Cingulate Cortex Structural Alterations in Substance Use Disorder Psychiatric Inpatients.

BACKGROUND AND OBJECTIVES: Substance use disorder (SUD) includes maladaptive patterns of substance use despite negative consequences. Previous structural neuroimaging studies showed some structural alterations in SUD, but it remains unknown whether these alterations are specifically associated with SUD or common comorbidities. This study attempts to validate the findings of structural differences between SUD, healthy controls (HC), and psychiatric controls (PC). METHODS: We used HC (N = 86) matched for demographics, and PC (N = 86) matched for demographics and psychiatric diagnoses to a group of SUD patients (N = 86). We assessed the group differences of subcortical volumes, cortical volumes, thickness, and surface areas between SUD and HC. We then analyzed the group differences between SUD and PC within regions showing differences between SUD and HC. RESULTS: SUD had smaller left nucleus accumbens, right thalamus, right hippocampus, left caudal anterior cingulate cortex (ACC) volume, and larger right caudal ACC volume, and right caudal ACC, right caudal middle frontal gyrus (MFG), and right posterior cingulate cortex (PCC) surface than HC. Increased right caudal ACC volume and right PCC surface in SUD were the only findings when compared with PC. Several areas showed thickness alterations between SUD and HC, but none survived multiple comparisons vs PC. DISCUSSION AND CONCLUSIONS: Our findings suggest that cingulate structures may be altered in SUD compared with both HC and PC. SCIENTIFIC SIGNIFICANCE: These results are among the first to indicate that some structural alterations may be SUD-specific, and highlight a cautionary note about using HC in psychiatric biomarker research. (Am J Addict 2021;30:72-79).

Morphine-mediated release of miR-138 in astrocyte-derived extracellular vesicles promotes microglial activation.

Opioids, such as morphine, are the mainstay for the management of postsurgical pain. Over the last decade there has been a dramatic increase in deaths related to opioid overdose. While opioid abuse has been shown to result in increased neuroinflammation, mechanism(s) underlying this process, remain less understood. In recent years, microRNAs have emerged as key mediators of gene expression regulating both paracrine signaling and cellular crosstalk. MiRNAs constitute the extracellular vesicle (EV) cargo and can shuttle from the donor to the recipient cells. Exposure of human primary astrocytes to morphine resulted in induction and release of miR-138 in the EVs isolated from conditioned media of cultured astrocytes. Released EVs were, in turn, taken up by the microglia, leading to activation of these latter cells. Interestingly, activation of microglia involved binding of the GUUGUGU motif of miR138 to the endosomal toll like receptor (TLR)7, leading, in turn, to cellular activation. These findings were further corroborated in vivo in wildtype mice wherein morphine administration resulted in increased microglial activation in the thalamus. In TLR7-/- mice on the other hand, morphine failed to induce microglial activation. These findings have ramifications for the development of EV-loaded anti-miRNAs as therapeutics for alleviating neuroinflammation in opioids abusers.

Treatment of stimulant use disorder: A systematic review of reviews.

