Drug Control Research Articles

B-054 Performance Evaluation of the VITROS HIV Combo Assay on the Ortho VITROS 3600 system

Abstract Background n 2014, the US CDC updated HIV screening algorithm, recommended any assay capable of reliably detecting p24 antigen and both IgG&IgM antibodies as starting point. In 2021 Chinese FDA approved VITROS HIV Combo assay as early detection of acute HIV infection with fourth-generation Ag/Ab combination test, with several declared earlier seroconversion panel reactivity than the third generation assay. This study records the experiment run to assess clinical performance using prospectively collected HIV-1 and HIV-2 antibody positive samples from Chinese CDC on the VITROS HIV Combo Assay on the VITROS 5600 Integrated System, Methods In total 450 serum/plasma samples, including 164 HIV antibody positive (162 HIV-1 antibody positive and 2 HIV-2 antibody positive) and 286 HIV negative. The HIV-2 antibody positive samples were purchased from Seracare (United States), and the remaining samples were prepared by the Chinese CDC reference laboratory. In the samples prepared in the reference laboratory, all HIV-1 antibody positive samples were tested by HIV antibody confirmation test, and the result was positive; The HIV negative samples were confirmed based on a comprehensive assessment of HIV antibodies, HIV-1 p24 antigen, HIV nucleic acid testing, and follow-up testing results, and window period has been ruled out. Ten linear and sensitivity reference samples were added to the HIV-1 p24 antigen national reference material (batch number 20190505, purchased from the China Academy of Food and Drug Control) . The antigen concentrations from L1 to L10 were 20, 10, 5, 2.5, 1.25, 0.625, 0.313, 0.156, 0.0781, and 0 IU/ml, respectively. Results The sensitivity for this positive population of samples in the VITROS Combo test was calculated as 100.00% (164/164) with an exact 95% confidence interval (Cl) of 99.26% to 100.00%. The specificity for this negative population was 99.58% (Cl 99.38%-99.73%). Conclusions The sensitivity and specificity of VITROS Combo assay are very high. With class leading antigen sensitivity doesn’t sacrifice specificity. This new assay delivers excellent confidence in results, and with more target (HIV-1 p24) being detected, can helps laboratory shortening HIV infection window, improve operators and technicians’ confidence in the outcome of HIV testing.

B-298 Quantitation and Abundance of Xylazine and Xylazine Metabolites in Human Urine by LC-MS/MS

Abstract Background The most common cause of drug overdose fatality in the US involves synthetic opioids such as fentanyl. Recently the Director of the White House Office of National Drug Control Policy designated fentanyl associated with xylazine as an emerging threat to the US, and a national response plan will include xylazine testing. Xylazine, a clonidine analog is not FDA-approved for use in humans but has been increasingly detected in unregulated illicit drugs supplies. Our understanding of xylazine detection, metabolism, and clinical impact on patients, however, is limited. The objectives of this study are to develop a liquid chromatography tandem mass spectrometry (LC-MS/MS) method to investigate the presence and abundance of xylazine metabolites in remnant urine samples submitted for clinical testing. Methods Remnant urine samples were identified when tested positive for xylazine during routine clinical LC-MS/MS testing. All experiments were performed using an Acquity HPLC coupled to a Waters TQS-micro triple quadrupole mass spectrometer. Urines were diluted with xylazine-D6 internal standard, hydrolyzed using β-glucuronidase and separated on a 100mm x 2.1mm, 2.6μm Kinetex C18 column (Phenomenex) with a 4 minute step gradient from 2% to 98% mobile phase B (0.1% formic acid and 2mM ammonium acetate in A: water; B: methanol) with a flow rate of 400 μl/min at 50°C. Xylazine and 4-OH-xylazine were detected in positive mode using multiple reaction monitoring, with transitions optimized from standards (Cayman Chemical and/or Sigma Aldrich), resulting in the following transitions: xylazine: 221>90, 221>164; 4-OH xylazine: 237>90, 237>137. Xylazine and 4-OH-xylazine were quantified using calibration curves prepared from 1 - 5,000 ng/mL in negative urine. Product ion scanning (PIS) was used to detect four additional xylazine metabolites, based on spectral matching to previously published full scan high resolution product ion spectra. The highest abundance fragment ions and identified retention times from PIS experiments were used to perform targeted detection for sulfone-xylazine (253>181, 253>147), oxo-xylazine (235>122, 235>114), OH-sulfone-xylazine (269>197, 269>163), and OH-oxo-xylazine (251>197, 251>148). Results Xylazine was detected at >=1 ng/mL in 38% (54/138) of fentanyl positive urines. A subset (n= 362) of urines that screened positive for opiates, amphetamines, or cocaine metabolite, were also tested but xylazine was detected in only 1 urine that did not contain fentanyl.Xylazine concentrations quantified in 61 remnant urines ranged from <1 to >5,000 ng/mL. 4-OH-xylazine concentrations ranged from <1 to 509 ng/mL. We observed five previously reported xylazine metabolites: 4-OH-xylazine, oxo-xylazine, sulfone-xylazine, OH-oxo-xylazine, OH-sulfone-xylazine. The mean concentration ratio of 4-OH-xylazine-to-xylazine was 0.11. The mean peak area ratios (metabolite-to-xylazine) for sulfone-xylazine, OH-oxo-xylazine, OH-sulfone-xylazine, and oxo-xylazine were 3.5, 3.8, 2.1, and <0.1, respectively. The proposed sulfone-xylazine and OH-oxo-xylazine metabolites were observed to have the most abundant signal of all detected metabolites, although there is currently no commercially available standard to facilitate quantification. Conclusions Xylazine and 4-OH-xylazine were quantitated in 61 patient urines. Four additional xylazine metabolites were observed and relative abundance to xylazine was estimated using peak areas. Future studies include quantitation of xylazine and xylazine metabolites in plasma and association of xylazine detection with clinical presentation and patient outcomes.

