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A critical evaluation of tetrahydroisoquinoline induced ethanol preference in rats.

It has been reported that certain tetrahydroisoquinoline compounds, especially salsolinol and tetrahydropaveroline (THP) when infused into the lateral ventricle of rats' brains results in increased preference for alcohol solutions. The effect is reported to be long-term, in that animals do not return to baseline drinking even months later. The current report provides a replicatin of the original experiments and also an extension of the work to complete dose-response curves for salsolinol and THP. Generally we have confirmed that rats of the Sprague-Dawley and Long-Evans strains do increase their alcohol intake in response to infused THP or salsolinol and that the effect is long lasting, up to 10 months. Such animals consume less alcohol at concentrations above 20% than below, in contrast to the previous reports where drinking was maintained at high concentrations of alcohol. While the animals will select alcohol in the face of a saccharin choice, they will not drink alcohol adulterated with quinine. We have failed to observe signs of dependence or withdrawal by these techniques and suggest that the original reports of these signs may have been a result of cellular damage caused by the long-term infusions. Additionally we have carried out extensive dose-response experiments with both salsolinol and THP. Doses of THP of 104 nmoles/day were inhibitory to alcohol drinking. We conclude that these compounds do shift these animals preference for alcohol relatively permanently, but not to the point of gross intoxication nor into the highly aversive range of alcohol concentration. We cannot confirm the reports that salsolinol or THP produce withdrawal symptoms when infused.

Alcohol Drinking↗

Laboratory detection of marijuana use. Experience with a photometric immunoassay to measure urinary cannabinoids.

The urinary excretion of cannabinoids was determined using a photometric immunoassay technique among adolescents and young adults who had an abrupt and closely supervised cessation of drug use on entering a strict rehabilitation program. No falsely positive urine test results were encountered among 70 persons admitted consecutively to the program. Among five subjects with a history of chronic, heavy marijuana use (approximately 56 g/mo [approximately 2 oz/mo]), urinary cannabinoids were detected for an average of 13 days (range, nine to 25 days), following cessation of use. Among four subjects with a history of moderate marijuana use (approximately 28 g/mo [approximately 1 oz/mo]), test results remained positive for an average of 4.7 days (range, two to eight days). Test results were negative 48 hours after cessation in two subjects with a history of infrequent use (less than 7 g/mo [0.25 oz/mo]), who had smoked marijuana within the preceding two days. The specificity of the method for detecting recent marijuana use appears excellent; the sensitivity depends on the potency of the cannabis preparation, the time of last use, the frequency of previous use, and the specific gravity of the urine specimen. On the basis of this preliminary experience, positive test results for more than eight consecutive days suggest either surreptitious continued use or previous chronic, heavy use in a newly abstinent person. Purposeful adulteration of known-positive urine specimens with bleach, blood, vinegar, salt, and liquid soap produced falsely negative results. Unless samples are collected under direct observation, urine color, temperature, specific gravity, and dipstick tests for blood and pH should be recorded.

Adolescent↗

Interpretation of sham feeding data: curve-shift studies.

We explored the possibility that quantitative analysis of the relationship between sucrose concentration and sham intake differentiated how various treatments affected the intake of sweet solutions. Rats were sham fed sucrose solutions varying in concentration from 0.03125 to 1.5 M. Under different treatment conditions, intake concentration functions were generated that plotted amount sham fed against sucrose concentration. Sucrose concentration that yielded 50% maximal sham intake were calculated to indicate the position of the concentration-intake function on the x-axis. Quinine adulteration of sucrose solutions and injection of 0.5 mg/kg i.p. of the dopamine antagonist pimozide reduced sham intake and shifted the concentration-intake function to the right. Lithium chloride (60 mg/kg i.p.) injected 30 min before sham feeding, a reduction of food deprivation from 18 to 6 h before sham feeding, and 6 micrograms/kg cholecystokinin octapeptide reduced sham intake equivalent amounts but did not shift the concentration-intake functions along the x-axis. The data indicate that of several factors that reduce sham feeding, only some also shift the position of concentration-intake curves, and these curve shifts may identify intake changes mediated by alterations in the processing of the taste input.

Animals↗

Liquid injectable silicone: a review of its history, immunology, technical considerations, complications, and potential.

