scholarly journals Dopamine Levels Induced by Substance Abuse Alter Efficacy of Maraviroc and Expression of CCR5 Conformations on Myeloid Cells: Implications for NeuroHIV

2021 ◽  
Vol 12 ◽  
Author(s):  
Stephanie M. Matt ◽  
Emily A. Nickoloff-Bybel ◽  
Yi Rong ◽  
Kaitlyn Runner ◽  
Hannah Johnson ◽  
...  
Keyword(s):  
Substance Abuse ◽  
Drugs Of Abuse ◽  
Receptor Gene ◽  
Myeloid Cells ◽  
Fluorescent Imaging ◽  
Public Health Issue ◽  
Common Mechanism ◽  
Drug Abusers ◽  
Drug Induced ◽  
Dopamine Signaling

Despite widespread use of antiretroviral therapy (ART), HIV remains a major public health issue. Even with effective ART many infected individuals still suffer from the constellation of neurological symptoms now known as neuroHIV. These symptoms can be exacerbated by substance abuse, a common comorbidity among HIV-infected individuals. The mechanism(s) by which different types of drugs impact neuroHIV remains unclear, but all drugs of abuse increase central nervous system (CNS) dopamine and elevated dopamine increases HIV infection and inflammation in human myeloid cells including macrophages and microglia, the primary targets for HIV in the brain. Thus, drug-induced increases in CNS dopamine may be a common mechanism by which distinct addictive substances alter neuroHIV. Myeloid cells are generally infected by HIV strains that use the chemokine receptor CCR5 as a co-receptor, and our data indicate that in a subset of individuals, drug-induced levels of dopamine could interfere with the effectiveness of the CCR5 inhibitor Maraviroc. CCR5 can adopt distinct conformations that differentially regulate the efficiency of HIV entry and subsequent replication and using qPCR, flow cytometry, Western blotting and high content fluorescent imaging, we show that dopamine alters the expression of specific CCR5 conformations of CCR5 on the surface of human macrophages. These changes are not affected by association with lipid rafts, but do correlate with dopamine receptor gene expression levels, specifically higher levels of D1-like dopamine receptors. These data also demonstrate that dopamine increases HIV replication and alters CCR5 conformations in human microglia similarly to macrophages. These data support the importance of dopamine in the development of neuroHIV and indicate that dopamine signaling pathways should be examined as a target in antiretroviral therapies specifically tailored to HIV-infected drug abusers. Further, these studies show the potential immunomodulatory role of dopamine, suggesting changes in this neurotransmitter may also affect the progression of other diseases.

scholarly journals Stimulant Drugs of Abuse and Cardiac Arrhythmias

2021 ◽  
Author(s):  
Paari Dominic ◽  
Javaria Ahmad ◽  
Hajra Awwab ◽  
Md. Shenuarin Bhuiyan ◽  
Christopher G. Kevil ◽  
...  
Keyword(s):  
Cardiac Arrhythmias ◽  
Drugs Of Abuse ◽  
Systolic Heart Failure ◽  
Drug Abusers ◽  
Nonprescription Drugs ◽  
Drug Induced ◽  
Substituted Amphetamines ◽  
Nonmedical Use ◽  
Chronic Systolic Heart Failure ◽  
Underlying Mechanisms

Nonmedical use of prescription and nonprescription drugs is a worldwide epidemic, rapidly growing in magnitude with deaths because of overdose and chronic use. A vast majority of these drugs are stimulants that have various effects on the cardiovascular system including the cardiac rhythm. Drugs, like cocaine and methamphetamine, have measured effects on the conduction system and through several direct and indirect pathways, utilizing multiple second messenger systems, change the structural and electrical substrate of the heart, thereby promoting cardiac dysrhythmias. Substituted amphetamines and cocaine affect the expression and activation kinetics of multiple ion channels and calcium signaling proteins resulting in EKG changes, and atrial and ventricular brady and tachyarrhythmias. Preexisting conditions cause substrate changes in the heart, which decrease the threshold for such drug-induced cardiac arrhythmias. The treatment of cardiac arrhythmias in patients who take drugs of abuse may be specialized and will require an understanding of the unique underlying mechanisms and necessitates a multidisciplinary approach. The use of primary or secondary prevention defibrillators in drug abusers with chronic systolic heart failure is both sensitive and controversial. This review provides a broad overview of cardiac arrhythmias associated with stimulant substance abuse and their management.

