pb were significantly more than Food and Agricultural Organization United Nations (FAOUN) maximum guidelines (p??Cu?>?Pb?>?Cd in the water and muscle tissue of C. carpio fish. Lowest and highest target hazard quotient (THQ) for adults was related to Cd (0.005) and Pb (0.252) and for children, Cd (0.003) and Pb (0.168), respectively. The rank order of THQ for adults and children are Pb?>?Zn?>?Cu?>?Cd. Since THQ and hazard index (HI) for both adults and children were significantly lower than 1 (p?C. Carpio fish consumption.     

Valve movement response of the mussel Mytilus galloprovincialis to metals (Cu, Hg, Cd and Zn) and phosphate industry effluents from Moroccan Atlantic coast

Valve activity was measured in the Mediterranean mussel Mytilus galloprovincialis in response to sublethal concentrations of four metals (Hg, Cu, Zn and Cd) and two phosphate industry effluents from the Atlantic coast of Morocco. Valve movements were monitored using a proximity inductive sensor which could display all activity figures from full closure to wide opening of the shell valves. In a 1 h exposure experiments, all metals induced a decrease in the time of normal opening and the appearance of sequences of stress behaviour, including enhanced valve adductions and complete closure at high concentrations. Mercury (tested from 5 to 75 μg Hg l⁻¹) was the most toxic to the valve activity, with a threshold effective concentration at 10 μg Hg l⁻¹ and full valve closure occurring at 50 μg Hg l⁻¹. Copper (15–150 μg Cu l⁻¹) showed a toxic effect starting at threshold concentration of 20 μg Cu l⁻¹ and induced full valve closure at 150 μg Cu l⁻¹. Zinc (100–500 μg Zn l⁻¹) was effective in reducing the time of normal opening (threshold concentration at 100 μg Zn l⁻¹) but no complete closure was recorded in any of the tested concentrations. For cadmium (1000–5000 μg Cd l⁻¹), the valve activity was insensitive for exposures under 2000 μg Cd l⁻¹. Results for the testing of several samplings of the phosphate industry effluents (Safi and Jorf Lasfar) showed that their toxicity varied over the time. The effluent of the Jorf Lasfar plant (2–9.4%) was, however, more toxic than that of Safi (1–25%). In the light of these results, the sensitivity of the valve activity of Mytilus galloprovincialis to pollutants and its usefulness for in situ monitoring of coastal pollution in Morocco are discussed.     

Detection of the organophosphorus nerve agent sarin by a competitive inhibition enzyme immunoassay

 Two artificial antigens, N ^α N ^ɛ-di(O, O-diisopropyl) phosphoryl L-lysine (DIP)- bovine serum albumin (BSA) conjugate (DIP-BSA) and DIP-KLH (keyhole limpet hemocyanin), were synthesized. Antibodies against sarin (O-isopropyl methylphosphonofluoridate) were obtained after immunization of rabbits with DIP-KLH conjugate. A competitive inhibition enzyme immunoassay (CIEIA) was developed to detect the organophosphorus nerve agent sarin. The antibody solutions could be inhibited by sarin as low as 10^-6 mol/l, and the standard curve was linear over 3 orders of magnitude. The coefficients of intraassay and interassay variation of this method were 5.4–6.2% (n=11) and 8.0–9.5% (n=6) at a sarin concentration range of 10^-3–10^-6 mol/l, respectively. The recovery of sarin in water samples at the concentration of 5×10^-5 mol/l was in the range of 96.8–102.5%. The specificity of the antiserum was assessed by comparing the inhibition induced by sarin with soman, Vx, isopropyl alcohol and isopropyl methyl phosphonic acid. The results showed that less than 5 mmol/l soman, 2 mmol/l Vx, 16 mmol/l isopropyl alcohol and 8 mmol/l isopropyl methyl phosphonic acid did not influence the determination of sarin in water samples. Received: 28 September 1994/Accepted: 2 February 1995     

Efficacy of activated charcoal versus gastric lavage half an hour after ingestion of moclobemide, temazepam, and verapamil

