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1.
Nat Commun ; 11(1): 4634, 2020 09 14.
Artigo em Inglês | MEDLINE | ID: mdl-32929078

RESUMO

The current opioid epidemic necessitates a better understanding of human addiction neurobiology to develop efficacious treatment approaches. Here, we perform genome-wide assessment of chromatin accessibility of the human striatum in heroin users and matched controls. Our study reveals distinct neuronal and non-neuronal epigenetic signatures, and identifies a locus in the proximity of the gene encoding tyrosine kinase FYN as the most affected region in neurons. FYN expression, kinase activity and the phosphorylation of its target Tau are increased by heroin use in the post-mortem human striatum, as well as in rats trained to self-administer heroin and primary striatal neurons treated with chronic morphine in vitro. Pharmacological or genetic manipulation of FYN activity significantly attenuates heroin self-administration and responding for drug-paired cues in rodents. Our findings suggest that striatal FYN is an important driver of heroin-related neurodegenerative-like pathology and drug-taking behavior, making FYN a promising therapeutic target for heroin use disorder.


Assuntos
Cromatina/metabolismo , Corpo Estriado/enzimologia , Dependência de Heroína/enzimologia , Terapia de Alvo Molecular , Proteínas Proto-Oncogênicas c-fyn/metabolismo , Animais , Sequência de Bases , Comportamento Animal/efeitos dos fármacos , Sinais (Psicologia) , Genoma , Células HEK293 , Heroína/efeitos adversos , Humanos , Masculino , Neurônios/metabolismo , Fosforilação/efeitos dos fármacos , Regiões Promotoras Genéticas/genética , Proteínas Proto-Oncogênicas c-fyn/antagonistas & inibidores , Ratos Long-Evans , Autoadministração , Transcrição Genética/efeitos dos fármacos , Proteínas tau/metabolismo
2.
Artigo em Inglês | MEDLINE | ID: mdl-32842510

RESUMO

The decreasing age of young people injecting illicit drugs is an under-reported challenge for the prevention of HIV transmission worldwide. Young people aged 15-24 years represent 1 in 5 persons living with HIV in Mauritius where the epidemic is driven by injecting drug use and risky sexual behaviours. We recruited 22 heroin users aged 18-24 and 5 service providers working in harm reduction (HR) for the present study. Qualitative data were collected through unstructured interviews. We adopted an economic framework and an inductive approach to the analysis, which implied revising codes and themes. The risks heroin users described as consumers of illicit drugs and as clients of HR services could not be analyzed in isolation. Polydrug use emerged as a recurrent coping mechanism resulting from the changing dynamics within the heroin market. The risks faced by women went beyond addiction and infection with HIV. How participants viewed the risks and benefits linked to using heroin was greatly influenced by gaps in knowledge that left room for uncertainty and reinforcing mechanisms such as peer influence. The study shows that qualitative research can produce in-depth socio-behavioural insights required to produce more effective services for young people.


Assuntos
Infecções por HIV/complicações , Redução do Dano , Conhecimentos, Atitudes e Prática em Saúde , Heroína/efeitos adversos , Abuso de Substâncias por Via Intravenosa/psicologia , Adolescente , Feminino , Infecções por HIV/epidemiologia , Infecções por HIV/psicologia , Heroína/administração & dosagem , Humanos , Entrevistas como Assunto , Masculino , Maurício , Percepção , Pesquisa Qualitativa , Medição de Risco , Abuso de Substâncias por Via Intravenosa/epidemiologia , Adulto Jovem
3.
BMC Med Genet ; 21(1): 157, 2020 07 31.
Artigo em Inglês | MEDLINE | ID: mdl-32736537

RESUMO

BACKGROUND: Heroin dependence is a complex disease with multiple phenotypes. Classification of heroin users into more homogeneous subgroups on the basis of these phenotypes could help to identify the involved genetic factors and precise treatments. This study aimed to identify the association between genetic polymorphisms of DA synthesis and metabolism genes, including tyrosine hydroxylase (TH), DOPA decarboxylase (DDC), solute carrier family 6 member 3 (SLC6A3) and DA beta-hydroxylase (DBH), with six important phenotypes of heroin dependence. METHODS: A total of 801 heroin dependent patients were recruited and fourteen potential functional single nucleotide polymorphisms (SNPs) were genotyped by SNaPshot. Associations between SNPs with six phenotypes were mainly assessed by binary logistic regression. Generalized multifactor dimensionality reduction was used to analyze the gene-by-gene and gene-by-environment interactions. RESULTS: We found that DBH rs1611114 TT genotype had a protective effect on memory impairment after heroin dependence (P = 0.002, OR = 0.610). We also found that the income-rs12666409-rs129915-rs1611114 interaction yielded the highest testing balance accuracy and cross-validation consistency for memory change after heroin dependence. CONCLUSIONS: Our results suggest that the memory change after heroin dependence was a result of a combination of genetics and environment. This finding could lead to a better understanding of heroin dependence and further improve personalized treatment.


