Home About us Contact
|
Home About us Contact | ||
|
|
||
Cocaine
Kinds of Cocaine Terms modified by Cocaine Selected AbstractsCognitive enhancement as a pharmacotherapy target for stimulant addictionADDICTION, Issue 1 2010Mehmet Sofuoglu ABSTRACT Background No medications have been proven to be effective for cocaine and methamphetamine addiction. Attenuation of drug reward has been the main strategy for medications development, but this approach has not led to effective treatments. Thus, there is a need to identify novel treatment targets in addition to the brain reward system. Aim To propose a novel treatment strategy for stimulant addiction that will focus on medications enhancing cognitive function and attenuating drug reward. Methods Pre-clinical and clinical literature on potential use of cognitive enhancers for stimulant addiction pharmacotherapy was reviewed. Results and conclusions Cocaine and methamphetamine users show significant cognitive impairments, especially in attention, working memory and response inhibition functions. The cognitive impairments seem to be predictive of poor treatment retention and outcome. Medications targeting acetylcholine and norepinephrine are particularly well suited for enhancing cognitive function in stimulant users. Many cholinergic and noradrenergic medications are on the market and have a good safety profile and low abuse potential. These include galantamine, donepezil and rivastigmine (cholinesterase inhibitors), varenicline (partial nicotine agonist), guanfacine (alpha2 -adrenergic agonist) and atomoxetine (norepinephrine transporter inhibitor). Future clinical studies designed optimally to measure cognitive function as well as drug use behavior would be needed to test the efficacy of these cognitive enhancers for stimulant addiction. [source] Can cocaine use be evaluated through analysis of wastewater?ADDICTION, Issue 5 2009A nation-wide approach conducted in Belgium ABSTRACT Aims Cocaine is the second most-used illicit drug world-wide and its consumption is increasing significantly, especially in western Europe. Until now, the annual prevalence has been estimated indirectly by means of interviews. A recently introduced and direct nation-wide approach based on measurements of the major urinary excreted metabolite of cocaine, benzoylecgonine, in wastewater is proposed. Design Wastewater samples from 41 wastewater treatment plants (WWTPs) in Belgium, covering approximately 3 700 000 residents, were collected. Each WWTP was sampled on Wednesdays and Sundays during two sampling campaigns in 2007,08. Samples were analysed for cocaine (COC) and its metabolites, benzoylecgonine (BE) and ecgonine methylester (EME) by a validated procedure based on liquid chromatography coupled with tandem mass spectrometry. Concentrations of BE were used to calculate cocaine consumption (g/day per 1000 inhabitants) for each WWTP region and for both sampling campaigns (g/year per 1000 inhabitants). Findings Weekend days showed significantly higher cocaine consumption compared with weekdays. The highest cocaine consumption was observed for WWTPs receiving wastewater from large cities, such as Antwerp, Brussels and Charleroi. Results were extrapolated for the total Belgian population and an estimation of a yearly prevalence of cocaine use was made based on various assumptions. An amount of 1.88 tonnes (t) per year [standard error (SE) 0.05 t] cocaine is consumed in Belgium, corresponding to a yearly prevalence of 0.80% (SE 0.02%) for the Belgian population aged 15,64 years. This result is in agreement with an earlier reported estimate of the Belgian prevalence of cocaine use conducted through socio-epidemiological studies (0.9% for people aged 15,64 years). Conclusions Wastewater analysis is a promising tool to evaluate cocaine consumption at both local and national scale. This rapid and direct estimation of the prevalence of cocaine use in Belgium corresponds with socio-epidemiological data. However, the strategy needs to be refined further to allow a more exact calculation of cocaine consumption from concentrations of BE in wastewater. [source] Cocaine,seen through users' eyesADDICTION, Issue 10 2004JOHN A. HENRY No abstract is available for this article. [source] Cocaine- and amphetamine-regulated transcript peptide (CART) is present in peptidergic C primary afferents and axons of excitatory interneurons with a possible role in nociception in the superficial laminae of the rat spinal cordEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 6 2007Márk Kozsurek Abstract Cocaine- and amphetamine-regulated transcript peptides (CART) have been implicated in the regulation of several physiological functions, including pain transmission. A dense plexus of CART-immunoreactive fibres has been described in the superficial laminae of the spinal cord, which are key areas in sensory information and pain processing. In this study, we used antibody against CART peptide, together with markers for various types of primary afferents, interneurons and descending systems to determine the origin of the CART-immunoreactive axons in the superficial laminae of the rat spinal cord. Calcitonin gene-related peptide (CGRP), a marker for peptidergic primary afferents in the dorsal horn, was present in 72.6% and 34.8% of CART-immunoreactive axons in lamina I and II, respectively. The majority of these fibres also contained substance P (SP), while a few were somatostatin (SOM)-positive. The other subpopulation of CART-immunoreactive boutons in lamina I and II also expressed SP and/or SOM without CGRP, but contained vesicular glutamate transporter 2, which is present mainly in excitatory interneuronal terminals. Our data demonstrate that the majority of CART-immunoreactive axons in the spinal dorsal horn originate from peptidergic nociceptive primary afferents, while the rest arise from excitatory interneurons that contain SP or SOM. This strongly suggests that CART peptide can affect glutamatergic neurotransmission as well as the release