Urotensin II acutely increases myocardial length and distensibility: potential implications for diastolic function and ventricular remodeling

Urotensin II (U-II) is a cyclic peptide that may be involved in cardiovascular dysfunction. In the present study, the acute effects of U-II on diastolic properties of the myocardium were investigated. Increasing concentrations of U-II (10⁻⁸ to 10⁻⁶ M) were added to rabbit papillary muscles in the absence (n = 15) or presence of: (1) damaged endocardial endothelium (EE; n = 9); (2) U-II receptor antagonist, urantide (10⁻⁵ M; n = 7); (3) nitric oxide (NO) synthase inhibitor, N^G-Nitro-l-Arginine (10⁻⁵ M; n = 9); (4) cyclooxygenase inhibitor, indomethacin (10⁻⁵ M; n = 8); (5) NO synthase and cyclooxygenase inhibitors, N^G-Nitro-l-Arginine (10⁻⁵ M) and indomethacin (10⁻⁵ M), respectively, (n = 8); or (6) protein kinase C (PKC) inhibitor, chelerythrine (10⁻⁵ M; n = 9). Passive length–tension relations were constructed before and after a single concentration of U-II (10⁻⁶ M; n = 3). U-II concentration dependently decreased inotropy and increased resting muscle length (RL). At 10⁻⁶ M, active tension decreased 13.8 ± 5.4%, and RL increased to 1.007 ± 0.001 L/L _max. Correcting RL to its initial value resulted in an 18.1 ± 3.0% decrease in resting tension, indicating decreased muscle stiffness, which was also suggested by the down and rightward shift of the passive length–tension relation. This effect remained unaffected by EE damage and PKC inhibition. In contrast, the presence of urantide and NO inhibition abolished the effects of U-II on myocardial stiffness, while cyclooxygenase inhibition significantly attenuated them. U-II decreases myocardial stiffness, an effect that is mediated by the urotensin-II receptor, NO, and prostaglandins. This represents a novel mechanism of acute neurohumoral modulation of diastolic function, suggesting that U-II is an important regulator of cardiac filling. Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users. Presented in part at the American Heart Association Scientific Sessions conference, 2006, in Chicago, Illinois.     

Voltammetric Determination of Mexidol

A new voltammetric method for determining mexidol in pharmaceuticals is proposed. Using this technique, mexidol was determined in model solutions (with R _s = of 1 – 6%) and in a ready-to-use preparation. The analytical range of mexidol determination using a glassy carbon composite electrode in 0.1 M H₂SO₄ extends from 4.8 × 10⁻³ to 1.8 × 10⁻² M. The detection limit is 1.9 × 10⁻³ M. The proposed procedure can be used for the quality control in the drug production technology. __________ Translated from Khimiko-Farmatsevticheskii Zhurnal, Vol. 39, No. 8, pp. 51 – 52, August, 2005.     

Comparison of dose requirement,serum erythropoietin and blood pressure following intravenous and subcutaneous erythropoietin treatment of dialysis patients IV and SC erythropoietin