Assuntos
Dopamina/biossíntese , Dopamina/metabolismo , Estudos de Associação Genética , Predisposição Genética para Doença , Dependência de Heroína/genética , Adulto , Euforia , Feminino , Interação Gene-Ambiente , Heroína/efeitos adversos , Dependência de Heroína/fisiopatologia , Humanos , Masculino , Memória , Metadona/efeitos adversos , Fenótipo , Polimorfismo de Nucleotídeo Único/genética
4.
Medicine (Baltimore) ; 99(24): e19963, 2020 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-32541447

RESUMO

Covertly using heroin during methadone maintenance treatment (MMT) is very common among heroin-dependent patients, which has posed threats to the physical health of heroin-dependent patients and social safety. Covertly using heroin may be influenced by many factors, especially social capital. Therefore, we aimed to investigate the relationship between behaviors of covertly using heroin during MMT and social capital heroin-dependent patients in Sichuan Province, China. A cross-sectional study was conducted between October and November 2018, with a total of 581 heroin-dependent patients participating in the study. In addition to socio-demographic characteristics and heroin use related behaviors, the questionnaire also included the measures of social capital: social network (SN), social support (SP), community participation (CP) and social trust (ST). Multivariate logistic regression analyses were used to estimate the association between different measures of social capital and heroin use. The prevalence of covertly using heroin of heroin during MMT was 31.0% among our participants in the 6 months before the study. After adjusting for socio-demographic factors and heroin-use related variables, SN (OR = 0.85, 95% CI: 0.76-0.95), SP (OR = 0.89, 95% CI: 0.83-0.95), and ST (OR = 0.88, 95% CI: 0.81-0.95) were significantly associated with heroin use. Results suggest that social capital may have a protective effect on behavior of covertly using heroin during MMT, which should be consider in the interventions for heroin-dependent patients, in order to reduce the incidence of heroin use during MMT as well as improve the compliance of MMT.


Assuntos
Dependência de Heroína/tratamento farmacológico , Heroína/efeitos adversos , Metadona/uso terapêutico , Tratamento de Substituição de Opiáceos/métodos , Adulto , China/epidemiologia , Participação da Comunidade/métodos , Estudos Transversais , Feminino , Heroína/administração & dosagem , Dependência de Heroína/epidemiologia , Dependência de Heroína/psicologia , Humanos , Masculino , Pessoa de Meia-Idade , Tratamento de Substituição de Opiáceos/estatística & dados numéricos , Cooperação do Paciente/psicologia , Cooperação do Paciente/estatística & dados numéricos , Prevalência , Capital Social , Rede Social , Apoio Social
5.
AIDS Behav ; 24(9): 2720-2731, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32185596

RESUMO

We studied mechanisms driving gender differences in HIV incidence among 651 women and men who inject drugs (PWID) in Tijuana, Mexico, hypothesizing that sex work will mediate the association between female gender and HIV incidence. Of 43 HIV seroconversions occurring between 2011 and 2018, 8.8% were among females and 5.2% among males. HIV incidence density was significantly higher among females versus males (1.75 per 100 person years [PY], 95% CI 1.16-2.66, vs. 0.95 per 100 PY, 95% CI 0.62-1.47). Factors significantly associated with HIV seroconversion were: sex work (adjusted hazard ratio [aHR] = 2.25, 95% CI 1.05-4.80); methamphetamine injection (aHR = 2.30, 95% CI 1.12-4.73); and methamphetamine and heroin co-injection in the past six months (aHR = 2.26, 95% CI 1.23-4.15). In mediation analyses, sex work mediated a substantial proportion (84.3%) of the association between female gender and HIV incidence. Interventions should target female PWID who engage in sex work to reduce gender-related disparities in HIV incidence.


