Chronic Drug Use Research Articles

Current and emerging perspectives on pathophysiology, diagnosis, and management of hypertrophic cardiomyopathy.

Hypertrophic cardiomyopathy (HCM) is the most common genetically inherited cardiomyopathy with an autosomal dominant inheritance pattern. A disease-causing gene is found between 34% and >60% of the times and the two most frequently mutated genes, which encode sarcomeric proteins, are MYBPC3 and MYH7. HCM is a diagnosis of exclusion since secondary causes of left ventricular hypertrophy should first be ruled out. These include hypertension, aortic stenosis, infiltrative disease, metabolic and endocrine disorders, mitochondrial cardiomyopathies, neuromuscular disorders, malformation syndromes and some chronic drug use. The disease is characterized by great heterogeneity of its clinical manifestations, however diastolic dysfunction and increased ventricular arrhythmogenesis are commonly seen. Current HCM therapies focus on symptom management and prevention of sudden cardiac death. Symptom management includes the use of pharmacological agents, elimination of medication promoting outflow track obstruction, control of comorbid conditions and invasive procedures, whereas in the prevention of sudden cardiac death, implantable cardiac defibrillators and antiarrhythmic drugs are used. A targeted therapy for LVOTO represented by allosteric cardiac myosin inhibitors has been developed. In terms of sport participation, a more liberal approach is recently recommended, after careful evaluation and common-shared decision. The application of the current therapies has lowered HCM mortality rates to <1.0%/year, however it appears to have shifted focus to heart failure and atrial fibrillation, as the predominant causes of disease-related morbidity and mortality and, therefore, unmet treatment need. With improved understanding of the genetic and molecular basis of HCM, the present decade will witness novel treatments for disease prevention and modification.

Can chronic therapeutic drug use by the elderly affect Alzheimer’s disease risk and rate of progression?

There is no approved drug capable of halting the progression of the most prevalent neurodegenerative disorders, namely Alzheimer’s disease (AD) and Parkinson’s disease (PD). Current therapeutic strategies focus mainly on the inhibition of the formation of protein aggregates and their deposition in the central nervous system. However, after almost a hundred years, proper management of the disease is still lacking. The fact of not finding effective management tools in the various clinical trials already carried out suggests that new hypotheses and strategies should be explored. Although vast resources have been allocated to the investigation of protein aggregates and the pathophysiology is now better understood, clues to the actual etiology are lacking. It is well known that brain homeostasis is of paramount importance for the survival of neurons. Drugs that target the periphery are often not subject to evaluation for their potential effect on the central nervous system. While acute treatments may be irrelevant, pills used for chronic conditions can be detrimental to neurons, especially in terms of progressive damage leading to a long-term decline in neuronal survival. Due to the lack of advances in the search for a curative treatment for neurodegenerative diseases, and the lack of new hypotheses about their etiology, a novel hypothesis is here proposed. It consists of assuming that the effects of the drugs most commonly used by the elderly, such as antihypertensive, hypoglycemic, and hypocholesterolemic, could have a negative impact on neuronal survival.

Perioperative Management of Patients Receiving Antithrombotic Therapy in Schemes and Algorithms

Currently, antithrombotic therapy is the basis of the pathogenetic treatment of many cardiovascular diseases, such as coronary heart disease, stroke, peripheral vascular disease, as well as mechanical heart valves, heart rhythm disturbances, venous thromboembolism. At the same time, chronic use of antiplatelet and/or anticoagulant drugs is a complicating factor in invasive and surgical procedures, as it increases the risk of bleeding. In this regard, a fundamentally important and complex question arises: how to minimize the risk of periprocedural bleeding without exposing the patient to an increased risk of ischemic and thromboembolic complications? Perioperative management of patients who take antithrombotic drugs for a long time is a complex problem that depends on many factors - the risk of surgery, anesthesia, cardiovascular risks, and the urgency of surgery. Each clinical situation should be assessed individually, collegially, with the participation of surgeons, anesthesiologists, and therapists. The introduction of a checklist into clinical practice for each planned surgical patient will allow us to calculate the individual risk of bleeding and thromboembolic complications, and provide an optimal preventive strategy for perioperative management of the patient. The algorithms and schemes presented in the article for the perioperative management of patients with non-cardiac interventions are aimed at standardizing the management of patients before non-cardiac surgical interventions, which will reduce hemorrhagic risks in the presence of the necessary antithrombotic therapy.

