Survey of current trends in the abuse of psychotropic substances and plants in Japan

In recent years, many analogs of narcotics have been widely distributed as easily available psychotropic substances and have become a serious problem in Japan. To counter the spread of these non-controlled substances, the Pharmaceutical Affairs Law in Japan was amended in 2006 to establish a new category, "designated substances", to more strictly control these psychotropic substances. Fifty-one substances have been listed in this category as of December 2010. However, many new analogs have appeared, one after the other. Although the distribution of tryptamine-type designer drugs has decreased since the amendment of the law, the distribution of cathinone derivatives, as well as of phenetylamine-type and piperazine-type designer drugs, has increased. Moreover, non-controlled psychotropic plants have become popular in place of chemical psychotropic substances, which are now subject to stricter controls. Additionally, since 2008, new herbal products containing synthetic cannabinoids (for example, a brand named "Spice") have appeared. Sixteen synthetic cannabinoids, classified into four groups, have been detected in products purchased up to December 2010 via Japanese-based websites. The distribution of products containing the psychoactive substances described above (so-called "legal highs" in European countries) is a worldwide problem. In this review, we survey current trends in the abuse of psychotropic substances and plants in Japan, focusing especially on synthetic cannabinoids, cathinone derivatives and psychotropic plants.     

Trasplante renal de donante vivo ABO incompatible. Estudio de 48 pacientes tras desensibilización

BackgroundABO-incompatible living-donor kidney transplantation was regarded as an absolute contraindication. However, it has been carried out for years with good outcomes.ObjectiveOur aim was to show the results obtained with this technique in our hospital.MethodsForty-eight patients with a mean age of 50.9 ± 10.9 years were included. Follow-up was 44.6 ± 30.9 months. Conditioning: rituximab 375 mg/m², tacrolimus, mycophenolate mofetil or mycophenolate sodium, prednisone, plasmapheresis/immunoadsorption and intravenous immunoglobulin. Accepted IgG and IgM titres for transplantation: < 1:8.ResultsPre-process IgG titre 1:124 ± 1:140, IgM titre 1:77 ± 1:55. After 6 ± 3 sessions, IgG decreased to < 1:8 in 47 patients and to < 1:16 in one. IgM was < 1:8 in all cases. Twenty-four patients (50%) had haematoma, 7 re-intervention (14.6%), 29 (60%) required transfusion. At 5 years, acute rejection had occurred in 5 cases (8.7%), CMV infection in 9 (19.7%), BK viraemia in 5 (12.4%), post-transplant diabetes in 10 (23.4%) and lymphocele in 3 (6.4%). Patient survival was 97.1% at 5 years and graft survival 95.7% at one year and 93% at 5 years. Causes of graft loss: thrombosis (n = 1); mixed rejection (n = 1); and death (n = 2). Serum creatinine levels were 1.4 ± 0.4 mg/dl at one and 3 years and 1.3 ± 0.3 mg/dl at 5 years. Proteinuria was 0.2 ± 0.2 g/24 h at one, 3 and 5 years.ConclusionsABO-incompatible living-donor kidney transplantation after conditioning with rituximab, plasmapheresis/immunoadsorption and immunoglobulins is a valid option offering excellent outcomes. There is a low incidence of acute rejection and no increase in infectious complications. An increased tendency for postoperative bleeding was found.     

Genetic predisposition to PEG-asparaginase hypersensitivity in children treated according to NOPHO ALL2008