Temperature-responsive two-dimensional polydopamine hydrogel: Preparation, mechanisms, and applications in cancer treatment

Temperature-responsive hydrogels are advanced materials that exhibit significant physical or chemical changes in response to temperature variations. When the temperature reaches a specific threshold, these hydrogels alter their properties accordingly. They offer significant advantages in cancer therapy, including precise control over drug release, minimized toxicity, improved therapeutic efficacy, and biodegradability. Advancing the development of novel temperature-responsive hydrogels is crucial for enhancing therapeutic strategies. Herein, two-dimensional polydopamine (2D PDA) was first combined with chitosan (CTS) to create a temperature-responsive hydrogel for the control and release of anticancer drugs. Leveraging the carbonyl-rich nature of 2D PDA, we initiated a reversible cyclization reaction between CTS and the carbonyl groups on the surface of 2D PDA, resulting in a temperature-responsive CTS@2D PDA (CP) hydrogel. Furthermore, the CP hydrogel template was incorporated with the photosensitizer zinc phthalocyanine (ZnPc) and sodium percarbonate (SPC), an oxygen (O2) donor, to form a composite hydrogel (CSZP hydrogel). O2 released from the CSZP hydrogel mitigated solid tumor hypoxia and suppressed the expression of hypoxia-inducible factor-1α (HIF-1α), thereby augmenting the efficacy of photodynamic therapy (PDT). This temperature-responsive hydrogel represented a highly promising platform for the precise and controlled release of various therapeutics, thereby advancing the field of targeted disease treatment.

Prevalence and Profile of Tapentadol Use in Patients Visiting a Drug De-addiction Center in Kashmir

Background: Misuse of prescription opioids has been a hazard lately with tapentadol being a recent addition to the list. Tapentadol is a schedule H1 opioid (Drugs and Cosmetics Rules, India), approved for the management of moderate-to-severe acute and chronic pain. Aims and Objectives: We examined the prevalence of tapentadol use among patients attending the Drug De-addiction Center, Government Medical College, Srinagar, Kashmir, along with their sociodemographic and clinical profiles. Materials and Methods: It was a cross-sectional study. Patients who reported current tapentadol use were included in the study. Results: In a span of 4 months, a total of 104 patients using tapentadol were seen. Our study mostly consisted of young, unmarried males. More than half of our study participants had concurrent opioid dependence. In our study, no participant had ever injected tapentadol. Conclusion: Tapentadol is becoming infamous as a cheap and ready-to-available drug, replacing other opioids during their nonavailability. This should be a potentially alarming sign for drug control authorities. As such, its sale and supply should be well regulated.

