Treating Alzheimer''s disease with cholinergic drugs, Part 2

PURPOSE: We sought to replicate and extend a previously reported positive association between juvenile myoclonic epilepsy and HLA-DR13. METHODS: Ninety-three subjects with juvenile myoclonic epilepsy and 93 normal blood donors, entirely of white origin with their families mostly of French extraction, underwent DNA-based HLA-DR13 and DQB6 typing. RESULTS: None of the investigated alleles or combination of alleles (DRB1*1301-DQB1*0603 or DRB1*1302-DQB1*0604) showed a significant difference between patients and controls. CONCLUSIONS: Unlike previously reported positive association, in this population, there is no evidence that susceptibility to juvenile myoclonic epilepsy is associated with HLA-DR13.     

Interactions between 192-IgG saporin and intraseptal cholinergic and GABAergic drugs: Role of cholinergic medial septal neurons in spatial working memory.

Rats were administered 192-IgG saporin (SAP) or vehicle into the medial septum-vertical limb of the diagonal band (MS-vDB). Starting 1 week later, the effects of intraseptal scopolamine, oxotremorine, and muscimol were tested in a T-maze alternation task. Choice accuracy in the absence of infusions did not differ between control and SAP-treated rats. Intraseptal scopolamine or muscimol impaired the choice accuracy of SAP-treated but not control rats. Oxotremorine impaired accuracy similarly in control and SAP-treated rats. The enhanced effects of scopolamine and muscimol produced by SAP are consistent with the hypothesis that cholinergic MS-vDB neurons are used in spatial working memory. The finding that SAP alone did not alter choice accuracy provides further evidence that cholinergic MS-vDB neurons are not necessary for spatial working memory. Thus, cholinergic MS-vDB neurons are involved in but not necessary for spatial working memory. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Central cholinergic nervous system and cholinergic agents

Central cholinergic nervous system play important role in many physiological and behavioral functions in humans. The activity of the cholinergic nervous system depends upon the production and fate of acetylcholine and all compounds influenced its biosynthesis, storage, release, hydrolysis, interaction with different subtypes of cholinergic receptors, etc., there are very important drugs and therapeutics. This paper summarizes current views on many compounds which can interact with different parts of central cholinergic nervous system.     

The evaluation of sizing accuracy of particle counters for parenteral drugs

Our evaluation of electronic liquid-borne particle counter systems has shown that, for accurate measurement of particulate matter in injections, the half count values of voltage thresholds from the particle counter itself should be used in the calibration for the particle sizes being evaluated. The manual method which uses the half count values in the USP XXIII<788> was improved, and the validity of our calibration method was supported by the results based on the ratio test, at 10 microns to those obtained at 15 microns is between 1.5 and 3.5, as per the Seventh Supplement of USP XXII <788>. Additionally, computer-based systems with automated calibration routines which solve the approximate Gaussian distribution of calibration particles have advantages. For the proper determination of the sizing accuracy of a particle counter, criteria of the ratio test at 10 microns and 15 microns as per the Seventh Supplement of USP XXII <788> should be applied at all critical particle sizes.     

An international evaluation of the cancer-preventive potential of nonsteroidal anti-inflammatory drugs

The most common complication in children with varicella is cutaneous superimposed infection with pyogenic bacteria. Group A beta-hemolytic streptococci, which are known to cause life-threatening infections in both previously healthy children and those with underlying diseases, are the most frequently associated pathogens. A newly recognized disease, called streptococcal toxic shock syndrome, is associated with severe morbidity and mortality. We report a 3-year-old boy with a diagnosis of this syndrome who presented with increasing fever, vomiting, and lethargy 7 days after the development of a classic varicella skin lesion. In spite of aggressive fluid supply, administration of inotropic agents, and cardiopulmonary resuscitation, a rapidly deteriorating clinical course led to death 4 hours after hospitalization. This is the first report of this association in Taiwan. Pediatricians evaluating children with varicella must be mindful of the potential for Group A beta-hemolytic streptococcal infection.     

The evaluation of action of anesthetic drugs: Xylodont and Mepidont

The aim of the study was to establish the quality of the therapeutical action- of two local anaesthetics Xylodont and Mepidont, produced by MOLTENI pharmaceutical firm. The investigation was performed in 199 patients of our clinic undergoing teeth extractions or other small surgical procedures. The following data were specified in a questionnaire: name of a drug, applied doses, range of anaesthetic effect, kind and duration of a surgical procedure. We also paid the very attention to the systemic side effects of the used drugs. The significant number of surgical procedures (96, 5%) were painless. The application of additional drug was necessary only in few cases. The obtained results show that the tested anaesthetics Xylodont and Mepidont are safe and effectively acting drugs suitable for local anaesthesia.     

Place of in vitro models in preclinical evaluation of anticancer drugs

In vitro models have been intensively developed for several years for selecting new anticancer agents. The National Cancer Institute has even chosen as a primary screen of new molecules a panel of 60 human tumor cell lines. However, it may seem hazardous to rely too much on in vitro models for the discovery and selection of new anticancer drugs: (1 because no metabolism of the compounds occurs in cell culture; (2 because an in vitro cell line cannot be representative of an in situ tumor cell population; (3 because antiproliferative activity is only part of antitumor activity; (4 because the toxicologic properties of the molecules are not taken into account by in vitro systems; (5 because cell cultures do not allow any selectivity study between tumor cells and normal cells. With examples drawn from three different therapeutic classes, anthracyclines, taxoids and camptothecin derivatives, we show that in vitro tests are insufficiently predictive of antitumor potential. The excess of confidence allowed to these models may lead to premature decisions which are not after that justified by clinical trials.     