Assuntos
Infecções por HIV/epidemiologia , Heroína/efeitos adversos , Metanfetamina/efeitos adversos , Trabalho Sexual , Abuso de Substâncias por Via Intravenosa/epidemiologia , Adulto , Feminino , Infecções por HIV/diagnóstico , Humanos , Incidência , Masculino , México/epidemiologia , Pessoa de Meia-Idade , Fatores de Risco , Inquéritos e Questionários
6.
PLoS One ; 15(3): e0230408, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32210442

RESUMO

BACKGROUND: Opioid overdose mortality continues to increase in the United States despite significant investments to reverse the epidemic. The national response to-date has focused primarily on reducing opioid prescribing, yet reductions in prescribing have been associated with patients reporting uncontrolled pain, psychological distress, and transition to illicit substances. The aim of this study is to qualitatively explore chronic pain management experiences among PLWH with a history of illicit substance use after long-term opioid therapy reductions or discontinuations. METHODS: We analyzed 18 interviews, stopping upon reaching thematic saturation, with HIV-positive participants with a history of substance use who were enrolled in a longitudinal cohort study to assess the impact of prescribing changes among patients with chronic pain. Participants in this nested qualitative study had been reduced/discontinued from opioid pain relievers (OPRs) within the 12 months prior to interview. Interviews were audio-recorded and transcribed verbatim. Two analysts coded all interviews, interrater reliability was measured, and coding discrepancies discussed. The study took place in San Francisco, California in 2018. RESULTS: Eleven participants were male with a mean age of 55; 8 were African American and 8 were White. All participants were HIV-positive, actively engaged in primary care, and had a lifetime history of illicit substance use. Twelve reported using illicit substances within the past year, including non-prescription opioids/heroin (10), and stimulant use (10). After being reduced/discontinued from their long-term opioid therapy, patients reported developing complex multimodal pain management systems that often included both nonpharmacological approaches and illicit substance use. Participants encountered a range of barriers to nonpharmacological therapies including issues related to accessibility and availability. Participants often reported attempts to replicate their prior OPR prescription by seeking out the same medication and dose from illicit sources and reported transitioning to heroin after exhausting other options. CONCLUSION: After being reduced/discontinued from OPRs, HIV-positive patients with a history of substance use reported experimenting with a range of pain management modalities including nonpharmacological therapies and illicit substance use to manage symptoms of opioid withdrawal and pain. Providers should consider that any change to a patients' long-term opioid therapy may result in experimentation with pain management outside of the medical setting and may want to employ patient-centered, holistic approaches when managing patients' opioid prescriptions and chronic pain.


Assuntos
Analgésicos Opioides/uso terapêutico , Infecções por HIV/tratamento farmacológico , Transtornos Relacionados ao Uso de Opioides/tratamento farmacológico , Dor/tratamento farmacológico , Acupuntura , Analgésicos Opioides/efeitos adversos , Prescrições de Medicamentos , Feminino , Infecções por HIV/patologia , Infecções por HIV/virologia , Heroína/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Transtornos Relacionados ao Uso de Opioides/patologia , Transtornos Relacionados ao Uso de Opioides/virologia , Dor/patologia , Dor/virologia , Manejo da Dor , São Francisco/epidemiologia , Pessoas Transgênero
7.
Biomed Pharmacother ; 125: 109918, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32036213

RESUMO

OBJECTIVES: Drug abuse is one of the most severe global social and public health problems, especially in China. However, objective blood biomarkers that are easy to detect are still in great need. This study was aim to explore the expression pattern of circulating microRNAs (miRNAs) in subjects with drug addiction and test the potential of altered serum miRNAs as noninvasive diagnostic tools for drug abuse. METHODS: Serum samples were obtained from 42 heroin abusers, 42 methamphetamine (MA) abusers and 42 controls. Microarray-based miRNA analysis was first applied to screen unique serum miRNA profiles in drug abusers on a training set of serum samples from 12 heroin abusers, 12 MA abusers and 12 control subjects. The expression levels of selected candidate miRNAs were subsequently verified in individual samples of the training set and further confirmed independently in a validation set of samples from 30 heroin abusers, 30 MA abusers and 30 controls using real-time quantitative polymerase chain reaction (RT-qPCR). RESULTS: Microarray analysis identified 116 and 109 significantly altered miRNAs in heroin abusers and MA abusers, respectively. Three miRNAs, including let-7b-5p, miR-206 and miR-486-5p, were verified to be significantly and steadily increased in heroin abusers, and miR-9-3p was significantly increased in MA abusers compared with normal controls. The areas under the curve (AUCs) of the ROC curve of these miRNAs ranged from 0.718 to 0.867. CONCLUSIONS: Our study raises the possibility that the altered serum miRNAs could potentially be used as an auxiliary tool to identify individuals in drug abuse and addiction.


