Prevalence of psychoactive drugs in injured patients presenting to an emergency department.

OBJECTIVE: The aim of the present study was to obtain an unbiased understanding of the prevalence of psychoactive drugs in trauma patients presenting to a large ED. METHODS: Consecutive adult patients presenting to the ED with an injury resulting in a trauma call had an anonymised, additional blood test taken for detection of over 2000 drugs. Laboratory testing was to judicial standards. Drugs given by ambulance pre-hospital were detected but excluded from the analysis. RESULTS: Over 6 months 276 (74.7%) of 371 patients were tested. Of the 276 patients tested, 158 (57.2%) had one or more psychoactive drug present. Recreational drugs were detected in 101 (36.6%) patients and medicinal drugs in 88 (31.8%) patients, with a combination of both detected in 31 (11.2%) patients. The most common drugs detected were cannabis (22.1%), antidepressants (18.4%), alcohol (15.5%), opioids (10.1%), benzodiazepine/z-drugs (9.4%) and methamphetamine (7.2%). The prevalence of psychoactive drugs differed by age group, sex and cause of injury. CONCLUSIONS: The prevalence of psychoactive drugs in injury presentations to an ED is high, and provides an opportunity to reduce harm. The present study demonstrates the feasibility of an approach which limits bias and obtains results that accurately reflect the drug prevalence in injured cohorts. Systematic testing of injured patients is an important contribution to the epidemiology of injury.

The impact of traditional kava (Piper methysticum) use on cognition: Implications for driver fitness.

ETHNOPHARMACOLOGICAL RELEVANCE: Few studies have examined the impact of kava (Piper methysticum G. Forst. f.) on cognition when consumed at traditionally influenced volumes; most have used modified tablet-form kava, with the results erroneously overlaid on naturalistic kava consumption. Kava is a culturally significant Pacific drink with similar effects to Benzodiazepine. Traditionally influenced kava use sessions last, on average, 6 h in which attendees consume 3.6 L (7.6 pints) each of beverage kava, with some then driving home. AIM OF THE STUDY: This study evaluated the impact of traditionally influenced kava consumption on participants' neurological functioning. Testing occurred before, throughout and immediately following a typical faikava (kava-drinking) session, with the data then used to assess kava's potential impacts on driver functionality and safety. METHODS: Kava using participants (n = 20) were assessed with the Brain Gauge following and during a traditionally influenced kava session and compared against control (n = 19). Brain Gauge measures slight changes to six cognitive faculties: Speed, Accuracy, Temporal Order Judgement (TOJ), Timing Perception, Plasticity, and Focus. RESULTS AND CONCLUSIONS: Comparisons of the within-cohort data showed a positive change in the Focus for the active group at the final testing point following 6-h of kava consumption. Between-cohort data showed a significant level of regression in the active participants' TOJ at the final testing point. No statistically significant level of impairment for the other five cognitive domains was detected. Although the results suggest that kava when consumed at traditional levels may have a slight positive effect on Focus, this result needs to be treated with caution, given the significant level of impairment noted at the final testing point for participants' TOJ. Temporal Order Judgement is associated with executive function, including decision making, behavioral control and information processing, all crucial aspects of driver safety. This is a new finding and suggests kava effects following traditional use differ from those caused by other substances commonly used for social or recreational purposes, such as cannabis, alcohol and other euphoric substances, and may impair driver safety, although again, in a different way to other commonly consumed recreational substances. The findings also add quantitative understanding to ethnographic data on kava effects, suggesting the often-used term 'kava intoxication' is misleading and incorrect.

An outbreak of deaths associated with AMB-FUBINACA in Auckland NZ.

BACKGROUND: AMB-FUBINACA is a synthetic cannabinoid that has been associated with periodic outbreaks of acute poisonings, but few fatalities. In late May, June and July 2017 Auckland, New Zealand, experienced an outbreak of deaths associated with AMB-FUBINACA that continued at a rate of about 2-3 per month through February 2019. The aim of this study was to define the demographic, circumstantial, pathological and toxicological characteristics of this outbreak. METHODS: All records of the Northern Forensic Pathology Service, Auckland Hospital, were reviewed in which the word "AMB-FUBINACA" was referenced, including initial police reports, autopsy reports and toxicology reports. Recorded data included age, sex, race/ethnicity, times and locations, cause of death, autopsy and toxicology findings, and a brief summary of the circumstances of death. Descriptive statistics were performed using IBM® SPSS® Statistics Version 24 and Microsoft® Excel® Version 14.7.2. FINDINGS: Sixty-four cases were identified. One sudden infant death and five cases where cause of death was due to trauma were excluded. Of the remaining 58 cases, 88% were male. Mean age was 42 years. In 95% of the deaths, AMB-FUBINACA alone or in combination with alcohol or another drug was listed as the primary or contributory cause of death. In 41 cases postmortem blood concentrations of AMB-FUBINACA acid were available, ranging from <45 ng/mL to >1000 ng/mL, mean 229 ng/mL, median 140 ng/mL. Comorbidities identified included mixed intoxications (29%), heart disease (47%) and obesity (16%). A mental health diagnosis was reported in 50%, and 40% were on antipsychotic medications. INTERPRETATION: This study presents characteristics, comorbidities and toxicological findings in a unique outbreak of deaths associated with the synthetic cannabinoid AMB-FUBINACA in Auckland, NZ. FUNDING: All work was funded as part of the usual employment of the authors in their respective institutions. No special funding sources are reported.