AIMS: Stimulant use disorder contributes to a substantial worldwide burden of disease, although evidence-based treatment options are limited. This systematic review of reviews aims to: (i) synthesize the available evidence on both psychosocial and pharmacological interventions for the treatment of stimulant use disorder; (ii) identify the most effective therapies to guide clinical practice, and (iii) highlight gaps for future study. METHODS: A systematic database search was conducted to identify systematic reviews and meta-analyses. Eligible studies were those that followed standard systematic review methodology and assessed randomized controlled trials focused on the efficacy of interventions for stimulant use disorder. Articles were critically appraised using an assessment tool adapted from Palmeteer et al. and categorized for quality as 'core' or 'supplementary' reviews. Evidence from the included reviews were further synthesized according to pharmacological or non-pharmacological management themes. RESULTS: Of 476 identified records, 29 systematic reviews examining eleven intervention modalities were included. The interventions identified include: contingency management, cognitive behavioural therapy, acupuncture, antidepressants, dopamine agonists, antipsychotics, anticonvulsants, disulfiram, opioid agonists, N-Acetylcysteine, and psychostimulants. There was sufficient evidence to support the efficacy of contingency management programs for treatment of stimulant use disorder. Psychostimulants, n-acetylcysteine, opioid agonist therapy, disulfiram and antidepressant pharmacological interventions were found to have insufficient evidence to support or discount their use. Results of this review do not support the use of all other treatment options. CONCLUSIONS: The results of this review supports the use of contingency management interventions for the treatment of stimulant use disorder. Although evidence to date is insufficient to support the clinical use of psychostimulants, our results demonstrate potential for future research in this area. Given the urgent need for effective pharmacological treatments for stimulant use disorder, high-quality primary research focused on the role of psychostimulant medications for the treatment of stimulant use disorder is needed.

[FSGS collapsing variant during anabolic steroid abuse: Case Report].

Anabolic Androgenic Steroids (AAS) is an hormone family whose use has considerably increased among body-builders during the last decades. The AAS abuse, especially associated with other drugs or nutritional supplements and protein loads, may cause a variety of pathologies to several organs with a mechanism related to dosage, timing and substance. The kidney is the main metabolizer of these drugs and it can be acutely or chronically damaged with ESKD. The literature reports some cases of Focal Segmental Glomerulosclerosis (FSGS) in body-builders who abused of AAS. However, the link is not well understood and limited to some case-studies. In this paper, we report the case of a young body-builder who developed a FSGS collapsing variant with ESKD after prolonged abuse of AAS and a strongly hyperproteic diet and other dietary supplements. The patient underwent a genetic test because of the rapid and irreversibile onset of ESKD. The test showed a gene mutation of ACTN4, predisposing and causal of some genetic forms of FSGS. It was a very complex case, caused by several factors. The mutant protein of ACTN4 gene makes most vulnerable the cytoskeleton of the podocytes to external disturbances. That would explain why in those patients where the mutation has occurred, only those patients subject to "unfavorable environmental conditions", like the abuse of AAS, can develop a disease.

Protective effect of Lycium Barbarum polysaccharides on dextromethorphan-induced mood impairment and neurogenesis suppression.

Dextromethorphan (DXM) is one of the common drugs abused by adolescents. It is the active ingredient found in cough medicine which is used for suppressing cough. High dosage of DXM can induce euphoria, dissociative effects and even hallucinations. Chronic use of DXM may also lead to depressive-related symptoms. Lycium barbarum, commonly known as wolfberry, has been used as a traditional Chinese medicine for the treatment of ageing-related neurodegenerative diseases. A recent study has shown the potential beneficial effect of Lycium barbarum to reduce depression-like behavior. In the present study, we investigated the role of Lycium barbarum polysaccharide (LBP) to alleviate DXM-induced emotional distress. Sprague Dawley rats were divided into 4 groups (n=6 per group), including the normal control (vehicles only), DXM-treated group (40 mg/kg DXM), LBP-treated group (1 mg/kg LBP) and DXM+ LBP-treated group (40 mg/kg DXM and 1 mg/kg LBP). After two-week treatment, the DXM-treated group showed increased depression-like and social anxiety-like behaviors in the forced swim test and social interaction test respectively. On the other hand, the adverse behavioral effects induced by DXM were reduced by LBP treatment. Histological results showed that LBP treatment alone did not promote hippocampal neurogenesis when compared to the normal control, but LBP could lessen the suppression of hippocampal neurogenesis induced by DXM. The findings provide insights for the potential use of wolfberry as an adjunct treatment option for alleviating mood disturbances during rehabilitation of cough syrup abusers.

Decreased subcortical volumes in alcohol dependent individuals: effect of polysubstance use disorder.