Objective: The purpose of the study was to investigate the effect of route of administration of erythropoietin (EPO) on the dose requirement in dialysis patients after intravenous (IV) and subcutaneous (SC) therapy. Methods: The study was performed as a single centre, prospective, open, combined parallel and cross-over study of 50 dialysis patients, consecutively randomised to IV or SC treatment with EPO. The initial dose was 40 U⋅kg⁻¹ 3-times weekly, adjusted to increase haemoglobin (Hgb) from a median 5.3 mmol⋅l⁻¹ to a target of haemoglobin 6.5–7.5 mmol⋅l⁻¹. After reaching the target level, the haemoglobin was maintained for 4 months (Period 1). Then IV and SC treatment was switched for a further 4 months (Period 2). The study included high risk patients. The adjustment period was completed by 38 patients, Period one by 32 patients (IV/SC = 15/17; male/female = 19/13; age = 54 (24– 71) y), and Period two by 22 patients. Results: No significant difference was found between the two groups in the reticulocyte response, the rate of Hgb increase (IV 0.7 versus SC 0.5, mmol⋅l⁻¹⋅ month⁻¹), time to reach target level (IV 43 versus SC 60 days), or total EPO dose per increase in haemoglobin to target level (IV 663 versus SC 946 (U⋅kg⁻¹) per (mmol Hgb⋅l⁻¹). The overall median maintenance dose during the last month of the two four month periods was 105 (range IV 51–336) U⋅kg⁻¹⋅w⁻¹ and SC 104 (range 21–321) U⋅kg⁻¹⋅w⁻¹. Trough serum EPO levels were significantly higher during SC treatment. The blood pressure did not change significantly from the base level after either route of administration; start 133/80 versus 143/80 mmHg, target 127/78 versus 154/85 mmHg, and maintenance period 140/84 versus 142/85 mmHg. Thus, three-times weekly IV or SC EPO did not differ significantly in efficacy or in the effect on blood pressure in dialysis patients. Received: 13 June 1995/Accepted in revised form: 30 October 1995     

Lack of direct immunosuppressive effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on human peripheral blood lymphocyte subsets in vitro

A wide variety of immunosuppressive effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in experimental animals has been documented. In contrast, the impact of dioxin on the human immune system remains controversial, although adverse health effects have been reported in humans after occupational or accidental exposure to dioxin. Recently, Neubert et al. (1991) found that a dose-dependent decrease of peripheral blood lymphocyte (PBL) subpopulations in humans and non-human primates, including helper-inducer/memory cells (CD4⁺CD29⁺) and B cells (CD20⁺) occurred in pokeweed mitogen (PWM) stimulated cultures at concentrations as low as 10⁻¹²–10⁻¹⁴ M TCDD. Therefore, the direct effects of dioxin on human PBL subpopulations have been studied, in order to determine their usefulness as sensitive biomarkers for human dioxin exposure. Lymphocyte cultures from healthy individuals were treated with 10⁻⁷ M–10⁻¹⁴ M TCDD in the absence and presence of stimulation with pokeweed mitogen (PWM) or anti-CD3 monoclonal antibody (moAb; OKT3) for 3 days. Cytochrome P450 (CYP1A1) enzyme induction, one of the best studied direct biological effects of TCDD on numerous cell types, was assayed in parallel by ethoxyresorufin-O-deethylase (EROD) activity. Percentages of the different lymphocytes subsets, including CD2 (T cells); CD4; CD45 RA (suppressor-inducer/virgin T cells); CD4 CD29; CD8; CD19 (B cells) as well as interleukin 2 (IL-2) receptor (CD25) and class II antigen (HLA-DR) expression, were anlayzed by flow cytometry. DNA synthesis was determined by³H-thymidine uptake after 3 days of culture. In the present study, all stimulated lymphocyte cultures showed a dose-dependent significant increase of CYP1A1 activity at dioxin concentrations of 10⁻⁷ and 10⁻⁹ M. No enzyme activity could be detected at lower concentrations of TCDD. On the other hand, neither alteration in surface marker distribution nor suppression of lymphocyte proliferation could be demonstrated in mitogen-activated cells following any concentration of TCDD treatment. These data suggest that the inducibility of CYP1A1 enzyme activity is not correlated with direct immunotoxic effects in vitro in human PBL. In contrast to a previous report by Neubert et al. (1991), lymphoproliferation and phenotypes of human PBL are resistant to dioxin exposure in vitro and therefore appeared not to be useful as sensitive biomarkers in human exposure studies. The research described in this article has been reviewed by the Health Effects Research Laboratory, US Environmental Protection Agency, and apporved for puplication. Approval, does not signify that the contents reflect the views and policies of the Agency, nor does mention of trade names or commercial products consitute endorsement of recommendation for use.     