and effects of SP and SOM in nociception and other sensory processes. [source] Cocaine- and amphetamine-regulated transcript (CART) peptide as an in vivo regulator of cardiac function in Rana ridibunda frogEXPERIMENTAL PHYSIOLOGY, Issue 6 2007Iliyana V. Ivanova The aim of this study was to investigate the effect of CART peptide on cardiac performance and on the physiological signalling pathways involved using Rana ridibunda frog heart preparations in vivo. The CART peptide, when injected into the venous sinus, significantly and reproducibly increased the force of frog heart contractions by up to 33.0 ± 6.4% during the first 15 min after its application but did not influence the chronotropic activity of the frog heart. The positive inotropic effect was entirely blocked by prazosin, pertussis toxin, Rp -adenosine 3,,5,-cyclic monophosphorothioate, autosauvagine 30 or metyrapone, as well as by extirpation of the pituitary gland, functional elimination of the inter-renal glands and long-lasting starvation, and was not observed on isolated heart preparations. Propranolol and double pithing were without significant effect on this phenomenon. It was concluded that: (i) CART peptide, administered to frogs in vivo, increases the force of heart contractions; (ii) this effect of the peptide is exerted via activation of the hypothalamic,pituitary,inter-renal gland axis through a corticoliberin-sensitive mechanism; (iii) CART augments the pumping function of the heart via a corticosteroid-dependent potentiation of myocardial ,1 -adrenoreceptors signalling; and (iv) prolonged food deprivation abolishes the positive inotropic effect of CART, suggesting the participation of endogenous CART in the physiological adaptation of the circulatory system to limitations of energy consumption. [source] Relationships Between Concentrations of Cocaine and Its Hydrolysates in Peripheral Blood, Heart Blood, Vitreous Humor and UrineJOURNAL OF FORENSIC SCIENCES, Issue 2 2006Wayne C. Duer Ph.D. ABSTRACT: Cocaine is known to degrade in vivo and in vitro by several hydrolytic mechanisms. A previous study found that the initial amount of cocaine added to plasma could be accounted for by summing the molar concentrations of cocaine's hydrolysis products and the cocaine remaining after hydrolysis. The present study was undertaken to investigate whether or not relationships might exist between such molar concentration sums for different postmortem bodily fluids. Determinations of cocaine, benzoylecgonine, ecgonine methyl ester, and ecgonine were performed using liquid chromatography/mass spectrometry (LC/MS/MS) with heart blood, femoral blood, vitreous humor (VH), and urine (UR). The results demonstrate a strong correlation between blood and VH concentrations (correlation coefficients of 0.88,0.94), weak correlation between the UR and blood concentrations (correlation coefficients of 0.61,0.64), and weak correlation between UR and VH concentrations (correlation coefficient of 0.59). The results demonstrate that ecgonine is a significant hydrolysate with concentrations on the same order of magnitude as benzoylecgonine. The results are consistent with rapid distribution of the parent drug and its hydrolysates in the blood and VH. The strong correlation between the blood and VH demonstrates that VH is an important medium for toxicology testing when attempting to make a determination of cocaine intoxication. [source] Andean Cocaine: The Making of a Global Drug.JOURNAL OF LATIN AMERICAN & CARIBBEAN ANTHROPOLOGY, Issue 1 2010By Paul Gootenberg No abstract is available for this article. [source] Ethanol enhancement of cocaine- and amphetamine-regulated transcript mRNA and peptide expression in the nucleus accumbensJOURNAL OF NEUROCHEMISTRY, Issue 2 2006Armando Salinas Abstract Cocaine- and amphetamine-regulated transcript (CART) is a peptide neurotransmitter that has been implicated in drug reward and reinforcement. CART mRNA and peptide expression are highly concentrated in several compartments of the mesolimbic reward pathway. Several lines of evidence suggest that CART peptides may contribute to rewarding behaviors and the addiction liability of psychostimulants; however, there are no reports of basic work concerning CART in relation to alcohol and mechanisms of alcohol dependence development. Therefore, in this study we investigated the response of CART transcript and peptide to acute ethanol administration in vivo. Rats were administered ethanol (1 g/kg or 3.5 g/kg, 1 h, ip) and CART expression was measured by RT-PCR in the nucleus accumbens (NAcc). Ethanol (3.5 g/kg) increased CART transcription markedly. The interactions of dopamine on ethanol-induced CART expression were further evaluated pharmacologically using D1 and D2/D3 receptor antagonists. Both SCH 23390 (0.25 mg/kg) or raclopride (0.2 mg/kg) pre-treatment significantly suppressed ethanol-enhancement of CART mRNA transcription. Confocal immunofluorescence microscopy revealed that CART peptide immunoreactivity was also enhanced in both the core and the shell of the NAcc by ethanol administration. These findings demonstrate that CART mRNA and peptide expression are responsive to acute ethanol administrated in vivo and suggests that CART peptides may be important in regulating the rewarding and reinforcing properties of ethanol. [source] Introduction of a High-Energy Diet Acutely Up-Regulates Hypothalamic Cocaine and Amphetamine-Regulated Transcript, Mc4R and Brown Adipose Tissue Uncoupling Protein-1 Gene Expression in Male Sprague-Dawley RatsJOURNAL OF NEUROENDOCRINOLOGY, Issue 1 2005Z. A. Archer Abstract Obesity is an escalating problem in Western societies. Susceptibility to weight gain within an obesogenic environment is variable. It remains unclear how the range of weight gain responses are generated. It is possible that an individual's immediate and/or sustained appetite for apparently palatable foods, or metabolic adaptations to a new diet could be important. The present study therefore examined the