Drug delivery during pregnancy: evaluation in vitro of new drugs

Indications for the treatment of the pregnant woman fall into three general categories: mother and infant require treatment, only the mother should be treated, or only the infant. Directing therapy towards the affected subject is an important aspect of good care, although it is not the only one. It is argued that a rational selection of the appropriate drug can be made without endangering mother or infant, with the aid of select laboratory investigations, including placental perfusion, and a knowledge of placental physiology. Examples are presented to support this contention. The intra-amniotic administration of drugs is briefly discussed. A plea is made to develop drugs that are designed specifically for use during pregnancy.     

Behavioural phenotyping of transgenic mice.

This paper reviews the current work on mouse genetics, brain, and behaviour in my laboratory. It starts with an historical account of our research and shows how certain research themes, such as olfaction, learning, social behaviour, and environmental effects in rodents have led to our current research on behavioural phenotyping of inbred, mutant, knockout, and transgenic mice. We are concerned with finding neural and behavioural sequelae to genetic manipulations in mice and use a battery of tests to detect behaviours that are altered in genetically modified mice. In this way we are working to dissociate neural and behavioural effects of different gene manipulations in mouse models of neurodegenerative diseases. Sensory, motor, cognitive, affective, and social behaviours may all be affected by gene manipulation, thus careful behavioural techniques, with attention to the mice themselves, the apparatus, and procedure, experimenter variables, and environmental effects are necessary in order to determine a reliable and valid mouse behavioural phenotype. As both the genome and the environment have significant effects on the behavioural phenotype, our future research will utilize an epigenetic approach to examine how environmental cues modulate gene expression in the behavioural phenotyping of transgenic mice. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Role of dentate gyrus cells in retention of a radial arm maze task and sensitivity of rats to cholinergic drugs.

Male rats that received bilateral injections of colchicine into 2 rostrocaudal sites showed relatively long-lasting alterations in a previously acquired radial arm maze task and specific destruction of dentate granule cells. Subsequent experiments with cholinergic drugs indicate that physostigmine or nicotine had no effect on number of errors made in the maze, although other signs of cholinergic or pharmacological activity were present. RS-86, an analog of arecoline, decreased errors in colchicine-treated Ss, but effects were associated with signs of parasympathetic overstimulation and behavioral sedation. Pretreatment with scopolamine increased errors in controls but had no effect in colchicine-treated Ss. Colchicine-treated Ss were less sensitive to the motor stimulant effect of scopolamine. Effects appeared to be associated with increased levels of choline acetyltransferase in the hippocampus and a down regulation of muscarinic postsynaptic receptors. Intradentate colchicine may destroy granule cells, leading to compensatory reinnervation of cholinergic nerve terminals having cell bodies in the septum. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Behavioural research in telematics.

Discusses telematics, a new field of behavioral research in Canada that has grown with the technical developments in which computers and telecommunications have been combined. Three domains of behavioral research reflect relationships between humans and the technology and use the evidence and methods of different areas of psychology: (1) interface studies address perception and performance questions, (2) dialog studies focus on cognitive processes, and (3) impact studies investigate social relations and how institutions and individuals are affected by telematics. Studies conducted during the past 5 yrs by the Behavioural Research and Evaluation division of the Department of Communications, Government of Canada, are described in each of these 3 domains. Behavioral research in telematics is expected to be an increasingly important activity in which psychologists may play an active part as the technology disseminates. (French abstract) (47 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The effect of cholinergic drugs on [3H]acetylcholine release from slices of rat hippocampus, striatum and cortex

Slices from rat hippocampus, striatum or cortex were incubated with l mum [3H] choline and following 75 min superfusion with Krebs solution the efflux of radioactivity was measured. The slices were stimulated either electrically (1 Hz) or with 25 mM potassium and the rate constant of the evoked release and the size of the releasable pool were estimated. The spontaneous efflux of radioactivity and the releasable pool but not the rate of evoked release correlated with the reported endogenous ACh content of the 3 areas. Raised potassium released radioactivity at a lower rate but from a larger pool than electrical stimulation from all 3 areas. In all 3 areas atropine alone potentiated while physostigmine, oxotremorine and carbamylcholine decreased the rate of evoked release. This depression was fully antagonized by atropine. The drugs had no effect on the size of the releasable pool. Findings suggest that muscarinic receptors located on cholinergic axons or terminals have a physiological role in the autoregulation of ACh release from these 3 areas.     

Neuropsychiatric adverse effects of antiparkinsonian drugs. Characteristics, evaluation and treatment

Parkinson's disease (PD) is a progressive neurological condition that causes considerable disability in the elderly. Drugs used to treat PD, such as levodopa, offer symptomatic relief but often have neuropsychiatric adverse effects, most prominently psychosis and delirium. Aged patients and those with dementia are particularly vulnerable to these adverse effects. Evaluating PD patients with drug-induced neuropsychiatric adverse effects is made difficult by their complex clinical presentations. The treatment of drug-induced psychosis and delirium begins with manipulating the antiparkinsonian drug regimen, but this frequently worsens motor function. Atypical antipsychotics such as clozapine have been successfully employed to treat the psychosis without worsening the motor disability. Patient intolerance of clozapine therapy has prompted open-label studies with newer agents such as risperidone, remoxipride, zotepine, mianserin and ondansetron.