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Journal of Pharmaceutical Analysis May 2024The presence of -nitroso compounds, particularly -nitrosamines, in pharmaceutical products has raised global safety concerns due to their significant genotoxic and... (Review)
Review
The presence of -nitroso compounds, particularly -nitrosamines, in pharmaceutical products has raised global safety concerns due to their significant genotoxic and mutagenic effects. This systematic review investigates their toxicity in active pharmaceutical ingredients (APIs), drug products, and pharmaceutical excipients, along with novel analytical strategies for detection, root cause analysis, reformulation strategies, and regulatory guidelines for nitrosamines. This review emphasizes the molecular toxicity of -nitroso compounds, focusing on genotoxic, mutagenic, carcinogenic, and other physiological effects. Additionally, it addresses the ongoing nitrosamine crisis, the development of nitrosamine-free products, and the importance of sensitive detection methods and precise risk evaluation. This comprehensive overview will aid molecular biologists, analytical scientists, formulation scientists in research and development sector, and researchers involved in management of nitrosamine-induced toxicity and promoting safer pharmaceutical products.
PubMed: 38799236
DOI: 10.1016/j.jpha.2023.12.009 -
Journal of Cannabis Research Feb 2024The primary components driving the current commercial fascination with cannabis products are phytocannabinoids, a diverse group of over 100 lipophilic secondary... (Review)
Review
BACKGROUND
The primary components driving the current commercial fascination with cannabis products are phytocannabinoids, a diverse group of over 100 lipophilic secondary metabolites derived from the cannabis plant. Although numerous phytocannabinoids exhibit pharmacological effects, the foremost attention has been directed towards Δ-tetrahydrocannabinol (THC) and cannabidiol, the two most abundant phytocannabinoids, for their potential human applications. Despite their structural similarity, THC and cannabidiol diverge in terms of their psychotropic effects, with THC inducing notable psychological alterations. There is a clear need for accurate and rapid THC measurement methods that offer dependable, readily accessible, and cost-effective analytical information. This review presents a comprehensive view of the present state of alternative technologies that could potentially facilitate the creation of portable devices suitable for on-site usage or as personal monitors, enabling non-intrusive THC measurements.
METHOD
A literature survey from 2017 to 2023 on the development of portable technologies and commercial products to detect THC in biofluids was performed using electronic databases such as PubMed, Scopus, and Google Scholar. A systematic review of available literature was conducted using Preferred Reporting Items for Systematic. Reviews and Meta-analysis (PRISMA) guidelines.
RESULTS
Eighty-nine studies met the selection criteria. Fifty-seven peer-reviewed studies were related to the detection of THC by conventional separation techniques used in analytical laboratories that are still considered the gold standard. Studies using optical (n = 12) and electrochemical (n = 13) portable sensors and biosensors were also identified as well as commercially available devices (n = 7).
DISCUSSION
The landscape of THC detection technology is predominantly shaped by immunoassay tests, owing to their established reliability. However, these methods have distinct drawbacks, particularly for quantitative analysis. Electrochemical sensing technology holds great potential to overcome the challenges of quantification and present a multitude of advantages, encompassing the possibility of miniaturization and diverse modifications to amplify sensitivity and selectivity. Nevertheless, these sensors have considerable limitations, including non-specific interactions and the potential interference of compounds and substances existing in biofluids.
CONCLUSION
The foremost challenge in THC detection involves creating electrochemical sensors that are both stable and long-lasting while exhibiting exceptional selectivity, minimal non-specific interactions, and decreased susceptibility to matrix interferences. These aspects need to be resolved before these sensors can be successfully introduced to the market.
PubMed: 38414071
DOI: 10.1186/s42238-024-00216-0 -
Frontiers in Public Health 2023Services to treat problematic alcohol use (PAU) should be highly accessible to optimize treatment engagement. We conducted a scoping review to map characteristics of...
INTRODUCTION
Services to treat problematic alcohol use (PAU) should be highly accessible to optimize treatment engagement. We conducted a scoping review to map characteristics of services for the treatment of PAU that have been reported in the literature to be barriers to or facilitators of access to treatment from the perspective of individuals with PAU.
METHODS
A protocol was developed , registered, and published. We searched MEDLINE, Embase, the Cochrane Library, and additional grey literature sources from 2010 to April 2022 to identify primary qualitative research and surveys of adults with current or past PAU requiring treatment that were designed to identify modifiable characteristics of PAU treatment services (including psychosocial and pharmacologic interventions) that were perceived to be barriers to or facilitators of access to treatment. Studies of concurrent PAU and other substance use disorders were excluded. Study selection was performed by multiple review team members. Emergent barriers were coded and mapped to the accessibility dimensions of the Levesque framework of healthcare access, then descriptively summarized.