Efficacy of antiviral therapy in the treatment of peripheral facial paralysis: a tertiary institution experience

Objective: For the treatment of peripheral facial paralysis, the superiority of the use of steroid alone and the use of steroid + antiviral over each other has not been clarified in the literature. In this study, the efficacy of using steroid treatment alone and using a combination of steroid+antiviral treatment in patients we followed up with peripheral facial paralysis in our clinic was questioned retrospectively. It was aimed to clarify the efficacy and superiority of steroid alone and steroid+antiviral therapy in patients with peripheral facial paralysis. Materials and Methods: One hundred and ten patients who received only steroids and 62 patients who received combination therapy were included in the study. Age, gender, regular drug use, smoking, previous history of facial paralysis, comorbid diseases, initial stage of the disease (House-Brackman/HB staging), treatment protocol and response to treatment were recorded from the files examined. Patients with HB stage ≤2 at the 6th month follow-up were considered to have responded well or completely to the treatment. Results: When the group receiving only steroid treatment and the group receiving steroid + antiviral treatment were compared in terms of age, chronic drug use, gender, and previous facial paralysis, no statistically significant difference was observed. The groups were compared in terms of response to treatment, 88.2% improvement was observed in the steroid group (HB stage ≤2), and 91.9% improvement was observed in the combined treatment group. No statistically significant difference was observed (p=0.605). Conclusion: For the treatment of peripheral facial paralysis, the superiority of steroid use alone and combined antiviral + steroid use has not been proven. In the light of the literature, it is recommended that the patient be treated with steroids at the earliest stage.

Retrospective Analysis of Walking Distance and Use of Medication After Bariatric Surgery

Aim: The objective of this study was to ascertain the drug use and walking distance of individuals after bariatric surgery.&#x0D; Material and Methods: The sample of the study consisted of 165 individuals. Individuals who underwent bariatric surgery were examined retrospectively after their operations. Data were collected using the Personal Information Form and the Walking Impairment Questionnaire.&#x0D; Results: The mean age of the individuals included in the study was 40.22±9.63. 52.1% of individuals were female. The body mass index of individuals was 39.63±4.69 before bariatric surgery and 23.94±2.57 in the first year follow-up after bariatric surgery. Forty percent of individuals did not have any chronic illnesses. Among individuals who had been on medication before surgery, 72.4% of those taking psychiatric medications, 57.5% of those taking diabetes medications, and 16% of those taking heart medications discontinued medications after their operations. 81.8% of individuals reported improved sleep quality compared to the period before the operation. The walking distance level of the individuals showed a significant increase in the first year after bariatric surgery compared to the period&#x0D; before the surgery.&#x0D; Conclusion: The study showed that bariatric surgery is an effective method for weight loss and reduction of comorbidities, as well as leading to a statistically significant reduction in chronic drug use and an increase in sleep quality and walking distance of individuals

Possible Mechanisms of the Interplay between Drugs and Mycotoxins—Is There a Possible Impact?