Assuntos
Transtornos Relacionados ao Uso de Anfetaminas/sangue , Perfilação da Expressão Gênica/métodos , Dependência de Heroína/sangue , Heroína/efeitos adversos , Metanfetamina/efeitos adversos , MicroRNAs/sangue , Adulto , Transtornos Relacionados ao Uso de Anfetaminas/genética , Biomarcadores/sangue , Feminino , Dependência de Heroína/genética , Humanos , Masculino , MicroRNAs/biossíntese , MicroRNAs/genética , Pessoa de Meia-Idade
8.
Curr Top Med Chem ; 20(7): 585-597, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32003694

RESUMO

BACKGROUND: The differential utility of neurocognitive impulsivity and externalizing/ internalizing traits as putative endophenotypes for dependence on heroin vs. amphetamine is unclear. OBJECTIVE: This exploratory study aims to determine: (1) whether neurocognitive impulsivity dimensions and externalizing/internalizing traits are correlated between siblings discordant for heroin and amphetamine dependence; and (2) which of these associations are common across substances and which are substance- specific. METHODS: Pearson correlations between individuals with 'pure' heroin and amphetamine dependence and their unaffected biological siblings (n = 37 heroin sibling pairs; n = 30 amphetamine sibling pairs) were run on 10 neurocognitive measures, 6 externalizing measures, and 5 internalizing measures. Sibling pair effects were further examined using regression. RESULTS: Siblings discordant for heroin dependence were significantly correlated on delay aversion on the Cambridge Gambling Task, risk-taking on the Balloon Analogue Risk Task, sensation seeking, and hopelessness. Siblings discordant for amphetamine dependence were significantly correlated on the quality of decision-making on the Cambridge Gambling Task, discriminability on the Immediate Memory Task, commission errors on the Go/No Go Task, trait impulsivity, ADHD and anxiety sensitivity. CONCLUSION: Dimensions of impulsivity and externalizing/internalizing traits appear to aggregate among siblings discordant for substance dependence. Risk-taking propensity, sensation seeking and hopelessness were specific for heroin sibling pairs. Motor/action impulsivity, trait impulsivity, and anxiety sensitivity were specific to amphetamine sibling pairs. Decisional/choice impulsivity was common across both heroin and amphetamine sibling pairs. These findings provide preliminary evidence for the utility of neurocognitive impulsivity and externalizing/ internalizing traits as candidate endophenotypes for substance dependence in general and for substance-specific dependencies.


Assuntos
Anfetamina/efeitos adversos , Comportamento Aditivo/psicologia , Endofenótipos/metabolismo , Heroína/efeitos adversos , Transtornos Relacionados ao Uso de Substâncias/psicologia , Adulto , Análise de Variância , Cognição , Tomada de Decisões , Feminino , Humanos , Comportamento Impulsivo , Testes de Estado Mental e Demência , Inventário de Personalidade , Medição de Risco , Irmãos/psicologia
9.
Psychopharmacology (Berl) ; 237(4): 1055-1062, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31915860

RESUMO

RATIONALE: Deficits in response inhibition associated with heroin use could last several months after abstinence in heroin users, and their response inhibition can also be interfered with task-irrelevant drug-related cues. However, it is unclear whether exposure to drug-related cues affects subsequent response inhibition in heroin users following abstinence. OBJECTIVES: The present study aimed to investigate how drug-related cues with different durations between stimulus presentations, referred to as stimulus onset asynchronies (SOAs), affect subsequent response inhibition in heroin abstainers (HAs) with different length of abstinence. METHODS: Sixty-seven male HAs performed a modified Go/NoGo task in which a motor response to frequent Go targets and no response to rare NoGo targets were required and a Go or NoGo target was displayed after either a heroin-related or a neutral picture presented for the 200 ms and 600 ms SOAs. RESULTS: The HAs responded significantly faster to Go targets following the neutral pictures for the 600 ms SOA compared to other conditions. They also made more commission errors following heroin-related pictures compared to neutral pictures regardless of the SOAs. The shorter-term HAs made more commission errors compared to the longer-term HAs following the 200 ms SOA, and it was only a trend when the SOA was 600 ms. Additionally, negative correlations between the duration of current abstinence and commission errors were observed following cues with the 200 ms SOA. CONCLUSIONS: Impaired response inhibition in HAs can be improved through protracted drug abstinence. However, that effect can be reduced by exposure to drug-related cues, which may increase the risk of relapse.


Assuntos
Sinais (Psicologia) , Dependência de Heroína/psicologia , Heroína/efeitos adversos , Inibição Psicológica , Tempo de Reação/efeitos dos fármacos , Adulto , Heroína/administração & dosagem , Dependência de Heroína/diagnóstico , Humanos , Masculino , Pessoa de Meia-Idade , Estimulação Luminosa/métodos , Tempo de Reação/fisiologia , Fatores de Tempo
10.
Sci Rep ; 10(1): 833, 2020 01 21.
Artigo em Inglês | MEDLINE | ID: mdl-31964994