short- to medium-term effects of a high-energy (HE) diet on bodyweight, food intake, and energy balance-related signalling systems. Sprague-Dawley rats were fed either chow or an HE diet for 12 h, 24 h, 48 h or 14 days. Blood hormones and metabolites were assayed, and expression of uncoupling protein-1 (UCP-1) and hypothalamic energy-balance related genes were determined by Northern blotting or in situ hybridisation, respectively. Short-term exposure (12 h, 24 h, 48 h) to the HE diet had no effect on grams of food consumed, but caloric intake was increased. Exposure to HE diet for 14 days (medium term) established a bodyweight differential of 7.7 g, and animals exhibited a transient increase in caloric intake of 5 days duration. Terminal levels of leptin, insulin, glucose and non-esterified fatty acids (NEFAs) were all increased in HE-fed animals. UCP-1 mRNA was elevated in interscapular brown adipose tissue from HE-fed rats only at 12 h. Cocaine and amphetamine-regulated transcript (CART) and Mc4R gene expression in the hypothalamus were increased after 12 h and 24 h on an HE diet, respectively. The rats appear to passively over-consume calories as a result of consuming a similar weight of a more energy dense food. This evokes physiological responses, which adjust caloric intake over several days. Circulating NEFA and insulin concentrations, UCP-1, Mc4R and CART gene expression are increased as an immediate consequence of consuming HE diet, and may be involved in countering hypercaloric intake. Circulating leptin is increased in the HE-fed animals after 48 h, reflecting their increasing adiposity. [source] Cocaine- and Amphetamine-Regulated Transcript is Present in Hypothalamic Neuroendocrine Neurones and is Released to the Hypothalamic-Pituitary Portal CircuitJOURNAL OF NEUROENDOCRINOLOGY, Issue 3 2003P. J. Larsen Abstract Cocaine- and amphetamine-regulated transcript (CART) is present in a number of hypothalamic nuclei. Besides actions in circuits regulating feeding behaviour and stress responses, the hypothalamic functions of CART are largely unknown. We report that CART immunoreactivity is present in hypothalamic neuroendocrine neurones. Adult male rats received a systemic injection of the neuronal tracer Fluorogold (FG) 2 days before fixation, and subsequent double- and triple-labelling immunoflourescence analysis demonstrated that neuroendocrine CART-containing neurones were present in the anteroventral periventricular, supraoptic, paraventricular (PVN) and periventricular nuclei of the hypothalamus. In the PVN, CART-positive neuroendocrine neurones were found in all of cytoarchitectonically identified nuclei. In the periventricular nucleus, approximately one-third of somatostatin cells were also CART-immunoreactive. In the medial parvicellular subnucleus of the PVN, CART and FG coexisted with thyrotrophin-releasing hormone, whereas very few of the corticotrophin-releasing hormone containing cells were CART-immunoreactive. In the arcuate nucleus, CART was extensively colocalized with pro-opiomelanocortin in the ventrolateral part, but completely absent from neuroendocrine neurones of the dorsomedial part. To assess the possible role of CART as a hypothalamic-releasing factor, immunoreactive CART was measured in blood samples from the long portal vessels connecting the median eminence with the anterior pituitary gland. Adult male rats were anaesthetized and the infundibular stalk exposed via a transpharyngeal approach. The long portal vessels were transected and blood collected in 30-min periods (one prestimulatory and three poststimulatory periods). Compared to systemic venous plasma samples, baseline concentrations of immunoreactive CART were elevated in portal plasma. Exposure to sodium nitroprusside hypotension triggered a two-fold elevation of portal CART42-89 immunoreactivity throughout the 90-min stimulation period. In contrast, the concentration of portal plasma CART immunoreactivity dropped in the vehicle infused rats. The current study provides further evidence that CART is a neuroendocrine-releasing factor with a possible impact on anterior pituitary function during states of haemodynamic stress. [source] Cocaine and Amphetamine-Regulated-Transcript Peptide Mediation of Leptin Stimulatory Effect on the Rat Gonadotropin-Releasing Hormone Pulse Generator In VitroJOURNAL OF NEUROENDOCRINOLOGY, Issue 5 2000Lebrethon Pulsatile gonadotropin-releasing hormone (GnRH) secretion was studied in vitro using explants of the retrochiasmatic hypothalamus from prepubertal male and female rats. Leptin caused a dose-dependent reduction of the GnRH interpulse interval in both sexes. We studied the effects of cocaine- and amphetamine-regulated transcript (CART) since this peptide was shown recently to mediate the anorectic effects of leptin in the hypothalamus. CART caused a reduction of the GnRH interpulse interval. This effect was prevented using an anti-CART antiserum which could partially overcome leptin stimulatory effects as well. Using hypothalamic explants from Zucker rats homozygous for the leptin receptor mutation ( fa/fa), GnRH pulse frequency was not affected by leptin, while a significant acceleration was caused by the CART-peptide. In conclusion, leptin involves the hypothalamic CART-peptide to stimulate the prepubertal GnRH pulse generator in vitro. [source] Alcohol, Cocaine, and Brain Stimulation-Reward in C57Bl6/J and DBA2/J MiceALCOHOLISM, Issue 1 2010Eric W. Fish Background:, Pleasure and reward are critical features of alcohol drinking that are difficult to measure in animal studies. Intracranial self-stimulation (ICSS) is a behavioral method for studying the effects of drugs directly on the neural circuitry that underlies brain reward. These experiments had 2 objectives: first, to establish the effects of alcohol on ICSS responding in the C57Bl6/J (C57) and DBA2/J (DBA) mouse strains; and second, to compare these effects to those of the psychostimulant cocaine. Methods:, Male C57 and DBA mice were implanted with