Chronic alcohol use has widespread effects on brain morphometry. Alcohol dependent individuals are often diagnosed with comorbid substance use disorders. Alterations in brain morphometry may be different in individuals that are dependent on alcohol alone and individuals dependent on alcohol and other substances. We examined subcortical brain volumes in 37 individuals with alcohol dependence only (ADO), 37 individuals with polysubstance use disorder (PS) and 37 healthy control participants (HC). Participants underwent a structural MR scan and a model-based segmentation tool was used to measure the volume of 14 subcortical regions (bilateral thalamus, caudate, putamen, globus pallidus, hippocampus, amygdala and nucleus accumbens). Compared to HC, ADO had smaller volume in the bilateral hippocampus, right nucleus accumbens and right thalamus. PS only had volume reductions in the bilateral thalamus compared to HC. PS had a larger right caudate compared to ADO. Subcortical volume was negatively associated with drinking measures only in the ADO group. This study confirms the association between alcohol dependence and reductions in subcortical brain volume. It also suggests that polysubstance use interacts with alcohol use to produce limited subcortical volume reduction and at least one region of subcortical volume increase. These findings indicate that additional substance use may mask damage through inflammation or may function in a protective manner, shielding subcortical regions from alcohol-induced damage.

Minding the brain: the role of pharmacotherapy in substance-use disorder treatment.

With its medicalization as a brain-based disease, addiction has come to be regarded as amenable to biomedical treatment approaches, most commonly pharmacotherapy. Various vulnerabilities are recognized to contribute to maladaptive substance use, and have been linked to diverse neurobiological alterations that may be targeted with pharmacotherapy: withdrawal, craving and cue reactivity, and aberrant reward processing are the most significant. Here, we summarize current thinking regarding pharmacotherapy for substance-use disorders, grouping medications by the type of vulnerability they propose to address and providing insight into their neurobiological mechanisms. We also examine the limitations of the brain-based disease model in addiction treatment, especially as these shortcomings pertain to the place of pharmacotherapy in recovery. We conclude by sketching a framework whereby medications might be integrated fruitfully with other interventions, such as behavioral, existential, or peer-based treatments, targeting aspects of addiction beyond neurobiological deficits.

La medicalización de la adicción como una enfermedad de base cerebral, ha llegado a ser considerada como una condición sensible a un abordaje terapéutico biomédico, en especial con farmacoterapia. Se han reconocido diversas vulnerabilidades que contribuyen a la mala adaptación al uso de sustancias, las cuales se han vinculado con diversas alteraciones neurobiológicas y con blancos farmacológicos; las más importantes son la abstinencia, el craving y la reactividad a señales, junto con el procesamiento aberrante de la recompensa. En este artículo se resume el pensamiento actual relacionado con la farmacoterapia para los trastornos por uso de sustancias, se agrupan los medicamentos de acuerdo con el tipo de vulnerabilidad a la que ellos están dirigidos y se proporciona una visión acerca de sus mecanismos neurobiológicos. También se examinan las limitaciones del modelo de enfermedad cerebral en el tratamiento de las adicciones, especialmente porque estas alteraciones se relacionan con el papel que tiene la farmacoterapia en la recuperación. Para concluir se propone un esquema en que los medicamentos se pueden integrar de manera fructífera con otras intervenciones como los tratamientos conductuales, existenciales o basados en pares, focalizando aspectos de la adicción más allá de las alteraciones neurobiológicas.