Biological effects of the dihydroorotate dehydrogenase inhibitor polyporic acid, a toxic constituent of the mushroom Hapalopilus rutilans , in rats and humans

Inhibitors of dihydroorotate dehydrogenase (DHO-DH), such as brequinar or leflunomide, have been intensively tested for their antitumour and immunomodulating effects. Polyporic acid (PA) from the mushroom Hapalopilus rutilans (H. r.) also is a DHO-DH inhibitor (50% inhibitory concn., IC₅₀, 10⁻⁴–10⁻³ M). As three people had been poisoned following ingestion of H. r. we wanted to investigate the effects of PA in rats and in cell cultures. Rats given PA via probang (100–800 mg/kg) within 24 h developed strongly reduced locomotor activity, depressed visual placing response and impaired wire manoeuvre. Laboratory investigation of blood revealed hepatorenal failure, metabolic acidosis as well as hypokalaemia and hypocalcaemia. All symptoms closely paralleled the effects seen in the poisoned people. Proliferation of cultured cells (including rat brain neurons and glia, fibroblasts, tumour cells) was depressed at 10⁻⁴–10⁻³ M PA. We conclude that the intoxication of people poisoned with H. r. is due to the high content of the DHO-DH inhibitor PA. Received: 6 July 1998 / Accepted: 7 September 1998     

Pharmacokinetics of glibenclamide and its metabolites in diabetic patients with impaired renal function

Background: Glibenclamide (Gb) may provoke long-lasting hypoglycaemic reactions, and one of the known risk factors is impaired renal function. We have demonstrated Gb to have a terminal elimination half-life of 15 h, and the main metabolites have a hypoglycaemic effect. With few exceptions, detailed studies on second generation sulphonylureas in diabetics with impaired renal function are lacking. Therefore, we analysed the pharmacokinetics of Gb and its active metabolites, 4-trans-hydroxyglibenclamide (M1) and 3-cis-hydroxyglibenclamide (M2) in this patient group. Methods: Two groups of 11 diabetic patients with impaired renal function (IRF, iohexol clearance range 7–42 ml · min⁻¹ · 1.73 m⁻²) or normal renal function (NRF, iohexol clearance range 75–140 ml · min⁻¹ · 1.73 m⁻²) were compared. A single oral 7-mg dose of Gb was administered after overnight fasting. Serum samples and urine collections were obtained over 48 h and 24 h, respectively. Concentrations of Gb, M1 and M2 were determined by a sensitive and selective high-performance liquid chromatography assay. Results: Peak serum values of M1 (24–85 ng · ml⁻¹ vs 16–57 ng · ml⁻¹), M2 (7–22 ng · ml⁻¹ vs <5–18 ng · ml⁻¹) and M1 + M2 (32–100 ng · ml⁻¹ vs 23–76 ng · ml⁻¹) were higher in the IRF group. AUC and C_max of Gb were lower and the clearance to bioavailability ratio (CL/f) was higher in the IRF group. AUC and C_max of M1 were higher and CL/f lower in the IRF group. Much lower amounts of M1 and M2 were excreted in the urine in the IRF group (7.2% vs 26.4% in 24 h). The fraction of the Gb dose excreted as metabolites (fe(met) 0–24 h), ranged between 0.005 and 0.36 and correlated significantly with renal function measured by iohexol clearance. No other pharmacokinetic differences were found. Conclusion: The differences in AUC, C_max and CL/f of Gb may be explained by a higher free fraction in the IRF group which would increase Gb metabolic clearance. The inverse findings regarding M1 may be explained by the fact that the metabolites are primarily eliminated by the kidneys. After a single dose of Gb, neither Gb, M1 nor M2 seemed to accumulate in diabetic subjects with IRF. As only small amounts of M1 and M2 were excreted in the urine, this indicates one or several complementary non-renal elimination routes, e.g. shunting of metabolised Gb to the biliary excretion route and/or enterohepatic recycling of both metabolites and unmetabolised Gb. Received: 21 April 1997 / Accepted in revised form: 14 October 1997     