Sociocultural Factors, Sensation Seeking, and Risk of Exposure to Substance Abuse Among Egyptian and Saudi Undergraduates

2021 ◽  
Vol 14 (1) ◽  
pp. 121-133
Author(s):  
Neama F. Kamel ◽  
Nagia I. Hassan ◽  
Wafaa E. Hashem ◽  
Friyal Mubarak Alqahtani ◽  
Mohammed AlAmer
Keyword(s):  
Substance Abuse ◽  
Sensation Seeking ◽  
Public Health Issue ◽  
Sociocultural Factors ◽  
Cluster Sampling ◽  
Late Adolescent ◽  
Raising Children ◽  
Saudi Students ◽  
Drug Involvement ◽  
Paternal Relationship

Background: Substance abuse is a major public health issue worldwide, particularly manifesting during the late adolescent and early adult period. Each culture has distinct beliefs and unique ways of raising children. Cultural differences in parenting beliefs and behaviors are an interesting area that enhances understanding of the nature of differences across cultures. Substance abuse risk may be related to family sociocultural factors; however, there are limited studies that address the relationships between pertinent variables. Objective: To examine and compare family sociocultural factors, sensation seeking, and risk of drug involvement among Egyptian and Saudi university students. Methods: The study employed a comparative correlational descriptive design using two-stage cluster sampling techniques. Data were collected using self-administered questionnaires distributed to students enrolled in Imam Abdulrahman Bin Faisal University (IAU) in Saudi Arabia and Damanhur University (DU) in Egypt. Results: The study showed that Egyptian and Saudi students with a higher percentage of supportive parent relationships have less risk of drug involvement. In both countries, cigarette smoking was the first substance used. Moreover, factors predicting the risk of drug involvement and regression analysis revealed that male students had five times more risk of drug involvement than their female peers, keeping all other factors constant (OR = 5.734; 95%CI:3.231-10.174), while highly supportive paternal relationship reduced the risk of drug involvement by 85% (OR = 0.148; 95% CI: 0.045-0.489). Conclusion: The risk for substance abuse in both cultural settings was moderate, and smoking was the most common substance used. Moreover, a highly supportive paternal relationship reduced the risk of drug involvement by 85%.

Evidence for tissue-specific alternative splicing of the ovine insulin receptor gene

1998 ◽  
Vol 1998 ◽  
pp. 96-96
Author(s):  
P.D. McGrattan ◽  
A.R.G. Wylie ◽  
A.J. Bjourson
Keyword(s):  
Alternative Splicing ◽  
Insulin Receptor ◽  
Receptor Gene ◽  
Protein Isoforms ◽  
Common Mechanism ◽  
Mrna Transcript ◽  
Insulin Receptor Gene ◽  
Tissue Specific ◽  
Specific Regulation ◽  
Exon 11

Alternative splicing of a discrete 36 base pair segment (exon 11) of the human and rat insulin receptor leads to the formation of high and low affinity isoforms differing as much as 3-fold in affinity for insulin. Alternative splicing is a common mechanism for generating protein isoforms and is often regulated in a tissue-specific fashion (Seino & Bell, 1989; Mosthaf et al., 1990). In humans, the lower affinity (B-isoform) mRNA transcript is predominantly expressed in tissues that are important for modulating glucose homeostasis such as the liver and muscle whereas the higher affinity (A-isoform) mRNA transcript is predominantly expressed in haematopoietic tissues such as spleen. Alternative splicing of the region of the ovine insulin receptor gene encoding exon 11 has recently been demonstrated (McGrattan et al., unpublished). The objective of the present study was to establish whether tissue-specific regulation of alternative splicing of the insulin receptor gene occurs in the ruminant animal.

scholarly journals Psychiatrists' knowledge of drug induced psychosis

1996 ◽  
Vol 20 (7) ◽  
pp. 410-412 ◽  
Author(s):  
Clare Brabbins ◽  
Rob Poole
Keyword(s):  
Drugs Of Abuse ◽  
Diagnostic Errors ◽  
Substantial Proportion ◽  
Drug Induced ◽  
Drug Induced Psychosis ◽  
Lack Of Knowledge

‘Drug induced psychosis' is a commonly used clinical label but lacks a universally accepted definition. Psychiatrists' understanding of the term was examined using a specifically designed questionnaire. Knowledge about the effects of drugs of abuse and their relationship with psychosis was also examined. A substantial proportion of clinicians did not have a logical and coherent scheme for understanding ‘drug-induced psychosis' and there was no consensus as to which reactions to drug taking should be included within the rubric. Diagnostic errors have potentially serious consequences, so lack of knowledge in this area needs attention and a proposed classification is given.

scholarly journals Gonadal and Cortisol Hormone Profile among Male Chronic Khat, Marijuana, and Heroin Abuses

2019 ◽  
Vol 2019 ◽  
pp. 1-8
Author(s):  
Meseret Yibrah ◽  
Abebe Edao Negesso ◽  
Atsbeha Gebregziabher ◽  
Feyissa Challa ◽  
Kissi Mudi ◽  
...  
Keyword(s):  
Luteinizing Hormone ◽  
Drugs Of Abuse ◽  
Gonadal Hormones ◽  
Control Group ◽  
Drug Abusers ◽  
Age Difference ◽  
Control Groups ◽  
Heroin Users ◽  
Hormone Levels ◽  
And Control