Objective: To compare the efficacy of activated charcoal and gastric lavage in preventing the absorption of moclobemide, temazepam, and verapamil 30 min after drug ingestion. Methods: In this randomized cross-over study with three phases, nine healthy volunteers received a single oral dose of 150 mg moclobemide, 10 mg temazepam, and 80 mg verapamil after an overnight fast. Thirty minutes later, they were assigned to one of the following treatments: 25 g activated charcoal as a suspension in 200 ml water, gastric lavage (10 × 200 ml), or 200 ml water (control). Plasma concentrations of moclobemide, temazepam, and verapamil were determined up to 24 h. Results: Activated charcoal reduced the area under the plasma concentration–time curve from 0 h to 24 h (AUC_0–24 h) of moclobemide and temazepam by 55% (P < 0.05) and by 45% (P < 0.05), respectively. The AUC_0–24 h of verapamil was not significantly reduced by charcoal. Gastric lavage decreased the AUC_0–24 h of moclobemide by 44% (P < 0.05), but had no significant effect on that of temazepam or verapamil. The peak plasma concentration (C_max) of moclobemide, temazepam, and verapamil was reduced by 40%, 29% (P < 0.05), and 16%, respectively, by activated charcoal. Gastric lavage did not significantly decrease the C_max of any of these drugs. Conclusion: The absorption of moclobemide, temazepam, and verapamil can be moderately reduced by activated charcoal given 30 min after drug ingestion, while gastric lavage seems to be less effective. Received: 15 December 1999 / Accepted in revised form: 16 March 2000     

Study of heavy metal levels in indoor dust and their health risk assessment in children of Ahvaz city,Iran

The concentration of heavy metals in household dust and their health risks on children living in different areas of Ahvaz city was investigated during November 2013 to October 2014 in Iran. Totally, 108 dust samples were taken from their houses in three different areas including S₁ (industrial), S₂ (heavy traffic) and S₃ (residential zone far away from industrial and traffic emission sources). The samples were analyzed for eight selected heavy metals (Cr, Ni, Cu, Mn, Pb, Zn, Co and Cd) using an inductively coupled plasma optical emission spectroscopy (ICP-OES, Spectro Arcos Model, Germany). Exposure and risk assessment of these metals were estimated using USEPA’s exposure parameters. Results showed that the mean values of all heavy metals in tempered months were significantly higher than the other months (p?<?0.05). Cancer risk and non-carcinogenic risk (hazard index) of Ni, Cr, Cd and Pb from indoor dust exposure were estimated for children via three exposure pathways (ingestion, inhalation and dermal contact). The non-cancer risks to children in all samples were lower than acceptable level of 1, while the potential cancer risks from Ni intake in S₁ and S₂ were 1.57E???06 and 1.19E???06, respectively, and for Cr in S₁ and S₂, it was 1.43E???06 and 1.15E???06, respectively, which these values were slightly higher than the acceptable level (1?×?10^?6). In conclusion, household dust of Ahvaz city would probably have a significant potential to cause cancer in most exposed children.     

Pharmacokinetics of intravenous N-acetylcysteine in pre-term new-born infants

Background: Reactive oxygen species have been considered to play a role in several clinical complications in pre-term infants. The aim of this study was to determine the pharmacokinetics of intravenous N-acetylcysteine in pre-term neonates. This information is needed to evaluate the use of N-acetylcysteine as an antioxidant in this patient group. Methods: N-acetylcysteine was infused intravenously in ten patients (gestational age 24.9–31.0 weeks, weight 500–1384 g) for 24 h (3.4–4.6 mg/kg/h), starting 2.0–11.2 h from birth (study I) and in six patients (gestational age 25.9–29.7 weeks, weight 520–1335 g) for 6 days (0.3–1.3 mg/kg/h), starting at the age of 24 h (study II). Arterial plasma N-acetylcysteine and cyst(e)ine concentrations were determined from timed samples taken during (study I and II) and after (study I) the N-acetylcysteine infusion. Results: In study I, the mean elimination half-life of N-acetylcysteine was 11 h (range 7.8–15.2 h). The mean plasma clearance of N-acetylcysteine was 37 ml/kg/h (range 13–62 ml/kg/h) and the mean volume of distribution was 573 ml/kg (range 167–1010 ml/kg). The plasma clearance and volume of distribution correlated with weight (r = 0.81, P < 0.01, and r = 0.78, P < 0.01, respectively) and with gestational age (r = 0.71, P < 0.05, and r = 0.64, P < 0.05, respectively). In study II, the steady-state concentration of N-acetylcysteine was reached in 2–3 days in five of six patients during a constant infusion. Conclusions: The pharmacokinetics of N-acetylcysteine in pre-term infants depend markedly on weight and gestational age. The elimination of N-acetylcysteine is much slower in pre-term new-borns than in adults. Received: 12 April 1999 / Accepted in revised form: 18 August 1999     