Mycotoxin contamination is a global food safety issue leading to major public health concerns. Repeated exposure to multiple mycotoxins not only has repercussions on human health but could theoretically also lead to interactions with other xenobiotic substances-such as drugs-in the body by altering their pharmacokinetics and/or pharmacodynamics. The combined effects of chronic drug use and mycotoxin exposure need to be well understood in order to draw valid conclusions and, in due course, to develop guidelines. The aim of this review is to focus on food contaminants, more precisely on mycotoxins, and drugs. First, a description of relevant mycotoxins and their effects on human health and metabolism is presented. The potential for interactions of mycotoxins with drugs using in vitro and in vivo animal experiments is summarized. Predictive software tools for unraveling mycotoxin-drug interactions are proposed and future perspectives on this emerging topic are highlighted with a view to evaluate associated risks and to focus on precision medicine. In vitro and in vivo animal studies have shown that mycotoxins affect CYP450 enzyme activity. An impact from drugs on mycotoxins mediated via CYP450-enzymes is plausible; however, an impact of mycotoxins on drugs is less likely considering the much smaller dose exposure to mycotoxins. Drugs that are CYP450 perpetrators and/or substrates potentially influence the metabolism of mycotoxins, metabolized via these CYP450 enzymes. To date, very little research has been conducted on this matter. The only statistically sound reports describe mycotoxins as victims and drugs as perpetrators in interactions; however, more analysis on mycotoxin-drug interactions needs to be performed.

Bifunctional Peptidomimetic G Protein-Biased Mu-Opioid Receptor Agonist and Neuropeptide FF Receptor Antagonist KGFF09 Shows Efficacy in Visceral Pain without Rewarding Effects after Subcutaneous Administration in Mice.

There is still an unmet clinical need to develop new pharmaceuticals for effective and safe pain management. Current pharmacotherapy offers unsatisfactory solutions due to serious side effects related to the chronic use of opioid drugs. Prescription opioids produce analgesia through activation of the mu-opioid receptor (MOR) and are major contributors to the current opioid crisis. Multifunctional ligands possessing activity at more than one receptor represent a prominent therapeutic approach for the treatment of pain with fewer adverse effects. We recently reported on the design of a bifunctional MOR agonist/neuropeptide FF receptor (NPFFR) antagonist peptididomimetic, KGFF09 (H-Dmt-DArg-Aba-βAla-Bpa-Phe-NH2), and its antinociceptive effects after subcutaneous (s.c.) administration in acute and persistent pain in mice with reduced propensity for unwanted side effects. In this study, we further investigated the antinociceptive properties of KGFF09 in a mouse model of visceral pain after s.c. administration and the potential for opioid-related liabilities of rewarding and sedation/locomotor dysfunction following chronic treatment. KGFF09 produced a significant dose-dependent inhibition of the writhing behavior in the acetic acid-induced writhing assay with increased potency when compared to morphine. We also demonstrated the absence of harmful effects caused by typical MOR agonists, i.e., rewarding effects (conditioned-place preference test) and sedation/locomotor impairment (open-field test), at a dose shown to be highly effective in inhibiting pain behavior. Consequently, KGFF09 displayed a favorable benefit/side effect ratio regarding these opioid-related side effects compared to conventional opioid analgesics, such as morphine, underlining the development of dual MOR agonists/NPFFR antagonists as improved treatments for various pain conditions.

Effect of human mesenchymal stem cell secretome administration on morphine self-administration and relapse in two animal models of opioid dependence

The present study investigates the possible therapeutic effects of human mesenchymal stem cell-derived secretome on morphine dependence and relapse. This was studied in a new model of chronic voluntary morphine intake in Wistar rats which shows classic signs of morphine intoxication and a severe naloxone-induced withdrawal syndrome. A single intranasal-systemic administration of MSCs secretome fully inhibited (>95%; p < 0.001) voluntary morphine intake and reduced the post-deprivation relapse intake by 50% (p < 0.02). Since several studies suggest a significant genetic contribution to the chronic use of many addictive drugs, the effect of MSCs secretome on morphine self-administration was further studied in rats bred as high alcohol consumers (UChB rats). Sub-chronic intraperitoneal administration of morphine before access to increasing concentrations of morphine solutions and water were available to the animals, led UChB rats to prefer ingesting morphine solutions over water, attaining levels of oral morphine intake in the range of those in the Wistar model. Intranasally administered MSCs secretome to UChB rats dose-dependently inhibited morphine self-administration by 72% (p < 0.001); while a single intranasal dose of MSC-secretome administered during a morphine deprivation period imposed on chronic morphine consumer UChB rats inhibited re-access morphine relapse intake by 80 to 85% (p < 0.0001). Both in the Wistar and the UChB rat models, MSCs-secretome administration reversed the morphine-induced increases in brain oxidative stress and neuroinflammation, considered as key engines perpetuating drug relapse. Overall, present preclinical studies suggest that products secreted by human mesenchymal stem cells may be of value in the treatment of opioid addiction.

