drug dependency
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2021 ◽  
Vol 15 (7) ◽  
pp. e0009622
Author(s):  
Dimitri Bulté ◽  
Lieselotte Van Bockstal ◽  
Laura Dirkx ◽  
Magali Van den Kerkhof ◽  
Carl De Trez ◽  
...  

Background Miltefosine (MIL) is currently the only oral drug available to treat visceral leishmaniasis but its use as first-line monotherapy has been compromised by an increasing treatment failure. Despite the scarce number of resistant clinical isolates, MIL-resistance by mutations in a single aminophospholipid transporter gene can easily be selected in a laboratory environment. These mutations result in a reduced survival in the mammalian host, which can partially be restored by exposure to MIL, suggesting a kind of drug-dependency. Methodology/Principal findings To enable a combined study of the infection dynamics and underlying immunological events for differential in vivo survival, firefly luciferase (PpyRE9) / red fluorescent protein (DsRed) double-reporter strains were generated of MIL-resistant (MIL-R) and syngeneic MIL-sensitive (MIL-S) Leishmania infantum. Results in C57Bl/6 and BALB/c mice show that MIL-R parasites induce an increased innate immune response that is characterized by enhanced influx and infection of neutrophils, monocytes and dendritic cells in the liver and elevated serum IFN-γ levels, finally resulting in a less efficient establishment in liver macrophages. The elevated IFN-γ levels were shown to originate from an increased response of hepatic NK and NKT cells to the MIL-R parasites. In addition, we demonstrated that MIL could increase the in vivo fitness of MIL-R parasites by lowering NK and NKT cell activation, leading to a reduced IFN-γ production. Conclusions/Significance Differential induction of innate immune responses in the liver was found to underlie the attenuated phenotype of a MIL-R parasite and its peculiar feature of drug-dependency. The impact of MIL on hepatic NK and NKT activation and IFN-γ production following recognition of a MIL-R strain indicates that this mechanism may sustain infections with resistant parasites and contribute to treatment failure.


2021 ◽  
Author(s):  
Dimitri Bulté ◽  
Lieselotte Van Bockstal ◽  
Laura Dirkx ◽  
Magali Van den Kerkhof ◽  
Carl De Trez ◽  
...  

AbstractMiltefosine (MIL) is currently the only oral drug available to treat visceral leishmaniasis but its use as first-line monotherapy has been compromised by an increasing treatment failure. Despite the scarce number of resistant clinical isolates, MIL-resistance by mutations in a single aminophospholipid transporter gene can easily be selected in a laboratory environment. These mutations result in a reduced survival in the mammalian host, which can partially be restored by exposure to MIL, suggesting a kind of drug-dependency. To enable a combined study of the infection dynamics and underlying immunological events for differential in vivo survival, firefly luciferase (PpyRE9) / red fluorescent protein (DsRed) double-reporter strains were generated of MIL-resistant (MIL-R) and syngeneic MIL-sensitive (MIL-S) Leishmania infantum. Results in C57Bl/6 and BALB/c mice show that MIL-R parasites induce an increased innate immune response that is characterized by enhanced influx and infection of neutrophils, monocytes and dendritic cells in the liver and elevated serum IFN-γ levels, finally resulting in a less efficient establishment in liver macrophages. The elevated IFN-γ levels were shown to originate from an increased response of hepatic NK and NKT cells to the MIL-R parasites. In addition, we demonstrated that MIL could increase the in vivo fitness of MIL-R parasites by lowering NK and NKT cell activation, leading to a reduced IFN-γ production. These data provide an immunological basis for the MIL-R-associated attenuated phenotype and for the peculiar drug-dependency that may constitute one of the mechanisms of treatment failure.ImportanceRecently, our laboratory demonstrated an in vivo fitness loss of experimentally selected MIL-R parasites in both the sand fly vector and vertebrate host. These findings could explain the scarce number of MIL-R clinical isolates. Surprisingly, MIL-R parasites developed a MIL-dependency which could partially rescue their fitness loss and which may constitute a mechanism of treatment failure. This research aimed to better understand the immunological basis of the attenuated phenotype and the effect of MIL on infectivity traits. Together, this study provides new insights into the complex interplay between the parasite, drug and host and discloses an immune-related mechanism of treatment failure.


2021 ◽  
Vol 693 (1) ◽  
pp. 141-157
Author(s):  
Brianna Remster

This study investigates patterns of homeless shelter use among formerly incarcerated men for nearly eight years postrelease and risk factors associated with pattern variation. I use life course theory and administrative data from Pennsylvania to identify four distinct forms of homelessness among formerly incarcerated men: persistent homelessness beginning soon after release, a short spell of homelessness years after release, long periods of homelessness years after release, and intermittent homelessness. The results also indicate that risk factors such as age, race, drug dependency, and full sentence completion are better at distinguishing whether formerly incarcerated men become homeless than they are at predicting what kind of homelessness the men experience.


2021 ◽  

There are huge differences between custody and freedom. In the former, life is dominated by the rhythm of the "total institution of prison" (Goffman), whereas, in the latter, it remains relatively self-determined—even in the case of drug dependency. How can the transition from one to the other be organised in such a way that people who are dependent on drugs suffer the least damage? This volume provides both answers to that question and examples of good practice in this respect: the requirements and strategies of drug users when they are released from prison current practice in treating prisoners who use drugs examples of good practice when it comes to release management (networks, counselling, etc.) needs, alternatives and management from a multi-professional perspective.


Author(s):  
Marina Bortyash ◽  
Marina Khanieva

Substantial intensity of side effects and low tolerance of drugs are reflected directly on the quality of patients' lives. In common with positive therapeutic results, antiepileptic drugs have a toxic impact on an organism of human including drug dependency and they can lead to fatality in different conditions (in case of overdose, drugs abuse, heightened sensitivity of organism).


2020 ◽  
Author(s):  
Cameron Thomas Langfield ◽  
Jason Leslie Payne

Understanding the connection between drug dependency and crime has long occupied the research agendas of both criminologists and public policy experts. However, there remains considerable uncertainty in the empirical literature, in part because different studies operationalise the measurement of drug dependency in different ways. Some, for example, use comprehensive and sophisticated clinical instruments, others use simplified screening tools, while some use single-item self-report measures. Whichever the method, each is an attempt to accurately operationalise the manifestation of drug dependency as an objective trait, yet through their mode of administration, they undoubtedly capture other confounds. The resulting bias can have significant implications for the subsequent estimation of the drug crime relationship, especially if a mode of administration (such as the single-measure self-report) crosses over into other important domains such as personal and social identity. The present study examined the correlation between self-reported drug dependency and crime among a large sample of Australian police detainees who were affirmatively screened for dependency on UNCOPE—a six item clinical screening tool which operationalises dependency as the presence of multiple behavioural and affective experiences of compulsive drug use (Hoffmann, Hunt, Rhodes, & Riley, 2003; Proctor & Hoffmann, 2016). Using a mix of descriptive and negative binominal regression techniques, we modelled the frequency of self-reported prior offending in the past 12 months using data from the Drug Use Monitoring in Australia program. After controlling for type, frequency, and longevity of drug use, as well as other demographic factors, we find that those who self-report a drug dependency have higher average rates of prior offending. We argue that these results reflect the social and cultural power of drug-dependency identities and the centrality of identity as a third, often unobserved variable in the drug-crime correlation. These result will assist criminologists and criminal justice professionals in further developing interventions to assist drug dependent offenders within the criminal justice system.


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