unipolar stimulating electrodes in the lateral hypothalamus and conditioned to spin a wheel for reinforcement by the delivery of rewarding electrical stimulation (i.e., brain stimulation-reward or BSR). Using the curve-shift method, the BSR threshold (,0) was determined immediately before and after oral gavage with alcohol (0.3, 0.6, 1.0, 1.7 g/kg) or water. Blood alcohol concentration (BAC) was measured to determine the influence of alcohol metabolism on BSR threshold. Separately, mice were administered cocaine (1.0, 3.0, 10.0, 30.0 mg/kg) or saline intraperitoneally. Results:, In C57 mice, the 0.6 g/kg dose of alcohol lowered BSR thresholds by about 20%, during the rising (up to 40 mg/dl), but not falling, phase of BAC. When given to the DBA mice, alcohol lowered BSR thresholds over the entire dose range; the largest reduction was by about 50%. Cocaine lowered BSR thresholds in both strains. However, cocaine was more potent in DBA mice than in C57 mice as revealed by a leftward shift in the cocaine dose,response curve. For both alcohol and cocaine, effects on BSR threshold were dissociable from effects on operant response rates. Conclusions:, In C57 and DBA mice, reductions in BSR threshold reflect the ability of alcohol to potentiate the neural mechanisms of brain reward. The DBA mice are more sensitive to the reward-potentiating effects of both alcohol and cocaine, suggesting that there are mouse strain differences in the neural mechanisms of brain reward that can be measured with the ICSS technique. [source] Gender Differences in Predictors of Treatment Attrition with High Dose Naltrexone in Cocaine and Alcohol DependenceTHE AMERICAN JOURNAL ON ADDICTIONS, Issue 6 2008Jesse J. Suh PsyD Recently, we reported that naltrexone at 150 mg/day significantly decreased cocaine and alcohol use for men but not women with co-occurring cocaine and alcohol dependence. The present study is an exploratory investigation of predictors that explain the different gender responses to naltrexone, with a particular focus on differential predictors of treatment attrition. No significant predictors were associated with treatment discontinuation in men. Women, however, were more likely to discontinue treatment when reporting severe pre-treatment psychiatric problems or nausea while in treatment. Further research on the impact of pre-treatment and in-treatment gender differences with naltrexone is warranted. [source] Characterization of CART neurons in the rat and human hypothalamusTHE JOURNAL OF COMPARATIVE NEUROLOGY, Issue 1 2001Carol F. Elias Cocaine- and amphetamine-regulated transcript (CART) is a recently described neuropeptide widely expressed in the rat brain. CART mRNA and peptides are found in hypothalamic sites such as the paraventricular nucleus (PVH), the supraoptic nucleus (SON), the lateral hypothalamic area (LHA), the dorsomedial nucleus of the hypothalamus (DMH), the arcuate nucleus (Arc), the periventricular nucleus (Pe), and the ventral premammillary nucleus (PMV). Intracerebroventricular administration of recombinant CART peptide decreases food intake and CART mRNA levels in the Arc are regulated by leptin. Leptin administration induces Fos expression in hypothalamic CART neurons in the PVH, the DMH, the Arc, and the PMV. In the current study, we used double label in situ hybridization histochemistry to investigate the potential direct action of leptin on hypothalamic CART neurons and to define the chemical identity of the hypothalamic CART neurons in the rat brain. We found that CART neurons in the Arc, DMH, and PMV express long form leptin-receptor mRNA, and the suppressor of cytokine signaling-3 (SOCS-3) mRNA after an acute dose of intravenous leptin. We also found that CART neurons in the parvicellular PVH, in the DMH and in the posterior Pe coexpress thyrotropin-releasing hormone (TRH) mRNA. CART neurons in the magnocellular PVH and in the SON coexpress dynorphin (DYN), and CART cell bodies in the LHA and in the posterior Pe coexpress melanin-concentrating hormone (MCH) and glutamic acid decarboxylase (GAD-67) mRNA. In the Arc, a few CART neurons coexpress neurotensin (NT) mRNA. In addition, we examined the distribution of CART immunoreactivity in the human hypothalamus. We found CART cell bodies in the PVH, in the SON, in the LHA, in the Arc (infundibular nucleus) and in the DMH. We also observed CART fibers throughout the hypothalamus, in the bed nucleus of the stria terminalis, and in the amygdala. Our results indicate that leptin directly acts on CART neurons in distinct nuclei of the rat hypothalamus. Furthermore, hypothalamic CART neurons coexpress neuropeptides involved in energy homeostasis, including MCH, TRH, DYN, and NT. The distribution of CART cell bodies and fibers in the human hypothalamus indicates that CART may also play a role in the regulation of energy homeostasis in humans. J. Comp. Neurol. 432:1,19, 2001. © 2001 Wiley-Liss, Inc. [source] Cocaine can turn you blue as well!ANAESTHESIA, Issue 6 2010A. Chakladar No abstract is available for this article. [source] Cocaine-related admissions to an intensive care unit: a five-year study of incidence and outcomesANAESTHESIA, Issue 2 2010S. Galvin Summary Cocaine misuse is increasing and it is evidently considered a relatively safe drug of abuse in Ireland. To address this perception, we reviewed the database of an 18-bed Dublin intensive care unit, covering all admissions from 2003 to 2007. We identified cocaine-related cases, measuring hospital mortality and long-term survival in early 2009. Cocaine-related admissions increased from around one annually in 2003,05 to 10 in 2007. Their median (IQR [range]) age was 25 (21,35 [17,47]) years and 78% were male. The median (IQR [range]) APACHE II score was 16 (11,27 [5,36]) and length of intensive care stay was 5 (3,9 [1,16]) days. Ten patients died during their hospital stay. A further five had died by the time of follow-up, a median of 24 months later. One was untraceable. Cocaine toxicity necessitating intensive care