Poppers, the Politics of Exemption and the Characteristics of Poppers Users in the annual English Festival Study, 2014–23

Abstract This paper explores the relationship between socio-demographic characteristics, self-reported alkyl nitrite (‘poppers’) use and sexual behaviours against a backdrop of UK policy change and ambiguity surrounding legal status. In 2024, the Advisory Council on the Misuse of Drugs recommended a unique, government-initiated, legal exemption from the Psychoactive Substances Act 2016 for poppers, because of its use by gay and bisexual men to reduce the risk of injury during anal sexual intercourse. Data from the annual convenience sample English Festival Study 2014–23 (n = 11,566) were used for Bayesian regression analyses of self-reported poppers use in three-time frames: lifetime, past year and past month use. Gay men were significantly more likely to report poppers use and particularly those reporting past-year participation in anal sex. Providing a critical analysis of recent trends in UK drug policy, the authors highlight how differential discrimination occurs within drug control where targeted exemption meets the politics of protected characteristics in UK law. This paper argues that poppers, therefore, provide a unique example in UK drug policy of how an apparent liberalization of legislative control could bolster the overarching drug prohibition regime while maintaining the appearance of rationality and fairness.

Increased lipoprotein (a) as an additional factor in the failure to achieve target blood pressure levels and lipid spectrum optimal parameters in patients with arterial hypertension and multifocal atherosclerosis

Aim. To establish the frequency of achieving target of blood pressure (BP) levels and lipid spectrum parameters (LS) in patients with arterial hypertension (AH) and multifocal atherosclerotic lesion (MFAL) with normal and elevated levels of lipoprotein (a) (Lp(a)) in real clinical practice.Material and methods. The study included 110 patients with AH and MFAL, median age was 59.0 (51.0; 64.3) years. Depending on the level of Lp(a), all patients were divided into 2 groups: group 1 — 72 patients (65.5%), Lp(a) level was ≤50 mg/dl (13.2 (3.7; 21.1)), group 2 — 38 patients (34.5%) Lp(a) level was >50 mg/dl (89.5 (62.5; 110.0)). The diagnosis of MFAL included damage to two or more arterial basins according to carotid artery, abdominal aorta and lower extremities arteries duplex scan. Patients of both groups received antihypertensive, lipid-lowering, and antiplatelet therapy.Results. Patients in groups 1 and 2 showed similar blood pressure levels and frequency of antihypertensive therapy use. In both groups, the majority of patients were on a free combination of antihypertensive drugs, only a third of patients used a fixed combination. In most cases, patients of both groups did not reach the target blood pressure levels (63.9% — group 1, 55.3% — group 2), despite the fact that the average blood pressure figures were relatively low (132;83 mmHg in each group). Drug control was also unsatisfactory in both groups, regardless of the level of Lp(a). However, all drug indicators were significantly worse in group 2, despite comparable lipid-lowering therapy, which more often included statin monotherapy. Combination therapy with lipid-lowering drugs was used in patients of groups 1 and 2 only in 20.8% and 10.5%, respectively. Parameters of low-grade inflammation high-sensitivity C-reactive protein and interleukin-6 did not differ between the groups and did not exceed the reference values.Conclusion. An increased level of Lp(a) may be accompanied by drug disorders and increased BP in patients with MFAL. Due to the lack of effective Lp(a) reducing therapy, the prevention of cardiovascular events in such patients should focus on BP and lipid spectrum correction. The use of fixed combinations, including antihypertensive and lipid-lowering drugs, can lead to improved adherence to therapy, increased BP and LS control.