For over five decades, liquid injectable silicone has been used for soft-tissue augmentation. Its use has engendered polarized reactions from the public and from physicians. Adherents of this product tout its inert chemical structure, ease of use, and low cost. Opponents of silicone cite the many reports of complications, including granulomas, pneumonitis, and disfiguring nodules that are usually the result of large-volume injection and/or industrial grade or adulterated material. Unfortunately, as recently as 2006, reports in The New England Journal of Medicine and The New York Times failed to distinguish between the use of medical grade silicone injected by physicians trained in the microdroplet technique and the use of large volumes of industrial grade products injected by unlicensed or unskilled practitioners. This review separates these two markedly different procedures. In addition, it provides an overview of the chemical structure of liquid injectable silicone, the immunology of silicone reactions within the body, treatment for cosmetic improvement including human immunodeficiency virus lipoatrophy, technical considerations for its injection, complications seen following injections, and some considerations of the future for silicone soft-tissue augmentation.

Animals↗

Analysis of products suspected of containing Aristolochia or Asarum species.

Aristolochia species have been administered by those trained in traditional Chinese medicine (TCM) for centuries. After determining Aristolochia fangchi was an adulterant that caused death due to renal failure in a number of patients at a Belgian weight loss clinic, many countries took steps to regulate products containing Aristolochia fangchi as well as other Aristolochia species. The US FDA issued a Consumer Advisory 'advising consumers to stop using any products that may likely contain aristolochic acid'. The Aristolochia and Asarum genera both have been found to contain aristolochic acids. A number of websites have been found from which individuals can order products containing either Aristolochia or Asarum as an ingredient through US merchants. We purchased 25 products from such sites and analyzed them for the presence of aristolochic acid I and II by HPLC with PDA. Six of the products contained detectable amounts of I and II.

Animals↗

Nodular regenerative hyperplasia of the liver associated with the toxic oil syndrome: report of five cases.

Nodular regenerative hyperplasia of the liver developed in five patients who had the toxic oil syndrome caused by ingestion of adulterated cooking oil. This hepatic complication was detected from 19 to 37 months (mean-2.5 years) after the onset of the toxic oil syndrome. Nodular regenerative hyperplasia was asymptomatic, although all patients had persistently abnormal liver function. Hepatomegaly was present in four cases, mild jaundice in three and signs of portal hypertension in two. Pathogenesis of nodular regenerative hyperplasia in toxic oil syndrome is unknown, but probably microcirculatory disturbances within the liver might have played a role. Fibrosis in Zone 3, sinusoidal dilatation and occasionally intralobular hemorrhage were seen in three cases; in one of them, characteristic lesions of veno-occlusive disease were also present. In another case, endarteritis changes of hepatic arterioles were evident.

Adolescent↗

Authentication of traditional Chinese medicine using infrared spectroscopy: distinguishing between ginseng and its morphological fakes.

The quality of pharmaceutical products such as ginseng is important for ensuring consumer safety and efficacy. Ginseng is an expensive herb, and adulteration with other cheaper products may occur. Quality assurance of ginseng is needed since many of its commercial products now come in various formulations such as capsules, powder, softgels and tea. Thus traditional means of authentication via smell, taste or physical appearance are hardly reliable. Herbs like ginseng tend to exhibit characteristic infrared fingerprints due to their different chemical constituents. Here we report for the first time a rapid means of distinguishing American and Asian ginsengs from two morphological fakes--sawdust and Platycodon grandiflorum, via pattern differences and principal component analysis of their infrared spectra. Our results show that ginseng can be distinguished from both sawdust and Platycodon grandiflorum, hence there is a potential of using infrared spectroscopy as a novel analytical technique in the authentication of ginseng.

Drugs, Chinese Herbal↗

The measurement of nitrite in adulterated urine samples by high-performance ion chromatography.

With the increased availability of nitrite-containing commercial products that are used for the adulteration of urine samples in the workplace, it is necessary for laboratories to be able to detect and confirm the presence of nitrite in these samples. We have developed a method to confirm the presence of nitrite in urine samples. The method uses the IonPac AS 14 analytical column with the Dionex series 45001 Bio LC system equipped with an anion self-generating suppressor and conductivity detector. Using a single-point calibration, the method is linear and accurately quantitates nitrite to 12,000 microg/mL. The limit of detection is 30 microg/mL, and the day-to-day precision of the assay has a coefficient of variation (CV) of 4.3% at 1200 microg/mL and 3.8% at 2700 microg/mL of nitrite.