RESULTS
One-hundred-and-nine included studies reported an extensive array of unique service-level barriers that could act alone or together to prevent treatment accessibility. These included but were not limited to lack of an obvious entry point, complexity of the care pathway, high financial cost, unacceptably long wait times, lack of geographically accessible treatment, inconvenient appointment hours, poor cultural/demographic sensitivity, lack of anonymity/privacy, lack of services to treat concurrent PAU and mental health problems.
DISCUSSION
Barriers generally aligned with recent reviews of the substance use disorder literature. Ranking of barriers may be explored in a future discrete choice experiment of PAU service users. The rich qualitative findings of this review may support the design of new or modification of existing services for people with PAU to improve accessibility.
SYSTEMATIC REVIEW REGISTRATION
Open Science Framework doi: 10.17605/OSF.IO/S849R.
Topics: Adult; Humans; Substance-Related Disorders; Alcoholism; Health Services Accessibility
PubMed: 38106884
DOI: 10.3389/fpubh.2023.1296239 -
Journal of Traditional Chinese Medicine... Jun 2024To investigate the efficacy of substances containing 3 types of active ingredients-saponins, flavones, and alkaloids on experimental animals with autoimmune diseases... (Meta-Analysis)
Meta-Analysis
Efficacy of substances containing 3 types of active ingredients-saponins, flavones, and alkaloids in regulation of cytokines in autoimmune diseases a systematic review and Meta-analysis based on animal studies.
OBJECTIVE
To investigate the efficacy of substances containing 3 types of active ingredients-saponins, flavones, and alkaloids on experimental animals with autoimmune diseases (AIDs).
METHODS
The protocol for this systematic review and Meta-analysis was prospectively registered with PROSPERO (CRD42023395741). Searches were conducted in the China National Knowledge Infrastructure, Wanfang, Chinese Science and Technology Journals, China Biomedical, PubMed, Cochrane Library, and Embase databases to screen for animal studies investigating the therapeutic effects of saponins, flavones, or alkaloids on autoimmune diseases; consequently, corresponding data extraction tables were prepared. Systematic Review Centre for Laboratory Animal Experimentation was used to assess the risk of methodological bias in the included literature. RevMan 5.4 was used for the Meta-analysis on the 8 serum cytokines.
RESULTS
A total of 31 studies were included, all of which were randomized controlled studies. Meta-analysis indicated that substances rich in saponins, flavones, and alkaloids reduced serum levels of interleukin (IL)-1β [standardized mean difference () = -1.94, 95% confidence interval () (-2.99, -0.90), 0.0003], IL-6 [ = -1.65, 95% (-2.33, -0.97,) 0.000 01], IL-17 [ = -2.41, 95% (-3.61, -1.20), 0.0001], tumor necrosis factor (TNF)-α [ = -1.84, 95% (-2.61, -1.06), 0.0001], and interferon (IFN)-γ [ = -1.54, 95% (-2.43, -0.65), 0.0007], but increased serum levels of IL-4 [ = 1.30, 95% (0.15, 2.44), 0.03) and IL-10 [ = 2.05, 95% (1.39, 2.70), 0.000 01) in animal models. However, no significant regulatory effect of these three active components was observed on serum levels of IL-2 [ = -0.63, 95% (-1.82, 0.57), 0.30].
CONCLUTIONS
Substances containing saponins, flavones, and alkaloids regulated the changes of immune-related cytokines, it may be a novel dietary substance to relieve and control autoimmune diseases in the future.
Topics: Animals; Flavones; Cytokines; Autoimmune Diseases; Saponins; Alkaloids; Humans; Drugs, Chinese Herbal
PubMed: 38767625
DOI: 10.19852/j.cnki.jtcm.20240402.003 -
Phytomedicine : International Journal... Jul 2024Sulforaphane (SFN) is a dietary isothiocyanate, derived from glucoraphanin, present in cruciferous vegetables belonging to the Brassica genus. It is a biologically... (Review)
Review
BACKGROUND
Sulforaphane (SFN) is a dietary isothiocyanate, derived from glucoraphanin, present in cruciferous vegetables belonging to the Brassica genus. It is a biologically active phytochemical that acts as a nuclear factor erythroid 2-related factor 2 (Nrf2) inducer. Thus, it has been reported to have multiple protective functions including anticancer responses and protection against a toxic agent's action.
PURPOSE
The present work systematically reviewed and synthesised the protective properties of sulforaphane against a toxic agent. This review reveals the mechanism of the action of SFN in each organ or system.