Prevalence of Ocular Surface Disease and Associated Risk Factors in Glaucoma Patients: A Survey Study of Ophthalmologists.

This survey study of ophthalmologists investigated the prevalence and clinical manifestations of ocular surface disease (OSD) in glaucoma patients, assessment methods used, risk factors, glaucoma drugs considered responsible, and treatment approaches. A questionnaire prepared jointly by the Turkish Ophthalmological Association Cornea and Ocular Surface Society and Glaucoma Society using SurveyMonkey was sent to ophthalmologists via e-mail. The distribution of parameters was compared with chi-square test and p&lt;0.05 was considered statistically significant. Forty-five percent of the ophthalmologists reported that OSD was evident in least 25% of their patients. The most common symptom was redness (91.9%), while the most common ocular surface finding was conjunctival hyperemia (75.6%). The tests considered to be the most important in ocular surface assessment were ocular staining (38.7%) and tear film break-up time (TBUT) (21.9%). Ninety percent of the physicians stated that the main cause of OSD was benzalkonium chloride (BAC) in medications. Prostaglandin analogs and alpha-2 agonists were reported to be the most common medications causing OSD. In case of OSD, the ophthalmologists often switch to a glaucoma drug from a different group (38%), a non-preservative glaucoma drug (33.7%) or a drug with a preservative other than BAC (20.4%). Most physicians prescribed artificial tears (84.6%). In this cross-sectional survey study, ophthalmologists detected varying rates of OSD in glaucoma patients depending on chronic drug use and BAC exposure. Although ocular surface examination was performed by physicians, tests such as TBUT and ocular surface staining were rarely used. Detecting OSD in glaucoma patients and planning personalized treatment increase patient comfort, drug compliance, and treatment effectiveness. For this reason, it is important to prepare an algorithm for the management of comorbid OSD in glaucoma patients.

Therapeutic Use and Chronic Abuse of CNS Stimulants and Anabolic Drugs.

The available evidence suggests that affective disorders, such as depression and anxiety, increase risk for accelerated cognitive decline and late-life dementia in aging individuals. Behavioral neuropsychology studies also showed that cognitive decline is a central feature of aging impacting the quality of life. Motor deficits are common after traumatic brain injuries and stroke, affect subjective well-being, and are linked with reduced quality of life. Currently, restorative therapies that target the brain directly to restore cognitive and motor tasks in aging and disease are available. However, the very same drugs used for therapeutic purposes are employed by athletes as stimulants either to increase performance for fame and financial rewards or as recreational drugs. Unfortunately, most of these drugs have severe side effects and pose a serious threat to the health of athletes. The use of performance-enhancing drugs by children and teenagers has increased tremendously due to the decrease in the age of players in competitive sports and the availability of various stimulants in many forms and shapes. Thus, doping may cause serious health-threatening conditions including, infertility, subdural hematomas, liver and kidney dysfunction, peripheral edema, cardiac hypertrophy, myocardial ischemia, thrombosis, and cardiovascular disease. In this review, we focus on the impact of doping on psychopathological disorders, cognition, and depression. Occasionally, we also refer to chronic use of therapeutic drugs to increase physical performance and highlight the underlying mechanisms. We conclude that raising awareness on the health risks of doping in sport for all shall promote an increased awareness for healthy lifestyles across all generations.

Vitamin D Concentration and Motoric Cognitive Risk in Older Adults: Results from the Gait and Alzheimer Interactions Tracking (GAIT) Cohort.

