Accumulation and Regulation of Zinc in Daphnia magna: Links with Homeostasis and Toxicity

Zinc accumulation in Daphnia magna was investigated, and the results were linked to the previously established optimal concentration range for zinc and D. magna. It was observed that organisms cultured in this optimal range (300–600 μg Zn/L) contained 212 ± 57 to 254 ± 79 μg Zn/g dry weight. Lower and higher zinc contents were obtained after acclimation to previously established culture concentrations inducing deficiency and toxicity, respectively. The calculation of bioconcentration factors indicated that zinc was actively regulated, at least up to a concentration of 600 μg Zn/L. Zinc uptake and elimination are rapid processes; major increases and decreases in body content occurred within 1 day. Zinc concentrations in daphnids exposed to 600 μg Zn/L fluctuated with 2- to 3-day intervals, suggesting a role of molting in the regulation and elimination of zinc. Received: 12 November 2001/Accepted: 15 April 2002     

No Threat-Related Processing Bias in Low Trait-Anxious/High State-Anxious Novice Parachuters

Earlier studies found that processing bias inanxious patients as measured by the modified Stroop taskis reduced after behavior therapy. This suggests thatthreat interference reflects an anxious state rather than a stable trait. Others (e.g.,Matthews & Macleod, 1994), however, have proposedthat it emerges from the interaction of state anxietyand some vulnerability trait. The experiment tested whether, in line with the state hypothesis andin contrast to the interaction hypothesis, state anxietyis sufficient to produce processing bias.Twenty-sixlow-trait-anxious participants who neverparachuted volunteered for a parachute jump and theirperformance on the modified Stroop task was comparedwith a control group matched on trait anxiety.Anticipation of the jump resulted in subjective anxietybut not in threat interference on the modifiedStroop, where there were no between group differences.The data suggest that state anxiety in itself isinsufficient to explain processing bias. The findingsare discussed critically.     

Synthesis and anti-HIV activity of different sugar-modified pyrimidine and purine nucleosides

A series of base-modified pyrimidine 3'-azido-2',3'-dideoxynucleosides and 3'-substituted purine and pyrimidine 2',3'-dideoxynucleosides have been synthesized and evaluated for their inhibitory activity against human immunodeficiency virus (HIV) replication in MT-4 cells. The following pyrimidine derivatives emerged as the most potent and/or selective inhibitors of HIV-induced cytopathogenicity (in order of decreasing selectivity: 3'-azido-3'-deoxythymidine (AZT), 3'-azido-2',3'-dideoxyuridine (AzddUrd), 3'-azido-2',3'-dideoxy-5-methylcytidine (AzddMeCyd), 3'-fluoro-ddUrd (FddUrd), 3'-fluoro-ddThd (FddThd), the N4-hydroxylated derivative of AzddMeCyd and the N4-methylated derivative of AzddMeCyd. Among the purine 2',3'-dideoxynucleosides, 3'-azido-2',3'-dideoxyguanosine (AzddGuo), 3'-fluoro-ddGuo (FddGuo), and 3'-fluoro-2,6-diaminopurine 2',3'-dideoxynucleoside (FddDAPR) were the most selective inhibitors of HIV replication.     

Pharmacological and hemodynamic profile of nebivolol, a chemically novel, potent, and selective beta 1-adrenergic antagonist

The pharmacological profile of nebivolol (N), a chemically novel beta-adrenergic antagonist, was assessed in investigations on isolated tissues, awake spontaneously hypertensive rats (SHR), closed-chest anesthetized dogs, and humans. In vitro, N was found to be a potent antagonist of beta 1-adrenergic receptors (A2 value, 5.8 X 10(-9) M) and only a weak beta 2-adrenergic antagonist (A2 value, 1.7 X 10(-6) M). The selectivity for the beta 1-adrenergic receptor was higher for N than for any of the reference compounds. In dogs--similarly with atenolol--N was more potent in blocking the isoprenaline (I)-induced increases in left ventricular performance than the I-induced decrease in arterial pressure. In dogs, as compared with propranolol, N (0.025 and 0.01 mg.kg-1 i.v.) increased cardiac output and stroke volume, lowered systemic vascular resistance, and had no significant effect on the variables related to left ventricular contraction. In contrast to other beta-adrenergic antagonists, N acutely lowered arterial blood pressure in SHR (1.25 mg.kg-1 i.p.) and in hypertensive patients (1 oral dose of 5 mg) for several hours. In healthy volunteers N (5 mg) lowered systemic vascular resistance during daily oral treatment and did not negatively affect left ventricular function. In conclusion, N is a potent and selective beta 1-adrenergic blocking agent with an interesting hemodynamic profile. In hypertensive subjects and SHR, a single dose lowers arterial blood pressure for substantial periods of time.     