Computational and experimental study of AC measurements performed by a double-nanohole plasmonic nanopore sensor on 20 nm silica nanoparticles

A novel method of AC sensing is presented that uses a double nanohole (DNH) nanoaperture atop a solid-state nanopore (ssNP) to trap analytes and measure their optical and electrical properties. In this method analytes are propelled by an external applied voltage towards the sensor until they are trapped at the DNH-ssNP interface via a self-induced back action (SIBA) plasmonic force. We have previously named this method SIBA Actuated Nanopore Electrophoresis (SANE) sensing and have shown its ability to perform concurrent optical and DC electrical measurements. Here, we extend this method to AC sensing of 20 nm SiO2 (silica) nanoparticles, using voltage modulation over a wide range of frequencies applied on top of a baseline DC bias. The sensor was constructed using two-beam GFIS Focused Ion Beam (FIB) lithography, incorporating Ne FIB to mill the DNH and He FIB to drill a central 30 nm ssNP. We utilized COMSOL Multiphysics simulations to explore the multi-frequency AC current conductance properties of the silica nanoparticles trapped at the SANE sensor. These simulations computed conductance changes and phase shifts induced by the presence of the nanoparticle over an AC frequency range of 20 Hz to 100 kHz. Experimental measurements confirmed the trends seen in the computational data. Additional computational studies were then performed to dissect the underlying mechanisms driving the observed AC measurements. Looking forward, we aim to adapt this technology for probing therapeutic nanoparticles non-invasively, offering a promising tool for enhancing quality control of nanoparticle-mediated drug and gene delivery systems.

Watch those OD numbers!

In a comment entitled “the new math,” Rob Kent, former general counsel for the federal Office of National Drug Control Policy, and before that general counsel for the New York Office of Addiction Services and Supports (OASAS), sent us this.

Nation's Response to the Substance Use Crisis.

Dr.Rahul Gupta, the first practicing physician to serve as Director of the White House Office of National Drug Control Policy, shares his perspective on the national response to the opioid crisis and how North Carolina is poised to take action to save lives from overdose.

Reversed‐Phase Analytical Method for Enantioselective Analysis of Ormeloxifene Hydrochloride: Application to Bulk Drug and Quality Control Analysis

ABSTRACTThe article reports simple, rapid, and novel enantioselective reversed‐phase high‐performance liquid chromatography (RP‐HPLC) for separation of (−)‐(3R, 4R)‐ormeloxifene hydrochloride (d‐ORM) and (+)‐(3S, 4S)‐ormeloxifene hydrochloride (l‐ORM) (ORM, centchroman) using chiral stationary phase (Chiral‐AGP, Chiracel OJ‐RH, and ChiraDEX HR). The best enantiomeric separation was obtained on the ChiraDEX HR (α = 0.89, Rs = 1.9) column with a gradient mode elution using a combination of ammonium acetate (10 mM, pH 4.0) and methanol as a mobile phase. The flow rate and column oven temperature were 0.7 mL/min and 30°C, respectively. The detection limits (λmax 280 nm) for d‐ORM and l‐ORM were 0.170 and 0.169 µg/mL, whereas quantification limits were 0.516 and 0.512 µg/mL. The method was validated according to the International Council on Harmonization (ICH) regulatory Guidelines Q2 (R1) in terms of its accuracy, precision, sensitivity, linearity, specificity, robustness, and solution stability. The designed analytical method could be extended as a quality control tool for pharmaceutical quality assessments as well as isomeric quantification of ORM in industrial bulk manufacturing.

