Medication prescribed to people with personality disorder: the influence of patient factors and treatment setting.

OBJECTIVE: To examine the extent of use and clinical rationale for the prescribing of psychotropic drugs for people with personality disorder (PD) who are in contact with mental health services. METHOD: Clinical records of 278 patients with a primary diagnosis of PD were examined. RESULTS: Just over 80% (N = 225) of patients were being prescribed psychotropic medication. One in five was prescribed three or more drugs. People with comorbid mental disorders were more likely to receive psychotropic medication. Half those prescribed antidepressants had no record of depression in their records. While drug treatments were mostly prescribed for depressive and psychotic symptoms, they were also used to try to manage behavioural problems such as self-harm or given in response to patient requests for treatment. People receiving specialist PD services (OR = 0.35, 95% CI = 0.13-0.95) or other specialist services (OR = 0.24, 95% CI = 0.10-0.60) were less likely to be prescribed drug treatments. CONCLUSION: Drug treatments are widely used for people with PD despite the relatively weak evidence base. Both the type of personality problem and the context in which treatment is delivered appear to have an impact on whether drug treatments are prescribed.

Author Correction: Radiological Investigation of High Background Radiation Areas.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Amantadine: neuromuscular blockade by suppression of ionic conductance of the acetylcholine receptor.

Amantadine hydrochloride decreases the sensitivity of denervated mammalian muscle to iontophoretically applied acetylcholine. The drug depresses the amplitude of the end-plate current and reverses the slope of the relation between half-decay time and membrane potential suggesting that it alters the ionic conductance that is mediated by the acetylcholine receptor. Binding studies confirm that amantadine acts on the ion conductance modulator rather than the acetylcholine receptor.

Radiological Investigation of High Background Radiation Areas.

In this paper, we used the Hyper-Pure Germanium (HPGe) detector to measure 30 samples which are collected from north of Nile Delta near Rosetta beach in Egypt. The activity of primordial radionuclides, such as 238U, 235U, 232Th, and 40K was estimated. Concentrations ranged between 36.5-177.4, 50-397.5 and 56.1-168.9 Bq.kg-1 for 238U, 232Th and 40K respectively. Activity concentration of 235U and the variation in uranium isotopic ratio 235U/238U was calculated. External hazard indices (Hex) (or radium equivalent activity Raeq), activity concentration indices (I), alpha index (Iα), absorbed outdoor gamma dose rate (Dout), effective outdoor gamma dose rate (Eout) and Excess Lifetime Cancer Risk (ELCR) due to different samples are estimated. External hazard indices (Hex) are ranged between 0.32-2.04, radium equivalent activity (Raeq) are ranged between 118.67-753.91, the activity concentration indices (I) are 0.42-2.61, and alpha index (Iα) are 0.18-0.89. External hazard indices (Hex) in some samples more than unity then it exceeds the upper limit of exposure. Also, the radium equivalent activities (Raeq) are higher than the exemption limits (370 Bq.kg-1).

Anticancer and Radiosensitization Efficacy of Nanocomposite Withania somnifera Extract in Mice Bearing Tumor Cells.

The objective of the present study was to evaluate the anticancer and radio-sensitizing efficacy of a Withania somnifera extract/Gadolinium III oxide nanocomposite (WSGNC) in mice. WSGNC was injected to solid Ehrlich carcinoma-bearing mice via i.p. (227 mg/kg body weight) 3 times/week during 3 weeks. Irradiation was performed by whole body fractionated exposure to 6Gy, applied in 3 doses of 2 Gy/week over 3 weeks. Biochemical analyses as well as DNA fragmentation were performed. Treatment of solid Ehrlich carcinoma bearing mice with WSGNC combined with γ-radiation led to a significant decrease in the tumor size and weight associated with a significant decrease in mitochondrial enzyme activities, GSH content and SOD activity as well as a significant increase in caspase-3 activity, MDA concentration and DNA fragmentation in cancer tissues. Combined treatment of WSGNC and low dose of γ-radiation showed great amelioration in lipid peroxidation and antioxidant status (GSH content and SOD activity) in liver tissues in animals bearing tumors. It is concluded that WSGNC can be considered as a radio-sensitizer and anticancer modulator, suggesting a possible role in reducing the radiation exposure dose during radiotherapy.

Reaction of tetraethylammonium with the open and closed conformations of the acetylcholine receptor ionic channel complex.

