Histopathological and inflammatory response in multiple organs of rats exposed to crack.

The aim of this study was to investigate histopathological and inflammatory response in liver and kidney of rats after crack exposure. For this purpose, a total of 32 male Wistar rats were distributed into four groups: (G1) and (G2): received 18 mg/kg of body weight (b.w) of crack cocaine, but Group G2 remained 72 h without exposure after the experimental period (5 days). Experimental group 3 (G3): received 36 mg/kg of body weight (b.w) of crack cocaine. Control Group (CTRL): received only the vehicle (DMSO) administered by intraperitoneal (i.p) route for 5 days. The results showed that crack cocaine induced histopathological changes in liver and kidney. Immunohistochemistry data revealed that G2 group showed a higher immunoexpression of Ki-67 in hepatic and renal tissues. Regarding inflammation, the results showed that all groups exposed to crack cocaine decreased the expression of TNF-α, IL-6, and IL-10 in liver and kidney. In summary, our results showed that the subacute doses of crack cocaine used in this study had cytotoxic, and immunosuppressive effects in liver and kidney of rats, especially at 36 mg/kg dose. Since cellular death and inflammation participates in the multi-step process of chemical carcinogenesis, these data offer new insights into potential ways to understand the pathobiological mechanisms induced by crack cocaine in several tissues and organs.

Maternal crack cocaine use in rats leads to depressive- and anxiety-like behavior, memory impairment, and increased seizure susceptibility in the offspring.

Crack users suffer the effects of cocaine present in the drug and the action of other active compounds from its pyrolysis. An emergent fact is an increase in the number of pregnant crack cocaine users. Studies suggest that crack cocaine and its metabolites cross the placenta, promoting premature birth, fever, irritability, sweating, and seizures in the early months of life. In children, the effects of crack cocaine have been associated with cognitive deficits, difficulty in verbalization, aggressiveness, and depression, besides enhancing the susceptibility to epileptic seizures, including status epilepticus (SE) in adulthood. Therefore, we investigated the effect of maternal exposure to smoke crack cocaine on several behavioral parameters in the offspring during adulthood. A series of behavioral tests and intrahippocampal pilocarpine (H-PILO) microinjection at sub-convulsive and convulsive doses in a rat model demonstrated that exposure to crack cocaine during the embryonic period leads to anxiogenic-like behavior and long-term memory impairment in both genders and promotes depressive-like behavior in the female. Besides, crack cocaine offspring exposed to a sub-convulsive H-PILO dose showed higher susceptibility to SE, increased seizure frequency, and neurodegeneration, while animals that received a convulsive dose of H-PILO displayed no alteration in SE severity. Taken together, our data suggest that crack cocaine exposure during the gestational period leads to an increased predilection for anxiety and depression, long-term memory deficits, and reduction in the threshold for developing epileptic seizures associated with neuronal death, which predispose crack cocaine babies to develop neuropsychological disorders.

Crack cocaine smoke on pregnant rats: Maternal evaluation and teratogenic effect.

This study aimed to evaluate maternal toxicity, teratogenic, and placental oxidative effects resulting from the exposure of rats to crack cocaine smoke during pregnancy. Pregnant rats were exposed either to the smoke of crack and ashes (Crack) or to the smoke of ashes alone, nonexposed or pair-fed with the Crack group. Crack group was exposed to the smoke resulting from the burning of 250 mg of crack for 10 min, twice a day, from 7 days prior to mating until cesarian on gestational day 20. Placental oxidative stress and classical parameters of maternal and fetal evaluation were studied, in addition to the morphometric analysis of the fetal metamers. Even in the absence of changes in body weight gain and feed intake, crack altered the reproductive performance of dams. Exposure to the drug promoted late closure of the fetal fontanel. Furthermore, the morphometric study of the brain mass (BM)/skull cap ratio revealed a decrease in the BM of the fetuses exposed to the drug. Exposure to crack has an oxidative potential in fetal development, since exposure to the drug promoted placental lipid peroxidation. Our study showed that daily exposure to crack, even in lower frequency than that performed by users, has a teratogenic potential.

Behavioral and neurobiological alterations induced by chronic use of crack cocaine.