Examining Drug Use and Misuse in India, and Evaluating Drug Control Laws

Examining Drug Use and Misuse in India, and Evaluating Drug Control Laws

Decoding the origins, spread, and global risks of mcr-9 gene

The global spread of the plasmid-mediated mcr (mobilized colistin resistance) gene family presents a significant threat to the efficacy of colistin, a last-line defense against numerous Gram-negative pathogens. The mcr-9 is the second most prevalent variant after mcr-1. A dataset of 698 mcr-9-positive isolates from 44 countries is compiled. The historical trajectory of the mcr-9 gene is reconstructed using Bayesian analysis. The effective reproduction number is used innovatively to study the transmission dynamics of this mobile-drug-resistant gene. Our investigation traces the origins of mcr-9 back to the 1960s, revealing a subsequent expansion from Western Europe to the America and East Asia in the late 20th century. Currently, its transmissibility remains high in Western Europe. Intriguingly, mcr-9 likely emerged from human-associated Salmonella and exhibits a unique propensity for transmission within the Enterobacter. Our research provides a new perspective that this host preference may be driven by codon usage biases in plasmids. Specifically, mcr-9-carrying plasmids prefer the nucleotide C over T compared to mcr-1-carrying plasmids among synonymous codons. The same bias is seen in Enterobacter compared to Escherichia (respectively as their most dominant genus). Furthermore, we uncovered fascinating patterns of coexistence between different mcr-9 subtypes and other resistance genes. Characterized by its low colistin resistance, mcr-9 has used this seemingly benign feature to silently circumnavigate the globe, evading conventional detection methods. However, colistin-resistant Enterobacter strains with high mcr-9 expression have emerged clinically, implying a strong risk of mcr-9 evolving into a global "true-resistance-gene". This study explores the mcr-9 gene, emphasizing its origin, adaptability, and dissemination potential. Given the high mcr-9 expression colistin-resistant strains was observed in clinically the prevalence of mcr-9 poses a significant challenge to drug resistance prevention and control within the One Health framework. This work was partially supported by the National Natural Science Foundation of China (Grant No. 32141001 and 81991533).

Quality and Safety of Extracted Humic Substances as Fundamental Factor of Natural Regulation for the Sustainable Development

Humic substances as natural biogeochemical macromolecules have been formed over tens of millions of years as a result of the processes of natural destruction of biological systems with a high degree of chemical diversity. The prospects and realities of today’s use of humic substances by humans in agriculture, pharmaceuticals and medicine raise the issue of strict safety control of various drugs derived from these natural substances. These technologies for the extraction and purification of final humic preparations should be carried out in accordance with the balanced development of natural ecosystems and biosafety requirements. In this publication we raise the issue of creating a single standard for the quality and safety of purified humic substances on a global scale.

Short- and long-term clinical outcomes of nintedanib therapy in IPF patients with different phenotypes: A retrospective registry-based study

BackgroundThere is a lack of data on the long-term effect of nintedanib on survival in specific groups of idiopathic pulmonary fibrosis (IPF) patients with different phenotypes. We investigated the outcomes of nintedanib therapy in an observational study of a large multicentre real-world cohort of IPF patients with various initial characteristics. MethodsThe analysis included IPF patients treated with nintedanib (NIN) and IPF patients not receiving antifibrotic treatment (NAF) enrolled for the EMPIRE registry in 2015–2020. The patients were stratified according to their initial FVC predicted, dyspnoea, UIP pattern and age. All-cause mortality and annual rate of FVC decline were the main endpoints. Cox proportional hazards model for survival assessment and linear mixed-effects model for FVC decline modelling were used. ResultsA total of 869 NIN patients and 691 NAF patients were eligible for the analysis. The annual FVC decline rate was significantly different (adjusted values −0.053 l/yr vs −0.122 l/yr; p = 0.001). The adjusted hazard ratio (HR) for mortality was 0.40 (95 % CI 0.3 to 0.53, p < 0.001). The most significant effect of nintedanib was demonstrated in patients with impaired lung function, i.e., with an FVC predicted to be less than 80 % and a NYHA II to IV. Nintedanib therapy also reduced the difference in survival between men and women. ConclusionsModelling confirmed that NIN therapy reduced differences in OS between patients with better and worse initial conditions and prognosis. Our results indicate that NIN is particularly beneficial for patients with advanced IPF and more severe phenotypes. Trial registrationEMPIRE was registered as a non-interventional post-registration study at the State Institute for Drug Control of the Czech Republic under ID 1412080000 on December 8, 2014.

APPLICATION OF NANOSENSOR BASED SCREEN PRINTED ELECTRODE FOR ANALYSIS OF ARTIFICIAL SWEETENER FOR PHARMACISTS AND ANALYST IN PONTIANAK