RESUMO

While it is known that opioid receptors (ORs) are densely expressed in both the brain and periphery, it is widely accepted that hypoxic effects of opioids result solely from their direct action in the CNS. To examine the role of peripheral ORs in triggering brain hypoxia, we used oxygen sensors in freely moving rats to examine how naloxone-HCl and naloxone-methiodide, the latter which is commonly believed to be peripherally restricted, affect brain oxygen responses induced by intravenous heroin at low, human-relevant doses. Similar to naloxone-HCl, naloxone-methiodide at a relatively low dose (2 mg/kg) fully blocked heroin-induced decreases in brain oxygen levels. As measured by mass spectrometry, naloxone-methiodide was found to be ~40-fold less permeable than naloxone-HCl across the blood-brain barrier, thus acting as a selective blocker of peripheral ORs. Despite this selectivity, a low but detectable amount of naloxone was found in brain tissue after naloxone-methiodide administration, potentially influencing our results. Therefore, we examined the effects of naloxone-methiodide at a very low dose (0.2 mg/kg; at which naloxone was undetectable in brain tissue) and found that this drug still powerfully attenuates heroin-induced brain oxygen responses. These data demonstrate the role of peripheral ORs in triggering heroin-induced respiratory depression and subsequent brain hypoxia.


Assuntos
Heroína/efeitos adversos , Hipóxia Encefálica/etiologia , Receptores Opioides/fisiologia , Animais , Barreira Hematoencefálica/metabolismo , Encéfalo/metabolismo , Hipóxia Encefálica/tratamento farmacológico , Naloxona/administração & dosagem , Naloxona/análogos & derivados , Naloxona/metabolismo , Naloxona/farmacologia , Oxigênio/metabolismo , Compostos de Amônio Quaternário/administração & dosagem , Compostos de Amônio Quaternário/metabolismo , Compostos de Amônio Quaternário/farmacologia , Ratos , Receptores Opioides/metabolismo
11.
Forensic Sci Int ; 306: 110093, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31816483

RESUMO

Studies on the mortalities of drug abusers in China are scarce. This study explores the deaths of methamphetamine, opioid, and ketamine abusers in Shanghai (2004-2017) and Wuhan (2005-2017). Chi-square/Fisher's exact tests were used to compare the differences in terms of region, gender, age, cause of death, and the method used in the last drug abuse. Poisson regression models were used to estimate the rate ratios ("RRs") and annual percentage changes ("APCs"). 314 heroin, 43 methamphetamine, and 4 ketamine abusers were included. Furthermore, simultaneously, 6 abusers used heroin and methamphetamine, and 7 abusers used methamphetamine and ketamine. Heroin-related deaths have declined in Shanghai (APC, -16.1; 95 % CI, -18.4 to -11.3) and Wuhan (APC, -16.0; 95 % CI, -18.9 to -10.6), whereas methamphetamine-related deaths have increased in Wuhan (APC, 12.8; 95 % CI, 0.0 to 29.2). On the whole, in the two cities, males were more frequently observed than females in heroin-related deaths (4.4, 230/52). However, the gender ratios for methamphetamine- (1.8, 34/19) and ketamine-related deaths (1.2, 6/5) were close to one. In view of the mortality rates of the drug abusers in most Chinese cities were still unclear, it is thus important to improve mortality surveillance of the drug abusers at the national level.


Assuntos
Analgésicos Opioides/envenenamento , Ketamina/envenenamento , Metanfetamina/envenenamento , Transtornos Relacionados ao Uso de Substâncias/mortalidade , Adolescente , Adulto , Distribuição por Idade , Analgésicos Opioides/efeitos adversos , Intoxicação por Monóxido de Carbono/mortalidade , China/epidemiologia , Feminino , Heroína/efeitos adversos , Heroína/envenenamento , Humanos , Drogas Ilícitas/efeitos adversos , Drogas Ilícitas/envenenamento , Ketamina/efeitos adversos , Masculino , Metanfetamina/efeitos adversos , Pessoa de Meia-Idade , Distribuição por Sexo , Suicídio/estatística & dados numéricos , Adulto Jovem
12.
PLoS One ; 14(12): e0215042, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31887142