In vivo effects of granulocyte-macrophage colony-stimulating factor and interleukin-3 on clonal and non-clonal cell populations in patients with clonal hematopoietic disorders.

Restriction fragment length polymorphisms (RFLP) of the X-chromosome genes phosphoglycerate kinase and hypoxanthine phosphoribosyl transferase were used in conjunction with cytogenetic analysis to study the clonality of hematopoiesis in four female patients with myelodysplastic syndromes, treated with either granulocyte-macrophage colony-stimulating factor (GM-CSF) or interleukin-3 (IL-3), and in one patient with essential thrombocythemia (ET) treated with IL-3. Both conventional karyotyping and X-inactivation analysis demonstrated the persistence of a monoclonal pattern of hematopoiesis in the two patients with refractory anemia (RA) treated either with GM-CSF or with IL-3. The partial restoration of non-clonal hematopoiesis was observed in one patient with RA and an excess of blasts following treatment with a combination of GM-CSF and low dose cytosine arabinoside. In a fourth patient with RA and in the patient with ET, treatment with IL-3 resulted in the complete restoration of a non-clonal pattern of peripheral blood cells. In contrast, the bone marrow cells remained monoclonal by Southern blot analysis in the patient with RA in whom it could be tested. Non-clonal lymphocytes appear to have been released into the peripheral blood in the two latter cases and are responsible for the non-clonal RFLP pattern. These results suggest that cytokine therapy may have diverse effects on hematopoiesis, including the release of residual normal cells into the peripheral blood.     

Effect on blood pressure of two diets differing in total fat but not in saturated and polyunsaturated fatty acids in healthy volunteers

The effects of a low-fat, carbohydrate-rich and a high-fat, olive-oil-rich diet on blood pressure were studied under strict dietary control. Forty-seven healthy normotensive men and women were fed a diet high in saturated fatty acids (20 en%) and total fat (38 en%) for 17 d. Twenty-four subjects then received a low-fat, carbohydrate-rich diet (total fat 22 en%) and the other 23 a high-fat, olive-oil-rich diet (oleic acid 24 en%, total fat 41 en%) for 36 d. Both test diets had the same level of saturated fatty acids (7-10 en%) and linoleic acid (4 en%). Systolic blood pressure fell by 2.3 and diastolic by 4.7 mm Hg in the carbohydrate group and by 2.7 and 4.4 mm Hg in the olive-oil group, respectively (differences between diets groups not significant). These results suggest that a high-fat diet rich in monounsaturated fatty acids has no deleterious effect on blood pressure in healthy normotensive subjects in comparison with a low-fat, carbohydrate-rich diet.     

Nebivolol is devoid of intrinsic sympathomimetic activity

Nebivolol is a chemically novel, potent and selective beta 1-adrenoceptor-blocking agent that acutely lowers arterial blood pressure in hypertensive patients and rats without depressing, or even enhancing, left ventricular function. These properties could be compatible with a partial agonistic effect of beta-adrenoceptor-blocking agents. It was the aim of the present study to investigate whether nebivolol has intrinsic sympathomimetic properties. The study was performed on reserpinized dogs and spontaneously hypertensive rats, and on various isolated tissues from various species. Unlike pindolol and practolol, nebivolol did not exert a stimulating effect on the heart rate and left ventricular function in reserpinized animals and/or in isolated atria of reserpinized rats at doses that are clinically active. Nebivolol did not induce relaxation of isolated coronary arteries and saphenous veins at concentrations that block beta-adrenoceptors. These findings indicate that nebivolol is devoid of intrinsic sympathomimetic activity at clinically relevant doses.