Background. Motoric Cognitive Risk (MCR) syndrome, which combines subjective memory complaint (SMC) and slower gait speed, is a newly-described predementia stage. Based on the involvement of vitamin D in the biology of both gait and cognition, we hypothesized that nondemented individuals with MCR would exhibit hypovitaminosis D more often compared to Cognitively Healthy Individuals (CHI). The objective of this cross-sectional analysis was to determine whether hypovitaminosis D was associated with MCR. Methods. Participants without dementia from the GAIT (Gait and Alzheimer Interactions Tracking) cohort study were classified into MCR or Cognitively Healthy Individuals (CHI) groups. Hypovitaminosis D was defined as the lowest quartile of serum 25-hydroxyvitamin D (25OHD) concentration compared to the other three combined. Age, sex, body mass index (BMI), the Frontal Assessment Battery (FAB) score, the Mini-Mental Short Examination (MMSE) score, education level, use of psychoactive drugs, and the number of chronic diseases were used as covariates. Results. Among 244 nondemented and nonMCInonMCR participants from the GAIT cohort (mean age 71.4 ± 3.7 years, 40.6% women), 66 participants were classified as MCR (36.9%) and 178 as CHI (63.1%). The lowest quartile of 25OHD concentration was directly associated with MCR (unadjusted OR = 2.85, p = 0.003) even after adjustment for studied potential confounders (fully adjusted OR = 2.61, p = 0.025). The BMI (adjusted OR = 6.65, p < 0.001), MMSE score (adjusted OR = 0.74, p = 0.009), FAB score (adjusted OR = 0.51, p < 0.001), number of chronic diseases (adjusted OR = 1.29, p = 0.043) and use of psychoactive drugs (adjusted OR = 2.55, p = 0.044) were also associated with MCR. Conclusions. Hypovitaminosis D was associated with MCR in older community-dwellers without dementia.

Using ethnography to understand the lives of street sex workers

This article examines the value of using ethnographic methodology in research with women involved in street sex work in an inner-city suburb of Melbourne, Australia. The aim is to draw attention to the importance of three fundamental elements of this type of research with marginalised populations: 1) researchers’ immersion into the field over a sustained period of time, 2) ethical considerations about informed consent for people with cognitive impairment as a result of chronic drug use, and 3) reflexivity and positionality in qualitative research. Data collected from two and a half years of ethnographic fieldwork, including participant observation and semi-structured interviews with women involved in street sex work, emphasises the importance of adopting these participatory methods to ensure authenticity, rigour and credibility of research findings with marginalised populations.

Incidence and risk factors for residual adverse events despite anticoagulation in atrial fibrillation: results from phase II/III of the GLORIA-AF registry

Abstract Background Residual risk of ischaemic stroke despite anticoagulation in patients with atrial fibrillation (AF) remains poorly investigated. We aimed to evaluate the incidence and risk factors for residual adverse events in AF. Methods Using data from phase II/III of the prospective GLORIA-AF registry, we studied anticoagulated patients from 935 centres across 38 participating who were consecutively enrolled with newly diagnosed AF and an increased risk of stroke (CHA2DS2-VASc ≥1). The primary outcome of interest was ischaemic stroke. Secondary outcomes were all-cause death, cardiovascular (CV) death and myocardial infarction. Risk factors for residual ischaemic stroke were identified using Cox proportional hazards analyses. Results 22410 patients were included; median age 65 (IQR 71–78) and 10044 (44.8%) females. Over 3.0 (IQR 2.2–3.1) years, the incidence per 100-PYs of ischaemic stroke was 0.60 (95% CI, 0.54–0.67), all-cause death 3.22 (95% CI, 3.08–3.37), CV death 1.08 (95% CI, 1.00–1.16) and myocardial infarction 0.59 (95% CI, 0.53–0.66). Using multivariable Cox proportional hazards analysis, independent predictors of residual ischaemic stroke were age (HR 1.05 [95% CI, 1.03–1.06]), diabetes mellitus (HR 1.42 [95% CI, 1.09–1.85]), prior thromboembolism (HR 2.32 [95% CI, 1.79–3.00]), chronic obstructive pulmonary disease (HR 1.53 [95% CI, 1.04–2.26]) and use of anti-arrhythmic drugs (HR 0.70 [95% CI, 0.51–0.96]). The incidence of ischaemic stroke was comparable among patients treated with non-vitamin K antagonist oral anticoagulants vs. vitamin K antagonist; however, there were differences in the independent predictors between both groups. Conclusion Patients with AF remain at significant risk of ischaemic stroke despite anticoagulation therapy. Risk factors for residual ischaemic stroke were prior thromboembolism, age, persistent AF, diabetes mellitus, chronic obstructive pulmonary disease and non-use of anti-arrhythmic drug therapy. This emphasises the need to treat these risk factors, if modifiable, beyond antithrombotic therapy. Funding Acknowledgement Type of funding sources: None.

