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Tolerance to amphetamine anorexia: role of learning versus body weight settling point.

Three experiments were conducted to clarify the role of learning and body weight settling point in the development of tolerance to amphetamine anorexia. In the first experiment, rats that had become tolerant to the suppressant effect of amphetamine on milk intake were anorexic when subsequently offered other foods or water during a transfer test. These results appear to support a conditioning interpretation, which predicts a loss of tolerance when cues associated with drug administration are altered. Subsequent experiments examined the long-term effect of changing diets. In Experiments 2 and 3, rats made tolerant with milk as the diet showed prolonged anorexia when switched to Purina pellets or slightly bitter milk. However, when switched from pellets or adulterated milk to milk, tolerant rats were anorexic only 1 day and then ingested significantly more of the new diet. These results are inconsistent with a conditioning interpretation. Further analysis revealed that tolerant rats maintained their weight below the level of saline controls despite the recovery of food intake. Moreover, the level at which they maintained their weight varied with the palatability of the diet. These results suggest that amphetamine lowers the settling point for body weight and that tolerance does not develop to this effect (cf. Stunkard, 1981). From this perspective, the reinstatement of prolonged anorexia when apparently tolerant rats were switched to a less palatable diet can be understood as an attempt to attain a lower weight level.

Animals↗

Regulation of biotechnology in the United States and Canada.

The regulation of biotechnology in the United States and Canada is based on principles that reflect respect for the new technology, yet also recognize that most traditional approaches to regulation, employing sound science and common sense, still apply. Four specific principles form the framework on which regulatory schemes are based: (1) the products of biotechnology will not differ fundamentally from unmodified organisms or from conventional products; (2) the product rather than the process shall be regulated; (3) regulation should be based on the end use of the product and will be conducted on a case-by-case basis; and (4) the existing laws provide adequate authority for regulating the products of biotechnology. This report summarizes the regulatory approaches taken in various organisms and products. Special emphasis is given to: (1) issuance of entry permits for genetically-engineered plants and micro-organisms; (2) licensing of genetically-engineered veterinary biological products; and (3) permits for movement and release into the environment. A three-category classification system is described for dealing with hybridomas and recombinant-derived products, based on their biological characteristics and safety concerns. Categories range from relatively simple inactivated recombinant animal vaccines to products using live vectors to carry recombinant-derived foreign genes that code for immunizing antigens and/or other immune stimulants. This paper stresses that few fields of contemporary science and technology hold forth more possibilities and greater expectations than biotechnology. It is therefore of utmost importance that animal health officials and scientists ensure that the products of biotechnology will not cause or transmit infectious disease, adversely affect the environment or adulterate food products.

Animals↗

Isolation rearing impairs the reinforcing efficacy of intravenous cocaine or intra-accumbens d-amphetamine: impaired response to intra-accumbens D1 and D2/D3 dopamine receptor antagonists.

Male Lister hooded rats were raised from weaning either alone (isolation reared) or in groups of five (socially reared controls). At 5 months of age, bilateral guide cannulae were implanted within the nucleus accumbens, and experiments began. The effect of isolation rearing upon the reinforcing efficacy of the intravenous self-administration of cocaine (experiment 1), or the bilateral intra-accumbens self-administration of d-amphetamine (experiment 2) was assessed. Self-administration was made contingent upon the acquisition of a novel lever-pressing response. Two identical levers were available within each operant chamber. Responding on one lever resulted in the delivery of drug (experiment 1: cocaine, 1.5 mg/kg per infusion; experiment 2: d-amphetamine, 0.25 micrograms/side), responding on the second, control lever was recorded but had no programmed consequences. Animals were not "primed" with noncontingent infusions at any time. For experiment 1, animals received intra-accumbens infusions of the D1 dopamine receptor antagonist SCH-23390, or the D2 dopamine receptor antagonist sulpiride over two test sessions. Within each session, animals received a cumulative series of doses of each dopamine receptor antagonist. A validation group received doses of each antagonist according to more conventional methods (one dose per session). In either case, intra-accumbens infusions of SCH-23390 or sulpiride enhanced the rate of the self-administration of cocaine in socially reared controls. However, isolation rearing impaired this response to intra-accumbens infusions of the dopamine receptor antagonists. Experiment 2a examined the acquisition of the intra-accumbens self-administration of d-amphetamine. Socially reared controls acquired readily a selective response upon the drug lever. However, isolation reared animals acquired a selective response at a greatly retarded rate. In experiment 2b, a full d-amphetamine dose-response function was examined. Isolation rearing impaired the response to a range of doses of d-amphetamine. In experiment 2c, the infusate (1 microgram d-amphetamine per infusion) was adulterated with either SCH-23390 or sulpiride. Adulteration with either dopamine receptor antagonist enhanced the rate of response by socially reared controls. Isolation rearing impaired this response to SCH-23390, and blocked the response to sulpiride. These data are discussed in relation to the functioning of cortico-limbic-striatal systems, with particular reference to the mesoaccumbens dopamine projection.