is increasingly common in Dublin. Hospital mortality in this series was 52%. These findings may help to inform public attitudes to cocaine. [source] Immunodetection of Cocaine- and Amphetamine-Regulated Transcript in the Rumen, Reticulum, Omasum and Abomasum of the SheepANATOMIA, HISTOLOGIA, EMBRYOLOGIA, Issue 1 2009M. B. Arciszewski Summary Enteric nerves harbour a wide array of neuropeptides playing a key role in the regulation of gastrointestinal tract functions. In this study, the distribution patterns of cocaine- and amphetamine-regulated transcript-immunoreactive (CART-IR) nerve fibres as well as the percentages of CART-positive enteric neurons were immunohistochemically assessed in the rumen, reticulum, omasum and abomasum of the sheep. Double staining were applied, to elucidate whether neuropeptide Y (NPY), vasoactive intestinal polypeptide (VIP), substance P (SP), somatostatin or serotonin co-exist in CART-IR gastric structures. In the rumen, reticulum, omasum and abomasum, a majority of myenteric neurons identified by immunoreactivity to Hu C/D were CART-positive (47.1 ± 3.6%, 45.1 ± 3.0%, 41.6 ± 2.6% and 40.9 ± 2.9% respectively). The smooth musculature of the forestomachs as well as abomasum was innervated with numerous CART-IR nerve fibres. Blood vessels-associated CART-positive nerve terminals were identified in the submucosa of the reticulum only. Lamina muscularis mucosae of the omasum and abomasum was moderately innervated with CART-IR nerve terminals. In the abomasum sparse CART-IR nerve fibres were seen between mucosal glands. A small population of endocrine cells of the abomasum also exhibited the presence of CART. All neuronal elements as well as endocrine cells IR to CART were negative to somatostatin and/or serotonin. No immunoreactivity to VIP, NPY and/or SP was found in myenteric ganglia-projecting CART-positive nerve fibres. The co-localization of CART with VIP, NPY and/or SP was regularly observed in myenteric neurons as well as the smooth muscle layer- and lamina muscularis mucosae-projecting nerve fibres. CART-IR nerve terminals located between mucosal glands of the abomasum frequently co-stored VIP, NPY and/or SP. Although the exact function of CART in the ovine forestomachs/stomach has to be elucidated, several potential functions (like enteric nerves protection) have been suggested. [source] Heart Rate Variability by Triangular Index in Infants Exposed Prenatally to CocaineANNALS OF NONINVASIVE ELECTROCARDIOLOGY, Issue 4 2002M.B.A., Sudhir Ken Mehta M.D. Background: In adults, heart rate variability triangular index (HRVi) is a highly reproducible measure of heart rate variability (HRV), which makes it more suitable for use in longitudinal studies. Although normative data have been published for newborns, studies in infants with pathological conditions are lacking. Methods: From 1997 to 2000, within the first 4 days of life, we prospectively evaluated HRVi in cocaine-exposed asymptomatic newborns (N = 97) by Holter monitoring. Their data were compared with infants from two control groups (one with no in utero drug exposure, N = 102; the other with exposure to alcohol, nicotine, or marijuana but no cocaine, N = 111). Results: In assessing concordance between and within operators for HRVi, the intraclass correlations were 0.983 (95% Cl: 0.958, 0.994) and 0.997 (95% Cl: 0.984, 0.999), respectively. Infants with in utero cocaine exposure had significantly (P < 0.0001) lower HRVi than those exposed to other drugs and to no drugs in utero. If abnormal HRVi is defined as < fifth percentile for the no drug exposed group (HRVi < 8), 10% of the cocaine-exposed newborns, in contrast to 2% in each of the control groups (P = 0.003) had abnormal values. Conclusion: HRVi is a reliable measure to study heart rate variability in newborns. Asymptomatic infants with in utero cocaine exposure have lower HRVi. Our study supports the clinical use of an abnormal HRVi as a value < 8 for newborn infants. A.N.E. 2002;7(4):374,378 [source] Cocaine and Ethanol: Combined Effects on Coronary Artery Blood Flow and Myocardial Function in DogsACADEMIC EMERGENCY MEDICINE, Issue 7 2009Lance D. Wilson MD Abstract Objectives:, In combination, cocaine and ethanol are more cardiotoxic than is either substance alone. These substances together constitute a drug abuse combination that commonly results in fatality. Previously the authors have demonstrated that cardiotoxicity of cocaine and ethanol is in part due to synergistic myocardial-depressant effects. However, it remains unclear whether this myocardial depression is associated with concomitant adverse effects on coronary blood flow in relation to these substances. The aim of this study was to investigate combined effects of cocaine and ethanol on myocardial blood flow, in relation to indices of myocardial function. Methods:, Anesthetized dogs were instrumented for hemodynamic monitoring with Doppler flow probes placed on the circumflex and left anterior descending (LAD) coronary arteries. Dogs were randomized to three groups (each n = 6): ethanol (E, 1.5 g/kg followed by placebo), cocaine (C, placebo followed by cocaine, 7.5 mg/kg IV), or cocaine plus ethanol (C + E). All measurements were made at control, after placebo or ethanol, and then at fixed time intervals after cocaine or placebo bolus over 3 hours. Results:, In both the C + E and the C groups, circumflex blood flow (CBF) decreased by 71% (95% confidence interval [CI] = 56% to 85%) and 57% (95% CI = 43% to 72%, both p < 0.04 vs. baseline) immediately after cocaine bolus. This was associated with transient depression of cardiac output, myocardial contractile function, and rate-pressure product (RPP), all indices of myocardial oxygen demand. A subsequent rebound increase of coronary sinus blood flow (CSBF) of 56% (95% CI = 26% to 137%, p < 0.03) compared to baseline occurred only in the C group and was associated with increases of myocardial contractile function and RPP. In the C + E group, 2 hours after drug administration, there