METHODS
The PRISMA guideline was followed in this sequence: researched literature, organised retrieved documents, abstracted relevant information, assessed study quality and bias, synthesised data, and prepared a comprehensive report. Searches were conducted on Science Direct and PubMed using the keywords "Sulforaphane" AND ("protective effects" OR "protection against").
RESULTS
Reports showed that liver and the nervous system are the target organs on which attention was focused, and this might be due to the key role of oxidative stress in liver and neurodegenerative diseases. However, protective activities have also been demonstrated in the lungs, heart, immune system, kidneys, and endocrine system. SFN exerts its protective effects by activating the Nrf2 pathway, which enhances antioxidant defenses and reduces oxidative stress. It also suppresses inflammation by decreasing interleukin production. Moreover, SFN inhibits apoptosis by preventing caspase 3 cleavage and increasing Bcl2 levels. Overall, SFN demonstrates multifaceted mechanisms to counteract the adverse effects of toxic agents.
CONCLUSION
SFN has potential clinical applications as a chemoprotective agent. Nevertheless, more studies are necessary to set the safe doses of SFN in humans.
Topics: Isothiocyanates; Sulfoxides; Humans; Animals; Brassica; Oxidative Stress; NF-E2-Related Factor 2; Protective Agents
PubMed: 38824824
DOI: 10.1016/j.phymed.2024.155731 -
Nutrients May 2024Liver cancer ranks third globally among causes of cancer-related deaths, posing a significant public health challenge. However, current treatments are inadequate,... (Review)
Review
Liver cancer ranks third globally among causes of cancer-related deaths, posing a significant public health challenge. However, current treatments are inadequate, prompting a growing demand for novel, safe, and effective therapies. Natural products (NPs) have emerged as promising candidates in drug development due to their diverse biological activities, low toxicity, and minimal side effects. This paper begins by reviewing existing treatment methods and drugs for liver cancer. It then summarizes the therapeutic effects of NPs sourced from various origins on liver cancer. Finally, we analyze the potential mechanisms of NPs in treating liver cancer, including inhibition of angiogenesis, migration, and invasion; regulation of the cell cycle; induction of apoptosis, autophagy, pyroptosis, and ferroptosis; influence on tumor metabolism; immune regulation; regulation of intestinal function; and regulation of key signaling pathways. This systematic review aims to provide a comprehensive overview of NPs research in liver cancer treatment, offering a foundation for further development and application in pharmaceuticals and functional foods.
Topics: Humans; Biological Products; Liver Neoplasms; Apoptosis; Signal Transduction; Antineoplastic Agents; Animals; Antineoplastic Agents, Phytogenic; Autophagy
PubMed: 38892575
DOI: 10.3390/nu16111642 -
Scientific Reports Jun 2024Classic psychedelics and MDMA have a colorful history of recreational use, and both have recently been re-evaluated as tools for the treatment of psychiatric disorders.... (Meta-Analysis)
Meta-Analysis
Classic psychedelics and MDMA have a colorful history of recreational use, and both have recently been re-evaluated as tools for the treatment of psychiatric disorders. Several studies have been carried out to assess potential long-term effects of a regular use on cognition, delivering distinct results for psychedelics and MDMA. However, to date knowledge is scarce on cognitive performance during acute effects of those substances. In this systematic review and meta-analysis, we investigate how cognitive functioning is affected by psychedelics and MDMA during the acute drug effects and the sub-acute ("afterglow") window. Our quantitative analyses suggest that acute cognitive performance is differentially affected by psychedelics when compared to MDMA: psychedelics impair attention and executive function, whereas MDMA primarily affects memory, leaving executive functions and attention unaffected. Our qualitative analyses reveal that executive functioning and creativity may be increased during a window of at least 24 h after the acute effects of psychedelics have subsided, whereas no such results have been observed for MDMA. Our findings may contribute to inform recommendations on harm reduction for recreational settings and to help fostering differential approaches for the use of psychedelics and MDMA within a therapeutic framework.
Topics: Humans; Hallucinogens; N-Methyl-3,4-methylenedioxyamphetamine; Cognition; Executive Function; Attention; Memory
PubMed: 38926480
DOI: 10.1038/s41598-024-65391-9 -
Journal of the International Society of... Dec 2024Caffeine, widely recognized as an ergogenic aid, has undergone extensive research, demonstrating its effectiveness to enhance endurance performance. However, there... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Caffeine, widely recognized as an ergogenic aid, has undergone extensive research, demonstrating its effectiveness to enhance endurance performance. However, there remains a significant gap in systematically evaluating its effects on time trial (TT) performance in cyclists.
PURPOSE
This meta-analysis aimed to determine the efficacy of caffeine ingestion to increase cycling TT performance in cyclists and to evaluate the optimal dosage range for maximum effect.