Crack cocaine is the crystal form of cocaine and can be smoked, and rapidly absorbed, and, in part for this reason, is potently addictive. It is hypothesized that crack cocaine is able to induce important changes in different tissues and organs, and thus dramatically alter behavior. Nevertheless, which alterations in the central nervous system are related to its frequent use is still a matter of discussion. The present study is a literature review of articles published between the years 2008 and 2018 on the theme 'crack cocaine and brain' available in PUBMED, MEDLINE, EMBASE, and Google scholar databases. The results show that the use of crack cocaine induces important behavioral, neuroanatomical, and biochemical alterations. The main behavioral sequelae include cognitive and emotional changes, such as increased anxiety and depressive symptoms, attention and memory deficits, and hyperactivity. Among the neurobiological alterations are reductions in the activity of the prefrontal, anterior cingulate cortex, and nucleus accumbens. Molecular changes include decreases in neurotrophic factors and increases in oxidative stress and inflammatory cytokines, which may be responsible for the morphological alterations observed. It is also hypothesized that these neurobiological changes might explain the emotional and cognitive dysfunctions experienced by crack cocaine addicts.

Epidemiology, clinical features and management of patients presenting to European emergency departments with acute cocaine toxicity: comparison between powder cocaine and crack cocaine cases.

Objective: To analyse the epidemiology, clinical picture and emergency department (ED) management of a large series of patients who presented to European EDs after cocaine consumption, comparing data from powder (C1 group) and crack (C2 group) consumers. Methods: Between October 2013 and December 2016, the Euro-DEN Plus Registry recorded 17,371 consecutive acute recreational drug toxicity presentations to 22 EDs in 14 European countries. Epidemiological and demographic data, co-ingestion of alcohol and other drugs, clinical features, ED management and outcome (death) were analysed for cocaine cases, and comparison of clinical picture in C1 and C2 patients were performed adjusting for alcohol and other drug co-ingestion. Results: We included 3002 cases (C1: 2600; C2: 376; mixed consumption: 26): mean age 32(9) years, 23% female. The proportion of presentations involving cocaine varied significantly between countries (>30% in Malta, Spain, France, Denmark) and only centres in France, United Kingdom, Poland, Ireland and Malta recorded crack-related cases. Cocaine was frequently used with ethanol (74.3%, C1>C2) and other drugs (56.8%, C2>C1), the most frequent amphetamine (19.4%, C1>C2) and opioids (18.9%, C2>C1). C2 patients were more likely to have clinically significant episodes of hypotension (adjusted OR = 2.35; 95%CI = 1.42-3.89), and bradypnea (1.81; 1.03-3.16) and systolic blood pressure >180 mmHg on ED arrival (2.59; 1.28-5.25); while less likely anxiety (0.51; 0.38-0.70), chest pain (0.47; 0.31-0.70), palpitations (0.57; 0.38-0.84), vomiting (0.54; 0.32-0.90), and tachycardia on ED arrival (0.52; 0.39-0.67). Sedative drugs were given in 29.3%. The median length of hospital stay was 4:02 h, 22.1% patients were hospitalized, and 0.4% (n = 12) died. Conclusion: Cocaine is commonly involved in European ED presentations with acute recreational drug toxicity, but there is variation across Europe not just in the involvement of cocaine but in the proportion related to powder versus crack. Some differences in clinical picture and ED management exist between powder cocaine and crack consumers.

Drogas ilícitas e gravidez Influência na morfologia fetal / Illicit drugs and pregnancy: influence on fetal morphology

Uso de drogas ilícitas como maconha, cocaína e crack durante a gestação tornou-se problema de saúde pública. O uso de drogas durante a gestação pode provocar má-formação, prematuridade, baixo peso, diminuição do perímetro cefálico, morte súbita. Aumenta a incidência de complicações como deslocamento de placenta, isquemias, infarto e morte. Conhecer os fatores de risco poderá ajudar a elaboração de programas de orientação para as gestantes e melhor conduta para os profissionais da saúde. Este estudo de revisão sistemática pesquisou nas bases de dados Bireme, Scielo, PubMed, Lilacs e Site Up to Date. A seleção levou em conta seus títulos e resumos relacionados ao assunto, no período de 2010 a 2017, utilizando os descritores drogas ilícitas/illict drug, cocaína/cocaine, gravidez/pregnancy e desenvolvimento fetal/fetal morphology. Foram encontrados 64 artigos; desses, foram selecionados 36, os mais recentes, estudos randomizados, relatos de casos e estudos coortes, os quais foram necessários para a construção do texto. Através desta análise observou-se que não existem artigos que falem diretamente sobre os riscos expostos e por qual motivo algumas pessoas, mesmo expostas aos riscos, possuem fetos normais. Portanto, novas pesquisas na área se tornam necessárias para melhor compreensão de como as drogas ilícitas interferem na formação fetal e adotar medidas profiláticas com o intuito de proteger o feto e a gestante, contribuindo para a melhoria da saúde pública.(AU)