Anions↗

The Jake Walk Blues. A toxicologic tragedy mirrored in American popular music.

In 1930 thousands of cases of muscle pain, weakness of upper and lower extremities, and minimal sensory impairment occurred in the United States. The illness was caused by the consumption of an adulterated Jamaica ginger extract ("Jake"), an illicit beverage then popularly used in the southern and midwestern United States to circumvent prohibition statutes. The additive tri-ortho-cresyl phosphate caused severe, only partially reversible damage to the spinal cord and peripheral nervous tissue. Victims with resultant gait impairment, sometimes permanent, were said to have the "Jake Leg" or "Jake Walk." Twelve commercial phonographic recordings made between 1928 and 1934 by southern rural artists, white and black, refer to Jake or Jake-induced infirmity. These reveal preepidemic cultural familiarity with Jake, and the later, postepidemic performances reflect a whimsical, even cynical, cultural attitude that those with "Jake Leg" were suffering the wages of sin and should not be regarded as objects of pity or sympathy.

Alcoholic Beverages↗

[Application of allele-specific primer in the identificatin of Hedyotis diffusa].

OBJECTIVE: To develop a convenient and effective method for the identification of Hedyotis diffusa. METHODS: DNA templates were extracted from H. diffusa and its adulterants samples on commercial markets. And DNA fragments of rDNA ITS-2 regions were amplified and sequenced subsequently. ITS-2 sequences of all samples were aligned. The allele-specific primer was designed for distinguishing H. diffusa. RESULTS: The nucleotide difference between H. diffusa and 8 other species is obvious in the ITS-2 region. In addition, the allele-specific primers were employed to amplify the DNA from H. diffusa and 8 other species. The result indicated that a 392 bp DNA fragment was amplified from H. diffusa, whereas no any fragment was amplified from 8 other species under the same reaction condition. CONCLUSION: The primers designed in the present study were highly specific for H. diffusa. They could be used as key components in the H. diffusa identification kit.

Alleles↗

The effects of naltrexone on cadmium-induced increases in oral ethanol self-administration.

Adult male rats were exposed to a standard laboratory diet (N = 20), or an adulterated diet containing 100 ppm added cadmium (N = 20), for 60 days. On Day 61, half the animals from each dietary condition received subcutaneous implants of two 30 mg naltrexone pellets, and the remaining half the animals received identical implants of 30 mg placebo pellets. One week later, animals from groups created by this interaction (Groups Control-Placebo, Control-Naltrexone, Cadmium-Placebo, Cadmium-Naltrexone) were tested in an ethanol self-administration paradigm that presented a 10% ethanol solution (v/v) in both a choice and nonchoice format. The results indicated that cadmium exposure increased the oral self-administration of ethanol in the choice setting where water was offered as an alternative, and the opiate antagonist naltrexone failed to attenuate this effect.

Alcohol Drinking↗

Aversive properties of the kappa opioid agonist U50,488 in the week-old rat pup.

mu Opioids have been shown to produce analgesia and to be reinforcing during the first week of life in the rat. kappa Opioids also have analgesic actions in both the infant and adult, but can be aversive in the mature animal. We examined the aversive effects of the kappa opioid agonist U50,488 during the first postnatal week in the rat pup in three ways. In the first experiment, U50,488, injected peripherally (1.0-30.0 mg/kg), was paired with an odor and pups were tested 8 h later for positional preference for avoidance of that odor. This task is similar to conditioned preference/aversion tests used with adult animals. Both 3- and 7-day-old pups learned to avoid the odor adulterated side at the two higher doses. When exposed to odors previously associated with U50,488, pups at both ages decreased locomotor activity. In a second experiment, acute treatment with U50,488 increased ultrasonic distress vocalizations (USV) equally at 3 and 7 days of age, increased locomotor activity, and decreased rectal temperature. Neither of the latter two effects was correlated with the increase in USV production. The third experiment showed that conditioned odor cues increased USV 8 h later in 3- and 7-day-old pups at 1.0-10.0 mg/kg without changes in activity or rectal temperature. The results from these studies suggest that U50,488 can produce aversions in the neonatal rat pup as it does in the adult.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗

Regulation of aversion to noxious food by Drosophila neuropeptide Y- and insulin-like systems.