The development of nanotechnology in the world is very rapid, and the applications of nanotechnology can be felt in various fields in everyday life. For instance, to control food, nanotechnology plays a role in creating early detection tools for food additives, which are known to be dangerous if consumed by humans in excess, such as the presence of colorants that are not permitted or food additives that exceed tolerance limits. Nanosensors based on screen print electrodes (SPE) are devices that can be used for detection with various notable properties such as fast, sensitive and portable. Seeing the importance of developing and down streaming nanotechnology to society, education regarding the role of nanotechnology needs to be carried out. In this activity, nanotechnology applied in the manufacture of nanosensor devices was introduced, especially to analysts at the drug and food control center and the health service. Apart from that, through this activity, sustainable collaboration can be established between the community service team who are researchers in the field of nanosensors and users in the field who are drug and food regulatory bodies, to develop nanosensor technology according to needs in the field. This activity will be carried out in Pontianak, West Kalimantan, specifically aimed at pharmacists and analysts in the drug and food control center, health service, and industry and trade service (Disperindag). This activity will include education about nanotechnology applications in various fields as well as a demonstration on the use of SPE-based naosensor devices. From this event, in future the analyst may do the analysis in field without waiting long time analysis in laboratory. From this community service activities, scientific articles and publications can be produced in print/electronic media, as well as videos of community service activities, in accordance with the main performance indicators determined nationally.

Myristica fragrans Houtt. methanol extract as a promising treatment for Cryptosporidium parvum infection in experimentally immunosuppressed and immunocompetent mice.

Cryptosporidiosis is a major waterborne disease affecting ruminants and humans worldwide. It causes diarrhea and neonatal mortality in buffalo calves, and watery diarrhea and mortality in children and immunodeficient patients. This study aimed to investigate the efficacy of Myristica fragrans methanolic extract in treatment of C. parvum infection in comparison with nitazoxanide (NZX) (a Food and Drug Administration-approved drug control) in immunosuppressed and immunocompetent mice. One hundred laboratory-bred male Swiss albino mice were equally divided into immunocompetent and immunosuppressed groups. Each group was further divided into five subgroups: (1) non-infected and non-treated control, (2) infected and non-treated control (infected with Cryptosporidium parvum oocysts 3 × 103), (3) NZX-treated (100 mg/kg, 200 μL/mouse), (4) M. fragrans Houtt. methanol extract-treated (500 mg/kg), and (5) combination-treated (NZX + M. fragrans extract). Number of oocysts/g of feces, serum immunoglobulin (Ig) G level, and interferon (IFN)-γ, and interleukin (IL)-4 levels were used to evaluate the therapeutic effect. C. parvum oocyst shedding in stool samples was significantly decreased in all treatment groups, with 79.7%, 81.2 %, and 85.5 % reduction in immunocompetent mice treated with NZX, M. fragrans, and their combination, respectively. In immunosuppressed mice, oocyst shedding was reduced by 77.7%, 80.5 %, and 83.7 % upon NZX, M. fragrans, and their combination treatments, respectively. The serum IgG level was lowest in mice treated with a mixture of M. fragrans and NZX, followed by those treated with NZX, and was highest in mice treated with M. fragrans alone. Regarding cytokine levels, all groups treated with M. fragrans had low levels of IFN-γ and IL4 on day 21 post-infection. Collectively, the treatment of cryptosporidiosis with M. fragrans extract was successful in mice, as demonstrated by the measured parameters. M. fragrans reduced C. parvum oocyst shedding and serum IgG, IFN-γ, and IL-4 levels in immunocompetent and immunosuppressed mice.

Current Status of Cannabis Legalization and Decriminalization Efforts in Nepal.

The unique historical and cultural background of Nepal has shaped its perspective on cannabis usage. Narcotic Drugs Control Act 1976 of Nepal prohibits the cultivation, production, manufacture, sales, and distribution of narcotic drugs, which also include various forms of cannabis. With proponents for cannabis legalization increasing in the country, it is equally crucial to analyze context and practices in countries already adopting legalization. As such, this article contextualizes the current debates in Nepal with global policies and practices and talks about the possible impacts of changing the laws on society, the economy, and public health. Policymakers in Nepal must make decisions based on evidence and facts when deciding how to regulate cannabis.