Médicalisée comme une maladie cérébrale, l'addiction est maintenant considérée comme étant susceptible de répondre à des traitements biomédicaux, le plus souvent de la pharmacothérapie. Des vulnérabilités diverses, responsables de l'utilisation inadaptée de substances, sont liées à différentes altérations neurobiologiques et représentent des cibles pharmacologiques dont les plus significatives sont le sevrage, l'état de manque, la réactivité aux indices environnementaux et un fonctionnement anormal du circuit de la récompense. Nous résumons ici les concepts actuels sur la pharmacothérapie des troubles liés à l'utilisation de substances en regroupant les médicaments par type de vulnérabilité traitée et en donnant un aperçu de leurs mécanismes neurobiologiques. Nous analysons aussi les limites du modèle de maladie cérébrale dans le traitement des addictions, surtout lorsque ces failles concernent la place de la pharmacothérapie dans la guérison. Nous concluons en esquissant un cadre selon lequel les médicaments pourraient trouver leur place avec succès aux côtés d'autres traitements comme les traitements comportementaux, existentiels ou collégiaux et qui ciblent des aspects de l'addiction au-delà des déficits neurobiologiques.

Heantos-4, a natural plant extract used in the treatment of drug addiction, modulates T-type calcium channels and thalamocortical burst-firing.

Heantos-4 is a refined combination of plant extracts currently approved to treat opiate addiction in Vietnam. In addition to its beneficial effects on withdrawal and prevention of relapse, reports of sedation during clinical treatment suggest that arousal networks in the brain may be recruited during Heantos administration. T-type calcium channels are implicated in the generation of sleep rhythms and in this study we examined whether a Heantos-4 extraction modulates T-type calcium channel currents generated by the Cav3.1, Cav3.2 and Ca3.3 subtypes. Utilizing whole-cell voltage clamp on exogenously expressed T-type calcium channels we find that Heantos inhibits Cav3.1 and Cav3.3 currents, while selectively potentiating Cav3.2 currents. We further examined the effects of Heantos-4 extract on low-threshold burst-firing in thalamic neurons which contribute to sleep oscillations. Using whole-cell current clamp in acute thalamic brain slices Heantos-4 suppressed rebound burst-firing in ventrobasal thalamocortical neurons, which express primarily Cav3.1 channels. Conversely, Heantos-4 had no significant effect on the burst-firing properties of thalamic reticular neurons, which express a mixed population of Cav3.2 and Cav3.3 channels. Examining Heantos-4 effects following oral administration in a model of absence epilepsy revealed the potential to exacerbate seizure activity. Together, the findings indicate that Heantos-4 has selective effects both on specific T-type calcium channel isoforms and distinct populations of thalamic neurons providing a putative mechanism underlying its effects on sedation and on the thalamocortical network.

The Role of Medicinal Cannabis in Clinical Therapy: Pharmacists' Perspectives.

BACKGROUND: Medicinal cannabis has recently attracted much media attention in Australia and across the world. With the exception of a few countries, cannabinoids remain illegal-known for their adverse effects rather than their medicinal application and therapeutic benefit. However, there is mounting evidence demonstrating the therapeutic benefits of cannabis in alleviating neuropathic pain, improving multiple sclerosis spasticity, reducing chemotherapy induced nausea and vomiting, and many other chronic conditions. Many are calling for the legalisation of medicinal cannabis including consumers, physicians and politicians. Pharmacists are the gatekeepers of medicines and future administrators/dispensers of cannabis to the public, however very little has been heard about pharmacists' perspectives. Therefore the aim of this study was to explore pharmacists' views about medicinal cannabis; its legalisation and supply in pharmacy. METHODS: Semi-structured interviews with 34 registered pharmacists in Australia were conducted. All interviews were audio-recorded, transcribed ad verbatim and thematically analysed using the NVivo software. RESULTS: Emergent themes included stigma, legislation, safety and collaboration. Overall the majority of pharmacists felt national legalisation of a standardised form of cannabis would be suitable, and indicated various factors and strategies to manage its supply. The majority of participants felt that the most suitable setting would be via a community pharmacy setting due to the importance of accessibility for patients. DISCUSSION: This study explored views of practicing pharmacists, revealing a number of previously undocumented views and barriers about medicinal cannabis from a supply perspective. There were several ethical and professional issues raised for consideration. These findings highlight the important role that pharmacists hold in the supply of medicinal cannabis. Additionally, this study identified important factors, which will help shape future policies for the successful implementation of medicinal cannabis in healthcare. We recommend that these views and strategies be incorporated in the development of policies and legislations.