Omnivores, including humans, have an inborn tendency to avoid noxious or unfamiliar foods. Such defensive foraging behaviors are modifiable, however, in response to physiological needs. Here we describe a method for assessing risk-sensitive food acquisition in Drosophila melanogaster. Food-deprived fly larvae become more likely to feed on noxious foods (adulterated with quinine) as the duration of deprivation increases. The neuropeptide F receptor NPFR1, a mammalian neuropeptide Y (NPY) receptor homolog, centrally regulates the response to noxious food in D. melanogaster. Overexpression of NPFR1 was sufficient to cause nondeprived larvae to more readily take in noxious food, whereas loss of NPFR1 signaling led to the opposite phenotype. Moreover, NPFR1 neuronal activity may be directly regulated by the insulin-like signaling pathway. Upregulation of insulin-like receptor signaling in NPFR1 cells suppressed the feeding response to noxious food. Our results suggest that the coordinated activities of the conserved NPY- and insulin-like receptor signaling systems are essential for the dynamic regulation of noxious food intake according to the animal's energy state.

Analgesics, Non-Narcotic↗

Genetic distinction of radix adenophorae from its adulterants by the DNA sequence of 5S-rRNA spacer domains.

Radix Adenophorae (Shashen), a traditional Chinese medicine commonly used as an antitussive and expectorant, is derived from roots of Adenophora stricta Miq. and Adenophora tetraphylla (Thunb.) Fisch. Twelve species and varieties of Adenophora and Glehnia, however, could act as substitutes or adulterants of Radix Adenophorae on the commercial markets in South East Asia, and roots of Adenophora hunanensis Nannf. and Glihnia littoralis F. Schmidt ex Miq. are the most common examples. The authentic identification of dried roots of A. stricta and A. tetraphylla, however, is difficult on the basis of appearance and morphology. A molecular genetic approach was developed here to identify the species of Radix Adenophorae. The 5S-rRNA spacer domains (approximately 250 bp) were amplified by the polymerase chain reaction (PCR) from genomic DNAs isolated from A. stricta, A. tetraphylla, A. hunanensis and G. littoralis, and subsequently, the nucleotide sequences were determined. Diversity in DNA sequence and restriction enzyme mapping among various species were found in their 5S-rRNA spacer domains, which could serve as markers for authentic identification of Radix Adenophorae.

Antitussive Agents↗

Worksite behavioral research. Results, sensitive methods, test batteries and the transition from laboratory data to human health.

Ample evidence demonstrates that many chemicals, at some concentration, affect the nervous system. Disastrous incidents resulting from food adulteration, medical experiments and pharmaceutical errors, and industrial and environmental exposures warn of the serious potential for neurotoxicants to affect human health. This article identifies the approximately 185 epidemiological behavioral neurotoxicology studies published through 1989 of extended workplace exposures to chemicals. Approximately 250 different tests have been administered to exposed workers in primarily cross sectional studies, and statistically significant decrements were reported in 43% of the approximately 1100 test/population administrations (virtually all 185 studies employed several of the 250 tests). In this research, 28 different chemicals as well as multiple chemical exposures have been studied. The most extensive findings are seen in research on carbon disulfide, lead, mercury, and multiple solvent exposures, although three or more independent studies also have been reported on workers exposed to styrene and organophosphates. Analyzing the consistent findings in these studies, they reveal a broad spectrum of cognitive, motor, and affective or personality changes. The most frequently reported functional deficits are in tests of intelligence, memory, spatial relations, coordination, and speed plus coordination. Individual behavioral measurement methods and significant test batteries that have been employed to assess changes in human nervous system functions to determine the degree of risk posed by new and established chemicals are described; two of those human behavioral test batteries are predicted to dominate research at the onset of the 1990's. There is a lack of parallelism between the human test methods found in these batteries and the US Environmental Protection Protection Agency (EPA) and Food and Drug Agency (FDA) guideline methods for pre-production screening of chemicals and food additives in animals, and it appears unlikely that the widely employed human and animal behavioral test batteries, as currently evaluated, could identify disease complexes newly suspected of having a chemical etiology.