Animals↗

Aminopyrine-induced blood dyscrasias--still a problem in many parts of the world.

The aminopyrines were introduced about a century ago as analgesics and antipyretics, but it was not until the 1930s that agranulocytosis, their major adverse reaction, was recognized. In patients receiving aminopyrines, although agranulocytosis is the most frequent blood dyscrasia, aplastic anaemia has also been reported. For these reasons, these drugs have been banned or withdrawn from the market in most industrialized countries. However, aminopyrines are still available in many parts of the world, including the Far East, Africa and Latin and South America and can be found as adulterants in some 'herbal' patent preparations. Their continuing availability in the Far East may have contributed in part to the higher incidence of aplastic anaemia, compared with the West.

Journal Article↗

Compulsory random drug testing of prisoners in England and Wales: design flaws in the system.

The Home Office has recently introduced compulsory testing of prisoners in England and Wales for drug abuse. From 1996 all prisons in the UK will be involved. Urine samples from approximately 10% of the prison population will be collected each month. The method of drug analysis selected by the Home Office is fast and economical but readily prone to interference from common substances giving false results. An elaborate procedure has therefore been evolved including a rigorous personal search of the prisoner to prevent sample adulteration. The definitive test gas chromotography - mass spectrometry (GC-MS), is more expensive but is resistant to sample adulteration, and currently all positive samples are confirmed by this method. In view of the proportion of samples that have tested positive, the extent of the unknown number of false negatives, and the possible rejection of the collection protocol by prisoners, savings could be made if the method of analysis employed in the first instance was GC-MS. This paper illustrates the inaccuracies produced in an assay technique similar to that used by the Home Office when urine is contaminated by simple, commonly available substances.

Journal Article↗

The routine profiling of forensic heroin samples.

A method for the routine profiling of illicit heroin samples received in casework has been developed which depends on simple and straightforward sample pretreatment, followed by gas chromatography on a capillary column using flame-ionization detection. The factors affecting the choice of each aspect of the procedure are discussed, as are the statistical data for sampling and the chromatography. Components of illicit heroin derived from opium and other adulterants have been identified. The significance of data from samples examined in 1986 is discussed.

Chromatography, Gas↗

[Authentication of Zanthexylum bungeanum Maxin population and adulterants by analysis of rDNA ITS sequences].

AIM: To study the difference of rDNA ITS sequences between Zanthexylum bungeanum populations and their adulterants in main habitants of China so as to provide molecular markers for identifying Zanthexylum bungeanum populations against adulterants. METHODS: rDNA ITS regions (including ITS-1, 5.8S and ITS-2) of 7 populations of Zanthexylum bungeanum which are separate located in Gansu, Shanxi, Sichuan, Hebei provinces, and 3 adulterants were sequenced by PCR products sequencing method or clone sequencing method. RESULTS: The sequences of rDNA ITS region of Zanthexylum bungeanum were reported for the first time, and the sequences of ITS region ranged from 619 to 620 bp, and the length difference amoung Zanthexylum bungeanum and their adulterants is 4 bp. There are 15 variable sites, 12 informative sites and 3 authenticable sites among Zanthexylum bungeanum populations. The difference of rDNA ITS regions amoung Zanthexylum bungeanum and their adulterants is obvious, the number of variable sites is 71. CONCLUSION: The difference of rDNA ITS sequences can be used to authenticate accurately the populations of Zanthexylum bungeanum and their adulterants. These populations of Z. bungeanum which have close relationship always distribute in near geographic areas. The characteristics of rDNA ITS sequence can be used as good markers for authenticating Zanthexylum bungeanum populations form their adulterants.

Base Sequence↗

Drug eruptions from phenylbutazone in Jamu.

Drug eruptions from indeginous medicine is often difficult to diagnosis and confirm. It is known that a number of these now supplied by bomohs and Chinese sinsehs contain known drugs and are dispensed as tablets and capsules. We report 3 cases of adverse drug eruption to "Jamu", a Malay herb. A particular brand, "Jamu Indonesia, Toko Air Pancur", from Johor Bahru, Malaysia, is especially recommended for "sakit pinggang" or backache. The cases occurred between January and February 1985, and all had taken brown kidney shaped tablets. The adverse reactions were moderately severe. Two had erythroderma with hepatitis, and one, Steven Johnson Syndrome. Analysis of this jamu for analgesics led to the discovery of adulteration with phenylbutazone and diazepam. Records from local cases from 1974-1984 showed that 8 other patients, all Chinese had adverse cutaneous eruptions from phenylbutazone, oxybutazone and propyphenazone. The skin manifestations were erythroderma (2 cases), vasculitis (2 cases) and toxic epidermal necrolysis (4 cases). Those with toxic epidermal necrolysis had 100% mortality.