The effect of tetraethylammonium (TEA) bromide on the neurally and iontophoretically evoked endplate current (EPC) of frog sartorius muscle was investigated using voltage-clamp and noise analysis techniques, and its binding to the acetylcholine (ACh) receptor ionic channel complex was determined on the electric organ of Torpedo ocellata. TEA (250-500 microM) produced an initial enhancement followed by a slow decline in the amplitude of the endplate potential and EPC, but caused only depression in the amplitude of the miniature endplate potential and current. In normal ringer's solution, the EPC current-voltage relationship was approximately linear, and the decay phase varied exponentially with membrane potential. Upon addition of 50-100 microM TEA, the current-voltage relationship became markedly nonlinear at hyperpolarized command potentials, and with 250-2000 microM TEA, there was an initial linear segment, an intermediate nonlinear segment, and a region of negative conductance. The onset of nonlinearity was dose-dependent, undergoing a 50 mV shift for a 10-fold increase in TEA concentration. The EPC decay phase was shortened by TEA at hyperpolarized but not depolarized potentials, and remained a single expotential function of time at all concentrations and membrane potentials examined. These actions of TEA were found to be independent of the sequence of polarizations, the length of the conditioning pulse, and the level of the initial holding potential. TEA shifted the power spectrum of ACh noise to higher frequencies and produced a significant depression of single channel conductance. The shortening in the mean channel lifetime agreed closely with the decrease in the EPC decay time constant. At the concentrations tested, TEA did not alter the EPC reversal potential, nor the resting membrane potential, and had little effect on the action potential duration. TEA inhibited the binding of both [3H] ACh (Ki = 200 microM) and [3H]perhydrohistrionicotoxin (Ki = 280 microM) to receptor-rich membranes from the electric organ of Torpedo ocellata, and inhibited the carbamylcholine-activated 22Na+ efflux from these microsacs. It is suggested that TEA reacts with the nicotinic ACh-receptor as well as its ion channel; the voltage-dependent actions are associated with blockade of the ion channel. The results are compatible with a kinetic model in which TEA first binds to the closed conformation of the receptor-ionicchannel complex to produce a voltage-depdndent depression of endplate conductance and sudsequently to its open conformation, giving rise to the shortening in the EPC decay and mean channel lifetime.

alpha-Phenyl-beta-(3,4-dimethoxy)phenethylamines: novel inhibitors of choline acetyltransferase from Torpedo electric organ.

Some derivatives of alpha-phenyl-beta-(3,4-dimethoxy)phenethylamine that might bear a certain conformational resemblance to choline were prepared. The in vitro inhibition of choline acetyltransferase from Torpedo electric organ was investigated. These compounds gave variable degrees of inhibition; the most potent inhibitor was, N,N,N,-trimethyl-alpha-phenyl-beta-(3,4-dimethoxy)phenethylammonium++ + iodide, with an I50 of 1.3 X 10(-5) M. The inhibition of choline acetyltransferase from Spodoptera littoralis larval brains was also determined for comparative study. The aforementioned compound has an I50 of 9 X 10(-6) M on choline acetyltransferase from this source.

Interactions of acetylcholine receptors with organic mercury compounds.

Micromolar concentrations of methylmercury and several organic mercury fungicides were found to block binding of [3H]acetylcholine (ACh) to the ACh-receptor of the electric organ of the electric ray, Torpedo ocellata. The same compounds had little or no effect on the catalytic activity of ACh-esterase of the same tissue. [14C]Methyl-mercury bound to the purified ACh-receptor with high affinity (Kd=7micrometer) and there were 6.5 +/- 0.5 binding sites for each ACh-binding site. Binding of methylmercury was highly cooperative with a Hill coefficient of 2.6. This binding was irreversible by redialysis in methylmercury - free medium, however, the bound [14C]methylmercury was easily displaced from the receptor protein with micrometer concentrations of BAL or penicillamine. Methylmercury also blocked binding of [3H] nicotine and [3H]pilocarpine to the nicotinic and muscarinic ACh-receptors of the rat brain, respectively. The data suggest that the ACh-receptor may be a target for methylmercury and other organic mercury compounds.

Evaluation of radionuclide concentrations and associated radiological hazard indexes in building materials used in Egypt.

Radionuclide concentrations of ²²6Ra, ²³²Th and 4°K in different types of building materials used in Egypt were measured using gamma-ray spectroscopy. The results showed relatively moderate radionuclide concentrations for all samples except granite, which showed extremely high concentrations of 78.75 ± 2.36, 2.82 ± 0.11 and 2.37 ± 0.07 kBq kg⁻¹ for ²²6Ra, ²³²Th and 4°K, respectively. The radiological hazard indexes of radium equivalent activity (Raeq), external hazard index (Hex) and internal hazard index (Hin), due to the presence of those radionuclides in the investigated building materials, were calculated. The released radon from the selected samples was measured using the AlphaGUARD radon monitor in order to use its value to calculate the radon emanation coefficient and the radon exhalation rate. The alpha equivalent dose (dose from indoor radon generated from building materials) was calculated using the measured values of the radium concentration and the radon emanation coefficient.