Effects of the Herbicide Isoproturon on Metallothioneins,Growth, and Antioxidative Defenses in the Aquatic Worm <Emphasis Type="Italic">Tubifex tubifex</Emphasis> (Oligochaeta,Tubificidae)

Metallothioneins (MTs) are low molecular weight proteins, mainly implicated in metal ion detoxification. Increase in MT contents is considered to be a specific biomarker of metal exposure. Recently it has been demonstrated that MTs participate in several cellular functions such as regulation of growth, and antioxidative defenses. Therefore, the induction of MTs as biomarkers of exposure to the pesticide isoproturon has been investigated in the aquatic worms Tubifex tubifex. MT levels in exposed worms increased significantly (p < 0.05) after 2, 4, and 7 days of exposure to different concentrations of isoproturon (maximum increase compared to unexposed controls: +148.56% for 10 mg l⁻¹ after 4 days of exposure). In response to isoproturon, the activity of glutathione-S-transferase (max. +52%), glutathione-reductase (max. +100%), and catalase (max. +117%) increased, demonstrating the occurrence of an oxidative stress response to the herbicide. Thus, the increase in MT contents caused by isoproturon was interpreted as a defense response towards increased oxidative stress generated by the herbicide. Residues of isoproturon and its metabolites, 1-(4-isopropylphenyl)-3-methylurea, 1-(4-isopropylphenyl) urea, and 4-isopropylanilin were detected in the worm growth medium. Half-life of the herbicide was shorter at a low (0.1 mg l⁻¹) initial concentration. The herbicide accumulated in T. tubifex but no metabolite could be detected.     

Inhibition of erythrocyte “apoptosis” by catecholamines

Osmotic shock, oxidative stress and Cl⁻ removal activate a non-selective Ca²⁺-permeable cation conductance in human erythrocytes. The entry of Ca²⁺ leads to activation of a scramblase with subsequent exposure of phosphatidylserine at the cell surface. Phosphatidylserine mediates binding to phosphatidylserine receptors on macrophages which engulf and degrade phosphatidylserine exposing cells. Moreover, phosphatidylserine exposure may lead to adherence of erythrocytes to the vascular wall. In the present study, we explored whether activation of the non-selective cation conductance and subsequent phosphatidylserine exposure might be influenced by catecholamines. Phosphatidylserine exposure has been determined by FITC-annexin V binding while cell volume was estimated from forward scatter in FACS analysis. Removal of Cl⁻ enhanced annexin binding and decreased forward scatter, an effect significantly blunted by the β agonist isoproterenol (IC₅₀ approx. 1 μM). Fluo-3 fluorescence measurements revealed an increase of cytosolic Ca²⁺ activity following Cl⁻ removal, an effect again significantly blunted by isoproterenol exposure (10 μM). Whole-cell patch-clamp experiments performed in Cl⁻ free bath solution indeed disclosed a time-dependent inactivation of a non-selective cation conductance following isoproterenol exposure (10 μM). Phenylephrine (IC₅₀<10 μM), dobutamine (IC₅₀ approx. 1 μM) and dopamine (IC₅₀ approx. 3 μM) similarly inhibited the effect of Cl⁻ removal on annexin binding and forward scatter. In conclusion, several catecholamines inhibit the Cl⁻ removal-activated Ca²⁺ entry into erythrocytes, thus preventing increase of cytosolic Ca²⁺ activity, subsequent cell shrinkage and activation of erythrocyte scramblase. The catecholamines thus counteract erythrocyte phosphatidylserine exposure and subsequent clearance of erythrocytes from circulating blood.     

