Lithium in drinking water and the incidences of crimes,suicides, and arrests related to drug addictions

Using data for 27 Texas counties from 1978-1987, it is shown that the incidence rates of suicide, homicide, and rape are significantly higher in counties whose drinking water supplies contain little or no lithium than in counties with water lithium levels ranging from 70-170 micrograms/L; the differences remain statistically significant (p less than 0.01) after corrections for population density. The corresponding associations with the incidence rates of robbery, burglary, and theft were statistically significant with p less than 0.05. These results suggest that lithium has moderating effects on suicidal and violent criminal behavior at levels that may be encountered in municipal water supplies. Comparisons of drinking water lithium levels, in the respective Texas counties, with the incidences of arrests for possession of opium, cocaine, and their derivatives (morphine, heroin, and codeine) from 1981-1986 also produced statistically significant inverse associations, whereas no significant or consistent associations were observed with the reported arrest rates for possession of marijuana, driving under the influence of alcohol, and drunkenness. These results suggest that lithium at low dosage levels has a generally beneficial effect on human behavior, which may be associated with the functions of lithium as a nutritionally-essential trace element. Subject to confirmation by controlled experiments with high-risk populations, increasing the human lithium intakes by supplementation, or the lithiation of drinking water is suggested as a possible means of crime, suicide, and drug-dependency reduction at the individual and community level.     

A new method for study of normal lens developmentin vitro using pulsatile delivery of PDGF or EGF in HL-1 serum-free medium

Summary A new culture method was used to study increases in wet and dry weight and soluble protein during normal development of the transparent lens. Seven different media with more than ten different additives were tested for their effects on cultured lens transparency.In vivo, rat lenses increased 53% in soluble protein content between 3 and 5.5 days of age. Only HL-1 serum-free medium containing 15 μg/ml insulin plus 1–2 ng/ml BB platelet-derived growth factor (PDGF), or 5–7 ng/ml epidermal growth factor (EGF) allowed similar growthin vitro, during the same time period. Normal lens grwoth occurred in culture when fresh medium was delivered to lenses as a pulse every 4–6 hours. Lenses decreased in dry weight and soluble protein content, and became opaque when the same medium was delivered continuously. Lenses increased only 26% and 32% in soluble protein content when delivered pulses of HL-1 medium containing BB PDGF or EGF in the absence of insulin. We suggest that pulsatile delivery of medium containing insulin and PDGF or EGF stimulates lens growth during developmentin vitro. This pulsatile organ culture system is presented as a new approach for studying the effects of growth factors on cell proliferation, differentiation, and receptor regulation in a developing tissue. This work was supported by grants from EY-07031 and EY-04542 from the National Eye Institute and a grant from the Oculon Corporation. Editor's statement This report documents an in vitro system that may mimic lens development and response to growth regulators and hormones. The system may be useful for application to other organs and provide a foundation for cell and molecular level analysis.     

Characterisation of Human 5-Hydroxytryptamine2A and 5-Hydroxytryptamine2C Receptors Expressed in the Human Neuroblastoma Cell Line SH-SY5Y: Comparative Stimulation by Hallucinogenic Drugs

Abstract: Stable transfection of the human neuroblastoma cell line SH-SY5Y with the human 5-hydroxytryptamine_2A (5-HT_2A) or 5-HT_2C receptor cDNA produced cell lines demonstrating ligand affinities that correlated closely with those for the corresponding endogenous receptors in human frontal cortex and choroid plexus, respectively. Stimulation of the recombinant receptors by 5-HT induced phosphoinositide hydrolysis with higher potency but lower efficacy at the 5-HT_2C receptor (pEC₅₀ = 7.80 ± 0.06) compared with the 5-HT_2A receptor (pEC₅₀ = 7.30 ± 0.08). Activation of the 5-HT_2A receptor caused a transient fourfold increase in intracellular Ca²⁺ concentration. Whole-cell recordings of cells clamped at ?50 mV demonstrated a small inward current (2 pA) in response to 10 µM 5-HT for both receptors. There were no differences in potency or efficacy of phosphoinositide hydrolysis among four hallucinogenic [d-lysergic acid diethylamide (LSD), 1-(4-iodo-2,5-dimethoxyphenyl)-2-aminopropane (DOI), 5-methoxy-N,N-dimethyltryptamine, and mescaline] and three nonhallucinogenic drugs (m-chlorophenylpiperazine, quipazine, and ergotamine). Comparison of equipotent doses producing 20% of the maximal response induced by 5-HT revealed selective activation of the 5-HT_2A receptor by LSD and to a lesser degree by DOI, mescaline, and ergotamine. Quipazine and 5-methoxy-N,N-dimethyltryptamine were relatively nonselective, whereas m-chlorophenylpiperazine selectively activated the 5-HT_2C receptor. It is unlikely therefore that hallucinosis is mediated primarily by activity at the 5-HT_2C receptor, whereas activity at the 5-HT_2A receptor may represent an important but not unique mechanism associated with hallucinogenic drug action.     

Prediction of location of active sites in biologically active peptides

In a previous paper we demonstrated that the short-range compact regions in atrial natriuretic factor (-hANF) predicted by the average distance map (ADM) correspond to its active sites [Kikuchi,J. Protein Chem.11, 579–581 (1992)]. In the present paper we apply the same method to other bioactive peptides and peptidic enzyme inhibitors. We again observe that active sites in each peptide are contained in short-range compact regions predicted by the ADM for the peptide. This demonstrates that the ADM method predicts the possible location of active sites in biologically active peptides in general. The possibility of practical application of the present method to rational drug design is also discussed.     