Accumulation of foamy macrophages in the bone marrow following chronic intravenous drug use.

Accumulation of foamy macrophages in the bone marrow following chronic intravenous drug use.

NORMAL INDICATORS OF OXIDATIVE STRESS AND THE DYNAMICS OF THEIR CHANGES AT DIFFERENT TERMS OF EXPERIMENTAL OPIOID INFLUENCE

In the modern world, there are a large number of exogenous factors that contribute to the emergence of disorders associated with changes in biochemical data. One of these factors is the long-term usage of the opioid analgesics for therapeutic purposes, as well, as the use of opioid drugs without medical indications by people belonging to the category of drug addicts. More often, doctors of various specialties are faced with the problem of treating various nosology in people with opioid addiction. The process of correction of the main pathology makes it diffi cult due to the consequences arising from the chronic use of opioid drugs. The aim of the study is to fi nd out the dynamics of changes in the oxidative stress indicators of the blood of rats under normal conditions and during subchronic and chronic experimental opioid exposure. Material and methods. The research material was sexually mature, purebred male rats in the amount of 38 animals, weighing 160.0-270.0 g, aged 4.5-7.5 months. The animals were injected with nalbuphine intramuscularly, once a day at one time (10-11 am) per 70 days. The initial dose of nalbuphine during the fi rst 2 weeks was 0.212 mg/kg, the next 2 weeks (II-IV weeks) – 0.225 mg/kg, the next (IV-VI weeks) – 0.252 mg/kg, the next (VI-VIII weeks) – 0.260 mg/kg, and during (VIII-X weeks) – 0.283 mg/kg. Thus, conditions for chronic opioid exposure were created. Research results and their discussion. As a result of our experimental study, the eff ect of an opioid analgesic on the indicators of oxidative stress in the blood of rats, at the end of the 2nd week, we observed an unreliable increase in malondialdehyde and diene conjugates with a signifi cant decrease in the ceruloplasmin indicator. At the end of the 6th week administration of opioid analgesics, we observed a steady and continued growth of malondialdehyde and diene conjugates and a further decrease in ceruloplasmin. All indicators had a statistically proven diff erence compared with the control group. The animals of the experimental group, after 10 weeks of experimental opioid exposure have shown that all indicators continued the previously identifi ed dynamics and reached their maximum value of the diff erence compared to the control group. Conclusions. The conducted studies make it possible to clarify the peculiarities of changes in the oxidative stress indicators of the blood of rats in the subchronic and chronic periods of experimental opioid exposure.

Lethal intoxications of medical staff with substances used in the profession – Presentation of a group of cases