Animals↗

Overview on the analytical tools for quality control of natural product-based supplements: a case study of ginseng.

The quality of pharmaceutical products like ginseng is important for ensuring consumer safety and efficacy. Many ginseng products sold today are in various formulations such as powder, capsules, tablets, soft-gels, liquid extracts, and tea. This renders ginseng less identifiable by smell, taste, or physical appearance. Furthermore, as ginseng is expensive, adulteration with other cheaper products occurs. Hence quality assurance of ginseng is needed. This paper reviews the major techniques for ascertaining the level of ginsenosides, the primary active ingredients for ginseng, and covers high-performance liquid, gas, and thin-layer chromatographies, infrared and nuclear magnetic resonance spectroscopies, enzyme immunoassays, and other molecular methods. Supporting techniques such as ultraviolet, fluorescence, diode array and evaporative light scattering detections, and mass spectrometry will also be touched upon. This review also discusses the principles and applications of biosensors-in particular fiber optic-based sensors-and their feasibility in ginseng analysis based on preliminary studies. Despite their potential, there is currently no or limited commercial exploitation of fiber optic-based sensors to perform ginseng quality analysis. The opportunity for biosensors to be used for the rapid quality surveillance of ginseng is appealing, but several key issues still need to be addressed before they find widespread applications in the traditional Chinese medicine industry.

Biosensing Techniques↗

Biochemical markers of ethanol effects on brain.

Because sialic acid is a potential biochemical marker of membrane development or alteration, we compared acute and chronic ethanol effects on sialic acid. Experiments were conducted with 50 adult male Wistar rats (approximately 400 gm), housed in groups of five. Rats drank ad libitum a vitamin-fortified diet (Nutrament) that was adulterated with ethanol; ethanol intake averaged for each rat 10-18 gm/kg/day. Controls were fed an equal total volume, made isocaloric with sucrose. Rats were sacrificed weekly for four weeks, and an acute challenge dose of ethanol (2 gm/kg, intraperitoneally) was given 45 minutes before sacrifice of both control and ethanol-consuming rats. Some controls were challenged only with saline. We replicated our earlier findings of regional differences in sialic acid and in cerebellar deoxyribose (measured as a necessary adjunct in the autoanalyzer modification of the Warren-Delmotte methods). In the saline-challenged controls, levels of both compounds were higher at four weeks than after one week. Similar increases occurred also in the chronic ethanol-consuming group, but not in the ethanol-challenged controls, which had significantly lower values. Results in saline-challenged controls suggest that the chronic treatment either 1) created a tolerance which protected cells from damage by the challenge dose of ethanol, or 2) killed neurons, thus promoting proliferation of glial cells.

Alcohol Drinking↗

Delayed neurotoxicity - do trichlorphon and/or dichlorvos cause delayed neuropathy in man or in test animals?

Many, but not all, reports of delayed neuropathy associated with acute poisoning by trichlorphon refer to cases in U.S.S.R. Adulteration of technical trichlorphon with the ethyl analogue would greatly increase the neurotoxic hazard but analysis of a few samples has not revealed such impurities. Simultaneous ingestion of alcohol does not appear to increase neuropathic hazard. In hens double doses of trichlorphon each exceeding unprotected LD50 can produce moderate neuropathy associated with appropriately high inhibitions of neurotoxic esterase. Similar results are obtained with 2 doses of 10 x LD50 of dichlorvos. In vitro the inhibitory power of dichlorvos against neurotoxic esterase of hen brain is 0.02 x the power against acetylcholinesterase. This ratio correlates reasonably with the ratio of LD50/neuropathic dose. The factor for human brain enzymes is 0.06 suggesting that man is more susceptible to neuropathic effects of near-lethal doses of circulating dichlorvos. It is concluded that the only neuropathic hazard to man from good quality trichlorphon arises from rapid ingestion of massive doses. To obtain critical levels of inhibition of neurotoxic esterase and to cause neuropathy in man by repeated doses would require each dose to be severely toxic. Dichlorvos ingested in large doses is likely to kill rather than to cause neuropathy.

Animals↗