Electrical conductivity dispersion as a probe of membrane modifications in mouse polyomavirus infected cells in culture

In this report we investigate the inhibition of membrane conductivity, due to the murine polyomavirus infection in permissive cells in culture. We define experimental conditions to have reproducible results and demonstrate that the intensity of the effects on the cell membrane, depends upon the virus titer used in the infection. Finally, the virus dependent effects disappear if the infection is performed in the presence of a drug that inhibits polymavirus DNA replication.     

Evaluation of Drugs for Treating Obesity

Criteria for the evaluation of new drugs to treat obesity are important as guides for designing clinical trials to test these agents. These criteria must be developed in relation to the realities of obesity, which is a chronic disease associated with morbidity and mortality that is increased by visceral fat deposits. The observation that patients regain weight after stopping drug treatment for obesity argues for the proposition that drugs work only when taken and NOT that the drugs are ineffective. The analogy between the development of treatments for obesity to those for the treatment of hypertension is used to highlight potential areas for new developments. Several features of an ideal drug for the treatment of obesity are suggested. Criteria for evaluating new drugs include both primary and secondary endpoints. The primary endpoint for an anti-obesity drug should be weight loss, possibly by category of success. Losses of total body fat or visceral fat might be alternative primary endpoints. Secondary endpoints include reduction in risk factors for associated diseases and improvement in the quality of life. In trials where vigorous placebo designs including highly aggressive behavior modification or very-low-calorie diets were used, it may be difficult or impossible to detect a response to a drug.     

Use of a gel-forming dipeptide derivative as a carrier for antigen presentation

A dipeptide of the formula Fmoc-Leu-Asp and some other related dipeptides were synthesized in solution by standard methods. When such peptides are dissolved in water at concentrations below 1% at 100 °C and cooled below 60 °C they form turbid solutions and eventaully visocelastic gels at lower temperatures. Such gels are thermoreversible and can also be disrupted by mechanical agitation. At a concentration of 2 mg/ml the peptide Fmoc-Leu-Asp forms an aqueous gel at 60 °C with a shear modulus of 80 Pa measured at a frequency of 1 rad/s. Peptide solutions undergo an abrupt increase in light scattering between 1 and 1.5 mg/ml at both 23 and 60 °C. By analogy with previous observations of other systems, this increse appears to be due to the formation of filamentous micelles and the aggregation of filamaents into a three-dimensional network. When low molecular weight adamantanamine derivatives, which are inherently non-antigenci antiviral drugs, were incorporated into the Fmoc-Leu-Asp gel and injected into rabbits, high titre specific antibodies were efficiently produced without the need for additional adjuvant. Both the physical properties of the gel and its effect on the antigenicity of low molecular weight compounds suggest a number of practical applications.     

Whisker-mediated plant transformation: An alternative technology

A number of different methods, involving direct DNA delivery are now available for plant transformation. Here we review the most recently developed technique which involves the mixing of silicon carbide whiskers with plant cells and plasmid DNA. Fertile transgenic plants have now been produced using whisker-mediated transformation, and this method can now be considered as a simple, inexpensive alternative for plant transformation. A brief review on transformation of animal cells andChlamydomonas using whiskers technology is also included.     

Enantioselective inhibitory effect of nicardipine on the hepatic clearance of propranolol in man

The influence of a single oral dose of 30 mg nicardipine on the pharmacokinetics of (R)- and (S)-propranolol, given orally as rac-propranolol 80 mg, was studied in 12 healthy volunteers. The plasma concentrations were higher for the (S)-enantiomer than for the (R)-enantiomer. The Cl_o and the Cl′_intr of (S)-propranolol were significantly lower than the Cl_o and Cl′_intr of (R)-propranolol. The unbound fraction of (R)-propranolol was significantly higher than that of (S)-propranolol. Coadministration of nicardipine significantly increased the AUC and C_max and significantly decreased the Cl_o and Cl′_intr for unbound drug of (R)- and (S)-propranolol. These changes were more important for (R)- than for (S)-propranolol. The protein binding was not altered by nicardipine. The enantioselective effect of nicardipine on the metabolic clearance of propranolol appears to be due to an interaction at the level of the metabolizing enzymes. The effect on blood pressure of rac-propranolol was little affected when nicardipine was coadministered with rac-propranolol, and its bradycardic effect was reduced. © 1994 Wiley-Liss, Inc.     

Transient expression of GUS and anthocyanin constructs in intact maize immature embryos following electroporation

Electroporation was used for the delivery and subsequent expression of GUS and anthocyanin reporter genes into intact maize immature embryos. The optimal conditions consisted of culturing immature embryos for 4 days on N6 1-100-25-Ag medium prior to electroporation (375 V/cm; 960 µF capacitance) in EPR buffer containing DNA and 0.07 M sodium glutamate at room temperature (22°C) after a 10 min heat shock at 37°C. Under these conditions, over 40 spots of GUS transient activity were observed per immature embryo. Transient gene expression after electroporation was further demonstrated using an anthocyanin construct, which is specific for expression in plant cells.