The access medical staff has to special drugs through the nature of the job can lead to undesirable situations (illicit consumption, abuse and addiction, accidental overdoses, suicide, homicide). We focus on identifying situations of lethal intoxication of the medical staff with substances used within the profession and we propose a forensic approach to these types of cases. We made a review of the literature using MEDLINE, EMBASE, Scopus, Cochrane and internet search data of deaths among nurses and doctors due to intoxication with special regime drugs used in the profession. Five cases of autopsies performed at INML “Mina Minovici” Bucharest and Ilfov Medical-Legal Service, Romania, are presented (a veterinarian, a nurse and three anesthesiologist doctors). A 27-year-old female, a veterinarian, was found dead in bed, in her apartment, next to a 10-mL syringe with an attached branch, containing 4 ml of transparent liquid. It's a case of intravenous self-administration of T61, with a suicidal intention. T61 is a solution used for animal euthanasia, a mixture of 3 substances: embutramide (opioid analgesic), mebezonium iodide (curare-compound) and tetracaine hydrochloride (local anesthetic). A 38-year-old man, a male nurse, was found dead in his home, surrounded by several empty containers of Fentanyl and Mialgin. A bag with partially empty containers of medicines was found in his car: Enalapril, Telmisartan, Mialgin, Diazepam, Fentanyl, Acupan (nefopan chloridate), Dormicum (Midazolam), syringes and needles, used, but also sealed. The cause of death was an acute intoxication with a cocktail medication (opioid analgesics and benzodiazepines), stolen from the workplace. A 37-year-old man, an anesthesiologist doctor, was found by a colleague, at 7.00 a.m, in the on call room of the hospital, at the end of his shift. The cause of death was the acute intoxication with morphine (0.448 μg/mL). A 34-year-old woman, anesthesiologist doctor, was found dead by her father, on the bathroom floor of her apartment. Next to the body were found: a 5 mL syringe with 3 mL liquid content and 2 ampoules of tramadol hydrochloride (Mabron). In the trash, there was an empty bottle of ketamine hydrochloride (Ketamidor, for veterinary use) and fragments of ampoules of Midazolam and Calypsol. More than 150 ampoules labeled with various substances used in anesthesia were found in the house. In the last period, the woman doctor was exhausted as she had been working both in the public and private system. Female, 51 years old, anesthesiologist doctor, known as a consumer of analgesic substances for about 3 years, was found dead at home by her husband, on the bedroom floor. Cause of death was acute pulmonary edema, the consequence of an acute intoxication with drugs (pethidine > 2/mL μg/mL and nordazepam 0.03 μg/mL). The paper analyzes all the findings: the on-site investigations (extremely important to gather information), the necropsy data and the results of the histopathological, toxicological, tanatochemical and serological examinations. The analytical methods currently used for highlighting and dosing the identified substances are also presented. Autopsy findings were nonspecific, except for the stigma of chronic injectable drug use. That is why an algorithm for step by step approaching these types of cases could be very useful in order not to go beyond the possibility of an acute drug intoxication of medical staff. Nurses and doctors are vulnerable to chemical dependence due to the high work-related stress associated with easy access to medicines. This must always be suspected by the forensic doctors when they perform an autopsy of a medical staff person and they must follow a special algorithm in such cases.

Disrupted Decision-Making: EcoHIV Inoculation in Cocaine Dependent Rats.

Independently, chronic cocaine use and HIV-1 viral protein exposure induce neuroadaptations in the frontal-striatal circuit as evidenced by both clinical and preclinical studies; how the frontal-striatal circuit responds to HIV-1 infection following chronic drug use, however, has remained elusive. After establishing experience with both sucrose and cocaine self-administration, a pretest-posttest experimental design was utilized to evaluate preference judgment, a simple form of decision-making dependent upon the integrity of frontal-striatal circuit function. During the pretest assessment, male rats exhibited a clear preference for cocaine, whereas female animals preferred sucrose. Two posttest evaluations (3 days and 6 weeks post inoculation) revealed that, independent of biological sex, inoculation with chimeric HIV (EcoHIV), but not saline, disrupted decision-making. Prominent structural alterations in the frontal-striatal circuit were evidenced by synaptodendritic alterations in pyramidal neurons in the medial prefrontal cortex. Thus, the EcoHIV rat affords a valid animal model to critically investigate how the frontal-striatal circuit responds to HIV-1 infection following chronic drug use.