Effect ofAlpha-2 adrenergic agonist onBeta adrenoceptor-mediated control of blood glucose in the fasted mouse

Dose-dependent increases in blood glucose were produced by epinephrine and clonidine in fasted male mice. Isoproterenol was ineffective in increasing blood glucose at lower doses (10⁻⁸ M/kg−10⁻⁷ M/kg); with higher dose (10⁻⁶ M/kg) the glucose level was increased. The hyperglycemia induced by epinephrine was inhibited by yohimbine, prazosin and propranolol, indicating that the hyperglycemic effect of epinephrine is mediated byalpha-1,alpha-2 andbeta adrenoceptor. When clonidine (10⁻⁶ M/kg) was administered simultaneously with isoproterenol (10⁻⁶ M/kg), an enhenced hyperglycemic effect was observed. The increment produced by clonidine plus isoproterenol was higher than that by clonidine alone. These results suggest that stimulation ofalpha-2 adrenoceptor may be responsible for the exertion of the hyperglycemic effect bybeta agonists in fasted mice.     

Comparison of Skin Esterase Activities from Different Species

Purpose Many topically applied drugs contain esters that are hydrolyzed in the skin. Minipigs have emerged as potential models of human dermatology and, in some aspects, may be superior to commonly used rat skin. The aims of this study were to evaluate the suitability of minipig and rat skin as in vitro models of human epidermal esterase activity. Methods Naphthyl acetate and para-nitrophenyl acetate were tested as prototypical substrates of carboxylesterases from skin, plasma, and liver. Reaction products were monitored by high-performance liquid chromatography/ultraviolet analysis. Results Hydrolysis efficiency in skin was higher than plasma, but lower than liver. The esterase efficiency of rat skin microsomes (580–1100 min⁻¹ mg⁻¹) was two to three orders of magnitude higher than human (1.3–4.2 min⁻¹ mg⁻¹) and minipig microsomes (1.2–4.2 min⁻¹ mg⁻¹). Rat skin cytosol (80–100 min⁻¹ mg⁻¹) was 2- to 10-fold more efficient than human (2.4–67 min⁻¹ mg⁻¹) or minipig cytosol (18–61 min⁻¹ mg⁻¹). Most importantly, human skin fractions displayed kinetics of hydrolysis very similar to minipig skin. Conclusions These studies show minipig skin as an appropriate, potentially valuable model for human epidermal ester metabolism and support the use of minipig skin in preclinical development of topically applied compounds.     

Comparative toxicity of hydrophobic contaminants to microalgae and higher plants

To enable rapid and sensitive screening of phytotoxic compounds in terrestrial system, a 4 day solid-phase microalgal bioassay was developed. Three species of microalgae (Selenastrum capricornutum, Chlorococcum hypnosporum and Chlorococcum meneghini) were chosen to investigate their responses to DDTs (DDT, DDD and DDE) and PAHs (naphthalene, phenanthrene and pyrene) spiked sands. The bioassay results showed that PAHs and DDTs were toxic to microalgae in a 4-day exposure tests but not to seed germination of ryegrass (Lolium perenne). Phenanthrene was the most phytotoxic. Among three investigated endpoints, fluorescence emissions by microalgae were less sensitive than cell density (optical density OD₆₅₀) and chlorophyll a concentration as endpoints. In general, S. capricornutum was the most sensitive species for PAHs (EC₅₀ for phenanthrene = 9.4 mg kg⁻¹), while C. meneghini for DDTs (EC₅₀ for DDE = 20.0 mg kg⁻¹). Comparison of the microalgal tests with US EPA standard seed germination/root elongation test (using Lolium perenne) demonstrated the superior screening potential of phytotoxic hydrophobic compounds using the proposed bioassay. Using OD₆₅₀ as the endpoint, EC₁₀ of selected microalgae for PAHs and DDTs were 0.43–64.3 mg kg⁻¹ and 0.67–117 mg kg⁻¹ respectively, which were much lower than the EC₁₀ of L. perenne for both PAHs (94–187 mg kg⁻¹) and DDTs (113–483 mg kg⁻¹). The results encourage further studies involving wider types of vascular plants and more comparison with standard phytotoxicity tests from different authorities using contaminated soils to verify the effectiveness of the microalgal bioassay.     