Styrene N-vinylpyrrolidone metal-nanocomposites as antibacterial coatings against Sulfate Reducing Bacteria.

Copolymer of styrene, and vinylpyrrolidone was prepared by various techniques. Different nanometals and nanometal oxides were added into the copolymer as antimicrobial agents against Sulfate Reducing Bacteria (SRB). The nanocomposite chemical structure was confirmed by using FTIR, (1)H NMR spectroscopy and thermogravimetric analysis (TGA). The biocidal action of these nanocomposites against the SRB was detected using sulfide determination method in Postgate medium B. The data indicated that the nanocomposites had an inhibitory effect on the growth of SRB and reduced the bacterial corrosion rate of mild steel coupons. The prepared nanocomposites have high inhibition efficiency when applied as coatings and show less efficiency when applied as solids or solution into SRB medium. The copolymer and its nanocomposites effectively reduced the total corrosion rate as determined by total weight loss method.

Human endometrial nuclear estrogen receptors among Norplant implant users.

Twenty-four parous women were included in this study. Sixteen cases were using the Norplant implant contraceptive system for more than 6 months (Group A) while eight cases served as matched controls in the secretory phase (Group B). Norplant implant users belonged to one of two equal subgroups according to whether they experienced regular menstrual bleeding (Subgroup A1) or prolonged episodes of amenorrhoea (Subgroup A2). Endometrial samples were processed for nuclear oestrogen receptor assay and for evaluation of the receptor's binding affinity to oestrogen. The results showed marked reduction in endometrial nuclear oestrogen receptors in Norplant users compared with controls as the majority of users had undetectable receptor levels. This down-regulation effect was significantly more pronounced among women with prolonged episodes of amenorrhoea. The affinity section of the study revealed no significant differences between groups or subgroups probably due to the small number of subjects with detectable receptor concentrations for comparison. These data may help in the understanding of contraceptive mechanisms and menstrual associated problems, and in the development of therapeutic measures.

Gossypol as an inducer or inhibitor in Spodoptera littoralis larvae.

Gossypol occurs naturally in the pigment glands in cotton. It has a role in protecting cotton plants from insect pests such as bollworms, yet it was not toxic to the cotton leafworm larvae Spodoptera littoralis up to 2-5% concentration in artificial diet or at 125 micrograms/ larva by topical application. The compound inhibited protease and lipid peroxidase activities in larvae with in vitro I50 values of 1.5 X 10(-3)M, and 4.4 X 10(-4)M respectively. When gossypol was fed to Spodoptera larvae, it stimulated the microsomal N-demethylase in vitro. This inductive effect was time-dependent similar to that of phenobarbital. Gossypol stimulates ATPase at lower concentrations and inhibited it at higher concentrations. The I50 for mitochondrial ATPase was 1.7 X 10(-4)M, while the corresponding values for DDT and fenvalerate were 1.1 X 10(-4)M and 7.0 X 10(-4)M respectively. Gossypol at 1.5% concentration in the diet reduced the larval weight to 50% of the control within two days, and increased the duration of each larval stage. The number of eggs and their hatchability was seriously decreased in larvae treated for three consecutive generations. Such an effect can be attributed to the ability of gossypol to interfere with protein bio-synthesis.

Biochemical interactions of carbamates and ecothiophate with the activated conformation of nicotinic acetylcholine receptor.