Qualitative and Quantitative Determination of Hydroquinone Content in Skin Whitening Cosmetics Sold in Lafia-Nigeria

Hydroquinone (HQ) is a whitening or therapeutic constituent in many cosmetic products, but only allowable at a very low concentration. The abuse of HQ via frequent and prolonged usage can lead to health issues such as damage to skin and the sensitive area on the face. In Nigeria, National Agency for Food and Drug Administration and Control (NAFDAC) on its cosmetic products prohibition of bleaching agents regulations 2019, stated that no cosmetic products should contain more than 2 % of HQ alone or 1 % in combination with other lightening ingredients. This study aimed at qualitative and quantitative determination of HQ content in selected skin whitening cosmetics sold in Lafia. A total of twenty-four (24) various skin bleaching cosmetics were sampled from Lafia modern market. Thin Layer Chromatography (TLC) and uv/visible spectrophotometry were used for qualitative (identification) and quantitative (quantitation) determination of their HQ concentration, respectively. Ethanol (96 %) was used to extract HQ, and then TLC analysis at two different laboratories. At the two laboratories,nine samples (same) out of 24 were found to contain hydroquinone. The uv/visible spectrophotometric analysis indicated that the concentration of hydroquinone ranged from 0.99 % to 1.47 % in the cosmetic products studied.This study revealed that some of the products were labelled free from HQ or not labelled, and yet contained HQ, unknown to the consumers. In general, percentage hydroquinone in all the samples was less than 2 % maximum permissible limit recommended by US FDA and NAFDAC.

Памяти Николая Федоровича Мурашова

The article is dedicated to the memory of Nikolai Fedorovich Murashov, a famous scientist and the oldest author of the Drug Control magazine.

LT-102, an AMPA receptor potentiator, alleviates depression-like behavior and synaptic plasticity impairments in prefrontal cortex induced by sleep deprivation

BackgroundSleep loss is closely related to the onset and development of depression, and the mechanisms involved may include impaired synaptic plasticity. Considering the important role of glutamate α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate receptors (AMPARs) in synaptic plasticity as well as depression, we introduce LT-102, a novel AMPARs potentiator, to evaluate the potential of LT-102 in treating sleep deprivation-induced depression-like behaviors. MethodsWe conducted a comprehensive behavioral assessment to evaluate the effects of LT-102 on depression-like symptoms in male C57BL/6J mice. This assessment included the open field test to measure general locomotor activity and anxiety-like behavior, the forced swimming test and tail suspension test to assess despair behaviors indicative of depressive states, and the sucrose preference test to quantify anhedonia, a core symptom of depression. Furthermore, to explore the impact of LT-102 on synaptic plasticity, we utilized a combination of Western blot analysis to detect protein expression levels, Golgi-Cox staining to visualize neuronal morphology, and immunofluorescence to examine the localization of synaptic proteins. Additionally, we utilized primary cortical neurons to delineate the signaling pathway modulated by LT-102. ResultsTreatment with LT-102 significantly reduced depression-like behaviors associated with sleep deprivation. Quantitative Western blot (WB) analysis revealed a significant increase in GluA1 phosphorylation in the prefrontal cortex (PFC), triggering the Ca2+/calmodulin-dependent protein kinase II/cAMP response element-binding protein/brain-derived neurotrophic factor (CaMKII/CREB/BDNF) and forkhead box protein P2/postsynaptic density protein 95 (FoxP2/PSD95) signaling pathways. Immunofluorescence imaging confirmed that LT-102 treatment increased spine density and co-labeling of PSD95 and vesicular glutamate transporter 1 (VGLUT1) in the PFC, reversing the reductions typically observed following sleep deprivation. Golgi staining further validated these results, showing a substantial increase in neuronal dendritic spine density in sleep-deprived mice treated with LT-102. Mechanistically, application of LT-102 to primary cortical neurons, resulted in elevated levels of phosphorylated AKT (p-AKT) and phosphorylated glycogen synthase kinase-3 beta (p-GSK3β), key downstream molecules in the BDNF signaling pathway, which in turn upregulated FoxP2 and PSD95 expression. LimitationsIn our study, we chose to exclusively use male mice to eliminate potential influences of the estrous cycle on behavior and physiology. As there is no widely accepted positive drug control for sleep deprivation studies, we did not include one in our research. ConclusionOur results suggest that LT-102 is a promising therapeutic agent for counteracting depression-like behaviors and synaptic plasticity deficits induced by sleep deprivation, primarily through the activation of CaMKII/CREB/BDNF and AKT/GSK3β/FoxP2/PSD95 signaling pathways.