Use of illicit drugs such as marijuana, cocaine and crack during pregnancy has become a public health problem. The use of drugs during pregnancy can cause malformation, prematurity, low weight, decreased head circumference, sudden death. It increases the incidence of complications such as placental dislocation, ischaemia, infarction and death. Knowing the risk factors can help the development of programs for counseling pregnant women and better conduct for health professionals. This systematic review study searched the Bireme, Scielo, PubMed, Lilacs and Site Up to Date databases. The selection took into account the titles and summaries related to the subject, from 2010 to 2017, using the descriptors illicit drug / illict drug, cocaine / cocaine, pregnancy / pregnancy and fetal development / fetal morphology. We found 64 articles, of which 36 were selected, the most recent, randomized studies, case reports, cohort studies, which were necessary for the construction of the text. Through this analysis it was observed that there are no articles that speak directly about the risks exposed and for which reason some people even exposed to the risks have normal fetuses. Therefore, new research in the area is necessary to better understand how illicit drugs interfere in fetal formation and adopt prophylactic measures to protect the fetus and pregnant women, contributing to the improvement of public health.(AU)

Exposure to crack cocaine causes adverse effects on marine mussels Perna perna.

Our study aimed to evaluate crack cocaine effects in different life stages of the marine mussel Perna perna. For this purpose, fertilization rate, embryo-larval development, lysosomal membrane stability and DNA strand breaks were assessed. Effect concentrations in gametes and in larval development were found after 1h (IC50=23.53mg·L-1) and 48h (IC50=16.31mg·L-1), respectively. The highest tested concentration showing no acute toxicity (NOEC) was 10mg·L-1, while the lowest observed effect concentration (LOEC) was 20mg·L-1. NOEC concerning embryo-larval development was 0.625mg·L-1, while the LOEC was 1.25mg·L-1. Cyto-genotoxic effects were evidenced in mussels exposed to crack cocaine concentrations ranging from 5 to 500µg·L-1. Our results report the first data on effects of an illicit drug to marine organisms and should encourage further ecotoxicological studies of these contaminants of emerging concern in coastal ecosystems.

Crack cocaine inhalation induces schizophrenia-like symptoms and molecular alterations in mice prefrontal cortex.

Crack cocaine (crack) addiction represents a major social and health burden, especially seeing as users are more prone to engage in criminal and violent acts. Crack users show a higher prevalence of psychiatric comorbidities - particularly antisocial personality disorders - when compared to powder cocaine users. They also develop cognitive deficits related mainly to executive functions, including working memory. It is noteworthy that stimulant drugs can induce psychotic states, which appear to mimic some symptoms of schizophrenia among users. Social withdraw and executive function deficits are, respectively, negative and cognitive symptoms of schizophrenia mediated by reduced dopamine (DA) tone in the prefrontal cortex (PFC) of patients. That could be explained by an increased expression of D2R short isoform (D2S) in the PFC of such patients and/or by hypofunctioning NMDA receptors in this region. Reduced DA tone has already been described in the PFC of mice exposed to crack smoke. Therefore, it is possible that behavioral alterations presented by crack users result from molecular and biochemical neuronal alterations akin to schizophrenia. Accordingly, we found that upon crack inhalation mice have shown decreased social interaction and working memory deficits analogous to schizophrenia's symptoms, along with increased D2S/D2L expression ratio and decreased expression of NR1, NR2A and NR2B NMDA receptor subunits in the PFC. Herein we propose two possible mechanisms to explain the reduced DA tone in the PFC elicited by crack consumption in mice, bringing also the first direct evidence that crack use may result in schizophrenia-like neurochemical, molecular and behavioral alterations.

Periodontal status in crack and cocaine addicted men: a cross-sectional study.

This cross-sectional study evaluated the association between crack/cocaine addiction and periodontal disease in men. Periodontal examination (probing depth, clinical attachment level, bleeding on probing, and plaque index) and interviews were performed in 160 patients (≥18 years) from the Federal University of Bahia. Crack and cocaine dependence was defined according to the medical records and interviews of each patient; all drug addicted volunteers used both crack and cocaine. T test, Chi-square test, and logistic regression were used to assess the associations between destructive periodontal disease and crack/cocaine dependence (p ≤ 0.05). Probing depth was significantly greater in crack/cocaine addicted individuals (2.84 ± 0.76 mm) compared with non-addicted individuals (2.55 ± 0.73 mm, p = 0.04). After adjusting for covariates, periodontitis was not significantly associated with crack/cocaine addiction (OR = 2.31, 95 % CI = 0.82-6.46, p = 0.11), which was only associated with age ≥35 years (OR = 4.16, 95 % CI = 1.65-10.50, p = 0.003) and higher dental plaque index (OR = 6.46, 95 % CI = 1.95-21.42, p = 0.002). In conclusion, although probing depth was greater in crack/cocaine addicted individuals, destructive periodontal disease was not associated with crack and cocaine addiction in the present population. Destructive periodontal disease was associated with age and dental plaque. Further studies in a larger sample size are required to confirm the results.