was a decrease in CSBF of 49% (95% CI = 32% to 67%; p < 0.01) compared to baseline, which was associated with concomitant numerical decreases of the indices of myocardial oxygen demand and accumulation of cocaethylene. Conclusions:, Acute decreases in myocardial flow secondary to cocaine, and cocaine and ethanol in combination, were similar and temporally associated with cocaine's direct myocardial-depressant effects. Rebound increases in myocardial function and blood flow due to cocaine were attenuated by ethanol. Delayed myocardial depression and decreases in myocardial blood flow were observed only with coadministration of cocaine and ethanol. [source] Successful transplantation of organs from a donor who died from acute cocaine intoxicationCLINICAL TRANSPLANTATION, Issue 2 2003Francisco Caballero One to two percent of the general population of western countries are regular consumers of cocaine, 10% being sporadic consumers. This proportion increases considerably in the population age groups which are most frequently organ donors. Cocaine may directly cause brain death, or be present in those with brain death who died from other causes, especially head trauma. We present a 30-yr-old female donor, a regular consumer of inhaled cocaine, who died of brain anoxia after cocaine inhalation. Twenty-five hours after cocaine inhalation, the liver and kidneys were removed for transplantation. The liver was transplanted to a patient with acute hepatocellular failure caused by isoniazids, and the kidneys to two recipients with renal polycystosis. Toxicity attributable to the cocaine was not observed in any of the three recipients. All three grafts presented immediate function, and the clinical evolution of all three recipients and the function of all three grafts were excellent during the 5 yr of follow-up. The serum creatinines of the two kidney recipients 5 yr from transplantation were 76 and 72 ,mol/L, respectively. [source] Drug misuse and acquisitive crime among clients recruited to the National Treatment Outcome Research Study (NTORS)CRIMINAL BEHAVIOUR AND MENTAL HEALTH, Issue 1 2000Duncan Stewart Background Criminal activity among drug-misusing populations can result in considerable costs. This paper examines the relationship between acquisitive criminal behaviour and drug use among a cohort of 1075 clients recruited to the National Treatment Outcome Research Study (NTORS). Method Clients were recruited from 54 drug misuse treatment programmes in England. A structured interview was administered by clinical staff. The majority of clients were opiate-dependent poly-drug users. Results 27 000 acquisitive criminal offences were reported by the cohort in the three months prior to starting treatment, of which shoplifting was the most common offence. There was marked variation in the amount of acquisitive crime reported; just 10% of the sample were responsible for three-quarters of the crimes committed. Two other groups were identified: low-rate offenders, and those who did not commit an acquisitive crime. Multivariate analyses revealed that frequency of illicit drug use was associated with increased levels of criminal behaviour. Compared with the no-crime group, the high-rate offenders were 11 times more likely to be regular users of heroin, and three times more likely to have used cocaine regularly. Discussion These findings suggest that the most dependent and problematic drug misusers present treatment services with the greatest challenge in terms of reducing levels of criminality. Copyright © 2000 Whurr Publishers Ltd. [source] EXAMINING THE "CRIMINAL CAREERS" OF PROSTITUTES WITHIN THE NEXUS OF DRUG USE, DRUG SELLING, AND OTHER ILLICIT ACTIVITIES,CRIMINOLOGY, Issue 3 2000SHEILA ROYO MAXWELL This paper examines the co-occurrence of prostitution, drug use, drug selling, and involvement in non-drug crimes among women who have used serious drugs (e.g., crack, heroin). Existing perspectives on the drug use-prostitution nexus are re-examined using three dimensions of the criminal career paradigm: prevalence, lambda, and age of onset. Results show that approximately one-half of the women who reported regular drug use never prostituted, and that, except for use of crack cocaine, use of other drugs was unrelated to the prevalence, frequency, or age of onset into prostitution. The results also show that committing property crime was associated with an increased prevalence and early onset into prostitution, while selling drugs coincided with a decreased prevalence and delayed onset into prostitution. [source] Early and transient ontogenetic expression of the cocaine- and amphetamine-regulated transcript peptide in the rat mesencephalon: Correlation with tyrosine hydroxylase expressionDEVELOPMENTAL NEUROBIOLOGY, Issue 3 2002F. Brischoux Abstract The ontogeny of cocaine- and amphetamine-regulated transcript (CART) expression has been analyzed by immunohistochemistry in the mesencephalon of the rat central nervous system, and compared to the pattern of tyrosine hydroxylase- (TH-) expression. CART-producing neurons were first detected on the embryonic day 11 (E11) in the ventral mesencephalic vesicle. These neurons are among the first cells of the mantle layer to differentiate. From E13, a complementary pattern of distribution was observed, dividing the mantle layer into an external TH zone and an internal CART zone. Many TH-positive neurons were found to migrate from the neuroepithelium through the area containing the CART-immunoreactive neurons to settle more laterally. These TH cells exhibited prominent leading and trailing dendrites in the immediate vicinity of CART perikarya. On E16, the number of CART neurons appeared to diminish, and they were confined near the ventricle and around the fasciculus retroflexus. On E18 and E20, only the Edinger-Westphal nucleus exhibited a strong CART staining as described in the adult brain. Thus, the very early detection of CART during prenatal ontogeny led us to speculate that this peptide might have a role