Purified Torpedo nobiliana electric organ acetylcholine receptor (AChR) was reconstituted into membranes containing natural phospholipids supplemented with cholesterol (25% w/w). The reconstituted system facilitates the study of the effects of drugs on the regulation of the AChR channel complex under both resting and carbachol (carb)-stimulated conditions. Neostigmine (Neo) was the only carbamate to induce activation of [3-H]-phencyclidine ([3-H]-PCP) binding to the channel sites, acting as a weak agonist. The activation of [3-H]-PCP binding is dependent upon the nature of the reconstituted systems, with carb/Neo activation ratios of 8, 3, and 1 for the intact purified AChR vesicles fraction (PVF), the PVF reconstituted in phospholipid/cholesterol (CRPVF), and the PVF reconstituted in phospholipid (RPVF), respectively. The carbamates Neo, physostigmine (Physo), and pyridostigmine (Pyrido) inhibited carb-activated [3-H]-PCP binding with Ki values of 10, 20, and 1,600 microM, respectively. The inhibition was mixed competitive-noncompetitive in nature. The characteristic response of CRPVF to carb-stimulated [22-Na] influx was inhibited by the three carbamates, with IC-50 values of 6, 50, and 1,000 microM for Neo, Physo, and Pyrido, respectively. The quaternary ammonium organophosphate ecothiophate (Eco) inhibited carb-stimulated [22-Na] influx with potency similar to that of Neo. Preincubation of AChR preparation with the carbamates and ecothiophate caused a reduction in the binding of [125-I]-alpha-bungarotoxin ([125-I]-alpha-BGT) with the following decreasing order of potency: Neo less than Physo less than Eco less than Pyrido. Calcium has a direct modulatory role on the time-course inhibition of [125-I]-alpha-BGT binding by these drugs. While we observed a high potency of Neo and Physo in inhibiting [125-I]-alpha-BGT binding, it was undetectable for the carbamate insecticide 2-methyl-2-(methylthio)propionaldehyde-O-(methylcarbamoyl)oxime (aldicarb). These data suggest that the potent anticholinesterase carbamate agents interact differently with the AChR and its ionic channel. Their interactions with the nicotinic AChR channel system can be described as (a) weakly agonist, (b) directly acting on the open conformation of the channel, and (c) blocking the AChR-binding sites.

Structure and synthesis of a potent glutamate receptor antagonist in wasp venom.

A low molecular weight toxin isolated from the venom of the digger wasp Philanthus triangulum, first noted by T. Piek, is a potent antagonist of transmission at quisqualate-sensitive glutamate synapses of locust leg muscle. This philanthotoxin 433 (PTX-433) has been purified, chemically characterized, and subsequently synthesized along with two closely related analogues. It has a butyryl/tyrosyl/spermine sequence and a molecular weight of 435. Its two analogues, PTX-343 and PTX-334 (the numerals denoting the number of methylenes between the amino groups of the spermine moiety), are also active on the glutamate synapse of the locust leg muscle; PTX-334 was more potent and PTX-343 was less potent than the natural toxin. Such chemicals are useful for studying, labeling, and purifying glutamate receptors and may become models for an additional class of therapeutic drugs and possibly insecticides.

Acetylcholine receptor and ionic channel of Torpedo electroplax: binding of perhydrohistrionicotoxin to membrane and solubilized preparations.

The electric organ of the ray, Torpedo ocellata, can serve as a source for both the acetylcholine (ACh) receptor and its ionic channel. The two entities were identified by their specific binding of [3H]ACh and [3H]perhydrohistrionicotoxin ([3H]H12-HTX), respectively. Binding of [3H]H12-HTX was inhibited by certain drugs and toxins, e.g., histrionicotoxin (HTX), amantadine, and tetraethylammonium (TEA) ions at concentrations that did not inhibit [3H]ACh binding. However, the specific carbamoylcholine-induced 22Na efflux from microsacs from the electric organ membranes was blocked by inhibitors of either the receptor or its ionic channel. The ionic channel had the properties of a protein as judged by heat sensitivity and the inhibition of [3H]H12-HTX binding, after incubation of the electric organ membranes with protein reagents such as p-chloromercuribenzenesulfonic acid (PCMBS) or N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ). The "binding" of [3H]H12-HTX at 4 X 10(-8) M to lipids in the microsacs was 12% of the total binding to intact microsacs and was nonsaturable and insensitive to heat or specific drugs. After solubilization with cholate, the [3H]H12-HTX binding subunits retained the same affinities for toxins and drugs. The Kd for [3H]H12-HTX was 3 X 10(-7) M. The majority of the ionic channel could be separated from the ACh receptors in the cholate extract by incubation with ACh-receptor affinity gel and ACh-receptor antibodies. The ACh receptor purified by this affinity gel contained only a few active ionic channel units as judged by low levels of high affinity binding of [3H]H12-HTX. On the other hand, after solubilization with Triton X-100, all the ionic channel molecules were either separated or denatured so that the purified ACh receptor did not exhibit high affinity binding for [3H]H12-HTX.

Further toxicologic studies with commercial and candidate flame retardant chemicals. Part II.

A number of commercial and candidate flame retardants were studied with regard to their toxicity to goldfish, inhibition of cholinesterase, inhibition of acetyl choline binding to its receptor and insecticidal properties. Several of the flame retardants were notably toxic to fish. Some of the compounds showed modest inhibition of cholinesterase and/or microsomal oxidases, but none inhibited acetyl choline receptor binding. Whereas several of the flame retardants showed little or no insecticidal properties when added alone to a housefly diet, piperonyl butoxide greatly synergised their toxicity to houseflies.