In Silico and In Vitro Anticancer Activity of Isolated Novel Marker Compound from Chemically Modified Bioactive Fraction from Curcuma longa (NCCL).

BACKGROUND: Turmeric (Curcuma longa) is reported to possess wide array of biological activities. Herbal Medicament (HM) is a standardized hexane-soluble fraction of C. longa and is well known for its neuroprotective effect. OBJECTIVE: In this study, we attempted to synthesize a novel chemically modified bioactive fraction from HM (NCCL) along with isolation and characterization of a novel marker compound (I). MATERIALS AND METHODS: NCCL was prepared from HM. The chemical structure of the marker compound isolated from NCCL was determined from 1D/2D nuclear magnetic resonance, mass spectroscopy, and Fourier transform infrared. The compound so isolated was subjected to in silico and in vitro screenings to test its inhibitory effect on estrogen receptors. RESULTS: Molecular docking studies revealed that the binding poses of the compound I was energetically favorable. Among NCCL and compound I taken for in vitro studies, NCCL had exhibited good anti-cancer activity over compound I against MCF-7, MDA-MB-231, DU-145, and PC-3 cells. CONCLUSION: This is the first study about the synthesis of a chemically modified bioactive fraction which used a standardized extract since the preparation of the HM. It may be concluded that NCCL fraction having residual components induce more cell death than compound I alone. Thus, NCCL may be used as a potent therapeutic drug. SUMMARY: In the present paper, a standardized hexane soluble fraction of Curcuma longa (HM) was chemically modified to give a novel bioactive fraction (NCCL). A novel marker compound was isolated from NCCL and was characerized using various spectral techniques. The compound so isolated was investigated for in-silico screenings. NCCL and isolated compound was subjected to in-vitro anti-cancer screenings against MCF 7, MDA MB 231 (breast adenocarcinoma) and DU 145 and PC 3 cell lines (androgen independent human prostate cancer cells). The virtual screenings reveals that isolated compound has shown favourable drug like properties. NCCL fraction having residual components induces more cell death in these four cancer cell lines than isolated compound alone. Abbreviations used: HM: Herbal Medicament; NCCL: Chemically modified HM; FT-IR: Fourier transform-infrared spectroscopy; NMR: Nuclear magnetic resonance spectroscopy; MS: Mass spectroscopy; HPLC: High-performance liquid chromatography; ER: Estrogen receptor; MTT: 3-(4,5 dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide; MIC: Minimum inhibitory concentration; TAM: Tamoxifen KBr: Potassium bromide; DMSO: Dimethyl sulfoxide; ACN: Acetonitrile; PDB: Protein Data Bank; PDA: Photodiode array detector.

Assay method for quality control and stability studies of a new anti-diabetic and anti-dyslipidemic flavone (S002-853).

BACKGROUND: Flavonoid-rich extract of the plant is long known for its anti-diabetic activities in traditional medicine. S002-853, a new flavone derivative synthesized by Central Drug Research Institute (CDRI) has been used for the present study. OBJECTIVES: The present study aimed at development of an assay method for quality control (QC) and stability studies of a new anti-diabetic and anti-dyslipidemic agent CDRI compound S002-853. MATERIALS AND METHODS: A validated high-performance liquid chromatography analysis method for S002-853 was developed for in process QC and stability studies. The separation was achieved on a RP-C18 (25 cm × 0.4 cm, 5 µm, Phenomenex) at 240 nm with flow rate of 1.0 ml/min. This method was applied successfully in establishing forced degradation and drug-excipient testing protocols as per International Conference on Harmonization guidelines. RESULTS: The result of estimation and stress testing studies indicated a high degree of selectivity of this method. S002-853 was most stable at pH 7 and under photolytic conditions. The temperature degradation pattern of S002-853 was found to follow the zero order degradation. CONCLUSION: The method described is easy and simple hence can be easily reproduced. This method can be very useful for bulk manufacture QC, and drug development process.