in the development of specific regions of the rat brain. In particular, our observations suggest that CART-expressing neurons might help the migration of the dopaminergic neurons of the substantia nigra. © 2002 Wiley Periodicals, Inc. J Neurobiol 52: 221,229, 2002 [source] Early adolescents show enhanced acute cocaine-induced locomotor activity in comparison to late adolescent and adult ratsDEVELOPMENTAL PSYCHOBIOLOGY, Issue 2 2008Kimberly A. Badanich Abstract Initiation of drug use during adolescence is associated with an increased probability to develop a drug addiction. The present study examined dose,response effects of cocaine (0, 5, 10, or 20 mg/kg, i.p.) on locomotor activity in early adolescent (postnatal day (PND) 35), late adolescent (PND 45), and young adults (PND 60) by measuring total distance moved (TDM) and frequency of start,stops. In response to 20 mg/kg cocaine, early adolescents showed the greatest cocaine-induced increase in TDM in comparison to late adolescent and adult rats. At this same dose, early adolescents showed the greatest cocaine-induced attenuation of start,stops relative to older rats. Results suggest that early adolescents engage in more cocaine-induced locomotor activity and less stationary behavior indicating that early adolescents are more sensitive to locomotor activating effects of high dose cocaine than older rats. © 2008 Wiley Periodicals, Inc. Dev Psychobiol 50: 127,133, 2008. [source] Foster mother care but not prenatal morphine exposure enhances cocaine self-administration in young adult male and female ratsDEVELOPMENTAL PSYCHOBIOLOGY, Issue 5 2007I. Vathy Abstract The present study was designed to investigate cocaine self-administration in adult male and female rats exposed prenatally to morphine. Pregnant dams were injected two times a day with either saline, analgesic doses of morphine or no drug at all (controls) on gestation Days 11,18. One day after birth, litters were cross-fostered such that control dams were paired with one another and their litters were crossed; saline- and morphine-treated dams were paired and half of each saline litter was crossed with half of each morphine litter. Thus, each mother (control, saline, and morphine) raised half of her own and half of the adopted litter. At the age of 60 days, males and females were trained first to lever press for sucrose pellets and then for cocaine. Once the lever-pressing behavior was learned and baseline level of this activity was established, animals received a cocaine (.5 mg/kg per infusion) reward for each correct response on the active lever during the next 9-day session. The data demonstrate that adult control, saline- and morphine-exposed male rats self-administer cocaine at a similar rate independent of their prenatal treatment. Adult female rats self-administer cocaine at a higher rate than male rats. Further, saline- and morphine-exposed females in diestrus self-administer more than females in proestrus phase of the estrous cycle, while control females show no such differences. In addition, fostering induces increase in cocaine self-administration in all groups of male rats regardless of prenatal drug exposure. In females, the only fostering-induced increase is in prenatally saline-exposed female rats raised by morphine-treated foster mother. Thus, our results suggest that the prenatal drug exposure does not induce changes in lever-pressing behavior for cocaine reward in adult male and female rats, but it sensitizes the animals to postnatal stimuli such as gonadal hormones and/or rearing conditions that result in increased drug self-administration. © 2007 Wiley Periodicals, Inc. Dev Psychobiol 49: 463-473, 2007. [source] Prognostic impact of psychoactive substances use during hospitalization for intentional drug overdoseACTA PSYCHIATRICA SCANDINAVICA, Issue 2 2005M. Tournier Objective:, To assess whether current use of psychoactive substance(s) is a prognostic factor during hospitalization for intentional drug overdose (IDO). Method:, Current intoxication with psychoactive substance(s) [cannabis, opiate, buprenorphine, amphetamine/ecstasy, cocaine, lysergic acid diethylamide (LSD)] was identified using toxicological urinalysis in 671 patients with IDO. An IDO was a priori defined as serious if associated with one of the following events: death, hospitalization in intensive care unit longer than 48 h, respiratory support, use of vasopressive drugs, cardiac massage or dialysis. Results:, Subjects positive for toxicological assays were twice as likely to present with serious IDO (OR = 1.9, 95% CI: 1.3,2.8, P = 0.001), independently from a large range of confounding factors. The risk of serious IDO was especially marked in subjects using LSD, buprenorphine or opiates. Conclusion:, Systematic investigation of substance use could be important to adapt medical management of subjects with IDO in general hospital, but also in primary care and psychiatric settings. [source] Neuropeptides and appetite controlDIABETIC MEDICINE, Issue 8 2002J. P. H. Wilding Abstract Obesity is important in the aetiology of type 2 diabetes, and presents a major barrier to its successful prevention and management. Obesity develops when energy intake exceeds energy expenditure over time. A complex system has evolved to maintain energy homeostasis, but this is biased towards weight gain. Meal size is controlled by a series of short-term hormonal and neural signals that derive from the gastrointestinal tract, such as cholecystokinin whereas others may initiate meals, such as the recently discovered hormone, ghrelin. Other hormones such as insulin and leptin, together with circulating nutrients, indicate long-term energy stores. All these signals act at several central nervous system (CNS) sites but the pathways converge on the hypothalamus, which contains a large number of peptide and other neurotransmitters that influence food intake. As energy deficit is most likely to compromise survival, it is not surprising that the most powerful of these