Enabling successful life engagement in young people with ADHD: new components beyond adult models of recovery

Purpose To examine the lived experiences of young people successfully managing life with ADHD and investigate the applicability of adult models of Recovery to these individuals. Methods Twenty-seven young people aged 15–31 years participated in qualitative interviews. Participants’ success was indicated by employment, school attendance, absence of acute mental health episodes, or absence of chronic alcohol or drug use. Thematic analysis identified specific components of their life successes and challenges. Results The emergent framework comprised four elements: (i) Recovernance (RE) (a portmanteau merging ‘Recovery’ and ‘Maintenance’; ongoing adjustment to maintain one’s personal best without an end point); (ii) Personal Optimization (PO) (continuously striving to maximize function and adjust one’s goals given fluctuating impairments and internal resources); (iii) Self (S) (facing internal challenges and developing internal resilience); and (iv) Environment (E) (facing external challenges and fostering external resilience). These four elements yielded the acronym ‘REPOSE’. Conclusions Recovery in young people with ADHD was not a linear journey, with many missteps leading to greater self-knowledge, life skills and mastery. Progress was leveraged on securely anchored internal and external resilience factors against the prospect of setbacks. Findings provide new concepts and novel lexicons to extend existing concepts in Recovery. Implications for rehabilitation Counselling and therapy for young people with ADHD should foster self-understanding, goal setting and self-vigilance as an ongoing process to build their capacity to tackle setbacks and adversities. Counselling and therapy for young people with ADHD focus on a strengths-based approach building internal and external resources, such as developing skills and establishing social connections that build infrastructure in the environment for meaningful participation.

CREB Binding at the Zfp189 Promoter Within Medium Spiny Neuron Subtypes Differentially Regulates Behavioral and Physiological Adaptations Over the Course of Cocaine Use

BackgroundOver the course of chronic drug use, brain transcriptional neuroadaptation is thought to contribute to a change in drug use behavior over time. The function of the transcription factor CREB (cAMP response element binding protein) within the nucleus accumbens (NAc) has been well documented in opposing the rewarding properties of many classes of drugs, yet the gene targets through which CREB causally manifests these lasting neuroadaptations remain unknown. Here, we identify zinc finger protein 189 (Zfp189) as a CREB target gene that is transcriptionally responsive to acute and chronic cocaine use within the NAc of mice. MethodsTo investigate the role of the CREB-Zfp189 interaction in cocaine use, we virally delivered modified clustered regularly interspaced short palindromic repeats (CRISPR)/dCas9 constructs capable of selectively localizing CREB to the Zfp189 gene promoter in the NAc of mice. ResultsWe observed that CREB binding to the Zfp189 promoter increased Zfp189 expression and diminished the reinforcing responses to cocaine. Furthermore, we showed that NAc Zfp189 expression increased within D1 medium spiny neurons in response to acute cocaine but increased in both D1- and D2-expressing medium spiny neurons in response to chronic cocaine. CREB-mediated induction of Zfp189 potentiated electrophysiological activity of D1- and D2-expressing medium spiny neurons, recapitulating the known effect of CREB on these neurons. Finally, targeting CREB to the Zfp189 promoter within NAc Drd2-expressing neurons, but not Drd1-expressing neurons, was sufficient to diminish cocaine-conditioned behaviors. ConclusionsTogether, these findings point to the CREB-Zfp189 interaction within the NAc Drd2+ neurons as a molecular signature of chronic cocaine use that is causal in counteracting the reinforcing effects of cocaine.

Laboratory Diagnosis of Drug of Abuse-Latest Update

Substance abuse, also known as drug abuse, is the use of a drug in amounts or by methods which are harmful to the individual or others. It is a form of substance-related disorder. Substance use disorders (SUD) are mental health conditions that arise from chronic drug use. There is an increased recognition of this problem in Saudi Arabia. Drugs of abuse testing is the detection of one or more illegal and/or prescribed substances in the urine, blood, saliva, hair, or sweat. Testing detects substances not normally found in the body. Drug abuse testing usually involves an initial screening test followed by a second test that identifies and/or confirms the presence of a drug or drugs. Initial screening is done by urine tests and confirmation is done by blood tests. Major drug class screened are Amphetamines, Barbiturates, Benzodiazapines, Cannibinoids, Cocaine, methadone and opiates. In this article we reviewed lab diagnosis of drug of abuse.