Acute crack cocaine exposure induces genetic damage in multiple organs of rats.

Crack cocaine is a very toxic product derived from cocaine. The aim of this study was to evaluate genetic damage in multiple organs of rats following acute exposure to crack cocaine. A total of 20 Wistar rats were distributed into four groups (n = 5), as follows: 0, 4.5, 9, and 18 mg/kg body weight (b.w.) of crack cocaine administered by intraperitoneal route (i.p.). All animals were killed 24 h after intraperitoneal (i.p.) injection. The results showed that crack cocaine increased the number of micronucleated cells in bone marrow cells exposed to 18 mg/kg crack cocaine (p < 0.05). Peripheral blood and liver cells presented genetic damage as depicted by single cell gel (comet) assay at 9 and 18 mg/kg doses (p < 0.05). Immunohistochemistry data revealed significant increase in 8-hydroxy-20-deoxyguanosine (8-OHdG) immunoexpression in hepatocytes of animals exposed to crack cocaine at 9 and 18 mg/kg (p < 0.05) when compared with negative controls. Taken together, our results demonstrate that crack cocaine is able to induce genomic damage in multiple organs of Wistar rats.

Genotoxicity and mutagenicity induced by acute crack cocaine exposure in mice.

CONTEXT: Crack cocaine is an illicit drug derived from cocaine, in which use and abuse have increased around the world, especially in developing countries. OBJECTIVES: The aim of this study was to evaluate genomic damage in multiple organs of mice following acute exposure to crack cocaine. For this purpose, single cell gel (comet) assay in peripheral blood, liver, kidney, and brain cells was performed and micronucleus test for bone narrow and liver cells was also made in this setting. MATERIAL AND METHODS: A total of 20 C57BL/10 male mice were distributed into four groups, as follows: 0, 4.5, 9, and 18 mg/kg b.w. of crack cocaine dissolved to 1% dimethyl sulfoxide by intraperitoneal (i.p.) route. All animals were sacrificed 24 h after i.p. injection. RESULTS: The results showed that crack cocaine induced DNA damage in peripheral blood, and brain cells for higher doses used as depicted by single cell gel (comet) assay data. Analysis of kidney cells showed no genetic damage for all groups tested. The number of micronucleated cells did not increase after crack cocaine exposure in bone narrow or liver cells. CONCLUSION: In summary, crack cocaine is a genotoxic agent in peripheral blood, liver, and brain cells but not mutagenic in multiple organs of mice.

Emerging patterns of crack use in Mexico City.

BACKGROUND: Recent studies in Mexico have documented a significant increase in crack cocaine use, indicating the potential for an emerging drug epidemic. METHODS: Ethnographic observations and interviews were used describe the profiles and patterns of use among street-recruited crack users in Mexico City. The data came from an international research collaboration funded by the National Institutes of Health. RESULTS: A polythetic typology was developed based on five dimensions central to categorizing patterns of crack use behavior: frequency of use, duration of use, context, social networks, and social contracts. Four types of users were discovered applying these dimensions: dabblers, stable users, crack heads, and old heads. Although several similarities were documented between patterns of crack use in Mexico and those in the United States and Western Europe, several key aspects distinguished crack users in this population: (1) self-regulated use; (2) non-linear progression of crack; and (3) the influence of the dimensions pertaining to setting, social networks, and social contract as contributing to understanding of the previous two. Further, we provide a discussion of how specific contextual factors in Mexico may be giving rise to these emerging patterns. CONCLUSION: Compared to the U.S. and Europe, this study finds that the majority of crack users were able to self-regulate their use without major disruption to daily social functioning. As crack use spreads in Mexico and other Latin American countries, we need to recognize the importance of social context in developing more tailored health and social responses that are specific to these developing countries.

Representações sociais do crack elaboradas por usuários em tratamento / Crack social representations elaborated by useres under treatment / Representaciones sociales del crack elaboradas por usuarios en tratamento

Objetivou-se conhecer e analisar o conteúdo e a estrutura da representação social do crack elaborada por dependentes químicos em tratamento. Este estudo foi realizado em uma instituição psiquiátrica de João Pessoa-PB, com 30 usuários de crack. Foram utilizados dois instrumentos: uma entrevista, a qual foi analisada por meio da análise de conteúdo temática e a técnica de associação livre de palavras, com o estímulo "crack", que foi analisada a partir do programa EVOC. Constatou-se uma representação negativa do crack, em que ele é personificado na figura do Diabo, tendo o poder de destruir a vida de seus usuários e da sociedade em geral. Observou-se, ainda, que essa representação é composta por elementos negativos que evidenciam a tristeza e o sofrimento que permeiam a realidade do usuário de crack. Espera-se que os resultados encontrados possam auxiliar os órgãos competentes na formação de políticas públicas voltadas para esta problemática, capazes de abarcar os aspectos psicossociais do consumo de crack.