METHODS
A search of four databases was completed on 1 December 2023. The selected studies comprised crossover, placebo-controlled investigations into the effects of caffeine ingestion on cycling TT performance. Completion time (Time) and mean power output (MPO) were used as performance measures for TT. Meta-analyses were performed using a random-effects model to assess the standardized mean differences (SMD) in individual studies.
RESULTS
Fifteen studies met the inclusion criteria for the meta-analyses. Subgroup analysis showed that moderate doses of caffeine intake (4-6 mg/kg) significantly improved cycling performance (SMD = -0.55, 95% confidence interval (CI) = -0.84 ~ -0.26, < 0.01, = 35%; SMD = 0.44, 95% CI = 0.09 ~ 0.79, < 0.05, = 39%), while the effects of low doses (1-3 mg/kg) of caffeine were not significant (SMD = -0.34, 95% CI = -0.84 ~ 0.17, = 0.19, = 0%; SMD = 0.31, 95% CI = -0.02 ~ 0.65, = 0.07, = 0%).
CONCLUSION
A moderate dosage (4-6 mg/kg) of caffeine, identified as the optimal dose range, can significantly improve the time trial performance of cyclists, while a low dose (1-3 mg/kg) does not yield improvement. In addition, the improvements in completion time and mean power output resulting from a moderate dose of caffeine are essentially the same in cycling time trails.
Topics: Caffeine; Bicycling; Humans; Athletic Performance; Performance-Enhancing Substances; Dose-Response Relationship, Drug; Physical Endurance
PubMed: 38836626
DOI: 10.1080/15502783.2024.2363789 -
Toxics Apr 2024Biomonitoring of human populations exposed to chemical substances that can act as potential mutagens or carcinogens, may enable the detection of damage and early disease... (Review)
Review
Biomonitoring of human populations exposed to chemical substances that can act as potential mutagens or carcinogens, may enable the detection of damage and early disease prevention. In recent years, the comet assay has become an important tool for assessing DNA damage, both in environmental and occupational exposure contexts. To evidence the role of the comet assay in human biomonitoring, we have analysed original research studies of environmental or occupational exposure that used the comet assay in their assessments, following the PRISMA-ScR method (preferred reporting items for systematic reviews and meta-analyses extension for scoping reviews). Groups of chemicals were designated according to a broad classification, and the results obtained from over 300 original studies (n = 123 on air pollutants, n = 14 on anaesthetics, n = 18 on antineoplastic drugs, n = 57 on heavy metals, n = 59 on pesticides, and n = 49 on solvents) showed overall higher values of DNA strand breaks in the exposed subjects in comparison with the unexposed. In summary, our systematic scoping review strengthens the relevance of the use of the comet assay in assessing DNA damage in human biomonitoring studies.
PubMed: 38668493
DOI: 10.3390/toxics12040270 -
Naunyn-Schmiedeberg's Archives of... May 2024Curcumin is an ingredient of the root Curcuma longa, which is responsible for the characteristic yellow color of curcuma. Curcumin is said to have the potential ability... (Review)
Review
Curcumin is an ingredient of the root Curcuma longa, which is responsible for the characteristic yellow color of curcuma. Curcumin is said to have the potential ability to fight malignant diseases and to have an anti-inflammatory effect. In addition, it is used as a dietary supplement. However, one problem with the use of curcumin is its extremely low bioavailability. The aim of this study is to systematically review and critically analyze clinical studies related to the pharmacokinetics (or bioavailability) and to the use of curcumin in the treatment of malignant diseases. The platforms clinicaltrials.gov and PubMed served as the database for the literature research. A total of 293 available studies on curcumin were filtered according to their focus (bioavailability, therapy of malignant diseases) and other criteria (study results, main substance, topic reference, existing disease/other research purpose, reference to malignant diseases). The studies were further analyzed regarding their outcome measures, their design (number of participants, randomization, placebo group, masking, ethical standards, sponsor, primary outcome measures, secondary outcome measures, study bias) and their findings. The analysis failed to convincingly demonstrate that curcumin has a significant, positive effect on the therapy of malignant diseases. Regarding the increase in bioavailability, positive results have been obtained, which are in proximity to the pharmaceutical industry. Independent studies could not achieve increased bioavailability of curcumin. The available reviews in the literature also do not provide convincing evidence for the efficacy of curcumin. Thus, at the time being, the use of curcumin in malignant diseases is not justified scientifically.
Topics: Animals; Humans; Antineoplastic Agents; Biological Availability; Clinical Trials as Topic; Curcumin; Neoplasms
PubMed: 37966571
DOI: 10.1007/s00210-023-02825-7