Evaluation of the use of salivary lead levels as a surrogate of blood lead or plasma lead levels in lead exposed subjects

We conducted a study to evaluate the use of parotid salivary lead (Pb-saliva) levels as a surrogate of the blood lead (Pb-B) or plasma lead levels (Pb-P) to diagnose lead exposure. The relationship between these biomarkers was assessed in a lead exposed population. Pb-saliva and Pb-P were determined by inductively coupled plasma mass spectrometry, while in whole blood lead was determined by graphite furnace atomic absorption spectrometry. We studied 88 adults (31 men and 57 women) from 18 to 60 years old. Pb-saliva levels varied from 0.05 to 4.4 μg/l, with a mean of 0.85 μg/l. Blood lead levels varied from 32.0 to 428.0 μg/l in men (mean 112.3 μg/l) and from 25.0 to 263.0 μg/l (mean 63.5 μg/l) in women. Corresponding Pb-Ps were 0.02–2.50 μg/l (mean 0.77 μg/l) and 0.03–1.6 μg/l (mean 0.42 μg/l) in men and women, respectively. A weak correlation was found between Log Pb-saliva and Log Pb-B (r=0.277, P<0.008), and between Log Pb-saliva and Log Pb-P (r=0.280, P=0.006). The Pb-saliva/Pb-P ratio ranged from 0.20 to 18.0. Age or gender does not affect Pb-saliva levels or Pb-saliva/Pb-P ratio. Taken together, these results suggest that salivary lead may not be used as a biomarker to diagnose lead exposure nor as a surrogate of plasma lead levels at least for low to moderately lead exposed population.     

The mysid <Emphasis Type="Italic">Siriella armata</Emphasis> as a model organism in marine ecotoxicology: comparative acute toxicity sensitivity with <Emphasis Type="Italic">Daphnia magna</Emphasis>

Siriella armata (Crustacea, Mysidacea) is a component of the coastal zooplankton that lives in swarms in the shallow waters of the European neritic zone, from the North Sea to the Mediterranean. Juveniles of this species were examined as standard test organisms for use in marine acute toxicity tests. The effects of reference toxicants, three trace metals (Copper, Cadmium and Zinc), and one surfactant, sodium dodecyl sulfate (SDS) were studied on S. armata neonates (<24 h) reared in the laboratory. Acute toxicity tests were carried out with filtered sea water on individual chambers (microplate wells for metals or glass vials for SDS) incubated in an isothermal room at 20°C, with 16 h light: 8 h dark photoperiod for 96 h. Each neonate was fed daily with 10–15 nauplii of Artemia salina. Acute (96 h) LC₅₀ values, in increasing order, were 46.9 μg/L for Cu, 99.3 μg/L for Cd, 466.7 μg/L for Zn and 8.5 mg/L for SDS. The LC₁₀, NOEC and LOEC values were also calculated. Results were compared with Daphnia magna, a freshwater cladoceran widely used as a standard ecotoxicological test organism. Acute (48 h) LC₅₀ values were 56.2 μg/L for Cu, 571.5 μg/L for Cd, 1.3 mg/L for Zn and 27.3 mg/L for SDS. For all the reference toxicants studied, the marine mysid Siriella armata showed higher sensitivity than the freshwater model organism Daphnia magna, validating the use of Siriella mysids as model organisms in marine acute toxicity tests.     

Characterization of bacterial communities exposed to Cr(III) and Pb(II) in submerged fixed-bed biofilms for groundwater treatment

Two pilot-scale submerged-bed microbial biofilms were set up for the removal of Cr(III) and Pb(II) from groundwater, and the biological activities and structure of the bacterial communities developed in the presence of the heavy metals were analyzed. Artesian groundwater was polluted with Cr(III) or Pb(II) (15 mg/l) and amended with sucrose (250 mg/l) as carbon source. While Pb(II) was over 99% removed from groundwater during long-term operation (130 days), the efficiency of the removal of Cr(III) significantly decreased in time (95–73% after 60 days). Cr(III)-amended biofilms displayed significant lower sucrose consumption, ATP cell contents and alkaline phosphatase activity, compared to biofilms formed in the presence of Pb(II), while analysis of exopolymers demonstrated significant differences in their composition (content of carbohydrates and acetyl groups) in response to each heavy metal. According to transmission electron microscopy (TEM) and electron-dispersive X-ray analysis (EDX), Cr(III) bioaccumulated in the exopolymeric matrix without entering bacterial cells, while Pb(II) was detected both extra and intracellularly, associated to P and Si. Temperature-gradient gel electrophoresis (TGGE) profiling based on partial amplification of 16S rRNA genes was used to analyze the differences in the structure of the biofilm bacterial communities developed under exposure to each heavy metal. Prevalent populations in the biofilms were further identified by reamplification and sequencing of isolated TGGE bands. 75% of the sequences in the Pb(II) biofilter were evolutively close to the Rhodobacterales, while in the Cr(III) biofilter 43% of the sequences were found affiliated to the Rhizobiales and Sphingomonadales, and 57% to Betaproteobacteria.     