RESUMO

BACKGROUND AND AIMS: Using mathematical modeling to illustrate and predict how different heroin source-forms: "black tar" (BTH) and powder heroin (PH) can affect HIV transmission in the context of contrasting injecting practices. By quantifying HIV risk by these two heroin source-types we show how each affects the incidence and prevalence of HIV over time. From 1997 to 2010 PH reaching the United States was manufactured overwhelmingly by Colombian suppliers and distributed in the eastern states of the United States. Recently Mexican cartels that supply the western U.S. states have started to produce PH too, replacing Colombian distribution to the east. This raises the possibility that BTH in the western U.S. may be replaced by PH in the future. DESIGN: We used an agent-based model to evaluate the impact of use of different heroin formulations in high- and low-risk populations of persons who inject drugs (PWID) who use different types of syringes (high vs. low dead space) and injecting practices. We obtained model parameters from peer-reviewed publications and ethnographic research. RESULTS: Heating of BTH, additional syringe rinsing, and subcutaneous injection can substantially decrease the risk of HIV transmission. Simulation analysis shows that HIV transmission risk may be strongly affected by the type of heroin used. We reproduced historic differences in HIV prevalence and incidence. The protective effect of BTH is much stronger in high-risk compared with low-risk populations. Simulation of future outbreaks show that when PH replaces BTH we expect a long-term overall increase in HIV prevalence. In a population of PWID with mixed low- and high-risk clusters we find that local HIV outbreaks can occur even when the overall prevalence and incidence are low. The results are dependent on evidence-supported assumptions. CONCLUSIONS: The results support harm-reduction measures focused on a reduction in syringe sharing and promoting protective measures of syringe rinsing and drug solution heating.


Assuntos
Infecções por HIV/epidemiologia , Dependência de Heroína/epidemiologia , Abuso de Substâncias por Via Intravenosa/epidemiologia , Redução do Dano , Heroína/efeitos adversos , Humanos , Incidência , Modelos Teóricos , Uso Comum de Agulhas e Seringas , Prevalência , Fatores de Risco , Assunção de Riscos , Seringas , Estados Unidos , Carga Viral/efeitos dos fármacos
13.
Am J Case Rep ; 20: 1715-1718, 2019 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-31747388

RESUMO

BACKGROUND With the increasing prevalence of substance use in pregnancy, the rates of neonatal abstinence syndrome (NAS) are dramatically increasing. There is little information on the use of multiple substances in adults, even less so of polysubstance abuse during pregnancy and the consequences for the fetus as well as the mother. CASE REPORT A newborn male born at 35 weeks presented post-delivery with hips bilaterally dislocated and hyperflexed. The patient's legs fully extended and their shoulders were bilaterally mid-flexed with arms fully extended. This neonate was also reported to have bilateral hearing and vision loss as well as NAS symptoms of high-pitched crying and respiratory distress. During pregnancy the mother in this case study admitted to using buprenorphine, benzodiazepines, gabapentin, and heroin. The consequences of using this combination has not been well studied in pregnancy. CONCLUSIONS The presented case had severe complications, likely due to maternal polysubstance use and poor prenatal care in pregnancy. Clonidine was used to control the NAS symptoms, ranitidine was used to treat the gastroesophageal reflux, and glycopyrronium bromide was used for the neonate's excessive secretions. After delivery, the patient was placed on a nasal noninvasive cannula for respiratory distress and was transferred to a different hospital for treatment of the more serious comorbid conditions.


Assuntos
Hipóxia-Isquemia Encefálica/induzido quimicamente , Síndrome de Abstinência Neonatal/etiologia , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Benzodiazepinas/efeitos adversos , Buprenorfina/efeitos adversos , Feminino , Gabapentina/efeitos adversos , Heroína/efeitos adversos , Humanos , Recém-Nascido , Masculino , Gravidez
14.
J Am Podiatr Med Assoc ; 109(6): 437-444, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31755766

RESUMO

BACKGROUND: On a national level, heroin-related hospital admissions have reached an all-time high. With the foot being the fourth most common injection site, heroin-related lower-extremity infections have become more prevalent owing to many factors, including drug preparation, injection practices, and unknown additives. METHODS: We present a 16-month case series in which eight patients with lower-extremity infections secondary to heroin abuse presented to The Jewish Hospital in Cincinnati, Ohio. RESULTS: Three cases of osteomyelitis were seen. All of the infections were cultured and yielded a wide array of microbes, including Staphyloccoccus, Streptococcus, Bacillus, Serratia, Prevotella, and Eikenella. All of the patients were treated with intravenous antibiotic agents, with nearly all receiving combination therapy. Seven of the eight patients underwent surgery during their hospital stay, with two undergoing amputation. Only half of the patients followed up after discharge. CONCLUSIONS: This case series brings to light many considerations in the diagnosis and management of the heroin user, including multivariable attenuation of immunity, existing predisposition to infection backed by unsterile drug preparation and injection practices, innocuous presentation of deep infections, microbial spectrum, and recommendations on antimicrobial intervention, noncompliance, and poor follow-up. By having greater knowledge in unique considerations of diagnosis and treatment, more efficient care can be provided to this unique patient population.