The main goal of this research was to know and to analyze the content and the structure of crack social representation, elaborated by drug addicts under treatment. This study was conducted in a psychiatric institution of João Pessoa-PB (Brazil), with 30 crack users. Two instruments were used: an interview, which was analyzed by the Thematic Content Analysis; and the Free Word Association Technique, with the tag "crack," which was analyzed from the EVOC program. It was found a negative representation of the crack, where it is embodied in the figure of the Devil, having enough power to destroy its users' lives and the society in general. It was also observed that this representation is made up by negative elements which evidence the sadness and the suffering that permeate the crack users reality. The results found are expected to aid state offices to bring out public policies in order to find this problematic issue a solution, which is able to encompass the psychosocial aspects of the crack usage.

El objetivo fue conocer y analizar el contenido y la estructura de la representación social del crack, elaborada por dependientes químicos en tratamiento. Este estudio fue realizado en una institución psiquiátrica de João Pessoa-Pb, con 30 usuarios de crack. Fueron utilizados dos instrumentos: una entrevista, que fue analizada por medio del Análisis de Contenido Temático; y, la Técnica de Asociación Libre de Palabras, con el estímulo "crack", que fue analizada a partir del programa EVOC. Se constató una representación negativa del crack, el que es personificado en la figura del Diablo, teniendo el poder de destruir la vida de sus usuarios y de la sociedad en general. Se observó aún que esa representación está compuesta por elementos negativos que evidencian la tristeza y el sufrimiento que comprenden la realidad del usuario de crack. Se espera que los resultados encontrados puedan auxiliar a los órganos competentes en la formación de políticas públicas dirigidas hacia esta problemática, capaces de abarcar los aspectos psicosociales del consumo de crack.

Genomic instability in human lymphocytes from male users of crack cocaine.

Recent research suggests that crack cocaine use alters systemic biochemical markers, like oxidative damage and inflammation markers, but very few studies have assessed the potential effects of crack cocaine at the cellular level. We assessed genome instability by means of the comet assay and the cytokinesis-block micronucleus technique in crack cocaine users at the time of admission to a rehabilitation clinic and at two times after the beginning of withdrawal. Thirty one active users of crack cocaine and forty control subjects were evaluated. Comparison between controls and crack cocaine users at the first analysis showed significant differences in the rates of DNA damage (p = 0.037). The frequency of micronuclei (MN) (p < 0.001) and nuclear buds (NBUDs) (p < 0.001) was increased, but not the frequency of nucleoplasmic bridges (NPBs) (p = 0.089). DNA damage decreased only after the end of treatment (p < 0.001). Micronuclei frequency did not decrease after treatment, and nuclear buds increased substantially. The results of this study reveal the genotoxic and mutagenic effects of crack cocaine use in human lymphocytes and pave the way for further research on cellular responses and the possible consequences of DNA damage, such as induction of irreversible neurological disease and cancer.

Correlation between cocaine prices and purity with trends in emergency department visits in a major metropolitan area.

Illicit drug use not only causes acute and chronic adverse health outcomes but also results in a significant burden to health care providers. The objective of this study is to examine the relationship between cocaine prices and purity with emergency department (ED) visits for the Chicago-Naperville-Joliet metropolitan area. Our primary outcome was number of cocaine-related ED visits per quarter provided by the Drug Abuse Warning Network. The predictor variables of cocaine purity and price were provided by the System to Retrieve Information from Drug Evidence database. Autoregressive integrated moving average (ARIMA) regressions were used to estimate the effects of cocaine price and purity on cocaine-related ED visits. Although cocaine prices did not change substantially over time, cocaine purity decreased by over 30 % between 2006 and 2010. ARIMA regression results suggest that cocaine-related ED visits were not significantly associated with powder or crack cocaine prices; however, a decrease in powder cocaine purity was associated with 2,081 fewer ED visits overall from 2007 to 2010. The cocaine trade continues to be a major public health and law enforcement threat to large metropolitan cities like Chicago. Regular monitoring of cocaine purity levels may provide early warning of impending changes in cocaine-related ED visits for law enforcement and health care providers.