pathways are those that increase food intake and decrease energy expenditure when stores are depleted. When energy stores are low, production of leptin from adipose tissue, and thus circulating leptin concentrations fall, leading to increased production of hypothalamic neurotransmitters that strongly increase food intake, such as neuropeptide Y (NPY), galanin and agouti-related protein (AGRP) and decreased levels of ,-melanocyte-stimulating hormone (,-MSH), cocaine and amphetamine-regulated transcript (CART) and neurotensin that reduce food intake and increase energy expenditure. The finding that mutations in leptin and POMC lead to severe early onset obesity in bumans has highlighted the importance of these peptides in humans. This new understanding may eventually lead to new treatments for obesity that will be of particular benefit in the prevention and treatment of type 2 diabetes. Diabet. Med. 19, 619,627 (2002) [source] Are we becoming more alike?DRUG AND ALCOHOL REVIEW, Issue 5 20082004 national household surveys, Comparison of substance use in Australia, the United States as seen in the 199 Abstract Introduction. This paper reports the results of the 1995, 1998, 2001 and 2004 Australian and US household surveys, with emphasis on changes since 2001. Design and Methods. The US survey data were recalculated to match age groups in the Australian data. Statistically significant changes are reported. Differences in prevalence of use by gender within age group were tested for significance. Results. The past-year use of ,any illicit drug', cannabis, cocaine, tranquillisers and injecting drugs decreased between 2001 and 2004 in Australia, but remained stable for all these drugs except ecstasy between 2002 and 2004 in the United States. The use of hallucinogens decreased in both countries. Alcohol and use of many illicit drugs by teenage girls in both countries increased to rates similar to or higher than boys, and teens in both countries reported binge and heavy drinking in the past month. Australians in their 20s had the highest rates of use, but in the United States, past-year use of many drugs was highest among teenagers. Discussion. More treatment services are needed, particularly for people dependent upon non-opiate drugs. The changes in acceptability of use of different drugs and their perceived availability are related to changes in prevalence rates. Even with the similarities in levels of use, there are differences in patterns of use and preferences for certain drugs in each country, and geographic proximity to drug sources is a factor. [source] Injecting and non-injecting cocaine use in Sydney, Australia: physical and psychological morbidityDRUG AND ALCOHOL REVIEW, Issue 4 2004SHARLENE KAYE Abstract This study aimed to examine the physical and psychological harms of cocaine use and investigate the role of injecting versus non-injecting routes of administration in the severity of such harms. Two hundred and twelve cocaine users from inner-city and southwestern Sydney were administered a structured interview containing sections on demographics, drug treatment history, drug use history, cocaine use patterns, cocaine dependence and physical and psychological problems associated with cocaine use. Serious physical and psychological symptoms were prevalent among both injecting and non-injecting cocaine users. The prevalence and extent of symptoms was greater among injecting cocaine users, however route of administration did not prove to be a significant independent predictor of harm when other factors, such as frequency of use and level of dependence, were taken into account. While the level of physical and psychological harm was greater among cocaine injectors, it would appear that factors engendered by injecting, such as more frequent use and higher levels of dependence, result in higher levels of harm, rather than the route of administration per se. Physical and psychological problems were also reported among infrequent users, suggesting that cocaine can cause harm irrespective of frequency or method of use. Harm reduction initiatives should be targeted towards all cocaine users, not just those who seek treatment for dependence or present with acute medical complications. [source] Impact of the heroin ,drought' on patterns of drug use and drug-related harmsDRUG AND ALCOHOL REVIEW, Issue 2 2004Dr MARIE C. LONGO Senior Research Officer Abstract Since late 2000, anecdotal reports from drug users and health professionals have suggested that there was a reduction in the supply of heroin in Adelaide in the first half of 2001, referred to as a heroin ,drought'. The aim of this paper was to critically review evidence for this, using data obtained from 100 injecting drug users surveyed for the 2001 Illicit Drug Reporting System (IDRS). This project is carried out annually in all Australian jurisdictions, and collects up-to-date information on the markets for heroin, methamphetamine, cocaine and cannabis. This paper also investigates the possible implications of this ,drought' on patterns of drug use and drug-related harms. The 2001 IDRS found consistent reports by users of an increase in the price of heroin, together with decreases in purity and availability. These factors resulted in a decrease in the frequency of self-reported heroin use among those surveyed in 2001, and a concomitant increase in the use of other drugs, in particular methamphetamine and morphine. The heroin ,drought' appears to have had a substantial impact on several indices of drug-related harm. There was a marked decrease in the number of opioid-related fatalities, and hospital data also showed reductions in heroin-related presentations. Treatment service data showed an increase in the number of admissions related to amphetamines. There is a need for health promotion and education on the adverse effects of methamphetamine use, and the development of improved treatment protocols for methamphetamine abuse and dependence. [source] | |||||||||||||||||||||||||||||||||||||