Modulation of the hyperpolarization-activated inward current (If) by antiarrhythmic agents in isolated human atrial myocytes

The hyperpolarization-activated inward current (I _f) has been discussed to contribute to arrhythmias in human atrial myocardium. I _f was found to be increased by β-adrenergic stimulation. In the present study, we evaluate the modulation of I _f by carbachol, adenosine and by class Ic, III and IV antiarrhythmic drugs in isolated human atrial myocytes. The whole-cell patch-clamp technique was used to record I _f in isolated myocytes from 18 human right atrial appendages. A typical time- and voltage-dependent hyperpolarization-activated inward current could be recorded in all cells investigated (n=56). Mean current density recorded at –130 mV was –2.8±1.2 pApF^–1. Both adenosine and carbachol were found to directly inhibit I _f in human atrial myocytes by shifting the activation curves to more negative potentials. Adenosine 10^–5 mol/l shifted the potential of half-maximal activation by –5.9±0.4 mV from –99.4±0.6 mV to –105.3±0.4 mV (n=8; P<0.05), and carbachol 10^–5 mol/l by –5.7±0.5 mV from –99.2±0.5 mV to –104.9±0.6 mV (n=6; P<0.05). The concentration-response curve of adenosine calculated by a Hill function yielded a half-maximal effect of adenosine (EC₅₀) at a concentration of 3.6±0.5 μmol/l, a maximal shift of –6.5±0.3 mV, and a Hill coefficient (h) of 2.40. We did not observe any effect of flecainide (10^–5 mol/l; n=8), sotalol (10^–5 mol/l; n=6), amiodarone (10^–5 mol/l; n=6) or verapamil (10^–5 mol/l; n=5) on I _f in human atrial myocytes. However, propafenone (10^–5 mol/l) was found to reversibly reduce I _f current size (9/13 cells) by shifting the activation curve by –5.2±0.4 mV (P<0.05). In human atria adenosine- and muscarinic receptor stimulation might function as endogenous protective mechanisms inhibiting the initiation of ectopic tachycardia by reducing I _f current size. Propafenone may be more effective in some patients with atrial tachycardias that do not respond to other class Ic, III and IV antiarrhythmic drugs. However, it has yet to be defined whether these agents suppress atrial tachycardias via an inhibition of I _f in vivo. Received: 27 May 1998 / Accepted: 15 September 1998     

New triterpenoid saponins from <Emphasis Type="Italic">Argania spinosa</Emphasis>

Five new triterpene saponins, arganine L (1), O (2), P (3), Q (4) and R (5), were isolated from the barks of Argania spinosa (L.) Skeels. Arganines L-P and R are bidesmosidic saponins. The structures of 1–5 were elucidated as 3-O-[β-d-xylopyranosyl-(1–4)-β-d-glucuronopyranosyl]-28-O-[β-d-apiofuranosyl-(1–3)-β-d-xylopyranosyl-(1–4)-α-l-rhamnopyranosyl-(1–2)-α-l-arabinopyranosyl] bayogenin, 3-O-[β-d-xylopyranosyl-(1–4)-β-d-glucuronopyranosyl]-28-O-[β-d-xylopyranosyl-(1–4)-α-l-arabinopyranosyl] bayogenin, 3-O-[β-d-xylopyranosyl-(1–4)-β-d-glucuronopyranosyl]-28-O-[α-l-arabinopyranosyl] bayogenin, 3-O-[β-d-xylopyranosyl-(1–4)-β-d-glucuronopyranosyl] bayogenin, and 3-O-[β-d-apiofuranosyl-(1–4)-β-d-glucuronopyranosyl]-28-O-[β-d-xylopyranosyl-(1–4)-α-l-rhamnopyranosyl-(1–2)-α-l-arabinopyranosyl] bayogenin, respectively, mainly on the basis of their spectroscopic data.