Uptake and accumulation and oxidative stress in garlic (Allium sativum L.) under lead phytotoxicity

The effects of different concentrations of Pb on growth of Allium sativum L, Pb uptake and accumulation, antioxidant enzyme activity and malondialdehyde content were investigated. The results indicated that shoot growth at high concentration of Pb (10⁻³ M) and roots growth at 10⁻³ M and 10⁻⁴ M Pb were significantly inhibited. Lead ions were accumulated mainly in the roots and only small amounts were translocated to bulbs and shoots. SOD activities in shoot and roots exposed to 10⁻³ M Pb were observed to be high. Plants exposed to 10⁻³ M Pb showed a significant increase in POD activity in roots versus the control and other Pb treatments. In roots, CAT activity and MDA concentration at 10⁻³ M Pb is high significantly. The mechanisms of Pb toxicity and tolerance in garlic are briefly discussed.     

Inhibitory effect of papaverine on the contraction induced by transmural stimulation in the isolated mouse vas deferens

The effect of papaverine on the contractions induced by adrenergic neurotransmission in the isolated mouse vas deferens was investigated. Papaverine, 10⁻⁷–10⁻⁵M, showed a dose-dependent and reversible inhibition on the induced contractions. When the frequency of stimulation was varied (2.5–20.0 Hz), the inhibitory effect tended to be marked at the lower frequencies.     

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.     

In vitro and in vivo effects of cadmium on cholinesterases in Nile tilapia fingerlings: implications for biomonitoring aquatic pollution

Effects of cadmium on in vitro and in vivo cholinesterase (ChE) activities of brain and muscle tissues of Oreochromis niloticus fingerlings were evaluated, considering its potential use in biomonitoring tropical water pollution. Results show that in vitro ChE activities were depressed significantly by millimolar concentration ranges of Cd²⁺. The IC₅₀ values of Cd²⁺ on in vitro ChE activity in brain and muscle tissues were 1.56 and 4.31 mM, respectively. Exposure of fish to environmentally relevant concentrations of Cd²⁺ (5–30 μg l^−l) for 28 days evoked only a transient inhibition (21–34%) of in vivo ChE activities. Prior exposure and co-exposure of fish to 15 μg l⁻¹ of Cd²⁺ enhanced the extent of inhibition of ChE levels induced by the organophosphorous insecticide chlorpyrifos. As high concentrations of cadmium have the potential to depress ChE activities, monitoring of metal levels in water bodies with suspected high levels of metal inputs is necessary to accurately interpret the fish ChE inhibition data in relation to insecticide contaminations.     

Change in life cycle parameters and feeding rate of <Emphasis Type="Italic">Ceriodaphnia silvestrii</Emphasis> Daday (Crustacea,Cladocera) exposure to dietary copper

Changes in life cycle parameters (survival, growth, reproduction) and feeding rate of the tropical cladoceran Ceriodaphnia silvestrii as affected by Cu contaminated algae Pseudokirchneriella subcapitata were investigated. The dietary copper exposure ranged from 3 × 10⁻¹⁵ to 68 × 10⁻¹⁵ g Cu algal cell⁻¹. Low waterborne copper exposure (around 10⁻¹⁰ mol l⁻¹ free Cu²⁺ ions) was kept in the experiments. The results show an increasing toxic effect on C. silvestrii with copper increase in algal cells; at the highest copper exposure, all life cycle parameters were significantly affected. A concentration of 38 × 10⁻¹⁵ g Cu algal cell⁻¹ reduced egg hatching percentile and the number of neonates produced per female, but did not cause any statistically significant effect on animals survival nor to the number of eggs produced per female. The following sequence of events was observed from the lowest to the highest copper contamination: reproduction, feeding rate, body length and, at last, survival was affected. We conclude that algal cells are an important route of copper exposure and toxicity to cladocerans.     