Adult↗

Epidemiology of MDMA and associated club drugs in the Seattle area.

Club drug use, MDMA in particular, appeared as a growing problem in the Seattle area in the late 1990s. To understand more about the patterns of MDMA use and to evaluate the current state of MDMA use, multiple data sources were examined. The seven data sources utilized included local community-based club drug surveys collected in 2003 at raves, treatment agencies, and gay-oriented bars and sex clubs; school surveys (collected in 2002); mortality data (deaths between 2000 and 2002); data from the sexually transmitted disease clinic (October 2002 to October 2003); focus groups (2003) with men who have sex with men; emergency department drug mentions (1995 to 2002); and drug treatment admissions (1999 to 2003). Taken together, these data indicate moderate levels of MDMA use and relatively low levels of mortality and acute morbidity. However, there are several areas of concern including possible mental health effects and high levels of suspected adulteration of MDMA. Some data point to a relationship between MDMA use and risky behaviors including unprotected sex. Implications for prevention, intervention, and treatment are discussed.

Adolescent↗

Laboratory confirmation of scopolamine co-intoxication in patients using tainted heroin.

BACKGROUND: First described in 1995, at least 325 patients with a history of heroin use have since required emergency medical evaluation in several eastern US cities, because of an anticholinergic toxidrome following use of heroin. This co-intoxication has been alleged to result from an atropine-like compound. We report the clinical findings and laboratory analysis of one of several individuals who presented to our Emergency Department during this epidemic. CASE REPORT: A 23-year-old male was one of 3 patients brought to the Emergency Department due to agitated behavior after insufflating heroin. Following physical and chemical restraint, vital signs were pulse 134 bpm, BP 160/90 mm Hg, RR 24/min, and T 37.3 degrees C. Physical examination was remarkable for dilated pupils 8-9 mm without nystagmus, along with dry mouth, decreased bowel sounds, and flushed dry skin. A bladder catheter was placed and 500 mL of urine was obtained. Electrocardiogram revealed sinus tachycardia only. Additional sedation was required for 12 hours until normal mental status returned. A small sample of the "heroin" used was obtained and analyzed. Scopolamine was confirmed by gas chromatography-mass spectrometry. Further evidence of scopolamine intoxication was supported by identifying scopolamine in the urine of this patient. CONCLUSION: Gas chromatography-mass spectrometry revealed scopolamine to be the cause of anticholinergic findings in a patient following use of tainted heroin. It is unclear whether scopolamine is an adulterant or contaminant in this heroin. Patients with anticholinergic findings following use of heroin may be co-intoxicated with scopolamine.

Adult↗

[Identification of notoginseng(Panax notoginseng) and its adulterants using DNA sequencing].

OBJECTIVE: To analyze the nuclear ribosomal RNA small subunit (18S rRNA) and chloroplast matK gene sequence of notoginseng (Panax notoginseng) in order to provide molecular evidence for its genuine origin identification. METHODS: To sequence 18S rRNA and matK genes of Panax notoginseng and its four adulterants such as P. japonicus, Curcuma phaeocaulis, C. wenyujin, C. kwangsiensis using PCR direct sequencing and to detect their variation of sequences. RESULTS: The sequence length of notoginseng and its adulterants is 1809-1811 bp for 18S rRNA gene and 1259-1548 bp for matK gene, respectively. Multiple sequence alignment shows that there are much sequence variation between notoginseng and its adulterants. CONCLUSION: DNA sequencing is an accurate and reliable method in origin identification of the genuine notoginseng.

Amino Acid Sequence↗

Validation of the Cozart Amphetamine Microplate EIA for the analysis of amphetamines in oral fluid.

The purpose of this study was to determine the performance characteristics of the Cozart Amphetamine Microplate EIA for detecting amphetamine in oral fluid. Oral fluid samples were collected using the Cozart RapiScan Collection System from 135 volunteer donors from drug treatment clinics. A further 35 oral fluid samples were collected from volunteer donors who were not drug users. The samples were analyzed in the laboratory using the Cozart Amphetamine Microplate EIA and confirmed using gas chromatography-mass spectrometry (GC-MS). The samples were stored frozen until analysis by GC-MS. The intra-assay precision for the Cozart Amphetamine Microplate EIA for amphetamine in oral fluid over forty assays was 2.74-7.1% CV (within assay) and 3.4-7.0% CV (within day). A total of 78 samples were positive for various amphetamines and related designer drugs. The Cozart Amphetamine Microplate EIA, using a cutoff of 45 ng/ml amphetamine equivalents in neat oral fluid, had a sensitivity of 91.7+/-3.3% and a specificity of 95.9+/-1.9% versus GC-MS using a cutoff of 30 ng/ml. A series of potential adulterants of oral fluid were evaluated and shown not to alter the outcome of the test result.

Amphetamine-Related Disorders↗