What does addiction medicine expect from neuroscience? From genes and neurons to treatment responses.

The field of neuroscience is rapidly growing as evidenced by the mapping of the human genome, the progress in brain imaging technologies, and the refinement of sophisticated molecular tools that can be combined with innovative preclinical models. With these advances, it seems that our understanding of processes underlying addiction has never been so great. In comparison, the clinical domain has evolved at a much slower pace. Nonetheless, the addiction medical field has seen some gradual improvements in clinical care with the availability of a larger range of pharmacological options. Notably, several therapeutic alternatives are now offered for the treatment of nicotine, alcohol, and opioid use disorders. Some of these developments in treatment regimens have directly emerged from basic neuroscience research and represent a success story for the bench to beside translational approach. However, the clinical and research needs in addiction medicine are huge. There are still no pharmacological interventions available for psychostimulant and cannabis use disorders. Further, major questions remain unanswered: Would a better understanding of the neurocircuitry of addiction lead to therapeutic intervention? Would a better understanding of the neurochemical signature of addiction lead to the validation of a therapeutic target? Will pharmacogenetics hold its promise as a personalized medicine treatment approach? Using recent research developments, we will illustrate the potential of neuroscience to address some of the pressing questions in Addiction Medicine.

Striatal activity and reduced white matter increase frontal activity in youths with family histories of alcohol and other substance-use disorders performing a go/no-go task.

INTRODUCTION: Youths with a family history of alcohol and other drug use disorders (FH+) are at greater risk of developing substance-use disorders relative to those with no such family histories (FH-). We previously reported that FH+ youths have elevated activity in the supplementary motor area (SMA) and dorsal striatum while performing go/no-go tasks and have reduced frontal white matter integrity. A better understanding of relationships between these variables would provide insight into how frontostriatal circuitry is altered in FH+ youths, which may be an important contributor to their elevated risk. METHODS: In this study, we used structural equation modeling (SEM) to test interactions between activity in the SMA and dorsal striatum in 72 FH+ and 32 FH- youths during go/no-go task performance and to determine whether increased activity in these regions in FH+ youths can be at least partially explained by reduced frontal white matter integrity, as indexed by anterior corona radiata fractional anisotropy and N-acetylaspartate. RESULTS: Increased dorsal striatum activity explained most (∽75%) of the elevated SMA activity in FH+ youths, and the combined contributions of increased dorsal striatal activity, and decreased white matter integrity fully explained the elevated SMA activity. CONCLUSIONS: These results suggest the elevated frontal cortical activity in FH+ youths is driven both by their increased striatal activity via downstream projections and reduced white matter integrity in frontal cortical projections, the latter likely increasing frontal cortical activity due to increased energy demands required for action potential propagation. As part of our ongoing longitudinal studies we will examine how these frontostriatal alterations relate to risk for developing substance-use disorders.

Khat Use: What Is the Problem and What Can Be Done?

The chewing of khat leaves is an established tradition in East Africa but is much less prevalent in other areas of the world and is mostly limited to Somali communities. However, our understanding of what constitutes problematic khat use in the Somali community in Victoria, Australia, is limited. The objectives of this study were to better understand the views of Somali community representatives and primary care practitioners regarding problematic khat use, to consider relevant harm minimisation strategies, and to develop resources to assist individuals with problematic khat use and their families. Qualitative research methods were used to investigate the experiences and perceptions of khat use among Somalis and mainstream primary care practitioners. Six focus groups were conducted with 37 members of the Somali community and 11 primary care practitioners. Thematic analysis was used to analyse transcripts. Various indicators of the problematic use of khat were identified, including adverse physical and mental health effects, social isolation, family breakdown, and neglect of social responsibilities. Potential harm minimisation strategies were identified including the adoption of health promotion through education, outreach to the community, and the use of universal harm minimisation strategies specifically tailored to khat use.