Asparaginase is essential in childhood acute lymphoblastic leukaemia (ALL) treatment, however hypersensitivity reactions to pegylated asparaginase (PEG-asparaginase) hampers anti-neoplastic efficacy. Patients with PEG-asparaginase hypersensitivity have been shown to possess zero asparaginase enzyme activity. Using this measurement to define the phenotype, we investigated genetic predisposition to PEG-asparaginase hypersensitivity in a genome-wide association study (GWAS). From July 2008 to March 2016, 1494 children were treated on the Nordic Society of Paediatric Haematology and Oncology ALL2008 protocol. Cases were defined by clinical hypersensitivity and no enzyme activity, controls had enzyme activity ≥ 100 iu/l and no hypersensitivity symptoms. PEG-asparaginase hypersensitivity was reported in 13·8% (206/1494) of patients. Fifty-nine cases and 772 controls fulfilled GWAS inclusion criteria. The CNOT3 variant rs73062673 on 19q13.42, was associated with PEG-asparaginase allergy (P = 4·68 × 10⁻⁸). We further identified two signals on chromosome 6 in relation to HLA-DQA1 (P = 9·37 × 10⁻⁶) and TAP2 (P = 1·59 × 10⁻⁵). This study associated variants in CNOT3 and in the human leucocyte antigen (HLA) region with PEG-asparaginase hypersensitivity, suggesting that not only genetic variations in the HLA region, but also regulation of these genes are of importance in the biology of this toxicity. Furthermore, our study emphasizes the importance of using asparaginase enzyme activity measurements to identify PEG-asparaginase hypersensitivity.     

Psychological and social determinants of health,antiretroviral therapy (ART) adherence,and viral suppression among HIV-positive black women in care

Black women are disproportionately affected by HIV, accounting for 61% of women diagnosed in 2016. Black women with HIV are less likely to be adherent to antiretroviral therapy (ART) and virally suppressed compared to women of other racial/ethnic groups. We analyzed 2013–2014 data from 1703 black women patients in the Centers for Disease Control and Prevention’s Medical Monitoring Project to examine whether select psychological and social determinants of health (SDH) factors were associated with ART adherence and viral suppression. We calculated weighted estimates and used multivariable logistic regression with adjusted prevalence ratios (aPR) and 95% confidence intervals (CI) to examine correlates of ART adherence and viral suppression. Women who had not been incarcerated in the past 12 months (aPR?=?1.24; CI: 1.04–1.48) and had not experienced discrimination in a health care setting since their HIV diagnosis (aPR?=?1.06; 1.00–1.11) were slightly more likely to be adherent to ART. Women who lived above the federal poverty level were more likely to be virally suppressed during the past 12 months (aPR?=?1.09; CI: 1.01–1.18). More research is warranted to identify the best strategies to create health care settings that encourage black women’s HIV care engagement, and to address other key SDH and/or psychological factors.     

The effect of flutamide on expression of androgen and estrogen receptors in the gubernaculum and surrounding structures during testicular descent

Background/Purpose

Inguinoscrotal testicular descent is controlled by androgens between embryonic days E16-19, but androgen receptor (AR) and estrogen receptor (ER) locations are unknown. We aimed to find AR, ERα, and ERβ in the gubernaculum and inguinal fat pad (IFP) in normal rats and after flutamide treatment.

Methods

Sprague-Dawley timed-mated rats were injected with flutamide (75 mg/kg body weight/5% ethanol + oil) on E16-19 or vehicle alone. Male fetuses or pups (5-10/group) were collected at E16; E19; and postnatal (P) days 0, 2, 4, 8. Sections were prepared for hematoxylin and eosin or immunohistochemistry for AR, ERα, and ERβ. Receptor labeling was quantitated as distinct nuclear labeling/100 μm² in gubernaculum and IFP.

Results

There was minimal gubernacular AR-labeling until E19, dramatically increasing postnatally. By contrast, at E16-E19 there was significant IFP AR immunoreactivity suppressed by flutamide (P < .05). No ERα expression was observed, but ERβ was expressed in both gubernaculum and IFP, maximally at E16, but unchanged by flutamide.

Conclusions

During the androgen sensitivity window (E16-19), the gubernaculum contains ERβ but minimal ERα or AR, while the IFP, which is supplied by the genitofemoral nerve, contains abundant AR that are flutamide-sensitive. These results suggest that the IFP could be the site of androgenic action controlling gubernacular development.