Male reproductive toxicity of four bisphenol antioxidants in mice and rats and their estrogenic effect

Male mice and rats were fed a diet containing four bisphenol antioxidants, 2,2′-methylenebis(4-ethyl-6-tert-butylphenol) (ME), 2,2′-methylenebis(4-methyl-6-tert-butylphenol) (MM), 4,4′-butylidenebis(3-methyl-6-tert-butylphenol) (BM), or 4,4′-thiobis(3-methyl-6-tert-butylphenol) (TM) at levels of 0.06–0.25% for 2 months. BM and TM decreased epididymal, seminal vesicular, prostate and preputial weights, and injured seminiferous tubules in mice in a dose-dependent fashion. BM and TM also reduced sex accessory organ weights and sperm production capacity in rats, but MM and ME were more toxic to rats than BM and TM. ME and MM did not bind ER_α up to 10⁻³ M, while BM and TM competitively bound ER_α against β-estradiol (E2). Fifty percent inhibitory concentrations (IC₅₀ s) of BM, TM, and bisphenol A (positive control) against E2-binding were 7.3×10⁻⁶ M, 1.8×10⁻⁵ M, and 1.4×10⁻⁵ M, respectively. When ovariectomized (OVX) mice were sc administered TM at doses of 60 and 300 mg/kg/day for 4 days, or when OVX mice were fed BM in the diet at a level of 0.25% for 2 months, uterine weight was significantly increased. These results suggest that BM and TM are weakly toxic, possibly through an estrogenic mechanism to male reproductive organs in mice as well as rats, while MM and ME may be the direct testicular toxins in rats but not mice. A part of this study was presented at the 74th annual meeting of the Japanese Society for Hygiene held from 24–27 March 2004 in Tokyo, Japan.     

Effects of selected heavy metals (Pb, Cu, Ni, and Cd) in the aquatic medium on the restoration potential and accumulation in the stem cuttings of the terrestrial plant, Talinum triangulare Linn

The heavy metal (Cu, Pb, Ni, and Cd) accumulation capacity of the stem cuttings of the terrestrial, ornamental plant, Talinum triangulare was assessed in hydroponic medium. The stem cuttings of T. triangulare, grew well in distilled water regenerating roots and aerial parts. On exposure to various concentrations of Cu, Pb, Ni, and Cd, a concentration dependent decrease was observed in the number of leaves produced and roots regenerated and an increase in the number of days required for the initiation of roots. The number of leaves produced showed an increasing trend in almost all treatment concentrations of Cu, Pb, Ni, and Cd with an increase in the duration of experiment, whereas, with an increase in the treatment concentration of metals a significant (P < 0.05) decrease was observed in the number of leaves produced. The number of days required for root initiation in metal solutions, however, increased with increasing concentration of Cu, Pb, Ni, and Cd. The root development was completely arrested from 10 mg l⁻¹ of Ni and 4 mg l⁻¹ of Cd. Compared to the control, a significant decrease was recorded in the number of roots produced in all treatment concentrations of Cu, Pb, Ni, and Cd. Pink colouration of metal solution consequent to leaching of plant pigment from T. triangulare was observed which was not persistent and disappeared after a few days. Decaying of stem was observed when exposed to Ni and Cd but not to Cu and Pb. Although, copper accumulation by T. triangulare at treatment concentration of 15 and 20 mg l⁻¹ exceeded 1,000 mg kg⁻¹ dry matter, necessary pot culture experiment is required before “T. triangulare” can be definitely classified as a Cu hyperaccumulator.     

Ionometric determination of cefotaxime in biological media

Ion-selective electrodes based on ion exchangers of tetradecylammonium (TDA) with cefotaxime (claforan) anions have been developed. The proposed electrodes are sensitive to cephalosporins in the concentration range from 1 × 10^{− 5} to 1 × 10^{− 1} M. The time for establishing a steady-state potential is 1–2 min. The potential drift does not exceed 2 mV/d. The detection threshold for cefotaxime is 3.6 × 10^{− 5} M in the optimum pH range of 4.3–6.5. Comparison of the main electrochemical characteristics of the ion-selective electrodes based on TDA associates with cephalosporins showed that the best parameters are found in electrodes with membranes containing claforan. __________ Translated from Khimiko-Farmatsevticheskii Zhurnal, Vol. 42, No. 3, pp. 48–50, March, 2008.