Assuntos
Dependência de Heroína/complicações , Osteomielite/diagnóstico , Infecções dos Tecidos Moles/diagnóstico , Abuso de Substâncias por Via Intravenosa/complicações , Adulto , Antibacterianos/uso terapêutico , Feminino , Heroína/efeitos adversos , Dependência de Heroína/imunologia , Humanos , Hiperalgesia/induzido quimicamente , Extremidade Inferior , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Osteomielite/tratamento farmacológico , Osteomielite/etiologia , Manejo da Dor , Cooperação do Paciente , Radiografia , Infecções dos Tecidos Moles/tratamento farmacológico , Infecções dos Tecidos Moles/microbiologia , Infecções dos Tecidos Moles/cirurgia
15.
PLoS Med ; 16(11): e1002956, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31714940

RESUMO

BACKGROUND: Opioid misuse and deaths are increasing in the United States. In 2017, Ohio had the second highest overdose rates in the US, with the city of Cincinnati experiencing a 50% rise in opioid overdoses since 2015. Understanding the temporal and geographic variation in overdose emergencies may help guide public policy responses to the opioid epidemic. METHODS AND FINDINGS: We used a publicly available data set of suspected heroin-related emergency calls (n = 6,246) to map overdose incidents to 280 census block groups in Cincinnati between August 1, 2015, and January 30, 2019. We used a Bayesian space-time Poisson regression model to examine the relationship between demographic and environmental characteristics and the number of calls within block groups. Higher numbers of heroin-related incidents were found to be associated with features of the built environment, including the proportion of parks (relative risk [RR] = 2.233; 95% credible interval [CI]: [1.075-4.643]), commercial (RR = 13.200; 95% CI: [4.584-38.169]), manufacturing (RR = 4.775; 95% CI: [1.958-11.683]), and downtown development zones (RR = 11.362; 95% CI: [3.796-34.015]). The number of suspected heroin-related emergency calls was also positively associated with the proportion of male population, the population aged 35-49 years, and distance to pharmacies and was negatively associated with the proportion aged 18-24 years, the proportion of the population with a bachelor's degree or higher, median household income, the number of fast food restaurants, distance to hospitals, and distance to opioid treatment programs. Significant spatial and temporal heterogeneity in the risks of incidents remained after adjusting for covariates. Limitations of this study include lack of information about the nature of incidents after dispatch, which may differ from the initial classification of being related to heroin, and lack of information on local policy changes and interventions. CONCLUSIONS: We identified areas with high numbers of reported heroin-related incidents and features of the built environment and demographic characteristics that are associated with these events in the city of Cincinnati. Publicly available information about opiate overdoses, combined with data on spatiotemporal risk factors, may help municipalities plan, implement, and target harm-reduction measures. In the US, more work is necessary to improve data availability in other cities and states and the compatibility of data from different sources in order to adequately measure and monitor the risk of overdose and inform health policies.


Assuntos
Overdose de Drogas/epidemiologia , Dependência de Heroína/epidemiologia , Teorema de Bayes , Bases de Dados Factuais , Serviços Médicos de Emergência/tendências , Serviço Hospitalar de Emergência/tendências , Feminino , Heroína/efeitos adversos , Humanos , Masculino , Ohio/epidemiologia , Fatores de Risco , Análise Espaço-Temporal , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Estados Unidos
16.
Nat Commun ; 10(1): 4140, 2019 09 12.
Artigo em Inglês | MEDLINE | ID: mdl-31515501

RESUMO

Persistent transcriptional and morphological events in the nucleus accumbens (NAc) and other brain reward regions contribute to the long-lasting behavioral adaptations that characterize drug addiction. Opiate exposure reduces the density of dendritic spines on medium spiny neurons of the NAc; however, the underlying transcriptional and cellular events mediating this remain unknown. We show that heroin self-administration negatively regulates the actin-binding protein drebrin in the NAc. Using virus-mediated gene transfer, we show that drebrin overexpression in the NAc is sufficient to decrease drug seeking and increase dendritic spine density, whereas drebrin knockdown potentiates these effects. We demonstrate that drebrin is transcriptionally repressed by the histone modifier HDAC2, which is relieved by pharmacological inhibition of histone deacetylases. Importantly, we demonstrate that heroin-induced adaptations occur only in the D1+ subset of medium spiny neurons. These findings establish an essential role for drebrin, and upstream transcriptional regulator HDAC2, in opiate-induced plasticity in the NAc.