Design, synthesis and molecular docking of substituted 3-hydrazinyl-3-oxo-propanamides as anti-tubercular agents.

Based on the anti-mycobacterial activity of various acid hydrazides, a series of substituted 3-hydrazinyl-3-oxo-propanamides has been designed. The target compounds have been synthesized from diethylmalonate using substituted amines and hydrazine hydrate in ethanol. Computational studies and anti-tubercular activity screenings were undertaken to test their inhibitory effect on protein kinase PknB from Mycobacterium tuberculosis. Binding poses of the compounds were energetically favorable and showed good interactions with active site residues. Designed molecules obey the Lipinski's rule of 5 and gave moderate to good drug likeness score. Among the sixteen compounds (1-16) taken for in silico and in vitro studies, 3 compounds (11, 12 and 15) have shown good binding energies along with exhibiting good anti-tubercular activity and thus may be considered as a good inhibitors of PknB.

Design and synthesis of γ-butyrolactone derivatives as potential spermicidal agents.

A series of γ-butyrolactone derivatives has been designed and synthesized from commercially available 2-acetyl butyrolactone (3-acetyldihydrofuran-2(3H)-one, 1) by aminoalkylating its active methylene followed by condensation with different aldehydes. Compounds having amino group were further converted to their respective tartrate salts and were evaluated for spermicidal activity against human sperm in vitro. Compounds showing appreciable spermicidal activity at ⩽0.5% [3c, 4d (0.5%); 2c, 3d (0.1%); 2d, 4c (0.05%)] were tested for safety studies against human cervical (HeLa) cell line. These compounds were found safer than, Nonoxynol-9. One of the two most active compounds was also found to be the safest (IC50=961 µg/ml; 4c), while the second compound exhibited lower safety against HeLa (IC50=269 µg/ml; 2d). The compound 4c significantly reduced the number of free thiols on human sperm. All the compounds were inactive against Trichomonas vaginalis.

Protein ß-interfaces as a generic source of native peptide tectons.

Motifs of 7-8 amino acids were designed from the ß-continuous interfaces of non-related homo-oligomeric proteins. These peptides intrinsically self-assembled into nanoarchitectures in water, while retaining some properties of their parent interfaces, especially reversibility of assembly. These results reveal a novel source of native peptide tectons.

Synthesis of 3-(1-alkyl/aminoalkyl-3-vinyl-piperidin-4-yl)-1-(quinolin-4-yl)-propan-1-ones and their 2-methylene derivatives as potential spermicidal and microbicidal agents.

A series of twenty two derivatives of 3-(1-alkyl/aminoalkyl-3-vinyl-piperidin-4-yl)-1-(quinolin-4-yl)-propan-1-one and their 2-methylene derivatives were synthesized from naturally abundant cinchonine (I). Tartarate salts of these compounds were prepared and evaluated for spermicidal activity. The most active compounds (24, 27, 34, 36, and 38) showing potent spermicidal activity were further evaluated against different strains of Trichomonas vaginalis, for antimicrobial activity, in HeLa cell lines for cytotoxicity and against Lactobacillus jensenii for eco-safety. The tartarate of 3-(1-pentyl-3-vinyl-piperidin-4-yl)-1-(quinolin-4-yl)-propan-1-one (27) was found to be more active than N-9 in spermicidal activity.

Chlorophenol stress affects aromatic amino acid biosynthesis-a genome-wide study.

Chlorophenols are a class of chemicals commonly used in preservatives, disinfectants, algaecides, herbicides and pesticides. However, there is a growing evidence that these compounds are a threat to human health. This is alarming as many chlorophenols are common pollutants found in the global environment at potentially biohazardous levels. Despite chlorophenols being abundant, widely used and poisonous, we know relatively little about their mechanism of toxicity in eukaryotes. Thus, we performed genome-wide growth screens using Saccharomyces cerevisiae to understand the molecular basis of chlorophenol toxicity. Of ∼4850 single gene knockout strains tested, 393 mutants showed growth sensitivity to treatment with 4-chlorophenol (4-CP), 2,4-dichlorophenol (2,4-DCP) or pentachlorophenol (PCP). Only eight mutants showed growth hypersensitivity to all the three treatments and harboured deletions in genes important for aromatic amino acid biosynthesis (ARO1, ARO7) or mitochondrial protein synthesis and respiration (ATP5, ISA1, RML2, GET2, SLS1, MRPL38).