Background. Drugs of abuse could interfere with the hypothalamic-pituitary-gonadal axis, causing impaired functions of the gland and associated functions of target organs. Drugs of abuse tend to cause changes in the endocrine system, and these changes could be physiological, molecular, biochemical, genetic, and cellular. Method. A case-control study design was conducted from a total of 171 male consented study participants (148 drug abusers and 23 controls). The serum gonadal and cortisol hormone levels were assayed using the electrochemiluminescence immunoassay method. Socio-demographic variables were collected using a semi-structured questionnaire by the interview method. Nonparametric statistical tools (Mann–Whitney test and median) were used to compare the groups. In all cases, P<0.05 was considered statistically significant. Result. The median age for drug abusers and control groups was 27, and the age difference between drug abusers and control group was not statistically important. The median estradiol levels among chronic khat chewers (39.4 pg/ml), marijuana (44 pg/mL), and users of heroin (40.2 pg/mL) were significantly higher than control groups (23 pg/mL), P<0.003. However, the median luteinizing hormone levels among chronic khat chewers (5 IU/L), marijuana users (5 IU/L), and heroin users (5.6 IU/L) were significantly lower than those of control groups (6.2 IU/L), P<0.02. The median testosterone levels among chronic khat chewers (6.1 ng/mL), marijuana users (6.3 ng/mL), and heroin users (6.6 ng/mL) were significantly lower than control groups (8.0 ng/mL), P<0.003. However, cortisol and follicle stimulating hormone did not show statistically significant difference between users of khat, marijuana, and heroin compared with the control group. Conclusion. The drug abuser group had significantly lower testosterone and luteinizing hormone levels compared with control groups. Drug abuse has been shown to affect gonadal hormones in an unusual physiological phenomenon. These findings reveal the need for intervention programs to solve these problems.

P.3.c.041 −759 C/T polymorphism of the 5-HT2C receptor gene and antipsychotic drug-induced weight gain

2006 ◽  
Vol 16 ◽  
pp. S418-S419
Author(s):  
S.H. Ryu ◽  
W.S. Jang ◽  
E.Y. Cho ◽  
S.K. Kim ◽  
D.S. Lee ◽  
...  
Keyword(s):  
Weight Gain ◽  
Antipsychotic Drug ◽  
Receptor Gene ◽  
Drug Induced

Music therapy and emotional exploration: Exposing substance abuse clients to the experiences of non-drug-induced emotions

2007 ◽  
Vol 34 (4) ◽  
pp. 321-330 ◽  
Author(s):  
Felicity A. Baker ◽  
Libby M. Gleadhill ◽  
Genevieve A. Dingle
Keyword(s):  
Substance Abuse ◽  
Music Therapy ◽  
Drug Induced

scholarly journals Oral Fluid Testing for Drugs of Abuse

2009 ◽  
Vol 55 (11) ◽  
pp. 1910-1931 ◽  
Author(s):  
Wendy M Bosker ◽  
Marilyn A Huestis
Keyword(s):  
Mental Health ◽  
Substance Abuse ◽  
Criminal Justice ◽  
Mental Health Services ◽  
Health Services ◽  
Oral Fluid ◽  
Drugs Of Abuse ◽  
Driving Under The Influence ◽  
Device Performance ◽  
Health Services Administration

Abstract Background: Oral fluid (OF) is an exciting alternative matrix for monitoring drugs of abuse in workplace, clinical toxicology, criminal justice, and driving under the influence of drugs (DUID) programs. During the last 5 years, scientific and technological advances in OF collection, point-of-collection testing devices, and screening and confirmation methods were achieved. Guidelines were proposed for workplace OF testing by the Substance Abuse and Mental Health Services Administration, DUID testing by the European Union’s Driving under the Influence of Drugs, Alcohol and Medicines (DRUID) program, and standardization of DUID research. Although OF testing is now commonplace in many monitoring programs, the greatest current limitation is the scarcity of controlled drug administration studies available to guide interpretation. Content: This review outlines OF testing advantages and limitations, and the progress in OF that has occurred during the last 5 years in collection, screening, confirmation, and interpretation of cannabinoids, opioids, amphetamines, cocaine, and benzodiazepines. We examine controlled drug administration studies, immunoassay and chromatographic methods, collection devices, point-of-collection testing device performance, and recent applications of OF testing. Summary: Substance Abuse and Mental Health Services Administration approval of OF testing was delayed because questions about drug OF disposition were not yet resolved, and collection device performance and testing assays required improvement. Here, we document the many advances achieved in the use of OF. Additional research is needed to identify new biomarkers, determine drug detection windows, characterize OF adulteration techniques, and evaluate analyte stability. Nevertheless, there is no doubt that OF offers multiple advantages as an alternative matrix for drug monitoring and has an important role in DUID, treatment, workplace, and criminal justice programs.

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