Assuntos
Proteínas dos Microfilamentos/metabolismo , Neuropeptídeos/metabolismo , Transtornos Relacionados ao Uso de Opioides/metabolismo , Animais , Comportamento Animal/efeitos dos fármacos , Epigênese Genética/efeitos dos fármacos , Heroína/efeitos adversos , Histona Desacetilase 2/metabolismo , Masculino , Plasticidade Neuronal/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Neuropeptídeos/genética , Núcleo Accumbens/metabolismo , Alcaloides Opiáceos/efeitos adversos , Transtornos Relacionados ao Uso de Opioides/fisiopatologia , Dor/metabolismo , Ratos Sprague-Dawley , Sinapses/efeitos dos fármacos , Sinapses/metabolismo
18.
Prev Med ; 126: 105736, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31152831

RESUMO

Pill mill laws impose strict regulations on pain management clinics to prevent them from issuing opioid prescriptions without medical indication. To date, little is known about the implementation or effects of these laws on opioid overdose deaths. A previously untested concern is that by restricting access to prescription opioids, pill mill laws could increase overdose from heroin and synthetic opioids, like illicitly produced fentanyl. We evaluated the effects of pill mill laws on opioid overdose deaths in Ohio and Tennessee. Of the 11 total U.S. states with pill mill laws, Ohio and Tennessee were the only two where: (1) the pill mill law was the only state law designed to curb opioid prescribing implemented in a two-year period, one-year pre/post law; and (2) high-quality drug-specific overdose death data were available from CDC. We conducted synthetic control analyses examining differences in post-pill mill law trends in overdose deaths in Ohio and Tennessee compared to weighted combinations of comparison states. We also conducted qualitative interviews with 11 leaders responsible for pill mill law implementation and enforcement in Ohio and Tennessee. Pill mill law enactment had no effects on overall, prescription opioid, heroin, or synthetic opioid overdose deaths in Ohio or Tennessee. Interview results suggest that both states engaged in robust enforcement and implementation of the law. A multi-pronged policy approach, including but not limited to pill mill laws, may be required to effectively address opioid overdose deaths.


Assuntos
Analgésicos Opioides/uso terapêutico , Overdose de Drogas/mortalidade , Padrões de Prática Médica , Uso Indevido de Medicamentos sob Prescrição/legislação & jurisprudência , Fentanila/efeitos adversos , Heroína/efeitos adversos , Humanos , Entrevistas como Assunto , Ohio , Transtornos Relacionados ao Uso de Substâncias , Tennessee
20.
Chem Biol Interact ; 308: 130-136, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31129131

RESUMO

Substance addiction is a chronic, relapsing mental disorder Characterized by compulsive drug seeking, and loss of control over drug intake and relapse after prolonged abstinence. Genetics has been shown to contribute towards an individual's vulnerability to addiction. Acetylecholine (ACh), a cholinergic neurotransmitter hydrolyzed by acetylcholinesterase (AChE), is an essential neurotransmitter and neuromodulator in central and peripheral nervous system and has regulatory influence on numerous neuronal functions including addiction. The present study was carried out to investigate the role of acetylcholinesterase (AChE) in addiction through measurement of enzyme activity and to find potential association of ACHE gene 3'UTR variants rs17228602 and rs17228616 in heroin, hashish and poly drug addicts. Both SNPs are located within microRNA (miRNA) recognition sites with potential to affect miRNA/transcript interaction. A total of 122 addicts of heroin, hashish and polydrug were recruited from local rehabilitation centers to participate in this study. AChE activity was measured in blood by Ellman's method. SNP genotyping was performed by restriction fragment length polymorphism (PCR-RFLP) and Sanger sequencing. The AChE activity was found significantly higher (p ≤ 0.005) in addicted cohort (mean ±â€¯standard error of mean 0.020 ±â€¯0.001 µmol/L/min; 95% confidence interval (CI) 0.018-0.022) in comparison to non-addicted healthy subjects (0.011 ±â€¯0.001 µmol/L/min; 95% confidence interval CI 0.010-0.013). A statistically significant association of ACHE rs17228602 SNP with addiction vulnerability in dominant (DM: Odd's ratio OR = 2.095, 95% CI = 1.157-3.807 p = 0.009) and allelic genetic models (OR = 1.854 95% CI = 1.082-3.187, p = 0.016) was observed. However, no statistically significant association of rs17228616 SNP with substance abuse disorder was found. The data presented here shows that AChE could play significant role in substance addiction. Further studies with larger sample size and other variants of AChE are recommended to identify novel therapeutic approaches for cholinergic based treatment of addiction.


Assuntos
Acetilcolinesterase/genética , Grupo com Ancestrais do Continente Asiático/genética , Transtornos Relacionados ao Uso de Substâncias/patologia , Regiões 3' não Traduzidas , Acetilcolinesterase/metabolismo , Alelos , Frequência do Gene , Predisposição Genética para Doença , Genótipo , Heroína/efeitos adversos , Humanos , Cinética , MicroRNAs/química , MicroRNAs/metabolismo , Razão de Chances , Paquistão , Polimorfismo de Nucleotídeo Único , Transtornos Relacionados ao Uso de Substâncias/genética
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