Influence of dorsolateral prefrontal cortex and ventral striatum on risk avoidance in addiction: a mediation analysis.

BACKGROUND: Alterations in frontal and striatal function are hypothesized to underlie risky decision making in drug users, but how these regions interact to affect behavior is incompletely understood. We used mediation analysis to investigate how prefrontal cortex and ventral striatum together influence risk avoidance in abstinent drug users. METHOD: Thirty-seven abstinent substance-dependent individuals (SDI) and 43 controls underwent fMRI while performing a decision-making task involving risk and reward. Analyses of a priori regions-of-interest tested whether activity in dorsolateral prefrontal cortex (DLPFC) and ventral striatum (VST) explained group differences in risk avoidance. Whole-brain analysis was conducted to identify brain regions influencing the negative VST-risk avoidance relationship. RESULTS: Right DLPFC (RDLPFC) positively mediated the group-risk avoidance relationship (p < 0.05); RDLPFC activity was higher in SDI and predicted higher risk avoidance across groups, controlling for SDI vs. CONTROLS: Conversely, VST activity negatively influenced risk avoidance (p < 0.05); it was higher in SDI, and predicted lower risk avoidance. Whole-brain analysis revealed that, across group, RDLPFC and left temporal-parietal junction positively (p ≤ 0.001) while right thalamus and left middle frontal gyrus negatively (p < 0.005) mediated the VST activity-risk avoidance relationship. CONCLUSION: RDLPFC activity mediated less risky decision making while VST mediated more risky decision making across drug users and controls. These results suggest a dual pathway underlying decision making, which, if imbalanced, may adversely influence choices involving risk. Modeling contributions of multiple brain systems to behavior through mediation analysis could lead to a better understanding of mechanisms of behavior and suggest neuromodulatory treatments for addiction.

[Functional magnetic resonance imaging and dynamic neuroanatomy of addictive disorders].

Research into the cerebral patterns that govern the formation and development of addictive behavior is one of the most interesting goals of neurophysiology. Authors of contemporary papers on the matter define a number of symptoms that are all part of substance or non-substance dependence, each one of them leading to abnormalities in the corresponding system of the brain. During the last twenty years the functional magnetic resonance imaging (fMR1) technology has been instrumental in locating such abnormalities, identifying specific parts of the brain that, when dysfunctional, may enhance addiction and cause its positive or negative symptoms. This article reviews fMRI studies aimed toward locating areas in the brain that are responsible for cognitive, emotional, and motivational dysfunction. Cerebral correlatives of impulsiveness, behavior control, and drug cravings are reviewed separately. The article also contains an overview of possibilities to further investigate the Selves of those dependent on substances, identify previously unknown diagnostic markers of substance dependence, and evaluate the effectiveness of therapy. The research under review in this article provides data that points to a special role of the nucleus caudatus as well as the nucleus accumbens, the thalamus, the insular cortex (IC), the anterior cingulate, prefrontal and orbitofrontal areas in psychological disorders that are part of substance dependence. General findings of the article are in accordance with contemporary models of addictive pattern.

Grey matter changes associated with medication-overuse headache: correlations with disease related disability and anxiety.

OBJECTIVES: Medication-overuse headache (MOH) is associated with psychiatric comorbidities. Neurobiological similarities to substance dependence have been suggested. This study investigated grey matter changes, focussing on pain and reward systems. METHODS: Using voxel-based morphometry, structural MRIs were compared between 29 patients with both, MOH and migraine, according to International Headache Society criteria, and healthy controls. The Migraine Disability Assessment (MIDAS) score was used. Anxiety and depression were screened for with the Hospital Anxiety and Depression Scale (HADS) and confirmed by a psychiatrist, using the Mini International Neuropsychiatric Interview. RESULTS: Nineteen patients (66%) had a present or past psychiatric disorder, mainly affective (N = 11) and anxiety disorders (N = 8). In all patients a significant increase of grey matter volume (GMV) was found in the periaqueductal grey matter of the midbrain, which correlated positively with the MIDAS and the HADS-anxiety subscale. A GMV increase was found bilaterally in the thalamus, and the ventral striatum. A significant GMV decrease was detected in frontal regions including orbitofrontal cortex, anterior cingulate cortex, the left and right insula, and the precuneus. CONCLUSION: These findings are consistent with dysfunction of antinociceptive systems in MOH, which is influenced by anxiety. Dysfunction of the reward system may be a neurobiological basis for dependence in a subgroup of MOH patients.

Association between the DRD2 A1 allele and opium addiction in the Iranian population.

Dysfunction of the central dopaminergic neurotransmission has been suggested to play an important role in the etiology of certain neuropsychiatric disorders such as drug abuse. It has been shown that the dopamine D2 receptor (DRD2) gene dysfunction is associated with multi-drug addiction. Addiction to opium is the most common form of drug abuse in Iran. We studied the allelic association between DRD2 Taq I A polymorphism in 100 opium-dependent Iranian patients and 130 unrelated controls. A 310 bp (base pair) region surrounding Taq I site at the DRD2 locus was amplified by polymerase chain reaction (PCR) and the PCR product was incubated with Taq I restriction enzyme. The A1 allele remained intact while the A2 allele was cut. Significant association was observed between A1 allele and addiction in the patients group (P < 0.0001). Moreover, the frequency of A1A1 genotype was significantly higher in opium users than controls (P < 0.0001). Our result indicates that DRD2 might be involved in the pathophysiology of opium addiction.

The spectrum of neuroimaging abnormalities in solvent abuse and their clinical correlation.

The brain magnetic resonance (MR) images and medical records of 6 patients with a history of chronic toluene abuse were reviewed retrospectively. The imaging findings were correlated with clinical impairment. The major findings consisted of atrophy (6 patients), white matter T2 hyperintensity (6 patients), and T2 hypointensity involving the basal ganglia and thalami (5 patients). Also seen was focal enhancement, previously unreported for patients who abused toluene. This study showed a correlation between the degree of neurological impairment and extent of white matter disease. There was no correlation between the severity of white matter changes on MR images and the presence of T2 hypointensity or duration of toluene abuse. There was no definite clinical evidence of damage to the basal ganglia and thalami despite the MR imaging finding of T2 hypointensity. Temporal evidence against the theory that toluene accumulation causes the T2 hypointensity was found.

Coin-rubbing injuries.

Two cases of injuries caused by "coin rubbing" (Kuasha) are presented. In one case these injuries were confined to the neck, raising the possibility of strangulation, and in the other to the trunk and limbs, suggesting torture. Coin rubbing is practiced by most South-East Asian cultures, which believe that it relieves the symptoms of headache, fever, and flu. The causation and characteristics of these injuries and their medicolegal importance are discussed.

Ultrastructure sperm defects in addicts.

Addiction is a major problem confronting the whole world today. Disruption of interpersonal relationships, economic loss, and crimes against property are frequent consequences. Harm to the individual himself extends to all physiological systems. In the present study, we examined semen samples of six addicts by light and electron microscopy. Oligoasthenospermia was demonstrated in five patients, and necrospermia was observed in one patient. Severe degenerative changes of the sperm heads were noted. Granular condensation of the chromatin with nuclear vacuoles was demonstrated. Persistent cytoplasmic droplets were frequently observed. Degenerated tails showing fragmentation of the plasma membranes and numerical aberrations of the 9 + 2 configuration were also present, together with thickened and disorganized fibrous sheaths. These results confirm the deleterious effects of addiction on the entire sperm structure.